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Antimicrobial Agents and Chemotherapy Oct 2020is a genus of nonfermenting Gram-negative bacteria under order Although primarily isolated from respiratory tract of people with cystic fibrosis, spp. can cause a... (Review)
Review
is a genus of nonfermenting Gram-negative bacteria under order Although primarily isolated from respiratory tract of people with cystic fibrosis, spp. can cause a broad range of infections in hosts with other underlying conditions. Their rare occurrence and ever-changing taxonomy hinder defining their clinical features, risk factors for acquisition and adverse outcomes, and optimal treatment. spp. are intrinsically resistant to several antibiotics (e.g., most cephalosporins, aztreonam, and aminoglycosides), and are increasingly acquiring resistance to carbapenems. Carbapenem resistance is mainly caused by multidrug efflux pumps and metallo-β-lactamases, which are not expected to be overcome by new β-lactamase inhibitors. Among the other new antibiotics, cefiderocol, and eravacycline were used as salvage therapy for a limited number of patients with infections. In this article, we aim to give an overview of the antimicrobial resistance in species, highlighting the possible place of new antibiotics in their treatment.
Topics: Achromobacter; Anti-Bacterial Agents; Carbapenems; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans
PubMed: 32816734
DOI: 10.1128/AAC.01025-20 -
Microbiological Research Oct 2022Bacteria belonging to the genus Achromobacter are widely distributed in natural environments and have been recognized as emerging pathogens for their contribution to a... (Review)
Review
Bacteria belonging to the genus Achromobacter are widely distributed in natural environments and have been recognized as emerging pathogens for their contribution to a wide range of human infections. In particular, patients with cystic fibrosis (CF) are the subjects most frequently colonized by Achromobacter spp., which can cause persistent infections in their respiratory tract. Although many clinical aspects and pathogenic mechanisms still remain to be elucidated, Achromobacter spp. have been a source of expanding interest in recent years. This review examines the current literature regarding Achromobacter spp. role in CF, focusing on taxonomy, prevalence in CF lung infections, genomic characteristics, and adaptation strategies including modifications of metabolism and virulence, acquisition of antibiotic resistance, exchange of mobile genetic elements and development of hypermutation.
Topics: Achromobacter; Achromobacter denitrificans; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Lung; Prevalence
PubMed: 35931003
DOI: 10.1016/j.micres.2022.127140 -
Journal of Clinical Microbiology Mar 2021species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more-severe...
species are increasingly being detected in patients with cystic fibrosis (CF), and this emerging pathogen is associated with antibiotic resistance and more-severe disease outcomes. Nonetheless, little is known about the extent of transmission and antibiotic resistance development in infections. We sequenced the genomes of 101 clinical isolates (identified as based on matrix-assister laser desorption ionization-time of flight [MALDI-TOF] or API N20 typing) collected from 51 patients with CF-the largest longitudinal data set to date. We performed phylogenetic analysis on the genomes and combined this with epidemiological and antibiotic resistance data to identify patient-to-patient transmission and the development of antibiotic resistance. We confirmed that the MALDI-TOF or API N20 method was not sufficient for species-level typing and that the population of isolates was composed of five different species, among which accounted for 52% of infections. Most patients were infected by unique clone types; nonetheless, suspected patient-to-patient transmission cases identified by shared clone types were observed in 35% ( = 18) of patients. In 15 of 16 cases, the suspected transmissions were further supported by genome- or clinic visit-based epidemiological analysis. Finally, we found that resistance developed over time. We show that whole-genome sequencing (WGS) is essential for species typing and identification of patient-to-patient transmission, which was revealed for , , and, for the first time, Furthermore, we show that the development of antibiotic resistance is associated with chronic infections. Our findings emphasize that transmission and antibiotic resistance should be considered in future treatment strategies.
Topics: Achromobacter; Cystic Fibrosis; Drug Resistance, Microbial; Gram-Negative Bacterial Infections; Humans; Phylogeny
PubMed: 33472899
DOI: 10.1128/JCM.02911-20 -
and activity of cefiderocol against spp. and complex, including carbapenem-non-susceptible isolates.Antimicrobial Agents and Chemotherapy Dec 2023spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the...
spp. and complex (Bcc) are rare but diverse opportunistic pathogens associated with serious infections, which are often multidrug resistant. This study compared the antibacterial activity of the siderophore antibiotic cefiderocol against spp. and Bcc isolates with that of other approved antibacterial drugs, including ceftazidime-avibactam, ciprofloxacin, colistin, imipenem-relebactam, and meropenem-vaborbactam. Isolates were collected in the SIDERO multinational surveillance program. Among 334 spp. isolates [76.6% from respiratory tract infections (RTIs)], cefiderocol had minimum inhibitory concentration (MIC) of 0.06/0.5 µg/mL overall and 0.5/4 µg/mL against 52 (15.6%) carbapenem-non-susceptible (Carb-NS) isolates. Eleven (3.3%) spp. isolates overall and 6 (11.5%) Carb-NS isolates were not susceptible to cefiderocol. Among 425 Bcc isolates (73.4% from RTIs), cefiderocol had MIC of ≤0.03/0.5 µg/mL overall and ≤0.03/1 µg/mL against 184 (43.3%) Carb-NS isolates. Twenty-two (5.2%) Bcc isolates overall and 13 (7.1%) Carb-NS isolates were not susceptible to cefiderocol. Cumulative MIC distributions showed cefiderocol to be the most active of the agents tested against both spp. and Bcc. In a neutropenic murine lung infection model and a humanized pharmacokinetic immunocompetent rat lung infection model, cefiderocol showed significant bactericidal activity against two meropenem-resistant strains compared with untreated controls ( < 0.05) and vehicle-treated controls ( < 0.05), respectively. Meropenem, piperacillin-tazobactam, ceftazidime, and ciprofloxacin comparators showed no significant activity in these models. The results suggest that cefiderocol could be a possible treatment option for RTIs caused by spp. and Bcc.
Topics: Rats; Animals; Mice; Cefiderocol; Meropenem; Carbapenems; Cephalosporins; Burkholderia cepacia complex; Achromobacter; Drug Resistance, Multiple, Bacterial; Anti-Bacterial Agents; Ceftazidime; Respiratory Tract Infections; Ciprofloxacin; Microbial Sensitivity Tests
PubMed: 37971240
DOI: 10.1128/aac.00346-23 -
Microbial Genomics Jul 2021spp. are emerging pathogens in patients with cystic fibrosis (CF) and spp. caused infections are associated with more severe disease outcomes and high intrinsic...
spp. are emerging pathogens in patients with cystic fibrosis (CF) and spp. caused infections are associated with more severe disease outcomes and high intrinsic antibiotic resistance. While conventional CF pathogens are studied extensively, little is known about the genetic determinants leading to antibiotic resistance and the genetic adaptation in spp. infections. Here, we analysed 101 spp. genomes from 51 patients with CF isolated during the course of up to 20 years of infection to identify within-host adaptation, mutational signatures and genetic variation associated with increased antibiotic resistance. We found that the same regulatory and inorganic ion transport genes were frequently mutated in persisting clone types within and between species, indicating convergent genetic adaptation. Genome-wide association study of six antibiotic resistance phenotypes revealed the enrichment of associated genes involved in inorganic ion transport, transcription gene enrichment in β-lactams, and energy production and translation gene enrichment in the trimethoprim/sulfonamide group. Overall, we provide insights into the pathogenomics of spp. infections in patients with CF airways. Since emerging pathogens are increasingly recognized as an important healthcare issue, our findings on evolution of antibiotic resistance and genetic adaptation can facilitate better understanding of disease progression and how mutational changes have implications for patients with CF.
Topics: Achromobacter; Adaptation, Physiological; Cystic Fibrosis; Denmark; Disease Progression; Drug Resistance, Multiple, Bacterial; Energy Metabolism; Genome, Bacterial; Genome-Wide Association Study; Gram-Negative Bacterial Infections; Host-Pathogen Interactions; Humans; Respiratory Tract Infections
PubMed: 34232117
DOI: 10.1099/mgen.0.000582 -
Frontiers in Bioscience (Landmark... Dec 2021In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the... (Review)
Review
In recent years, advances in diagnosis and treatment have significantly modified the short- and long-term prognosis of cystic fibrosis (CF) patients. However, as in the past, the most important health problem that has significantly reduced the quality of life in CF patients is the progressive deterioration of lung structure and function. In recent years, Achromobacter species have emerged with increasing incidence in the respiratory secretions of CF subjects. The significance of this detection remains debated. In this review article, the characteristics of these pathogens, the importance of their presence in CF patients, and possible antibiotic treatment of treatments for colonization and infection are discussed. Literature analysis shows that Achromobacter species, mainly A. xylosoxidans, are pathogens with intrinsic characteristics that favour persistent lung colonization and several virulence factors and secretion systems that significantly interfere with respiratory cell survival. However, although it seems undebatable that Achromobacterspecies detection is a marker of CF severity, the role of these pathogens as a cause of lung structure and functional deterioration is not definitively established. Nonetheless, there is general agreement about the need for antibiotic therapy to eradicate these pathogens when they are detected in CF patients. Unfortunately, eradication is difficult, and no standard treatment is recommended by scientific societies. New possibilities are potentially offered by some recently developed drugs, such as cefiderocol, but further studies on the dosage, treatment duration and efficacy and safety of this new antibiotic in CF patients of different ages are urgently needed.
Topics: Achromobacter; Anti-Bacterial Agents; Cystic Fibrosis; Gram-Negative Bacterial Infections; Humans; Lung; Quality of Life
PubMed: 34994175
DOI: 10.52586/5054 -
Viruses Jul 2023species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced...
species colonization of Cystic Fibrosis respiratory airways is an increasing concern. Two adult patients with Cystic Fibrosis colonized by CF418 or CF116 experienced fatal exacerbations. spp. are naturally resistant to several antibiotics. Therefore, phages could be valuable as therapeutics for the control of . In this study, thirteen lytic phages were isolated and characterized at the morphological and genomic levels for potential future use in phage therapy. They are presented here as the Kumeyaay phage collection. Six distinct phage genome clusters were identified based on a comprehensive phylogenetic analysis of the Kumeyaay collection as well as the publicly available phages. The infectivity of all phages in the Kumeyaay collection was tested in 23 clinical isolates; 78% of these isolates were lysed by at least one phage. A cryptic prophage was induced in CF418 when infected with some of the lytic phages. This prophage genome was characterized and is presented as phage CF418-P1. Prophage induction during lytic phage preparation for therapy interventions require further exploration. Large-scale production of phages and removal of endotoxins using an octanol-based procedure resulted in a phage concentrate of 1 × 10 plaque-forming units per milliliter with an endotoxin concentration of 65 endotoxin units per milliliter, which is below the Food and Drugs Administration recommended maximum threshold for human administration. This study provides a comprehensive framework for the isolation, bioinformatic characterization, and safe production of phages to kill spp. in order to potentially manage Cystic Fibrosis (CF) pulmonary infections.
Topics: Adult; Humans; Bacteriophages; Cystic Fibrosis; Phylogeny; Achromobacter; Achromobacter denitrificans; Prophages; Endotoxins
PubMed: 37632008
DOI: 10.3390/v15081665 -
Applied and Environmental Microbiology Nov 2021In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in sp. strain As-55. Genomic analyses of sp. As-55 showed...
In this study, comprehensive analyses were performed to determine the function of an atypical MarR homolog in sp. strain As-55. Genomic analyses of sp. As-55 showed that this is located adjacent to an gene. ArsV is a flavin-dependent monooxygenase that confers resistance to the antibiotic methylarsenite [MAs(III)], the organoarsenic compound roxarsone(III) [Rox(III)], and the inorganic antimonite [Sb(III)]. Similar genes are widely distributed in arsenic-resistant bacteria. Phylogenetic analyses showed that these MarRs are found in operons predicted to be involved in resistance to inorganic and organic arsenic species, so the subfamily was named MarR. MarR orthologs have three conserved cysteine residues, which are Cys36, Cys37, and Cys157 in sp. As-55, mutation of which compromises the response to MAs(III)/Sb(III). GFP-fluorescent biosensor assays show that AdMarR (MarR protein of Achromobacter deleyi As-55) responds to trivalent As(III) and Sb(III) but not to pentavalent As(V) or Sb(V). The results of RT-qPCR assays show that is expressed constitutively in a deletion mutant, indicating that represses transcription of . Moreover, electrophoretic mobility shift assays (EMSAs) demonstrate that AdMarR binds to the promoters of both and in the absence of ligands and that DNA binding is relieved upon binding of As(III) and Sb(III). Our results demonstrate that AdMarR is a novel As(III)/Sb(III)-responsive transcriptional repressor that controls expression of which confers resistance to MAs(III), Rox(III), and Sb(III). AdMarR and its orthologs form a subfamily of MarR proteins that regulate genes conferring resistance to arsenic-containing antibiotics. In this study, a MarR family member, AdMarR was shown to regulate the gene, which confers resistance to arsenic-containing antibiotics. It is a founding member of a distinct subfamily that we refer to as MarR, regulating genes conferring resistance to arsenic and antimony antibiotic compounds. AdMarR was shown to be a repressor containing conserved cysteine residues that are required to bind As(III) and Sb(III), leading to a conformational change and subsequent derepression. Here we show that members of the MarR family are involved in regulating arsenic-containing compounds.
Topics: Achromobacter; Anti-Bacterial Agents; Arsenic; Arsenicals; Cysteine; Drug Resistance, Bacterial; Genes, Bacterial; Multigene Family; Phylogeny; Roxarsone
PubMed: 34613763
DOI: 10.1128/AEM.01588-21 -
Frontiers in Microbiology 2022genus (including , the most prevalent species in patients with cystic fibrosis) is poorly susceptible to most conventional antibiotics. Contribution of efflux by...
genus (including , the most prevalent species in patients with cystic fibrosis) is poorly susceptible to most conventional antibiotics. Contribution of efflux by AxyABM, AxyXY-OprZ, and AxyEF-OprN and of target mutations were studied in clinical isolates of and Forty-one isolates longitudinally collected from 21 patients with CF were studied by whole-genome sequencing (WGS)-typing, determination of minimum inhibitory concentrations (MICs) of β-lactams, aminoglycosides, colistin, azithromycin, ciprofloxacin, chloramphenicol, and doxycycline, and expression (quantitative RT-PCR) and function (measure of the uptake of a fluorescent substrate) of efflux pumps. WGS-based typing resulted in 10 clusters comprising 2 or 3 isolates and 20 singletons. The efflux activity was high in strains with elevated MICs for amikacin or azithromycin. This work sheds a new light on the impact of efflux and target mutations in resistance of to several drugs.
PubMed: 35418957
DOI: 10.3389/fmicb.2022.762307 -
Pathogens (Basel, Switzerland) Jan 2022is an opportunistic pathogen that mainly causes chronic lung infections in cystic fibrosis (CF) patients and is associated with increased mortality. Little is known...
is an opportunistic pathogen that mainly causes chronic lung infections in cystic fibrosis (CF) patients and is associated with increased mortality. Little is known about spp. in the lung transplant recipient (LTXr) population. We aimed at describing rates of spp. infection in LTXr prior to, in relation to, and after transplantation, as well as all-cause mortality proportion in infected and uninfected LTXr. We included 288 adult LTXr who underwent lung transplantation (LTX) between 1 January 2010 and 31 December 2019 in Denmark. Bronchoalveolar lavage was performed at regular intervals starting two weeks after transplantation. Positive cultures of spp. were identified in nationwide microbiology registries, and infections were categorized as persistent or transient, according to the proportion of positive cultures. A total of 11 of the 288 LTXr had transient ( = 7) or persistent ( = 4) spp. infection after LTX; CF was the underlying disease in 9 out of 11 LTXr. Three out of the four patients, with persistent infection after LTX, also had persistent infection before LTX. The cumulative incidence of the first episode of infection one year after LTX was 3.8% (95% CI: 1.6-6.0). The incidence rates of transient and persistent infection in the first year after LTX were 27 (12-53) and 15 (5-37) per 1000 person-years of follow-up, respectively. The all-cause mortality proportion one year after LTX was 27% in the spp. infected patients and 12% in the uninfected patients ( = 0.114). spp. mainly affected LTXr with CF as the underlying disease and was rare in non-CF LTXr. Larger studies are needed to assess long-term outcomes of spp. in LTXr.
PubMed: 35215124
DOI: 10.3390/pathogens11020181