Evaluation of the Antibacterial Activity of Piperacillin–tazobactam Against Burkholderia Pseudomallei in Vitro

Evaluation of the Antibacterial Activity of Piperacillin–tazobactam Against Burkholderia Pseudomallei in Vitro | 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 note Evaluation of the Antibacterial Activity of Piperacillin–tazobactam Against Burkholderia Pseudomallei in Vitro Mei hui Huang, Hua Wu, Xiao jun Zhou, Qin fang Cao, Xu ming Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-322273/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: Melioidosis is a zoonotic disease caused by Burkholderia pseudomallei ( B. pseudomallei ). Because B. pseudomallei is naturally resistant to a variety of antibiotics, such as penicillin, ampicillin, first-and second-generation cephalosporins, macrolides, aminoglycosides, streptomycin, polymyxin, etc., the selection of drugs is limited. The present study aimed to evaluate the antibacterial activity of piperacillin/tazobactam against B. pseudomallei in vitro to provide a theoretical basis and a variety of therapeutic options for clinical application.The antimicrobial susceptibilities of all B. pseudomallei isolated from melioidosis patients were detected by Etest method. Results: The MIC 50 values of piperacillin/tazobactam, imipenem, meropenem, doxycycline, trimethoprim–sulfamethoxazole, ceftazidime, tetracycline, and amoxicillin/clavulanic acid were 0.25 μg/ml, 0.5 μg/ml, 0.5 μg/ml, 0.5 μg/ml, 1 μg/ml, 1 μg/ml, 2 μg/ml, and 2 μg/ml, respectively. Their MIC 90 values were 0.5 μg/ml, 0.5 μg/ml, 1 μg/ml, 2 μg/ml, 2 μg/ml, 2 μg/ml, 4 μg/ml, and 4 μg/ml, respectively. All the isolates were uniformly sensitive (100%) to ceftazidime, imipenem and amoxicillin–clavulanic acid. The rate of antimicrobial sensitivity for doxycycline was 99.08%, for tetracycline-sulfamethoxazole 94.50%, and for tetracycline 94.49%.Both the MIC 50 and MIC 90 values of piperacillin/tazobactam were lower than those of the seven other antibiotics, indicating that it has strong antibacterial activity against B. pseudomallei in vitro. General Microbiology Health Economics & Outcomes Research Burkholderia pseudomallei Piperacillin/tazobactam Antimicrobial susceptibility MIC50 and MIC90 Etest Introduction Melioidosis is a zoonotic disease caused by Burkholderia pseudomallei ( B. pseudomallei ). The disease is mainly epidemic in tropical and subtropical areas between latitudes of 20 degrees north and south, such as Southeast Asia and Northern Australia[1-3]. Hainan Island is the largest tropical island in southern China and is close to Thailand, Vietnam, Laos and other countries with a high incidence of melioidosis.The high temperature and humid tropical monsoon climate make Hainan Island become a major epidemic focus of B. pseudomallei . The clinical manifestations of melioidosis are complex and changeable. It can present acutely with fever and chills secondary to a localized infection or septicaemia. Chronic cases are seen when abscesses develop insidiously at various tissue sites or organs. Consistent with international guidelines[4-5], melioidosis is treated in Hainan with intravenous ceftazidime or meropenem for a minimum 2-week intensive phase, with longer intensive therapy for critically ill patients, followed by a minimum 3-month eradication phase with oral antibiotics (trimethoprim–sulfamethoxazole is the preferred agent, and amoxicillin/clavulanic acid or doxycycline is the second choice). However, recently, there have been reports of B. pseudomallei resistant to ceftazidime, trimethoprim–sulfamethoxazole (TMP–SMX), and amoxicillin–clavulanic acid from different melioidosis endemic countries of the world, including neighbouring India[1,6-10]. Piperacillin/tazobactam has a broad antibacterial spectrum, strong tissue permeability and high-concentration distribution in body fluid and blood after injection. However, it is rarely used in the clinic because of the lack of a recommendation of an MIC breakpoint from the American for Clinical and Laboratory Standards Institute (CLSI) for B. pseudomallei . In this study, we reviewed the treatment of 109 hospitalized patients with melioidosis and found that 2 patients were cured successfully with piperacillin/tazobactam. This observation aroused our interest in the activity of piperacillin/tazobactam against B. pseudomallei in vitro. With this information, the present study was undertaken to compare the MIC 50 and MIC 90 values of piperacillin/tazobactam, meropenem(with an EUCAST MIC breakpoint) and imipenem, doxycycline, amoxicillin/clavulanic acid, tetracycline, TMP–SMX, and ceftazidime (with CLSI-recommended MIC breakpoint)[11] for B. pseudomallei isolated from patients during the period of 2010–2018 in Hainan General Hospital by Etest to provide a theoretical basis for clinical application and provide additional choices for the treatment of melioidosis. Materials And Methods Bacterial isolates A total of 109 B. pseudomallei isolated from melioidosis patients over a period of 8 years (June 2010 to May 2018) were collected in the Department of Microbiology of a 3000-bed tertiary care referral hospital in Haikou city (Hainan Province, China). B. pseudomallei isolates were presumptively identified by characteristic growth, Gram staining, oxidase test, and biochemical speciation (Vitek 2 Compact VT2.R 7.01; bioMérieux,France). Isolate identification was confirmed by Vitek MS (bioMérieux, France), and isolates were typed by multilocus sequence typing (MLST)[12]. The specimens included 70 blood cultures, 8 respiratory specimens, 5 urine samples and 26 purulent secretions. Determination of MIC Antimicrobial susceptibility testing was performed by Etest (bioMérieux) according to the manufacturer’s instructions. This method of testing has previously been shown to be comparable with the gold standard of microbroth dilution[13-14]. Minimum inhibitory concentrations (MICs) were read after 18 h and 24 h of incubation at 37 °C under aerobic conditions. For TMP/SMX, the MIC was read at 80% inhibition as per the manufacturer’s instructions. The MIC (μg/ml) interpretations for susceptible (S), intermediate (I), and resistant (R) to imipenem, doxycycline, amoxicillin/clavulanic acid, tetracycline, TMP/SMX, and ceftazidime were carried out following the CLSI published guideline M45-A2 [11]. The MIC interpretation for meropenem was carried out following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. The MIC 50 and MIC 90 of all antibiotics were calculated. The quality control strains were Escherichia coli (ATCC25922) and Pseudomonas aeruginosa (ATCC27853). All the quality control results were in accordance with the CLSI. Results The results show that the mainly MIC values of imipenem, meropenem, ceftazidime, amoxicillin/clavulanic acid and tetracycline were 0.25-0.5 μg/ml, 0.5-1.0 μg/ml, 1.0-2.0 μg/ml, 2.0-4.0 μg/ml and 1.0-4.0 μg/ml, respectively. The mainly MIC values of piperacillin/tazobactam, doxycycline and TMP/SMX were 0.25-0.5 μg/ml, 0.25-1.0 μg/ml, and 0.5-2.0 μg/ml, respectively. The detailed MIC interpretive values used in the study are shown in Table 1. Table 1 The concentration distribution and accumulation rate o f eight antimicrobial agents against 109 Burkholderia pseudomallei isolates from Haikou , Hainan Province , China. Drug concentration (μg/ml) Meropenem Amox–Clav Pip–Tazo TMP–SMX Imipenem Doxycycline Ceftazidime Tetracycline N Cumulative rate (%) N Cumulative rate (%) N Cumulative rate (%) N Cumulative rate (%) N Cumulative rate (%) N Cumulative rate (%) N Cumulative rate (%) N Cumulative rate (%) 0.008 0 0.0 — — — — 0 0.0 0 0.0 — — — — — — 0.016 0 0.0 — — — — 0 0.0 0 0.0 — — — — — — 0.032 0 0.0 — — — — 0 0.0 0 0.0 — — — — — — 0.064 0 0.0 0 0.0 0 0.0 1 1.0 0 0.0 0 0.0 0 0.0 0 0.0 0.125 0 0.0 0 0.0 1 1.0 4 4.6 0 0.0 0 0.0 0 0.0 0 0.0 0.25 1 1.0 0 0.0 89 82.6 12 15.6 20 18.3 18 16.5 0 0.0 0 0.0 0.5 71 66.1 1 1.0 17 98.2 29 42.2 86 97.2 44 56.9 2 1.8 4 3.7 1 33 96.3 1 1.8 2 100.0 42 80.7 2 100.0 35 89.0 71 67.0 20 22.0 2 1 97.2 77 72.5 0 100.0 16 95.4 0 100.0 7 95.4 35 99.1 60 77.1 4 0 97.2 29 99.9 0 100.0 5 100.0 0 100.0 4 99.1 1 100.0 19 94.5 8 3 100.0 1 100.0 0 100.0 0 100.0 0 100.0 0 99.1 0 100.0 5 99.1 16 0 100.0 0 100.0 0 100.0 0 100.0 0 100.0 1 100.0 0 100.0 0 99.1 32 0 100.0 0 100.0 0 100.0 0 100.0 0 100.0 0 100.0 0 100.0 0 99.1 64 — — 0 100.0 0 100.0 — — — — 0 100.0 0 100.0 1 100.0 128 — — 0 100.0 0 100.0 — — — — 0 100.0 0 100.0 0 100.0 256 — — 0 100.0 0 100.0 — — — — 0 100.0 0 100.0 0 100.0 N: Number of strains, Amox –Clav: amoxicillin/clavulanic acid, Pip – Tazo : piperacillin–tazobactam, TMP – SMX : trimethoprim/sulfamethoxazole The sensitivity of the 109 strains of B. pseudomallei to the eight antibiotics was as follows. Piperacillin/tazobactam had no MIC breakpoint in the CLSI guidelines. All the isolates were uniformly sensitive (100%) to ceftazidime, imipenem, and amoxicillin–clavulanic acid. Of the 109 isolates, 103 (94.49%) were susceptible to tetracycline at the MIC breakpoint of ≤4.0 μg/ml; 5 isolates had intermediate resistance to tetracycline (MIC=8 μg/ml); and 1 isolate was resistant (MIC ≥ 16.0 μg/ml). Moreover, 108 isolates (99.08%) were susceptible to doxycycline at the MIC breakpoint of ≤4 μg/ml, and 1 isolate was resistant (MIC≥16.0 μg/ml), whereas none had intermediate breakpoint. Finally, 104 (94.5%) were susceptible to TMP/SMX at the MIC breakpoint of ≤2/38 μg/ml, and 6 isolates was resistant (MIC≥4.0/76 μg/ml). There was no intermediate breakpoint according to the CLSI guidelines for TMP/SMX. In addition,isolates with an MIC of >2 μg/ml for meropenem were considered resistant, and isolates with an MIC≤2 μg/ml were susceptible based on the EUCAST guidelines. Therefore, 106 isolates (97.24%) were susceptible, and 3 isolates (2.76%) were resistant to meropenem. The MICs of antibiotics that inhibited 50% (MIC 50 ) and 90% (MIC 90 ) of the 109 isolates are shown in Table 2. Table 2 Minimum inhibitory concentrations (MICs) of eight antimicrobial agents against 109 Burkholderia pseudomallei isolates from Haikou, Hainan Province, China. Antimicrobial agent MIC 50 (μg/ml) MIC 90 (μg/ml) Imipenem 0.5 0.5 Meropenem 0.5 1 Ceftazidime 1 2 Amoxicillin/clavulanic acid 2 4 Tetracycline 2 4 Doxycycline 0.5 2 TMP/SMX 1 2 Piperacillin–tazobactam 0.25 0.5 All the results were analysed, and the order of the MIC 50 for the eight antimicrobial agents was piperacillin/tazobactam MIC 50 (0.25 μg/ml) < imipenem MIC 50 (0.5 μg/ml), meropenem MIC 50 (0.5 μg/ml), doxycycline MIC 50 (0.5 μg/ml) <TMP/SMX MIC 50 (1 μg/ml), ceftazidime MIC 50 (1 μg/ml) < tetracycline MIC 50 (2 μg/ml), amoxicillin/clavulanic acid MIC 50 (2 μg/ml). In addition, the MIC 90 from low to high was piperacillin/tazobactam (0.5 μg/ml), imipenem (0.5 μg/ml), meropenem (1 μg/ml), ceftazidime (2 μg/ml), doxycycline (2 μg/ml), TMP/SMX (2 μg/ml), amoxicillin/clavulanic acid (4 μg/ml), tetracycline (4 μg/ml) and so on. In addition, based on the peak blood concentration (Cmax) of China and Italy dosage forms of piperacillin/tazobactam commonly used in the clinic, the ratios of C max to MIC 50 and MIC 90 are shown in Table 3. Table 3 Piperacillin/tazobactam dosage forms and the ratios of peak blood concentration (Cmax) to MIC 50 and MIC 90 are listed Dosage form (China) 1.25 g 2.5 g 5.0 g Dosage form(Italy) 2.25 g 3.375 g 4.5 g C max (μg/ml) 42.7 80.3 192.5 C max (μg/ml) 134 242 298 C max /MIC 50 170.8 321.2 770 C max /MIC 50 536 968 1192 C max /MIC 90 85.4 160.5 385 C max /MIC 90 268 484 596 Dosage form, C max from piperacillin/tazobactam instructions Discussion Melioidosis is an important public health disease in Southeast Asia and Australia, but it is still considered a potential emerging infectious disease in tropical developing countries[2,13-18]. A 2016 modelling study estimated that there are ~165,000 cases of melioidosis in humans per year worldwide, of which 89,000 (54%) are estimated to be fatal[19]. Although quinolones have slight antibacterial activity in vitro, their treatment failure rate is relatively high[8,20]. The mortality of melioidosis ranges from 14 to 40% and may be as high as 80% if effective antibiotics are not given[21]. With the early use of antibiotics, the mortality rate can also be reduced to under 10%[22]. However, B. pseudomallei is intrinsically resistant to many antibiotics (such as penicillin, ampicillin, first- and second-generation cephalosporins, macrolides, aminoglycosides, streptomycin, polymyxin, etc.)[23-24]. At present, only TMP/SMX, ceftazidime, tetracycline, doxycycline, amoxicillin/clavulanic acid and imipenem have MIC breakpoints for B. pseudomallei in the CLSI guidelines[11]. Therefore, the selection of antimicrobial agents is limited for the treatment of melioidosis. Piperacillin, as with all other β-lactam antibiotics, interferes with the final stage of peptidoglycan synthesis by inhibiting penicillin-binding proteins (PBPs), which crosslink peptidoglycan polymers[25]. Tazobactam extends piperacillin’s spectrum of activity to include bacteria producing many Ambler class A β-lactamases, narrow- and extended-spectrum (TEM-, SHV-, and CTX-M-type) β-lactamases and some class C (AmpC-type) β-lactamases[26-27]. Piperacillin-tazobactam has the broadest spectrum of activity among the penicillin class of β-lactam antibiotics and is generally active against most of the typical human pathogens, including aerobic and anaerobic gram-positive and gram-negative bacteria[25]. Piperacillin/tazobactam is widely distributed in various tissues and body fluids after injection, and its clinical indications are also relatively broad, such as respiratory tract infection, bacterial septicaemia, and subcutaneous abscess[25]. The clinical infection of the target bacteria we studied is also complex and diverse and is considered "like a hundred diseases". Piperacillin/tazobactam has a sensitive CLSI breakpoint for Enterobacteriaceae bacteria but no MIC breakpoints for non-fermentative bacteria except Pseudomonas aeruginosa , Acinetobacter baumannii and Haemophilus influenzae . Therefore, we compared the MICs of piperacillin/tazobactam with those of six antibiotics(with a CLSI MIC breakpoints) and meropenem (with an EUCAST MIC breakpoint) to provide additional choices for the treatment of melioidosis in this study. The results showed that the MIC 50 and MIC 90 of piperacillin/tazobactam were 0.25 μg/ml and 0.5 μg/ml, respectively. The MIC 50 of piperacillin/tazobactam was lower than that of the other seven antibiotics. In addition, the MIC 90 was also lower than that of the other six antibiotics, except for imipenem (the MIC 90 of piperacillin/tazobactam was equal to that of imipenem). This result indicates that the antibacterial activity of piperacillin/tazobactam is stronger than that of the other tested antibiotics in vitro. Regarding the pharmacokinetic characteristics in vivo (see Table 3), it was found that both the peak value of the plasma concentration of China and Italy formulations is far higher than the MIC 50 and MIC 90 values of piperacillin/tazobactam. It is generally believed that antibiotics have bacteriostatic or bactericidal effects in vivo when the blood concentration of antibiotics is 4-6 times higher than the MIC value of target bacteria. In the published literature, the criteria used in these studies to analyse the susceptibility to piperacillin/tazobactam and meropenem to B. pseudomallei were mostly based on the MIC breakpoint of P. aeruginosa in the CLSI guidelines[28]. In studies published in Bangladesh, Dutta et al. found that 20 isolates of B. pseudomallei were uniformly sensitive (100%) to piperacillin–tazobactam (refer to the MIC breakpoint of P. aeruginosa in the CLSI guidelines), and both the MIC 50 and MIC 90 values were 2 μg/ml[28]. These values are obviously higher than the results of our study. However, the number of samples in Dutta’s study may be too few, and both the MIC 50 and MIC 90 values of all isolates to three common antibiotics (imipenem, ceftazidime, and amoxicillin/clavulanic acid) were relatively higher (great than or equal to 2 μg/ml, agar dilution method). This result indicated that the MIC values of the 20 isolates of B. pseudomallei in Dutta's study were relatively high. In view of the above information, this study still has certain reference significance. It can be used as the theoretical basis for the clinical treatment of B. pseudomallei infection with piperacillin–tazobactam. In this study, we conducted a preliminary study on the MIC of piperacillin– tazobactam for B. pseudomallei in vitro. We hope that this study can play a valuable role, arousing more attention to antibiotic selection for B. pseudomallei infection to improve the cure rate and reduce mortality. Therefore, the laboratory should work closely with the clinic to obtain a more clinical pharmacodynamic summary of piperacillin/tazobactam in the treatment of B. pseudomallei infection and provide more powerful evidence for its treatment. Limitations In this paper, we have not summarized the MIC breakpoint of piperacillin-tazobactam to B. pseudomallei , but still need a lot of data analysis and summary. Abbreviations MIC: minimum inhibitory concentration ; TMP–SMX:trimethoprim–sulfamethoxazole; Amox –Clav: amoxicillin/clavulanic acid; Pip – Tazo : piperacillin–tazobactam; CLSI:Clinical and Laboratory Standards Institute;EUCAST:the European Committee on Antimicrobial Susceptibility Testing;MLST: multilocus sequence typing; N: Number of strains;PBPs:penicillin-binding proteins. Declarations Ethics approval and consent to participate The Medical Ethics Committee of Hainan general hospital approved this study protocol. Consent for publication Not applicable. Availability of data and materials All relevant data of this study are within the paper. Competing interests The authors declare that they have no competing interests. Funding This work was funded by the Key Research and Development Program of Hainan Province (No. ZDYF2018113). Authors’ contributions Meihui Huang performed the culture, identifcation, literature search and manuscript writing. Hua Wu performed the antimicrobial susceptibility tests. Xiaojun Zhou was involved in storage and identifcation of organisms and primary data analysis. Qinfang Cao was involved in analyzed the clinical data.Xuming Wang was involved in study design, analysis of the data and manuscript writing. All authors read and approved the fnal manuscript. Acknowledgements Not applicable. References Nhung PH, Van VH, Anh NQ, Phuong DM.Antimicrobial susceptibility of Burkholderia pseudomallei isolates in Northern Vietnam.J Glob Antimicrob Resist 2019;18:34-36. 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Currie BJ.Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment. Semin. Respir Crit Care Med 2015;36, 111–125. Wiersinga WJBJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med 2012;367: 1035–44. Schweizer HP. Mechanisms of antibiotic resistance in Burkholderia pseudomallei: implications for treatment of melioidosis. Future Microbiol 2012;7:1389–99. Hayashi Y,Roberts JA,Paterson DL, Lipman J. Pharmacokinetic evaluation of piperacillin-tazobactam. Expert Opin Drug Met 2010;6(8):1017-31. Toussaint KA, Gallagher JC. β-Lactam/β-lactamase inhibitor combinations: from then to now. Ann Pharmacother 2015; 49(1):86 –98. Gin A, Dilay L, Karlowsky JA, Walkty A, Rubinstein E, Zhanel GG. Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther 2007;5:365–383. Dutta S, Haq S, Hasan MR, Haq JA. Antimicrobial susceptibility pattern of clinical isolates of Burkholderia pseudomallei in Bangladesh. BMC Res Notes. 2017;10(1):299. 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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-322273","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research note","associatedPublications":[],"authors":[{"id":16270939,"identity":"3e695024-7dd9-4a11-8c67-2238f2e44db9","order_by":0,"name":"Mei hui Huang","email":"","orcid":"https://orcid.org/0000-0002-5610-9975","institution":"Hainan General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mei","middleName":"hui","lastName":"Huang","suffix":""},{"id":16270940,"identity":"ffa622de-bb28-432a-9ffd-203d25b8a3a7","order_by":1,"name":"Hua Wu","email":"","orcid":"","institution":"Hainan General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Hua","middleName":"","lastName":"Wu","suffix":""},{"id":16270941,"identity":"1255a16c-7eba-4d5e-97ff-1ae57d8497d9","order_by":2,"name":"Xiao jun Zhou","email":"","orcid":"","institution":"Hainan General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xiao","middleName":"jun","lastName":"Zhou","suffix":""},{"id":16270942,"identity":"93ec25e3-6cd7-4eec-87d9-6771a85c4f1b","order_by":3,"name":"Qin fang Cao","email":"","orcid":"","institution":"Hainan General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qin","middleName":"fang","lastName":"Cao","suffix":""},{"id":16270943,"identity":"8c1f5904-0983-4b94-b54e-b48b55a8cfc7","order_by":4,"name":"Xu ming Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwUlEQVRIiWNgGAWjYHACNgYGAxs5NvbGxocfiNdSkGbMz3O42ViCeC0fDidKzkhvE+AhRr3Bjey0xwUGzAkGNx+2MUgw2MnpNhDScubsduMZBmx5BrcT2x4UMCQbmx0goMXseO82aR4DnmKglnYDCYYDidsIajnMC9Iikbjh5sE2CR6itEBsMUicOYORSC32Z86CtCQAAzkRGMgGRPhFckYuUMuf/8CoPP7w4YcKOzmCWtCAAWnKR8EoGAWjYBTgAAB3wEG5DJKqSwAAAABJRU5ErkJggg==","orcid":"","institution":"Hainan General Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xu","middleName":"ming","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2021-03-12 16:49:10","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-322273/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-322273/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13683560,"identity":"01e851bf-92f2-4f27-8328-2a475fb3c8e4","added_by":"auto","created_at":"2021-09-17 12:03:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":339495,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-322273/v1/efc5c1d6-cf1c-40c3-b4aa-cb29bfae458b.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eEvaluation of the Antibacterial Activity of Piperacillin–tazobactam\u0026nbsp;Against Burkholderia Pseudomallei\u0026nbsp;in Vitro\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMelioidosis is a zoonotic disease caused by \u003cem\u003eBurkholderia pseudomallei \u003c/em\u003e(\u003cem\u003eB.\u0026nbsp;\u003c/em\u003e\u003cem\u003epseudomallei\u003c/em\u003e). The disease is mainly epidemic in tropical and subtropical areas between latitudes of 20 degrees north and south, such as Southeast Asia and Northern Australia[1-3]. Hainan Island is the largest tropical island in southern China and is close to Thailand, Vietnam, Laos and other countries with a high incidence of melioidosis.The high temperature and humid tropical monsoon climate make Hainan Island become a major epidemic focus of \u003cem\u003eB. pseudomallei\u003c/em\u003e. The clinical manifestations of melioidosis are complex and changeable. It can present acutely with fever and chills secondary to a localized infection or septicaemia. Chronic cases are seen when abscesses develop insidiously at various tissue sites or organs. Consistent with international guidelines[4-5], melioidosis is treated in Hainan with intravenous ceftazidime or meropenem for a minimum 2-week intensive phase, with longer intensive therapy for critically ill patients, followed by a minimum 3-month eradication phase with oral antibiotics (trimethoprim\u0026ndash;sulfamethoxazole is the preferred agent, and amoxicillin/clavulanic acid or doxycycline is the second choice). However, recently, there have been reports of \u003cem\u003eB. pseudomallei\u003c/em\u003e resistant to ceftazidime, trimethoprim\u0026ndash;sulfamethoxazole (TMP\u0026ndash;SMX), and amoxicillin\u0026ndash;clavulanic acid from different melioidosis endemic countries of the world, including neighbouring India[1,6-10]. Piperacillin/tazobactam has a broad antibacterial spectrum, strong tissue permeability and high-concentration distribution in body fluid and blood after injection. However, it is rarely\u0026nbsp;used in the clinic because of the lack of a recommendation of an MIC breakpoint from the American for Clinical and Laboratory Standards Institute (CLSI) for \u003cem\u003eB. pseudomallei\u003c/em\u003e\u003cem\u003e. \u003c/em\u003eIn this study, we reviewed the treatment of 109 hospitalized patients with\u0026nbsp;melioidosis and found that 2 patients were cured successfully with piperacillin/tazobactam. This observation aroused our interest in the activity of piperacillin/tazobactam against \u003cem\u003eB. pseudomallei\u003c/em\u003e in vitro. With this information, the present study was undertaken to compare the MIC\u003csub\u003e50 \u003c/sub\u003eand MIC\u003csub\u003e90 \u003c/sub\u003evalues of piperacillin/tazobactam, meropenem(with an EUCAST MIC breakpoint) and imipenem, doxycycline, amoxicillin/clavulanic acid, tetracycline, TMP\u0026ndash;SMX, and ceftazidime (with CLSI-recommended MIC breakpoint)[11] for \u003cem\u003eB. pseudomallei\u003c/em\u003e isolated from patients during the period of 2010\u0026ndash;2018 in Hainan General Hospital by Etest to provide a theoretical basis for clinical application and provide additional choices for the treatment of melioidosis.\u003c/p\u003e"},{"header":"Materials And Methods","content":"\u003ch2\u003eBacterial isolates\u003c/h2\u003e\n\u003cp\u003eA total of 109 \u003cem\u003eB. pseudomallei\u003c/em\u003e isolated from melioidosis patients over a period of 8 years (June 2010 to May 2018) were collected in the Department of Microbiology of a 3000-bed tertiary care referral hospital in Haikou city (Hainan Province, China). \u003cem\u003eB. pseudomallei\u003c/em\u003e isolates were presumptively identified by characteristic growth, Gram staining, oxidase test, and biochemical speciation (Vitek 2 Compact VT2.R 7.01; bioM\u0026eacute;rieux,France). Isolate identification was confirmed by Vitek MS (bioM\u0026eacute;rieux, France), and isolates were typed by multilocus sequence typing (MLST)[12]. The specimens included 70 blood cultures, 8 respiratory specimens, 5 urine samples and 26 purulent secretions.\u003c/p\u003e\n\u003ch2\u003eDetermination of MIC\u003c/h2\u003e\n\u003cp\u003eAntimicrobial susceptibility testing was performed by Etest (bioM\u0026eacute;rieux) according to the manufacturer\u0026rsquo;s instructions. This method of testing has previously been shown to be comparable with the gold standard of microbroth dilution[13-14]. Minimum\u0026nbsp;inhibitory concentrations (MICs) were read after 18 h and 24 h of incubation at 37 \u0026deg;C under aerobic conditions. For TMP/SMX, the MIC was read at 80% inhibition as per the manufacturer\u0026rsquo;s instructions. The MIC (\u0026mu;g/ml) interpretations for susceptible (S),\u003c/p\u003e\n\u003cp\u003eintermediate (I), and resistant (R) to imipenem, doxycycline, amoxicillin/clavulanic\u0026nbsp;acid, tetracycline, TMP/SMX, and ceftazidime were carried out following the CLSI published guideline M45-A2 [11]. The MIC interpretation for meropenem was carried out following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. The MIC\u003csub\u003e50 \u003c/sub\u003eand MIC\u003csub\u003e90\u003c/sub\u003e of all antibiotics were calculated. The quality control strains were \u003cem\u003eEscherichia coli\u003c/em\u003e (ATCC25922) and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (ATCC27853). All the quality control results were in accordance with the CLSI.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe results show that the mainly MIC values of imipenem, meropenem, ceftazidime, amoxicillin/clavulanic acid and tetracycline were 0.25-0.5 \u0026mu;g/ml, 0.5-1.0 \u0026mu;g/ml, 1.0-2.0 \u0026mu;g/ml, 2.0-4.0 \u0026mu;g/ml and 1.0-4.0 \u0026mu;g/ml, respectively. The mainly MIC values of piperacillin/tazobactam, doxycycline and TMP/SMX were 0.25-0.5\u0026nbsp;\u0026mu;g/ml, 0.25-1.0 \u0026mu;g/ml, and 0.5-2.0 \u0026mu;g/ml, respectively. The detailed MIC interpretive values used in the study are shown in Table 1.\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eTable 1 \u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eThe concentration distribution and accumulation rate o\u003c/strong\u003e\u003cstrong\u003ef \u003c/strong\u003e\u003cstrong\u003eeight\u003c/strong\u003e\u0026nbsp;\u003cstrong\u003eantimicrobial agents against 109 \u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eBurkholderia pseudomallei\u003c/em\u003e\u003c/strong\u003e \u003cstrong\u003eisolates from Haikou\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e\u003cstrong\u003eHainan \u003c/strong\u003e\u003cstrong\u003eProvince\u003c/strong\u003e\u003cstrong\u003e,\u003c/strong\u003e\u003cstrong\u003eChina.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"margin-left: auto; margin-right: auto;\" border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd rowspan=\"2\" width=\"69\"\u003e\n\u003cp\u003eDrug concentration\u003c/p\u003e\n\u003cp\u003e(\u0026mu;g/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMeropenem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmox\u0026ndash;Clav\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePip\u0026ndash;Tazo\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTMP\u0026ndash;SMX\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Imipenem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDoxycycline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCeftazidime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd colspan=\"2\" width=\"86\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTetracycline\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003ch4\u003eCumulative rate (%)\u003c/h4\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003eCumulative rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003eCumulative rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003eCumulative rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003eCumulative rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003eCumulative rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003eCumulative rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003eN\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003eCumulative rate (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e0.008\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e0.016\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e0.032\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e0.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd 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width=\"25\"\u003e\n\u003cp\u003e29\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e99.9\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e99.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e19\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e94.5\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e99.1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e99.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e16\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e99.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e32\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e99.1\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e64\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e128\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"69\"\u003e\n\u003cp\u003e256\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e\u0026mdash;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"25\"\u003e\n\u003cp\u003e0\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"61\"\u003e\n\u003cp\u003e100.0\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"17\" width=\"69\"\u003e\n\u003cp\u003eN: Number of strains, \u003cem\u003eAmox\u003c/em\u003e\u0026ndash;Clav: amoxicillin/clavulanic acid, \u003cem\u003ePip\u003c/em\u003e\u0026ndash;\u003cem\u003eTazo\u003c/em\u003e: piperacillin\u0026ndash;tazobactam, \u003cem\u003eTMP\u003c/em\u003e\u0026ndash;\u003cem\u003eSMX\u003c/em\u003e: trimethoprim/sulfamethoxazole\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eThe sensitivity of the 109 strains of \u003cem\u003eB. pseudomallei\u003c/em\u003e to the eight antibiotics was as follows. Piperacillin/tazobactam had no MIC breakpoint in the CLSI guidelines. All the isolates were uniformly sensitive (100%) to ceftazidime, imipenem, and amoxicillin\u0026ndash;clavulanic acid. Of the 109 isolates, 103 (94.49%) were susceptible to tetracycline at the MIC breakpoint of \u0026le;4.0 \u0026mu;g/ml; 5 isolates had intermediate resistance to tetracycline (MIC=8 \u0026mu;g/ml); and 1 isolate was resistant (MIC \u0026ge; 16.0 \u0026mu;g/ml). Moreover, 108 isolates (99.08%) were susceptible to doxycycline at the MIC breakpoint of \u0026le;4 \u0026mu;g/ml, and 1 isolate was resistant (MIC\u0026ge;16.0 \u0026mu;g/ml), whereas none had intermediate breakpoint. Finally, 104 (94.5%) were susceptible to TMP/SMX at the MIC breakpoint of \u0026le;2/38 \u0026mu;g/ml, and 6 isolates was resistant (MIC\u0026ge;4.0/76 \u0026mu;g/ml). There was no intermediate breakpoint according to the CLSI guidelines for TMP/SMX. In addition,isolates with an MIC of \u0026gt;2 \u0026mu;g/ml for meropenem were considered resistant, and isolates with an MIC\u0026le;2 \u0026mu;g/ml were susceptible based on the EUCAST guidelines. Therefore, 106 isolates (97.24%) were susceptible, and 3 isolates (2.76%) were resistant to meropenem. The MICs of antibiotics that inhibited 50% (MIC\u003csub\u003e50\u003c/sub\u003e) and 90% (MIC\u003csub\u003e90\u003c/sub\u003e) of the 109 isolates are shown in Table 2.\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eTable 2 \u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eMinimum inhibitory concentrations (MICs) of \u003c/strong\u003e\u003cstrong\u003eeight\u003c/strong\u003e\u003cstrong\u003e antimicrobial agents against 109 \u003c/strong\u003e\u003cstrong\u003e\u003cem\u003eBurkholderia pseudomallei\u003c/em\u003e\u003c/strong\u003e \u003cstrong\u003eisolates from Haikou, Hainan \u003c/strong\u003e\u003cstrong\u003eProvince,\u003c/strong\u003e\u003cstrong\u003e China.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"margin-left: auto; margin-right: auto;\" border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr style=\"height: 15.9517px;\"\u003e\n\u003ctd style=\"height: 31.9517px;\" rowspan=\"2\" width=\"191\"\u003e\n\u003cp\u003eAntimicrobial agent\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 31.9517px;\" rowspan=\"2\" width=\"174\"\u003e\n\u003cp\u003eMIC\u003csub\u003e50\u003c/sub\u003e (\u0026mu;g/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 31.9517px;\" rowspan=\"2\" width=\"175\"\u003e\n\u003cp\u003eMIC\u003csub\u003e90\u003c/sub\u003e (\u0026mu;g/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 15.9517px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 16px;\"\u003e\n\u003ctd style=\"height: 16px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003eImipenem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003eMeropenem\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003eCeftazidime\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003eAmoxicillin/clavulanic acid\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003eTetracycline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003eDoxycycline\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003eTMP/SMX\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e1\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr style=\"height: 35px;\"\u003e\n\u003ctd style=\"height: 35px;\" width=\"191\"\u003e\n\u003cp\u003ePiperacillin\u0026ndash;tazobactam\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"174\"\u003e\n\u003cp\u003e0.25\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"175\"\u003e\n\u003cp\u003e0.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd style=\"height: 35px;\" width=\"0\"\u003e\u0026nbsp;\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAll the results were analysed, and the order of the MIC\u003csub\u003e50\u003c/sub\u003e for the eight antimicrobial agents was piperacillin/tazobactam MIC\u003csub\u003e50\u003c/sub\u003e (0.25 \u0026mu;g/ml) \u0026lt; imipenem MIC\u003csub\u003e50\u003c/sub\u003e (0.5 \u0026mu;g/ml), meropenem MIC\u003csub\u003e50\u003c/sub\u003e (0.5 \u0026mu;g/ml), doxycycline MIC\u003csub\u003e50\u003c/sub\u003e (0.5 \u0026mu;g/ml) \u0026lt;TMP/SMX MIC\u003csub\u003e50\u003c/sub\u003e (1 \u0026mu;g/ml), ceftazidime MIC\u003csub\u003e50\u003c/sub\u003e (1 \u0026mu;g/ml) \u0026lt; tetracycline MIC\u003csub\u003e50\u003c/sub\u003e (2 \u0026mu;g/ml), amoxicillin/clavulanic acid MIC\u003csub\u003e50\u003c/sub\u003e (2 \u0026mu;g/ml). In addition, the MIC\u003csub\u003e90\u003c/sub\u003e from low to high was piperacillin/tazobactam (0.5 \u0026mu;g/ml), imipenem (0.5 \u0026mu;g/ml), meropenem (1 \u0026mu;g/ml), ceftazidime (2 \u0026mu;g/ml), doxycycline (2 \u0026mu;g/ml), TMP/SMX (2 \u0026mu;g/ml), amoxicillin/clavulanic acid (4 \u0026mu;g/ml), tetracycline (4 \u0026mu;g/ml) and so on.\u003c/p\u003e\n\u003cp\u003eIn addition, based on the peak blood concentration (Cmax) of China and Italy dosage forms of piperacillin/tazobactam commonly used in the clinic, the ratios of C\u003csub\u003emax\u003c/sub\u003e to MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90\u003c/sub\u003e are shown in Table 3.\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003eTable 3 \u003c/strong\u003e\u003c/p\u003e\n\u003cp style=\"text-align: center;\"\u003e\u003cstrong\u003ePiperacillin/tazobactam dosage forms and the ratios of peak blood concentration (Cmax) to MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90\u003c/sub\u003e are listed\u003c/strong\u003e\u003c/p\u003e\n\u003ctable style=\"margin-left: auto; margin-right: auto;\" border=\"1\" width=\"0\"\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003eDosage\u0026nbsp;form (China)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e1.25 g\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e2.5 g\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e5.0 g\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eDosage form(Italy)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"67\"\u003e\n\u003cp\u003e2.25 g\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e3.375 g\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e4.5 g\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003eC\u003csub\u003emax\u003c/sub\u003e (\u0026mu;g/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e42.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e80.3\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e192.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eC\u003csub\u003emax\u003c/sub\u003e (\u0026mu;g/ml)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"67\"\u003e\n\u003cp\u003e134\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e242\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e298\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003eC\u003csub\u003emax\u003c/sub\u003e/MIC\u003csub\u003e50\u003c/sub\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e170.8\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e321.2\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e770\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"94\"\u003e\n\u003cp\u003eC\u003csub\u003emax\u003c/sub\u003e/MIC\u003csub\u003e50 \u003c/sub\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"67\"\u003e\n\u003cp\u003e536\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e968\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e1192\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd width=\"102\"\u003e\n\u003cp\u003eC\u003csub\u003emax\u003c/sub\u003e/MIC\u003csub\u003e90\u003c/sub\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e85.4\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e160.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003e385\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"73\"\u003e\n\u003cp\u003eC\u003csub\u003emax\u003c/sub\u003e/MIC\u003csub\u003e90\u003c/sub\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"67\"\u003e\n\u003cp\u003e268\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"63\"\u003e\n\u003cp\u003e484\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd width=\"64\"\u003e\n\u003cp\u003e596\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"8\" width=\"102\"\u003e\n\u003cp\u003eDosage form, C\u003csub\u003emax \u003c/sub\u003efrom piperacillin/tazobactam instructions\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMelioidosis is an important public health disease in Southeast Asia and Australia, but it is still considered a potential emerging infectious disease in tropical developing countries[2,13-18]. A 2016 modelling study estimated that there are ~165,000 cases of melioidosis in humans per year worldwide, of which 89,000 (54%) are estimated to be fatal[19]. Although quinolones have slight antibacterial activity in vitro, their treatment failure rate is relatively high[8,20]. The mortality of melioidosis ranges from 14 to 40% and may be as high as 80% if effective antibiotics are not given[21]. With the early use of antibiotics, the mortality rate can also be reduced to under 10%[22]. However, \u003cem\u003eB. pseudomallei\u003c/em\u003e is intrinsically resistant to many antibiotics (such as penicillin, ampicillin, first- and second-generation cephalosporins, macrolides, aminoglycosides, streptomycin, polymyxin, etc.)[23-24]. At present, only TMP/SMX, ceftazidime, tetracycline, doxycycline, amoxicillin/clavulanic acid and imipenem have MIC breakpoints for \u003cem\u003eB. pseudomallei \u003c/em\u003ein the CLSI guidelines[11]. Therefore, the selection of antimicrobial agents is limited for the treatment of melioidosis.\u003c/p\u003e\n\u003cp\u003ePiperacillin, as with all other \u0026beta;-lactam antibiotics, interferes with the final stage of peptidoglycan synthesis by inhibiting penicillin-binding proteins (PBPs), which crosslink peptidoglycan polymers[25]. Tazobactam extends piperacillin\u0026rsquo;s spectrum of activity to include bacteria producing many Ambler class A \u0026beta;-lactamases,\u003c/p\u003e\n\u003cp\u003enarrow- and extended-spectrum (TEM-, SHV-, and CTX-M-type) \u0026beta;-lactamases and some class C (AmpC-type) \u0026beta;-lactamases[26-27]. Piperacillin-tazobactam has the broadest spectrum of activity among the penicillin class of \u0026beta;-lactam antibiotics and is generally active against most of the typical human pathogens, including aerobic and anaerobic gram-positive and gram-negative bacteria[25]. Piperacillin/tazobactam is widely distributed in various tissues and body fluids after injection, and its clinical indications are also relatively broad, such as respiratory tract infection, bacterial septicaemia, and subcutaneous abscess[25]. The clinical infection of the target bacteria we studied is also complex and diverse and is considered \"like a hundred diseases\". Piperacillin/tazobactam has a sensitive CLSI breakpoint for Enterobacteriaceae bacteria but no MIC breakpoints for non-fermentative bacteria except \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e, \u003cem\u003eAcinetobacter baumannii\u003c/em\u003e and \u003cem\u003eHaemophilus influenzae\u003c/em\u003e.\u003c/p\u003e\n\u003cp\u003eTherefore, we compared the MICs of piperacillin/tazobactam with those of six antibiotics(with a CLSI MIC breakpoints) and meropenem (with an EUCAST MIC breakpoint) to provide additional choices for the treatment of melioidosis in this study. The results showed that the MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90\u003c/sub\u003e of piperacillin/tazobactam were 0.25 \u0026mu;g/ml and 0.5 \u0026mu;g/ml, respectively. The MIC\u003csub\u003e50\u003c/sub\u003e of piperacillin/tazobactam was lower than that of the other seven antibiotics. In addition, the MIC\u003csub\u003e90\u003c/sub\u003e was also lower than that of the other six antibiotics, except for imipenem (the MIC\u003csub\u003e90\u003c/sub\u003e of piperacillin/tazobactam was equal to that of imipenem). This result indicates that the antibacterial activity of piperacillin/tazobactam is stronger than that of the other tested antibiotics in vitro. Regarding the pharmacokinetic characteristics in vivo (see Table 3), it was found that both the peak value of the plasma concentration of China and Italy formulations is far higher than the MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90\u003c/sub\u003e values of piperacillin/tazobactam. It is generally believed that antibiotics have bacteriostatic or bactericidal effects in vivo when the blood concentration of antibiotics is 4-6 times higher than the MIC value of target bacteria. In the published literature, the criteria used in these studies to analyse the susceptibility to piperacillin/tazobactam and meropenem to \u003cem\u003eB. pseudomallei\u003c/em\u003e were mostly based on the MIC breakpoint of \u003cem\u003eP. aeruginosa \u003c/em\u003ein the CLSI guidelines[28]. In studies published in Bangladesh, Dutta et al. found that 20 isolates of \u003cem\u003eB. pseudomallei\u003c/em\u003e were uniformly sensitive (100%) to piperacillin\u0026ndash;tazobactam (refer to the MIC breakpoint of \u003cem\u003eP. aeruginosa\u003c/em\u003e in the CLSI guidelines), and both the MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90\u003c/sub\u003e values were 2 \u0026mu;g/ml[28]. These values are obviously higher than the results of our study. However, the number of samples in Dutta\u0026rsquo;s study may be too few, and both the MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90\u003c/sub\u003e values of all isolates to three common antibiotics (imipenem, ceftazidime, and amoxicillin/clavulanic acid) were relatively higher (great\u0026nbsp;than or\u0026nbsp;equal\u0026nbsp;to 2 \u0026mu;g/ml, agar dilution method). This result indicated that the MIC values of the 20 isolates of \u003cem\u003eB. pseudomallei\u003c/em\u003e in Dutta's study were relatively high. In view of the above information, this study still has certain reference significance. It can be used as the theoretical basis for the clinical treatment of \u003cem\u003eB. pseudomallei\u003c/em\u003e infection with piperacillin\u0026ndash;tazobactam.\u003c/p\u003e\n\u003cp\u003eIn this study, we conducted a preliminary study on the MIC of piperacillin\u0026ndash;\u003c/p\u003e\n\u003cp\u003etazobactam for \u003cem\u003eB. pseudomallei\u003c/em\u003e in vitro. We hope that this study can play a valuable role, arousing more attention to antibiotic selection for \u003cem\u003eB. pseudomallei \u003c/em\u003einfection to improve the cure rate and reduce mortality. Therefore, the laboratory should work closely with the clinic to obtain a more clinical pharmacodynamic summary of piperacillin/tazobactam in the treatment of \u003cem\u003eB. pseudomallei\u003c/em\u003e infection and provide more powerful evidence for its treatment.\u003c/p\u003e\n\u003ch2\u003eLimitations\u003c/h2\u003e\n\u003cp\u003eIn this paper, we have not summarized the MIC breakpoint of piperacillin-tazobactam to \u003cem\u003eB. pseudomallei\u003c/em\u003e, but still need a lot of data analysis and summary.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eMIC: minimum inhibitory\u003c/strong\u003e\u003cstrong\u003econcentration\u003c/strong\u003e\u003cstrong\u003e;\u003c/strong\u003eTMP\u0026ndash;SMX:trimethoprim\u0026ndash;sulfamethoxazole;\u0026nbsp;\u003cem\u003eAmox\u003c/em\u003e\u0026ndash;Clav: amoxicillin/clavulanic acid;\u003cem\u003ePip\u003c/em\u003e\u0026ndash;\u003cem\u003eTazo\u003c/em\u003e: piperacillin\u0026ndash;tazobactam;\u0026nbsp;CLSI:Clinical and Laboratory Standards Institute;EUCAST:the European Committee on Antimicrobial Susceptibility Testing;MLST: multilocus sequence typing; N: Number of strains;PBPs:penicillin-binding proteins.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eEthics approval and consent to participate\u003c/h2\u003e\n\u003cp\u003eThe Medical Ethics Committee of Hainan general hospital approved this study protocol.\u003c/p\u003e\n\u003ch2\u003eConsent for publication\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAvailability of data and materials\u003c/h2\u003e\n\u003cp\u003eAll relevant data of this study are within the paper.\u003c/p\u003e\n\u003ch2\u003eCompeting interests\u003c/h2\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch2\u003eFunding\u003c/h2\u003e\n\u003cp\u003eThis work was funded by the Key Research and Development Program of Hainan Province (No. ZDYF2018113).\u003c/p\u003e\n\u003ch2\u003eAuthors\u0026rsquo; contributions\u003c/h2\u003e\n\u003cp\u003eMeihui Huang performed the culture, identifcation, literature search and manuscript writing. Hua Wu performed the antimicrobial susceptibility tests. Xiaojun Zhou was involved in storage and identifcation of organisms and primary data analysis. Qinfang Cao was involved in analyzed the\u0026nbsp;clinical\u0026nbsp;data.Xuming Wang was involved in study design, analysis of the data and manuscript writing. All authors read and approved the fnal manuscript.\u003c/p\u003e\n\u003ch2\u003eAcknowledgements\u003c/h2\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eNhung PH, Van VH, Anh NQ, Phuong DM.Antimicrobial susceptibility of Burkholderia pseudomallei isolates in Northern Vietnam.J Glob Antimicrob Resist 2019;18:34-36.\u003c/li\u003e\n\u003cli\u003eCrowe A,McMahon N,Currie BJ,Baird RW.Current antimicrobial susceptibility of first-episode melioidosis Burkholderia pseudomallei isolates from the Northern Territory, Australia. Int J Antimicrob Agents 2014;44(2):160-2.\u003c/li\u003e\n\u003cli\u003eZueter AR,Rahman ZA,Abumarzouq M,Harun A.Multilocus sequence types of clinical Burkholderia pseudomallei isolates from peninsular Malaysia and their associations with disease outcomes. BMC Infect Dis 2018;18(1):5.\u003c/li\u003e\n\u003cli\u003eWiersinga WJBJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med 2012;367:1035\u0026ndash;44.\u003c/li\u003e\n\u003cli\u003eWiersinga WJ,Virk HS,Torres AG, Currie BJ, Peacock SJ, Dance DAB,et al. Melioidosis.Nat Rev Dis Primers 2018;4:17107.\u003c/li\u003e\n\u003cli\u003eIrmawanti-Rahayu S, Noorhamdani AS, Santoso S. Resistance pattern of\u0026nbsp;\u003cem\u003eBurkholderia pseudomallei\u003c/em\u003e from clinical isolates at Dr. Saiful Anwar general hospital, Malang-Indonesia. J Clin Microbiol Infect Dis 2014;1(1):17\u0026ndash;20.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"7\"\u003e\n\u003cli\u003eSarovich DS,Price EP,Von Schulze AT,Cook JM,Mayo M, Watson LM, et al. Characterization of ceftazidime resistance mechanisms in clinical isolates of \u003cem\u003eBurkholderia pseudomallei\u003c/em\u003e from Australia. PLoS ONE 2012;7:e30789.\u003c/li\u003e\n\u003cli\u003eHassan MR, Vijayalakshmi N, Pani SP, Peng NP, Mehenderkar R, Voralu K, et al. Antimicrobial susceptibility patterns of Burkholderia pseudomallei among melioidosis cases in Kedah, Malaysia. Southeast Asian J Trop Med Public Health 2014;45(3):680-8.\u003c/li\u003e\n\u003cli\u003eWuthiekanun V, Amornchai P, Saiprom N, Chantratita N, Chierakul W, Koh GCKW, et al. Survey of antimicrobial resistance in clinical \u003cem\u003eBurkholderia\u0026nbsp;\u003c/em\u003e\u003cem\u003epseudomallei\u003c/em\u003e isolates over two decades in northeast Thailand. Antimicrob Agents Chemother 2011;11:5388\u0026ndash;91.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"10\"\u003e\n\u003cli\u003eBehera B, Prasad Babu TL, Kamalesh A, Reddy G. Ceftazidime resistance in \u003cem\u003eBurkholderia pseudomallei\u003c/em\u003e: frst report from India. Asian Pac J Trop Med 2012;5(4):329\u0026ndash;30.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"11\"\u003e\n\u003cli\u003eCLSI. Methods for antimicrobial dilution and disk susceptibility testing for infrequently isolated or fastidious bacteria. 3rd ed. CLSI guidelin M45. Wayne, PA: Clinical and Laboratory Standards Institute. 2015.\u003c/li\u003e\n\u003cli\u003eWang XM, Zheng X, Wu H, Zhou XJ,Kuang HH,Guo HL,et al. Multilocus Sequence Typing of Clinical Isolates of Burkholderia pseudomallei Collected in Hainan, a Tropical Island of Southern China. Am J Trop Med Hyg 2016;95(4):760-764.\u003c/li\u003e\n\u003cli\u003eJenney AWJ,Lum G, Fisher DA, Currie BJ. Antimicrobial susceptibility of Burkholderia pseudomallei from tropical northern Australia and implications for therapy of melioidosis. Int J Antimicrob Agents 2001;17:109\u0026ndash;13.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"14\"\u003e\n\u003cli\u003ePiliouras P,Ulett GC, Ashhurst-Smith C, Hirst RG, Norton RE. A comparison of antibiotic susceptibility testing methods for cotrimoxazole with Burkholderia pseudomallei. Int J Antimicrob Agents 2002;19:427\u0026ndash;9.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"15\"\u003e\n\u003cli\u003eCurrie, B. J., Dance, D. A. \u0026amp; Cheng, A. C. The global distribution of \u003cem\u003eBurkholderia pseudomallei \u003c/em\u003eand melioidosis: an update. Trans. R. Soc. Trop. Med. Hyg 2008;102 Suppl 1:S1-4.\u003c/li\u003e\n\u003cli\u003eLimmathurotsakul D, Dance DAB, Wuthiekanun V, Kaestli M, Mayo M, Warner J, et al. Systematic review and consensus guidelines for environmental sampling of \u003cem\u003eBurkholderia pseudomallei\u003c/em\u003e. PLoS Negl Trop Dis 2013;7(3):e2105.\u003c/li\u003e\n\u003cli\u003eLimmathurotsakul D, Peacock SJ. Melioidosis: a clinical overview. Br Med Bull 2011;99:125\u0026ndash;39.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"18\"\u003e\n\u003cli\u003eBarai L, Jilani MSA, Haq JA. Melioidosis\u0026mdash;case reports and review of cases recorded among Bangladeshi population from 1988\u0026ndash;2014. Ibrahim Med College J 2014;8:25\u0026ndash;31.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"19\"\u003e\n\u003cli\u003eLimmathurotsakul D, Golding N, Dance DA, Messina JP,et al. Predicted global distribution of \u003cem\u003eBurkholderia pseudomallei \u003c/em\u003eand burden of melioidosis. Nat Microbiol 2016; 11(1):15008.\u003c/li\u003e\n\u003cli\u003eDance DA, Wuthiekanun V, Chaowagul W, White NJ. The antimicrobial susceptibility of Pseudomonas pseudomallei. Emergence of resistance in vitro and during treatment. J Antimicrob Chemother 1989;24:295\u0026ndash;309.\u003c/li\u003e\n\u003cli\u003eCheng AC, West TE, Limmathurotsakul D, Peacock SJ. Strategies to reduce mortality from bacterial sepsis in adults in developing countries. PLOS Med 2008;5:1173\u0026ndash;9.\u003c/li\u003e\n\u003cli\u003eCurrie BJ.Melioidosis: evolving concepts in epidemiology, pathogenesis, and treatment. Semin. Respir Crit Care Med 2015;36, 111\u0026ndash;125.\u003c/li\u003e\n\u003cli\u003eWiersinga WJBJ, Currie BJ, Peacock SJ. Melioidosis. N Engl J Med 2012;367: 1035\u0026ndash;44.\u003c/li\u003e\n\u003c/ol\u003e\n\u003col start=\"24\"\u003e\n\u003cli\u003eSchweizer HP. Mechanisms of antibiotic resistance in Burkholderia pseudomallei: implications for treatment of melioidosis. Future Microbiol 2012;7:1389\u0026ndash;99.\u003c/li\u003e\n\u003cli\u003eHayashi Y,Roberts JA,Paterson DL,\u003ca href=\"https://xueshu.baidu.com/s?wd=author:(Jeffrey%20Lipman)%20\u0026amp;tn=SE_baiduxueshu_c1gjeupa\u0026amp;ie=utf-8\u0026amp;sc_f_para=sc_hilight=person\"\u003eLipman\u003c/a\u003e J. Pharmacokinetic evaluation of piperacillin-tazobactam. Expert Opin Drug Met 2010;6(8):1017-31.\u003c/li\u003e\n\u003cli\u003eToussaint KA, Gallagher JC. \u0026beta;-Lactam/\u0026beta;-lactamase inhibitor combinations: from then to now. Ann Pharmacother 2015; 49(1):86 \u0026ndash;98.\u003c/li\u003e\n\u003cli\u003eGin A, Dilay L, Karlowsky JA, Walkty A, Rubinstein E, Zhanel GG. Piperacillin-tazobactam: a beta-lactam/beta-lactamase inhibitor combination. Expert Rev Anti Infect Ther 2007;5:365\u0026ndash;383.\u003c/li\u003e\n\u003cli\u003eDutta S, Haq S, Hasan MR, Haq JA. Antimicrobial susceptibility pattern of clinical isolates of Burkholderia pseudomallei in Bangladesh. BMC Res Notes. 2017;10(1):299.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Burkholderia pseudomallei,Piperacillin/tazobactam,Antimicrobial susceptibility,MIC50 and MIC90,Etest","lastPublishedDoi":"10.21203/rs.3.rs-322273/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-322273/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003eMelioidosis is a zoonotic disease caused by \u003cem\u003eBurkholderia pseudomallei \u003c/em\u003e(\u003cem\u003eB. pseudomallei\u003c/em\u003e). Because \u003cem\u003eB. pseudomallei\u003c/em\u003e is naturally resistant to a variety of antibiotics, such as penicillin, ampicillin, first-and second-generation cephalosporins, macrolides, aminoglycosides, streptomycin, polymyxin, etc., the selection of drugs is limited. The present study aimed to evaluate the antibacterial activity of piperacillin/tazobactam against\u003cem\u003e B. pseudomallei \u003c/em\u003ein vitro to provide a theoretical basis and a variety of therapeutic options for clinical application.The\u003cstrong\u003e \u003c/strong\u003eantimicrobial susceptibilities of all \u003cem\u003eB. pseudomallei\u003c/em\u003e isolated from melioidosis patients were detected by Etest method. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThe MIC\u003csub\u003e50\u003c/sub\u003e values of piperacillin/tazobactam, imipenem, meropenem, doxycycline, trimethoprim–sulfamethoxazole, ceftazidime, tetracycline, and amoxicillin/clavulanic acid were 0.25 μg/ml, 0.5 μg/ml, 0.5 μg/ml, 0.5 μg/ml, 1 μg/ml, 1 μg/ml, 2 μg/ml, and 2 μg/ml, respectively. Their MIC\u003csub\u003e90 \u003c/sub\u003evalues were 0.5 μg/ml, 0.5 μg/ml, 1 μg/ml, 2 μg/ml, 2 μg/ml, 2 μg/ml, 4 μg/ml, and 4 μg/ml, respectively. All the isolates were uniformly sensitive (100%) to ceftazidime, imipenem and amoxicillin–clavulanic acid. The rate of antimicrobial sensitivity for doxycycline was 99.08%, for tetracycline-sulfamethoxazole 94.50%, and for tetracycline 94.49%.Both the MIC\u003csub\u003e50\u003c/sub\u003e and MIC\u003csub\u003e90 \u003c/sub\u003evalues of piperacillin/tazobactam were lower than those of the seven other antibiotics, indicating that it has strong antibacterial activity against \u003cem\u003eB. pseudomallei\u003c/em\u003e in vitro.\u003c/p\u003e","manuscriptTitle":"Evaluation of the Antibacterial Activity of Piperacillin–tazobactam\u0026nbsp;Against Burkholderia Pseudomallei\u0026nbsp;in Vitro","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-04-01 20:53:18","doi":"10.21203/rs.3.rs-322273/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":"8f2af84b-632e-4344-beed-9eec4af954f1","owner":[],"postedDate":"April 1st, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":3351245,"name":"General Microbiology"},{"id":3351246,"name":"Health Economics \u0026 Outcomes Research"}],"tags":[],"updatedAt":"2021-04-01T20:53:18+00:00","versionOfRecord":[],"versionCreatedAt":"2021-04-01 20:53:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-322273","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-322273","identity":"rs-322273","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}