ANTIBIOTIC COMBINATIONS WITH COLISTIN AGAINST CARBAPENEM-RESISTANT Klebsiella pneumoniae - in vitro ASSESSMENT (original) (raw)
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Mediterranean journal of infection, microbes & antimicrobials, 2021
Introduction: Carbapenem-resistant (CR) Klebsiella pneumoniae is one of the most common CR Enterobacteriaceae species and is resistant to many antibiotics. Generally, combined use of antibiotics is preferred during infections of these microorganisms. This study aimed to demonstrate the in vitro synergy between meropenem (MEM), fosfomycin (FOS), colistin (CS), and tigecycline (TGC) in CR-K. pneumoniae (Kp) strains. Materials and Methods: A total of 52 CR-Kp strains were included. MicroScan WalkAway (Beckman Culture) plus system were used to identify strains. Antibiotic susceptibilities of the isolates were detected in the MicroScan WalkAway device (Beckman Culture) using MicroScan Gramnegative panel type 44 (Beckman Culture), and the minimal inhibitory concentrations (MIC) of antibiotics and extended-spectrum beta-lactamases (ESBL) formation were detected. Synergy studies were performed by the microdilution checkerboard method. A fractional inhibitory concentration index was used to interpret the results. Results: Of 52 strains, 11 had only carbapenem (MEM) resistance. Twenty-three of strains were also resistant to FOS, 27 to CS, and eight to TGC. When antibiotic combinations were compared, MEM + FOS, MEM + CS, and CS + TGC showed the best synergy in our strains. By contrast, the lowest synergy was observed with MEM + TGC, and the difference was significant (p<0.005). In addition, when the antibiotic combinations were compared in terms of MIC values, the lowest MIC concentration was observed with MEM + FOS. Ten of our strains had ESBL positivity besides CR. No combination showed >50% synergistic effect in these strains. Conclusion: This study showed that high FOS and CS resistance was also present in our CR-Kp strains. However, even in case of resistance to one or more of the antibiotics mentioned in this study, the results showed that, in combination with these antibiotics, especially MEM + FOS, MEM + CS, and CS + TGC, a significant amount of in vitro synergy can be achieved.
Egyptian Journal of Medical Microbiology
Health crisis of Multi-drug resistant gram negative bacilli (MDRGNB), including Enterobacteriaceae, seems overwhelming as its worldwide spread causes clinical failure in the therapeutic care of diseases by these pathogens and results in significant morbidity and mortality. Combination therapy, using two or more drugs, may be the last resort for treatment of these multi-drug resistant (MDR) organisms. Objective: to update the antibiotic policy to improve treatment of MDR Enterobacteriaceae infections and to reduce morbidity and mortality rates due to these infections. Methodology: Out of 219 of Enterobacteriaceae strains isolated from different types of infections in Suez Canal University Hospitals (SCUHs), 48 isolates (21.91%) were proved to be MDR, including resistance to imipenem. In vitro assessment of Imipenem-colistin combination on the MDR-Enterobacteriaceae strains was performed using the checkerboard technique. Results: The combination had a synergistic effect on 63.04% of the isolates and additive effect on 23.9%. Indifferent effect was shown in 10.8%, while antagonism was shown in 2.1% of the strains. At least, four-fold reduction in imipenem MIC was proved in 86.9% of the strains, 30.43% turned to be imipenem sensitive with drop of their MICs from ≥ 4 to ≤ 1μg/ml, 15.21% changed to intermediate resistance with MIC decrease from ≥ 4 to 2 μg/ml. Three of the 5 strains that showed indifference and the only strain which showed antagonism were colistin resistant strains. Conclusion: High rates of synergy, in addition to reversal of imipenem resistance, were reported by colistin-imipenem combination against MDR-Enterobacteriaceae, which may encourage clinical trials of combination therapy in treatment of Hospital acquired infections (HAI) by MDR pathogens.
Antimicrobial Agents and Chemotherapy, 2012
ABSTRACTColistin resistance, although uncommon, is increasingly being reported among Gram-negative clinical pathogens, and an understanding of its impact on the activity of antimicrobials is now evolving. We evaluated the potential for synergy of colistin plus trimethoprim, trimethoprim-sulfamethoxazole (1/19 ratio), or vancomycin against 12 isolates ofAcinetobacter baumannii(n= 4),Pseudomonas aeruginosa(n= 4), andKlebsiella pneumoniae(n= 4). The strains included six multidrug-resistant clinical isolates,K. pneumoniaeATCC 700603,A. baumanniiATCC 19606,P. aeruginosaATCC 27853, and their colistin-resistant derivatives (KPm1, ABm1, and PAm1, respectively). Antimicrobial susceptibilities were assessed by broth microdilution and population analysis profiles. The potential for synergy of colistin combinations was evaluated using a checkerboard assay, as well as static time-kill experiments at 0.5× and 0.25× MIC. The MIC ranges of vancomycin, trimethoprim, and trimethoprim-sulfamethoxazole...
2019
The use of combined antibiotic therapy has became an option for infections caused by multidrug-resistant (MDR) bacteria. Time-kill (TK) assay is the gold standard method for evaluation of in vitro synergy; however, it is a time consuming and expensive method. The purpose of this study was to evaluate in vitro synergy using ETEST and disk diffusion methods that can be used routinely in clinical microbiology laboratories. Sixty-two MDR Gram-negative clinical isolates (28 Pseudomonas aeruginosa, 20 Acinetobacter baumannii and 14 Serratia marcescens) were submitted to TK, disk approximation (DA) and MIC:MIC ratio synergy methods. Overall, the agreement between the DA and TK assays for P. aeruginosa and S. marcescens isolates ranged from 57 to 93%. MIC:MIC ratio concordance with TK ranged from 57 to 71%. The best agreement with the TK assay was observed using DA method for A. baumannii isolates for the combination of fosfomycin with meropenem (80%; k= 0,60; P= 0,003). The concordance was...
International Journal of Antimicrobial Agents, 2019
Background: New antibiotics are urgently needed for the treatment of multidrug resistant infections. However, the production of novel antibiotics is diminishing. The enhancement of activity of available antibiotics through synergistic combination drug therapy may help in the management of patients with resistant infections. Methods: Colistin-resistant Klebsiella pneumoniae isolates were collected from inpatients in 10 Greek hospitals and used in the study of combination activity of colistin plus azidothymidine. The combination activity was evaluated with the sum of fractional inhibitory concentrations (ΣFIC), using the mini checkerboard broth microdilution method. Results: 100 individual strains were tested. Synergistic activity was noted in 79% of the isolates (79/100) and additive activity in the rest 21% (21/100). ΣFIC 50 and ΣFIC 90 were 0.28 and 0.56, respectively. Conclusion: Colistin with azidothymidine exhibited promising synergistic activity against colistin-resistant carbapenem resistant Klebsiella pneumoniae isolates warranting further investigations of the combination.
International Journal of Basic & Clinical Pharmacology, 2017
Colistin belongs to the polymyxin class of cationic polypeptide antibiotics. It is administered as the prodrug ABSTRACT Background: Multi drug resistant (MDR) bacteria are usually defined as when it is resistant to three or more group of antibiotics. The objective of this study was to determine the efficacy and safety of colistin when compared with other antibiotics for the treatment of infections caused by MDR Acinetobacter baumannii and Pseudomonas aeruginosa. Methods: A single centre, prospective cohort study was conducted at Krishna Institute of medical Sciences, Hyderabad, India between September 2016 to March 2017. Seventy-four patients (74) were included in the study. Primary outcome were good clinical response and thirty days' mortality, secondary outcome were microbiological response and adverse drug reactions of the drug. Results: A total of 74 patients were enrolled into the study. Forty patients (40) were received intravenous colistin dose of 2.5mg-5mg/kg/day. Remaining thirty-four patients (34) received other antibiotics which includes carbapenem, aminoglycosides. etc. The mean age, gender, underlying conditions and severity of illness of the patients in both groups were significantly same. In colistin group 27 (67.5%) patients and 11 (32.3%) patients had good clinical response. The overall mortality of the patients in the colistin group was 17.5% and that in the non-colistin group was 38.2%. The incidence of nephrotoxicity in colistin was 15% and 35.2% in non colistin group. No neurotoxicity was observed in present study. Conclusions: Our study concludes treatment with colistin decreases patient mortality and increase the clinical response in multidrug-resistant A. baumannii and P. aeruginosa infected patients. However large multicentric clinical trials are needed to demonstrate the safety and efficacy of colistin.
Journal of Antimicrobial Chemotherapy, 2014
Combination therapy is recommended for the treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp), but the optimal regimen for colistin-resistant strains is unknown. We compared the synergistic activity and post-antibiotic effect (PAE) of colistin in combination with other antimicrobials against colistin-susceptible and-resistant KPC-Kp bloodstream isolates. Methods: The genotypes of nine colistin-susceptible and eight colistin-resistant KPC-Kp bloodstream isolates were analysed using PCR and amplicon sequencing. Combinations of colistin, meropenem, tigecycline, rifampicin and teicoplanin were then screened using the Etest, a chequerboard assay and time-kill studies. Synergistic combinations were also analysed with respect to the PAE in time-kill curves and the PAE at clinically achievable concentrations. Results: Insertional inactivation of the PhoQ/PhoB two-component regulatory system by mgrB-IS5 was identified in 6/8 (75%) colistin-resistant KPC-Kp. Colistin/rifampicin combinations resulted in no interactions [fractional inhibitory concentration (FIC) indices 1.5-2] for colistin-susceptible strains, but were uniformly synergistic (FIC indices 0.1-0.4) against colistin-resistant KPC-Kp. Time-kill kinetic analysis, at clinically achievable fixed concentrations of rifampicin and colistin, confirmed synergy and produced persistent growth inhibition (3 h) of colistin-resistant KPC-Kp strains exposed to colistin/rifampicin or colistin/rifampicin/tigecycline combinations. Conclusions: Combinations of colistin plus rifampicin, and less frequently tigecycline, exhibited synergistic activity in vitro against colistin-resistant KPC-Kp strains.
Synergistic Combination of Carbapenems and Colistin against P. aeruginosa and A. baumannii
Open Journal of Medical Microbiology, 2013
Background: Intubated patients are particularly at risk of developing infections caused by these pathogens, specifically, P. aeruginosa and A. baumannii. In the past fifteen years, Carbapenems were known to be the drugs of choice for these bacteria. With the increase in the use and misuse of antibiotics, these bacteria became highly resistant, and almost all available antibiotics, including Carbapenems, became inefficient. Synergistic combination therapy may be a useful strategy in slowing as well as overcoming the emergence of resistance. The aim of this study was to evaluate the antibacterial activity on P. aeruginosa and A. baumannii of the combination of two antibiotics: Colistin and a Carbapenem (Meropenem or Imipenem). Methods: The antibacterial activity was assessed by determining the MIC. Then, the effect of combining the antibiotics was studied using the Checkerboard Technique described by . The Fractional Inhibitory Concentration (FIC) for each strain was then calculated and classified as synergy, additive, indifference or antagonism. 11 strains of A. baumannii and 11 strains of P. aeruginosa were tested in the presence of Meropenem combined with Colistin or Imipenem combined with Colistin. Results: For the combination of Meropenem and Colistin, 6 strains of A. baumannii and 3 strains of P. aeruginosa showed synergy while 5 strains of A. baumannii and 7 strains of P. aeruginosa showed additive effect, only 1 strain of P. aeruginosa showed antagonism. For Imipenem and Colistin, only 1 strain of A. baumannii and 3 strains of Pseudomonas showed synergy while 8 strains of Acinetobacter and 8 strains of Pseudomonas showed additive effect. Conclusion: The "in vitro" combination Colistin-Carbapenem is associated with an improvement in MIC. In the majority of the cases, this improvement suggests a synergistic combination or an additive effect.
International Journal of Pharmacy and Pharmaceutical Sciences, 2014
Objective: Combination therapy is recommended for carbapenem resistant Gram negative bacilli (CR GNB) infections. However, limited data exists on the clinical effectiveness of antibiotic combinations. The purpose of this study was to evaluate the efficacy of colistin-carbapenem combination against CR GNB infection in a clinical study and an in vitro synergy study using Etest. Methods: A study was conducted in a tertiary care hospital to evaluate the clinical outcome of patients with CR GNB infections who were treated with colistin-carbapenemcombination between January to April, 2013. It was comprised of 33 patients with CR GNB infection. Detection of in vitro synergy was performed by Etest for colistin-meropenem combination on five isolates. These isolates were also screened for the resistant genes blaOXA-23, blaVIMand blaNDM Results: 33 CR GNB included Acinetobacterspp. (19), Pseudomonas aeruginosa (7) and Enterobacteriaceae spp. (7). Overall clinical success of 60.6% was observed in patients receiving colistin-carbapenem combination therapy. In respiratory infection, the clinical success rate was only 25%, whereas in soft tissue infection it was 57.1%. In bloodstream infection 100% clinical success was observed. All five isolates screened using PCR was carrying bla NDM gene, whereas isolate of Acinetobacter baumannii also carried bla using single target PCR. OXA-23 and blaVIM Conclusion: We observed low clinical success rate for colistin-carbapenem combination therapy, probably due to indifferent interactions between colistin and meropenem against NDM producing strain. In addition, probable pharmacokinetic concern of colistin may have a role to play. gene. Indifferent interactions were observed between colistin and meropenem against all five isolates.
BIOCELL
The aim of this study is to detect in vitro the synergetic activity of colistin in combination with imipenem, amikacin or ciprofloxacin, at sub-inhibitory concentrations, against carbapenems-resistant (CR) Acinetobacter baumannii and Pseudomonas aeruginosa strains isolated from various wards in Annaba teaching hospital in eastern Algeria. Materials and Methods: The minimal inhibitory concentrations (MIC) were determined by broth macrodilution (BMD). Carbapenemase encoding genes were screened using polymerase chain reaction (PCR). The activity of colistin in combination with second antibiotic was evaluated by the Checkerboard Technique. Results: 39 CR P. aeruginosa and 21 CR A. baumanni strains where collected. The MIC values ranging from (0.25 to 4 µg/ml) to colistin, ≥16 µg/ml for imipenem, ≥4 µg/ml to amikacin and ≥8 µg/ml ciprofloxacin. The PCR reveals the presence of the genes bla OXA23 (n = 12), bla OXA24 (n = 6), bla NDM1 (n = 3) in A. baumannii and bla VIM2 (n = 12) in P. aeruginosa. The combination of colistin with imipenem showed synergistic effect on 57.14% and 46.15% of A. baumannii and P. aeruginosa isolates, respectively. For colistin and amikacin, the synergistic effect is detected in 28.6% of A. baumannii and 30.8% of P. aeruginosa. While colistin and ciprofloxacin showed synergy on 14.29% and 15.38% of A. baumannii and P. aeruginosa isolates, respectively. Conclusion: CR A. baumannii and P. aeruginosa remain the most prevalent infection agents in patients from high-risk wards at Annaba Hospital. Colistin associated with imipenem or with amikacin at sub-inhibitory concentrations gives very encouraging results allowing better management of infections caused by this type of bacteria.