Dissemination of a clone of unusual phenotype of pandrug-resistant Acinetobacter baumannii at a university hospital in Taiwan.
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ABSTRACT:
SUBMITTER: Kuo LC
PROVIDER: S-EPMC387598 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:New Delhi metallo-β-lactamase (NDM-1) was initially identified in various Enterobacteriaceae and recently in Acinetobacter baumannii. This study described the clonal dissemination of an NDM-2-producing A. baumannii isolate in an Israeli rehabilitation ward and the genetic surroundings of the gene. The bla(NDM-2) gene was surrounded by the ble and trpF genes downstream and two copies of the ISAba125 on both sides. These are the first NDM-producing A. baumannii strains in Israel from patients with no previous travel or hospitalization on the Indian subcontinent.
| S-EPMC3195055 | biostudies-literature
Project description:Acinetobacter baumannii strains belonging to global clone 2 (GC2) contain resistance islands (AbGRIs), which are composed of genes conferring resistance to older and newer antibiotics. Here, to locate these genes in AbGRIs, the GC2 strains from Tehran, Iran were examined. Among the 170 A. baumannii, 90 isolates were identified as GC2. Of the genes that confer resistance to older antibiotics, tetA(B), tetR(B) (tetracyclines), strA, and strB (aminoglycosides) were located in AbGRI1 of 65 GC2 isolates (72.2%). Of the other aminoglycosides, the aphA1b was located in AbGRI2-12b (63.6%), AbGRI2-12a (21.2%), or AbGRI2-1 (15.1%). The aacC1 and aadA1 genes were co-located within AbGRI2-1 (5.5%). The armA was located in AbGRI3-4 (77.7%) and AbGRI3ABI221 (22.2%). Of sulfonamides, the sul1 was located within AbGRI2-1 (5.5%). Of beta-lactams, the blaTEM was located in AbGRI2-12b (42%), AbGRI2-12a (14%), AbGRI2-1 (10%), or AbGRI2ABI257 (34%). The oxa23 gene conferring resistance to newer antibiotics (carbapenems) was located in AbaR4 (81.1%); of them, the AbaR4 was located within AbGRI1 in 45.2% of the isolates. This study showed that the GC2 isolates, which contained at least one AbGRI, disseminate in the hospital. Hence, it is likely that the AbGRIs play a significant role in conferring resistance to older and newer antibiotics in GC2 isolates from Iran. IMPORTANCE The majority of Acinetobacter baumannii isolates that are resistant to multiple antibiotics belong to one of the two major global clones, namely global clone 1 (GC1) and global clone 2 (GC2). The resistance islands, which contain variable assortments of transposons, integrons, and specific resistance genes, have been characterized in the genome of these GCs. In GC2 A. baumannii, the chromosomally located A. baumannii genomic resistance islands (AbGRIs) carry the genes conferring resistance to older and newer antibiotics. In this context, we tested whether GC2 isolates collected from a referral hospital carry the AbGRIs containing these genes. This study provided evidence for the circulation of the GC2 A. baumannii strains harboring AbGRI resistance islands between different wards of a referral hospital.
| S-EPMC10581056 | biostudies-literature
Project description:The emergence of pandrug-resistant bacteria breaks through the last line of defense and raises fear among people of incurable infections. In the post-antibiotic era, the pharmaceutical field turns to seek non-conventional anti-infective agents. Antimicrobial peptides are considered a prospective solution to the crisis of antimicrobial resistance. In this study, we evaluated the antimicrobial efficiency of an ApoE mimetic peptide, COG1410, which has been confirmed to exhibit strong neural protective activity and immunomodulatory function. COG1410 showed potent antimicrobial activity against pandrug-resistant Acinetobacter baumannii, even eliminating large inocula (108 CFU/ml) within 30 min. LC99.9 in PBS and 50% pooled human plasma was 2 μg/ml (1.4 μM) and 8 μg/ml (5.6 μM), respectively. Moreover, COG1410 exhibited biofilm inhibition and eradication activity, excellent stability in human plasma, and a low propensity to induce resistance. Although COG1410 easily entered bacterial cytoplasm and bound to DNA nonspecifically, the major mechanism of COG1410 killing was to disrupt the integrity of cell membrane and lead to leakage of cytoplasmic contents, without causing obvious pores on the cell surface or cell lysis. Additionally, transcriptome analysis showed that treatment with COG1410-enriched genes involved a series of oxidation–reduction processes. DCFH-DA probe detected an increased ROS level in the presence of COG1410, indicating ROS was another hit of this AMP. Furthermore, the action of COG1410 did not depend on the electronic interaction with the LPS layer, in contrast to polymyxin B. The strong synergistic interaction between COG1410 and polymyxin B dramatically reduced the working concentration of COG1410, expanding the safety window of the application. C. elegans infection model showed that combined therapy of COG1410 and polymyxin B was capable of significantly rescuing the infected nematodes. Taken together, our study demonstrates that COG1410 is a promising drug candidate in the battle against pandrug-resistant A. baumannii.
| S-EPMC9445589 | biostudies-literature
Project description: Not available
| S-EPMC3647512 | biostudies-literature
Project description:BACKGROUND: The systemic surveillance of imipenem-resistant Acinetobacter baumannii (IRAB) from multicenters in Taiwan revealed the emergence of isolates with bla(OXA-72). This study described their genetic makeup, mechanism of spread, and contribution to carbapenem resistance. METHODS: Two hundred and ninety-one non-repetitive isolates of A. baumannii were collected from 10 teaching hospitals from different geographical regions in Taiwan from June 2007 to September 2007. Minimal inhibitory concentrations (MICs) were determined by agar dilution. Clonality was determined by pulsed-field gel electrophoresis. Plasmid was extracted and digested by restriction enzymes, and subsequently analyzed by electrophoresis and Southern blot for bla(OXA-72). The flanking regions of bla(OXA-72) were determined by inverse PCR. The contribution of bla(OXA-72) to imipenem MIC was determined by transforming plasmids carrying bla(OXA-72) into imipenem-susceptible A. baumannii. RESULTS: Among 142 IRAB in Taiwan, 27 harbored bla(OXA-72); 22 originated from Southern Taiwan, 5 from Central Taiwan, and none from Northern Taiwan. There were two major clones. The bla(OXA-72) was identified in the plasmids of all isolates. Two genetic structures flanking plasmid-borne bla(OXA-72) were identified and shared identical sequences in certain regions; the one described in previous literature was present in only one isolate, and the new one was present in the remaining isolates. Introduction of bla(OXA-72) resulted in an increase of imipenem MIC in the transformants. The overexpression of bla(OXA-72) mRNA in response to imipenem further supported the contribution of bla(OXA-72). CONCLUSIONS: In conclusion, isolates with new plasmid-borne blaOXA-72 were found to be disseminated successfully in Southern Taiwan. The spread of the resistance gene depended on clonal spread and dissemination of a new plasmid. Bla(OXA-72) in these isolates directly led to their imipenem-resistance.
| S-EPMC3728158 | biostudies-literature
Project description:Antimicrobial combinations are at the moment the only potential treatment option for pandrug-resistant A. baumannii. A systematic review was conducted in PubMed and Scopus for studies reporting the activity of antimicrobial combinations against A. baumannii resistant to all components of the combination. The clinical relevance of synergistic combinations was assessed based on concentrations achieving synergy and PK/PD models. Eighty-four studies were retrieved including 818 eligible isolates. A variety of combinations (n = 141 double, n = 9 triple) were tested, with a variety of methods. Polymyxin-based combinations were the most studied, either as double or triple combinations with cell-wall acting agents (including sulbactam, carbapenems, glycopeptides), rifamycins and fosfomycin. Non-polymyxin combinations were predominantly based on rifampicin, fosfomycin, sulbactam and avibactam. Several combinations were synergistic at clinically relevant concentrations, while triple combinations appeared more active than the double ones. However, no combination was consistently synergistic against all strains tested. Notably, several studies reported synergy but at concentrations unlikely to be clinically relevant, or the concentration that synergy was observed was unclear. Selecting the most appropriate combinations is likely strain-specific and should be guided by in vitro synergy evaluation. Furthermore, there is an urgent need for clinical studies on the efficacy and safety of such combinations.
| S-EPMC8615225 | biostudies-literature
Project description:The aim of this study was to find the source of Acinetobacter baumannii in the intensive care unit (ICU) after an outbreak during the coronavirus disease 2019 (COVID-19) pandemic, as there was no A. baumannii detected on usually screened susceptible surfaces. The screening of the ICU environment was done in April 2021 when eleven different samples were taken. One A. baumannii isolate was recovered from the air conditioner and was compared with four clinical A. baumannii isolates obtained from patients hospitalized in January 2021. Isolates were confirmed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), minimum inhibitory concentrations (MICs) were determined, and the multilocus sequence typing (MLST) was performed. The molecular identification of A. baumannii isolates as ST208, the presence of the same blaOXA-23 carbapenemase gene, and the same antibiotic susceptibility profile suggest that the isolate recovered from the air conditioner is the same as the isolates recovered from hospitalized patients. The environmental isolate was recovered three months later than the clinical isolates, emphasizing the ability of A. baumannii to survive on dry abiotic surfaces. The air conditioner in the clinical environment is an important but undoubtedly neglected source of A. baumannii outbreaks, hence, frequent disinfection of hospital air conditioners with appropriate disinfectants is mandatory to mitigate the circulation of A. baumannii between patients and the hospital environment.
| S-EPMC10057452 | biostudies-literature
Project description:Acinetobacter baumannii is an opportunistic pathogen primarily associated with multidrug-resistant nosocomial infections, for which polymyxins are the last-resort antibiotics. This study investigated carbapenem-resistant A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, including four isolates considered locally pan drug-resistant (LPDR), isolated from inpatients during an outbreak at a teaching hospital in Brazil. ApaI DNA macrorestriction followed by PFGE clustered the strains in three pulsotypes, named A to C, among carbapenem-resistant A. baumannii strains. Pulsotypes A and B clustered six polymyxin-resistant A. baumannii strains. MLST analysis of representative strains of pulsotypes A, B, and C showed that they belong, respectively, to sequence types ST1 (clonal complex, CC1), ST79 (CC79), and ST903. Genomic analysis of international clones ST1 and ST79 representative strains predicted a wide resistome for β-lactams, aminoglycosides, fluoroquinolones, and trimethoprim-sulfamethoxazole, with bla OXA-23 and bla OXA-72 genes encoding carbapenem resistance. Amino acid substitutions in PmrB (Thr232Ile or Pro170Leu) and PmrC (Arg125His) were responsible for polymyxin resistance. Although colistin MICs were all high (MIC ≥ 128 mg/L), polymyxin B MICs varied; strains with Pro170Leu substitution in PmrB had MICs > 128 mg/L, while those with Thr232Ile had lower MICs (16-64 mg/L), irrespective of the clone. Although the first identified polymyxin-resistant A. baumannii strain belonged to ST79, the ST1 strains were endemic and caused the outbreak most likely due to polymyxin B use. The genome comparison of two ST1 strains from the same patient, but one susceptible and the other resistant to polymyxin, revealed mutations in 28 ORFs in addition to pmrBC. The ORF codifying an acyl-CoA dehydrogenase has gained attention due to its fatty acid breakdown and membrane fluidity involvement. However, the role of these mutations in the polymyxin resistance mechanism remains unknown. To prevent the dissemination of XDR bacteria, the hospital infection control committee implemented the patient bathing practice with a 2% chlorhexidine solution, a higher concentration than all A. baumannii chlorhexidine MICs. In conclusion, we showed the emergence of polymyxin resistance due to mutations in the chromosome of the carbapenem-resistant A. baumannii ST1, a high-risk global clone spreading in this hospital.
| S-EPMC8063854 | biostudies-literature
Project description:The dominant carbapenem resistant Acinetobacter baumannii harboring blaOXA-23-like carbapenemase was replaced by blaOXA-40-like carriers in a Hungarian tertiary-care center with high meropenem but relatively low imipenem use. We hypothesized that alterations in antibiotic consumption may have contributed to this switch. Our workgroup previous study examined the relation between resistance spiral and the antibiotic consumption, and the results suggest that the antibiotic usage provoked the increasing resistance in case of A. baumannii. We aimed at measuring the activity of imipenem and meropenem to compare the selection pressure exerted by the different carbapenems in time-kill assays. Strain replacement was confirmed by whole genome sequencing, core-genome multilocus sequence typing (cgMLST), and resistome analysis. Based on results of the time-kill assays, we found a significant difference between two different sequence-types (STs) in case of meropenem, but not in case of imipenem susceptibility. The newly emerged ST636 and ST492 had increased resistance level against meropenem compared to the previously dominant ST2 and ST49. On the other hand, the imipenem and colistin resistance profiles were similar. These results suggest, that the uniform meropenem usage may have contributed to A. baumannii strain replacement in our setting.
| S-EPMC7911629 | biostudies-literature
Project description:BACKGROUND:Carbapenem resistance in Acinetobacter baumannii in China was mainly mediated by OXA-23-like carbapenemases, while OXA-24/40-like carbapenemases were rarely identified. OXA-72 is one variant of OXA-24/40-like carbapenemases. This study aimed to demonstrate the epidemiology and characterizations of OXA-72-producing A. baumannii in a Chinese hospital. METHODS:A total of 107 clinical A. calcoaceticus-A. baumannii (Acb) complex isolates were collected in a Chinese hospital during between 2014 and 2016. These isolates were identified using Vitek 2 system and gyrB multiplex PCR. Vitek 2 system was used for antibiotic susceptibility testing. Genes encoding for major classes of carbapenemases were investigated by PCR. Rep-PCR was used for genotyping of all the A. baumannii isolates. The risk factors for carriage of OXA-72-producing or OXA-23-producing A. baumannii were analyzed through univariate and multivariate logistic regression. RESULTS:Of the 107 Acb isolates collected, 101 isolates (94.4%) and 6 isolates (5.6%) were identified as A. baumannii and A. pittii, respectively. 78 A. baumannii isolates (77.2%) were carbapenem resistant and mainly cultured from intensive care unit (ICU). blaOXA-72 and blaOXA-23 genes were identified in 45(57.7%) and 33(42.3%) carbapenem-resistant A. baumannii (CRAB), respectively. Multivariate risk factor analyses showed that prior carbapenem usage and nasogastric intubation were significantly associated with carriage of OXA-72-producing A. baumannii or OXA-23-producing A. baumannii. Rep-PCR analysis showed that 9 and 22 Rep-PCR types were assigned to 78 CRAB isolates and 23 carbapenem-susceptible A. baumannii (CSAB) isolates, respectively. A higher diverstiy of Rep-PCR patterns was observed among OXA-72-producing A. baumannii isolates than OXA-23-producing A. baumannii isolates, but all of them belonged to the same clone complex. MLST analysis suggested that the OXA-72 isolates from this study correspond to CC92/CC2 clone complex. CONCLUSIONS:This study demonstrates high prevalence and potential clonal spread of closely related genotypes of OXA-72-producing A. baumannii within a Chinese hospital. Continuous surveillance is necessary to monitor the dissemination of these strains in other healthcare settings to guide infection control policies in order to curb the spread of this bacterium.
| S-EPMC6162926 | biostudies-literature