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Carbapenem-Resistant Pseudomonas aeruginosa in Chronic Lung Infection: Current Resistance Profile and Hypermutability
Mila M Almeida1, Meyvianne T Freitas1, Tania W Folescu2
1Departamento de Microbiologia, Imunologia e Parasitologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Abstract:
Pseudomonas aeruginosa is associated with chronic and progressive lung disease and is closely related to increased morbidity and mortality in cystic fibrosis (CF) patients. Hypermutable (HPM) P. aeruginosa isolates have been described in these patients and are usually associated with antibiotic resistance. This study aimed to investigate the occurrence of carbapenem resistance and hypermutable phenotype in 179 P. aeruginosa isolates from 8 chronically CF patients assisted at two reference centers in Rio de Janeiro, Brazil. Using disk diffusion test, non-susceptible (NS) rates higher than 40% were observed for imipenem, amikacin, and gentamicin. A total of 79 isolates (44.1%), 71 (39.6%), and 8 (4.4%) were classified as carbapenem-resistant (CR resistance to at least one carbapenem), multidrug-resistant (MDR), and extensively drug-resistant (XDR), respectively. Minimal inhibitory concentration was determined for 79 CR P. aeruginosa and showed the following variations: 4 and 128 μg/mL to imipenem, 4 and 64 µg/mL to meropenem, and 4 and ≥ 32 µg/mL to doripenem. We have found only four (2.23%) HPM isolates from 4 patients. Analyzing the genetic relationship among the HPM isolates, 3 pulsed-field gel electrophoresis/pulsotypes (D, M, and J) were observed. Only M pulsotype was recovered from two patients in different years. Polymerase chain reaction screening for blaGES, blaIMP, blaKPC, blaNDM, blaOXA-48, blaSPM, and blaVIM genes was performed for all CR isolates and none of them were positive. Our results demonstrate a high occurrence of CR and MDR P. aeruginosa of CF patients follow-up in both centers studied, while the presence of HPM is still unusual.
Insights
High rates of carbapenem-resistant Pseudomonas aeruginosa were found in cystic fibrosis patients in Brazil. However, hypermutable P. aeruginosa strains, often linked to antibiotic resistance, were rare in this study.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Pseudomonas aeruginosa is a major cause of lung disease in cystic fibrosis (CF) patients, increasing morbidity and mortality.
- Hypermutable (HPM) P. aeruginosa strains are associated with antibiotic resistance in CF patients.
- Carbapenem resistance is a growing global health concern.
Purpose of the Study:
- To investigate the prevalence of carbapenem resistance and hypermutable phenotypes in P. aeruginosa isolates from CF patients in Rio de Janeiro, Brazil.
- To characterize the antibiotic resistance profiles and genetic relatedness of these isolates.
Main Methods:
- Disk diffusion and minimal inhibitory concentration (MIC) tests were used to determine antibiotic susceptibility.
- Hypermutability was assessed, and genetic relatedness of HPM isolates was analyzed using pulsed-field gel electrophoresis (PFGE).
- PCR screening was performed for carbapenemase genes (blaGES, blaIMP, blaKPC, blaNDM, blaOXA-48, blaSPM, and blaVIM).
Main Results:
- High non-susceptible rates (>40%) were observed for imipenem, amikacin, and gentamicin.
- 44.1% of isolates were carbapenem-resistant (CR), 39.6% were multidrug-resistant (MDR), and 4.4% were extensively drug-resistant (XDR).
- Only 2.23% of isolates were hypermutable (HPM), and no carbapenemase genes were detected in CR isolates.
Conclusions:
- There is a high occurrence of carbapenem-resistant and multidrug-resistant P. aeruginosa in CF patients in the studied Brazilian centers.
- The prevalence of hypermutable P. aeruginosa strains remains unusual in this patient population.
- The absence of common carbapenemase genes suggests other resistance mechanisms may be involved.
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