Piperacillin-tazobactam Consumption Research Articles

Antimicrobial Consumption and Resistance of Restricted Antibiotics in a Level III Government Hospital.

The objectives of the study were to determine the antibiotic consumption of restricted antibiotics and to correlate this with resistance rate. A retrospective review of pharmacy dispensing records was conducted in the adult internal medicine wards of a tertiary level teaching hospital in the Philippines between March 2019 to February 2020. Antibiotic consumption was determined using Defined Daily Dose (DDD) per 1000 patient-days (PD). Correlations between antibiotic consumption and antibiotic resistance of restricted antibiotics were done. Outcomes were compared between Ward 1 (with the presence of a unit-dose pharmacist) and Ward 3 (without a unit-dose pharmacist). Both wards showed decreasing trends of piperacillin-tazobactam consumption and increasing trends of ceftazidime consumption from quarter 1 to quarter 4. It was observed that levofloxacin was the most prescribed fluoroquinolone with the highest consumption recorded from March to May 2019 in Ward 3 of 350.2 DDD/1000 PD as compared with ciprofloxacin which has the highest consumption (23.3 DDD/1000 PD) during the period June to August 2019 in Ward 1. Antibiotic resistance of Acinetobacter baumannii against ciprofloxacin, levofloxacin, and piperacillin-tazobactam were statistically significantly different between the wards. In Ward 1, ciprofloxacin consumption was strongly positively correlated with Escherichia coli resistance (r = 0.90). In Ward 3, a significantly moderately positive association was observed for ceftazidime consumption and A. baumannii resistance (r = 0.61), positive correlation between piperacillin-tazobactam and E. coli resistance (r = 0.65), and a strong positive correlation in Ward 3 between levofloxacin and Pseudomonas aeruginosa resistance (r = 0.71). The restriction and pre-authorization strategy of the AMS program has greatly contributed to the decrease in the consumption of almost all restricted antibiotics. This strategy has been helpful in minimizing unnecessary antibiotic use associated with inappropriate drug therapy. The success of the AMS program has been based on the collective efforts of the AMS team with the implementation of hospital policies, such as the AMS program, across the different sites in the hospital in order to achieve optimum patient health outcomes. It was noted that the resistance rates of A. baumannii against ciprofloxacin, levofloxacin, and piperacillin-tazobactam were higher in Ward 3 compared to Ward 1 which makes infections very difficult to treat which may result to prolonged hospital stay, increased health-care costs and increased mortality rate. This study has supported the involvement of pharmacists in the AMS team by conducting auditing activities that promote safe compliance of restricted antibiotic use among patients. Pharmacists can greatly participate on either prospective or retrospective review of antibiotic utilization and analyze trends of antibiotic consumption data to provide feedback to prescribing physicians on prescribing patterns and possible correlation with occurrence of antibiotic resistance.

Microbiological and clinical changes following the transition to the 2010 revised CLSI breakpoints for extended-spectrum cephalosporin in Enterobacterales

In 2016, our laboratory adopted the 2010 CLSI extended-spectrum cephalosporins (ESC) breakpoint criteria in Enterobacterales. ESBL testing had continued in Blood cultures but discontinued in General Cultures. The aims of this study were to examine the effect of this transition on (1) the resistance rates to ESC; (2) the consumption of parenteral β-lactam antimicrobials, and (3) the therapeutic use of ESC and the outcome of patients infected by ESBL-producing Enterobacterales. In K. pneumoniae and E. coli, the ESC resistance rates had increased, declined or remained unchanged in Urine, General and Blood cultures, respectively. In P. mirabilis, the resistance rates declined for ceftazidime but remained unchanged for ceftriaxone. Carbapenem consumption had not replaced ESC, but the consumption of piperacillin-tazobactam had increased. The use of ESC in suspected ESBL infections had increased slightly, without effect on clinical outcome.

Impact of an empiric antimicrobial therapy manual on antimicrobial usage and multidrug resistant organism trends in a large Italian teaching hospital

SummaryAimTo evaluate the changes in antimicrobial consumption and multidrug-resistant microorganism trends after introducing an empiric antimicrobial therapy manual to support antimicrobial stewardship.MethodsA 4-year prospective interventional study assessed the effect of introducing an empiric antimicrobial therapy manual in medical and surgical wards during two periods: pre-intervention period (January 2015–May 2017) and post-intervention period (June 2017–December 2019). Outcomes included microorganism trends of bloodstream infections (BSI) for Klebsiella pneumoniae carbapenemase-producing bacteria (KPC), extended spectrum beta-lactamase ESBL-E. coli, meticillin-resistant Staphylococcus aureus (MRSA) and Candida albicans. Also, Clostridioides difficile infection (CDI) episodes were included. Rates were normalised per 1000 patient-days (PD). Antimicrobial consumption was assessed as defined daily dose (DDD)/1000 PD in interrupted time series analysis.ResultsIn medical wards, we observed a significant decrease in the consumption of piperacillin-tazobactam and a decrease in the trends of tigecycline and vancomycin consumption. In surgical wards, there was a significant decrease in consumption of fluoroquinolones and piperacillin-tazobactam. This decrease was maintained in trend for all the antimicrobials but was significant for tigecycline only. In medical wards, there was a significant reduction of MRSA and C. albicans. In surgical wards, we observed a decrease in MRSA, ESBL-E. coli, C. albicans and CDI. KPC cases decreased by 22.5% in medical wards and 74.3% in surgical wards.ConclusionThe results suggest that a persuasive educational approach to antimicrobial stewardship, with the introduction of an empiric antimicrobial manual and continuous education, resulted in reductions in both antimicrobial use and healthcare-associated BSI caused by multidrug-resistant organisms. More studies with longer follow up are needed to investigate the effect of antimicrobial stewardship on clinical outcomes.

Long-Term Carbapenems Antimicrobial Stewardship Program.

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.

Metapopulation ecology links antibiotic resistance, consumption, and patient transfers in a network of hospital wards.

Antimicrobial resistance (AMR) is a global threat. A better understanding of how antibiotic use and between-ward patient transfers (or connectivity) impact population-level AMR in hospital networks can help optimize antibiotic stewardship and infection control strategies. Here, we used a metapopulation framework to explain variations in the incidence of infections caused by seven major bacterial species and their drug-resistant variants in a network of 357 hospital wards. We found that ward-level antibiotic consumption volume had a stronger influence on the incidence of the more resistant pathogens, while connectivity had the most influence on hospital-endemic species and carbapenem-resistant pathogens. Piperacillin-tazobactam consumption was the strongest predictor of the cumulative incidence of infections resistant to empirical sepsis therapy. Our data provide evidence that both antibiotic use and connectivity measurably influence hospital AMR. Finally, we provide a ranking of key antibiotics by their estimated population-level impact on AMR that might help inform antimicrobial stewardship strategies.

The Impact of a Best-Practice Advisory on Inpatient Use of Piperacillin-Tazobactam

Background: Antibiotic “time outs” have been identified as a way to decrease inappropriate use of antibiotics in hospitals.1 The University of Vermont Medical Center created a best-practice advisory (BPA) to alert clinicians to review piperacillin-tazobactam prescriptions after 72 hours (Fig. 1). Data examining the use of a BPA as a method to prompt clinicians to perform an antibiotic “time out” are limited. Objective: The purpose of our retrospective study was to evaluate the effectiveness of the BPA on the rate of piperacillin-tazobactam prescribing as measured by defined daily dose per 1,000 patient days (DDD). Methods: The BPA was integrated into the electronic health record and designed to activate once piperacillin-tazobactam has been prescribed for ≥72 hours. Under approval of the University of Vermont’s Institutional Review Board, administered data for piperacillin-tazobactam and 3 control antibiotics (cefazolin, ceftriaxone, and meropenem) were collected for 1 year prior to and 1 year following the launch of the BPA. Administered data were converted to DDD, and an interrupted time-series analysis was performed to evaluate for changes in antibiotic use. Results: The data included 7,094 patients in the preintervention group and 6,661 patients in the postintervention group. The BPA fired 1,478 times. The prescribing rate of piperacillin-tazobactam 1 year prior to the BPA was 32.34 DDD and decreased every month both before (−1.22 DDD) and after (−0.27 DDD) the BPA initiation, with no significant difference in prescribing trends (P = .10). Meropenem prescribing in the BPA era increased each month compared to the pre-BPA period (1.16 DDD; P = 0.02), whereas cefazolin use (P = .93) and ceftriaxone (P = .09) use did not significantly change. Conclusions: The data show that piperacillin-tazobactam utilization at our institution is decreasing. Considering that this trend started prior to the launch of the BPA and that rate of decline remained unchanged post-BPA, we conclude that the BPA did not further impact our piperacillin-tazobactam consumption. It is possible that other factors influencing prescribing account for the observed decline, including an institution-wide educational campaign regarding the appropriate use of broad-spectrum antibiotics that was initiated in the months prior to the BPA. The reason for the significant rise in meropenem post-BPA is unclear. This may be unrelated to the BPA; however, it requires further investigation.1. Core elements of hospital antibiotic stewardship programs. Centers for Disease Control and Prevention website. https://www.cdc.gov/antibioticuse/healthcare/implementation/core-elements.html. Updated July 19, 2019. Accessed October 6, 2019.Funding: NoneDisclosures: None

Urinary tract infection by Acinetobacter baumannii and Pseudomonas aeruginosa: evolution of antimicrobial resistance and therapeutic alternatives.

Purpose. Acinetobacter baumannii and Pseudomonas aeruginosa are responsible for numerous nosocomial infections. The objective of this study was to determine the development of their susceptibility to ten antibiotics and the antibiotic consumption of patients with suspicion of urinary tract infection (UTI).Methodology. A retrospective study was conducted on the susceptibility profiles of A. baumannii and P. aeruginosa isolates from 749 urine samples gathered between January 2013 and December 2016, and on the consumption of imipenem, meropenem and piperacillin-tazobactam between 2014 and 2016.Results. Hospital patients were the source of 82 (91.1 %) of the 90 A. baumannii isolates detected and 555 (84.2 %) of the 659 P. aeruginosa isolates. Globally, the lowest percentage susceptibility values were found for fosfomycin, aztreonam and ciprofloxacin, while colistin continued to be the most active antibiotic in vitro. In 2016, the susceptibility of A. baumannii to carbapenem and piperacillin-tazobactam decreased to very low values, while the susceptibility of P. aeruginosa to carbapenem remained stable but its susceptibility to piperacillin-tazobactam decreased. There was a marked increase in the consumption of piperacillin-tazobactam.Conclusion. In our setting, it is no longer possible to use carbapenems and piperacillin-tazobactam for empirical treatment of UTI due to A. baumannii or to use piperacillin-tazobactam for empirical treatment of UTI due to P. aeruginosa. Colistin was found to be the most active antibiotic in vitro. There was a marked increase in the consumption of piperacillin-tazobactam.

Long-term effectiveness of infection and antibiotic control programs on the transmission of carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex in central Taiwan

ObjectivesA carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex (CRA complex) infection is one of most the difficult infections to control worldwide. We evaluated the long-term effects of infection control interventions on the incidence densities of healthcare-associated infection (HAI) and CRA complex infection, and the rates of Acinetobacter calcoaceticus-Acinetobacter baumannii complex bacteremia (AB). Patients and methodsWe performed a cross-sectional analysis at the Changhua Christian Hospital from January 2002 to December 2013. Interventions for infection control were implemented from 2002 to 2009 (period 1). From 2010 to 2013 (period 2), infection control programs were improved by in-service education and a hand hygiene campaign to prepare for international and national hospital accreditation. The effectiveness of infection and antibiotic control programs was assessed according to the incidence densities of HAI and CRA complex, rates of CRA complex and of AB, chlorhexidine consumption density, and defined daily dose of antibiotics. ResultsThe incidence density of HAI decreased from 4.56‰ to 1.52‰ from periods 1 to 2 (P<0.001). Likewise, the incidence of AB decreased from 177.79 to 137.76 per person-years per 100,000 admissions (P<0.001). The incidence density of CRA complex ranged from 3.17–7.38‰. The chlorhexidine consumption density increased from 5.5 to 45.5 L per 1000 patient-days (P<0.001). The consumption of piperacillin-tazobactam was lower in period 2 than in period 1 (P<0.001). ConclusionEducation for infection control programs, hand hygiene campaigns, and antibiotics control programs may decrease the incidence density of AB and HAI, and may help control CRA complex infection.

Mathematical model to quantify the effects of risk factors on carbapenem-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections are increasing, and they are associated with an increased risk of mortality in hospitalized patients. Linear regression is commonly used to identify concurrent trends, but it cannot quantify the relationship between risk factors and resistance. We developed a model to quantify the impact of antibiotic consumption on the prevalence of CRAB over time. Data were collected from January 2007 to June 2013 from our institution. Quarterly antibiotic consumption was expressed as defined daily dose/1,000 inpatient days. Six-month prevalence of CRAB was expressed as a percentage of all nonrepeat A. baumannii isolates tested. Individual trends were identified using linear regression. Antibiotic consumption from 2007 to 2011 was input as a step function in a relationship with CRAB. Model fit was evaluated by visual inspection and the residual sum of squares. The final model was validated using the best-fit (95% confidence interval) parameter estimates and antibiotic consumption to predict CRAB prevalence from January 2012 to June 2013. Cefepime, ertapenem, and piperacillin-tazobactam consumption and CRAB prevalence increased significantly over time. CRAB prevalence was best correlated to ertapenem (use sensitive; r2=0.76), and accounting for additional concurrent antibiotic use did not significantly improve model fit. Prospective validation with ertapenem consumption correlated well with CRAB observations, suggesting good predicting ability of the model. Our model provided the quantitative impact of antibiotic consumption on CRAB. We plan to further refine this model to account for multiple risk factors. Interventions should focus on controlling risk factors with the highest impact on resistance.

Changes in the Use of Broad-Spectrum Antibiotics after Cefepime Shortage: a Time Series Analysis

The original cefepime product was withdrawn from the Swiss market in January 2007 and replaced by a generic 10 months later. The goals of the study were to assess the impact of this cefepime shortage on the use and costs of alternative broad-spectrum antibiotics, on antibiotic policy, and on resistance of Pseudomonas aeruginosa toward carbapenems, ceftazidime, and piperacillin-tazobactam. A generalized regression-based interrupted time series model assessed how much the shortage changed the monthly use and costs of cefepime and of selected alternative broad-spectrum antibiotics (ceftazidime, imipenem-cilastatin, meropenem, piperacillin-tazobactam) in 15 Swiss acute care hospitals from January 2005 to December 2008. Resistance of P. aeruginosa was compared before and after the cefepime shortage. There was a statistically significant increase in the consumption of piperacillin-tazobactam in hospitals with definitive interruption of cefepime supply and of meropenem in hospitals with transient interruption of cefepime supply. Consumption of each alternative antibiotic tended to increase during the cefepime shortage and to decrease when the cefepime generic was released. These shifts were associated with significantly higher overall costs. There was no significant change in hospitals with uninterrupted cefepime supply. The alternative antibiotics for which an increase in consumption showed the strongest association with a progression of resistance were the carbapenems. The use of alternative antibiotics after cefepime withdrawal was associated with a significant increase in piperacillin-tazobactam and meropenem use and in overall costs and with a decrease in susceptibility of P. aeruginosa in hospitals. This warrants caution with regard to shortages and withdrawals of antibiotics.