Medicare Prescription Plans Limit Access to Recommended Drugs for Clostridioides difficile Infection.

We analyzed June 2021 Medicare Advantage/Part D enrollment and formulary data. Oral vancomycin and fidaxomicin, frontline Clostridioides difficile treatments, were in the formulary for 100% (42314676 of 42314676) and 84.1% (35598385 of 42314676) of enrollees, respectively. However, they were broadly accessible (formulary, unrestricted, tier 1 or 2) to only 14.4% (6104348 of 42314676) and 1.1% (483004 of 42314676), respectively.

Impact of Revised Infectious Diseases Society of America and Society for Healthcare Epidemiology of America Clinical Practice Guidelines on the Treatment of Clostridium difficile Infections in the United States.

BACKGROUND: Our objective was to determine if oral vancomycin, fidaxomicin, and oral metronidazole use in the United States changed after publication of revised clinical practice guidelines for Clostridium difficile infection (CDI) in February 2018. METHODS: We obtained US antibiotic prescription data (IQVIA) from 2006-August 2019 and used guideline-recommended dosing regimens to estimate monthly numbers of 10-day treatment courses of vancomycin, fidaxomicin and metronidazole. Interrupted time-series analyses were performed, adjusted by month. We compared linear trends for monthly numbers of treatment courses in different time periods. RESULTS: Cumulative treatment courses of oral vancomycin and fidaxomicin increased by 54% (n = 226 166) and 48% (n = 18 518), respectively, in 18 months following guidelines compared with 18 months before; those of oral metronidazole decreased by 3% (n = 238 372). Monthly vancomycin and fidaxomicin use significantly increased throughout the period following revised guidelines (P < .0001 and P = .0002, respectively), whereas that of metronidazole decreased significantly (P < .0001). Monthly vancomycin use increased and metronidazole use decreased to a significantly greater extent after publication of revised guidelines than after publication of clinical trials establishing superiority of vancomycin over metronidazole (P < .0001). CONCLUSIONS: Revised practice guidelines have had a significant impact on CDI treatment in the US. Clinical trial data used for the revised guidelines were available since 2007-2014 and 2011-2012 for oral vancomycin and fidaxomicin, respectively. Guidelines or guidance documents for treating CDI and other infections should be updated in more timely fashion.

Single Dose of an mRNA Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) Vaccine Is Associated With Lower Nasopharyngeal Viral Load Among Nursing Home Residents With Asymptomatic Coronavirus Disease 2019 (COVID-19).

In nursing home residents with asymptomatic COVID-19 diagnosed through twice-weekly surveillance testing, single-dose BNT162b2 vaccination (Pfizer-BioNTech) was associated with -2.4 mean log10 lower nasopharyngeal viral load than detected in absence of vaccination (P = .004). Since viral load is linked to transmission, single-dose mRNA SARS-CoV-2 vaccination may help control outbreaks.

Outpatient Fluoroquinolone Prescription Fills in the United States, 2014 to 2020: Assessing the Impact of Food and Drug Administration Safety Warnings.

The impact of United States Food and Drug Administration (FDA) safety warnings on outpatient fluoroquinolone use is unclear. Annual changes in outpatient ciprofloxacin, levofloxacin, and moxifloxacin prescription fills (IQVIA National Prescription Audit databases) were assessed using a regression model. Monthly fills during baseline (August 2014 to April 2016) and first (May 2016 to June 2018) and second FDA warning periods (July 2018 to February 2020) were compared by interrupted time series analysis. From 2015 through 2019, total fluoroquinolone fills decreased from 35,616,786 (111.1/1,000 persons) to 21,100,050 (64.3/1,000 persons) annually (10.8% annually [P = 0.001]). Ciprofloxacin, levofloxacin, and moxifloxacin fills decreased annually by 10.4% (P = 0.001), 11.2% (P < 0.001), and 17.7% (P = 0.008), respectively. During the baseline period, there was no significant change in monthly fluoroquinolone fills. In May 2016 and during the first warning period, monthly fluoroquinolone fills decreased significantly (P < 0.001); the trend of decreased fills was significantly greater than that of the baseline period (P = 0.02). There was no change in fluoroquinolone fills in July 2018. Monthly fills decreased significantly throughout the second warning period (P < 0.001), but the trend did not differ from that of the first warning period. Trends for ciprofloxacin, the most commonly prescribed fluoroquinolone, were similar to those for the class. Fills of prescriptions by infectious diseases specialists (P < 0.005) and nurse practitioners (P = 0.04) significantly increased during the study. U.S. outpatient fluoroquinolone prescription fills significantly decreased from August 2014 to February 2020, most strongly in association with May 2016 FDA warnings. FDA safety warnings are useful tools for leveraging outpatient antimicrobial stewardship.

Sustained Reductions in Overall and Unnecessary Antibiotic Prescribing at Primary Care Clinics in a Veterans Affairs Healthcare System Following a Multifaceted Stewardship Intervention.

BACKGROUND: Most antibiotic prescribing is in outpatient settings. However, antibiotic stewardship has focused overwhelmingly on hospitalized patients. In a few studies, behavioral interventions decreased unnecessary outpatient prescribing against acute respiratory infections, but data are conflicting on sustained benefits after intervention discontinuation. METHODS: We conducted a prospective, observational study in 7 primary care clinics, in which an intervention comprised of clinician education, peer comparisons, and computer decision support order sets was directed against all antibiotic prescribing. After 6 months, peer comparisons were discontinued. Antibiotic prescribing was compared in the baseline (January-June 2016), intervention (January-June 2017), and postintervention (January-June 2018) periods. RESULTS: Mean antibiotic prescriptions significantly decreased from 76.9 (baseline) to 49.5 (intervention) and 56.3 (postintervention) per 1000 visits (35.6% and 26.8% reductions, respectively; P values < .001). The rate of unnecessary antibiotic prescribing (ie, antibiotic not indicated) decreased from 58.8% (baseline) to 37.8% (intervention) and 44.3% (postintervention) (35.7% and 24.7% decreases, respectively; P = .001 and P = .01). Overall, 19.9% (27/136), 36.6% (66/180), and 34.9% (67/192) of antibiotics were prescribed optimally (ie, antibiotics were indicated, and a guideline-concordant agent was prescribed for guideline-concordant duration) during the baseline, intervention, and postintervention periods, respectively (baseline vs intervention and postintervention, P = .001 and P = .003, respectively). Differences between intervention and postintervention periods in overall, unnecessary, or optimal antibiotic prescribing were not significant. CONCLUSIONS: A multifaceted outpatient stewardship intervention achieved reductions in overall, unnecessary, and suboptimal antibiotic prescription rates, which were sustained for a year after components of the intervention were discontinued. There is opportunity for further improvement, as inappropriate and suboptimal prescribing remained common.

Decreased Overall and Inappropriate Antibiotic Prescribing in a Veterans Affairs Hospital Emergency Department following a Peer Comparison-Based Stewardship Intervention.

Antibiotic prescribing is very common in emergency departments (EDs). Optimal stewardship intervention strategies in EDs are not well defined. We conducted a prospective, observational cohort study in a Veterans Affairs ED in which clinician education and monthly e-mail-based peer comparisons were directed against all oral antibiotic prescribing for discharged patients. Oral antibiotic prescriptions were compared in baseline (June 2016 to December 2017) and intervention (January to June 2018) periods using an interrupted time series regression model. Prescribing appropriateness was compared during January to June 2017 and the intervention period. During the intervention period, antibiotic prescriptions decreased monthly by 10.4 prescriptions per 1,000 ED visits (P = 0.07 [95% confidence interval {CI}, -21.7 to 1.0]). The relative decrease in the trend of antibiotic prescriptions during the intervention period compared to baseline was 9.9 prescriptions per 1,000 ED visits per month (P = 0.07 [95% CI, -20.9 to 1.0]). The intervention was associated with a significant decrease and increase in amoxicillin-clavulanate and cephalexin prescriptions, respectively (P < 0.001, P = 0.004). Decreasing trends in ciprofloxacin prescriptions during the baseline period were maintained during the intervention. Unnecessary antibiotic prescribing (i.e., antibiotic not indicated) decreased from 55.6% to 38.7% during the intervention (30.4% decrease, P = 0.003). Optimal antibiotic prescribing (i.e., antibiotics were indicated, and a guideline-concordant agent was prescribed for guideline-concordant duration) increased by 36% (21.6% to 29.3%, P = 0.12). A peer comparison-based stewardship intervention directed at ED clinicians was associated with reductions in overall and unnecessary oral antibiotic prescribing. There is potential to further improve antibiotic use as suboptimal prescribing remained common.

Antibiotic Consumption and Stewardship at a Hospital outside of an Early Coronavirus Disease 2019 Epicenter.

There are scant data on the impact of coronavirus disease 2019 (COVID-19) on hospital antibiotic consumption, and no data from outside epicenters. At our nonepicenter hospital, antibiotic days of therapy (DOT) and bed days of care (BDOC) were reduced by 151.5/month and 285/month, respectively, for March to June 2020 compared to 2018-2019 (P = 0.001 and P < 0.001). DOT per 1,000 BDOC was increased (8.1/month; P = 0.001). COVID-19 will impact antibiotic consumption, stewardship, and resistance in ways that will likely differ temporally and by region.

Improved Antibiotic Prescribing within a Veterans Affairs Primary Care System through a Multifaceted Intervention Centered on Peer Comparison of Overall Antibiotic Prescribing Rates.

Reducing inappropriate outpatient antibiotic use is an important national goal. Limited data exist on targeted education and peer comparison of overall antibiotic prescribing rates as an antimicrobial stewardship strategy. Primary care professionals (PCPs) from all seven clinics within our health care system were offered an education session, followed by monthly e-mails with their antibiotic prescribing rate, peer prescribing rates, and a system target. A pre-post analysis was conducted to compare prescribing rates during the intervention period (January to June 2017) to a seasonal baseline (January to June 2016) using a regression model. A random sample of prescriptions was reviewed for adherence to consensus guidelines. Educational sessions were attended by 68.5% (50/73) of PCPs. From the baseline to the intervention period, the mean rate of monthly antibiotic prescriptions declined from 76.9 to 49.5 per 1,000 office visits (35.6% reduction [P < 0.001]). Among reviewed cases, unnecessary antibiotic prescribing declined (58.8% [80/136] versus 38.9% [70/180]; 33.9% reduction [P = 0.0006]), and the rate of optimally prescribed antibiotics increased (19.9% [27/136] versus 30% [54/180]; 50.8% increase [P = 0.05]). If an antibiotic was indicated, there were no significant differences in prescribing of guideline-discordant agents (21.4% [12/56] versus 19.1% [21/110] [P = 0.8]) or guideline-concordant agents for a guideline-discordant duration (38.6% [17/44] versus 39.3% [35/89] [P = 1]). There were significant reductions in azithromycin and fluoroquinolone prescriptions (50.9% and 59.4% [P values of <0.001], respectively), but most prescriptions for these agents in the intervention period remained inappropriate. Initial education followed by monthly peer comparison of overall antibiotic prescribing rates reduced total and unnecessary antibiotic prescribing in primary care clinics.

Prevalence of Inappropriate Antibiotic Prescribing in Primary Care Clinics within a Veterans Affairs Health Care System.

Data are needed from outpatient settings to better inform antimicrobial stewardship. In this study, a random sample of outpatient antibiotic prescriptions by primary care providers (PCPs) at our health care system was reviewed and compared to consensus guidelines. Over 12 months, 3,880 acute antibiotic prescriptions were written by 76 PCPs caring for 40,734 patients (median panel, 600 patients; range, 33 to 1,547). PCPs ordered a median of 84 antibiotic prescriptions per 1,000 patients per year. Azithromycin (25.8%), amoxicillin-clavulanate (13.3%), doxycycline (12.4%), amoxicillin (11%), fluoroquinolones (11%), and trimethoprim-sulfamethoxazole (10.6%) were prescribed most commonly. Medical records corresponding to 300 prescriptions from 59 PCPs were analyzed in depth. The most common indications for these prescriptions were acute respiratory tract infection (28.3%), urinary tract infection (23%), skin and soft tissue infection (15.7%), and chronic obstructive pulmonary disease (COPD) exacerbation (6.3%). In 5.7% of cases, no reason for the prescription was listed. No antibiotic was indicated in 49.7% of cases. In 12.3% of cases, an antibiotic was indicated, but the prescribed agent was guideline discordant. In another 14% of cases, a guideline-concordant antibiotic was given for a guideline-discordant duration. Therefore, 76% of reviewed prescriptions were inappropriate. Ciprofloxacin and azithromycin were most likely to be prescribed inappropriately. A non-face-to-face encounter prompted 34% of prescriptions. The condition for which an antibiotic was prescribed was not listed in primary or secondary diagnosis codes in 54.5% of clinic visits. In conclusion, there is an enormous opportunity to reduce inappropriate outpatient antibiotic prescriptions.

Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia: Risk Factors for Mortality and Microbiologic Treatment Failure.

We reviewed 37 patients treated for bacteremia due to carbapenem-resistant (CR) Pseudomonas aeruginosa Although 65% of isolates were multiple-drug resistant, therapeutic options were available, as all were susceptible to ≥1 antibiotic. A total of 92% of patients received active antimicrobial therapy, but only 57% received early active therapy (within 48 h). Fourteen-day mortality was 19%. Microbiologic failure occurred in 29%. The Pitt bacteremia score (P = 0.046) and delayed active therapy (P = 0.027) were predictive of death and microbiologic failure, respectively.

Evaluation of the In Vitro Activity of Ceftazidime-Avibactam and Ceftolozane-Tazobactam against Meropenem-Resistant Pseudomonas aeruginosa Isolates.

We compared ceftazidime-avibactam, ceftolozane-tazobactam, ceftazidime, cefepime, and piperacillin-tazobactam MICs for 38 meropenem-resistant Pseudomonas aeruginosa isolates. No isolates harbored carbapenemases; 74% were oprD mutants. Ceftazidime-avibactam and ceftolozane-tazobactam were active against 92% of the isolates, including 80% that were resistant to all three ß-lactams. Forty-three percent of ceftazidime-avibactam-susceptible isolates and 6% of ceftolozane-tazobactam-susceptible isolates exhibited MICs at the respective breakpoints. Ceftolozane-tazobactam and ceftazidime-avibactam are therapeutic options for meropenem-resistant P. aeruginosa infections that should be used judiciously to preserve activity.

A Review of Treatment and Prevention of Coronavirus Disease 2019 among Solid Organ Transplant Recipients.

Therapeutic management of solid organ transplant (SOT) recipients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), may challenge healthcare providers given a paucity of clinical data specific to this cohort. Herein, we summarize and review the studies that have formed the framework for current COVID-19 consensus management guidelines. Our review focuses on COVID-19 treatment options including monoclonal antibody products, antiviral agents such as remdesivir, and immunomodulatory agents such as corticosteroids, interleukin inhibitors, and kinase inhibitors. We highlight the presence or absence of clinical data of these therapeutics related to the SOT recipient with COVID-19. We also describe data surrounding COVID-19 vaccination of the SOT recipient. Understanding the extent and limitations of observational and clinical trial data for the prevention and treatment of COVID-19 specific to the SOT population is crucial for optimal management. Although minimal data exist on clinical outcomes among SOT recipients treated with varying COVID-19 therapeutics, reviewing these agents and the studies that have led to their inclusion or exclusion in clinical management of COVID-19 highlights the need for further studies of these therapeutics in SOT patients with COVID-19.

Exploratory Cost-Effectiveness Analysis for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: Is Linezolid or Daptomycin Favored Over Vancomycin?

BACKGROUND AND OBJECTIVE: Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality, and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. Our objective was to compare the cost-effectiveness of vancomycin and other antibiotic regimens against MRSAB. METHODS: We estimated the cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin) for Veterans Health Administration patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure at 7 days and adverse drug event (ADE)-related discontinuation after at least 7 days. RESULTS: In base-case analyses, intravenous linezolid was the least expensive regimen at 4 and 6 weeks. Daptomycin was more expensive and more effective than linezolid, with an incremental cost-effectiveness ratio (ICER) of ~$13,000 (4 weeks) per composite failure avoided. With 6 weeks of treatment, daptomycin was more expensive and more effective than vancomycin (ICER ~$21,000 per composite failure avoided). Vancomycin and ceftaroline/daptomycin were dominated strategies at both 4 and 6 weeks. In one-way sensitivity analyses, vancomycin was favored when its microbiological failure risk was less than 20.1% (base-case: 27.2%), assuming a willingness to pay (WTP) threshold of $40,000/composite treatment failure avoided. In two-way sensitivity analyses, intravenous linezolid was favored if linezolid microbiological failure and ADE-related discontinuation rates were < 22.5% and < 17.3%, respectively. Daptomycin, vancomycin, and linezolid were favored in 50%, 31%, and 17% of 4-week probabilistic iterations, respectively, at $40,000 WTP. CONCLUSION: Daptomycin is likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed on the safety of linezolid against MRSAB.

Introduction of the BNT162b2 vaccine during a COVID-19 nursing home outbreak.

BACKGROUND: Coronavirus disease 2019 (COVID-19) outbreaks often occur in nursing homes and prompt frequent surveillance testing for SARS-CoV-2. A single dose of the BNT162b2 vaccine reduces viral load and transmission. In this study, we describe the real-world efficacy of BNT162b2 single-dose vaccination during a COVID-19 outbreak at a Veterans Affairs Community Living Center (CLC). METHODS: From 12/2/20 to 5/14/21, twice weekly antigen testing was used to detect COVID-19 among 146 residents at the CLC. Residents without a prior history of COVID-19 who agreed to immunization were vaccinated with the BNT162b2 vaccine on 12/16/20 and 1/6/21. Single-dose vaccine efficacy was determined for days 1-21 and days 14-21 after the first vaccine dose. RESULTS: The outbreak occurred from 12/2/20 to 1/7/21 with an attack rate of 30.8% (45/146); 46.7% (21/45) of the cases were due to asymptomatic COVID-19. One unit accounted for 77.8% (35/45) of the cases. In the vaccine analysis, 116 residents were a median age of 74.5 years and 93.1% (108/116) had ≥ 1 comorbid condition. Between the first and second dose, 15.5% (15/97) of vaccinated residents, and 21.2% (4/19) of unvaccinated residents developed COVID-19 (P = .81). One week after the second dose, no cases of COVID-19 occurred. CONCLUSIONS: Albeit limited by the small numbers, a single dose of the BNT162b2 vaccine was not efficacious at preventing COVID-19 during this nursing home outbreak.

SARS-CoV-2 is associated with high viral loads in asymptomatic and recently symptomatic healthcare workers.

BACKGROUND: Healthcare workers (HCW) are at increased risk of SARS-CoV-2 infection from both patients and other HCW with coronavirus disease 2019 (COVID-19). RT-PCR cycle threshold (Ct) values of SARS-CoV-2 ≤ 34 and the first 7-9 days of symptoms are associated with enhanced infectivity. We determined Ct values and duration of symptoms of HCW with a positive SARS-CoV-2 test. As HCW often assume their greatest risk of acquiring SARS-CoV-2 is working on a COVID-19 unit, we also determined Ct values and symptom duration of inpatients with a positive SARS-CoV-2 test. METHODS: From 6/24/2020-8/23/2020, Ct values and duration of symptoms from 13 HCW, 12 outpatients, and 28 inpatients who had a positive nasopharyngeal swab for SARS-CoV-2 were analyzed. RESULTS: Among HCW with a positive SARS-CoV-2 test, 46.2% (6/13) were asymptomatic and requested testing due to an exposure to someone with COVID-19; 83.3% (5/6) of those exposures occurred in the community rather than in the hospital. The median Ct value of HCW was 23.2, and 84.6% (11/13) had a Ct value ≤ 34. The median Ct value of 29.0 among outpatients with COVID-19 did not significantly differ from HCW. In contrast, inpatients with a positive SARS-CoV-2 test had a median Ct value of 34.0 (p = 0.003), which translated into a median ~1,000-fold lower viral load than observed in HCW. Among those with symptoms related to COVID-19, no (0/6) HCW compared to 50% (6/12) of inpatients had symptoms for at least one week (p = 0.04). CONCLUSIONS: At our institution, asymptomatic COVID-19 accounted for nearly half of the cases among HCW. Symptomatic HCW had high viral loads and short duration of symptoms, both of which are associated with peak infectivity. Infection prevention programs should educate HCW on these findings in an effort to increase adherence to the requirement to maintain six feet separation in workspaces and breakrooms, in addition to consistently wearing personal protection equipment.

PRO: The COVID-19 pandemic will result in increased antimicrobial resistance rates.

We argue that the COVID-19 pandemic will result in increased antimicrobial resistance (AMR). Broad-spectrum antibiotic use is common among hospitalized COVID-19 patients and in excess of reported secondary infection rates, suggesting unnecessary prescribing. Selection pressure is likely to be particularly intense in COVID-19 epicentres and within non-epicentre hospital units dedicated to COVID-19 care. Risk factors that increase the likelihood of hospitalization or poor outcomes among COVID-19 patients, such as advanced age, nursing home residence, debilitation, diabetes and cardiopulmonary or other underlying systemic diseases, also predispose to AMR infections. Worry for AMR emergence is heightened since first-wave COVID-19 epicentres were also AMR epicentres. Disruptive direct and indirect effects of COVID-19 globally on economic systems, governance and public health expenditure and infrastructure may fuel AMR spread. We anticipate that the impact of COVID-19 on AMR will vary between epicentres and non-epicentres, by geographic region, hospital to hospital within regions and within specific hospital units.

Suprapubic catheter placement improves antimicrobial stewardship among Veterans Affairs nursing care facility residents.

In a Veterans Affairs nursing facility, suprapubic catheters were associated with significantly fewer urinary tract infections (catheter-associated urinary tract infection) than were indwelling urinary catheters (mean: 0.95 vs 4.5/1,000 device-days, P = .05) among 18 patients with a history of both catheter types. Suprapubic catheters were associated with significantly shorter antibiotic treatment courses for catheter-associated urinary tract infection or asymptomatic bacteriuria (mean: 28.3 vs 88.8 days, P = .02).