Fatal Outbreak of an Emerging Clone of Extensively Drug-Resistant<i>Acinetobacter baumannii</i>With Enhanced Virulence

Jones, Crystal L.; Clancy, Megan; Honnold, Cary L.; Singh, Shweta; Snesrud, Erik; Onmus-Leone, Fatma; McGann, Patrick; Ong, Ana; Kwak, Yoon I.; Waterman, Paige; Zurawski, Daniel V.; Clifford, Robert; Lesho, Emil

doi:10.1093/cid/civ225

Cited by 86 publications

(40 citation statements)

References 40 publications

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“…In addition, the T6SS of DSM30011 is required for host colonization of the G. mellonella model organism (Repizo et al, 2015). Similar results were obtained from a comparative analysis of the genomes of MDR A. baumannii clinical strains (Wright et al, 2014; Jones et al, 2015). A. baumannii isolates of a particular clade exhibit complete loss of the T6SS genomic locus.…”

Section: Acinetobacter Baumannii Virulence Factors and Pathogenesissupporting

confidence: 79%

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Lee

Park

et al. 2017

Front. Cell. Infect. Microbiol.

643

527

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Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized.

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Section: Acinetobacter Baumannii Virulence Factors and Pathogenesissupporting

confidence: 79%

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Lee

Park

et al. 2017

Front. Cell. Infect. Microbiol.

643

527

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“…To our knowledge, this was a novel outbreak due to ST79 possessing bla OXA-24/40 , although bla OXA-24/40 was mostly detected among CC2 (9). None of the MDRAB isolates belonged to ST10, which has been associated with enhanced virulence among fatal outbreak strains (54).…”

Section: Discussionmentioning

confidence: 84%

Next-Generation Sequencing and Comparative Analysis of Sequential Outbreaks Caused by Multidrug-Resistant Acinetobacter baumannii at a Large Academic Burn Center

Kanamori

Parobek

Weber

et al. 2016

Antimicrob Agents Chemother

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f Next-generation sequencing (NGS) analysis has emerged as a promising molecular epidemiological method for investigating health care-associated outbreaks. Here, we used NGS to investigate a 3-year outbreak of multidrug-resistant Acinetobacter baumannii (MDRAB) at a large academic burn center. A reference genome from the index case was generated using de novo assembly of PacBio reads. Forty-six MDRAB isolates were analyzed by pulsed-field gel electrophoresis (PFGE) and sequenced using an Illumina platform. After mapping to the index case reference genome, four samples were excluded due to low coverage, leaving 42 samples for further analysis. Multilocus sequence types (MLST) and the presence of acquired resistance genes were also determined from the sequencing data. A transmission network was inferred from genomic and epidemiological data using a Bayesian framework. Based on single-nucleotide variant (SNV) differences, this MDRAB outbreak represented three sequential outbreaks caused by distinct clones. The first and second outbreaks were caused by sequence type 2 (ST2), while the third outbreak was caused by ST79. For the second outbreak, the MLST and PFGE results were discordant. However, NGS-based SNV typing detected a recombination event and consequently enabled a more accurate phylogenetic analysis. The distribution of resistance genes varied among the three outbreaks. The first-and second-outbreak strains possessed a bla OXA-23-like group, while the thirdoutbreak strains harbored a bla OXA-40-like group. NGS-based analysis demonstrated the superior resolution of outbreak transmission networks for MDRAB and provided insight into the mechanisms of strain diversification between sequential outbreaks through recombination.H ealth care-associated infections (HAI) are a substantial cause of morbidity and mortality in acute-care hospitals (1). Acinetobacter baumannii is an important opportunistic pathogen causing HAI (2) and has become one of the most common colonizing pathogens in burn patients (3, 4). A. baumannii may cause serious outbreaks despite the implementation of rigorous infection prevention interventions and control measures, which occur most commonly in intensive care units (5-8). Furthermore, the emergence of multidrug-resistant A. baumannii (MDRAB), especially carbapenem-resistant A. baumannii (CRAB), has become a global concern (5, 9). Patients infected by multidrug-resistant Acinetobacter strains are likely to have higher mortality rates and longer lengths of hospitalization than those infected by susceptible strains (10).Pulsed-field gel electrophoresis (PFGE) has been the gold standard approach for bacterial strain typing in hospital outbreak investigations, but several disadvantages have been described, including that it is a time-consuming, labor-intensive, and technically demanding assay and that is has limited reproducibility among laboratories; also, the interpretation of the relative relatedness of strains using this method may be discordant and subjective (11-13). For these reasons, next...

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“…Capsule and its negative surface charge may well be the primary virulence function of the pathogen, as it is the primary defense the bacteria have against complement-mediated destruction and opsonization, as well as phagocytic uptake (74,(104)(105)(106)(107). Hypervirulent strains have been reported that resist innate immune uptake, which may have unusual or mutated capsular phenotypes (70,105,(108)(109)(110). In one compelling study, the investigators used the lack of virulence of the lab-adapted A. baumannii strain ATCC 17978 to demonstrate a remarkable gain of function of virulence by treating the strain with small molecules that triggered overexpression of capsule (107).…”

Section: Acinetobacter Virulence Factorsmentioning

confidence: 99%

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

et al. 2017

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SUMMARY Acinetobacter is a complex genus, and historically, there has been confusion about the existence of multiple species. The species commonly cause nosocomial infections, predominantly aspiration pneumonia and catheter-associated bacteremia, but can also cause soft tissue and urinary tract infections. Community-acquired infections by Acinetobacter spp. are increasingly reported. Transmission of Acinetobacter and subsequent disease is facilitated by the organism's environmental tenacity, resistance to desiccation, and evasion of host immunity. The virulence properties demonstrated by Acinetobacter spp. primarily stem from evasion of rapid clearance by the innate immune system, effectively enabling high bacterial density that triggers lipopolysaccharide (LPS)–Toll-like receptor 4 (TLR4)-mediated sepsis. Capsular polysaccharide is a critical virulence factor that enables immune evasion, while LPS triggers septic shock. However, the primary driver of clinical outcome is antibiotic resistance. Administration of initially effective therapy is key to improving survival, reducing 30-day mortality threefold. Regrettably, due to the high frequency of this organism having an extreme drug resistance (XDR) phenotype, early initiation of effective therapy is a major clinical challenge. Given its high rate of antibiotic resistance and abysmal outcomes (up to 70% mortality rate from infections caused by XDR strains in some case series), new preventative and therapeutic options for Acinetobacter spp. are desperately needed.

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Fatal Outbreak of an Emerging Clone of Extensively Drug-ResistantAcinetobacter baumanniiWith Enhanced Virulence

Abstract: Clade B warrants continued surveillance and investigation.

Cited by 86 publications

References 40 publications

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

Next-Generation Sequencing and Comparative Analysis of Sequential Outbreaks Caused by Multidrug-Resistant Acinetobacter baumannii at a Large Academic Burn Center

Clinical and Pathophysiological Overview of Acinetobacter Infections: a Century of Challenges

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