PmrB mutations including a novel 10-amino acid repeat sequence insertion associated with low-level colistin resistance in carbapenem-resistant Acinetobacter baumannii

2020 ◽  
Vol 85 ◽  
pp. 104577
Author(s):  
Kamonwan Lunha ◽  
Khin Thet Thet ◽  
Arisa Ngudsuntia ◽  
Nicha Charoensri ◽  
Aroonlug Lulitanond ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acinetobacter Baumannii ◽  
Repeat Sequence ◽  
Colistin Resistance ◽  
Amino Acid Repeat ◽  
Low Level ◽  
Carbapenem Resistant

scholarly journals Tigecycline susceptibility of multidrug-resistant Acinetobacter baumannii from intensive care units in the western Balkans

2020 ◽  
Vol 67 (3) ◽  
pp. 176-181
Author(s):  
Ina Gajic ◽  
Lazar Ranin ◽  
Dusan Kekic ◽  
Natasa Opavski ◽  
Aleksandra Smitran ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Inappropriate Therapy ◽  
Antibiotic Susceptibility Testing ◽  
Broth Microdilution ◽  
Western Balkans ◽  
Colistin Resistance ◽  
European Committee ◽  
Carbapenem Resistant

AbstractTigecycline can be effective to treat infections of carbapenem-resistant Acinetobacter baumannii (CRAB) however, no interpretive criteria have been approved so far. The objectives of this study were to evaluate the proportion of CRAB isolates and to compare gradient test with a broth microdilution (BMD) method for tigecycline susceptibility testing of A. baumannii.This study included 349 multidrug-resistant (MDR) Acinetobacter spp. collected from Serbia, Montenegro, Bosnia and Herzegovina in 2016 and 2017. Antibiotic susceptibility testing was performed by disk diffusion, VITEK2, gradient, ComASP Colistin. Tigecycline susceptibilities were interpreted according to breakpoints of European Committee on Antimicrobial Susceptibility Testing (EUCAST) and Food and Drug Administration (FDA).Majority of the tested isolates were CRAB (92.8%). Tigecycline MIC50/MIC90 values were 4/8 μg/mL by BMD and 0.5/4 μg/mL by gradient test. Essential agreement for BMD and gradient test amounted to 65.1%. With EUCAST breakpoints, categorical agreement (CA) was achieved in 38% isolates. Major discordance (MD-false susceptibility/resistance) and minor discordance (mD-false categorization involving intermediate results) were observed in 10% and 57% A. baumannii, respectively. With FDA breakpoints, CA, MD and mD were observed in 44%, 16% and 47% isolates, respectively. Colistin resistance was 2.1%.The study highlights a high proportion of CRAB and several discordances between BMD and gradient test which may lead to inappropriate therapy.

scholarly journals Amino Acid Substitutions of CrrB Responsible for Resistance to Colistin through CrrC in Klebsiella pneumoniae

2016 ◽  
Vol 60 (6) ◽  
pp. 3709-3716 ◽  
Author(s):  
Yi-Hsiang Cheng ◽  
Tzu-Lung Lin ◽  
Yi-Tsung Lin ◽  
Jin-Town Wang
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Site Directed Mutagenesis ◽  
Amino Acid Substitutions ◽  
Missense Mutations ◽  
Colistin Resistance ◽  
Two Component System ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Elevated Expression

Colistin is a last-resort antibiotic for treatment of carbapenem-resistantKlebsiella pneumoniae. A recent study indicated that missense mutations in the CrrB protein contribute to colistin resistance. In our previous study, mechanisms of colistin resistance were defined in 17 of 26 colistin-resistantK. pneumoniaeclinical isolates. Of the remaining nine strains, eight were highly resistant to colistin. In the present study,crrABsequences were determined for these eight strains. Six separate amino acid substitutions in CrrB (Q10L, Y31H, W140R, N141I, P151S, and S195N) were detected. Site-directed mutagenesis was used to generatecrrBloci harboring individual missense mutations; introduction of the mutated genes into a susceptible strain, A4528, resulted in 64- to 1,024-fold increases in colistin MICs. ThesecrrBmutants showed increased accumulation ofH239_3062,H239_3059,pmrA,pmrC, andpmrHtranscripts by quantitative reverse transcription (qRT)-PCR. Deletion ofH239_3062(but not that ofH239_3059) in the A4528crrB(N141I) strain attenuated resistance to colistin, andH239_3062was accordingly namedcrrC. Similarly, accumulation ofpmrA,pmrC, andpmrHtranscripts induced bycrrB(N141I) was significantly attenuated upon deletion ofcrrC. Complementation ofcrrCrestored resistance to colistin and accumulation ofpmrA,pmrC, andpmrHtranscripts in acrrB(N141I) ΔcrrCstrain. In conclusion, novel individual CrrB amino acid substitutions (Y31H, W140R, N141I, P151S, and S195N) were shown to be responsible for colistin resistance. We hypothesize that CrrB mutations induce CrrC expression, thereby inducing elevated expression of thepmrHFIJKLMoperon andpmrC(an effect mediated via the PmrAB two-component system) and yielding increased colistin resistance.

scholarly journals Carbapenem-Resistant Acinetobacter baumannii Isolates from Tunisia Producing the OXA-58-Like Carbapenem-Hydrolyzing Oxacillinase OXA-97

2008 ◽  
Vol 52 (5) ◽  
pp. 1613-1617 ◽  
Author(s):  
Laurent Poirel ◽  
Wejdene Mansour ◽  
Olfa Bouallegue ◽  
Patrice Nordmann
Keyword(s):  
Amino Acid ◽  
Acinetobacter Baumannii ◽  
Amino Acid Substitution ◽  
Multidrug Resistant ◽  
Single Amino Acid Substitution ◽  
Single Amino Acid ◽  
The Novel ◽  
Cloning And Sequencing ◽  
Carbapenem Resistant ◽  
Genetic Structures

ABSTRACT The basis of the β-lactam resistance of 39 multidrug-resistant Acinetobacter baumannii isolates recovered from hospitalized patients was studied. These isolates were collected from 2001 to 2005 at the Sahloul Hospital in Sousse, Tunisia. They belonged to two distinct clones. One clone that grouped 19 isolates produced a carbapenem-hydrolyzing oxacillinase, OXA-97, that differed from OXA-58 by a single amino acid substitution and conferred the same β-lactam resistance profile as OXA-58. The bla OXA-97 gene was located on plasmids that varied in size in 18 isolates and was chromosomally located in a single isolate. Cloning and sequencing identified genetic structures surrounding the bla OXA-97 gene similar to those reported to be adjacent to the bla OXA-58 gene. In addition, the novel ISAba8 element (which is of the IS21 family) was identified. This is the first report of the nosocomial spread of carbapenemase producers in A. baumannii isolates in Africa.

Treatment Outcomes of Colistin- and Carbapenem-resistant Acinetobacter baumannii Infections: An Exploratory Subgroup Analysis of a Randomized Clinical Trial

2018 ◽  
Vol 69 (5) ◽  
pp. 769-776 ◽  
Author(s):  
Yaakov Dickstein ◽  
Jonathan Lellouche ◽  
Maayan Ben Dalak Amar ◽  
David Schwartz ◽  
Amir Nutman ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Acinetobacter Baumannii ◽  
Bacterial Infections ◽  
Primary Outcome ◽  
Controlled Trial ◽  
Secondary Analysis ◽  
Mortality Rates ◽  
Colistin Resistance ◽  
Randomized Controlled ◽  
Carbapenem Resistant

Abstract Background We evaluated the association between mortality and colistin resistance in Acinetobacter baumannii infections and the interaction with antibiotic therapy. Methods This is a secondary analysis of a randomized controlled trial of patients with carbapenem-resistant gram-negative bacterial infections treated with colistin or colistin-meropenem combination. We evaluated patients with infection caused by carbapenem-resistant A. baumannii (CRAB) identified as colistin susceptible (CoS) at the time of treatment and compared patients in which the isolate was confirmed as CoS with those whose isolates were retrospectively identified as colistin resistant (CoR) when tested by broth microdilution (BMD). The primary outcome was 28-day mortality. Results Data were available for 266 patients (214 CoS and 52 CoR isolates). Patients with CoR isolates had higher baseline functional capacity and lower rates of mechanical ventilation than patients with CoS isolates. All-cause 28-day mortality was 42.3% (22/52) among patients with CoR strains and 52.8% (113/214) among patients with CoS isolates (P = .174). After adjusting for variables associated with mortality, the mortality rate was lower among patients with CoR isolates (odds ratio [OR], 0.285 [95% confidence interval {CI}, .118–.686]). This difference was associated with treatment arm: Mortality rates among patients with CoR isolates were higher in those randomized to colistin-meropenem combination therapy compared to colistin monotherapy (OR, 3.065 [95% CI, 1.021–9.202]). Conclusions Colistin resistance determined by BMD was associated with lower mortality among patients with severe CRAB infections. Among patients with CoR isolates, colistin monotherapy was associated with a better outcome compared to colistin-meropenem combination therapy. Clinical Trials Registration NCT01732250

scholarly journals eliability of phenotypic methods for detection of colistin resistance among carbapenem-resistant Acinetobacter baumannii clinical isolates from Egypt

GERMS ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 303-309
Author(s):  
Nevine S Fam ◽  
Sara H Mohamed ◽  
Doaa Gamal ◽  
Reham M Wasfy ◽  
May S Soliman ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
Clinical Isolates ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Phenotypic Methods

scholarly journals Colistin Resistance Mechanisms in Klebsiella pneumoniae Strains from Taiwan

2015 ◽  
Vol 59 (5) ◽  
pp. 2909-2913 ◽  
Author(s):  
Yi-Hsiang Cheng ◽  
Tzu-Lung Lin ◽  
Yi-Jiun Pan ◽  
Yu-Ping Wang ◽  
Yi-Tsung Lin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Klebsiella Pneumoniae ◽  
Resistance Mechanisms ◽  
Single Amino Acid ◽  
Colistin Resistance ◽  
Amino Acid Mutation ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Resistant Strains ◽  
Sequence Types

ABSTRACTColistin is one of the antibiotics of last resort for the treatment of carbapenem-resistantKlebsiella pneumoniaeinfection. This study showed that capsular type K64 (50%) and ST11 (53.9%) are the prevalent capsular and sequence types in the colistin-resistant strains in Taiwan. The interruption of transcripts (38.5%) and amino acid mutation (15.4%) inmgrBare the major mechanisms contributing to colistin resistance. In addition, novel single amino acid changes in MgrB (Stop48Tyr) and PhoQ (Leu26Pro) were observed to contribute to colistin resistance.

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