Evaluation of a carbapenem antimicrobial stewardship program and clinical outcomes in a Japanese hospital
Toshiaki KomatsuRyosuke InagakiShintaro AzumaShunya MochidaSato YosukeYoshinori SetoShin NihonyanagiTakayuki HoshiyamaTatsuhiko WadaYoko TakayamaKoichiro Atsuda
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Keywords:
Piperacillin/tazobactam
Antimicrobial Stewardship
Tazobactam
Carbapenem
Piperacillin/tazobactam
Antimicrobial Stewardship
Tazobactam
Carbapenem
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Cefepime
Piperacillin/tazobactam
Antimicrobial Stewardship
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Carbapenem
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Objective: To provide an overview of pathophysiological changes to the pancreas during infected necrotizing pancreatitis (INP), optimal drug properties needed to penetrate the pancreas, human and animal studies supporting the use of antimicrobials, and carbapenem-sparing strategies in INP. Data Sources: A literature analysis of PubMed/MEDLINE was performed (from 1960 to September 2020) using the following key terms: infected necrotizing pancreatitis, necrotizing acute pancreatitis, and infected pancreatitis antimicrobial concentration. Individual antimicrobials were investigated with these search terms. Study Selection and Data Extraction: All relevant studies describing the management of INP, and human and animal pharmacokinetic (PK) data supporting antimicrobial use in the pancreas were reviewed for possible inclusion regardless of sample size or study design. Data Synthesis: Piperacillin/tazobactam and cefepime achieve adequate pancreatic tissue concentrations in INP studies. A majority of the literature supporting carbapenem use in INP involves imipenem, and meropenem Monte Carlo simulations suggest that standard dosing regimens of meropenem may not achieve PK targets to eradicate Pseudomonas aeruginosa. Relevance to Patient Care and Clinical Practice: Carbapenems are often utilized for INP treatment based on guideline recommendations. This review discusses PK data, the history of carbapenem use in INP, and the pathophysiology of pancreatitis to suggest carbapenem-sparing strategies and provides stewardship tactics such as when to start antimicrobials, which empirical antimicrobial to use, and when to discontinue antimicrobials in the INP setting. Conclusions: Noncarbapenem antipseudomonals, such as piperacillin/tazobactam and cefepime, are appropriate carbapenem-sparing options in INP, based on PK data, spectrum of activity, and risk of collateral damage.
Carbapenem
Piperacillin/tazobactam
Antimicrobial Stewardship
Cefepime
Tazobactam
Ertapenem
Doripenem
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There is widespread overuse of ultra-broad spectrum antibiotics (UBSA) such as meropenem and piperacillin/tazobactam (PTZ). Reductions in their use are needed to preserve their effectiveness. Using electronic prescribing data we recorded administrations of meropenem and PTZ per month in a 12-bed medical high dependency unit (HDU) from April 2016 to March 2019. During this time there were three interventions (an antimicrobial stewardship round began in March 2017, PTZ was removed from empirical prescribing guidelines in May 2017, and a restricted antimicrobial audit began in June 2017). The latter two interventions were prompted by a national PTZ shortage. In 2016/17 meropenem and PTZ use was 56 and 113 daily defined doses/100 acute occupied bed days (AOBD) respectively, falling to 32 and 60 in 2017/18, and to 25 and 38 in 2018/19. This represented a 55% reduction in meropenem use and a 77% reduction in PTZ use over 2 years. The drop in use was due to both fewer patients being started on UBSA and shorter durations of treatment. The use of 4C antibiotics (clindamycin, cephalosporins, co-amoxiclav and ciprofloxacin/levofloxacin) did not increase. There was no increase in unit mortality, or change in the prevalence of ESBL-producing organisms. We describe a multi-modal intervention that, coupled with strong clinical engagement, resulted in a safe, sustained reduction in both meropenem and PTZ use in a medical HDU, without using more 4C antibiotics. We hypothesize that “top down” policies helped reduce UBSA initiation, whereas a “bottom-up” ward-based initiative helped review and stop unnecessary use.
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Objective. To evaluate clinical and antibiotic resistance impact of carbapenems stewardship programs. Methods: descriptive study, pre-post-intervention, between January 2012 and December 2019; 350-bed teaching hospital. Prospective audit and feedback to prescribers was carried out between January 2015 and December 2019. We evaluate adequacy of carbapenems prescription to local guidelines and compare results between cases with accepted or rejected intervention. Analysis of antibiotic-consumption and hospital-acquired multidrug-resistant (MDR) bloodstream infections (BSIs) was performed. Results: 1432 patients were followed. Adequacy of carbapenems prescription improved from 49.7% in 2015 to 80.9% in 2019 (p < 0.001). Interventions on prescription were performed in 448 (31.3%) patients without carbapenem-justified treatment, in 371 intervention was accepted, in 77 it was not. Intervention acceptance was associated with shorter duration of all antibiotic treatment and inpatient days (p < 0.05), without differences in outcome. During the period 2015–2019, compared with 2012–2014, decreased meropenem consumption (Rate Ratio 0.58; 95%CI: 0.55–0.63), candidemia and hospital-acquired MDR BSIs rate (RR 0.62; 95%CI: 0.41–0.92, p = 0.02), and increased cefepime (RR 2; 95%CI: 1.77–2.26) and piperacillin-tazobactam consumption (RR 1.17; 95%CI: 1.11–1.24), p < 0.001. Conclusions: the decrease and better use of carbapenems achieved could have clinical and ecological impact over five years, reduce inpatient days, hospital-acquired MDR BSIs, and candidemia, despite the increase in other antibiotic-consumption.
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Cefepime
Tazobactam
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Piperacillin/tazobactam
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Introduction: Urinary tract infections (UTIs) are the most common infection in humans. The retrospective study was aimed to analyze a new AAE (antibiotic adjuvant entity) of ceftriaxone+sulbactam with adjuvant disodium edetate as a carbapenem sparing drug in the management of UTIs caused by Escherichia coli. Methods: A retrospective review of patients treated for UTIs caused by Escherichia coli between January 2014 to April 2015 was conducted. Demographic characteristics, antibiotic therapy, length of hospital stay and clinical and microbiological outcome have been evaluated. Results: Data of 322 patients were reviewed. Of these, 112 patients who are diagnosed with UTI and having culture positive with E. coli were included in the study. Characterization of these isolates indicated that 48.2% were ESBL positive, 11.6% were MBL positive and 49.0% were found to be non ESBL/MBL. In microbiological evaluation, AAE appeared to be the most active drug against E. coli (89.3%) followed by meropenem (62.5%), imipenem plus cilastatin (58.03%) and piperacillin plus tazobactam (52.65%). Clinical success rate was 82.9% in AAE treated patients followed by 76% in meropenem, 71.4% in imipenem plus cilastatin and 63.1% in piperacillin plus tazobactam treated patients. Conclusion: The present study advocates that AAE can be considered as a drug of choice to carbapenem. Overall, this study results indicate approximately 6 to 11.5% superiority of AAE over penems (meropenem and imipenem plus cilastatin) and 19.8% to piperacillin plus tazobactam.
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Cilastatin
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Sulbactam
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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.
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Background:Overuse of antibiotics has been linked to the global growth of antimicrobial resistance (AMR). In 2018, increase in meropenem usage in our hospital revealed that we achieved the “Start Smart” but not “Then Focus” element. Following revised carbapenem stewardship, we aimed to evaluate the adherence to guidelines, by monitoring patients initiated on meropenem. Methods:As part of the antimicrobial stewardship (AMS) at our 1800-bed teaching hospital, carbanepem stewardship was revised in September 2018 and required consultant approval for all carbapenem initiation or continuation following specialist advice. Meropenem prescriptions in adult and paediatric patients were generated from the electronic prescription system and reviewed daily for one week in August 2019 to ascertain if prescribed in line with guideline recommendations or on the advice of microbiology or infectious diseases. Results:Sixty patients were reviewed. Microbiology or Infectious Diseases recommendation was obtained in 37% of patients. 95% had samples taken where blood cultures accounted for 85% but over a third of these had no growth reported. Meropenem was initiated empirically in 50% of patients mainly for neutropenic sepsis while 28% were culture directed. 35% of patients were escalated from piperacillin-tazobactam of which 57% had neutropenia while de-escalation occurred in 10%. Conclusion:AMR is related directly to antibiotic use at a patient level. Our revised strategy resulted in a reduction of total carbapenem DDD/1000 Admission from 128 (June 2018) to 87 (June 2019) through improved adherence to guideline and infection specialists recommendations however more work is required to promote switch to narrower-spectrum choice.
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Carbapenem
Guideline
Piperacillin/tazobactam
Tazobactam
Antibiotic Stewardship
Stewardship
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The optimal treatment for extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae bloodstream infections has yet to be defined. Retrospective studies have shown conflicting results, with most data suggesting the non-inferiority of beta-lactam-beta-lactamase inhibitor combinations compared with carbapenems. However, the recently published MERINO trial failed to demonstrate the non-inferiority of piperacillin-tazobactam to meropenem. The potential implications of the MERINO trial are profound, as widespread adoption of carbapenem treatment will have detrimental effects on antimicrobial stewardship in areas endemic for ESBL and carbapenem-resistant bacteria. Therefore, we believe that it is justified to re-examine the comparison in a second randomised controlled trial prior to changing clinical practice.PeterPen is a multicentre, investigator-initiated, open-label, randomised controlled non-inferiority trial, comparing piperacillin-tazobactam with meropenem for third-generation cephalosporin-resistant Escherichia coli and Klebsiella bloodstream infections. The study is currently being conducted in six centres in Israel and one in Canada with other centres from Israel, Italy and Canada expected to join. The two primary outcomes are all-cause mortality at day 30 from enrolment and treatment failure at day seven (death, fever above 38°C in the last 48 hours, continuous symptoms, increasing Sequential Organ Failure Assessment Score or persistent blood cultures with the index pathogen). A sample size of 1084 patients was calculated for the mortality endpoint assuming a 12.5% mortality rate in the control group with a 5% non-inferiority margin and assuming 100% follow-up for this outcome.The study is approved by local and national ethics committees as required. Results will be published, and trial data will be made available.ClinicalTrials.gov Registry (NCT03671967); Israeli Ministry of Health Trials Registry (MOH_2018-12-25_004857).
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Abstract Background Overutilization of antibiotics remains an issue in the inpatient setting. What is more, many protocols geared toward curbing improper antibiotic use rely heavily on resource- and personnel-intensive interventions. Thus, the potential for using the EMR to facilitate antibiotic stewardship remains largely unexplored. Methods We implemented a novel change for ordering certain antibiotics in our EMR: ceftriaxone, daptomycin, ertapenem, imipenem, meropenem, and piperacillin-tazobactam. When ordering one of these antibiotics, providers had to note a usage indication, which assigned a usage duration as per our Antibiotic Stewardship Committee guidelines. Pre-intervention, manual discontinuation was required if a provider did not enter a duration. The intervention was enacted August 2019 in 13 hospitals. Data was collected from January 2018 to February 2020. Antibiotic usage was reported monthly as rate per 1000-patient days. Monthly pre- and post-intervention rates were averaged, respectively. Paired samples t-tests were used to compare pre- and post-intervention rates per unit type per hospital. A p-value of less than 0.05 was considered significant. Units with minimal usage, as defined by a pre- or post-intervention mean of 0, were excluded from analysis. Example of Ordering an Antibiotic Prior to Intervention Example of Ordering an Antibiotic After Intervention Results Ertapenem was noted to have a statistically significant decrease in utilization in seven units at three hospitals. Piperacillin-tazobactam was found to have a decrease in utilization in 19 units at eight hospitals. Daptomycin was found to have a decrease in utilization in one unit. Significant decreases in the utilization of ceftriaxone, imipenem, and meropenem were not noted. Example of Statistically Significant Decreased Utilization in Piperacillin-Tazobactam on a Medical-Surglcal Unit Conclusion Our study showed a statistically significant decrease in use of ertapenem, piperacillin-tazobactam and daptomycin using a simple built-in EMR prompt that curtails provider error. This should allow for an increased ease of integration, as the protocol does not require a host of resources for maintenance. Of note is decreased utilization of piperacillin-tazobactam and ertapenem across multiple hospitals, most notably on the medical and surgical wards. Thus, usage of the EMR without personnel-intensive protocols is a viable method for augmenting antibiotic stewardship in health systems. Disclosures All Authors: No reported disclosures
Ertapenem
Antimicrobial Stewardship
Piperacillin/tazobactam
Tazobactam
Carbapenem
Cilastatin
Daptomycin
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