Outcomes of Treatment for Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia

Outcomes of Treatment for Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia | 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 Outcomes of Treatment for Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia Felipe Tuon, Ademir Salomao, Valdir Sabbaga Amato, Leticia Dantas, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9281378/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: Ventilator-associated pneumonia (VAP) due to methicillin-resistant Staphylococcus aureus (MRSA) remains a therapeutic challenge. Vancomycin is the recommended first-line therapy; however, trimethoprim-sulfamethoxazole (SMX-TMP) presents a potential alternative due to its pharmacokinetic properties and cost-effectiveness. Clinical data supporting its use in VAP are limited. The aim of this study was to compare the clinical outcomes of patients with MRSA-VAP treated with SMX-TMP versus vancomycin. Methods: We conducted a retrospective, single-center, cross-sectional study between January 2020 and July 2021 at a tertiary academic hospital in southern Brazil. Adult patients with confirmed MRSA-VAP and documented susceptibility to both SMX-TMP and vancomycin were included. The primary outcome was in-hospital mortality. Secondary outcomes included clinical response at day 5, ICU and hospital length of stay, and VAP duration. Statistical comparisons were made using chi-square and t-tests, with significance set at p < 0.05. Results: A total of 125 patients were analyzed (vancomycin: n=60; SMX-TMP: n=65). Mortality was 37% in the vancomycin group versus 28% in the SMX-TMP group ( p = 0.285). Clinical cure at day 5 was similar (52% vs. 55%, respectively). No significant differences were observed in SOFA scores, ICU or hospital stay, or VAP duration between groups. Conclusion: SMX-TMP was associated with clinical outcomes comparable to vancomycin in patients with MRSA-VAP. These findings suggest SMX-TMP may represent a viable therapeutic alternative in selected patients. Further prospective studies are warranted to validate its role in this context. Staphylococcus aureus ventilator-associated pneumonia trimethoprim-sulfamethoxazole vancomycin antimicrobial therapy Take-Home Message Trimethoprim-sulfamethoxazole achieved clinical outcomes comparable to vancomycin for MRSA ventilator-associated pneumonia in a real-world cohort, with similar mortality, early clinical response, and resource use. These findings add to the limited clinical evidence on SMX-TMP for MRSA pneumonia and support its consideration as a pragmatic therapeutic alternative in carefully selected patients, especially in resource-constrained settings. Introduction Staphylococcus aureus is a Gram-positive, coagulase-positive coccus associated with a wide range of infections, including bacteremia, infective endocarditis, osteomyelitis, pneumonia, arthritis, and skin infections 1, 2 . The rise in antimicrobial resistance has made treatment increasingly challenging (1). Multiple studies conducted in different regions of the world demonstrate that these infections are a significant cause of hospital morbidity and mortality, consuming substantial healthcare resources 3 . The clinical use of beta-lactams led to the emergence of methicillin-resistant S. aureus (MRSA), which involves alterations in penicillin-binding proteins (PBPs), rendering the bacterium broadly resistant to beta-lactams 4 . Many countries have experienced a substantial rise in MRSA infections, with important geographic variations—low prevalence in Scandinavia and high rates in Latin American and Asian countries 5 . Despite the significant attention given to MRSA, infections caused by methicillin-susceptible S. aureus (MSSA) continue to have a major impact (5). Mortality rates for S. aureus bacteremia remain high, with little progress achieved over recent decades 6 . The use of beta-lactams (e.g., cephalosporins, oxacillin), linezolid, glycopeptides and daptomycin for the treatment of S. aureus infections remains the standard recommendation 7, 8 ; however, literature data remain scarce about other option. Treatment of ventilator-associated pneumonia (VAP) caused by S. aureus depends on whether the strain is MSSA or MRSA. For MSSA, first-line therapy typically includes anti-staphylococcal β-lactams such as oxacillin or cefazolin. In contrast, vancomycin or linezolid are commonly the drugs of choice for MRSA 9 . Trimethoprim-sulfamethoxazole (TMP-SMX) is an anti-staphylococcal agents that may have utility in treating skin and soft tissue infections and osteomyelitis, but clinical data supporting their efficacy in VAP remain limited 10-12 . Even though clinical treatment guidelines recommend vancomycin and linezolid as first choice, TMP-SMX is attractive alternative considering the possibility of sequential therapy, price, susceptibility profile to MRSA, and pulmonary tissue penetration 13, 14 . The present cross-sectional study aims to evaluate the impact of TMP-SMX therapy in patients with MRSA VAP in comparison with vancomycin. Methods Study Design In accordance with international recommendations, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used to ensure adequate reporting of the following sections. This was a retrospective, single-center, cross sectional study conducted among hospitalized patients at Cajuru University Hospital, Curitiba, Paraná, Brazil. The study aimed to compare clinical outcomes between patients diagnosed with MRSA infections who were treated with either vancomycin or TMP-SMX. The protocol was reviewed and approved by the Institutional Review Board (IRB) of the Pontifical Catholic University of Paraná (PUC-PR), under approval number 69077623.9.0000.0020. Setting Cajuru University Hospital is a tertiary-care, academic teaching hospital located in Curitiba, Paraná, Brazil. It serves as a referral center for trauma, emergency care, and complex medical and surgical cases. The hospital has more than 220 inpatient beds, including intensive care units (ICUs) for medical, surgical, and neurological patients. It is affiliated with the Pontifical Catholic University of Paraná (PUC-PR) and provides care through both public and private health systems. The institution actively participates in clinical research, residency training, and interdisciplinary healthcare education. The study period extended from January 2020 to July 2024. Patients were followed from inclusion until hospital discharge or death. Participants All adult patients hospitalized at Cajuru University Hospital between January 2020 and July 2024 were screened for eligibility. Patients were included if they were (i) aged 18 years or older, (ii) had been hospitalized for more than 48 hours, and (iii) had a diagnosis of Staphylococcus aureus infection resistant to methicillin (MRSA) confirmed by clinical evaluation, laboratory findings, and microbiological culture from the respiratory tract (either tracheal aspirate or bronchoalveolar lavage). Only isolates susceptible to both trimethoprim-sulfamethoxazole (TMP-SMX) and vancomycin were considered eligible. Patients were excluded if they were (i) pregnant, (ii) had incomplete clinical or laboratory data, (iii) had received TMP-SMX prior to the study period, (iv) were treated for refractory infection, or (v) had secondary bacteremia. Variables The primary exposure variable was the antibiotic regimen used for the treatment of Staphylococcus aureus ventilator-associated pneumonia (VAP), categorized as vancomycin or trimethoprim-sulfamethoxazole (TMP-SMX). The primary outcome was in-hospital mortality, defined as death occurring during the same hospital admission in which VAP was diagnosed. The secondary outcome was clinical response at day 5, classified as clinical cure, improvement, or failure according to predefined clinical criteria. Independent risk factors for mortality were also evaluated. Ventilator-associated pneumonia was defined as a new or progressive pulmonary infiltrate observed on chest X-ray in patients under mechanical ventilation for more than 48 hours, associated with a positive culture for MRSA (tracheal aspirate or bronchoalveolar lavage), and at least one of the following: fever >37.8°C or 11,000 or 24 breaths/min); or signs of hypoxia. Clinical cure was defined as complete resolution of pneumonia-related signs and symptoms compared with baseline, without the need for additional antibiotic therapy. Clinical improvement referred to partial resolution (improvement in at least two symptoms) without escalation or change of antibiotics. Clinical failure was defined as persistence or worsening of signs and symptoms after at least three days of therapy or the appearance of new pulmonary or systemic findings. The protocol of vancomycin in the institution included a loading dose of 30 mg/kg followed by continuous infusion 30 mg/kg as previously described 15 . The protocol of SMX-TMP is 50 mg/kg/day divided in three infusions of 1 hour. The duration of therapy is five to seven days in patients without complications 16 . The hospital protocol for empirical VAP treatment included SMX-TMP or vancomycin associated with gentamicin until cultures results. In general, 24h was a time to species identification, allowing an early antibiotic adequacy. Covariates collected for analysis included demographic variables (age, sex), comorbidities (diabetes mellitus, chronic kidney disease, heart failure, chronic obstructive pulmonary disease, hypertension, cirrhosis, neoplasm, prior myocardial infarction, stroke, HIV infection), disease severity (Sequential Organ Failure Assessment [SOFA] score), and clinical parameters (length of ICU stay, total hospital stay, and VAP duration). Measurement Clinical, laboratory, and microbiological data were retrieved from electronic medical records. Collected variables included demographics (age, sex), comorbidities, antibiotic regimen, and patient outcomes (mortality and clinical response). Antibiotic impact was assessed through length of hospital stay, need for intensive care support, and in-hospital mortality. Microbiological analyses followed standardized institutional protocols: identification of Staphylococcus aureus by MALDI-TOF (Bruker, Billerica, MA) and susceptibility testing using the VITEK2 system (bioMérieux, Marcy-l’Étoile, France). Interpretations were made according to the Clinical and Laboratory Standards Institute (CLSI) criteria valid for the study period 17, 18 . Demographic, clinical, and therapeutic data (including antibiotic regimen, duration of therapy, SOFA score, comorbidities, and clinical outcomes) were collected at a single point in time during the hospitalization in which the VAP diagnosis occurred. All data were entered into a secure database and cross-checked by a third investigator for consistency before statistical analysis. Statistical analysis Statistical analyses were performed to explore associations between clinical variables, antibiotic regimen, and patient outcomes. Continuous variables—including clinical, laboratory, therapeutic, and prognostic parameters—were expressed as means and standard deviations (SD) or medians and interquartile ranges (IQR), according to data distribution. Normality was assessed using the Shapiro–Wilk test. Comparisons between groups were performed using Student’s t -test for normally distributed variables and the Mann–Whitney U test for non-normally distributed data. Categorical variables were presented as absolute and relative frequencies and compared using the chi-square test or Fisher’s exact test when appropriate. The significance threshold was set at p < 0.05 for all analyses. When the sample size allowed, multivariable logistic regression models were constructed to identify independent factors associated with in-hospital mortality, including variables with p < 0.10 in univariate analyses. Statistical analyses were conducted using standard statistical software packages. Results Participants A total of 125 patients with MRSA ventilator-associated pneumonia met eligibility criteria and were included in the analysis (Table 1). Descriptive data The cohort was predominantly male (73%; 91/125), with a mean age of 52.1 years (SD 18.3). Illness severity at admission was SOFA 8.96 (SD 3.55). The most frequent comorbidities were arterial hypertension 34% (42/125) and diabetes mellitus 21% (26/125); other conditions occurred less often: cirrhosis 10% (12/125), chronic heart failure 8% (10/125), previous stroke 6% (8/125), COPD 6% (8/125), previous myocardial infarction 4% (5/125), neoplasm 3% (4/125), and HIV 2% (3/125). Health-care utilization was substantial, with hospital length of stay 36.5 days (SD 33.6) and ICU length of stay 18.4 days (SD 12.5); VAP duration averaged 8.1 days (SD 8.3). Complete baseline characteristics and denominators are shown in Table 1. Outcomes Overall mortality was 32% (40/125). By day 5, clinical cure was observed in 54% (67/125), treatment failure in 27% (34/125), and partial improvement in 19% (24/125) (Table 1). Baseline demographic and clinical profiles were broadly similar between vancomycin (n=60) and SMX-TMP (n=65) (Table 2). Male sex: 73% (44/60) vs 72% (47/65), p=0.412. Comorbidities were balanced (e.g., diabetes 18% [11/60] vs 23% [15/65], p=0.368; arterial hypertension 37% [22/60] vs 31% [20/65], p=0.262), with no significant between-group differences across tested conditions. Early clinical response at day 5 was comparable between groups: in the vancomycin arm, cure 52% (31/60), improvement 17% (10/60), failure 32% (19/60); in the SMX-TMP arm, cure 55% (36/65), improvement 22% (14/65), failure 23% (15/65) (non-significant across categories). Indices of severity and resource use did not differ meaningfully: SOFA 9.15 (SD 3.0) vs 8.78 (SD 4.1), p=0.124; hospital stay 25.6 (SD 23.1) vs 28.1 (SD 28.3) days, p=0.289; ICU stay 15.3 (SD 10.7) vs 16.2 (SD 14.3) days, p=0.412; VAP duration 8.3 (SD 10.3) vs 7.9 (SD 6.2) days, p=0.776. The mortality rate was numerically higher with vancomycin (37% [22/60]) than with SMX-TMP (28% [18/65]), without statistical significance (p=0.285). Full between-group comparisons and p-values are summarized in Table 2. Discussion This retrospective study assessed the clinical outcomes of patients with VAP due to MRSA treated with either vancomycin or SMX-TMP. Our findings suggest that SMX-TMP may be a viable alternative to vancomycin in selected patients, showing similar rates of clinical cure and mortality without statistically significant differences in hospital or ICU length of stay. Despite guideline recommendations prioritizing vancomycin or linezolid for MRSA pneumonia, real-world data on the efficacy of SMX-TMP remain limited. There are, in fact, clinical trials comparing SMX-TMP with other options such as vancomycin or linezolid; however, none of these studies are specific to pneumonia 11 . In one study, 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole plus rifampicin group experienced clinical success (risk difference 4%, 95% CI −9.7% to 17.6%), and with a non-inferiority margin of −20% no statistically significant difference was found. Additionally, there were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure 19 . On the other hand, another study showed that, in a multivariable logistic regression analysis, SMX-TMP was significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65), while the 30-day mortality rate was 32/252 (13%), with no significant difference between arms 12 ; however, among patients with bacteraemia, 14/41 (34%) treated with SMX-TMP and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93) (25977146). Beyond the paucity of randomized trials, there is also a discrepancy in the depth of pharmacokinetic/pharmacodynamic evidence across drugs. While SMX-TMP still has relatively under-studied parameters and less clearly defined PD targets—though AUC/MIC is considered a plausible driver 20 —alternatives such as vancomycin and linezolid have more extensively characterized PD as well as better-established toxicodynamics. PK/PD studies of SMX-TMP indicate high variability and suggest that higher doses (e.g., 15 mg/kg/day of the trimethoprim component) may produce faster and more effective in vitro bactericidal activity 21 . Consequently, comparative studies involving SMX-TMP remain open to criticism given the fragile state of knowledge regarding its PD target. Despite these PK/PD uncertainties, the use of SMX-TMP is urgent in many settings—particularly in LMICs that must optimize resources, whether due to limited access to alternative agents or lack of therapeutic drug monitoring needed to mitigate vancomycin- or linezolid-related toxicity. Accordingly, comparative studies are warranted. In our cohort, clinical cure was observed in over half of the patients in both treatment arms (52% in vancomycin vs. 55% in SMX-TMP), while mortality was numerically lower in the SMX-TMP group (28% vs. 37%), though this difference did not reach statistical significance. These findings are consistent with prior cited studies exploring the use of SMX-TMP for MRSA infections in multiple site of infections settings, where SMX-TMP has shown non-inferiority to standard regimens 19 . Additionally, more specific regarding pneumonia scenario, in a single-centre retrospective case–control study comparing SMX-TMP (n=42) with vancomycin (n=39) for healthcare-/ventilator-associated MRSA pneumonia, Eliakim-Raz et al. reported significantly lower 30-day mortality with SMX-TMP (26.2% vs 51.3%) and fewer clinical failures (35.7% vs 59.0%) 10 ; these differences persisted after propensity-score matching (mortality 16.7% vs 54.1%; clinical failure 25.0% vs 58.3%). Notably, vancomycin monitoring was limited, and baseline imbalances (e.g., lower albumin, higher urinary catheterization in the vancomycin arm) could have biased results despite adjustment—limitations acknowledged by the authors. In contrast, in our larger VAP-only cross-sectional study (n=125), early clinical response at day 5 and resource-use metrics were comparable between SMX-TMP and vancomycin, and the numerically higher mortality with vancomycin (37% vs 28%) was not statistically significant. Moreover, in our study, no significant differences were observed in baseline severity indices (SOFA scores), comorbidities, or in markers of resource utilization such as ICU stay and VAP duration. This strengthens the internal validity of the comparison and suggests that the two treatment groups were clinically comparable. Taken together, studies such as ours and that of Eliakim-Raz et al. reinforce the need for adequately powered randomized trials focused on pneumonia, with rigorous PK-PD targets for comparators 10 . Importantly, SMX-TMP has pharmacokinetic advantages, including excellent oral bioavailability, which may also offer practical benefits, particularly in resource-limited settings or for patients requiring step-down oral therapy [19-21]. Its lower cost, ease of administration, and favorable susceptibility profile against certain MRSA strains make it an appealing option. However, cautious patient selection is essential, particularly considering the potential hematologic and renal toxicities associated with SMX-TMP and the need to confirm susceptibility prior to initiation. Our study has limitations, including its retrospective, single-centre design and limited sample size, which may reduce the power to detect small but clinically meaningful differences between treatment arms. Furthermore, microbiological eradication rates were not assessed, and long-term outcomes beyond hospital discharge were not captured. Despite these limitations, our data add to the growing body of evidence suggesting that SMX-TMP could serve as a therapeutic alternative in well-selected cases of MRSA-VAP. In this single-centre retrospective cross-sectional study of patients with MRSA ventilator-associated pneumonia, trimethoprim–sulfamethoxazole achieved clinical outcomes comparable to vancomycin, with no significant differences in early response, mortality, or resource utilization. While these findings support SMX-TMP as a pragmatic therapeutic option in appropriately selected patients, definitive conclusions are limited by the observational design and sample size. Rigorous, adequately powered randomized trials—incorporating PK/PD-informed dosing and standardized monitoring—are warranted to establish the comparative effectiveness and safety of SMX-TMP for MRSA VAP. Declarations Participant consent - Consent was waived by the approving ethics committee. ACKNOWLEDGMENTS: We thank Carolline Konzen Klein, Caroline Menuzzi Klein, and Hélcio Giffhorn for manuscript review. Clinical trial number: not applicable. Funding: This research received no external funding. Institutional Review Board Statement: The protocol was reviewed and approved by the Institutional Review Board (IRB) of the Pontifical Catholic University of Paraná (PUC-PR), under approval number 69077623.9.0000.0020. Informed Consent Statement: Not applicable. Data Availability Statement: Data are available under request. AI declaration : ChatGPT was used to improve the English language. Conflicts of Interest: The authors declare no conflicts of interest. Authors’ contributions Conceptualization: FFT, JPT Data Curation: AS, VSA Formal Analysis: JPT, FFT, GHL, MMONL Investigation: AS, LRD Methodology: JPT, FFT Project Administration: FFT, LRD Supervision: FFT Validation: GHL, MMONL Writing – Original Draft Preparation: AS, FFT, VSA Writing – Review & Editing: JPT, FFT References Tuon FF, Suss PH, Telles JP, Dantas LR, Borges NH, Ribeiro VST. Antimicrobial Treatment of Staphylococcus aureus Biofilms. Antibiotics (Basel). 2023;12(1). Serra N, Di Carlo P, Andriolo M, Mazzola G, Diprima E, Rea T, et al. Staphylococcus aureus and Coagulase-Negative Staphylococci from Bloodstream Infections: Frequency of Occurrence and Antimicrobial Resistance, 2018-2021. Life (Basel). 2023;13(6):1356. Lee AS, de Lencastre H, Garau J, Kluytmans J, Malhotra-Kumar S, Peschel A, et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers. 2018;4:18033. Pulingam T, Parumasivam T, Gazzali AM, Sulaiman AM, Chee JY, Lakshmanan M, et al. 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Trimethoprim-sulfamethoxazole activity and pharmacodynamics against glycopeptide-intermediate Staphylococcus aureus. Pharmacotherapy. 2002;22(8):983-9. Tables Table 1. Data of patients with methicillin-resistant S. aureus ventilator associated pneumonia treated with trimethoprim-sulfamethoxazole or vancomycin. n % Male 91 73% Mortality 40 32% HIV 3 2% Diabetes mellitus 26 21% Chronic renal failure 6 5% Previsou miocardial infarct 5 4% Chronic heart failure 10 8% Previous stroke 8 6% COPD 8 6% Arterial hypertension 42 34% Neoplasm 4 3% Cirrhosis 12 10% Clinical response (5 days) 0 0% Cure 67 54% Improvement 24 19% Failure 34 27% Mean SD Age (year) 52.13 18.27 SOFA 8.96 3.55 Hospital Lengh of stay (days) 36.47 33.56 ICU Lengh of stay (days) 18.37 12.54 VAP duration (days) 8.12 8.29 * ICU - intensive care unit; HIV - human immunodeficiency virus; COPD - chronic obstructive pulmonary disease; SD - standard deviation; VAP - ventilator associated pneumoniae; SOFA - Sequential Organ Failure Assessment Table 2 — Demographics, comorbidities, and clinical outcomes in patients with methicillin-resistant S. aureus ventilator associated pneumonia treated with trimethoprim-sulfamethoxazole or vancomycin. Vancomycin SMX-TMP (n = 60) % (n = 65) % p value Male 44 73% 47 72% 0.412 Mortality 22 37% 18 28% 0.285 HIV 1 2% 2 3% 0.542 Diabetes mellitus 11 18% 15 23% 0.368 Chronic renal failure 2 3% 4 6% 0.395 Previous myocardial infarct 3 5% 2 3% 0.447 Chronic heart failure 6 10% 4 6% 0.538 Previous stroke 4 7% 4 6% 0.577 COPD 4 7% 4 6% 0.577 Arterial hypertension 22 37% 20 31% 0.262 Neoplasm 3 5% 1 2% 0.268 Cirrhosis 5 8% 7 11% 0.462 Clinical response (5 days) Cure 31 52% 36 55% NS Improvement 10 17% 14 22% Failure 19 32% 15 23% Mean SD Mean SD Age (year) 53.7 17.3 50.5 19.2 0.333 SOFA 9.15 3.0 8.78 4.1 0.124 Hospital Lengh of stay (days) 25.6 23.1 28.1 28.3 0.289 ICU Lengh of stay (days) 15.3 10.7 16.2 14.3 0.412 VAP duration (days) 8.3 10.3 7.9 6.2 0.776 Note: ICU - intensive care unit; HIV - human immunodeficiency virus; COPD - chronic obstructive pulmonary disease; SD - standard deviation; VAP - ventilator associated pneumoniae; SOFA - Sequential Organ Failure Assessment; NS – non-significant Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9281378","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":616053495,"identity":"e3a09953-9e20-4391-9ee6-11f578d0e13e","order_by":0,"name":"Felipe Tuon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBAC9gbmhgNQNuMDCM2DXwvPAUawFgkgZjYgWgsDVAubBHFa2BsbDxdUMNQZHO89Vl3YZpdn3sB77ANeLTwHGw7POMMgYXDmXNrtmW3JxTIH+JJn4NNiL5HYcJi3DajlRo7Zbd62A4kzGHiM8TtM/iFQyz+IlmLitEgwArU0QLQwE6eFB+iwGcckJGeeOWMsPeNccrEEM18yfi3shw9/Lqix4ec73mP4uaDMLk+CvfcwXi0gwAyJFjCDIQFMEqEFwUggQsMoGAWjYBSMMAAALapEH8YL460AAAAASUVORK5CYII=","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":true,"prefix":"","firstName":"Felipe","middleName":"","lastName":"Tuon","suffix":""},{"id":616053496,"identity":"84c34047-2f5d-47f2-9d1a-4b0ed06ae05a","order_by":1,"name":"Ademir Salomao","email":"","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":false,"prefix":"","firstName":"Ademir","middleName":"","lastName":"Salomao","suffix":""},{"id":616053497,"identity":"37768fd1-c7c6-4010-ad72-95a4a6947a56","order_by":2,"name":"Valdir Sabbaga Amato","email":"","orcid":"","institution":"Universidade de São Paulo","correspondingAuthor":false,"prefix":"","firstName":"Valdir","middleName":"Sabbaga","lastName":"Amato","suffix":""},{"id":616053498,"identity":"afba9881-f0cc-4896-8f69-cfcb0b4b1b0a","order_by":3,"name":"Leticia Dantas","email":"","orcid":"","institution":"Pontifícia Universidade Católica do Paraná","correspondingAuthor":false,"prefix":"","firstName":"Leticia","middleName":"","lastName":"Dantas","suffix":""},{"id":616053499,"identity":"39167cab-9686-40da-9c75-0284d7f8c015","order_by":4,"name":"Gustavo Henrique Loesch","email":"","orcid":"","institution":"Florida Christian University","correspondingAuthor":false,"prefix":"","firstName":"Gustavo","middleName":"Henrique","lastName":"Loesch","suffix":""},{"id":616053500,"identity":"7e922e8f-9801-4081-9271-2c17babef6ac","order_by":5,"name":"Maíra de Mayo Oliveira Nogueira Loesch","email":"","orcid":"","institution":"Florida Christian University","correspondingAuthor":false,"prefix":"","firstName":"Maíra","middleName":"de Mayo Oliveira Nogueira","lastName":"Loesch","suffix":""},{"id":616053501,"identity":"d12a73cd-b121-4a40-986d-0c199a4f6ca4","order_by":6,"name":"Joao Paulo Telles","email":"","orcid":"","institution":"AC Camargo Hospital","correspondingAuthor":false,"prefix":"","firstName":"Joao","middleName":"Paulo","lastName":"Telles","suffix":""}],"badges":[],"createdAt":"2026-03-31 14:38:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9281378/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9281378/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106352143,"identity":"f6640425-602f-465c-982f-7710b60f7e39","added_by":"auto","created_at":"2026-04-07 17:26:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":657494,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9281378/v1/c49ef993-cba8-4074-93ed-d88e0d5fe778.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Outcomes of Treatment for Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia","fulltext":[{"header":"Take-Home Message","content":"\u003cp\u003eTrimethoprim-sulfamethoxazole achieved clinical outcomes comparable to vancomycin for MRSA ventilator-associated pneumonia in a real-world cohort, with similar mortality, early clinical response, and resource use. These findings add to the limited clinical evidence on SMX-TMP for MRSA pneumonia and support its consideration as a pragmatic therapeutic alternative in carefully selected patients, especially in resource-constrained settings.\u003c/p\u003e"},{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eStaphylococcus\u003c/em\u003e \u003cem\u003eaureus\u003c/em\u003e is a Gram-positive, coagulase-positive coccus associated with a wide range of infections, including bacteremia, infective endocarditis, osteomyelitis, pneumonia, arthritis, and skin infections \u003csup\u003e1, 2\u003c/sup\u003e. The rise in antimicrobial resistance has made treatment increasingly challenging (1). Multiple studies conducted in different regions of the world demonstrate that these infections are a significant cause of hospital morbidity and mortality, consuming substantial healthcare resources \u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe clinical use of beta-lactams led to the emergence of methicillin-resistant \u003cem\u003eS. aureus\u003c/em\u003e (MRSA), which involves alterations in penicillin-binding proteins (PBPs), rendering the bacterium broadly resistant to beta-lactams \u003csup\u003e4\u003c/sup\u003e. Many countries have experienced a substantial rise in MRSA infections, with important geographic variations\u0026mdash;low prevalence in Scandinavia and high rates in Latin American and Asian countries \u003csup\u003e5\u003c/sup\u003e. Despite the significant attention given to MRSA, infections caused by methicillin-susceptible \u003cem\u003eS. aureus\u003c/em\u003e (MSSA) continue to have a major impact (5). Mortality rates for \u003cem\u003eS. aureus\u003c/em\u003e bacteremia remain high, with little progress achieved over recent decades \u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe use of beta-lactams (e.g., cephalosporins, oxacillin), linezolid, glycopeptides and daptomycin for the treatment of \u003cem\u003eS. aureus\u003c/em\u003e infections remains the standard recommendation \u003csup\u003e7, 8\u003c/sup\u003e; however, literature data remain scarce about other option. Treatment of ventilator-associated pneumonia (VAP) caused by \u003cem\u003eS. aureus\u003c/em\u003e depends on whether the strain is MSSA or MRSA. For MSSA, first-line therapy typically includes anti-staphylococcal \u0026beta;-lactams such as oxacillin or cefazolin. In contrast, vancomycin or linezolid are commonly the drugs of choice for MRSA \u003csup\u003e9\u003c/sup\u003e. Trimethoprim-sulfamethoxazole (TMP-SMX) is an anti-staphylococcal agents that may have utility in treating skin and soft tissue infections and osteomyelitis, but clinical data supporting their efficacy in VAP remain limited \u003csup\u003e10-12\u003c/sup\u003e. Even though clinical treatment guidelines recommend vancomycin and linezolid as first choice, TMP-SMX is attractive alternative considering the possibility of sequential therapy, price, susceptibility profile to MRSA, and pulmonary tissue penetration \u003csup\u003e13, 14\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe present cross-sectional study aims to evaluate the impact of TMP-SMX therapy in patients with MRSA VAP in comparison with vancomycin.\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStudy Design\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn accordance with international recommendations, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used to ensure adequate reporting of the following sections. This was a retrospective, single-center, cross sectional study conducted among hospitalized patients at Cajuru University Hospital, Curitiba, Paran\u0026aacute;, Brazil. The study aimed to compare clinical outcomes between patients diagnosed with MRSA infections who were treated with either vancomycin or TMP-SMX. The protocol was reviewed and approved by the Institutional Review Board (IRB) of the Pontifical Catholic University of Paran\u0026aacute; (PUC-PR), under approval number 69077623.9.0000.0020.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eSetting\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCajuru University Hospital is a tertiary-care, academic teaching hospital located in Curitiba, Paran\u0026aacute;, Brazil. It serves as a referral center for trauma, emergency care, and complex medical and surgical cases. The hospital has more than 220 inpatient beds, including intensive care units (ICUs) for medical, surgical, and neurological patients. It is affiliated with the Pontifical Catholic University of Paran\u0026aacute; (PUC-PR) and provides care through both public and private health systems. The institution actively participates in clinical research, residency training, and interdisciplinary healthcare education. The study period extended from January 2020 to July 2024. Patients were followed from inclusion until hospital discharge or death.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eParticipants\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll adult patients hospitalized at Cajuru University Hospital between January 2020 and July 2024 were screened for eligibility. Patients were included if they were (i) aged 18 years or older, (ii) had been hospitalized for more than 48 hours, and \u0026nbsp;(iii) had a diagnosis of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e infection resistant to methicillin (MRSA) confirmed by clinical evaluation, laboratory findings, and microbiological culture from the respiratory tract (either tracheal aspirate or bronchoalveolar lavage). Only isolates susceptible to both trimethoprim-sulfamethoxazole (TMP-SMX) and vancomycin were considered eligible. Patients were excluded if they were (i) pregnant, (ii) had incomplete clinical or laboratory data, (iii) had received TMP-SMX prior to the study period, (iv) were treated for refractory infection, or (v) had secondary bacteremia.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVariables\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe primary exposure variable was the antibiotic regimen used for the treatment of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e ventilator-associated pneumonia (VAP), categorized as vancomycin or trimethoprim-sulfamethoxazole (TMP-SMX). The primary outcome was in-hospital mortality, defined as death occurring during the same hospital admission in which VAP was diagnosed. The secondary outcome was clinical response at day 5, classified as clinical cure, improvement, or failure according to predefined clinical criteria. Independent risk factors for mortality were also evaluated.\u003c/p\u003e\n\u003cp\u003eVentilator-associated pneumonia was defined as a new or progressive pulmonary infiltrate observed on chest X-ray in patients under mechanical ventilation for more than 48 hours, associated with a positive culture for MRSA (tracheal aspirate or bronchoalveolar lavage), and at least one of the following: fever \u0026gt;37.8\u0026deg;C or \u0026lt;36.1\u0026deg;C; leukocyte count \u0026gt;11,000 or \u0026lt;4,000/mm\u0026sup3;; purulent sputum or increased suction requirement; new or worsening cough; abnormal pulmonary auscultation; dyspnea or tachypnea (respiratory rate \u0026gt;24 breaths/min); or signs of hypoxia.\u003c/p\u003e\n\u003cp\u003eClinical cure was defined as complete resolution of pneumonia-related signs and symptoms compared with baseline, without the need for additional antibiotic therapy. Clinical improvement referred to partial resolution (improvement in at least two symptoms) without escalation or change of antibiotics. Clinical failure was defined as persistence or worsening of signs and symptoms after at least three days of therapy or the appearance of new pulmonary or systemic findings.\u003c/p\u003e\n\u003cp\u003eThe protocol of vancomycin in the institution included a loading dose of 30 mg/kg followed by continuous infusion 30 mg/kg as previously described \u003csup\u003e15\u003c/sup\u003e. The protocol of SMX-TMP is 50 mg/kg/day divided in three infusions of 1 hour. The duration of therapy is five to seven days in patients without complications \u003csup\u003e16\u003c/sup\u003e. The hospital protocol for empirical VAP treatment included SMX-TMP or vancomycin associated with gentamicin until cultures results. In general, 24h was a time to species identification, allowing an early antibiotic adequacy.\u003c/p\u003e\n\u003cp\u003eCovariates collected for analysis included demographic variables (age, sex), comorbidities (diabetes mellitus, chronic kidney disease, heart failure, chronic obstructive pulmonary disease, hypertension, cirrhosis, neoplasm, prior myocardial infarction, stroke, HIV infection), disease severity (Sequential Organ Failure Assessment [SOFA] score), and clinical parameters (length of ICU stay, total hospital stay, and VAP duration).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMeasurement\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eClinical, laboratory, and microbiological data were retrieved from electronic medical records. Collected variables included demographics (age, sex), comorbidities, antibiotic regimen, and patient outcomes (mortality and clinical response). Antibiotic impact was assessed through length of hospital stay, need for intensive care support, and in-hospital mortality.\u003c/p\u003e\n\u003cp\u003eMicrobiological analyses followed standardized institutional protocols: identification of \u003cem\u003eStaphylococcus aureus\u003c/em\u003e by MALDI-TOF (Bruker, Billerica, MA) and susceptibility testing using the VITEK2 system (bioM\u0026eacute;rieux, Marcy-l\u0026rsquo;\u0026Eacute;toile, France). Interpretations were made according to the Clinical and Laboratory Standards Institute (CLSI) criteria valid for the study period \u003csup\u003e17, 18\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemographic, clinical, and therapeutic data (including antibiotic regimen, duration of therapy, SOFA score, comorbidities, and clinical outcomes) were collected at a single point in time during the hospitalization in which the VAP diagnosis occurred. All data were entered into a secure database and cross-checked by a third investigator for consistency before statistical analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed to explore associations between clinical variables, antibiotic regimen, and patient outcomes. Continuous variables\u0026mdash;including clinical, laboratory, therapeutic, and prognostic parameters\u0026mdash;were expressed as means and standard deviations (SD) or medians and interquartile ranges (IQR), according to data distribution. Normality was assessed using the Shapiro\u0026ndash;Wilk test. Comparisons between groups were performed using Student\u0026rsquo;s \u003cem\u003et\u003c/em\u003e-test for normally distributed variables and the Mann\u0026ndash;Whitney \u003cem\u003eU\u003c/em\u003e test for non-normally distributed data.\u003c/p\u003e\n\u003cp\u003eCategorical variables were presented as absolute and relative frequencies and compared using the chi-square test or Fisher\u0026rsquo;s exact test when appropriate. The significance threshold was set at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05 for all analyses. When the sample size allowed, multivariable logistic regression models were constructed to identify independent factors associated with in-hospital mortality, including variables with \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.10 in univariate analyses. Statistical analyses were conducted using standard statistical software packages.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003eParticipants\u003c/h2\u003e\n\u003cp\u003eA total of 125 patients with MRSA ventilator-associated pneumonia met eligibility criteria and were included in the analysis (Table 1).\u003c/p\u003e\n\u003ch2\u003eDescriptive data\u003c/h2\u003e\n\u003cp\u003eThe cohort was predominantly male (73%; 91/125), with a mean age of 52.1 years (SD 18.3). Illness severity at admission was SOFA 8.96 (SD 3.55). The most frequent comorbidities were arterial hypertension 34% (42/125) and diabetes mellitus 21% (26/125); other conditions occurred less often: cirrhosis 10% (12/125), chronic heart failure 8% (10/125), previous stroke 6% (8/125), COPD 6% (8/125), previous myocardial infarction 4% (5/125), neoplasm 3% (4/125), and HIV 2% (3/125). Health-care utilization was substantial, with hospital length of stay 36.5 days (SD 33.6) and ICU length of stay 18.4 days (SD 12.5); VAP duration averaged 8.1 days (SD 8.3). Complete baseline characteristics and denominators are shown in Table 1.\u003c/p\u003e\n\u003ch2\u003eOutcomes\u003c/h2\u003e\n\u003cp\u003eOverall mortality was 32% (40/125). By day 5, clinical cure was observed in 54% (67/125), treatment failure in 27% (34/125), and partial improvement in 19% (24/125) (Table 1). Baseline demographic and clinical profiles were broadly similar between vancomycin (n=60) and SMX-TMP (n=65) (Table 2). Male sex: 73% (44/60) vs 72% (47/65), p=0.412. Comorbidities were balanced (e.g., diabetes 18% [11/60] vs 23% [15/65], p=0.368; arterial hypertension 37% [22/60] vs 31% [20/65], p=0.262), with no significant between-group differences across tested conditions.\u003c/p\u003e\n\u003cp\u003eEarly clinical response at day 5 was comparable between groups: in the vancomycin arm, cure 52% (31/60), improvement 17% (10/60), failure 32% (19/60); in the SMX-TMP arm, cure 55% (36/65), improvement 22% (14/65), failure 23% (15/65) (non-significant across categories). Indices of severity and resource use did not differ meaningfully: SOFA 9.15 (SD 3.0) vs 8.78 (SD 4.1), p=0.124; hospital stay 25.6 (SD 23.1) vs 28.1 (SD 28.3) days, p=0.289; ICU stay 15.3 (SD 10.7) vs 16.2 (SD 14.3) days, p=0.412; VAP duration 8.3 (SD 10.3) vs 7.9 (SD 6.2) days, p=0.776. The mortality rate was numerically higher with vancomycin (37% [22/60]) than with SMX-TMP (28% [18/65]), without statistical significance (p=0.285). Full between-group comparisons and p-values are summarized in Table 2.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective study assessed the clinical outcomes of patients with VAP due to MRSA treated with either vancomycin or SMX-TMP. Our findings suggest that SMX-TMP may be a viable alternative to vancomycin in selected patients, showing similar rates of clinical cure and mortality without statistically significant differences in hospital or ICU length of stay.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite guideline recommendations prioritizing vancomycin or linezolid for MRSA pneumonia, real-world data on the efficacy of SMX-TMP remain limited. There are, in fact, clinical trials comparing SMX-TMP with other options such as vancomycin or linezolid; however, none of these studies are specific to pneumonia \u003csup\u003e11\u003c/sup\u003e. In one study, 56/75 (74.7%) in the linezolid group and 59/75 (78.7%) in the trimethoprim/sulfamethoxazole plus rifampicin group experienced clinical success (risk difference 4%, 95% CI \u0026minus;9.7% to 17.6%), and with a non-inferiority margin of \u0026minus;20% no statistically significant difference was found. Additionally, there were no statistically significant differences between the two groups in any of the secondary outcomes, including microbiologically documented failure \u003csup\u003e19\u003c/sup\u003e. On the other hand, another study showed that, in a multivariable logistic regression analysis, SMX-TMP was significantly associated with treatment failure (adjusted odds ratio 2.00, 1.09 to 3.65), while the 30-day mortality rate was 32/252 (13%), with no significant difference between arms \u003csup\u003e12\u003c/sup\u003e; however, among patients with bacteraemia, 14/41 (34%) treated with SMX-TMP and 9/50 (18%) with vancomycin died (risk ratio 1.90, 0.92 to 3.93) (25977146).\u003c/p\u003e\n\u003cp\u003eBeyond the paucity of randomized trials, there is also a discrepancy in the depth of pharmacokinetic/pharmacodynamic evidence across drugs. While SMX-TMP still has relatively under-studied parameters and less clearly defined PD targets\u0026mdash;though AUC/MIC is considered a plausible driver \u003csup\u003e20\u003c/sup\u003e\u0026mdash;alternatives such as vancomycin and linezolid have more extensively characterized PD as well as better-established toxicodynamics. PK/PD studies of SMX-TMP indicate high variability and suggest that higher doses (e.g., 15 mg/kg/day of the trimethoprim component) may produce faster and more effective in vitro bactericidal activity \u003csup\u003e21\u003c/sup\u003e. Consequently, comparative studies involving SMX-TMP remain open to criticism given the fragile state of knowledge regarding its PD target.\u003c/p\u003e\n\u003cp\u003eDespite these PK/PD uncertainties, the use of SMX-TMP is urgent in many settings\u0026mdash;particularly in LMICs that must optimize resources, whether due to limited access to alternative agents or lack of therapeutic drug monitoring needed to mitigate vancomycin- or linezolid-related toxicity.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccordingly, comparative studies are warranted. In our cohort, clinical cure was observed in over half of the patients in both treatment arms (52% in vancomycin vs. 55% in SMX-TMP), while mortality was numerically lower in the SMX-TMP group (28% vs. 37%), though this difference did not reach statistical significance. These findings are consistent with prior cited studies exploring the use of SMX-TMP for MRSA infections in multiple site of infections settings, where SMX-TMP has shown non-inferiority to standard regimens \u003csup\u003e19\u003c/sup\u003e. Additionally, more specific regarding pneumonia scenario, in a single-centre retrospective case\u0026ndash;control study comparing SMX-TMP (n=42) with vancomycin (n=39) for healthcare-/ventilator-associated MRSA pneumonia, Eliakim-Raz et al. reported significantly lower 30-day mortality with SMX-TMP (26.2% vs 51.3%) and fewer clinical failures (35.7% vs 59.0%) \u003csup\u003e10\u003c/sup\u003e; these differences persisted after propensity-score matching (mortality 16.7% vs 54.1%; clinical failure 25.0% vs 58.3%). Notably, vancomycin monitoring was limited, and baseline imbalances (e.g., lower albumin, higher urinary catheterization in the vancomycin arm) could have biased results despite adjustment\u0026mdash;limitations acknowledged by the authors. In contrast, in our larger VAP-only cross-sectional study (n=125), early clinical response at day 5 and resource-use metrics were comparable between SMX-TMP and vancomycin, and the numerically higher mortality with vancomycin (37% vs 28%) was not statistically significant. Moreover, in our study, no significant differences were observed in baseline severity indices (SOFA scores), comorbidities, or in markers of resource utilization such as ICU stay and VAP duration. This strengthens the internal validity of the comparison and suggests that the two treatment groups were clinically comparable. Taken together, studies such as ours and that of Eliakim-Raz et al. reinforce the need for adequately powered randomized trials focused on pneumonia, with rigorous PK-PD targets for comparators \u003csup\u003e10\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eImportantly, SMX-TMP has pharmacokinetic advantages, including excellent oral bioavailability, which may also offer practical benefits, particularly in resource-limited settings or for patients requiring step-down oral therapy [19-21]. Its lower cost, ease of administration, and favorable susceptibility profile against certain MRSA strains make it an appealing option. However, cautious patient selection is essential, particularly considering the potential hematologic and renal toxicities associated with SMX-TMP and the need to confirm susceptibility prior to initiation.\u003c/p\u003e\n\u003cp\u003eOur study has limitations, including its retrospective, single-centre design and limited sample size, which may reduce the power to detect small but clinically meaningful differences between treatment arms. Furthermore, microbiological eradication rates were not assessed, and long-term outcomes beyond hospital discharge were not captured. Despite these limitations, our data add to the growing body of evidence suggesting that SMX-TMP could serve as a therapeutic alternative in well-selected cases of MRSA-VAP.\u003c/p\u003e\n\u003cp\u003eIn this single-centre retrospective cross-sectional study of patients with MRSA ventilator-associated pneumonia, trimethoprim\u0026ndash;sulfamethoxazole achieved clinical outcomes comparable to vancomycin, with no significant differences in early response, mortality, or resource utilization. While these findings support SMX-TMP as a pragmatic therapeutic option in appropriately selected patients, definitive conclusions are limited by the observational design and sample size. Rigorous, adequately powered randomized trials\u0026mdash;incorporating PK/PD-informed dosing and standardized monitoring\u0026mdash;are warranted to establish the comparative effectiveness and safety of SMX-TMP for MRSA VAP.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eParticipant consent -\u003c/strong\u003e Consent was waived by the approving ethics committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS:\u0026nbsp;\u003c/strong\u003eWe thank Carolline Konzen Klein, Caroline Menuzzi Klein, and H\u0026eacute;lcio Giffhorn for manuscript review.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number:\u003c/strong\u003e not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis research received no external funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInstitutional Review Board Statement:\u0026nbsp;\u003c/strong\u003eThe protocol was reviewed and approved by the Institutional Review Board (IRB) of the Pontifical Catholic University of Paran\u0026aacute; (PUC-PR), under approval number 69077623.9.0000.0020.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent Statement:\u0026nbsp;\u003c/strong\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability Statement:\u0026nbsp;\u003c/strong\u003eData are available under request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAI declaration\u003c/strong\u003e: ChatGPT was used to improve the English language.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest:\u0026nbsp;\u003c/strong\u003eThe authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization: FFT, JPT\u003c/p\u003e\n\u003cp\u003eData Curation: AS, VSA\u003c/p\u003e\n\u003cp\u003eFormal Analysis: JPT, FFT, GHL, MMONL\u003c/p\u003e\n\u003cp\u003eInvestigation: AS, LRD\u003c/p\u003e\n\u003cp\u003eMethodology: JPT, FFT\u003c/p\u003e\n\u003cp\u003eProject Administration: FFT, LRD\u003c/p\u003e\n\u003cp\u003eSupervision: FFT\u003c/p\u003e\n\u003cp\u003eValidation: GHL, MMONL\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; Original Draft Preparation: AS, FFT, VSA\u003c/p\u003e\n\u003cp\u003eWriting \u0026ndash; Review \u0026amp; Editing: JPT, FFT\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTuon FF, Suss PH, Telles JP, Dantas LR, Borges NH, Ribeiro VST. Antimicrobial Treatment of Staphylococcus aureus Biofilms. Antibiotics (Basel). 2023;12(1).\u003c/li\u003e\n\u003cli\u003eSerra N, Di Carlo P, Andriolo M, Mazzola G, Diprima E, Rea T, et al. Staphylococcus aureus and Coagulase-Negative Staphylococci from Bloodstream Infections: Frequency of Occurrence and Antimicrobial Resistance, 2018-2021. Life (Basel). 2023;13(6):1356.\u003c/li\u003e\n\u003cli\u003eLee AS, de Lencastre H, Garau J, Kluytmans J, Malhotra-Kumar S, Peschel A, et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Primers. 2018;4:18033.\u003c/li\u003e\n\u003cli\u003ePulingam T, Parumasivam T, Gazzali AM, Sulaiman AM, Chee JY, Lakshmanan M, et al. Antimicrobial resistance: Prevalence, economic burden, mechanisms of resistance and strategies to overcome. Eur J Pharm Sci. 2022;170:106103.\u003c/li\u003e\n\u003cli\u003eMonaco M, Pimentel de Araujo F, Cruciani M, Coccia EM, Pantosti A. Worldwide Epidemiology and Antibiotic Resistance of Staphylococcus aureus. Curr Top Microbiol Immunol. 2017;409:21-56.\u003c/li\u003e\n\u003cli\u003eAdeiza SS, Aminul I. Meta-meta-analysis of the mortality risk associated with MRSA compared to MSSA bacteraemia. Infez Med. 2024;32(2):131-7.\u003c/li\u003e\n\u003cli\u003eLi J, Echevarria KL, Traugott KA. beta-Lactam Therapy for Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Comparative Review of Cefazolin versus Antistaphylococcal Penicillins. Pharmacotherapy. 2017;37(3):346-60.\u003c/li\u003e\n\u003cli\u003eMcDanel JS, Perencevich EN, Diekema DJ, Herwaldt LA, Smith TC, Chrischilles EA, et al. Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals. Clin Infect Dis. 2015;61(3):361-7.\u003c/li\u003e\n\u003cli\u003eCollins CD, Schwemm AK. Linezolid Versus Vancomycin in the Empiric Treatment of Nosocomial Pneumonia: A Cost-Utility Analysis Incorporating Results from the ZEPHyR Trial. Value Health. 2015;18(5):614-21.\u003c/li\u003e\n\u003cli\u003eEliakim-Raz N, Hellerman M, Yahav D, Cohen J, Margalit I, Fisher S, et al. Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of healthcare/ventilator-associated MRSA pneumonia: a case-control study. J Antimicrob Chemother. 2017;72(3):882-7.\u003c/li\u003e\n\u003cli\u003eHong J, Ensom MHH, Lau TTY. What Is the Evidence for Co-trimoxazole, Clindamycin, Doxycycline, and Minocycline in the Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Pneumonia? Ann Pharmacother. 2019;53(11):1153-61.\u003c/li\u003e\n\u003cli\u003ePaul M, Bishara J, Yahav D, Goldberg E, Neuberger A, Ghanem-Zoubi N, et al. Trimethoprim-sulfamethoxazole versus vancomycin for severe infections caused by meticillin resistant Staphylococcus aureus: randomised controlled trial. BMJ. 2015;350:h2219.\u003c/li\u003e\n\u003cli\u003eDubar V, Lopez I, Gosset P, Aerts C, Voisin C, Wallaert B. The penetration of co-trimoxazole into alveolar macrophages and its effect on inflammatory and immunoregulatory functions. J Antimicrob Chemother. 1990;26(6):791-802.\u003c/li\u003e\n\u003cli\u003eMorel C, Langeard M, Vergnaud M, Monrocq N. [Lung tissue diffusion of intravenous trimethoprim-sulfamethoxazole combination (author\u0026apos;s transl)]. Pathol Biol (Paris). 1982;30(6):380-4.\u003c/li\u003e\n\u003cli\u003eYamada CH, Telles JP, Oliveira DDS, Cieslinski J, Ribeiro VST, Gasparetto J, et al. Comparison of intermittent versus continuous-infusion vancomycin for treating severe patients in intensive care units. Braz J Infect Dis. 2020;24(4):356-9.\u003c/li\u003e\n\u003cli\u003eMo Y, Booraphun S, Li AY, Domthong P, Kayastha G, Lau YH, et al. Individualised, short-course antibiotic treatment versus usual long-course treatment for ventilator-associated pneumonia (REGARD-VAP): a multicentre, individually randomised, open-label, non-inferiority trial. Lancet Respir Med. 2024:6.\u003c/li\u003e\n\u003cli\u003eTelles JP, Leme RCP, Campos ML, Ito C, Bail L, Nogueira KDS, et al. Ceftriaxone and methicillin-susceptible staphylococcus aureus: a perspective from pharmacokinetics/pharmacodynamics studies. Expert Opin Drug Metab Toxicol. 2021;17(9):1039-48.\u003c/li\u003e\n\u003cli\u003eCLSI. Clinical Laboratory Standard Insitute - Performance Standard for Antimicrobial Susceptibility Testing; Twenty-Third Informational Supplement. 2017.\u003c/li\u003e\n\u003cli\u003eHarbarth S, von Dach E, Pagani L, Macedo-Vinas M, Huttner B, Olearo F, et al. Randomized non-inferiority trial to compare trimethoprim/sulfamethoxazole plus rifampicin versus linezolid for the treatment of MRSA infection. J Antimicrob Chemother. 2015;70(1):264-72.\u003c/li\u003e\n\u003cli\u003eAbdul-Aziz MH, Alffenaar JC, Bassetti M, Bracht H, Dimopoulos G, Marriott D, et al. Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper(). Intensive Care Med. 2020;46(6):1127-53.\u003c/li\u003e\n\u003cli\u003eClose SJ, McBurney CR, Garvin CG, Chen DC, Martin SJ. Trimethoprim-sulfamethoxazole activity and pharmacodynamics against glycopeptide-intermediate Staphylococcus aureus. Pharmacotherapy. 2002;22(8):983-9.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Data of patients with methicillin-resistant \u003cem\u003eS. aureus\u003c/em\u003e ventilator associated pneumonia treated with trimethoprim-sulfamethoxazole or vancomycin.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"342\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e\u003cstrong\u003en\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003eMortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e32%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003eHIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e2%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e21%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eChronic renal failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003ePrevisou miocardial infarct\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e4%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eChronic heart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e8%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003ePrevious stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eArterial hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e34%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003eNeoplasm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e10%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eClinical response (5 days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e0%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003eCure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e54%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003eImprovement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e19%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003eFailure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e27%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e52.13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e18.27\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 16.6204%;\"\u003e\n \u003cp\u003eSOFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 24.1265%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e8.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e3.55\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eHospital Lengh of stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e36.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e33.56\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eICU Lengh of stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e18.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e12.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 40.7469%;\"\u003e\n \u003cp\u003eVAP duration (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.6506%;\"\u003e\n \u003cp\u003e8.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.4719%;\"\u003e\n \u003cp\u003e8.29\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" valign=\"bottom\" style=\"width: 59.6906%;\"\u003e\n \u003cp\u003e* ICU - intensive care unit; HIV - human immunodeficiency virus; COPD - chronic obstructive pulmonary disease; SD - standard deviation; VAP - ventilator associated pneumoniae; SOFA - Sequential Organ Failure Assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2 \u0026mdash; Demographics, comorbidities, and clinical outcomes in patients with methicillin-resistant \u003cem\u003eS. aureus\u003c/em\u003e ventilator associated pneumonia treated with trimethoprim-sulfamethoxazole or vancomycin.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"554\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVancomycin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSMX-TMP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e(n = 60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e(n = 65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e72%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.412\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eMortality\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e37%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e28%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003eHIV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.542\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eDiabetes mellitus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e18%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e23%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.368\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eChronic renal failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.395\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003ePrevious myocardial infarct\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e3%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.447\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eChronic heart failure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.538\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003ePrevious stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eCOPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e7%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e6%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eArterial hypertension\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e37%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e31%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.262\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eNeoplasm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e2%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.268\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eCirrhosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e11%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.462\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" valign=\"bottom\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eClinical response (5 days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003eCure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e31\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e52%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e36\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003eNS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003eImprovement\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e17%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e22%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003eFailure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e32%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e23%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMean\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSD\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eAge (year)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e53.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e17.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e50.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e19.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.333\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" style=\"width: 6.3782%;\"\u003e\n \u003cp\u003eSOFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 15.7329%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e9.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e3.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e8.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e4.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.124\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eHospital Lengh of stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e23.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e28.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e28.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.289\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eICU Lengh of stay (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e15.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e10.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e16.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e14.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.412\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd nowrap=\"\" colspan=\"2\" style=\"width: 22.1111%;\"\u003e\n \u003cp\u003eVAP duration (days)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 9.7799%;\"\u003e\n \u003cp\u003e8.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e10.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 1.9135%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 8.9295%;\"\u003e\n \u003cp\u003e7.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" style=\"width: 3.508%;\"\u003e\n \u003cp\u003e6.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd nowrap=\"\" valign=\"bottom\" style=\"width: 7.9728%;\"\u003e\n \u003cp\u003e0.776\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\" valign=\"bottom\" style=\"width: 57.829%;\"\u003e\n \u003cp\u003eNote: ICU - intensive care unit; HIV - human immunodeficiency virus; COPD - chronic obstructive pulmonary disease; SD - standard deviation; VAP - ventilator associated pneumoniae; SOFA - Sequential Organ Failure Assessment; NS \u0026ndash; non-significant\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Staphylococcus aureus, ventilator-associated pneumonia, trimethoprim-sulfamethoxazole, vancomycin, antimicrobial therapy","lastPublishedDoi":"10.21203/rs.3.rs-9281378/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9281378/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eVentilator-associated pneumonia (VAP) due to methicillin-resistant \u003cem\u003eStaphylococcus aureus\u003c/em\u003e(MRSA) remains a therapeutic challenge. Vancomycin is the recommended first-line therapy; however, trimethoprim-sulfamethoxazole (SMX-TMP) presents a potential alternative due to its pharmacokinetic properties and cost-effectiveness. Clinical data supporting its use in VAP are limited. The aim of this study was to compare the clinical outcomes of patients with MRSA-VAP treated with SMX-TMP versus vancomycin.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods: \u003c/strong\u003eWe conducted a retrospective, single-center, cross-sectional study between January 2020 and July 2021 at a tertiary academic hospital in southern Brazil. Adult patients with confirmed MRSA-VAP and documented susceptibility to both SMX-TMP and vancomycin were included. The primary outcome was in-hospital mortality. Secondary outcomes included clinical response at day 5, ICU and hospital length of stay, and VAP duration. Statistical comparisons were made using chi-square and t-tests, with significance set at \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eA total of 125 patients were analyzed (vancomycin: n=60; SMX-TMP: n=65). Mortality was 37% in the vancomycin group versus 28% in the SMX-TMP group (\u003cem\u003ep\u003c/em\u003e= 0.285). Clinical cure at day 5 was similar (52% vs. 55%, respectively). No significant differences were observed in SOFA scores, ICU or hospital stay, or VAP duration between groups.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eSMX-TMP was associated with clinical outcomes comparable to vancomycin in patients with MRSA-VAP. These findings suggest SMX-TMP may represent a viable therapeutic alternative in selected patients. Further prospective studies are warranted to validate its role in this context.\u003c/p\u003e","manuscriptTitle":"Outcomes of Treatment for Methicillin-Resistant Staphylococcus aureus Ventilator-Associated Pneumonia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-07 17:26:24","doi":"10.21203/rs.3.rs-9281378/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":"45d969a5-8fd0-43df-ba96-10037bba2390","owner":[],"postedDate":"April 7th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-07T17:26:24+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-07 17:26:24","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9281378","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9281378","identity":"rs-9281378","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}