1. |
- Frenk, Sammy, et al.
(författare)
-
Large-scale WGS of carbapenem-resistant Acinetobacter baumannii isolates reveals patterns of dissemination of ST clades associated with antibiotic resistance
- 2022
-
Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 77:4, s. 934-943
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe the population genetics and antibiotic resistance gene distribution of carbapenem-resistant Acinetobacter baumannii (CRAB) isolates causing infections in three Mediterranean countries.Methods: Isolates were collected during the 2013-17 AIDA clinical trial in six hospitals in Israel, Greece and Italy. WGS, bioinformatic characterization and antibiotic resistance profiling were performed.Results In the 247 CRAB isolates characterized in this study, ST distribution varied by country: 29/31 (93.5%) Greek isolates, 34/41 (82.9%) Italian isolates and 70/175 (40.0%) Israeli isolates belonged to ST2. The identified ST2 isolates included eight distinct clades: 2C, 2D and 2H were significantly more common in Italy, while 2F was unique to Greece. The uncommon ST3 was not present among Greek isolates and constituted only 5/41 (12%) Italian isolates. On the other hand, it was much more common among Israeli isolates: 78/175 (44.6%) belonged to ST3. The vast majority of isolates, 240/247 (97.2%), were found to harbour acquired carbapenemases, primarily bla(OXA-23.) The chromosomal oxaAb (bla(OXA-51-like)) and ampC genes characteristic of this organism were also ubiquitous. Most (96.4%) ST3 isolates carried a broad-host-range plasmid IncP1 alpha.Conclusions The geographical differences in CRAB populations support the theory that clonal spread of CRAB leads to endemicity in hospitals and regions. The close association between antibiotic resistance genes and clades, and between plasmids and STs, suggest that de novo creation of MDR A. baumannii is rare. The clustering of antibiotic resistance genes and plasmids that is unique to each clade/ST, and nearly uniform within clades/STs, suggests that horizontal transmission is rare but crucial to the clade's/ST's success.
|
|
2. |
- Kon, Hadas, et al.
(författare)
-
Prevalence and Clinical Consequences of Colistin Heteroresistance and Evolution into Full Resistance in Carbapenem-Resistant Acinetobacter baumannii
- 2023
-
Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- Colistin heteroresistance (HR) refers to a bacterial population comprised of several subpopulations with different levels of resistance to colistin. In this study, we discuss the classic form of HR, in which a resistant subpopulation exists within a predominantly susceptible population. We investigated the prevalence of colistin HR and its evolution into full resistance among 173 clinical carbapenem-resistant Acinetobacter baumannii isolates and examined the effect of HR on clinical outcomes. To determine HR, we performed population analysis profiling. Our results showed a high prevalence of HR (67.1%). To examine evolution of HR strains into full resistance, the HR strains were grown in colistin-containing broth, transferred onto colistin-containing plates, and colonies on these plates were transferred into colistin-free broth. Many of the HR strains (80.2%) evolved into full resistance, 17.2% reverted to HR, and 2.6% were borderline. We used logistic regression to compare 14-day clinical failure and 14-day mortality between patients infected by HR versus susceptible non-HR carbapenem-resistant A. baumannii. In the subgroup of patients with bacteremia, HR was significantly associated with 14-day mortality.IMPORTANCE To our knowledge, this is the first large-scale study to report on HR in Gram-negative bacteria. We described the prevalence of colistin HR in a large sample of carbapenem-resistant A. baumannii isolates, the evolution of many colistin HR isolates to a resistant phenotype following colistin exposure and withdrawal, and the clinical consequences of colistin HR. We found a high prevalence of HR among clinical carbapenem-resistant A. baumannii isolates; most evolved into a resistant phenotype following colistin exposure and withdrawal. In patients treated with colistin, evolution of HR A. baumannii into full resistance could lead to higher rates of treatment failure and contribute to the reservoir of colistin-resistant pathogens in health care settings. To our knowledge, this is the first large-scale study to report on HR in Gram-negative bacteria. We described the prevalence of colistin HR in a large sample of carbapenem-resistant A. baumannii isolates, the evolution of many colistin HR isolates to a resistant phenotype following colistin exposure and withdrawal, and the clinical consequences of colistin HR.
|
|
3. |
- Nutman, Amir, et al.
(författare)
-
Colistin plus meropenem for carbapenem-resistant Gram-negative infections : in vitro synergism is not associated with better clinical outcomes
- 2020
-
Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 26:9, s. 1185-1191
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectivesIn vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem.MethodsThis was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin–meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin–meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure.ResultsThe sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31–1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22–2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26–1.04) or 14-day mortality (aOR1.09, 95% CI 0.60–1.96).DiscussionIn vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.
|
|
4. |
- Nutman, Amir, et al.
(författare)
-
In vivo fitness of carbapenem-resistant Acinetobacter baumannii strains in murine infection is associated with treatment failure in human infections
- 2022
-
Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 28:1, s. 73-78
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Mortality among patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections varies between studies. We examined whether in vivo fitness of CRAB strains is associated with clinical outcomes in patients with CRAB infections.Methods: Isolates were collected from patients enrolled in the AIDA trial with hospital-acquired pneumonia, bloodstream infections and/or urinary tract infections caused by CRAB. The primary outcome was 14-day clinical failure, defined as failure to meet all criteria: alive; haemodynamically stable; improved or stable Sequential Organ Failure Assessment (SOFA) score; improved or stable oxygenation; and microbiological cure of bacteraemia. The secondary outcome was 14-day mortality. We tested in vivo growth using a neutropenic murine thigh infection model. Fitness was defined based on the CFU count 24 hours after injection of an inoculum of 105 CFU. We used mixed-effects logistic regression to test the association between fitness and the two outcomes.Results: The sample included 266 patients; 215 (80.8%) experienced clinical failure. CRAB fitness ranged from 5.23 to 10.08 log CFU/g. The odds of clinical failure increased by 62% for every 1-log CFU/g increase in fitness (OR 1.62, 95% CI 1.04-2.52). After adjusting for age, Charlson score, SOFA score and acquisition in the intensive care unit, fitness remained significant (adjusted OR 1.63, 95% CI 1.03-2.59). CRAB fitness had a similar effect on 14-day mortailty, although the association was not statistically significant (OR 1.56, 95% CI 0.95-2.57). It became significant after adjusting for age, Charlson score, SOFA score and recent surgery (adjusted OR 1.88, 95% CI 1.09-3.25).Conclusions: In vivo CRAB fitness was associated with clinical failure in patients with CRAB infection.
|
|