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Vancomycin plus piperacillin/tazobactam and acute kidney injury in adults: a systematic review and meta-analysis

Objectives: The objective of this systematic review and meta-analysis was to assess acute kidney injury with combination therapy of vancomycin plus piperacillin-tazobactam, in general, adult patients and in critically ill adults. Rates of acute kidney injury, time to acute kidney injury, and odds of acute kidney injury were compared with vancomycin monotherapy, vancomycin plus cefepime or carbapenem, or piperacillin-tazobactam monotherapy. Data Sources: Studies were identified by searching Pubmed, Embase, Web of Science, and Cochrane from inception to April 2017. Abstracts from selected conference proceedings were manually searched. Study Selection: Articles not in English, pediatric studies, and case reports were excluded. Data Extraction: Two authors independently extracted data on study methods, rates of acute kidney injury, and time to acute kidney injury. Effect estimates and 95% CIs were calculated using the random effects model in RevMan 5.3. Data Synthesis: Literature search identified 15 published studies and 17 conference abstracts with at least 24,799 patients. The overall occurrence rate of acute kidney injury was 16.7%, with 22.2% for vancomycin plus piperacillin-tazobactam and 12.9% for comparators. This yielded an overall number needed to harm of 11. Time to acute kidney injury was faster for vancomycin plus piperacillin-tazobactam than vancomycin plus cefepime or carbapenem, but not significantly (mean difference, –1.30; 95% CI, –3.00 to 0.41 d). The odds of acute kidney injury with vancomycin plus piperacillin-tazobactam were increased versus vancomycin monotherapy (odds ratio, 3.40; 95% CI, 2.57–4.50), versus vancomycin plus cefepime or carbapenem (odds ratio, 2.68; 95% CI, 1.83–3.91), and versus piperacillin-tazobactam monotherapy (odds ratio, 2.70; 95% CI, 1.97–3.69). In a small subanalysis of 968 critically ill patients, the odds of acute kidney injury were increased versus vancomycin monotherapy (odds ratio, 9.62; 95% CI, 4.48–20.68), but not significantly different for vancomycin plus cefepime or carbapenem (odds ratio, 1.43; 95% CI, 0.83–2.47) or piperacillin-tazobactam monotherapy (odds ratio, 1.35; 95% CI, 0.86–2.11). Conclusions: The combination of vancomycin plus piperacillin-tazobactam increased the odds of acute kidney injury over vancomycin monotherapy, vancomycin plus cefepime or carbapenem, and piperacillin-tazobactam monotherapy. Limited data in critically ill patients suggest the odds of acute kidney injury are increased versus vancomycin monotherapy, and mitigated versus the other comparators. Further research in the critically ill population is needed

Antimicrobial Stewardship in Long-Term Care Facilities: A Call to Action

Antimicrobial resistance is a global public health crisis and a national security threat to the United States, as stated in an executive order signed by the president in September 2014. This crisis is a result of indiscriminant antimicrobial use, which promotes selection for resistant organisms, increases the risk of adverse drug events, and renders patients vulnerable to drug-resistant infections. Antimicrobial stewardship is a key measure to combat antimicrobial resistance and specifically seeks to do this by improving antimicrobial use. Antimicrobial stewardship compliments infection control practices and it is important to note that these 2 disciplines are distinct and cannot be discussed interchangeably. Antimicrobial stewardship promotes the appropriate diagnosis, drug, dose, and duration of treatment. The appropriate diagnosis falls into the hands of the prescriber and clinical staff. Optimal antimicrobial drug selection, dosing strategy, and duration of treatment, however, often require expertise in antimicrobial therapy, such as an infectious disease–trained physician or pharmacist. Therefore, successful antimicrobial stewardship programs must be comprehensive and interdisciplinary. Most antimicrobial stewardship programs focus on hospitals; yet, in long-term care, up to 75% of antimicrobial use is inappropriate or unnecessary. Thus, one of the most pressing areas in need for antimicrobial stewardship is in long-term care facilities. Unfortunately, there is little evidence that describes effective antimicrobial stewardship interventions in this setting. This review discusses the need for and barriers to antimicrobial stewardship in long-term care facilities. Additionally, this review describes prior interventions that have been implemented and tested to improve antimicrobial use in long-term care facilities

Antibiotic Resistance Rates for Pseudomonas aeruginosa Clinical Respiratory and Bloodstream Isolates Among the Veterans Affairs Healthcare System from 2009 to 2013

Pseudomonas aeruginosa is a major cause of healthcare-associated infections and resistance among isolates is an increasing burden. The study purpose was to describe national resistance rates for clinical P. aeruginosa respiratory and bloodstream cultures and the prevalence of multidrug-resistant (MDR) P. aeruginosa within the Veterans Affairs (VA). MDR was defined as non-susceptibility to at least one drug in at least 3 of the following 5 categories: carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam. We reviewed 24,562 P. aeruginosa respiratory and bloodstream isolates across 126 VA facilities between 2009 to 2013. Most isolates were collected from inpatient settings (82%). Resistance was highest in fluoroquinolones (33%) and exceeded 20% for all classes assessed (carbapenems, extended-spectrum cephalosporins, aminoglycosides, and piperacillin/tazobactam). Resistance was higher in inpatient settings and in respiratory isolates. Prevalence of MDR was 20% overall (22% for inpatient isolates, 11% outpatient, 21% respiratory, 17% bloodstream). Our findings are consistent with previous surveillance report

1238. A National Comparison of Antibiograms Between Veterans Affairs Long-Term Care Facilities and Affiliated Hospitals

Background: Long-term care facilities (LTCFs) face several barriers to creating antibiograms. Here, we evaluate if LTCFs can use antibiograms from affiliated hospitals as their own antibiogram. Methods: Facility-specific antibiograms were created for all Veterans Affairs (VA) LTCFs and VA Medical Centers (VAMCs) for 2017. LTCFs and affiliated VAMCs were paired and classified as being on the same campus or geographically distinct campuses based on self-report. For each pair, Escherichia colisusceptibility rates (%S) to cefazolin, ceftriaxone, cefepime, ciprofloxacin, nitrofurantoin, sulfamethoxazole/trimethoprim, ampicillin/sulbactam, piperacillin/tazobactam, and imipenem were compared. As guidelines discourage empiric use of antibiotics if susceptibility rates are Results: A total of 119 LTCFs and their affiliated VAMCs were included in this analysis, with 70.6% (n = 84) of facilities located on the same campus and 29.4% (n = 35) on geographically distinct campuses. The table below shows the overall clinical concordance (agreement) of LTCFs with their affiliated VAMC in regards to E. coli %S to the compared antibiotics. No significant differences were found when comparing LTCFs on the same campus vs. geographically distinct campuses. [Abstract contains a chart of Agreement Rates between LTCFs and Affiliated VAMCs and Antibiotics ] Conclusion: Antibiograms between LTCFs and affiliated VAMCs had a high concordance, except for sulfamethoxazole/trimethoprim, cefazolin and ceftriaxone in regards to susceptibility rates of E. coli. Facilities on the same campus were found to have similar concordance rates to geographically distinct facilities. Future studies are needed to investigate how the various approaches to creating LTCF-specific antibiograms are associated with clinical outcomes

National trends in the treatment of urinary tract infections among Veterans’ Affairs Community Living Center residents

Objective: To describe urinary tract infection (UTI) treatment among Veterans’ Affairs (VA) Community Living Centers (CLCs) nationally and to assess related trends in antibiotic use. Design: Descriptive study. Setting and participants: All UTI episodes treated from 2013 through 2017 among residents in 110 VA CLCs. UTI episodes required collection of a urine culture, antibiotic treatment, and a UTI diagnosis code. UTI episodes were stratified into culture-positive and culture-negative episodes. Methods: Frequency and rate of antibiotic use were assessed for all UTI episodes overall and were stratified by culture-positive and culture-negative episodes. Joinpoint software was used for regression analyses of trends over time. Results: We identified 28,247 UTI episodes in 14,983 Veterans. The average age of Veterans was 75.7 years, and 95.9% were male. Approximately half of UTI episodes (45.7%) were culture positive and 25.7% were culture negative. Escherichia coli was recovered in 34.1% of culture-positive UTI episodes, followed by Proteus mirabilis and Klebsiellaspp, which were recovered in 24.5% and 17.4% of culture-positive UTI episodes, respectively. The rate of total antibiotic use in days of therapy (DOT) per 1,000 bed days decreased by 10.1% per year (95% CI, −13.6% to −6.5%) and fluoroquinolone use (ciprofloxacin or levofloxacin) decreased by 14.5% per year (95% CI, −20.6% to −7.8%) among UTI episodes overall. Similar reductions in rates of total antibiotic use and fluoroquinolone use were observed among culture-positive UTI episodes and among culture-negative UTI episodes. Conclusion: Over a 5-year period, antibiotic use for UTIs significantly decreased among VA CLCs, as did use of fluoroquinolones. Antibiotic stewardship efforts across VA CLCs should be applauded, and these efforts should continue

1829. A Systems Approach to Nursing Home Antimicrobial Stewardship

Background: Up to 70% of nursing home (NH) residents receive one or more courses of antibiotics (ATB) annually, of which over half may be inappropriate and risk harm. The current availability of in-house NH data is often insufficient to measure and track appropriateness, due to incomplete data or unusable formatting. Our 3-year project to improve antimicrobial stewardship (AMS) used the Centers for Disease Control and Prevention’s (CDC) Core Elements of AMS for NHs, with guided input from NH providers to develop and implement an electronic ATB de-escalation decision support tool that also captures otherwise inaccessible data. Methods: Our baseline assessment identified wide variation in providers’ knowledge, attitudes, and beliefs regarding ATB prescribing, leading us to identify de-escalation as the most feasible NH AMS intervention. Using facilitated open-ended conversations with leaders from three NH corporations, we developed an electronic decision support tool to systematically prompt de-escalation 48–72 hours post-prescribing. Subsequent site visits with NH clinical teams at a convenience sample of sites allowed us to explore how to incorporate decision support into their electronic health record (EHR). Results: We developed a tool anchored on data capture for the “acute change in condition” that triggers prescriber interactions. It uses clinical and laboratory data to prompt structured communication between nurses and prescribers. Placing this tool in the EHR reduced duplicate charting, enabled guidance from McGeer and Loeb criteria, and promoted its adoption into practice while ensuring data capture to assess appropriateness of ATB prescribing. Conclusion: Our electronic decision support tool captures clinical and laboratory data, which it then uses to systematically prompt conversations about de-escalation between nurses and prescribers, reducing variation in practice. Upon completion, the assessment ensures availability of data to assess, track, and report appropriate prescribing practices among prescribers. This tool proved acceptable to NH providers in three different corporations, suggesting feasibility of further expansion of this approach to a broader group of NH providers

Predictors of potentially suboptimal treatment of urinary tract infections in long-term care facilities

Background: Suboptimal antibiotic treatment of urinary tract infection (UTI) is high in long-term care facilities (LTCFs) and likely varies between facilities. Large-scale evaluations have not been conducted. Aim: To identify facility-level predictors of potentially suboptimal treatment of UTI in Veterans Affairs (VA) LTCFs and to quantify variation across facilities. Methods: This was a retrospective cohort study of 21,938 residents in 120 VA LTCFs (2013–2018) known as Community Living Centers (CLCs). Potentially suboptimal treatment was assessed from drug choice, dose frequency, and/or treatment duration. To identify facility characteristics predictive of suboptimal UTI treatment, LTCFs with higher and lower rates of suboptimal treatment (≥median, \u3c median) were compared using unconditional logistic regression models. Joinpoint regression models were used to quantify average percentage difference across facilities. Multilevel logistic regression models were used to quantify variation across facilities. Findings: The rate of potentially suboptimal antibiotic treatment varied from 1.7 to 34.2 per 10,000 bed-days across LTCFs. The average percentage difference in rates across facilities was 2.5% (95% confidence interval (CI): 2.4–2.7). The only facility characteristic predictive of suboptimal treatment was the incident rate of UTI per 10,000 bed-days (odds ratio: 4.9; 95% CI: 2.3–10.3). Multilevel models demonstrated that 94% of the variation between facilities was unexplained after controlling for resident and CLC characteristics. The median odds ratio for the full multilevel model was 1.37. Conclusion: Potentially suboptimal UTI treatment was variable across VA LTCFs. However, most of the variation across LTCFs was unexplained. Future research should continue to investigate factors that are driving suboptimal antibiotic treatment in LTCFs