The Clinical Outcomes and Safety of Tigecycline in Monotherapy or Combination with Cefoperazone/sulbactam for Carbapenem-Resistant Acinetobacter baumannii-Associated Pneumonia: A Multicenter Retrospective Study

The Clinical Outcomes and Safety of Tigecycline in Monotherapy or Combination with Cefoperazone/sulbactam for Carbapenem-Resistant Acinetobacter baumannii-Associated Pneumonia: A Multicenter Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Clinical Outcomes and Safety of Tigecycline in Monotherapy or Combination with Cefoperazone/sulbactam for Carbapenem-Resistant Acinetobacter baumannii-Associated Pneumonia: A Multicenter Retrospective Study Xiaotong Tian, Jing Lin, Menglan Zhou, Ying Ge, Taisheng Li, Li Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4176720/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective We aimed to evaluate clinical outcomes and safety in tigecycline (TGC) monotherapy or in combination with cefoperazone/sulbactam (CPS) treatment for patients with hospital-acquired pneumonia (HAP) infected by carbapenem-resistant Acinetobacter baumannii(CRAB). Methods This was a retrospective analysis of multicenter data from patients with CRAB HAP in 62 Chinese hospitals. Risk factors of receiving TGC with CPS therapy and predictors of mortality were used multivariate logistic and Cox regression analyses, respectively. Propensity score matching (PSM) evaluated the efficacies and safety of antimicrobial regimens. Results 180 patients included in our study, 95 used TGC monotherapy, and 85 used TGC with CPS therapy. The multivariate logistic regression analysis revealed that the risk factors were significantly associated with TGC with CPS therapy included the older age [ P = 0.011], intensive care unit (ICU) admission[ P = 0.007]. The multivariate Cox regression demonstrated that there was a significantly higher risk of 90-day mortality [ P = 0.031] among subjects in TGC-CPS group. The subgroup of patients who received Standard dose TGC (SDT) plus CPS had a significantly higher rate of SOFA score ≧ 7( P = 0.009), and the 30/90-day mortality rate of patients was also higher. The variation of ALT, TBIL, Cr, Hb, and PLT did not differ between different antimicrobial regimens after PSM. Conclusion The severity of patient conditions and TGC doses were significantly associated with mortality. HDT combined with CPS was the prior treatment option for patients with CRAB HAP who were elderly, had ICU admission. We observed that different antimicrobial regimens had similar safety in liver/kidney/coagulation. Tigecycline Cefoperazone/Sulbactam Carbapenem-Resistant Acinetobacter baumannii Hospital Acquired Pneumonia Figures Figure 1 Figure 2 Introduction The gram-negative bacilli [ 1 ] were primary pathogens of HAP in our country, among which AB [ 2 ] was the most common, accounting for 25.6%. AB was limited in the availability of antimicrobial agents, due to increasing resistance to various antibiotics, especially carbapenems, as well as had the ability to survive long-term in vitro, which spread widely in the hospital. Besides, the conditions for patients with AB infections were severe, resulting in longer lengths of hospital stay (LOS), more medical costs, and worse prognosis[ 3 ]. It was why AB, as a priority on the global priority list for research and development of new antibiotics, has been classified by the World Health Organization(WHO) [ 4 ]. Accordingly, AB infection has long become a focus issue of global public health, bringing a heavy challenge to the safety of the international medical and health environment. It was critical to strengthen surveillance and control AB spread. In 2020, Chen CH et al. [ 5 ] conducted a study on the in vitro activity of multiple antimicrobials against AB in the Asia-Pacific region, including novel β-lactam combination agents, TGC and colistin, which showed that drug-resistant strains of AB in China exceeded 70.0%, being third only after South Korea and India. According to the China Antimicrobial Surveillance Network (CHINET) continuous drug resistance monitoring program in 2021, it was also reported that among clinical isolates of CRAB amounted to 71.5% [ 6 ], a rising trend over the years. Although CRAB had greater than 88.0% susceptibility to polymyxin B and tigecycline [ 7 ], which were considered the last resource antibiotics currently used in CRAB infection, a superior treatment for CRAB infection is still a matter of debate. For severe CRAB infections, TGC monotherapy may lead to higher mortality, especially in the case of bacteremia or pneumonia[ 8 ]. According to the Infectious Diseases Society of America (IDSA) guidelines and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for AMR treatment for the antimicrobial resistance (AMR) treatment, as well as 2023 IDSA Guidelines for the treatment of drug-resistant gram-negative bacterial infections, which were recommended that patients with severe CRAB infections should receive a combination of at least two in vitro active drugs[ 9 – 11 ]. Moreover, it also mentioned that ampicillin-sulbactam combined with TGC or cefiderocol was the preferred treatment for CRAB-associated pneumonia. Likewise, the Chinese Expert Consensus on Diagnosis, Treatment, Prevention, and Control of AB Infections also proposed that the two-drug combination therapy for CRAB was suggested sulbactam compound (or sulbactam)-based, with CPS being the mainly used in China [ 12 ], followed by polymyxin E and TGC. However, colistin with additional antibacterial agents was associated with a higher risk of nephrotoxicity [ 13 ]. Even both TGC-based combination therapy and polymyxin-based combination therapy are equally preferable for the treatment of pulmonary infection caused by CRAB. However, there are currently only well-controlled, unsampled clinical case studies or case reports regarding the treatment of AB pneumonia with TGC, which had low quality of evdience monotherapy or combination therapy [ 9 , 10 , 14 , 15 ], and there remains a need for further validation concerning the clinical efficacy and safety of regimens. Therefore, it is essential and of significant clinical value to explore the treatment of CRAB-infected patients with hospital-acquired pneumonia based on different doses of TGC in monotherapy or combination with CPS. Methods Study design and patients population We performed a multicenter retrospective study in 62 hospitals in China from October 2019 to June 2021. We selected 180 hospitalized adult patients with CRAB pneumonia who received either TGC monotherapy or combination with CPS. The inclusion criteria were as fllowed: (1) patients were infected with CRAB HAP; (2) patients who received either TGC monotherapy or combined with CPS. The exclusion criteria included the following: (1) pathogenic bacteria other than CRAB; (2) pathology not derived from sputum or BALF; (3) treatment for fewer than two days [ 16 ]. ( Figs. 1 ) Data Collection The collected data were as follows: demographic characteristics (Gender, Age, BMI), history of chronic illness (Charlson comorbidity index score, CCI), the severity of the condition (Sequential Organ Failure Assessment score, SOFA), comorbid conditions (septic shock), intensive care unit (ICU) admission, Mechanical Ventilation (MV), Continuous Renal Replacement Therapy (CRRT), laboratory findings, and follow-up. The primary clinical outcome was defined as all-cause 30/90-day mortality. The secondary outcomes included length of hospital stays (LOS), variations in white blood cell (WBC), C-reactive protein (CRP), and procalcitonin (PCT) within 1 week of antibiotic use. To assess the incidence of adverse events, we calculated the variation in ALT/TBIL/Cr/PLT/Hb( maximum minus minimum of alanine aminotransferase (ALT)/total bilirubin (TBIL)/creatinine (Cr)/platelet (PLT)/ hemoglobin (Hb)within 1 week of antibiotic use). Definitions Pneumonia caused by CRAB was defined as clinical evidence of HAP with a qualified sample positive for CRAB [ 17 ]. Patients were treated with an intravenous 100mg dose, followed after 12 h by a maintenance dose of 50 mg every 12 hours, defined as Standard-dose-TGC(SDT), while High-Dose-TGC(HDT) was an initial dose of 200 mg followed by 100 mg every 12 hrs(q12h). Cefoperazone/Sulbactam(cefoperazone: sulbactam, 1:1/ 2:1) at a dose of 6-9g administered intravenously one day. Statistical analysis All statistical analyses were performed using SPSS software (version 26.0). Continuous variables were assessed for normality with the Shapiro-Wilk test. The data that conformed to normal distribution were presented as the mean and standard deviation (SD) and analyzed using a t-test. Otherwise, data would be presented as the median and interquartile range (IQR) with the Mann-Whitney U test. Categorical Data were presented as the number and proportions (%). The chi-square test or Fisher's exact test was used to test comparisons between groups for categorical variables. The relative efficacies and adverse effects of the different antimicrobial regimens were assessed by conducting propensity score matching (PSM). Multi-logistic regression analysis and ROC curves were used to predict the independent risk factors for different antibiotic regiments. The Kaplan-Meier product-limit method was used to estimate the survival distribution function. The predictors of 30-day and 90-day mortality for CRAB Pneumonia were identified using Cox regression analysis. P values less than 0.05 were considered statistically significant. Results We included data from 180 patients with CRAB HAP and analyzed their characteristics, including 95 receiving TGC monotherapy, and 85 receiving TGC combined with CPS therapy. Patients with TGC monotherapy were defined as the control group, and TGC combined with CPS therapy as the observation group. The age(73(63,85) vs 65(56.5,76) , P = 0.009)、BMI (23.0(21.3,24.8) vs 21.6(20.1,24.4), P = 0.049)、CCI score(2(1,4)vs1(0,2), P = 0.002)、SOFA score(9(6,11)vs5(4,9), P = 0.000) were significantly higher in observation group. In subsequent analysis, a significant increase was found in patients receiving TGC plus CPS combination compared to those with TGC monotherapy, including the SOFA score ≥7(72.9% vs 35.8%, P = 0.000) and ≥65yr(68.2% vs 52.6%, P = 0.033); however, there were no significant differences in the BMI subgroup( P > 0.05). The ICU admission, used MV, and CRRT rates of patients given TGC with CPS were also higher than that of patients given TGC monotherapy (91.8% vs 56.8%, 87.1% vs 45.3%, 25.9% vs 5.3%; respectively, P = 0.000). Additionally, a similar difference was noticed in the incidence of shock (57.6% vs 34.7%, P = 0.002). (Table 1) There was a significant difference in the primary outcomes of all-cause 30-day mortality when comparing TGC monotherapy and TGC combined with CPS therapy ( 6.3% vs 16.5%, P = 0.03). Additionally, the all-cause 90-day mortality of patients receiving TGC combined with CPS regimen was also higher; however, no statistical difference was observed (25.9% vs 15.8%, P = 0.094). Despite these circumstances, the LOS was similar in both two groups (26(21,41) vs 30(20,42), P = 0.627). The PSM was performed to adjust the WBC, PCT, ALT, TBIL, Hb, and PLT; it demonstrated that TGC plus CPS therapy was superior to those with TGC monotherapy in reducing CRP level(88.2(36.2,152) vs 22.6(9.5,71), P = 0.009). Furthermore, TGC plus CPS therapy did not differ in adverse effects when compared to TGC monotherapy( P > 0.05). (Table 2) The multivariate logistic regression analysis revealed that independent risk factors associated with TGC plus CPS therapy included age [ P = 0.011; odds ratio, OR(95% CI): 1.083 (1.018–1.152)], ICU [ P = 0.007; OR(95% CI): 12.801 (1.980–82.747)], WBC [ P = 0.023; OR(95% CI): 0.877 (0.784–0.982)], and Hb [ P = 0.047; OR(95% CI): 0.951 (0.904–0.999)] ( Table 3 ), with the AUC of 0.931 and 95% confidence interval of 0.887-0.975. The validation of this risk model demonstrated that the model had good prediction ability. In addition, the cut-off value was 0.3, and the sensitivity and specificity were 100% and 75.4%, respectively ( Supplementary Figure 1 ). A significant increase in the all-cause 30-day mortality (X 2 =4.202, P= 0.04) in patients with CRAB HAP receiving TGC with CPS, according to the Kaplan-Meier survival curve( Figures 2a ). The 90-day mortality of patients receiving TGC with CPS was also higher than that of patients with TGC monotherapy; however, the difference was not significant (Figures 2b) . The multivariate Cox regression analysis showed that shock and PLT were independent predictors of 30-day and 90-day mortality ( P < 0.05). After adjusting for confounding factors, it revealed that TGC with CPS therapy was also an independent predictor of the 90-day mortality[ P = 0.031, HR (95% CI): 2.934(1.104–7.802)]. The data were presented in Table 4 . We included data from 43 receiving SDT and 52 receiving HDT monotherapy. Similar baseline characteristics were shown between both groups, including gender、age、BMI、CCI score、SOFA score, ICU stay, MV, CRRT, and shock( P > 0.05). ( Supplementery Table 1 ) There was no significant difference between primary and secondary outcomes in those patients( P > 0.05). Regarding adverse events, the variation of ALT, TBIl, Cr, Hb, and PLT was not statistically significant when comparing the SDT and HDT groups( P > 0.05). ( Supplementery Table 2 ) We included data from 59 receiving SDT with CPS, and 26 receiving HDT with CPS. Some baseline characteristics in both groups were similar, including gender, age, BMI, CCI score, SOFA score, ICU stay, CRRT, and shock ( P > 0.05); however, the used MV was higner in the SDT combined with CPS group (93.2% vs 73.1%, P = 0.028). In subsequent analysis, the BMI≧28 of patients was significantly lower rate in the SDT combined with CPS group (0% vs 15.4%, P = 0.006); however, The SOFA score≧7 for patients in SDT combined with CPS was higher than it was for those in HDT combined with CPS (81.4% vs 53.8%, P = 0.009). ( Supplementery Table 3 ) No significant difference was found between the SDT and HDT combined with CPS groups in primary and secondary outcomes ( P > 0.05). Similarly, the variation of ALT、TBIl、Cr、Hb、PLT were not statistically significant in terms of adverse events( P > 0.05). ( Supplementery Table 4 ) Discussion CRAB HAP has become a challenging clinical dilemma worldwide due to its high antimicrobial resistance, limited availability of regimens, and high mortality[18]. There were controversial treatments for patients with CRAB HAP, according to previous research. We summarized the clinical features, treatment effectiveness, and safety of various TGC doses in monotherapy or combined with CPS treatment for CRAB pneumonia. Moreover, we evaluated the independent predictors of all-cause 30/90-day mortality and risk factors of different antibiotic regimens in patients with CRAB pneumonia. The followings were the primary findings of this study. We found a significant increase in all-cause 30/90-day mortality in TGC plus CPS therapy, which was an independent predictor of all-cause 90-day mortality following adjustment of compound factors. Meanwhile, we noticed that shock was significantly associated with 30-day and 90-day mortality. Notably, patients receiving TGC with CPS therapy were significantly superior to those with TGC monotherapy in reducing CRP levels; however, similar safety was shown in different antimicrobial regimens, including liver/kidney/coagulation. The subgroup analysis indicated that HDT combined with CPS therapy was a prior treatment option for patients with CRAB HAP who were the older age, ICU admissions particularly. In addition, the primary and secondary outcomes were similar in SDT and HDT monotherapy or combination with CPS therapy group. It first demonstrated the difference between TGC monotherapy and TGC combined with CPS in large-scale real-world data to offer the optimal drug regimens for CRAB HAP in the clinic. Our research showed that TGC combined with CPS treatment had different clinical features when compared to TGC monotherapy for CRAB HAP. Patients with TGC plus CPS therapy had significantly higher rates than those with TGC monotherapy with a history of hospital exposure, including ICU admission, used MV and CRRT. In addition, multivariate logistic regression analysis showed that older age and ICU admission were independent risk factors for TGC plus CPS treatment for CRAB HAP. ICU patients were usually critically ill and immunocompromised, most of whom underwent invasive operations, which therefore increased the chance of contracting CRAB. However, in our study, invasive operations were not an independent risk factor for receiving tigecycline combined with cefoperazone sulbactam therapy. This might be because almost all patients experienced invasive practices during their hospitalization in the ICU, and some patients had more than one simultaneously installed invasive device. Thus, these factors could interfere with and influence each other. In conclusion, the treatment regimen for patients in the combination therapy group is under guideline and expert consensus recommendations [9-11], and the TGC in combination with CPS therapy is the preferred treatment for infections in patients with severe CRAB. We observed an increase in the all-cause 30/90 mortality (16.5% VS 6.3%, P =0.03; 25.9% VS 15.8%, P = 0.094; respectively) in patients receiving TGC-CPS combination therapy in comparison to TGC monotherapy; however, the difference in 90-day mortality was not significant. The further multivariate Cox regression demonstrated that shock and TGC-CPS combination treatment were independent predictors of 30/90 mortality and 90-day mortality, respectively. Attributing to older age (73 VS 65, P = 0.009) and more comorbidities among TGC with CPS treatment of patients with CRAB HAP, who had a worse condition and more susceptible to multiple organ failure and septic shock, after severe infections, resulting in higher SOFA scores(9 (6, 11) VS 5 (4, 9), P = 0.000) and mortality. Although we noticed that Food and Drugs Administration (FDA)-approved indications were only for cIAI, cSSSI, and CAP, not including HAP, due to ascended multidrug-resistant infections, TGC had been widely used for non-approved indications, among whom used in research related to CRAB HAP accounted for 1/3 [8]. A previous meta-analysis of 5 trials [19] analyzed the prognosis of patients with CRAB HAP receiving TGC monotherapy compared to those with TGC combination, no significant difference was from two prospective cohort studies (OR = 2.22, 95% CI 0.79–6.20, P = 0.13). Except for in-hospital mortality, Li Y et al. [20] found that regimens containing TGC-CPS combination therapy patients with CRAB HAP were not superior to those with TGC monotherapy in clinical and microbiological efficacies. However, we only found in some laboratory findings that patients with TGC plus CPS therapy had higher CRP decline compared with TGC monotherapy, which indicated better outcomes in reducing inflammatory response, consistent with previous results[21]. Therefore, the efficacy of patients with CRAB HAP receiving TGC monotherapy or combination regimens was controversial. In addition, the mortality and efficacy of various doses of TGC monotherapy were also unclear [22,23]. As a previous Systematic Review and Meta-Analysis[24] reported, although the microbiological eradication rate in those given HDT did not differ from SDT monotherapy for CR pathogens (OR 1.07, 95% CI 0.44-2.60, P = 0.87), mortality was reduced（OR 0.20，95% CI 0.09-0.45，p = 0.0001). And Shields RK [25] also found that HDT combined with in-vitro active antibiotics in improving prognosis was superior to SDT. Accordingly, we supposed that the high mortality in patients with severe infection might be related to tigecycline dose. In our study, subgroup analysis showed that mortality and laboratory findings of infections in SDT and HDT monotherapy or combination were no statistical difference, although lack of microbiological data. Notably, the 30/90-day mortality and SOFA scores in patients receiving SDT with CPS were also higher than those receiving HDT with CPS, which indicated that more severe infection occurred in patients with SDT combination CPS. TGC, as a bacteriostatic agent, inevitably resulted in delayed bacterial clearance and higher mortality when the organism had severely infection, if the concentration of the drug in the tissues was low and the bacteriostatic activity was descend. The difference in mortality between the two groups of patients in this study was not statistical significant, which may be due to insufficient sample size. Accordingly, There is a great need for well-designed studies to evaluate the effectiveness of various doses of TGC in monotherapy when compared to combination therapies. On the other hand, the safety needed to be taken into consideration when prescribing TGC or CPS. TGC[26,27] and CPS[38-30]could cause coagulation disorders, raising safety concerns. Besides, severe infection could lead to coagulation factors and PLT heavier consumption, and bleeding events occurred commonly. Notably, there was controversy about whether TGC-CPS combination treatment would increase bleeding events[31-33]. Despite lack of coagulation data, we found no difference in the variation of PLT and HGB between the TGC monotherapy and TGC-CPS combination group, and no bleeding events occurred in our retrospective study. Our study revealed that TGC-CPS treatment did not increase bleeding risk compared to TGC monotherapy. TGC was eliminated from the body through biliary excretion in the feces (59%) and urine (22%), leading to a lower prevalence of abnormal liver/kidney function[34]. It showed that the variation of ALT, TBIL, and Cr did not differ between TGC monotherapy and TGC combination with CPS therapy groups, indicating without increasing liver/kidney adverse events rates for combination treatments. In general, TGC plus CPS therapy would significantly reduce inflammation levels for patients with HAP infected by CRAB, not increasing adverse effects in clinics. The several limitations of our study were as follows. Firstly, it was a retrospective study with small sample sizes and high risks of bias. Secondly, subcenters had missed details such as subjective symptoms, pulmonary signs, imaging, microbiological, and coagulation data, affecting the assessment of treatment efficacy, which were not in our analysis. Conclusion The mortality associated with the severity of patient condition and TGC dose for patients with CRAB HAP. HDT combined with CPS was the prior treatment option for patients with CRAB HAP who were elderly, had ICU admission, and used MV. What was more significant, the TGC plus CPS combination group significantly could reduce inflammation levels, and different antimicrobiotical regiments had similar safety in liver/kidney/coagulation. It is the first study to compare the clinical outcomes and safety of TGC in monotherapy or combination with CPS therapy for CRAB infections. Considering high rates of mortality and the lack of effective treatment options for CRAB infection, we feel that there is an emerging need to be further confirmed in greater sample prospective studies for our results. Declarations Acknowledgements Funding This research was supported by grants from Beijing Medical Award Foundation (grant number: 2019-1002 and grant number: YXJL-2021-0385), and National High Level Hospital Clinical Research Funding (grant number: 2022-PUMCH-B-043). Contribution XT T acquired the data, drafted and revised the manuscript. ZY L and LZ designed the study, provided supervision and critically revised the manuscript. All authors approve the final version of the manuscript and agree to be accountable for all aspects of the study. Ethics approval and consent to participate This study was approved by Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College (Protocol No. JS-3029B) and has been performed in accordance with the ethical standards laid down in "Declaration of Helsinki 1964" and its later amendments or comparable ethical standards. Our multicenter study used only one ethics committee; as the content and procedure were based on muticenter research. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. References Yin K, Liu L, Fan G (2022) Classification and Drug Resistance Analysis of Pathogenic Bacteria in Patients with Bacterial Pneumonia in Emergency Intensive Care Unit. 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Adv Ther 37(3):1049–1064 Tables Table 1 Characteristics of Patients with CRAB HAP Receiving TGC Monotherapy and TGC Combined with CPS Therapy Characteristics TGC n = 95 TGC + CPS n = 85 P value Gender, male, n (%) 65(68.4) 63(74.1) 0.4 Age/years (IQR) 65(56.5,76) 73(63,85) 0.009 Age/years, n (%) <65 45(47.4) 27(31.8) 0.033 ≧65 50(52.6) 58(68.2) BMI (M±SD) 21.6(20.1,24.4) 23.0(21.3,24.8) 0.049 BMI, n (%) <24 69(72.6) 55(64.7) 0.433 [24,27.9] 21(22.1) 26(30.6) ≧28 5(5.3) 4(4.7) CCI score (IQR) 1(0,2) 2(1,4) 0.002 CCI score, n (%) <2 50(52.6) 33(38.8) 0.064 ≧2 45(47.4) 52(61.2) SOFA score (IQR) 5(4,9) 9(6,11) 0.000 SOFA acore, n (%) <7 61(64.2) 23(27.1) 0.000 ≧7 34(35.8) 34(62,72.9) ICU admission, n (%) 54(56.8) 78(91.8) 0.000 MV, n (%) 43(45.3) 74(87.1) 0.000 CRRT, n (%) 5(5.3) 22(25.9) 0.000 Shock, n (%) 33(34.7) 49(57.6) 0.002 Abbreviations : BMI, Body Mass Index; CCI, Charlson comorbidity index; SOFA, Sequential Organ Failure Assessment; ICU, ntensive care unit; MV, Mechanical Ventilation; CRRT, Continuous Renal Replacement Therapy. Table 2 The Clinical Outcome and Adverse Effect of TGC Monotherapy and TGC Combined with CPS Regimens Variable Before PSM P value After PSM P value TGC n = 95 TGC + CPS n = 85 TGC n = 35 TGC + CPS n = 35 Baseline(IQR) WBC, ×10 9 /L 26.8(22,35) 18.7(16,22.4) 0.000 20.4±6.4 20.5±7.5 0.975 CRP, mg/dL 70.9(45.9,120) 139(93,198) 0.127 68(26,214.8) 139(86.5,245.9) 0.097 PCT, ng/mL 4.97(3.9,11.4) 3.4(0.6,18.8) 0.004 5.4(2.2,11.0) 3(0.6,20.9) 0.452 ALT, U/L 8.9(7.9,12) 18.4(9,32) 0.017 11(7.6,35) 16(9,28) 0.851 TBIL, μmol/L 1.3(1.2,2.5) 4.3(1.8,7.2) 0.000 2.5(1.2,11.8) 2.2(1.7,5.4) 0.991 Cr, μmol/L 64(54,67.4) 48(38,71) 0.146 55(42.5,66.2) 45(38.2,73.5) 0.551 Hb, g/L 96(90,106) 116(101,127) 0.007 116.5±25.2 121.2±24.1 0.435 PLT,×10 9 /L 301(144,345) 323(266,410) 0.045 326.6±152.5 296.3±126.9 0.370 Variation (IQR) WBC, ×10 9 /L 9(3.7,11.6) 7.5(4.1,9.9) 0.726 7.3(4.6,10.0) 7.8(5.5,12.3) 0.466 CRP, mg/dL 46(14,70) 85(16,127.2) 0.003 22.6(9.5,71) 88.2(36.2,152) 0.009 PCT, ng/mL 2.8(1.7,7) 2.4(0.8,7.0) 0.009 1.95(1.02,6.62) 2.44(0.42,14.3) 0.934 ALT, U/L 25.8(12.1,38.1) 27.3(8.7,52) 0.851 35(23.5,61.7) 20(6,37.5) 0.114 TBIL, μmol/L 0.2(0.14) 2.4(0.8,7.0) 0.000 1.18(0.18,8.4) 1(0.3,3.5) 0.643 Cr, μmol/L 96(42,125) 25.1(12,59) 0.001 52(31.5,111) 132(68.5,223) 0.366 Hb, g/L 16(12,21) 16(7,26) 0.472 16(9.5,25) 18(7,26) 0.533 PLT, ×10 9 /L 80(75,110) 132(55,220) 0.004 84(72,110) 132(68.5,223) 0.175 LOS, days (IQR) 26(21,41) 30(20,42) 0.627 31(20.5,50.5) 35(23,44.5) 0.869 Thirty,Mortality,N(%) (6,6.3) (14,16.5) 0.03 (2,5.7) (7,20) 0.153 Ninety,Mortality,N(%) (15,15.8) (22,25.9) 0.094 (6,17.1) (10,28.6) 0.255 Abbreviations : WBC, white blood cell; CRP, C-reactive protein; PCT,procalcitonin; ALT, alanine aminotransferase; TBIL, total bilirubin; Cr, creatinine; Hb, hemoglobin; PLT, procalcitonin; LOS, length of hospital stays. Table 3 Risk Factors for Patients with TGC plus CPS Therapy Variable Multivariable Analysis OR (95% CI) P value age 1.083 (1.018-1.152) 0.011 BMI 1.225 (0.951-1.578) 0.117 CCI score 1.009 (0.595-1.713) 0.972 SOFA score 1.123 (0.843-1.496) 0.427 ICU admission 12.801 (1.980-82.747) 0.007 MV 1.340 (0.145-12.358) 0.796 CRRT 14.404 (0.498-416.385) 0.120 Shock 1.051 (0.241-4.581) 0.947 WBC 0.877 (0.784-0.982) 0.023 CRP 1.004 (0.997-1.011) 0.255 PCT 1.013 (0.983-1.044) 0.399 ALT 1.027 (0.989-1.066) 0.167 TBIL 0.913 (0.821-1.014) 0.089 Cr 0.998 (0.979-1.018) 0.871 Hb 0.951 (0.904-0.999) 0.047 PLT 1.001 (0.996-1.007) 0.679 Abbreviations : BMI, Body Mass Index; CCI, Charlson comorbidity indexi; SOFA, Sequential Organ Failure Assessment; ICU, ntensive care unit; MV, Mechanical Ventilation; CRRT, Continuous Renal Replacement Therapy; WBC, white blood cell; CRP, C-reactive protein; PCT,procalcitonin; ALT, alanine aminotransferase; TBIL, total bilirubin; Cr, creatinine; Hb, hemoglobin; PLT, procalcitonin. Table 4 Analysis of the Risk Factors for 30-Day and 90-Day Mortality in Patients with CRAB HAP Variable 30-day mortality Cox regression 90-day mortality Cox regression Univariate Multivariate Univariate Multivariate OR(95% CI) P value OR(95% CI) P value OR(95% CI) P value OR(95% CI) P value Gender,male, n (%) 1.356 (0.541-3.399) 0.516 0.968 (0.478-1.961) 0.927 Age, years 1.023 (0.992-1.054) 0.144 - 0.521 1.025 (1.002-1.049) 0.030 - 0.151 BMI 0.93 (0.821-1.052) 0.249 0.962 (0.884-1.046) 0.365 CCI score 1.208 (1.022-1.429) 0.027 - 0.271 1.186 (1.038-1.356) 0.012 - 0.268 SOFA score 1.290 (1.144-1.454) 0.000 - 0.470 1.270 (1.158-1.393) 0.000 - 0.156 ICU admission 33.216(0.515-2144.2) 0.099 - 0.110 2.882 (1.020-8.138) 0.046 - 0.194 MV 37.902(0.742-1936.0) 0.070 - 0.157 7.186(1.725-29.933) 0.007 - 0.086 CRRT 6.398 (1.874-21.847) 0.003 - 0.979 2.963 (1.482-5.926) 0.002 - 0.550 Shock 2.388(0.918-6.217) 0.074 18.845(2.484-142.935) 0.005 5.704(2.378-13.682) 0.000 15.690(3.672-67.053) 0.000 WBC 0.941(0.882-1.003) 0.061 - 0.568 0.960(0.917-1.005) 0.081 - 0.834 CRP 1.0 (0.994-1.006) 0.980 - 1.002(0.998-1.007) 0.270 PCT 0.997(0.983-1.011) 0.655 - 0.998(0.991-1.005) 0.599 ALT 0.982(0.944-1.021) 0.362 - 0.982(0.956-1.008) 0.178 TBIL 1.008(0.999-1.018) 0.090 - 0.923 1.008(1.002-1.015) 0.014 - 0.472 Cr 1.005(0.996-1.014) 0.255 - 1.003(0.995-1.010) 0.476 Hb 0.990(0.946-1.035) 0.647 - 0.986(0.954-1.019) 0.394 PLT 0.995(0.991-0.999) 0.014 0.995(0.991-0.999) 0.017 0.994(0.991-0.997) 0.000 0.994 (0.991-0.997) 0.000 TGC+CPS 2.615(1.004-6.808) 0.049 - 0.114 1.603(0.831-3.090) 0.159 2.934 (1.104-7.802) 0.031 Abbreviations : BMI, Body Mass Index; CCI, Charlson comorbidity indexi; SOFA, Sequential Organ Failure Assessment; ICU, ntensive care unit; MV, Mechanical Ventilation; CRRT, Continuous Renal Replacement Therapy; WBC, white blood cell; CRP, C-reactive protein; PCT,procalcitonin; ALT, alanine aminotransferase; TBIL, total bilirubin; Cr, creatinine; Hb, hemoglobin; PLT, procalcitonin;TGC, Tigecycline; CPS, Cefoperazone/Sulbactam. Additional Declarations No competing interests reported. Supplementary Files Supplementarymaterials.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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Lin","email":"","orcid":"","institution":"Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jing","middleName":"","lastName":"Lin","suffix":""},{"id":284878301,"identity":"14474524-8f21-46c9-b133-d3b2cd2e262d","order_by":2,"name":"Menglan Zhou","email":"","orcid":"","institution":"Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Menglan","middleName":"","lastName":"Zhou","suffix":""},{"id":284878302,"identity":"f62a4ed3-d5f8-4a11-8a99-cec5b8e62bcd","order_by":3,"name":"Ying Ge","email":"","orcid":"","institution":"Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Ying","middleName":"","lastName":"Ge","suffix":""},{"id":284878303,"identity":"bdb9723f-9806-4a1c-af65-ef99e6a9dd7d","order_by":4,"name":"Taisheng Li","email":"","orcid":"","institution":"Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Taisheng","middleName":"","lastName":"Li","suffix":""},{"id":284878305,"identity":"68409bb3-ec51-4c19-ab67-21e5ace3d4f8","order_by":5,"name":"Li Zhang","email":"","orcid":"","institution":"Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Li","middleName":"","lastName":"Zhang","suffix":""},{"id":284878307,"identity":"4f7183cb-f903-4bab-a303-deeabc83f7da","order_by":6,"name":"ZhengyL Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAp0lEQVRIiWNgGAWjYBACPmYGBiCyAbHZiNPCBtGSRooWBrCWw6RoYecx/lzYdj7P4NrhZw8Yau4Q4zAeA+OZbbeLDW6nmRswHHtGnJZk3rbbiRtu57BJMDYcJk7LYd62c6RpMWzmbTtAkha2Ymaec8nFkrfTzCQSjhGhhZ//8ObPPGV2eXy3k59JfKghQgsYMLIxJIAZCURqAII/pCgeBaNgFIyCEQcALrwyRHx7G0AAAAAASUVORK5CYII=","orcid":"","institution":"Department of Infectious Disease, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College","correspondingAuthor":true,"prefix":"","firstName":"ZhengyL","middleName":"","lastName":"Liu","suffix":""}],"badges":[],"createdAt":"2024-03-27 14:18:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4176720/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4176720/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53878131,"identity":"2bc879b5-d6ea-4704-abd8-386a5381e62e","added_by":"auto","created_at":"2024-04-01 16:59:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":147104,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of parients with CRAB HAP\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4176720/v1/0231c099ca89ebe250026dc1.png"},{"id":53878130,"identity":"00ae0e6e-649d-4f5d-8752-752312d8f187","added_by":"auto","created_at":"2024-04-01 16:59:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":50492,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ea\u003c/strong\u003e 30-Day Survival Curve of Patients with CRAB HAP\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eb \u003c/strong\u003e90-Day Survival Curve of Patients with CRAB HAP\u003c/p\u003e","description":"","filename":"floatimage26.png","url":"https://assets-eu.researchsquare.com/files/rs-4176720/v1/69f67341ae54c77f10b6d6a7.png"},{"id":54003412,"identity":"ff48b4b5-fab1-4d56-9b8d-055faec25104","added_by":"auto","created_at":"2024-04-03 08:55:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":625615,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4176720/v1/d736a963-571e-41f2-a52f-e31a12c424db.pdf"},{"id":53879209,"identity":"877bfe86-cc4a-4f2e-8521-fa0acea71bfa","added_by":"auto","created_at":"2024-04-01 17:07:07","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":50888,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.docx","url":"https://assets-eu.researchsquare.com/files/rs-4176720/v1/c7ab5aa2d7c40d68178e8bb1.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Clinical Outcomes and Safety of Tigecycline in Monotherapy or Combination with Cefoperazone/sulbactam for Carbapenem-Resistant Acinetobacter baumannii-Associated Pneumonia: A Multicenter Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe gram-negative bacilli [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] were primary pathogens of HAP in our country, among which AB [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] was the most common, accounting for 25.6%. AB was limited in the availability of antimicrobial agents, due to increasing resistance to various antibiotics, especially carbapenems, as well as had the ability to survive long-term in vitro, which spread widely in the hospital. Besides, the conditions for patients with AB infections were severe, resulting in longer lengths of hospital stay (LOS), more medical costs, and worse prognosis[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It was why AB, as a priority on the global priority list for research and development of new antibiotics, has been classified by the World Health Organization(WHO) [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Accordingly, AB infection has long become a focus issue of global public health, bringing a heavy challenge to the safety of the international medical and health environment. It was critical to strengthen surveillance and control AB spread.\u003c/p\u003e \u003cp\u003eIn 2020, Chen CH et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] conducted a study on the in vitro activity of multiple antimicrobials against AB in the Asia-Pacific region, including novel β-lactam combination agents, TGC and colistin, which showed that drug-resistant strains of AB in China exceeded 70.0%, being third only after South Korea and India. According to the China Antimicrobial Surveillance Network (CHINET) continuous drug resistance monitoring program in 2021, it was also reported that among clinical isolates of CRAB amounted to 71.5% [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], a rising trend over the years. Although CRAB had greater than 88.0% susceptibility to polymyxin B and tigecycline [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], which were considered the last resource antibiotics currently used in CRAB infection, a superior treatment for CRAB infection is still a matter of debate. For severe CRAB infections, TGC monotherapy may lead to higher mortality, especially in the case of bacteremia or pneumonia[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. According to the Infectious Diseases Society of America (IDSA) guidelines and the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for AMR treatment for the antimicrobial resistance (AMR) treatment, as well as 2023 IDSA Guidelines for the treatment of drug-resistant gram-negative bacterial infections, which were recommended that patients with severe CRAB infections should receive a combination of at least two in vitro active drugs[\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Moreover, it also mentioned that ampicillin-sulbactam combined with TGC or cefiderocol was the preferred treatment for CRAB-associated pneumonia. Likewise, the Chinese Expert Consensus on Diagnosis, Treatment, Prevention, and Control of AB Infections also proposed that the two-drug combination therapy for CRAB was suggested sulbactam compound (or sulbactam)-based, with CPS being the mainly used in China [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], followed by polymyxin E and TGC. However, colistin with additional antibacterial agents was associated with a higher risk of nephrotoxicity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Even both TGC-based combination therapy and polymyxin-based combination therapy are equally preferable for the treatment of pulmonary infection caused by CRAB.\u003c/p\u003e \u003cp\u003eHowever, there are currently only well-controlled, unsampled clinical case studies or case reports regarding the treatment of AB pneumonia with TGC, which had low quality of evdience monotherapy or combination therapy [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and there remains a need for further validation concerning the clinical efficacy and safety of regimens. Therefore, it is essential and of significant clinical value to explore the treatment of CRAB-infected patients with hospital-acquired pneumonia based on different doses of TGC in monotherapy or combination with CPS.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and patients population\u003c/h2\u003e \u003cp\u003eWe performed a multicenter retrospective study in 62 hospitals in China from October 2019 to June 2021. We selected 180 hospitalized adult patients with CRAB pneumonia who received either TGC monotherapy or combination with CPS.\u003c/p\u003e \u003cp\u003eThe inclusion criteria were as fllowed: (1) patients were infected with CRAB HAP; (2) patients who received either TGC monotherapy or combined with CPS. The exclusion criteria included the following: (1) pathogenic bacteria other than CRAB; (2) pathology not derived from sputum or BALF; (3) treatment for fewer than two days [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. \u003cb\u003e(\u003c/b\u003eFigs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eThe collected data were as follows: demographic characteristics (Gender, Age, BMI), history of chronic illness (Charlson comorbidity index score, CCI), the severity of the condition (Sequential Organ Failure Assessment score, SOFA), comorbid conditions (septic shock), intensive care unit (ICU) admission, Mechanical Ventilation (MV), Continuous Renal Replacement Therapy (CRRT), laboratory findings, and follow-up.\u003c/p\u003e \u003cp\u003eThe primary clinical outcome was defined as all-cause 30/90-day mortality.\u003c/p\u003e \u003cp\u003eThe secondary outcomes included length of hospital stays (LOS), variations in white blood cell (WBC), C-reactive protein (CRP), and procalcitonin (PCT) within 1 week of antibiotic use.\u003c/p\u003e \u003cp\u003eTo assess the incidence of adverse events, we calculated the variation in ALT/TBIL/Cr/PLT/Hb( maximum minus minimum of alanine aminotransferase (ALT)/total bilirubin (TBIL)/creatinine (Cr)/platelet (PLT)/ hemoglobin (Hb)within 1 week of antibiotic use).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDefinitions\u003c/h2\u003e \u003cp\u003ePneumonia caused by CRAB was defined as clinical evidence of HAP with a qualified sample positive for CRAB [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePatients were treated with an intravenous 100mg dose, followed after 12 h by a maintenance dose of 50 mg every 12 hours, defined as Standard-dose-TGC(SDT), while High-Dose-TGC(HDT) was an initial dose of 200 mg followed by 100 mg every 12 hrs(q12h). Cefoperazone/Sulbactam(cefoperazone: sulbactam, 1:1/ 2:1) at a dose of 6-9g administered intravenously one day.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eAll statistical analyses were performed using SPSS software (version 26.0). Continuous variables were assessed for normality with the Shapiro-Wilk test. The data that conformed to normal distribution were presented as the mean and standard deviation (SD) and analyzed using a t-test. Otherwise, data would be presented as the median and interquartile range (IQR) with the Mann-Whitney U test. Categorical Data were presented as the number and proportions (%). The chi-square test or Fisher's exact test was used to test comparisons between groups for categorical variables. The relative efficacies and adverse effects of the different antimicrobial regimens were assessed by conducting propensity score matching (PSM). Multi-logistic regression analysis and ROC curves were used to predict the independent risk factors for different antibiotic regiments. The Kaplan-Meier product-limit method was used to estimate the survival distribution function. The predictors of 30-day and 90-day mortality for CRAB Pneumonia were identified using Cox regression analysis. \u003cem\u003eP\u003c/em\u003e values less than 0.05 were considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eWe included data from 180 patients with CRAB HAP and analyzed their characteristics, including 95 receiving TGC monotherapy, and 85 receiving TGC combined with CPS therapy.\u003c/p\u003e\n\u003cp\u003ePatients with TGC monotherapy were defined as the control group, and TGC combined with CPS therapy as the observation group. The age(73(63,85) vs 65(56.5,76) , \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.009)、BMI (23.0(21.3,24.8) vs 21.6(20.1,24.4), \u003cem\u003eP\u003c/em\u003e = 0.049)、CCI score(2(1,4)vs1(0,2),\u003cem\u003eP\u003c/em\u003e = 0.002)、SOFA score(9(6,11)vs5(4,9), P = 0.000) were significantly higher in observation group. In subsequent analysis, a significant increase was found in patients receiving TGC plus CPS combination compared to those with TGC monotherapy, including the SOFA score \u0026ge;7(72.9% vs 35.8%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.000) and \u0026ge;65yr(68.2% vs 52.6%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.033); however, there were no significant differences in the BMI subgroup(\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05). The ICU admission, used MV, and CRRT rates of patients given TGC with CPS were also higher than that of patients given TGC monotherapy (91.8% vs 56.8%, 87.1% vs 45.3%, 25.9% vs 5.3%; respectively, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.000). Additionally, a similar difference was noticed in the incidence of shock (57.6% vs 34.7%, \u003cem\u003eP\u003c/em\u003e = 0.002). \u003cstrong\u003e(Table 1)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was a significant difference in the primary outcomes of all-cause 30-day mortality when comparing TGC monotherapy and TGC combined with CPS therapy ( 6.3% vs 16.5%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.03). Additionally, the all-cause 90-day mortality of patients receiving TGC combined with CPS regimen was also higher; however, no statistical difference was observed (25.9% vs 15.8%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.094). Despite these circumstances, the LOS was similar in both two groups (26(21,41) vs 30(20,42), \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.627). The PSM was performed to adjust the WBC, PCT, ALT, TBIL, Hb, and PLT; it demonstrated that TGC plus CPS therapy was superior to those with TGC monotherapy in reducing CRP level(88.2(36.2,152) vs 22.6(9.5,71), \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.009). Furthermore, TGC plus CPS therapy did not differ in adverse effects when compared to TGC monotherapy(\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05).\u003cstrong\u003e\u0026nbsp;(Table 2)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe multivariate logistic regression analysis revealed that independent risk factors associated with TGC plus CPS therapy included age [\u003cem\u003eP\u003c/em\u003e = 0.011; odds ratio, OR(95% CI): 1.083 (1.018\u0026ndash;1.152)], ICU [\u003cem\u003eP\u003c/em\u003e = 0.007; OR(95% CI): 12.801 (1.980\u0026ndash;82.747)], WBC [\u003cem\u003eP\u003c/em\u003e = 0.023; OR(95% CI): 0.877 (0.784\u0026ndash;0.982)], and Hb [\u003cem\u003eP\u003c/em\u003e = 0.047; OR(95% CI): 0.951 (0.904\u0026ndash;0.999)] (\u003cstrong\u003eTable 3\u003c/strong\u003e), with the AUC of 0.931 and 95% confidence interval of 0.887-0.975. The validation of this risk model demonstrated that the model had good prediction ability. In addition, the cut-off value was 0.3, and the sensitivity and specificity were 100% and 75.4%, respectively (\u003cstrong\u003eSupplementary Figure 1\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003eA significant increase in the all-cause 30-day mortality (X\u003csup\u003e2\u003c/sup\u003e=4.202, \u003cem\u003eP=\u003c/em\u003e0.04) in patients with CRAB HAP receiving TGC with CPS, according to the Kaplan-Meier survival curve(\u003cstrong\u003eFigures 2a\u003c/strong\u003e). The 90-day mortality of patients receiving TGC with CPS was also higher than that of patients with TGC monotherapy; however, the difference was not significant \u003cstrong\u003e(Figures 2b)\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eThe multivariate Cox regression analysis showed that shock and PLT were independent predictors of 30-day and 90-day mortality (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.05). After adjusting for confounding factors, it revealed that TGC with CPS therapy was also an independent predictor of the 90-day mortality[\u003cem\u003eP\u003c/em\u003e = 0.031, HR (95% CI): 2.934(1.104\u0026ndash;7.802)]. The data were presented in \u003cstrong\u003eTable 4\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003eWe included data from 43 receiving SDT and 52 receiving\u0026nbsp;HDT monotherapy. Similar baseline characteristics were shown between both groups, including gender、age、BMI、CCI score、SOFA score, ICU stay, MV, CRRT, and shock(\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05). (\u003cstrong\u003eSupplementery Table 1\u003c/strong\u003e)\u003c/p\u003e\n\u003cp\u003eThere was no significant difference between primary and secondary outcomes in those patients(\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05). Regarding adverse events, the variation of ALT, TBIl, Cr, Hb, and PLT was not statistically significant when comparing the SDT and HDT groups(\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05). (\u003cstrong\u003eSupplementery Table 2\u003c/strong\u003e)\u003c/p\u003e\n\u003cp\u003eWe included data from 59 receiving SDT with CPS, and 26 receiving HDT with CPS. Some baseline characteristics in both groups were similar, including gender, age, BMI, CCI score, SOFA score, ICU stay, CRRT, and shock (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05); however, the used MV was higner in the SDT combined with CPS group (93.2% vs 73.1%, \u003cem\u003eP\u003c/em\u003e = 0.028). In subsequent analysis, the BMI≧28\u0026nbsp;of patients was significantly lower rate in the SDT combined with\u0026nbsp;CPS group\u0026nbsp;(0% vs 15.4%, \u003cem\u003eP\u003c/em\u003e = 0.006); however, The SOFA score≧7 for patients in SDT\u0026nbsp;combined with\u0026nbsp;CPS\u0026nbsp;was higher than it was for those in HDT\u0026nbsp;combined with\u0026nbsp;CPS (81.4% vs 53.8%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.009). (\u003cstrong\u003eSupplementery Table 3\u003c/strong\u003e)\u003c/p\u003e\n\u003cp\u003eNo significant difference was found between\u0026nbsp;the SDT and HDT\u0026nbsp;combined with\u0026nbsp;CPS groups\u0026nbsp;in primary and secondary outcomes (\u003cem\u003eP\u003c/em\u003e \u0026gt; 0.05). Similarly, the variation of ALT、TBIl、Cr、Hb、PLT were not statistically significant in terms of adverse events(\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05).\u0026nbsp;(\u003cstrong\u003eSupplementery Table 4\u003c/strong\u003e)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCRAB HAP has become a challenging clinical dilemma worldwide due to its high antimicrobial resistance, limited availability of regimens, and high mortality[18]. There were controversial treatments for patients with CRAB HAP, according to previous research. We summarized the clinical features, treatment effectiveness, and safety of various TGC doses in monotherapy or combined with CPS treatment for CRAB pneumonia. Moreover, we evaluated the independent predictors of all-cause 30/90-day mortality and risk factors of different antibiotic regimens in patients with CRAB pneumonia. The followings were the primary findings of this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe found a significant increase in all-cause 30/90-day mortality in TGC plus CPS therapy, which was an independent predictor of all-cause 90-day mortality following adjustment of compound factors. Meanwhile, we noticed that shock was significantly associated with 30-day and 90-day mortality. Notably, patients receiving TGC with CPS therapy were significantly superior to those with TGC monotherapy in reducing CRP levels; however, similar safety was shown in different antimicrobial regimens, including liver/kidney/coagulation. The subgroup analysis indicated that HDT combined with CPS therapy was a prior treatment option for patients with CRAB HAP who were the older age, ICU admissions particularly. In addition, the primary and secondary outcomes were similar in SDT and HDT monotherapy or combination with CPS therapy group. It first demonstrated the difference between TGC monotherapy and TGC combined with CPS in large-scale real-world data to offer the optimal drug regimens for CRAB HAP in the clinic.\u003c/p\u003e\n\u003cp\u003eOur research showed that TGC combined with CPS treatment had different clinical features when compared to TGC monotherapy for CRAB HAP. Patients with TGC plus CPS therapy had significantly higher rates than those with TGC monotherapy with a history of hospital exposure, including ICU admission, used MV and CRRT. In addition, multivariate logistic regression analysis showed that older age and ICU admission were independent risk factors for TGC plus CPS treatment for CRAB HAP. ICU patients were usually critically ill and immunocompromised, most of whom underwent invasive operations, which therefore increased the chance of contracting CRAB. However, in our study, invasive operations were not an independent risk factor for receiving tigecycline combined with cefoperazone sulbactam therapy. This might be because almost all patients experienced invasive practices during their hospitalization in the ICU, and some patients had more than one simultaneously installed invasive device. Thus, these factors could interfere with and influence each other. In conclusion, the treatment regimen for patients in the combination therapy group is under guideline and expert consensus recommendations [9-11], and the TGC in combination with CPS therapy is the preferred treatment for infections in patients with severe CRAB.\u003c/p\u003e\n\u003cp\u003eWe observed an increase in the all-cause 30/90 mortality (16.5% VS 6.3%, \u003cem\u003eP\u003c/em\u003e=0.03; 25.9% VS 15.8%, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.094; respectively) in patients receiving TGC-CPS combination therapy in comparison to TGC monotherapy; however, the difference in 90-day mortality was not significant. The further multivariate Cox regression demonstrated that shock and TGC-CPS combination treatment were independent predictors of 30/90 mortality and 90-day mortality, respectively. Attributing to older age (73 VS 65, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.009) and more comorbidities among TGC with CPS treatment of patients with CRAB HAP, who had a worse condition and more susceptible to multiple organ failure and septic shock, after severe infections, resulting in higher SOFA scores(9 (6, 11) VS 5 (4, 9), \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.000) and mortality. Although we noticed that Food and Drugs Administration (FDA)-approved indications were only for cIAI, cSSSI, and CAP, not including HAP, due to ascended multidrug-resistant infections, TGC had been widely used for non-approved indications, among whom used in research related to CRAB HAP accounted for 1/3 [8]. A previous meta-analysis of 5 trials [19] analyzed the prognosis of patients with CRAB HAP receiving TGC monotherapy compared to those with TGC combination, no significant difference was from two prospective cohort studies (OR\u0026thinsp;=\u0026thinsp;2.22, 95% CI 0.79\u0026ndash;6.20, \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.13). Except for in-hospital mortality, Li Y et al. [20] found that regimens containing TGC-CPS combination therapy patients with CRAB HAP were not superior to those with TGC monotherapy in clinical and microbiological efficacies. However, we only found in some laboratory findings that patients with TGC plus CPS therapy had higher CRP decline compared with TGC monotherapy, which indicated better outcomes in reducing inflammatory response, consistent with previous results[21]. Therefore, the efficacy of patients with CRAB HAP receiving TGC monotherapy or combination regimens was controversial.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn addition, the mortality and efficacy of various doses of TGC monotherapy were also unclear [22,23]. As a previous Systematic Review and Meta-Analysis[24] reported, although the microbiological eradication rate in those given HDT did not differ from SDT monotherapy for CR pathogens (OR 1.07, 95% CI 0.44-2.60, P = 0.87), mortality was reduced（OR 0.20，95% CI 0.09-0.45，p = 0.0001). And Shields RK [25] also found that HDT combined with in-vitro active antibiotics in improving prognosis was superior to SDT. Accordingly, we supposed that the high mortality in patients with severe infection might be related to tigecycline dose. In our study, subgroup analysis showed that mortality and laboratory findings of infections in SDT and HDT monotherapy or combination were no statistical difference, although lack of microbiological data. Notably, the 30/90-day mortality and SOFA scores in patients receiving SDT with CPS were also higher than those receiving HDT with CPS, which indicated that more severe infection occurred in patients with SDT combination CPS. TGC, as a bacteriostatic agent, inevitably resulted in delayed bacterial clearance and higher mortality when the organism had severely infection, if the concentration of the drug in the tissues was low and the bacteriostatic activity was descend. The difference in mortality between the two groups of patients in this study was not statistical significant, which may be due to insufficient sample size. Accordingly, There is a great need for well-designed studies to evaluate the effectiveness of various doses of TGC in monotherapy when compared to combination therapies.\u003c/p\u003e\n\u003cp\u003eOn the other hand, the safety needed to be taken into consideration when prescribing TGC or CPS. TGC[26,27] and CPS[38-30]could cause coagulation disorders, raising safety concerns. Besides, severe infection could lead to coagulation factors and PLT heavier consumption, and bleeding events occurred commonly. Notably, there was controversy about whether TGC-CPS combination treatment would increase bleeding events[31-33]. Despite lack of coagulation data, we found no difference in the variation of PLT and HGB between the TGC monotherapy and TGC-CPS combination group, and no bleeding events occurred in our retrospective study. Our study revealed that TGC-CPS treatment did not increase bleeding risk compared to TGC monotherapy. TGC was eliminated from the body through biliary excretion in the feces (59%) and urine (22%), leading to a lower prevalence of abnormal liver/kidney function[34]. It showed that the variation of ALT, TBIL, and Cr did not differ between TGC monotherapy and TGC combination with CPS therapy groups, indicating without increasing liver/kidney adverse events rates for combination treatments. In general, TGC plus CPS therapy would significantly reduce inflammation levels for patients with HAP infected by CRAB, not increasing adverse effects in clinics.\u003c/p\u003e\n\u003cp\u003eThe several limitations of our study were as follows. Firstly, it was a retrospective study with small sample sizes and high risks of bias. Secondly, subcenters had missed details such as subjective symptoms, pulmonary signs, imaging, microbiological, and coagulation data, affecting the assessment of treatment efficacy, which were not in our analysis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe mortality associated with the severity of patient condition and TGC dose for patients with CRAB HAP. HDT combined with CPS was the prior treatment option for patients with CRAB HAP who were elderly, had ICU admission, and used MV. What was more significant, the TGC plus CPS combination group significantly could reduce inflammation levels, and different antimicrobiotical regiments had similar safety in liver/kidney/coagulation. It is the first study to compare the clinical outcomes and safety of TGC in monotherapy or combination with CPS therapy for CRAB infections. Considering high rates of mortality and the lack of effective treatment options for CRAB infection, we feel that there is an emerging need to be further confirmed in greater sample prospective studies for our results.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by grants from Beijing Medical Award Foundation (grant number: 2019-1002 and grant number: YXJL-2021-0385), and National High Level Hospital Clinical Research Funding (grant number: 2022-PUMCH-B-043).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eContribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXT T acquired the data, drafted and revised the manuscript. ZY L and LZ designed the study, provided supervision and critically revised the manuscript. All authors approve the final version of the manuscript and agree to be accountable for all aspects of the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College (Protocol No. JS-3029B) and has been performed in accordance with the ethical standards laid down in \u0026quot;Declaration of Helsinki 1964\u0026quot; and its later amendments or comparable ethical standards. Our multicenter study used only one ethics committee; as the content and procedure were based on muticenter research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eYin K, Liu L, Fan G (2022) Classification and Drug Resistance Analysis of Pathogenic Bacteria in Patients with Bacterial Pneumonia in Emergency Intensive Care Unit. 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Clin Infect Dis. :ciad428\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZeng M, Xia J, Zong Z, Society of Bacterial Infection and Resistance of Chinese Medical Association; Expert Committee on Clinical Use of Antimicrobial Agents and Evaluation of Antimicrobial Resistance of the National Health Commission; Infectious Diseases Society of Chinese Medical Education Association et al (2023) Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli. J Microbiol Immunol Infect 56(4):653\u0026ndash;671\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J, Shu Y, Zhu F et al (2021) Comparative efficacy and safety of combination therapy with high-dose sulbactam or colistin with additional antibacterial agents for multiple drug-resistant and extensively drug-resistant Acinetobacter baumannii infections: A systematic review and network meta-analysis. J Glob Antimicrob Resist 24(3):136\u0026ndash;147\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTamma PD, Aitken SL, Bonomo RA et al (2022) Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum β-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis 75(2):187\u0026ndash;212\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSy CL, Chen PY, Cheng CW et al (2022) Recommendations and guidelines for the treatment of infections due to multidrug resistant organisms. J Microbiol Immunol Infect 55(3):359\u0026ndash;386\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang SH, Yang KY, Sheu CC et al (2021) Efficacies of Colistin-Carbapenem versus Colistin-Tigecycline in Critically Ill Patients with CR-GNB-Associated Pneumonia: A Multicenter Observational Study. Antibiot (Basel) 10(9):1081\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInfectology Group of Respiratory Diseases Branch of Chinese Medical Association (CMA) (2018) Guidelines for the diagnosis and treatment of hospital-acquired pneumonia and ventilator-associated pneumonia in Chinese adult hospitals (2018 edition). Chin J Tuberc Respir Dis 41:255\u0026ndash;280\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDu X, Xu X, Yao J et al (2019) Predictors of mortality in patients infected with carbapenem-resistant Acinetobacter baumannii: A systematic review and meta-analysis. Am J Infect Control 47(9):1140\u0026ndash;1145\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBai XR, Liu JM, Jiang DC et al (2018) Efficacy and safety of tigecycline monotherapy versus combination therapy for the treatment of hospital-acquired pneumonia (HAP): a meta-analysis of cohort studies. J Chemother 30(3):172\u0026ndash;178\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Xie J, Chen L et al (2020) Treatment efficacy of tigecycline in comparison to cefoperazone/ sulbactam alone or in combination therapy for carbapenenm-resistant Acinetobacter baumannii infections. Pak J Pharm Sci 33(1):161\u0026ndash;168\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDuan WW, Qin C (2023) Clinical effect of cefoperazone sulbactam combined with tegacyclin in the treatment of pan-drug-resistant acinetobacter baumannii pulmonary infection. Qingdao Med 55(2):123\u0026ndash;125\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYao F, Wang XP, Wang YF et al (2021) The clinical efficacy of high-dose tigecycline in ICU patients with pulmonary infections[J]. Pharm Today 31(6):449\u0026ndash;453\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHan H, Qin W, Zheng Y et al (2021) High-Dose versus Standard-Dose Tigecycline Treatment of Secondary Bloodstream Infections Caused by Extensively Drug-Resistant Acinetobacter baumannii: An Observational Cohort Study. Infect Drug Resist 14(9):3837\u0026ndash;3848\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu J, Yan Y, Zhang F (2021) Risk Factors for Tigecycline-Associated Hypofibrinogenemia. Ther Clin Risk Manag 17(4):325\u0026ndash;332\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShields RK, Paterson DL, Tamma PD (2023) Navigating Available Treatment Options for Carbapenem-Resistant Acinetobacter baumannii-calcoaceticus Complex Infections. Clin Infect Dis 76(5):S179\u0026ndash;S193\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLei H, Liu X, Li Z et al (2023) Analysis of the clinical characteristics of tigecycline-induced hypofibrinogenemia. J Chemother 35(4):292\u0026ndash;297\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang W, Liu Y, Yu C et al (2020) Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study. Expert Opin Drug Saf 19(3):339\u0026ndash;347\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuclu E, Kaya G, Ogutlu A et al (2020) The effect of cefoperazone sulbactam and piperacillin tazobactam on mortality in Gram-negative nosocomial infections. J Chemother 32(3):118\u0026ndash;123\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang W, Liu Y, Yu C et al (2020) Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study. Expert Opin Drug Saf 19(3):339\u0026ndash;347\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin C, Tan M, Wang D et al (2023) Safety of Tigecycline in Patients on Antithrombotic Therapy: A Single-Center Retrospective Study. Pharmacology 108(6):540\u0026ndash;549\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang L, Cai X, Peng F et al (2023) Comparison of bleeding risk and hypofibrinogenemia-associated risk factors between tigecycline with cefoperazone/sulbactam therapy and other tigecycline-based combination therapies. Front Pharmacol 14(6):1182644\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMiao W, Guo J, Cheng H et al (2023) Risk Factors for Cefoperazone/Sulbactam-Induced Coagulation Disorder. Infect Drug Resist 16(9):6277\u0026ndash;6284\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaPlante KL, Dhand A, Wright K et al (2022) Re-establishing the utility of tetracycline-class antibiotics for current challenges with antibiotic resistance. Ann Med 54(1):1686\u0026ndash;1700\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZha L, Pan L, Guo J et al (2020) Effectiveness and Safety of High Dose Tigecycline for the Treatment of Severe Infections: A Systematic Review and Meta-Analysis. Adv Ther 37(3):1049\u0026ndash;1064\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Characteristics of Patients with CRAB HAP Receiving\u0026nbsp;TGC Monotherapy and TGC Combined with\u0026nbsp;CPS\u0026nbsp;Therapy\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTGC\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u0026nbsp;\u003c/em\u003e= 95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTGC + CPS\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003en\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e= 85\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eGender, male, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65(68.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e63(74.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge/years (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e65(56.5,76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e73(63,85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eAge/years, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e45(47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e27(31.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.033\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; ≧65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e50(52.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e58(68.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBMI (M\u0026plusmn;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21.6(20.1,24.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23.0(21.3,24.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBMI, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026lt;24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e69(72.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e55(64.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.433\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;[24,27.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21(22.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e26(30.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; ≧28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5(5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e4(4.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCCI score (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1(0,2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2(1,4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCCI score, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e50(52.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33(38.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; ≧2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e45(47.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e52(61.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSOFA score (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5(4,9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e9(6,11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSOFA acore, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026lt;7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e61(64.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e23(27.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; ≧7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e34(35.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e34(62,72.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eICU admission, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e54(56.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e78(91.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMV, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e43(45.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e74(87.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCRRT, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5(5.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e22(25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eShock, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e33(34.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e49(57.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eBMI, Body Mass Index; CCI, Charlson comorbidity index; SOFA, Sequential Organ Failure Assessment; ICU, ntensive care unit; MV, Mechanical Ventilation; CRRT, Continuous Renal Replacement Therapy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e The Clinical Outcome and Adverse Effect of TGC Monotherapy and TGC Combined with CPS Regimens\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eBefore PSM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003eAfter PSM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTGC\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e = 95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTGC + CPS\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e = 85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eTGC\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e = 35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eTGC + CPS\u003c/p\u003e\n \u003cp\u003e\u003cem\u003en\u003c/em\u003e = 35\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eBaseline(IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; WBC, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e26.8(22,35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18.7(16,22.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20.4\u0026plusmn;6.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20.5\u0026plusmn;7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.975\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; CRP, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e70.9(45.9,120)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e139(93,198)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e68(26,214.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e139(86.5,245.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; PCT, ng/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.97(3.9,11.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3.4(0.6,18.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e5.4(2.2,11.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e3(0.6,20.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.452\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; ALT, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e8.9(7.9,12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18.4(9,32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e11(7.6,35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16(9,28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.851\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; TBIL, \u0026mu;mol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.3(1.2,2.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e4.3(1.8,7.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.5(1.2,11.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.2(1.7,5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.991\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; Cr, \u0026mu;mol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e64(54,67.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e48(38,71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e55(42.5,66.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e45(38.2,73.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.551\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; Hb, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e96(90,106)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e116(101,127)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e116.5\u0026plusmn;25.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e121.2\u0026plusmn;24.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.435\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp;PLT,\u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e301(144,345)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e323(266,410)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.045\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e326.6\u0026plusmn;152.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e296.3\u0026plusmn;126.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.370\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eVariation (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; WBC, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e9(3.7,11.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.5(4.1,9.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.726\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.3(4.6,10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e7.8(5.5,12.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.466\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; CRP, mg/dL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e46(14,70)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e85(16,127.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e22.6(9.5,71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e88.2(36.2,152)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; PCT, ng/mL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.8(1.7,7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.4(0.8,7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.009\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.95(1.02,6.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.44(0.42,14.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.934\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; ALT, U/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.8(12.1,38.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e27.3(8.7,52)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.851\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e35(23.5,61.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e20(6,37.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; TBIL, \u0026mu;mol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.2(0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e2.4(0.8,7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1.18(0.18,8.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e1(0.3,3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.643\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; Cr, \u0026mu;mol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e96(42,125)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e25.1(12,59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e52(31.5,111)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e132(68.5,223)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.366\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; Hb, g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16(12,21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16(7,26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.472\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e16(9.5,25)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e18(7,26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.533\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u0026nbsp; PLT, \u0026times;10\u003csup\u003e9\u003c/sup\u003e/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e80(75,110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e132(55,220)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.004\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e84(72,110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e132(68.5,223)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.175\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLOS, days (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e26(21,41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e30(20,42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e31(20.5,50.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e35(23,44.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.869\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eThirty,Mortality,N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(6,6.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(14,16.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.03\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(2,5.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(7,20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eNinety,Mortality,N(%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(15,15.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(22,25.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e0.094\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(6,17.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e(10,28.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eWBC, white blood cell; CRP, C-reactive protein; PCT,procalcitonin; ALT, alanine aminotransferase; TBIL, total bilirubin; Cr, creatinine; Hb, hemoglobin; PLT, procalcitonin; LOS, length of hospital stays.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u0026nbsp;\u003c/strong\u003eRisk Factors for Patients with TGC plus CPS Therapy\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMultivariable Analysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eOR (95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eage\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.083 (1.018-1.152)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.011\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.225 (0.951-1.578)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.117\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCCI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.009 (0.595-1.713)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.972\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eSOFA score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.123 (0.843-1.496)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.427\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eICU admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e12.801 (1.980-82.747)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.340 (0.145-12.358)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.796\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCRRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e14.404 (0.498-416.385)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.120\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eShock\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.051 (0.241-4.581)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.947\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eWBC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.877 (0.784-0.982)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.023\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCRP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.004 (0.997-1.011)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.013 (0.983-1.044)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.399\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eALT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.027 (0.989-1.066)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.167\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eTBIL\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.913 (0.821-1.014)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eCr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.998 (0.979-1.018)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.871\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.951 (0.904-0.999)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.047\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.001 (0.996-1.007)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.679\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eBMI, Body Mass Index; CCI, Charlson comorbidity indexi; SOFA, Sequential Organ Failure Assessment; ICU, ntensive care unit; MV, Mechanical Ventilation; CRRT, Continuous Renal Replacement Therapy; WBC, white blood cell; CRP, C-reactive protein; PCT,procalcitonin; ALT, alanine aminotransferase; TBIL, total bilirubin; Cr, creatinine; Hb, hemoglobin; PLT, procalcitonin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4\u003c/strong\u003e Analysis of the Risk Factors for 30-Day and 90-Day Mortality in Patients with CRAB HAP\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.224489795918368%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"43.87755102040816%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e30-day mortality Cox regression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.0408163265306123%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"42.857142857142854%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003e90-day mortality Cox regression\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"24.41860465116279%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.58139534883721%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.3255813953488373%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.25581395348837%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eUnivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"24.41860465116279%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eMultivariate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.29268292682927%\" valign=\"top\"\u003e\n \u003cp\u003eOR(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.097560975609756%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.51219512195122%\" valign=\"top\"\u003e\n \u003cp\u003eOR(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.097560975609756%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.4390243902439024%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.073170731707318%\" valign=\"top\"\u003e\n \u003cp\u003eOR(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.097560975609756%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.29268292682927%\" valign=\"top\"\u003e\n \u003cp\u003eOR(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"6.097560975609756%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eGender,male,\u003cem\u003en\u003c/em\u003e (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e1.356 (0.541-3.399)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.516\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e0.968 (0.478-1.961)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.927\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eAge, years\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e1.023 (0.992-1.054)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.144\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.521\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e1.025 (1.002-1.049)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.030\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.151\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e0.93 (0.821-1.052)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e0.962 (0.884-1.046)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.365\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eCCI score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e1.208 (1.022-1.429)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.027\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e1.186 (1.038-1.356)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.012\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eSOFA score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e1.290 (1.144-1.454)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.470\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e1.270 (1.158-1.393)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.156\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eICU admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e33.216(0.515-2144.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.099\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e2.882 (1.020-8.138)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.046\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.194\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e37.902(0.742-1936.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.070\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.157\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e7.186(1.725-29.933)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.007\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.086\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eCRRT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e6.398 (1.874-21.847)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.979\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e2.963 (1.482-5.926)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.550\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eShock\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e2.388(0.918-6.217)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.074\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e18.845(2.484-142.935)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.005\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e5.704(2.378-13.682)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n 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valign=\"top\"\u003e\n \u003cp\u003e0.980\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e1.002(0.998-1.007)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.270\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003ePCT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e0.997(0.983-1.011)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.655\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e0.998(0.991-1.005)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n 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valign=\"top\"\u003e\n \u003cp\u003e0.923\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e1.008(1.002-1.015)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.472\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eCr\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e1.005(0.996-1.014)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.255\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e1.003(0.995-1.010)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.476\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eHb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e0.990(0.946-1.035)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.647\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e0.986(0.954-1.019)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003ePLT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e0.995(0.991-0.999)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.014\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e0.995(0.991-0.999)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.017\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e0.994(0.991-0.997)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e0.994 (0.991-0.997)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.000\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"11.827956989247312%\" valign=\"top\"\u003e\n \u003cp\u003eTGC+CPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e2.615(1.004-6.808)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.049\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.204301075268816%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"2.150537634408602%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.053763440860216%\" valign=\"top\"\u003e\n \u003cp\u003e1.603(0.831-3.090)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.159\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.129032258064516%\" valign=\"top\"\u003e\n \u003cp\u003e2.934 (1.104-7.802)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"5.376344086021505%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.031\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eBMI, Body Mass Index; CCI, Charlson comorbidity indexi; SOFA, Sequential Organ Failure Assessment; ICU, ntensive care unit; MV, Mechanical Ventilation; CRRT, Continuous Renal Replacement Therapy; WBC, white blood cell; CRP, C-reactive protein; PCT,procalcitonin; ALT, alanine aminotransferase; TBIL, total bilirubin; Cr, creatinine; Hb, hemoglobin; PLT, procalcitonin;TGC, Tigecycline; CPS, Cefoperazone/Sulbactam.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tigecycline, Cefoperazone/Sulbactam, Carbapenem-Resistant Acinetobacter baumannii, Hospital Acquired Pneumonia","lastPublishedDoi":"10.21203/rs.3.rs-4176720/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4176720/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eWe aimed to evaluate clinical outcomes and safety in tigecycline (TGC) monotherapy or in combination with cefoperazone/sulbactam (CPS) treatment for patients with hospital-acquired pneumonia (HAP) infected by carbapenem-resistant Acinetobacter baumannii(CRAB).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis was a retrospective analysis of multicenter data from patients with CRAB HAP in 62 Chinese hospitals. Risk factors of receiving TGC with CPS therapy and predictors of mortality were used multivariate logistic and Cox regression analyses, respectively. Propensity score matching (PSM) evaluated the efficacies and safety of antimicrobial regimens.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003e180 patients included in our study, 95 used TGC monotherapy, and 85 used TGC with CPS therapy. The multivariate logistic regression analysis revealed that the risk factors were significantly associated with TGC with CPS therapy included the older age [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.011], intensive care unit (ICU) admission[\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.007]. The multivariate Cox regression demonstrated that there was a significantly higher risk of 90-day mortality [\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.031] among subjects in TGC-CPS group. The subgroup of patients who received Standard dose TGC (SDT) plus CPS had a significantly higher rate of SOFA score\u0026thinsp;≧\u0026thinsp;7(\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009), and the 30/90-day mortality rate of patients was also higher. The variation of ALT, TBIL, Cr, Hb, and PLT did not differ between different antimicrobial regimens after PSM.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe severity of patient conditions and TGC doses were significantly associated with mortality. HDT combined with CPS was the prior treatment option for patients with CRAB HAP who were elderly, had ICU admission. We observed that different antimicrobial regimens had similar safety in liver/kidney/coagulation.\u003c/p\u003e","manuscriptTitle":"The Clinical Outcomes and Safety of Tigecycline in Monotherapy or Combination with Cefoperazone/sulbactam for Carbapenem-Resistant Acinetobacter baumannii-Associated Pneumonia: A Multicenter Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-01 16:59:02","doi":"10.21203/rs.3.rs-4176720/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9cf8208b-0d38-4cec-a8d6-3e16d5ff378b","owner":[],"postedDate":"April 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-03T08:47:40+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-01 16:59:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4176720","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4176720","identity":"rs-4176720","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}