150. Improved Susceptibility of Pseudomonas aeruginosa to Cefepime (CEF) at a Veterans Tertiary Care Hospital, over a 7-Year Period (2011-2017): The Impact of Antibiotic Rotation/Cycling and Reversal of Drug Resistance in P. aeruginosa

Background Background: Pseudomonas aeruginosa continues to be an important cause of nosocomial infections associated with a high morbidity and mortality. Despite the availability of ceftazidime-avibactam (CAZ-AVI) and ceftolozone-tazobactam (CFT-TAZO), CEF continues to be an empiric agent of choice in several institutions. Aim: To evaluate the prevalence and trend in susceptibilities of P. aeruginosa to CEF over a 7-year period, identify possible correlation with the use of CAZ, AZT, PTZ, CIP, and CAR, (DOT/1000 patient days), as a quality improvement (QI) measure for optimizing CEF use, introduce antibiotic cycling as a tool to avoid emergence of drug-resistance in P. aeuriginosa. Methods A retrospective review of antimicrobial susceptibility data of all isolates of P. aeruginosa, (inpatient and outpatient) at the Detroit VAMC pre and post implementation of antibiotic cycling, over a 7-year period (2011-2017) was performed. Susceptibility testing was performed by reference broth micro-dilution methods in a central laboratory. Data analysis was performed using Pearson correlation coefficient score. Being a QI project, clinical data were not reviewed. Results A total of 977 isolates were identified during the study period. (drug usage are in DOT/1000 PD); CAZ and AZT use surged during 2013-14 from 5 to 8 dropping in 2015-17 to < 3; PTZ usage increased to 100 during 2011-14 but dropped to 38 in 2015-17 (drug shortage); CAR use averaged at 10 until 2016 and dropped to 8 in 2017; CIP use dropped by 50% from 30 in 2012 to 15 in 2017; P. aeruginosa susceptible to CEF decreased from 88% in 2012 to 81% in 2014 mirroring the increased use of CEF, AZT, CAZ, and CIP; AG use was very low at < 5. With restrictions on the use of AZT, CAZ, and CIP, from 2014-15, CEF susceptibility increased significantly to 95.5% in 2015. Drug shortage of PTZ in 2015 and increased use of CEF from 2015-17 led to a drop in susceptibility to (82%); P. aeruginosa susceptible to CAR and AG averaged at 88% and 97% respectively (2011-17). However, reintroduction PTZ, resulted in improved susceptibility of P. aeuruginosa to CEF by 40% within a year. Conclusion Judicious antimicrobial use and antibiotic rotation play a significant role in reversing drug resistance in P. aeuruginosa. Disclosures All Authors: No reported disclosures

Antibiotic Cycling Reverts Extensive Drug Resistant Burkholderia multivorans

Antibiotic collateral sensitivity, in which acquired resistance to one drug leads to decreased resistance to a different drug, occurs in Burkholderia multivorans . Here we observed that treatment of extensive drug resistant variants from a CF sputum sample with either meropenem or sulfamethoxazole/trimethoprim, depending on past resistance phenotypes, resulted in increased sensitivity to five different classes of antibiotics. We further identified mutations that may be involved in this phenotype, including putative Resistance-Nodulation-Division efflux pump regulators and uncharacterized pumps in B. multivorans.

Systematic review of the effects of antimicrobial cycling on bacterial resistance rates within hospital settings

Aim Antimicrobial resistance is an evolving phenomenon with alarming public health consequences. Antibiotic cycling is a widely known antimicrobial stewardship initiative which encompasses periodical shifts in empirical treatment protocols with the aim to limit selective pressures on bacterial populations. Nonetheless, mathematical models have challenged its presumable efficacy by favouring a higher heterogeneity in antibiotic administration. We present a review of the evidence regarding the actual impact of antimicrobial cycling on bacterial resistance control within hospitals. Methods A systematic literature review was conducted using the PubMed/MedLine, Embase, CINAHL Plus and Global Health databases. Results A systematic search process retrieved a sole randomised study, and so we broadened inclusion criteria to encompass quasi-experimental designs. Fifteen studies formed our dataset including seven prospective trials and eight before-and-after studies. Nine studies evaluated cycling versus a control group and produced conflicting results whilst three studies compared cycling with antibiotic mixing, with none of the strategies appearing superior. The rest evaluated resistance dynamics of each of the on-cycle antibiotics with contradictory findings. Research protocols differed in parameters such as the cycle length, the choice of antibiotics, the opportunity to de-escalate to narrow-spectrum agents and the measurement of indicators of collateral damage. This limited our ability to evaluate the replicability of findings and the overall policy effects. Conclusions Dearth of robust designs and standardised protocols limits our ability to reach safe conclusions. Nonetheless, in view of the available data we find no reason to believe that cycling should be expected to improve antibiotic resistance rates within hospitals.

Antimicrobial Stewardship in a Hematological Malignancy Unit: Carbapenem Reduction and Decreased Vancomycin-Resistant Enterococcus Infection

Background Antibiotic stewardship is challenging in hematological malignancy patients. Methods We performed a quasiexperimental implementation study of 2 antimicrobial stewardship interventions in a hematological malignancy unit: monthly antibiotic cycling for febrile neutropenia that included cefepime (± metronidazole) and piperacillin-tazobactam and a clinical prediction rule to guide anti-vancomycin-resistant Enterococcus faecium (VRE) therapy. We used interrupted time-series analysis to compare antibiotic use and logistic regression in order to adjust observed unit-level changes in resistant infections by background community rates. Results A total of 2434 admissions spanning 3 years pre- and 2 years postimplementation were included. Unadjusted carbapenem and daptomycin use decreased significantly. In interrupted time-series analysis, carbapenem use decreased by −230 days of therapy (DOT)/1000 patient-days (95% confidence interval [CI], −290 to −180; P < .001). Both VRE colonization (odds ratio [OR], 0.64; 95% CI, 0.51 to 0.81; P < .001) and infection (OR, 0.41; 95% CI, 0.2 to 0.9; P = .02) decreased after implementation. This shift may have had a greater effect on daptomycin prescribing (−160 DOT/1000 patient-days; 95% CI, −200 to −120; P < .001) than did the VRE clinical prediction score (−30 DOT/1000 patient-days; 95% CI, −50 to 0; P = .08). Also, 46.2% of Pseudomonas aeruginosa isolates were carbapenem-resistant preimplementation compared with 25.0% postimplementation (P = .32). Unit-level changes in methicillin-resistant Staphylococcus aureus and extended-spectrum beta lactamase (ESBL) incidence were explained by background community-level trends, while changes in AmpC ESBL and VRE appeared to be independent. The program was not associated with increased mortality. Conclusions An antibiotic cycling-based strategy for febrile neutropenia effectively reduced carbapenem use, which may have resulted in decreased VRE colonization and infection and perhaps, in turn, decreased daptomycin prescribing.