Search

Background A systematic review and meta-analysis of real-world observational studies was conducted to summarize the impact of letermovir cytomegalovirus (CMV) primary prophylaxis (PP) among adult allogeneic hematopoietic cell transplant (allo-HCT) recipients. Methods Systematic searches in Medline/PubMed, Embase, and conferences (from database inception to October 2021) were conducted to identify studies for inclusion. Random-effects models were used to derive pooled estimates on the relative effectiveness of letermovir PP compared to controls. Results Forty-eight unique studies (N = 7104 patients) were included, most of which were comparative, single-center, and conducted in the United States. Letermovir PP was associated with statistically significant reduction in odds of CMV reactivation (pooled odds ratio [pOR], 0.13 and 0.24; P < .05), clinically significant CMV infection (pOR, 0.09 and 0.19; P < .05), and CMV disease (pOR, 0.31 and 0.35; P < .05) by day +100 and day +200 after allo-HCT, respectively. Letermovir PP was associated with significantly lower odds of all-cause (pOR, 0.73; P < .01) and nonrelapse mortality (pOR, 0.65; P = .01) beyond day 200 after allo-HCT. Conclusions Letermovir for CMV PP was effective in reducing the risk of CMV-related complications overall and mortality beyond day 200 among adult allo-HCT recipients.

Background Public health institutions including the World Health Organization and the United States Centers for Disease Control and Prevention (CDC) have recognized the threat of antibiotic resistant infections caused by Gram-negative bacteria. These bacteria are particularly concerning as they can demonstrate resistance to all available antibiotic classes through various mechanisms. We set out to assess antibiotic resistance trends in Gram-negative bacteria to optimize antimicrobial stewardship and infection control initiatives in our health system. Methods We identified positive cultures (1st per patient per month) of P. aeruginosa and select Enterobacterales (Citrobacter, Escherichia coli, Enterobacter, Klebsiella, Morganella morganii, Proteus mirabilis, Serratia marcescens) collected from patients hospitalized at Veterans Affairs (VA) Medical Centers nationally from 2011 to 2020. Time trends were assessed with joinpoint regression to estimate average annual percent changes (AAPC) with 95% confidence intervals (CIs) for the following resistance phenotypes utilizing CDC definitions: multi-drug resistance (MDR), extended-spectrum beta-lactamase (ESBL), and carbapenem (CR) and fluoroquinolone (FR) resistance. Results We included 496,384 isolates in our study: E. coli (32.6%), Klebsiella (20%), P. aeruginosa (18.9%), P. mirabilis (11.5%), Enterobacter (7.8%), Citrobacter (3.7%), S. marcescens (2.9%), and M. morganii (2.6%). Trends in resistance are shown in the figures. MDR, ESBL, CR, and FR decreased significantly (p< 0.05) over the study period for most of the organisms assessed, with the exception of MDR and ESBL E. coli and CR P. mirabilis which remained stable, and CR M. morganii which increased significantly by 7.1% per year (95% CI 0.2% to 14.5%). The largest decreases were in CR E. coli by 29.5% per year (95% CI -36.5% to -21.8%), CR Klebsiella by 23.7% per year (95% CI -27.6% to -19.5%), and MDR and CR S. marcescens by 12.2% (95% CI -14.4% to -9.9%) and 12.3% per year (95% CI -16.2% to -8.1%), respectively. Figure 1. Antibiotic resistance trends in Citrobacter spp., E. coli, Enterobacter spp., and Klebsiella spp. Antibiotic resistance trends (by percentage) in (a) Citrobacter spp, (b) E. coli, (c) Enterobacter spp, and (d) Klebsiella spp from 2011-2020. Abbreviations: MDR = multi-drug resistance (defined as non-susceptible to at least 1 drug in at least 3 of the following categories: extended-spectrum cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, piperacillin/tazobactam); ESBL = extended spectrum beta-lactamase (defined as non-susceptible to at least 1 of the following drugs: cefepime, ceftriaxone, cefotaxime, ceftolozane/tazobactam, ceftazidime/avibactam); CR = carbapenem resistance (defined as non-susceptible to at least 1 carbapenem); FR = fluoroquinolone resistance (defined as non-susceptible to at least 1 fluoroquinolone); AAPC = annual average percentage change; CI = confidence interval. Figure 2. Antibiotic resistance trends in Pseudomonas aeruginosa, Proteus mirabilis, Serratia marcescens, and Morganella morganii. Antibiotic resistance trends (by percentage) in (e) Pseudomonas aeruginosa, (f) Proteus mirabilis, (g) Serratia marcescens, and (h) Morganella morganii from 2011-2020. Abbreviations: MDR = multi-drug resistance (defined as non-susceptible to at least 1 drug in at least 3 of the following categories: extended-spectrum cephalosporins, fluoroquinolones, aminoglycosides, carbapenems, piperacillin/tazobactam); ESBL = extended spectrum beta-lactamase (defined as non-susceptible to at least 1 of the following drugs: cefepime, ceftriaxone, cefotaxime, ceftolozane/tazobactam, ceftazidime/avibactam); CR = carbapenem resistance (defined as non-susceptible to at least 1 carbapenem); FR = fluoroquinolone resistance (defined as non-susceptible to at least 1 fluoroquinolone); AAPC = annual average percentage change; CI = confidence interval. Conclusion Overall, MDR, ESBL, CR, and FR in Enterobacterales and P. aeruginosa decreased from 2011 to 2020 in the VA. These results may be related to the robust infection control and antimicrobial stewardship programs instituted among VA Medical Centers nationally. Disclosures Kerry LaPlante, PharmD, Merck (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc (Research Grant or Support) Aisling Caffrey, PhD, Merck (Research Grant or Support)Pfizer (Research Grant or Support)Shionogi, Inc (Research Grant or Support)

Background Antibiotic use (AU) and antibiotic resistance (AR; AUR) reporting to National Healthcare Safety Network (NHSN) is suboptimal by US hospitals. The Society of Infectious Diseases Pharmacists (SIDP) and the Society for Healthcare Epidemiology of America (SHEA) conducted a survey of their membership to 1) Identify characteristics of US health systems that report AUR data 2) Determine how NHSN AUR data are used by health systems and 3) Identify barriers to AUR reporting. Methods An anonymous survey was posted on SurveyMonkey from 1/21- 2/21/2020 and links were emailed to SIDP and SHEA Research Network members. Data were analyzed in Excel and RStudio. Respondent and hospital data were reported as frequencies and percentages. Fisher’s Exact test was used to compare survey responses from NHSN AUR reporters to non-reporters. Results A total of 238 individuals from 43 states responded to our survey. Respondents were primarily pharmacists (84%), from urban (45%), non-profit medical centers (80%) with >250 beds (65%). 62% of respondents reported to the AU option while 19% reported to the AR option. Respondents not using software for local AU or AR tracking were less likely than those using any software for local tracking to report to AU (19% vs 64%) and AR (2% vs 30%) options (P< 0.0001). Among AU and AR reporters 41% and 54% used clinical decision support software to aggregate compile data for upload while 54% and 38% used their electronic health record, and 5% and 8% used another method. Over half of AU (56%) and AR (51%) reporters upload data manually. Regular use of the NHSN data analysis tools was reported by 36% and 9% of those reporting AU and AR data respectively. The most common barriers to reporting were related to technical issues (software, IT support, data formatting) and time/salary support. Among non-reporters, increased expectations to report and better software solutions were most commonly identified as the best ways to increase reporting. Conclusion Efforts to improve AUR reporting should focus on software solutions and increasing the utility of AUR analytical tools. Increasing expectations to report may also help to improve reporting rates. The lower rate of AR vs AU reporting suggests that interventions should also target the AR option. Disclosures Brian J. Werth, PharmD, Shionogi Inc. (Grant/Research Support) Kerry LaPlante, PharmD, Merck (Advisor or Review Panel member, Research Grant or Support)Ocean Spray Cranberries, Inc. (Research Grant or Support)Pfizer Pharmaceuticals (Research Grant or Support)Shionogi, Inc. (Research Grant or Support)

Due to the rise of antibiotic resistance, and the decrease of novel antibiotics coming to market, the Centers for Disease Control and Prevention (CDC) has formally recognized that action must take place to ensure appropriate antibiotic use, and maintain public health. The RI Department of Health (RIDOH) Director responded by initiating the RI Antimicrobial Stewardship and Environmental Cleaning Task Force (RIAMSEC), a multidisciplinary team that set in motion a set of tasks for RIDOH. As a result, a survey of antibiotic stewardship programs (ASP) at the RI acute care hospitals (ACHs) and long-term care (LTC) facilities revealed gaps in addressing HAI prevention and AMS goals for the state. RIDOH has therefore expanded statewide coordination efforts to form the RI Healthcare-Associated Infection Prevention and Antimicrobial Stewardship Coalition which is intended to effectively prevent HAI and ultimate improve the Centers for Medicare and Medicaid Services Hospital-acquired Condition (HAC) Reduction scores in Rhode Island.[Full article available at http://rimed.org/rimedicaljournal-2018-06.asp].

The preventive effects of the American cranberry (Vaccinium macrocarpon) against urinary tract infections are supported by extensive studies which have primarily focused on its phenolic constituents. Herein, a phenolic-free carbohydrate fraction (designated cranf1b-F2) was purified from cranberry fruit using ion exchange and size exclusion chromatography. MALDI-TOF-MS analysis revealed that the cranf1b-F2 constituents are predominantly oligosaccharides possessing various degrees of polymerisation and further structural analysis (by GC-MS and NMR) revealed mainly xyloglucan and arabinan residues. In antimicrobial assays, cranf1b-F2 (at 1.25 mg/mL concentration) reduced biofilm production by the uropathogenic Escherichia coli CFT073 strain by over 50% but did not inhibit bacterial growth. Cranf1b-F2 (ranging from 0.625 - 10 mg/mL) also inhibited biofilm formation of the non-pathogenic E. coli MG1655 strain up to 60% in a concentration-dependent manner. These results suggest that cranberry oligosaccharides, in addition to its phenolic constituents, may play a role in its preventive effects against urinary tract infections.