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.

Background Antibacterial therapy is frequently used in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) without evidence of bacterial infection, prompting concerns about increased antimicrobial resistance (AMR). We evaluated trends in AMR before and during the SARS-CoV-2 pandemic. Methods This multicenter, retrospective cohort analysis included hospitalized adults aged ≥18 years with >1-day inpatient admission and a record of discharge or death from 271 US facilities in the BD Insights Research Database. We evaluated rates of AMR events, defined as positive cultures for select Gram-negative and Gram-positive pathogens from any source with nonsusceptibility reported by commercial panels before (7/1/19-2/29/20) and during (3/1/20-10/30/21) the SARS-CoV-2 pandemic. Results Of 5,518,666 admissions evaluated, AMR rates per 1000 admissions were 35.4 for the pre-pandemic period and 34.7 for the pandemic period (P ≤ 0.0001). In the pandemic period, AMR rates per 1000 admissions were 49.2 for SARS-CoV-2-positive admissions, 41.1 for SARS-CoV-2-negative admissions, and 25.7 for patients untested (P ≤ 0.0001). AMR rates per 1000 admissions among community-onset (CO) infections during the pandemic were lower versus pre-pandemic levels (26.1 vs 27.6; P < 0.0001), while AMR rates for hospital-onset (HO) infections were higher (8.6 vs 7.7; P < 0.0001), driven largely by SARS-Cov-2-positive admissions (21.8). AMR rates were associated with overall antimicrobial use, rates of positive cultures, and higher use of inadequate empiric therapy. Conclusions Although overall AMR rates did not substantially increase from pre-pandemic levels, patients tested for SARS-CoV-2 infection had a significantly higher rate of AMR and HO infections. Antimicrobial and diagnostic stewardship is key to identifying this high-risk AMR population.

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Background Management of pneumococcal disease is complicated by high rates of antimicrobial resistance (AMR). This study assessed AMR trends for Streptococcus pneumoniae isolates from adults with pneumococcal disease. Methods From January 2011 to February 2020, we evaluated 30-day non-duplicate S. pneumoniae isolates from 290 US hospitals (BD Insights Research Database) from adults (≥ 18 years) in inpatient and outpatient settings. Isolates were required to have at least one AMR result for invasive (blood, cerebrospinal fluid/neurologic) or non-invasive (respiratory or ear/nose/throat) pneumococcal disease samples. Determination of AMR was based on facility reports of intermediate or resistant. Descriptive statistics and generalized estimated equations were used to assess variations over time. Results Over the study period, 34,039 S. pneumoniae isolates were analyzed (20,749 [61%] from non-invasive sources and 13,290 [39%] from invasive sources). Almost half (46.6%) of the isolates were resistant to ≥ 1 drug and non-invasive isolates had higher rates of AMR than invasive isolates. Total S. pneumoniae isolates had high rates of resistance to macrolides (37.7%), penicillin (22.1%), and tetracyclines (16.1%). Multivariate modeling identified a significant increasing trend in resistance to macrolides (+1.8%/year; P < 0.001). Significant decreasing trends were observed for penicillin (-1.6%/year; P < 0.001), extended-spectrum cephalosporins (ESCs) (-0.35%/year; P < 0.001), and ≥3 drugs (-0.5%/year; P < 0.001). Conclusions Despite decreasing trends for penicillin, ESCs, and resistance to ≥3 drugs, AMR rates are persistently high in S. pneumoniae isolates among US adults. Increasing macrolide resistance suggests that efforts to address AMR in S. pneumoniae may require antimicrobial stewardship efforts and higher-valent pneumococcal conjugate vaccines.

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Background Urinary tract infections (UTIs), which are usually caused by bacteria in the Enterobacterales family, are a common reason for outpatient visits. Appropriate empiric therapy for UTIs requires an understanding of antibiotic resistance in the community. In this nationwide study, we examined trends in antibiotic resistance in urinary Enterobacterales isolates from ambulatory patients in the United States (US). Methods We analyzed the antimicrobial susceptibility profiles (extended-spectrum beta-lactamase [ESBL]-producing phenotype and not susceptible [NS] to beta-lactams, trimethoprim/sulfamethoxazole [TMP/SMX], fluoroquinolones [FQ], or nitrofurantoin [NFT]) of 30-day non-duplicate Enterobacterales isolates from urine cultures tested at ambulatory centers in the BD Insights Research Database (2011–2020). The outcome of interest was the percentage of resistant isolates by pathogen and year. Multi-variable generalized estimating equation models were used to assess trends in resistance over time and by additional covariates. Results A total of 338 US facilities provided data for > 2.2 million urinary Enterobacterales isolates during the 10-year study. Almost three-quarters (72.8%) of Enterobacterales isolates were Escherichia coli. Overall unadjusted resistance rates in Enterobacterales isolates were 57.5%, 23.1%, 20.6%, and 20.2% for beta-lactams, TMP/SMX, FQ, and NFT, respectively, and 6.9% had an ESBL-producing phenotype. Resistance to two or more antibiotic classes occurred in 16.4% of isolates and 5.5% were resistant to three or more classes. Among isolates with an ESBL-producing phenotype, 70.1%, 59.9%, and 33.5% were NS to FQ, TMP/SMX, and NFT, respectively. In multivariable models, ESBL-producing and NFT NS Enterobacterales isolates increased significantly (both P < 0.001), while other categories of resistance decreased. High rates (≥ 50%) of beta-lactam and NFT resistance were observed in Klebsiella isolates and in non-E. coli, non-Klebsiella Enterobacterales isolates. Conclusions Antimicrobial resistance was common in urinary Enterobacterales isolates. Isolates with an ESBL-producing phenotype increased by about 30% between 2011 and 2020, and significant increases were also observed in NFT NS Enterobacterales isolates. Resistance rates for all four antibiotic classes were higher than thresholds recommended for use as empiric therapy. Non-E. coli Enterobacterales isolates showed high levels of resistance to commonly used empiric antibiotics, including NFT. These data may help inform empiric therapy choices for outpatients with UTIs.

Clinicians often base antimicrobial therapeutic decisions on laboratory determinations of pathogen susceptibility to an antibiotic based on MIC breakpoints. MIC breakpoints evolve over time based on new information; between 2010 and 2012 the CLSI lowered carbapenem breakpoints for Enterobacterales and Pseudomonas aeruginosa , and these were subsequently adopted by the US Food and Drug Administration.

Background Antimicrobial resistance (AMR) poses a significant challenge for treating pneumococcal disease. This study assessed AMR trends in Streptococcus pneumoniae from US children. Methods We evaluated antibiotic resistance, defined as facility antimicrobial susceptibility reports of intermediate/resistant, in 30-day non-duplicate S. pneumoniae isolates from children (&lt;18 years) with invasive (blood or cerebrospinal fluid/neurological) or non-invasive (respiratory or ear/nose/throat) isolates at 219 US hospital inpatient/outpatient settings in the BD Insights Research Database (January 2011-February 2020). We used descriptive statistics to characterize the percentage of AMR isolates and generalized estimated equations to assess variations in resistance over time. Results Of 7,605 S. pneumoniae isolates analyzed, 6,641 (87.3%) were from non-invasive sources. Resistance rates were higher in non-invasive versus invasive isolates. Isolates showed high observed rates of resistance to ≥1 drug class (56.8%), ≥2 drug classes (30.7%), macrolides (39.9%), and penicillin (39.6%) and significant annual increases in resistance to ≥1 drug class (+0.9%), ≥2 drug classes (+1.8%), and macrolides (+5.0%). Conclusions Among US children over the last decade, S. pneumoniae isolates showed persistently high rates of resistance to antibiotics and significant increases in ≥1 drug class, ≥2 drug classes, and macrolide resistance rates. Efforts to address AMR in S. pneumoniae may require vaccines targeting resistant serotypes and antimicrobial stewardship efforts.