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Assessing the impact of meropenem exposure on ceftolozane/tazobactam-resistance development in Pseudomonas aeruginosa using in vitro serial passage.
Fouad, Aliaa; Nicolau, Samantha E; Tamma, Pranita D; Simner, Patricia J; Nicolau, David P; Gill, Christian M.
Afiliación
  • Fouad A; Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, USA.
  • Nicolau SE; mRNA Center of Excellence, Sanofi Pasteur, Waltham, MA, USA.
  • Tamma PD; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Simner PJ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Nicolau DP; Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, USA.
  • Gill CM; Division of Infectious Diseases, Hartford Hospital, Hartford, CT, USA.
J Antimicrob Chemother ; 79(5): 1176-1181, 2024 05 02.
Article en En | MEDLINE | ID: mdl-38562061
ABSTRACT

BACKGROUND:

Patients infected with difficult-to-treat Pseudomonas aeruginosa are likely to receive meropenem (MEM) empirically before escalation to ceftolozane/tazobactam (C/T). We assessed whether pre-exposure to MEM affected C/T resistance development on C/T exposure. MATERIALS AND

METHODS:

Nine clinical P. aeruginosa isolates were exposed to MEM 16 mg/L for 72 h. Then, isolates were serially passaged in the presence of C/T (concentration of 10 mg/L) for 72 h as two groups an MEM-exposed group inoculated with MEM pre-exposed isolates and a non-MEM control group. At 24 h intervals, samples were plated on drug-free and drug-containing agar (C/T concentration 16/8 mg/L) and incubated to quantify bacterial densities (log10 cfu/mL). Growth on C/T agar indicated resistance development, and resistant population was calculated by dividing the cfu/mL on C/T plates by the cfu/mL on drug-free agar.

RESULTS:

At 72 h, resistant populations were detected in 6/9 isolates. In five isolates, MEM exposure significantly increased the prevalence of ceftolozane/tazobactam-resistance development; the percentages of resistance population were 100%, 100%, 53.5%, 31% and 3% for the MEM-exposed versus 0%, 0%, 2%, 0.35% and ≤0.0003% in the unexposed groups. One isolate had a similar resistant population at 72 h between the two groups. The remaining isolates showed no development of resistance, regardless of previous MEM exposure.

CONCLUSIONS:

MEM exposure may pre-dispose to C/T resistance development and thus limit the therapeutic utility of this ß-lactam/ß-lactamase inhibitor. Resistance may be a result of stress exposure or molecular-level mutations conferring cross-resistance. Further in vivo studies are needed to assess clinical implications of these findings.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Infecciones por Pseudomonas / Cefalosporinas / Meropenem / Tazobactam / Antibacterianos Límite: Humans Idioma: En Revista: J Antimicrob Chemother Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pseudomonas aeruginosa / Infecciones por Pseudomonas / Cefalosporinas / Meropenem / Tazobactam / Antibacterianos Límite: Humans Idioma: En Revista: J Antimicrob Chemother Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido