[Piperacillin/Tazobactam Shortage: Central Restriction and Alternative Recommendations as Effective Antibiotic-Stewardship Intervention at a Maximal Care Hospital]. / Piperacillin/Tazobactam-Lieferengpass: Zentrale Restriktion und Alternativempfehlungen als effektive Antibiotic-Stewardship-Maßnahme an einem Klinikum der Maximalversorgung.

BACKGROUND: Drug supply bottleneck is a worldwide challenge, e. g. the antibiotics Piperacillin/Tazobactam shortage in 2016/2017. The efficacy of an appropriate replacement management was evaluated at the University Hospital Frankfurt (UHF). METHODS: The Antibiotic-Stewardship (ABS)-Team at UHF decreed a restriction of PIP/TAZ and provided alternative antibiotic therapy recommendations during the shortage period. Consequences of this intervention on antibiotic consumption and overall costs were investigated. RESULTS: Over 12-weeks, PIP/TAZ-mean application rate was reduced by 71 % and was predominantly used to treat hospital acquired pneumonia (62 %), febrile neutropenian children (12 %), followed by other indications (< 10 %, each). Alternative substances' use increased (Ceftazidim + 229 %, Imipenem/Cilastatin + 18 %, Meropenem + 27 %, Ceftriaxon + 26 %, Levofloxacin + 11 %, Ciprofloxacin + 14 %, Ampicillin/Sulbactam + 83 %), however the overall antibiotic consumption declined by -5.8 % (cost savings: 13 %). Simultaneously, additional personnel costs have been noted (+ 4300 €). The evidence rate of bloodstream infections with resistant bacteria and detection of Clostridium-difficile-toxin were both not significantly elevated, compared to windows just ahead, after and one year before intervention period. CONCLUSION: Drug shortages challenge hospital antibiotic-stewardship programs by enforced use of broad spectrum-antibiotics, endanger patient safety and require rational replacement strategies, following infectious diseases- and microbiological outlines. Whilst personnel expenditures are higher, antimicrobial-stewardship interventions may successfully contribute to prevent additional medication costs.

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

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.

Effective Antibiotic Conservation by Emergency Antimicrobial Stewardship During a Drug Shortage.

We present the first description of an antimicrobial stewardship program (ASP) used to successfully manage a multi-antimicrobial drug shortage. Without resorting to formulary restriction, meropenem utilization decreased by 69% and piperacillin-tazobactam by 73%. During the shortage period, hospital mortality decreased (P=.03), while hospital length of stay remained unchanged. Infect Control Hosp Epidemiol 2017;38:356-359.

Impact of piperacillin-tazobactam shortage on meropenem use: implications for antimicrobial stewardship programs.

Drug shortages pose a clear detriment to antimicrobial stewardship (AS) efforts. Our objective was to evaluate the effect of a piperacillin-tazobactam shortage on meropenem use, related costs, and associated changes in AS activity. A quasi-experimental quality improvement review compared adult patients receiving meropenem ≥72h three months pre-shortage and three months during the shortage. 320 patients were included (pre-shortage: 103; shortage: 217). Baseline characteristics were similar, but the length of stay was slightly longer in pre-shortage [19 (11-32) days] versus shortage [16 (11-32) days] (p=0.094). In pre-shortage and shortage, median days of therapy and estimated meropenem cost were 7 (5-11) and 7 (5-10) and $309.93 ($173.60-$507.03) and $255.30 ($204.24-$424.31), respectively (p=0.411 and p=0.050). Frequency of ID consultation was similar (16.8% in pre- and 25.3% in shortage, p=0.091). AS interventions increased during the shortage period (99 in pre-shortage and 205 in shortage). De-escalation occurred in 19.4% versus 32.7% of the patients in pre-shortage and shortage (p=0.014). The piperacillin-tazobactam shortage was associated with a 111% increase in meropenem prescriptions despite active AS, but was not associated with changes in mortality, length of therapy, or meropenem costs. AS should be aware that shortages may require proactive countermeasures to avoid inappropriate antimicrobial use during shortage periods.

Impact of a piperacillin-tazobactam shortage on antimicrobial prescribing and the rate of vancomycin-resistant enterococci and Clostridium difficile infections.

UNLABELLED: States in 2002 on antimicrobial prescribing and associated rates of vancomycin-resistant enterococci (VRE) and Clostridium difficile infections.Design. Retrospective chart review.Setting. University-affiliated medical center. Measurements and Main Results. Microbiologic reports, patient demographics, and antimicrobial utilization were evaluated for patients admitted 6 months before the shortage (March 1-August 31, 2001) and for 6 months during the shortage (March 1-August 31, 2002). Significant increases in usage of alternative mu-lactamase inhibitor combinations, cefepime, levofloxacin, vancomycin, clindamycin, and metronidazole were observed during the shortage; in contrast, a significant decrease in the use of ceftriaxone took place. No change in the rate of VRE infection was observed from before to during the piperacillin-tazobactam shortage. However, a paradoxical 47% decrease in the rate of C. difficile colitis was documented during the shortage. Subsequent multivariate analyses suggested the reduced use of ceftriaxone and increased use of levofloxacin, but not the reduced use of piperacillin-tazobactam, correlated with the decreased rate of C. difficile infections. CONCLUSION: The piperacillin-tazobactam shortage was associated with significant changes in antimicrobial prescribing, which resulted in a significant reduction in the rate of C. difficile but not VRE infections.