Infectious Diseases

GeoSentinel travelers’ diarrhea data show extensive FQ resistance and regionally high macrolide nonsusceptibility

Among 859 international travelers with culture-confirmed diarrhea, fluoroquinolone nonsusceptibility in Campylobacter reached 75%, substantially limiting this class for empiric therapy. Campylobacter macrolide nonsusceptibility was 12% overall but 88% in travelers to South Central Asia, challenging azithromycin-based self-treatment for that region. Nontyphoidal Salmonella showed 32% fluoroquinolone, 16% macrolide, and 5% third-generation cephalosporin nonsusceptibility, complicating oral empiric options. Shigella had 22% fluoroquinolone and 35% macrolide nonsusceptibility, while diarrheagenic E coli had 18% fluoroquinolone nonsusceptibility. 1

No geographic spillover of azithromycin MDA–induced macrolide resistance detected in Niger

After two years of azithromycin mass drug administration in 594 villages, investigators evaluated resistance in 30 neighboring placebo villages in Niger. Metagenomic sequencing of rectal swabs from 300 children showed macrolide resistance gene loads in placebo villages remained at baseline. Resistance in untreated villages did not correlate with surrounding azithromycin treatment intensity (Spearman ρ = -0.05; P = 0.83). Sensitivity analyses found no spillover for macrolides or other antibiotic classes at 24 months. 2

Phylodynamics quantify fitness effects of gonococcal resistance determinants under real-world antibiotic pressure

A hierarchical Bayesian phylodynamic model was applied to a 20-year collection of Neisseria gonorrhoeae isolates to link resistance determinants with lineage success. Fitness effects of resistance varied with contemporaneous ciprofloxacin, cefixime, ceftriaxone, and azithromycin use, integrating clinical drug pressure into the model. Distinct genetic pathways conferring the same phenotypic resistance showed different fitness profiles, indicating heterogeneous epidemic potential of resistance mechanisms. Competition experiments in vitro and in a mouse infection model supported the modeled fitness estimates. 3

ddPCR-guided stewardship and PCT-assisted discontinuation improve outcomes in suspected bloodstream infection

In a prospective cohort of 703 patients with suspected bloodstream infection, ddPCR results were used to judge and adjust initial antibiotic regimens. Patients with appropriate initial therapy or inappropriate therapy that was adjusted based on ddPCR had significantly lower 28-day mortality than unadjusted patients. Multivariable Cox analysis showed appropriate therapy (HR 0.47) and adjusted inappropriate therapy (HR 0.54) independently predicted lower 28-day mortality versus unadjusted inappropriate therapy. Among 257 patients on prolonged antibiotics, combining ddPCR with procalcitonin to guide discontinuation reduced 28-day mortality compared with ddPCR or PCT alone. 4