Is It Time to Rethink the Notion of Carbapenem-Sparing Therapy Against Extended-Spectrum β-Lactamase–Producing <i>Enterobacteriaceae</i> Bloodstream Infections? A Critical Review

Chastain, Daniel B; White, Bryan P.; Cretella, David A; Bland, Christopher M.

doi:10.1177/1060028017748943

Cited by 12 publications

(9 citation statements)

References 46 publications

(116 reference statements)

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“…They belong to a subclass of second-generation cephalosporins that confers resistance to degradation by ESBL enzymes. However, cephamycins are not active against AmpC cephalosporinases and porin mutations [48]. Eight observational studies comparing the efficacy of cephamycins and carbapenems in infections (mainly UTIs and bacteremia) due to ESBL-PE have been published to date and are illustrated in Table 2 [49][50][51][52][53][54][55][56].…”

Section: Cephamycinsmentioning

confidence: 99%

Carbapenem-Sparing Strategies for ESBL Producers: When and How

2020

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Extended spectrum β-lactamase (ESBL)-producing bacteria are prevalent worldwide and correlated with hospital infections, but they have been evolving as an increasing cause of community acquired infections. The spread of ESBL constitutes a major threat for public health, and infections with ESBL-producing organisms have been associated with poor outcomes. Established therapeutic options for severe infections caused by ESBL-producing organisms are considered the carbapenems. However, under the pressure of carbapenem overuse and the emergence of resistance, carbapenem-sparing strategies have been implemented. The administration of carbapenem-sparing antibiotics for the treatment of ESBL infections has yielded conflicting results. Herein, the current available knowledge regarding carbapenem-sparing strategies for ESBL producers is reviewed, and the optimal conditions for the “when and how” of carbapenem-sparing agents is discussed. An important point of the review focuses on piperacillin–tazobactam as the agent arousing the most debate. The most available data regarding non-carbapenem β-lactams (i.e., ceftolozane–tazobactam, ceftazidime–avibactam, temocillin, cephamycins and cefepime) are also thoroughly presented as well as non β-lactams (i.e., aminoglycosides, quinolones, tigecycline, eravacycline and fosfomycin).

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Section: Cephamycinsmentioning

confidence: 99%

Carbapenem-Sparing Strategies for ESBL Producers: When and How

2020

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“…The need for such strategies is widely accepted but because they are often implemented together, the relative importance of each is unclear (Chatterjee et al, 2018;Goff et al, 2017). The details of how to best implement these strategies are hotly debated (Lemmen and Lewalter, 2018), especially regarding which antibiotics should be restricted first as a part of antibiotic stewardship strategies (Chastain et al, 2018) or the riskbenefit balance of screening-based patient isolation procedures to reduce transmission (Kardaś-Słoma et al, 2017;Robotham et al, 2016). Designing effective antibiotic stewardship strategies has been hindered by the paucity of evidence concerning which antibiotics exert the strongest selection pressure.…”

Section: Introductionmentioning

confidence: 99%

Metapopulation ecology links antibiotic resistance, consumption, and patient transfers in a network of hospital wards

Shapiro

Leboucher

Myard-Dury

et al. 2020

eLife

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Antimicrobial resistance (AMR) is a global threat. A better understanding of how antibiotic use and between-ward patient transfers (or connectivity) impact population-level AMR in hospital networks can help optimize antibiotic stewardship and infection control strategies. Here, we used a metapopulation framework to explain variations in the incidence of infections caused by 7 major bacterial species and their drug-resistant variants in a network of 357 hospital wards. We found that ward-level antibiotic consumption volume had a stronger influence on the incidence of the more resistant pathogens, while connectivity had the most influence on hospital-endemic species and carbapenem-resistant pathogens. Piperacillin-tazobactam consumption was the strongest predictor of the cumulative incidence of infections resistant to empirical sepsis therapy. Our data provide evidence that both antibiotic use and connectivity measurably influence hospital AMR. Finally, we provide a ranking of key antibiotics by their estimated population-level impact on AMR that might help inform antimicrobial stewardship strategies.

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“…[6][7][8][9] A systematic review of carbapenem-sparing therapy against ESBL bloodstream infections concluded that complete avoidance of carbapenems cannot be justified and that consideration of PTZ as an alternative treatment depends heavily on the source of infection. 10 It has been proposed that utilization of PTZ for treatment of ESBL infections of mild to moderate severity should be considered, with infections of a urinary source being a primary area of discussion. 3,10,11 Because of the high proportion of ESBL infections that are of a urinary source, evidence and guidelines for optimal treatment of these infections is of the utmost importance to allow for the preservation of carbapenems.…”

Section: Introductionmentioning

confidence: 99%

“…10 It has been proposed that utilization of PTZ for treatment of ESBL infections of mild to moderate severity should be considered, with infections of a urinary source being a primary area of discussion. 3,10,11 Because of the high proportion of ESBL infections that are of a urinary source, evidence and guidelines for optimal treatment of these infections is of the utmost importance to allow for the preservation of carbapenems.…”

Section: Introductionmentioning

confidence: 99%

Piperacillin-Tazobactam Versus Carbapenems for the Treatment of Nonbacteremic Urinary Tract Infections due to Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae

2018

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Background: Carbapenems are the drug of choice for treatment of infections due to extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. Current evidence regarding piperacillin-tazobactam (PTZ) as an effective treatment alternative remains controversial. The purpose of this study was to determine the efficacy of PTZ versus carbapenems for treatment of nonbacteremic urinary tract infections (UTIs) due to ESBL-producing Enterobacteriaceae. Methods: A retrospective cohort study of patients treated for ESBL-related UTIs was conducted at three medical centers in the greater Middle Tennessee area. Patients were included if they were ≥ 18 years old, had a positive urine culture with an ESBL-producing organism, and received ≥ 48 hours of treatment with PTZ or carbapenem. Patients with bacteremia as well as those with isolates resistant to the treatment regimen selected were excluded. The primary objective was to determine the difference in clinical response between PTZ and carbapenem for treatment of ESBL-related UTIs. Clinical response was defined as absence of all of the following: (1) repeat admission for UTI caused by the same organism within 6 months, (2) repeat urine culture within 6 months showing growth of the same organism, or (3) a change in antimicrobial regimen due to subjective failure as determined by the ordering provider. Results: A total of 180 patients were included in the analysis (PTZ = 39; carbapenem = 141). There was no difference in clinical response between patients receiving PTZ and carbapenem (74.4% versus 80.9%; P = .38). Conclusion: PTZ may be an effective alternative to carbapenems for treatment of nonbacteremic UTIs due to ESBL-producing Enterobacteriaceae.

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Is It Time to Rethink the Notion of Carbapenem-Sparing Therapy Against Extended-Spectrum β-Lactamase–Producing Enterobacteriaceae Bloodstream Infections? A Critical Review

Abstract: Completely sparing carbapenem therapy cannot be justified among patients with ESBL BSIs. Determining the source of infection is critical to identify patients for whom carbapenem-sparing therapy is appropriate.

Cited by 12 publications

References 46 publications

Carbapenem-Sparing Strategies for ESBL Producers: When and How

Carbapenem-Sparing Strategies for ESBL Producers: When and How

Metapopulation ecology links antibiotic resistance, consumption, and patient transfers in a network of hospital wards

Piperacillin-Tazobactam Versus Carbapenems for the Treatment of Nonbacteremic Urinary Tract Infections due to Extended-Spectrum Beta-Lactamase-Producing Enterobacteriaceae

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