Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused byEnterobacter,CitrobacterorSerratiaspecies: a systematic review with meta-analysis

Harris, Patrick N A; Wei, Jane Y.; Shen, A; Abdile, Ahmed A.; Paynter, Stuart; Huxley, Rachel R.; Pandeya, Nirmala; Doi, Yohei; Huh, Kyungmin; O’Neal, Catherine; Talbot, Thomas R.; Paterson, David L.

doi:10.1093/jac/dkv346

Cited by 67 publications

(48 citation statements)

References 28 publications

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“…Our findings are consistent with those of other recent studies (16)(17)(18). A Spanish study spanning a 16-year time period (1991 to 2006) analyzed 377 episodes of Enterobacter spp.…”

Section: Discussionsupporting

confidence: 93%

“…A 2016 meta-analysis by Harris and colleagues evaluated 11 studies comparing carbapenems with noncarbapenems as treatment for bacteremia from AmpC-producing Enterobacteriaceae (primarily Enterobacter spp.) (18). In an unadjusted analysis, there was no difference in mortality between BLBLIs and carbapenems.…”

Section: Discussionmentioning

confidence: 91%

“…In an unadjusted analysis, there was no difference in mortality between BLBLIs and carbapenems. After adjusting for potential confounders such as age and severity of illness, the nonsignificant trend toward increased mortality in the carbapenem group was reduced (18). Most recently, a 2016 retrospective cohort study by Moy and colleagues (19) compared carbapenems to noncarbapenems for the treatment of bacteremia and urinary tract infections due to SPICE organisms (Serratia, Pseudomonas, indole-positive Proteus, Citrobacter, and Enterobacter).…”

Section: Discussionmentioning

confidence: 99%

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Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae

Cheng

Nelson

Mehta

et al. 2017

Antimicrob Agents Chemother

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In vivo induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in Enterobacteriaceae, often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillintazobactam (TZP), a weak inducer of AmpC beta-lactamases, is poorly understood. Here, we conducted a case-control study of adult inpatients with bloodstream infections (BSIs) due to Enterobacter, Serratia, or Citrobacter species from 2009 to 2015 to assess outcomes following treatment with TZP compared to FEP or meropenem (MEM). We collected clinical data and screened all isolates for the presence of ampC alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at Ն72 h from the time of treatment initiation. Of 493 patients with bacteremia, 165 patients met the inclusion criteria, of which 88 were treated with TZP and 77 with FEP or MEM. To minimize differences between covariates, we carried out propensity score matching, which yielded 41 matched pairs. Groups only differed by age, with patients in the TZP group significantly older (P ϭ 0.012). There were no significant differences in 30-day mortality, persistent bacteremia, 7-day mortality, or treatment escalation between the two treatment groups, including in the propensity score-matched cohort. PCR amplification and sequencing of ampC genes revealed the presence of ampC in isolates with cefoxitin MICs below 16 g/ml, in particular in Serratia spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC betalactamase-producing Enterobacteriaceae, diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings.

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“…Our findings are consistent with those of other recent studies (16)(17)(18). A Spanish study spanning a 16-year time period (1991 to 2006) analyzed 377 episodes of Enterobacter spp.…”

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae

Cheng

Nelson

Mehta

et al. 2017

Antimicrob Agents Chemother

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“…The role of PTZ in the treatment of serious AmpC-E infections is not well established. Tazobactam does not efficiently inhibit the AmpC enzyme, but limited observational data suggest that PTZ has similar effectiveness to carbapenems when AmpC-E test susceptible to PTZ [30,31]. Fluoroquinolones, which are not affected by AmpC enzymes, are another option in treating AmpC-E infections.…”

Section: Ampc β-Lactamase-producing Enterobacteriaceae (Ampc-e)mentioning

confidence: 99%

The growing threat of multidrug-resistant Gram-negative infections in patients with hematologic malignancies

Baker

Satlin

2016

Leukemia & Lymphoma

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Prolonged neutropenia and chemotherapy-induced mucositis render patients with hematologic malignancies highly vulnerable to Gram-negative bacteremia. Unfortunately, multidrug-resistant (MDR) Gram-negative bacteria are increasingly encountered globally, and current guidelines for empirical antibiotic coverage in these patients may not adequately treat these bacteria. This expansion of resistance, coupled with traditional culturing techniques requiring 2-4 days for bacterial identification and antimicrobial susceptibility results, have grave implications for these immunocompromised hosts. This review characterizes the epidemiology, risk factors, resistance mechanisms, recommended treatments, and outcomes of the MDR Gram-negative bacteria that commonly cause infections in patients with hematologic malignancies. We also examine infection prevention strategies in hematology patients, such as infection control practices, antimicrobial stewardship, and targeted decolonization. Finally, we assess strategies to improve outcomes of infected patients, including gastrointestinal screening to guide empirical antibiotic therapy, new rapid diagnostic tools for expeditious identification of MDR pathogens, and use of two new antimicrobial agents, ceftolozane/tazobactam and ceftazidime/avibactam.

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“…We direct them to a much larger meta-analysis also conducted by Harris et al in 2016 that included 11 studies and revealed no strong evidence to suggest the superiority of carbapenems to other treatment regimens, including ␤-lactamase/␤-lactamase inhibitors, in patients with bloodstream infections due to Enterobacteriaceae with AmpC ␤-lactamases (4). We welcome future studies of the efficacy of non-carbapenemcontaining regimens, such as piperacillin-tazobactam, for the treatment of AmpCharboring Enterobacteriaceae.…”

mentioning

confidence: 99%

Reply to Aitken et al., “Should Piperacillin-Tazobactam Be Used as Definitive Therapy against Enterobacteriaceae Harboring Inducible AmpC β-Lactamases?”

Cheng

Nelson

Mehta

et al. 2017

Antimicrob Agents Chemother

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We appreciate Aitken et al.'s careful review (1) of our recent paper assessing the use of piperacillin-tazobactam for the treatment of bloodstream infections caused by Enterobacteriaceae harboring AmpC ␤-lactamases (2). We respectfully disagree with their assertion that the numerical increase in mortality seen with the use of piperacillintazobactam compared to the mortalities of patients on carbapenems and/or cefepime in our and other studies suggests that inferior outcomes are to be expected with piperacillin-tazobactam.Aitken et al. are correct to point out that the odds ratio (OR) for the 30-day survival, not mortality, of patients receiving piperacillin-tazobactam versus that of patients receiving cefepime or meropenem was 0.5 in the propensity-matched data set. Therefore, the OR for 30-day mortality was 2.0 (95% confidence interval, 0.5 to 7.7), representing 3 additional deaths in the piperacillin-tazobactam group. This result was not statistically significant (P ϭ 0.33), indicating that we were unable to detect an association between the treatment regimen and the occurrence of mortality in this study. It is worth noting that the large confidence intervals reported here suggest a low level of the precision of the OR. Thus, it is inappropriate to draw a firm conclusion about the relative odds of mortality based on its numerical value alone. As we pointed out in our publication, propensity score matching lowered our ability to detect differences in outcomes. In the overall cohort, the OR for 30-day survival was 1.16, as reported, and the OR for 30-day mortality was 0.86 (95% confidence interval, 0.3 to 2.3; P ϭ 0.8). It is worth noting that in creating the propensity score-matched cohort, fewer deaths were excluded from the piperacillin-tazobactam group (3/9) than from the carbapenem/ cefepime group (6/9).Aitken et al. also suggested that using multivariable logistic regression is preferred to propensity score matching for some data sets. We opted for propensity score matching to minimize differences between baseline characteristics of treatment groups. In addition, a low number of outcome events in our data set made it difficult to perform multivariate models. Multivariable analyses of the overall cohort were attempted by incorporating variables that were significantly different between treatment groups, but these models demonstrated poor fit. However, they also showed no association between treatment groups and mortality, supporting our findings from the propensity score-matched analysis.The commenters further mention a paper by Harris and colleagues from 2017 with similar results (i.e., a numerically higher rate of recurrence of Enterobacter spp. bacteremia without a statistically significant difference) and a small patient population (3).

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Carbapenems versus alternative antibiotics for the treatment of bloodstream infections caused byEnterobacter,CitrobacterorSerratiaspecies: a systematic review with meta-analysis

Abstract: Despite limitations of available data, there was no strong evidence to suggest that BLBLIs, quinolones or cefepime were inferior to carbapenems. The reduced risk of mortality observed with quinolone use may reflect less serious illness in patients, rather than superiority over carbapenems.

Cited by 67 publications

References 28 publications

Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae

Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae

The growing threat of multidrug-resistant Gram-negative infections in patients with hematologic malignancies

Reply to Aitken et al., “Should Piperacillin-Tazobactam Be Used as Definitive Therapy against Enterobacteriaceae Harboring Inducible AmpC β-Lactamases?”

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