scholarly journals Extensively drug-resistant Acinetobacter baumannii in a Thai hospital: a molecular epidemiologic analysis and identification of bactericidal Polymyxin B-based combinations

Author(s):  
Jocelyn Teo ◽  
Tze-Peng Lim ◽  
Li-Yang Hsu ◽  
Thean-Yen Tan ◽  
Suranthran Sasikala ◽  
...  
2019 ◽  
Vol 64 (3) ◽  
Author(s):  
Fiona Hui-Sian Wong ◽  
Yiying Cai ◽  
Hui Leck ◽  
Tze-Peng Lim ◽  
Jocelyn Qi-Min Teo ◽  
...  

ABSTRACT Polymyxin B-based combinations are increasingly prescribed as a last-line option against extensively drug-resistant (XDR) Acinetobacter baumannii. It is unknown if such combinations can result in the development of nondividing persister cells in XDR A. baumannii. We investigated persister development upon exposure of XDR A. baumannii to polymyxin B-based antibiotic combinations using flow cytometry. Time-kill studies (TKSs) were conducted in three nonclonal XDR A. baumannii strains with 5 log10 CFU/ml bacteria against polymyxin B alone and polymyxin B-based two-drug combinations over 24 h. At different time points, samples were obtained and enumerated by viable plating and flow cytometry. Propidium iodide and carboxyfluorescein succinimidyl ester dyes were used to differentiate between live and dead cells and between dividing and nondividing cells, respectively, at the single-cell level, and nondividing live cells were resuscitated and characterized phenotypically. Our results from viable plating showed that polymyxin B plus meropenem and polymyxin B plus rifampin were each bactericidal (>99.9% kill compared to the initial inoculum) against 2/3 XDR A. baumannii strains at 24 h. By flow cytometry, however, none of the combinations were bactericidal against XDR A. baumannii at 24 h. Further analysis using cellular dyes in flow cytometry revealed that upon exposure to polymyxin B-based combinations, XDR A. baumannii entered a viable but nondividing persister state. These bacterial cells reinitiated division upon the removal of antibiotic pressure and did not have a growth deficit compared to the parent strain. We conclude that persister cells develop in XDR A. baumannii upon exposure to polymyxin B-based combinations and that nonplating methods appear to complement viable-plating methods in describing the killing activity of polymyxin B-based combinations against XDR A. baumannii.


2010 ◽  
Vol 55 (1) ◽  
pp. 436-438 ◽  
Author(s):  
Thean Yen Tan ◽  
Tze Peng Lim ◽  
Winnie Hui Ling Lee ◽  
Suranthran Sasikala ◽  
Li Yang Hsu ◽  
...  

ABSTRACTThis study examined thein vitroeffects of polymyxin B, tigecycline, and rifampin combinations on 16 isolates of extensively drug-resistantAcinetobacter baumannii, including four polymyxin-resistant strains.In vitrosynergy was demonstrated in 19 (40%) of a possible 48 isolate-antibiotic combinations by time-kill methods, 8 (17%) by checkerboard methods, and only 1 (2%) by Etest methods. There was only slight agreement between Etest and checkerboard methods and no agreement between results obtained by other methods.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Qin Peng ◽  
Fei Lin ◽  
Baodong Ling

Abstract Acinetobacter baumannii is a common pathogen of nosocomial infection, and its ability to form biofilms further contributes to its virulence and multidrug resistance, posing a great threat to global public health. In this study, we investigated the inhibitory effects of five biofilm inhibitors (BFIs) (zinc lactate, stannous fluoride, furanone, azithromycin, and rifampicin) on biofilm formation of nine extensively drug-resistant A. baumannii (XDRAB), and assessed the synergistic antibacterial effects of these BFIs when combined with one of four conventional anti-A. baumannii antibiotics (imipenem, meropenem, tigecycline, and polymyxin B). Each of the five BFIs tested was found to be able to significantly inhibit biofilm formation of all the clinical isolates tested under sub-minimal inhibitory concentrations. Then, we observed synergistic effects (in 22%, 56% and 11% of the isolates) and additive effects (56%, 44% and 44%) when zinc lactate, stannous fluoride and furanone were combined with tigecycline, respectively. When zinc lactate and stannous fluoride were each used with a carbapenem (imipenem or meropenem), in 33% and 56–67% of the isolates, they showed synergistic and additive effects, respectively. Additivity in > 50% of the isolates was detected when rifampicin was combined with imipenem, meropenem, tigecycline, or polymyxin B; and a 100% additivity was noted with azithromycin-polymyxin B combination. However, antagonism and indifference were noted for polymyxin B in its combination with zinc lactate and stannous fluoride, respectively. In conclusion, five BFIs in combination with four antibacterial drugs showed different degrees of in vitro synergistic and additive antibacterial effects against XDRAB.


2022 ◽  
Vol 14 (2) ◽  
Author(s):  
Rui Yang ◽  
Fang Li ◽  
Wei Wei Mao ◽  
Xin Wei ◽  
Xinzhu Liu ◽  
...  

Introduction: The incidence of postneurosurgical Acinetobacter baumannii ventriculitis/meningitis, primarily due to drug-resistant strains, has increased considerably in recent years. However, limited therapeutic options are available because most antibiotics poorly penetrate the blood-brain barrier, especially in pediatric patients. Case Presentation: A five-year-old boy developed ventriculitis due to extensively drug-resistant A. baumannii (XDRAB) after bilateral frontal external ventricular drainage for spontaneous intraventricular hemorrhage. The boy was safely and successfully treated with intraventricular (IVT)/intrathecal (ITH) polymyxin B together with intravenous tigecycline plus cefoperazone/sulbactam. Conclusions: In the present case, postneurosurgical XDRAB ventriculitis was closely associated with intraventricular hemorrhage and the placement of external ventricular drainage. IVT/ITH polymyxin B combined with intravenous tigecycline and cefoperazone sulbactam could be a therapeutic option against XDRAB ventriculitis in children.


2015 ◽  
Vol 59 (10) ◽  
pp. 6575-6580 ◽  
Author(s):  
Maria Helena Rigatto ◽  
Fabiane J. Vieira ◽  
Laura C. Antochevis ◽  
Tainá F. Behle ◽  
Natane T. Lopes ◽  
...  

ABSTRACTThere is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistantAcinetobacter baumanniiorPseudomonas aeruginosaisolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severeA. baumanniiorP. aeruginosainfections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lackingin vitroactivity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P= 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P= 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64;P= 0.001). Creatinine clearance of ≥60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with β-lactam or carbapenem was considered and in both subgroups of patients: those withA. baumanniiinfection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistantA. baumanniiorP. aeruginosainfections.


2014 ◽  
Vol 35 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Tat Ming Ng ◽  
Christine B. Teng ◽  
David C. Lye ◽  
Anucha Apisarnthanarak

Objective.Extensively drug resistant (XDR) Acinetobacter baumannii infections are increasing. Knowledge of risk factors can help to prevent these infections.Methods.We designed a 1: 1: 1 case-case-control study to identify risk factors for XDR A. baumannii bacteremia in Singapore and Thailand. Case group 1 was defined as having infection due to XDR A. baumannii, and case group 2 was defined as having infection due to non-XDR A. baumannii. The control group comprised patients with blood cultures obtained to determine possible infection.Results.There were 93 patients in each group. Pitt bacteremia score (adjusted odds ratio [aOR], 2.570 [95% confidence interval (CI), 1.528–4.322]), central venous catheters (CVCs; aOR, 12.644 [95% CI, 2.143–74.620]), use of carbapenems (aOR, 54.391 [95% CI, 3.869–764.674]), and piperacillin-tazobactam (aOR, 55.035 [95% CI, 4.803–630.613]) were independently associated with XDR A. baumannii bacteremia. In case group 2, Pitt bacteremia score (aOR, 1.667 [95% CI, 1.265–2.196]) and third-generation cephalosporins (aOR, 2.965 [95% CI, 1.224–7.182]) were independently associated with non-XDR A. baumannii bacteremia. Concurrent infections (aOR, 3.527 [95% CI, 1.479–8.411]), cancer (aOR, 3.172 [95% CI, 1.135–8.865]), and respiratory source (aOR, 2.690 [95% CI, 1.160–6.239]) were associated with an increased risk of 30-day mortality. Survivors received more active empirical therapy (16.7% vs 9.6%; P = .157), had fewer cases of XDR bacteremia (45.8% vs 52.6%; P = .452), and received higher median definitive polymyxin B doses (840,000 units vs 700,000 units; P = .339)Conclusions.Use of CVC and broad spectrum antibiotics were unique risk factors of XDR A. baumannii bacteremia. Effective antimicrobial stewardship together with use of a CVC bundle may reduce the incidence of these infections. Risk factors of acquisition and mortality may help identify patients for early initiation of polymyxin B therapy.


Author(s):  
Elham Abbasi ◽  
Hossein Goudarzi ◽  
Ali Hashemi ◽  
Alireza Salimi Chirani ◽  
Abdollah Ardebili ◽  
...  

AbstractA major challenge in the treatment of infections has been the rise of extensively drug resistance (XDR) and multidrug resistance (MDR) in Acinetobacter baumannii. The goals of this study were to determine the pattern of antimicrobial susceptibility, blaOXA and carO genes among burn-isolated A. baumannii strains. In this study, 100 A. baumannii strains were isolated from burn patients and their susceptibilities to different antibiotics were determined using disc diffusion testing and broth microdilution. Presence of carO gene and OXA-type carbapenemase genes was tested by PCR and sequencing. SDS-PAGE was done to survey CarO porin and the expression level of carO gene was evaluated by Real-Time PCR. A high rate of resistance to meropenem (98%), imipenem (98%) and doripenem (98%) was detected. All tested A. baumannii strains were susceptible to colistin. The results indicated that 84.9% were XDR and 97.9% of strains were MDR. In addition, all strains bore blaOXA-51 like and blaOXA-23 like and carO genes. Nonetheless, blaOXA-58 like and blaOXA-24 like genes were harbored by 0 percent and 76 percent of strains, respectively. The relative expression levels of the carO gene ranged from 0.06 to 35.01 fold lower than that of carbapenem-susceptible A. baumannii ATCC19606 and SDS – PAGE analysis of the outer membrane protein showed that all 100 isolates produced CarO. The results of current study revealed prevalence of blaOXA genes and changes in carO gene expression in carbapenem resistant A.baumannii.


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