Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli

Seo, Yu Bin; Jacob, Louis; Kim, Young Keun; Lee, Seung Soon; Lee, Jeong A; Kim, Hyo Youl; Uh, Young; Kim, Han Sung; Song, Wonkeun

doi:10.1186/s12879-017-2502-x

Cited by 89 publications

(85 citation statements)

References 40 publications

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“…Interestingly, despite this higher cefepime exposure, which initially demonstrated slight bacterial kill at 24 h, regrowth was noted during the following 24 h of therapy. These findings are reflective of clinical data in patients with ESBL-derived cUTIs (11). As expected, ertapenem was effective against both isolates, producing a large and sustained bacterial kill over 48 h. Our observations are consistent with the clinical and microbiologic outcomes reported for this compound in the setting of cUTIs (11)(12)(13).…”

supporting

confidence: 80%

“…These findings are reflective of clinical data in patients with ESBL-derived cUTIs (11). As expected, ertapenem was effective against both isolates, producing a large and sustained bacterial kill over 48 h. Our observations are consistent with the clinical and microbiologic outcomes reported for this compound in the setting of cUTIs (11)(12)(13). The use of murine infection models during the anti-infective research and development process has been a standard practice since the 1950s (14).…”

supporting

confidence: 79%

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Translational Efficacy of Humanized Exposures of Cefepime, Ertapenem, and Levofloxacin against Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Murine Model of Complicated Urinary Tract Infection

Monogue

Nicolau

2017

Antimicrob Agents Chemother

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Validated animal models are required as bridging tools to assess the utility of novel therapies and potential microbiologic outcomes. Herein, we utilized uropathogenic extended-spectrum-␤-lactamase (ESBL)-producing and non-ESBL-producing Escherichia coli in the neutropenic murine complicated urinary tract infection (cUTI) model with humanized exposures of cefepime, ertapenem, and levofloxacin to assess its translational value to human outcomes. Our data support the translational utility of this murine model to cUTI in humans as humanized exposures produced microbiologic outcomes consistent with the phenotypic profiles of the organisms.KEYWORDS ESBL, Escherichia coli, urinary tract infection, cefepime, ertapenem, levofloxacin U rinary tract infections (UTIs) are one of the most common types of communityacquired and nosocomial infections, impacting 150 million people per year globally (1). Escherichia coli is the leading cause of UTIs, and often displays resistance to currently available antibiotics due to the production of various enzymes, such as extended-spectrum ␤-lactamases (ESBLs) (1). ESBLs are enzymes produced by Gramnegative bacteria, namely, E. coli, and are responsible for the resistance against penicillins, cephalosporins, and aztreonam (2). Carbapenems, such as ertapenem, are standard for the treatment of infections caused by ESBL-producing organisms, although the potential clinical utility of extended-spectrum cephalosporins, notably cefepime, has yet to be clearly defined. Herein, we used humanized exposures of cefepime, 2 g every 8 h (q8h) (0.5-h infusion), ertapenem, 1 g every 24 h (q24h), and levofloxacin, 500 mg q24h, against uropathogenic ESBL-and non-ESBL-producing E. coli and assessed antimicrobial efficacy after 24 and 48 h of therapy in a neutropenic murine complicated UTI (cUTI) model.Commercially available cefepime 1g (lot no. 106014C), ertapenem 1g (lot no. m027105), and levofloxacin 500 mg (lot no. CLF150003) vials were acquired from Cardinal Health, Inc. Vials were reconstituted according to the package insert and further diluted with 0.9% normal saline solution (Hospira, Inc., Lake Forest, IL). Doses were administered as 0.2-ml subcutaneous injections to achieve humanized exposures of 2 g cefepime q8h (0.5-h infusion), 1 g ertapenem q24h, and 500 mg levofloxacin q24h, as previously described (3-5).Two clinical uropathogenic E. coli isolates (EC 429, ESBL; EC 430, non-ESBL) were used in this study. The MICs of cefepime, ertapenem, and levofloxacin were determined

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supporting

confidence: 80%

supporting

confidence: 79%

Translational Efficacy of Humanized Exposures of Cefepime, Ertapenem, and Levofloxacin against Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Murine Model of Complicated Urinary Tract Infection

Monogue

Nicolau

2017

Antimicrob Agents Chemother

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“…29 The management options for ESBL producing organisms is biggest health challenge around the globe. 30 A case series reported better outcomes for prophylactic use of a combination preparation, ceftibuten plus amoxicillin-clavulanic acid, ceftolozane/tazobactam and tegicycline even in ESBL producing organisms. [31][32][33] Therefore, knowledge about the commonly prevalent organisms and their susceptibility pattern can serve as an essential requirement for accurate management of urinary tract infections.…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial Sensitivity Pattern for Urine Isolates in Urinary Tract Infection

Bukhari¹,

Bukhari²,

Zafar³

et al. 2019

JIMDC

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Background:The increased frequency and management of antibiotic resistance pattern in urinary tract infection (UTI) is a challenging task for the clinicians. Therefore, the current study was planned to identify the microbial etiology of UTI and t he most suitable antibiotics used. The objective of the study was to assess the frequency of antimicrobial sensitivity pattern in patients with urinary tract infection. Material and Methods: This cross-sectional study was carried out at Al Sayed Hospital, Kidney Centre, Rawalpindi over a period of seven months i.e. June 30, 2018 to January 30, 2019. A total of 152 patients were enrolled according to the inclusion and exclusion criteria of the study. Urine culture proceedings were done as per latest recommended guidelines of Clinical and Laboratory Standard Institute (CLSI) for UTI. Results: Highest sensitivity was observed for carbapenems (83.5%), followed by polymyxin B (72.3%), phosphonic acid derivatives (65.8%), aminoglycoside group (65.7%), extended spectrum penicillin (63.1%), imidazolidinedione (59.9%) and tetracycline (59.9%) groups. The least sensitivity was observed for Oxazolidinone (linezolid) (14.5%), teicoplanin (13.8%), tigecycline (10.5%) and firstgeneration cephalosporins (1.3%). Conclusions: Carbapenems showed maximum sensitivity for all urine isolates. The second and third options were polymyxin B and phosphonic acid derivatives, respectively.

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“…Amoxicillin/clavulanic acid as an alternative treatment to carbapenems for infections involving ESBL-producing organisms remains debated [39].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CHROMagar ESBL and Double Disk Synergy Test (DDST) for Screening of Extended Spectrum Beta-lactamase Producing Uropathogens in South-South Nigeria

Uyanga

Ekundayo

Nwankwo

et al. 2019

JAMB

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Background/Purpose: The aim of this study was to evaluate the effectiveness of CHROMagar ESBL in comparison with Double Disc Synergy Test (DDST) for the detection of ESBL producing uropathogens. Methods: Six hundred and sixty urine samples were collected from pregnant women attending antenatal at General hospital Ikot Ekpene, Eket and Oron. Two hundred and fifty eight isolates were obtained while two hundred and thirty one isolates were ESBL producers. Microbact 24E(Oxoid, UK) was used in the identification of bacterial isolates, antibiotic susceptibility test was done using Kirby-Bauer disk diffusion method following CLSI guidelines using commercially available disc (Oxoid Ltd). Double disk synergy test was carried out on the isolates and inoculation was done using CHROMagar ESBL (France). Results: The prevalence of ESBL 35% was recorded. The sensitivity and specificity of DDST was Uyang et al.; JAMB, 17(4): 1-11, 2019; Article no.JAMB.50429 2 88% and 89%, respectively. CHROMagar showed an increase in sensitivity and specificity at 48 h with 98% and 99.0%, respectively. 80% of the ESBL producing isolates were multi drugs resistant. The predominant bacterial pathogens were Enterobacter cloacae (23%), Proteus mirabilis (14%) and Acinetobacter baumanii (13.4%).The ESBL producing isolates showed maximum resistance against Ceftazidime (90%), Cefotaxime (91%), Azetronam (95%), Amikacin (68.2%) followed by ofloxacin (70%) while maximum sensitivity was seen for imipenem (90%) and Augumentin (80%). The study demonstrated that CHROMagar was superior and more sensitive than DDST. Conclusion: CHROMagar ESBL seems to be the most reliable method among phenotypic methods for detection of ESBL in the absence of PCR. Original Research Article

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Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli

Cited by 89 publications

References 40 publications

Translational Efficacy of Humanized Exposures of Cefepime, Ertapenem, and Levofloxacin against Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Murine Model of Complicated Urinary Tract Infection

Translational Efficacy of Humanized Exposures of Cefepime, Ertapenem, and Levofloxacin against Extended-Spectrum-β-Lactamase-Producing Escherichia coli in a Murine Model of Complicated Urinary Tract Infection

Antimicrobial Sensitivity Pattern for Urine Isolates in Urinary Tract Infection

Evaluation of CHROMagar ESBL and Double Disk Synergy Test (DDST) for Screening of Extended Spectrum Beta-lactamase Producing Uropathogens in South-South Nigeria

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