The Effect of a Piperacillin/Tazobactam Shortage on Antimicrobial Prescribing and Clostridium difficile Risk in 88 US Medical Centers

Clin Infect Dis. 2017 Aug 15;65(4):613-618. doi: 10.1093/cid/cix379.


Background: Anti-infective shortages are a pervasive problem in the United States. The objective of this study was to identify any associations between changes in prescribing of antibiotics that have a high risk for CDI during a piperacillin/tazobactam (PIP/TAZO) shortage and hospital-onset Clostridium difficile infection (HO-CDI) risk in 88 US medical centers.

Methods: We analyzed electronically captured microbiology and antibiotic use data from a network of US hospitals from July 2014 through June 2016. The primary outcome was HO-CDI rate and the secondary outcome was changes in antibiotic usage. We fit a Poisson model to estimate the risk of HO-CDI associated with PIP/TAZO shortage that were associated with increased high-risk antibiotic use while controlling for hospital characteristics.

Results: A total of 88 hospitals experienced PIP/TAZO shortage and 72 of them experienced a shift toward increased use of high-risk antibiotics during the shortage period. The adjusted relative risk (RR) of HO-CDI for hospitals experiencing a PIP/TAZO shortage was 1.03 (95% confidence interval [CI], .85-1.26; P = .73). The adjusted RR of HO-CDI for hospitals that both experienced a shortage and also showed a shift toward increased use of high-risk antibiotics was 1.30 (95% CI, 1.03-1.64; P < .05).

Conclusions: Hospitals that experienced a PIP/TAZO shortage and responded to that shortage by shifting antibiotic usage toward antibiotics traditionally known to place patients at greater risk for CDI experienced greater HO-CDI rates; this highlights an important adverse effect of the PIP/TAZO shortage and the importance of antibiotic stewardship when mitigating drug shortages.

Keywords: Clostridium difficile; drug shortage; piperacillin/tazobactam.

MeSH terms

  • Anti-Bacterial Agents / supply & distribution*
  • Anti-Bacterial Agents / therapeutic use
  • Clostridioides difficile
  • Clostridium Infections / drug therapy*
  • Clostridium Infections / epidemiology
  • Drug Prescriptions / statistics & numerical data*
  • Humans
  • Penicillanic Acid / analogs & derivatives*
  • Penicillanic Acid / supply & distribution
  • Penicillanic Acid / therapeutic use
  • Piperacillin / supply & distribution
  • Piperacillin / therapeutic use
  • Piperacillin, Tazobactam Drug Combination
  • Treatment Outcome
  • United States / epidemiology


  • Anti-Bacterial Agents
  • Piperacillin, Tazobactam Drug Combination
  • Penicillanic Acid
  • Piperacillin