In vitro exposure to non-antipseudomonal antibiotics (NAPA) induces Pseudomonas aeruginosa resistance to antipseudomonal antibiotics (APA)
Abstract
Background: Pseudomonas aeruginosa readily evolves antimicrobial resistance through regulatory plasticity and stress-adaptive pathways. Clinically, antibiotics lacking intrinsic antipseudomonal activity are often favored with the assumption that they avoid selective pressure on P. aeruginosa . Whether subinhibitory exposure to such “non-antipseudomonal antibiotics” (NAPA) can nevertheless select for canonical resistance pathways remains incompletely defined.
Methods:: Three P. aeruginosa strains (ATCC 27853 and two bloodstream isolates) were serially passaged over 14 days in the presence of ertapenem, ceftriaxone, or moxifloxacin at one-third the baseline minimum inhibitory concentration (MIC). MICs for antipseudomonal antibiotics (meropenem, ceftazidime, ciprofloxacin) were measured at serial time points and after a 3-day antibiotic-free recovery (day 14). Whole-genome sequencing was performed longitudinally to identify mutations.
Results: NAPA exposure led to reproducible elevations in antipseudomonal MICs: ertapenem triggered up to a 29-fold increase in meropenem MIC, ceftriaxone up to a 31-fold rise in ceftazidime MIC, and moxifloxacin up to a 12-fold increase in ciprofloxacin MIC. Elevated MICs persisted on day 14 despite absence of further antibiotic pressure. Genomic analysis revealed convergent evolution of mutations in efflux regulator genes ( nfxB, nalC, nalD, amrR ) and the β-lactamase–regulating gene dacB , emerging during periods of MIC escalation and mapping to…
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Evidence Hub reads this as a preprint, done in cell cultures (in vitro), not in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.
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