Stenotrophomonas, Achromobacter, and Nonmelioid Burkholderia Species: Antimicrobial Resistance and Therapeutic Strategies

Abbott, Iain J.; Peleg, Anton Y.

doi:10.1055/s-0034-1396929

Cited by 105 publications

(37 citation statements)

References 94 publications

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“…The most active additive or synergistic combinations were chloramphenicol plus minocycline, ciprofloxacin plus imipenem, and ciprofloxacin plus meropenem (21). Consequently, first-line treatment options against A. xylosoxidans included piperacillintazobactam, carbapenems (imipenem and meropenem), and trimethoprim-sulfamethoxazole, while second-line drugs are ceftazidime, minocycline, colistin, and chloramphenicol (22). In addition, acquired resistance in Achromobacter spp., leading to multidrug resistance and pan-resistance, has been reported for CF strains (23,24).…”

Section: Discussionmentioning

confidence: 99%

Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing

et al. 2017

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Chronic colonization by opportunistic environmental bacteria is frequent in the airways of cystic fibrosis (CF) patients. Studies of Pseudomonas aeruginosa evolution during persistence have highlighted the emergence of pathoadaptive genotypes and phenotypes, leading to complex and diversified inpatient colonizing populations also observed at the intraspecimen level. Such diversity, including heterogeneity in resistance profiles, has been considered an adaptive strategy devoted to host persistence. Longitudinal genomic diversity has been shown for the emergent opportunistic pathogen Achromobacter, but phenotypic and genomic diversity has not yet been studied within a simple CF sputum sample. Here, we studied the genomic diversity and antimicrobial resistance heterogeneity of 132 Achromobacter species strains (8 to 27 strains of identical or distinct colonial morphotypes per specimen) recovered from the sputum samples of 9 chronically colonized CF patients. We highlighted the high within-sample and within-morphotype diversity of antimicrobial resistance (disk diffusion) and genomic (pulsed-field gel electrophoresis) profiles. No sputum sample included strains with identical pulsotypes or antibiotic susceptibility patterns. Differences in clinical categorization were observed for the 9 patients and concerned 3 to 11 antibiotics, including antibiotics recommended for use against Achromobacter. Within-sample antimicrobial resistance heterogeneity, not predictable from colonial morphology, suggested that it may represent a selective advantage against antibiotics in an Achromobacter persisting population and potentially compromise the antibiotic management of CF airway infections.KEYWORDS Achromobacter, antimicrobial susceptibility, cystic fibrosis, diversity, genome B acterial adaptation during persistence in the respiratory tract of cystic fibrosis (CF) patients has mainly been studied for Pseudomonas aeruginosa showing that pathoadaptation mechanisms are particularly efficient, leading to rare and hardly achievable P. aeruginosa eradication. Many studies have revealed a variety of phenotypic pathoadaptative traits during long-term colonization, such as auxotrophy and metabolic modifications, quorum-sensing alterations, biofilm production, loss of motility and virulence factors, emergence of mucoid colonies, and an increase of antibiotic resistance (for a review, see reference 1). Moreover, numerous genomic modifications, which were either directly related to phenotype or not, were observed (1, 2). Other species, such as the Burkholderia cepacia complex, Stenotrophomonas maltophilia, and

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Section: Discussionmentioning

confidence: 99%

Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing

et al. 2017

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“…2011; Trancassini et al. 2014), Achromobacter species can also cause infections such as bacteremia, pneumonia, meningitis, urinary tract infections, and nosocomial infections (reviewed in Abbott and Peleg 2015). This may be the reason why, after a decade of stagnation, research focusing on clinical Achromobacter isolates was revived ∼10 years ago (fig.…”

Section: Introductionmentioning

confidence: 99%

A Pan-Genomic Approach to Understand the Basis of Host Adaptation in Achromobacter

Jeukens

Freschi

Vincent

et al. 2017

Genome Biology and Evolution

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Over the past decade, there has been a rising interest in Achromobacter sp., an emerging opportunistic pathogen responsible for nosocomial and cystic fibrosis lung infections. Species of this genus are ubiquitous in the environment, can outcompete resident microbiota, and are resistant to commonly used disinfectants as well as antibiotics. Nevertheless, the Achromobacter genus suffers from difficulties in diagnosis, unresolved taxonomy and limited understanding of how it adapts to the cystic fibrosis lung, not to mention other host environments. The goals of this first genus-wide comparative genomics study were to clarify the taxonomy of this genus and identify genomic features associated with pathogenicity and host adaptation. This was done with a widely applicable approach based on pan-genome analysis. First, using all publicly available genomes, a combination of phylogenetic analysis based on 1,780 conserved genes with average nucleotide identity and accessory genome composition allowed the identification of a largely clinical lineage composed of Achromobacter xylosoxidans, Achromobacter insuavis, Achromobacter dolens, and Achromobacter ruhlandii. Within this lineage, we identified 35 positively selected genes involved in metabolism, regulation and efflux-mediated antibiotic resistance. Second, resistome analysis showed that this clinical lineage carried additional antibiotic resistance genes compared with other isolates. Finally, we identified putative mobile elements that contribute 53% of the genus’s resistome and support horizontal gene transfer between Achromobacter and other ecologically similar genera. This study provides strong phylogenetic and pan-genomic bases to motivate further research on Achromobacter, and contributes to the understanding of opportunistic pathogen evolution.

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“…B urkholderia multivorans is a member of a larger group of pathogens, the Burkholderia cepacia complex (BCC), that includes Ͼ20 different species (1,2). BCC bacteria can cause infections (e.g., pneumonia) in immunocompromised persons or in other individuals, such as those with cystic fibrosis (3)(4)(5)(6)(7). Currently, ␤-lactam antibiotics are recommended as a treatment option for infections due to BCC bacteria (8,9).…”

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Characterization of the AmpC β-Lactamase from Burkholderia multivorans

Becka

Zeiser

Barnes

et al. 2018

Antimicrob Agents Chemother

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is a member of the complex, a group of>20 related species of nosocomial pathogens that commonly infect individuals suffering from cystic fibrosis. β-Lactam antibiotics are recommended as therapy for infections due to , which possesses two β-lactamase genes, and PenA is a carbapenemase with a substrate profile similar to that of the carbapenemase (KPC); in addition, expression of PenA is inducible by β-lactams in Here, we characterize AmpC from ATCC 17616. AmpC possesses only 38 to 46% protein identity with non- AmpC proteins (e.g., PDC-1 and CMY-2). Among 49 clinical isolates of , we identified 27 different AmpC variants. Some variants possessed single amino acid substitutions within critical active-site motifs (Ω loop and R2 loop). Purified AmpC1 demonstrated minimal measurable catalytic activity toward β-lactams (i.e., nitrocefin and cephalothin). Moreover, avibactam was a poor inhibitor of AmpC1 ( > 600 μM), and acyl-enzyme complex formation with AmpC1 was slow, likely due to lack of productive interactions with active-site residues. Interestingly, immunoblotting using a polyclonal anti-AmpC antibody revealed that protein expression of AmpC1 was inducible in ATCC 17616 after growth in subinhibitory concentrations of imipenem (1 μg/ml). AmpC is a unique inducible class C cephalosporinase that may play an ancillary role in compared to PenA, which is the dominant β-lactamase in ATCC 17616.

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Stenotrophomonas, Achromobacter, and Nonmelioid Burkholderia Species: Antimicrobial Resistance and Therapeutic Strategies

Cited by 105 publications

References 94 publications

Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing

Impact of High Diversity of Achromobacter Populations within Cystic Fibrosis Sputum Samples on Antimicrobial Susceptibility Testing

A Pan-Genomic Approach to Understand the Basis of Host Adaptation in Achromobacter

Characterization of the AmpC β-Lactamase from Burkholderia multivorans

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