Antibiotic Resistance Patterns and Association With the Influenza Season in the United States: A Multicenter Evaluation Reveals Surprising Associations Between Influenza Season and Resistance in Gram-Negative Pathogens

Abstract

Background Viral infections are often treated with empiric antibiotics due to suspected bacterial co-infections, leading to antibiotic overuse. We aimed to describe antibiotic resistance (ABR) trends and their association with the influenza season in ambulatory and inpatient settings in the US. Methods We used the BD Insights Research Database (Franklin Lakes, NJ, US) to evaluate antibiotic susceptibility profiles in 30-day non-duplicate bacterial isolates collected from patients >17 years old at 257 US healthcare institutions from 2011-19. We investigated ABR in Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) and Gram-negative (Enterobacterales [ENT], Pseudomonas aeruginosa [PSA], and Acinetobacter baumannii spp. [ACB]) bacteria expressed as the proportion of isolates not susceptible (NS; intermediate or resistant) and resistance per 100 admissions (inpatients only). Antibiotics included carbapenems (Carb), fluoroquinolones (FQ), macrolides, penicillin, extended-spectrum cephalosporins (ESC), and methicillin. Generalized estimating equations models were used to evaluate monthly trends in ABR outcomes and associations with community influenza rates. Results We identified 8,250,860 non-duplicate pathogens, including 154,841 Gram-negative Carb-NS, 1,502,796 Gram-negative FQ-NS, 498,012 methicillin-resistant S. aureus (MRSA), and 44,131 NS S. pneumoniae. All S. pneumoniae rates per 100 admissions (macrolide-, penicillin-, and ESC-NS) were associated with influenza rates. Respiratory, but not non-respiratory, MRSA was also associated with influenza. For Gram-negative pathogens, influenza rates were associated with the percent of FQ-NS ENT, FQ-NS PSA, and Carb-NS ACB. Conclusions Our study showed expected increases in rates of ABR Gram-positive and identified small but surprising increases in ABR Gram-negative pathogens associated with influenza activity. These insights may help inform antimicrobial stewardship initiatives.

A Multicenter Evaluation of Trends in Antimicrobial Resistance Among Streptococcus pneumoniae Isolates From Adults in the United States

“…Reporting institutions consisted of US hospitals in the BD Insights Research Database (Becton, Dickinson and Company, Franklin Lakes, NJ, USA), which includes small and large hospitals in urban and rural areas, provides geographical representation across the United States, and contains electronically captured laboratory, pharmacy, patient demographics, administrative data, and admission, discharge, and transfer data feeds [ 2 , 6 , 26 ]. The study was approved as involving use of a limited retrospective data set for an epidemiology study and was exempt from consent by the New England Institutional Review Board/Human Subjects Research Committee (Wellesley, MA, USA) and conducted in compliance with Health Insurance Portability and Accountability Act requirements.…”

“…Other factors contributing to AMR include low pneumococcal vaccination rates, particularly in adults [ 21 , 22 ], and high antibiotic usage rates for common respiratory antibiotics, including inappropriate prescriptions [ 23–25 ]. Several recent studies have documented increased AMR in North American S. pneumoniae isolates in both hospitalized and ambulatory adults [ 6 , 7 , 26–28 ].…”

A multicenter analysis of inpatient antibiotic use during the 2015–2019 influenza seasons in the United States: Untapped opportunities for antimicrobial stewardship

“…4 We recently reported that antibiotic resistance also demonstrated seasonal trends and was associated with influenza rates. 5 Our observations on seasonal trends in IAU and antibiotic resistance may highlight an opportunity for improved antimicrobial stewardship efforts during the influenza and viral respiratory season and support the expansion of vaccination programs, a key component of the World Health Organization Action framework on leveraging vaccines to reduce antibiotic use and prevent antibiotic resistance. 8 In addition to documenting the seasonality of IAU for common antibiotics, our study provides data on trends over time in antibiotic use that update an earlier (2006-2012) study.…”

“…Data on influenza rates (percentage of positive tests) tracked well with influenza data from the Centers for Disease Control and Prevention. 5,7 Trends in IAU Unadjusted bivariate results showed ascending trends over time (2015-2019) for IAU for ESCs, BLICs, macrolides, and tetracyclines (Supplementary Table 4). In contrast, descending trends were observed in the IAUs of FQs, "other" antibiotics, specified anti-MRSA drugs, carbapenems, and lipopeptides.…”

“…the BD Insights Research Database (Franklin Lakes, NJ), which includes small and large hospitals with geographical representation across the United States. 5 Geographic localization was based on US Department of Health & Human Services (HHS) regions. Outcome studies using this retrospective, deidentified data set were approved and informed consent was waived by the New England Institutional Review Board (Wellesley, MA).…”