Assessing the impact of meropenem exposure on ceftolozane/tazobactam-resistance development in Pseudomonas aeruginosa using in vitro serial passage.
J Antimicrob Chemother
; 79(5): 1176-1181, 2024 05 02.
Article
em 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 ANDMETHODS:
Nine clinical P. aeruginosa isolates were exposed to MEM 16â mg/L for 72â h. Then, isolates were serially passaged in the presence of C/T (concentration of 10â mg/L) for 72â h as two groups an MEM-exposed group inoculated with MEM pre-exposed isolates and a non-MEM control group. At 24â h intervals, samples were plated on drug-free and drug-containing agar (C/T concentration 16/8â 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 72â 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 72â 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
/
Infecções por Pseudomonas
/
Cefalosporinas
/
Meropeném
/
Tazobactam
/
Antibacterianos
Limite:
Humans
Idioma:
En
Revista:
J Antimicrob Chemother
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos