OBJECTIVES: The main objective of this study was to investigate the relationship among the in vivo acquisition of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates, the underlying molecular mechanisms and previous exposure to antipseudomonal agents. METHODS: PFGE was used to study the molecular relatedness of the strains. The MICs of ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, ciprofloxacin and amikacin were determined. Outer membrane protein profiles were assessed to study OprD expression. RT-PCR was performed to analyse ampC, mexB, mexD, mexF and mexY expression. The presence of mutations was analysed through DNA sequencing. RESULTS: We collected 17 clonally related paired isolates [including first positive samples (A) and those with MICs increased ≥4-fold (B)]. Most B isolates with increased MICs of imipenem, meropenem and ceftazidime became resistant to these drugs. The most prevalent resistance mechanisms detected were OprD loss (65%), mexB overexpression (53%), ampC derepression (29%), quinolone target gene mutations (24%) and increased mexY expression (24%). Five (29%) B isolates developed multidrug resistance. Meropenem was the most frequently (71%) received treatment, explaining the high prevalence of oprD mutations and likely mexB overexpression. Previous exposure to ceftazidime showed a higher impact on selection of increased MICs than previous exposure to piperacillin/tazobactam. CONCLUSIONS: Stepwise acquisition of resistance has a critical impact on the resistance phenotypes of P. aeruginosa, leading to a complex scenario for finding effective antimicrobial regimens. In the clinical setting, meropenem seems to be the most frequent driver of multidrug resistance development, while piperacillin/tazobactam, in contrast to ceftazidime, seems to be the β-lactam least associated with the selection of resistance mechanisms.
OBJECTIVES: The main objective of this study was to investigate the relationship among the in vivo acquisition of antimicrobial resistance in Pseudomonas aeruginosa clinical isolates, the underlying molecular mechanisms and previous exposure to antipseudomonal agents. METHODS: PFGE was used to study the molecular relatedness of the strains. The MICs of ceftazidime, cefepime, piperacillin/tazobactam, imipenem, meropenem, ciprofloxacin and amikacin were determined. Outer membrane protein profiles were assessed to study OprD expression. RT-PCR was performed to analyse ampC, mexB, mexD, mexF and mexY expression. The presence of mutations was analysed through DNA sequencing. RESULTS: We collected 17 clonally related paired isolates [including first positive samples (A) and those with MICs increased ≥4-fold (B)]. Most B isolates with increased MICs of imipenem, meropenem and ceftazidime became resistant to these drugs. The most prevalent resistance mechanisms detected were OprD loss (65%), mexB overexpression (53%), ampC derepression (29%), quinolone target gene mutations (24%) and increased mexY expression (24%). Five (29%) B isolates developed multidrug resistance. Meropenem was the most frequently (71%) received treatment, explaining the high prevalence of oprD mutations and likely mexB overexpression. Previous exposure to ceftazidime showed a higher impact on selection of increased MICs than previous exposure to piperacillin/tazobactam. CONCLUSIONS: Stepwise acquisition of resistance has a critical impact on the resistance phenotypes of P. aeruginosa, leading to a complex scenario for finding effective antimicrobial regimens. In the clinical setting, meropenem seems to be the most frequent driver of multidrug resistance development, while piperacillin/tazobactam, in contrast to ceftazidime, seems to be the β-lactam least associated with the selection of resistance mechanisms.
Authors: Richard A Stanton; Davina Campbell; Gillian A McAllister; Erin Breaker; Michelle Adamczyk; Jonathan B Daniels; Joseph D Lutgring; Maria Karlsson; Kyle Schutz; Jesse T Jacob; Lucy E Wilson; Elisabeth Vaeth; Linda Li; Ruth Lynfield; Paula M Snippes Vagnone; Erin C Phipps; Emily B Hancock; Ghinwa Dumyati; Rebecca Tsay; P Maureen Cassidy; Jacquelyn Mounsey; Julian E Grass; Sandra N Bulens; Maroya Spalding Walters; Alison Laufer Halpin Journal: Antimicrob Agents Chemother Date: 2022-09-06 Impact factor: 5.938
Authors: F Scasso; G Ferrari; G C DE Vincentiis; A Arosio; S Bottero; M Carretti; A Ciardo; S Cocuzza; A Colombo; B Conti; A Cordone; M DE Ciccio; E Delehaye; L Della Vecchia; I DE Macina; C Dentone; P DI Mauro; R Dorati; R Fazio; A Ferrari; G Ferrea; S Giannantonio; I Genta; M Giuliani; D Lucidi; L Maiolino; G Marini; P Marsella; D Meucci; T Modena; B Montemurri; A Odone; S Palma; M L Panatta; M Piemonte; P Pisani; S Pisani; L Prioglio; A Scorpecci; L Scotto DI Santillo; A Serra; C Signorelli; E Sitzia; M L Tropiano; M Trozzi; F M Tucci; L Vezzosi; B Viaggi Journal: Acta Otorhinolaryngol Ital Date: 2018-04 Impact factor: 2.124
Authors: Erlangga Yusuf; Bruno Van Herendael; Walter Verbrugghe; Margareta Ieven; Emiel Goovaerts; Kristof Bergs; Kristien Wouters; Philippe G Jorens; Herman Goossens Journal: Ann Intensive Care Date: 2017-06-29 Impact factor: 6.925
Authors: A Hernández; G Yagüe; E García Vázquez; M Simón; L Moreno Parrado; M Canteras; J Gómez Journal: Rev Esp Quimioter Date: 2018-03-21 Impact factor: 1.553