Emergence of colistin resistance without loss of fitness and virulence after prolonged colistin administration in a patient with extensively drug-resistant Acinetobacter baumannii

Acinetobacter baumannii has emerged as a major cause of healthcare-associated infections. It commonly expresses clinical resistance to multiple antimicrobial agents, and hence, it is considered the paradigm of an extensively drug-resistant (XDR) bacterium. XDR A. baumannii is a rapidly emerging pathogen, especially in the intensive care unit (ICU), causing nosocomial infections including sepsis, ventilatorassociated pneumonia, meningitis, peritonitis, urinary tract infection, and central venous catheter-related infection. In the present report, we described an in vivo evolution of A. baumannii strain from a colistinsusceptibility to a colistin-resistance state. A 65-year-old male, who suffered a duodenal ulcer, two days after hospitalization and during the stay in ICU, contracted a pneumonia and peritoneal infection by a carbapenem-resistant A. baumannii strain. After a combination treatment with colistin, vancomycin plus imipenem, and within seven days, the pathogen rapidly evolved in seven days to a pandrug-resistant phenotype. As the antimicrobial treatment was stopped, the A. baumannii isolate changed another time its profile to colistin, becoming newly susceptible, showing a very high level of adaptability to external conditions. We also have reviewed here the current literature on this worryingly public health threat.

Download Full-text

Dissecting Colistin Resistance Mechanisms in Extensively Drug-Resistant Acinetobacter baumannii Clinical Isolates

mBio ◽

10.1128/mbio.01083-19 ◽

2019 ◽

Vol 10 (4) ◽

Cited By ~ 18

Author(s):

Vincent Trebosc ◽

Sarah Gartenmann ◽

Marcus Tötzl ◽

Valentina Lucchini ◽

Birgit Schellhorn ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Nosocomial Infections ◽

Drug Target ◽

Resistance Mechanism ◽

Clinical Isolates ◽

Drug Resistant ◽

Colistin Resistance ◽

Content Type ◽

Extensively Drug Resistant ◽

Direct Targeting

ABSTRACT Nosocomial infections with Acinetobacter baumannii are a global problem in intensive care units with high mortality rates. Increasing resistance to first- and second-line antibiotics has forced the use of colistin as last-resort treatment, and increasing development of colistin resistance in A. baumannii has been reported. We evaluated the transcriptional regulator PmrA as potential drug target to restore colistin efficacy in A. baumannii. Deletion of pmrA restored colistin susceptibility in 10 of the 12 extensively drug-resistant A. baumannii clinical isolates studied, indicating the importance of PmrA in the drug resistance phenotype. However, two strains remained highly resistant, indicating that PmrA-mediated overexpression of the phosphoethanolamine (PetN) transferase PmrC is not the exclusive colistin resistance mechanism in A. baumannii. A detailed genetic characterization revealed a new colistin resistance mechanism mediated by genetic integration of the insertion element ISAbaI upstream of the PmrC homolog EptA (93% identity), leading to its overexpression. We found that eptA was ubiquitously present in clinical strains belonging to the international clone 2, and ISAbaI integration upstream of eptA was required to mediate the colistin-resistant phenotype. In addition, we found a duplicated ISAbaI-eptA cassette in one isolate, indicating that this colistin resistance determinant may be embedded in a mobile genetic element. Our data disprove PmrA as a drug target for adjuvant therapy but highlight the importance of PetN transferase-mediated colistin resistance in clinical strains. We suggest that direct targeting of the homologous PetN transferases PmrC/EptA may have the potential to overcome colistin resistance in A. baumannii. IMPORTANCE The discovery of antibiotics revolutionized modern medicine and enabled us to cure previously deadly bacterial infections. However, a progressive increase in antibiotic resistance rates is a major and global threat for our health care system. Colistin represents one of our last-resort antibiotics that is still active against most Gram-negative bacterial pathogens, but increasing resistance is reported worldwide, in particular due to the plasmid-encoded protein MCR-1 present in pathogens such as Escherichia coli and Klebsiella pneumoniae. Here, we showed that colistin resistance in A. baumannii, a top-priority pathogen causing deadly nosocomial infections, is mediated through different avenues that result in increased activity of homologous phosphoethanolamine (PetN) transferases. Considering that MCR-1 is also a PetN transferase, our findings indicate that PetN transferases might be the Achilles heel of superbugs and that direct targeting of them may have the potential to preserve the activity of polymyxin antibiotics.

Download Full-text

Decreased carO gene expression and OXA-type carbapenemases among extensively drug-resistant Acinetobacter baumannii strains isolated from burn patients in Tehran, Iran

Acta Microbiologica et Immunologica Hungarica ◽

10.1556/030.2020.01138 ◽

2020 ◽

Cited By ~ 1

Author(s):

Elham Abbasi ◽

Hossein Goudarzi ◽

Ali Hashemi ◽

Alireza Salimi Chirani ◽

Abdollah Ardebili ◽

...

Keyword(s):

Gene Expression ◽

Acinetobacter Baumannii ◽

High Rate ◽

Burn Patients ◽

Drug Resistant ◽

Disc Diffusion ◽

Carbapenem Resistant ◽

Extensively Drug Resistant ◽

Sds Page ◽

Extensively Drug Resistance

AbstractA major challenge in the treatment of infections has been the rise of extensively drug resistance (XDR) and multidrug resistance (MDR) in Acinetobacter baumannii. The goals of this study were to determine the pattern of antimicrobial susceptibility, blaOXA and carO genes among burn-isolated A. baumannii strains. In this study, 100 A. baumannii strains were isolated from burn patients and their susceptibilities to different antibiotics were determined using disc diffusion testing and broth microdilution. Presence of carO gene and OXA-type carbapenemase genes was tested by PCR and sequencing. SDS-PAGE was done to survey CarO porin and the expression level of carO gene was evaluated by Real-Time PCR. A high rate of resistance to meropenem (98%), imipenem (98%) and doripenem (98%) was detected. All tested A. baumannii strains were susceptible to colistin. The results indicated that 84.9% were XDR and 97.9% of strains were MDR. In addition, all strains bore blaOXA-51 like and blaOXA-23 like and carO genes. Nonetheless, blaOXA-58 like and blaOXA-24 like genes were harbored by 0 percent and 76 percent of strains, respectively. The relative expression levels of the carO gene ranged from 0.06 to 35.01 fold lower than that of carbapenem-susceptible A. baumannii ATCC19606 and SDS – PAGE analysis of the outer membrane protein showed that all 100 isolates produced CarO. The results of current study revealed prevalence of blaOXA genes and changes in carO gene expression in carbapenem resistant A.baumannii.

Download Full-text

Complete Genome Sequences of Four Extensively Drug-Resistant Acinetobacter baumannii Isolates from Thailand

Microbiology Resource Announcements ◽

10.1128/mra.00949-20 ◽

2020 ◽

Vol 9 (40) ◽

Author(s):

Peechanika Chopjitt ◽

Thidathip Wongsurawat ◽

Piroon Jenjaroenpun ◽

Parichart Boueroy ◽

Rujirat Hatrongjit ◽

...

Keyword(s):

Acinetobacter Baumannii ◽

Complete Genome ◽

Sequence Type ◽

Clinical Isolates ◽

Drug Resistant ◽

Genome Sequences ◽

Content Type ◽

Type Isolate ◽

Resistant Genes ◽

Extensively Drug Resistant

ABSTRACT Here, we report the complete genome sequences of four clinical isolates of extensively drug-resistant Acinetobacter baumannii (XDRAB), isolated in Thailand. These results revealed multiple antimicrobial-resistant genes, each involving two sequence type 16 (ST16) isolates, ST2, and a novel sequence type isolate, ST1479.

Download Full-text

Molecular characterization of an extensively drug-resistant Acinetobacter baumannii isolated from a corn culture soil

Pedosphere ◽

10.1016/s1002-0160(21)60039-5 ◽

2021 ◽

Vol 31 (6) ◽

pp. 973-976

Author(s):

João Pedro Rueda FURLAN ◽

Eliana Guedes STEHLING

Keyword(s):

Acinetobacter Baumannii ◽

Molecular Characterization ◽

Drug Resistant ◽

Extensively Drug Resistant

Download Full-text

Extensively drug-resistant Acinetobacter baumannii nosocomial pneumonia successfully treated with a novel antibiotic combination

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00924-21 ◽

2021 ◽

Author(s):

Noor Zaidan ◽

J. Patrik Hornak ◽

David Reynoso

Keyword(s):

Septic Shock ◽

Drug Development ◽

Acinetobacter Baumannii ◽

Nosocomial Infections ◽

Drug Resistant ◽

Access Protocol ◽

The Poor ◽

Extensively Drug Resistant ◽

Poor Outcomes ◽

Antibiotic Combination

Extremely drug resistant (XDR) Acinetobacter baumannii cause challenging nosocomial infections. We report the case of a patient with XDR A. baumannii pneumonia and septic shock successfully treated with cefiderocol and a novel antibiotic obtained via expanded access protocol. With focused research and drug development efforts, the poor outcomes associated with these infections may be mitigated.

Download Full-text