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Polymyxin B Heteroresistance and Adaptive Resistance in Multidrug- and Extremely Drug-Resistant Acinetobacter
Gabrielle Limeira Genteluci1,2, Paula Araujo de Souza3, Daniela Betzler Cardoso Gomes3,4
1Department of Microbiology, National Institute of Quality Control in Heath, Fiocruz, Rio de Janeiro, Brazil. genteluci2@hotmail.com.
Abstract:
Acinetobacter baumannii is an emerging pathogen associated with nosocomial infections and multidrug resistance. Polymyxin B has been used to treat infections caused by multidrug-resistant (MDR) A. baumannii but an increase in polymyxin B resistance has been observed. We aimed to determine the diversity, antimicrobial susceptibility, presence of polymyxin B heteroresistance and adaptive resistance in 72 A. baumannii clinical isolates from two public hospitals in Rio de Janeiro. The isolates were identified by sequencing of rpoB gene. Determination of the genetic diversity of isolates was performed by pulsed-field gel electrophoresis and oxacillinases genes were detected by polymerase chain reaction. The polymyxin B heteroresistance was analyzed by population analysis profile and adaptive resistance was evaluated after serial daily passages of isolates in broth containing increasing polymyxin B concentrations. The results showed that 49% of the isolates were collected from respiratory system and 62% were MDR, while 35% were extensively drug resistant. Additionally, all the isolates carried blaOXA-23-like, blaOXA-51-like genes and ISAba1, while 1% had blaOXA-24-like gene. The association of ISAba1-blaOXA-23 was found in 96% of the isolates. Polymyxin B heteroresistance was found in 36% of the isolates and polymyxin B adaptive resistance was not found in the isolates. Our study demonstrated the high resistance to antimicrobials used in clinical practice and the spread of oxacillinases genes and insertion sequence (IS). We also reported the presence of heteroresistance to polymyxin B used as a last-resort therapy for MDR A. baumannii.
Insights
Multidrug-resistant Acinetobacter baumannii infections are a growing concern. This study found widespread oxacillinase genes and polymyxin B heteroresistance in clinical isolates, but no adaptive resistance, highlighting treatment challenges.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Antimicrobial Resistance
Background:
- Acinetobacter baumannii is a significant cause of hospital-acquired infections.
- Multidrug resistance (MDR) in A. baumannii complicates treatment options.
- Polymyxin B is a last-resort antibiotic, but resistance is emerging.
Purpose of the Study:
- To investigate the genetic diversity and antimicrobial susceptibility of A. baumannii clinical isolates.
- To determine the prevalence of polymyxin B heteroresistance and adaptive resistance.
- To analyze the presence of oxacillinase genes and insertion sequences in MDR A. baumannii.
Main Methods:
- Identification of 72 A. baumannii isolates using rpoB gene sequencing.
- Genetic diversity assessed by pulsed-field gel electrophoresis.
- Detection of oxacillinase genes (blaOXA) and ISAba1 using PCR.
- Polymyxin B heteroresistance evaluated by population analysis profile.
- Adaptive resistance assessed through serial passage in increasing polymyxin B concentrations.
Main Results:
- 62% of isolates were multidrug-resistant (MDR), and 35% were extensively drug-resistant (XDR).
- All isolates harbored blaOXA-23-like and blaOXA-51-like genes; 96% showed ISAba1-blaOXA-23 association.
- Polymyxin B heteroresistance was detected in 36% of isolates; no adaptive resistance was observed.
- Respiratory tract infections were the most common source (49% of isolates).
Conclusions:
- High levels of antimicrobial resistance and the spread of oxacillinase genes are evident in A. baumannii clinical isolates.
- The presence of polymyxin B heteroresistance poses a significant challenge for treating MDR A. baumannii infections.
- Further strategies are needed to combat the increasing resistance of this opportunistic pathogen.
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