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

• Published in: Antimicrobial agents and chemotherapy 2017-06, Vol.61 (6)
• Main Authors: Cheng, Lucy, Nelson, Brian C, Mehta, Monica, Seval, Nikhil, Park, Sarah, Giddins, Marla J, Shi, Qiuhu, Whittier, Susan, Gomez-Simmonds, Angela, Uhlemann, Anne-Catrin
• Format: Article
• Language: English
• Subjects: Aged; Anti-Bacterial Agents; Anti-Bacterial Agents - pharmacology; Bacteremia - microbiology; Bacterial Proteins; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; beta-Lactamases; beta-Lactamases - genetics; beta-Lactamases - metabolism; Case-Control Studies; Citrobacter; Clinical Therapeutics; Enterobacter; Enterobacteriaceae; Enterobacteriaceae - enzymology; Enterobacteriaceae - genetics; Genotype; Humans; Male; Middle Aged; Penicillanic Acid; Penicillanic Acid - analogs & derivatives; Penicillanic Acid - therapeutic use; Phenotype; Piperacillin - therapeutic use; Serratia; Serratia marcescens - drug effects; Serratia marcescens - genetics
• ISSN: 0066-4804; 1098-6596
• DOI: 10.1128/AAC.00276-17

induction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics in , often resulting in the need to use carbapenems or cefepime (FEP). The clinical effectiveness of piperacillin-tazobactam (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 , , or 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 alleles by PCR. Primary study outcomes were 30-day mortality and persistent bacteremia at ≥72 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 ( = 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 C genes revealed the presence of C in isolates with cefoxitin MICs below 16 μg/ml, in particular in spp., and demonstrated that these alleles were highly genetically diverse. Taken together, TZP may be a valuable treatment option for BSIs due to AmpC beta-lactamase-producing , diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings.