Search

Background In the USA, nirmatrelvir/ritonavir is authorized for the treatment of mild-to-moderate COVID-19 in patients at least 12 years of age, at high risk for progression to severe COVID-19. Objectives To estimate the impact of outpatient nirmatrelvir/ritonavir on COVID-19 hospitalization risk in a US healthcare system. Methods We conducted a cohort study using electronic health records among outpatients with a positive SARS-CoV-2 PCR test between January and August 2022. We evaluated the association of nirmatrelvir/ritonavir therapy with time to hospitalization by estimating adjusted HRs and assessed the impact of nirmatrelvir/ritonavir on predicted COVID-19 hospitalizations using machine-learning methods. Results Among 44 671 patients, 4948 (11%) received nirmatrelvir/ritonavir, and 201 (0.4%) were hospitalized within 28 days of COVID-19 diagnosis. Nirmatrelvir/ritonavir recipients were more likely to be older, white, vaccinated, have comorbidities and reside in areas with higher average socioeconomic status. The 28 day cumulative incidence of hospitalization was 0.06% (95% CI: 0.02%–0.17%) among nirmatrelvir/ritonavir recipients and 0.52% (95% CI: 0.46%–0.60%) among non-recipients. For nirmatrelvir/ritonavir versus no therapy, the age-adjusted HR was 0.08 (95% CI: 0.03–0.26); the fully adjusted HR was 0.16 (95% CI: 0.05–0.50). In the machine-learning model, the primary features reducing predicted hospitalization risk were nirmatrelvir/ritonavir, younger age, vaccination, female gender and residence in a higher socioeconomic status area. Conclusions COVID-19 hospitalization risk was reduced by 84% among nirmatrelvir/ritonavir recipients in a large, diverse healthcare system during the Omicron wave. These results suggest that nirmatrelvir/ritonavir remained highly effective in a setting substantially different than the original clinical trials. [ABSTRACT FROM AUTHOR]

Background Multidrug-resistant Enterobacterales (MDR-E) are important pathogens. People living with human immunodeficiency virus (HIV; PLWH) may be at greater risk for MDR-E infection given relatively high antibiotic exposure and burden of comorbidities. Methods We analyzed data from 36 521 patients in a healthcare system in North Carolina who had a clinical culture with growth of an Enterobacterales species from 2000 to 2018; 440 were PLWH. We used generalized linear models to estimate prevalence ratios and differences, contrasting PLWH and people not living with HIV (PNLWH) for resistance to individual antibiotic classes, as well as MDR-E. We assessed trends in prevalence over time by calculating the 5-year moving average and fitting restricted cubic spline models. Results The overall prevalence of MDR-E was higher among PLWH (21.5%; 95% confidence interval [CI], 18.2%–25.1%) vs PNLWH (16.5%; 95% CI, 16.2%–16.9%), with an adjusted prevalence ratio of 1.38 (95% CI, 1.14–1.65). PLWH had higher rates of antimicrobial resistance than PNLWH for all antibiotic classes analyzed, including penicillins, penicillin/beta lactamase inhibitor combinations, and sulfonamides. MDR-E prevalence was 3 to 10 percentage points higher among PLWH than PNLWH throughout the study period based on the 5-year moving average. Conclusions In a large clinical study population in the southeastern United States from 2000 to 2018, the prevalence of antibacterial resistance among Enterobacterales was consistently higher among PLWH than PNLWH. These data highlight the importance of identifying and mitigating the factors that contribute to antimicrobial resistance in PLWH, given the potential clinical consequences of these resistant pathogens. [ABSTRACT FROM AUTHOR]

Background Urinary tract infection (UTI) is the most common clinical manifestation of carbapenem-resistant Klebsiella pneumoniae (CR Kp). Persistent CR Kp bacteriuria is associated with the spread of CR Kp and antibiotic overuse. Risk factors for persistent CR Kp bacteriuria are uncertain. Methods CRACKLE-1 was a multicenter, prospective study that included 960 patients with at least one carbapenem-resistant Enterobacteriaceae (CRE)-positive culture from December 2011 to June 2016 collected from 18 hospitals encompassing 8 healthcare systems in the Midwestern US and North Carolina. Patients with CR Kp bacteriuria who were discharged alive from index hospitalization were included in the current study, and sporadic (single positive CR Kp urine culture) and persistent (≥2 CR Kp urine cultures during independent hospital admissions occurring at least 2 days apart) cases were compared. Antibiotic susceptibility testing was performed by local laboratories. Amikacin, gentamicin (GENT), and trimethoprim/sulfamethoxazole were included in the analysis based on variance and frequency of testing. The CDC/National Healthcare Safety Network criteria for UTI were used. Results CR Kp was the most common CRE isolate (n = 869, prevalence 91%). In patients with CR Kp , 527 had CR Kp isolated from the urine (prevalence 61%, 95% CI 0.57, 0.64). Of these, 486 patients, of whom 129 (27%) were diagnosed with a UTI, were discharged alive. Notably, 135/486 (28%) patients with CR Kp bacteriuria were readmitted and yielded a second urine culture of CR Kp. Most patients with persistent bacteriuria, 99/135 (73%), were asymptomatic at initial admission. Of these patients, 20/99 (20%) were diagnosed with a UTI at second admission. In multivariable analysis, only GENT non-susceptibility was associated with an increased risk (adjusted OR 1.66, 95% CI 1.10–2.49) of persistent bacteriuria. Persistent bacteriuria was independent of GENT treatment during index hospitalization (GENT was used in 15% of patients). Conclusion Bacteriuria with GENT non-susceptible CR Kp strains was associated with persistent bacteriuria. As this was independent of GENT treatment, GENT resistance determinants may be co-transmitted along with traits that promote bacterial persistence in CR Kp. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]