Piperacillin-Tazobactam versus Other Antibacterial Agents for Treatment of Bloodstream Infections Due to AmpC β-Lactamase-Producing Enterobacteriaceae.
In vivoinduction of AmpC beta-lactamases produces high-level resistance to many beta-lactam antibiotics inEnterobacteriaceae, 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 toEnterobacter,Serratia, orCitrobacterspecies 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 ofampCalleles 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 (P= 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 ofampC genes revealed the presence ofampC in isolates with cefoxitin MICs below 16 μg/ml, in particular inSerratiaspp., 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-producingEnterobacteriaceae, diminishing the need for broader-spectrum agents. Future studies are needed to validate these findings.
Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Lucy
L
Cheng
NewYork-Presbyterian Hospital, New York, New York, USA.
Brian C
BC
Nelson
NewYork-Presbyterian Hospital, New York, New York, USA.
Monica
M
Mehta
Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Nikhil
N
Seval
Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Sarah
S
Park
Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Marla J
MJ
Giddins
New York Medical College, Valhalla, New York, USA.
Qiuhu
Q
Shi
Department of Pathology and Cell Biology, Clinical Microbiology Laboratory, Columbia University Medical Center, New York, New York, USA.
Susan
S
Whittier
Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA.
Angela
A
Gomez-Simmonds
Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA au2110@columbia.edu.
Anne-Catrin
AC
Uhlemann
D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010641:Phenotype; D010878:Piperacillin / Q000627:therapeutic use; D000077725:Piperacillin, Tazobactam Drug Combination; D012706:Serratia marcescens / Q000187:drug effects / Q000235:genetics; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000077725:Piperacillin, Tazobactam Drug Combination; D010397:Penicillanic Acid; C048795:AmpC beta-lactamases; D001618:beta-Lactamases; D010878:Piperacillin
AmpC beta-lactamases; bacteremia; piperacillin-tazobactam