Publications

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture.

METHODS: This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures.

RESULTS: CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55-13.73) and CRPA (OR 2.82, 95% CI 2.04-3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures.

CONCLUSIONS: Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.

BACKGROUND: The drug supply chain is global and at risk of disruption and subsequent drug shortages, especially during unanticipated events.

OBJECTIVE: Our objective was to determine the impact of coronavirus disease 2019 (COVID-19) on drug purchases overall, by class, and for specific countries.

METHODS: A cross-sectional time series analysis of country-level drug purchase data from August 2014 to August 2020 from IQVIA MIDAS was conducted. Standardized units per 100 population and percentage increase in units purchased were assessed from 68 countries and jurisdictions in March 2020 (when the World Health Organization declared COVID-19 a pandemic). Analyses were compared by United Nations development status and drug class. Autoregressive integrated moving average models tested the significance of changes in purchasing trends.

RESULTS: Before COVID-19, standardized medication units per 100 population ranged from 3990 to 4760 monthly. In March 2020, there was a global 15% increase in units of drugs purchased to 5309.3 units per 100 population compared with the previous year; the increase was greater in developed countries (18.5%; P < 0.001) than in developing countries (12.8%; P < 0.0001). After the increase in March 2020, there was a correction in the global purchase rate decreasing by 4.7% (April to August 2020 rate, 21,334.6/100 population; P < 0.001). Globally, we observed high purchasing rates and large changes for respiratory medicines such as inhalers and systemic adrenergic drugs (March 2020 rate, 892.7/100 population; change from 2019, 28.5%; P < 0.001). Purchases for topical dermatologic products also increased substantially (42.2%), although at lower absolute rates (610.0/100 population in March 2020; P < 0.0001). Interestingly, purchases for systemic anti-infective agents (including antiviral drugs) increased in developing countries (11.3%; P < 0.001), but decreased in developed countries (1.0%; P = 0.06).

CONCLUSION: We observed evidence of global drug stockpiling in the early months of the COVID-19 pandemic, especially among developed countries. Actions toward equitable distribution of medicines through a resilient drug supply chain should be taken to increase global response to future unanticipated events, such as pandemics.

BACKGROUND: Little is known about the effect of the COVID-19 pandemic on antimicrobial consumption worldwide.

OBJECTIVES: To describe the impact of the WHO Global Action Plan on Antimicrobial Resistance (GAP-AMR) on antimicrobial consumption pre-pandemic and to evaluate the impact of the COVID-19 pandemic on antimicrobial consumption worldwide.

METHODS: A cross-sectional time-series analysis using a dataset of monthly purchases of antimicrobials (antibiotics, antivirals and antifungals) from August 2014 to August 2020. Antimicrobial consumption per 1000 population was assessed pre-pandemic by economic development status using linear regression models. Interventional autoregressive integrated moving average (ARIMA) models tested for significant changes with pandemic declaration (March 2020) and during its first stage from April to August 2020, worldwide and by country development status.

RESULTS: Prior to the pandemic, antimicrobial consumption decreased worldwide, with a greater apparent decrease in developed versus developing countries (-8.4%, P = 0.020 versus -1.2%, P = 0.660). Relative to 2019, antimicrobial consumption increased by 11.2%, P < 0.001 in March 2020. The greatest increase was for antivirals in both developed and developing countries (48.2%, P < 0.001; 110.0%, P < 0.001) followed by antibiotics (6.9%, P < 0.001; 5.9%, P = 0.003). From April to August 2020, antimicrobial consumption decreased worldwide by 18.7% (P < 0.001) compared with the previous year. Specifically, antibiotic consumption significantly decreased in both developed and developing countries (-28.0%, P < 0.001; -16.8%, P < 0.001).

CONCLUSIONS: The global decrease in antimicrobial consumption pre-pandemic suggests a positive impact of the WHO GAP-AMR. During the pandemic, an initial increase in antimicrobial consumption was followed by a decrease worldwide. AMR plans should specify measures to ensure full implementation of AMR efforts during health crises such as the COVID-19 pandemic.

OBJECTIVE: To evaluate opportunities for assessing penicillin allergies among patients presenting to dental clinics.

DESIGN: Retrospective cross-sectional study.

SETTING: VA dental clinics.

PATIENTS: Adult patients with a documented penicillin allergy who received an antibiotic from a dentist between January 1, 2015, and December 31, 2018, were included.

METHODS: Chart reviews were completed on random samples of 100 patients who received a noncephalosporin antibiotic and 200 patients who received a cephalosporin. Each allergy was categorized by severity. These categories were used to determine patient eligibility for 3 testing groups based on peer-reviewed algorithms: (1) no testing, (2) skin testing, and (3) oral test-dose challenge. Descriptive and bivariate statistics were used to compare facility and patient demographics first between true penicillin allergy, pseudo penicillin allergy, and missing allergy documentation, and between those who received a cephalosporin and those who did not at the dental visit.

RESULTS: Overall, 19% lacked documentation of the nature of allergic reaction, 53% were eligible for skin testing, 27% were eligible for an oral test-dose challenge, and 1% were contraindicated from testing. Male patients and African American patients were less likely to receive a cephalosporin.

CONCLUSIONS: Most penicillin-allergic patients in the VA receiving an antibiotic from a dentist are eligible for penicillin skin testing or an oral penicillin challenge. Further research is needed to understand the role of dentists and dental clinics in assessing penicillin allergies.

To investigate factors that influence antibiotic prescribing decisions, we interviewed 49 antibiotic stewardship champions and stakeholders across 15 hospitals. We conducted thematic analysis and subcoding of decisional factors. We identified 31 factors that influence antibiotic prescribing decisions. These factors may help stewardship programs identify educational targets and design more effective interventions.

OBJECTIVE: To describe national trends in testing and detection of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE) and associate testing with culture and facility characteristics.

DESIGN: Retrospective cohort study.

SETTING: Department of Veterans' Affairs medical centers (VAMCs).

PARTICIPANTS: Patients seen at VAMCs between 2013 and 2018 with cultures positive for CRE, defined by national VA guidelines.

INTERVENTIONS: Microbiology and clinical data were extracted from national VA data sets. Carbapenemase testing was summarized using descriptive statistics. Characteristics associated with carbapenemase testing were assessed with bivariate analyses.

RESULTS: Of 5,778 standard cultures that grew CRE, 1,905 (33.0%) had evidence of molecular or phenotypic carbapenemase testing and 1,603 (84.1%) of these had carbapenemases detected. Among these cultures confirmed as carbapenemase-producing CRE, 1,053 (65.7%) had molecular testing for ≥1 gene. Almost all testing included KPC (n = 1,047, 99.4%), with KPC detected in 914 of 1,047 (87.3%) cultures. Testing and detection of other enzymes was less frequent. Carbapenemase testing increased over the study period from 23.5% of CRE cultures in 2013 to 58.9% in 2018. The South US Census region (38.6%) and the Northeast (37.2%) region had the highest proportion of CRE cultures with carbapenemase testing. High complexity (vs low) and urban (vs rural) facilities were significantly associated with carbapenemase testing (P < .0001).

CONCLUSIONS: Between 2013 and 2018, carbapenemase testing and detection increased in the VA, largely reflecting increased testing and detection of KPC. Surveillance of other carbapenemases is important due to global spread and increasing antibiotic resistance. Efforts supporting the expansion of carbapenemase testing to low-complexity, rural healthcare facilities and standardization of reporting of carbapenemase testing are needed.

BACKGROUND: Viridans group streptococci (VGS) are typically part of the commensal flora but can also cause severe invasive diseases such as infective endocarditis. There are limited data available showing antibiotic susceptibility over time for VGS.

OBJECTIVES: To evaluate antibiotic susceptibility trends in VGS over time.

METHODS: In vitro susceptibility patterns for 33 antibiotics were examined for Streptococcus mitis, Streptococcus oralis, and non-speciated VGS isolates from patients in Veterans Affairs (VA) Medical Centers in the United States between 2010 and 2020. Susceptibility determinations were made by the individual clinical microbiology laboratories and data were retrospectively collected from the VA Corporate Data Warehouse. Susceptibility trends were analysed using Poisson regression.

RESULTS: A total of 14 981 VGS isolates were included of which 19.5%, 0.7% and 79.8% were S. mitis, S. oralis and non-speciated VGS isolates, respectively. Cumulative susceptibility rates across all years were similar between species for ceftriaxone (range: 96.0% to 100%), clindamycin (81.3% to 84.5%), and vancomycin (99.7% to 100%). For penicillin, susceptibility rates were 71.0%, 80.9% and 86.3% for S. mitis, S. oralis and non-speciated isolates, respectively. From 2010 to 2020, susceptibility of non-speciated VGS isolates decreased for erythromycin (P = 0.0674), penicillin (P = 0.0835), and tetracycline (P = 0.0994); though the decrease was only significant for clindamycin (P = 0.0033). For S. mitis, a significant susceptibility rate decrease was observed for erythromycin (P = 0.0112).

CONCLUSIONS: Susceptibility rates for some clinically relevant antibiotics declined between 2010 and 2020. This worrisome trend highlights the need to improve antimicrobial stewardship efforts to limit unnecessary antibiotic use and preserve empirical treatment options.

INTRODUCTION: Prescribing antibiotic prophylaxis is common yet unnecessary for many dental visits. In this analysis, our objective was to assess whether the appropriateness of antibiotic prophylaxis has improved over time.

METHODS: A retrospective cohort study was conducted using dental visits from 2016 to 2018 (data analyzed in 2021) using medical and prescriptions claims data of patients from the U.S. with commercial dental insurance. Antibiotic prophylaxis was defined as a ≤2 days' supply prescription dispensed within 7 days before a dental visit. Appropriateness of prophylaxis was defined on the basis of the manipulation of the gingiva/tooth periapex or oral mucosa perforation in patients with appropriate cardiac diagnoses. Associations between patient and visit characteristics and appropriateness of antibiotic prophylaxis were assessed using multiple Poisson regression.

RESULTS: Unnecessary antibiotic prophylaxis was highly prevalent in this cohort, ranging from 77.0% in 2016 to 78.5% in 2018. In the adjusted analysis, factors associated with unnecessary antibiotic prophylaxis included younger age, female sex, geographic region, rurality, type of antibiotic, and certain dental procedures. The factors associated with the highest risk of unnecessary prophylaxis in the adjusted analysis were orthodontic procedures and having a history of a prosthetic joint. Notably, the risk of unnecessary antibiotic prophylaxis decreased over time in the adjusted analysis.

CONCLUSIONS: Unnecessary prescription of antibiotic prophylaxis by dentists continues to be common. Antimicrobial stewardship strategies are needed to improve prescribing by dentists.

INTRODUCTION: Evidence suggests that U.S. dentists prescribe opioids excessively. There are limited national data on recent trends in opioid prescriptions by U.S. dentists. In this study, we examined trends in opioid prescribing by general dentists and dental specialists in the U.S. from 2012 to 2019.

METHODS: Dispensed prescriptions for oral opioid analgesics written by dentists were identified from IQVIA Longitudinal Prescription Data from January 2012 through December 2019. Autoregressive integrated moving average and joinpoint regression models described monthly population-based prescribing rates (prescriptions/100,000 individuals), dentist-based prescribing rates (prescriptions/1,000 dentists), and opioid dosages (mean daily morphine milligram equivalents/day). All analyses were performed in 2020.

RESULTS: Over the 8 years, dentists prescribed >87.2 million opioid prescriptions. Population- and dentist-based prescribing rates declined monthly by -1.97 prescriptions/100,000 individuals (95% CI= -9.98, -0.97) and -39.12 prescriptions/1,000 dentists (95% CI= -58.63, -17.65), respectively. Opioid dosages declined monthly by -0.08 morphine milligram equivalents/day (95% CI= -0.13, -0.04). Joinpoint regression identified 4 timepoints (February 2016, May 2017, December 2018, and March 2019) at which monthly prescribing rate trends were often decreasing in greater magnitude than those in the previous time segment.

CONCLUSIONS: Following national trends, dentists became more conservative in prescribing opioids. A greater magnitude of decline occurred post 2016 following the implementation of strategies aimed to further regulate opioid prescribing. Understanding the factors that influence prescribing trends can aid in development of tailored resources to encourage and support a conservative approach by dentists, to prescribing opioids.

A survey of Veterans' Affairs Medical Centers on control of carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-producing CRE (CP-CRE) demonstrated that most facilities use VA guidelines but few screen for CRE/CP-CRE colonization regularly or regularly communicate CRE/CP-CRE status at patient transfer. Most respondents were knowledgeable about CRE guidelines but cited lack of adequate resources.