الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Acinetobacter spp. has emerged as one of the leading opportunistic hospital-associated pathogens, A. baumannii is the the most significant species in clinical settings, as it causes a spectrum of diseases especially in ICUs, and is linked to high morbidity and mortality as well as extended hospital stays.
A. baumannii is characterized by its tendency to acquire resistance to several classes of antimicrobials. An increase in infections due to MDR, XDR and PDR A. baumannii isolates has been reported in the last two decades. Accordingly, the CDC considered A. baumannii a “serious” threat and the WHO has defined CR A. baumannii as one of the global priority superbugs.
The presence of clinical isolates resistant to all available antibiotics has led to dependence on the colistin as the last therapeutic option. Unfortunately, variable rates of colistin-resistance have been reported in A. baumannii isolates. Also its neurotoxicity and nephrotoxicity are of concern when used as a monotherapy. Another problem is colistin heteroresistance which has been noticed in vitro and during treatment, raising concerns that colistin alone may have insufficient bacterial eradication activity to be used as a monotherapy. Thus, the use of combinations of two or more agents has emerged as an alternative strategy for treating MDR A. baumannii infections. Combination therapy of synergistic antibiotics might be the last resource to treat severe A. baumannii infections.
One of the suggested combinations is colistin with anti-gram positive antibiotics. One of these anti-gram positive antibiotics is the glycopeptide teicoplanin, which might be effective in combination with colistin. The adjuvant permeabilizing effect of colistin on the A. baumannii outer membrane can allow teicoplanin to act by inhibiting cell wall synthesis in dividing organisms.
The present study aimed to:
1. Evaluate the synergistic activity of colistin and teicoplanin combination against multidrug resistant A. baumannii.
2. Determine the minimum inhibitory concentration of colistin for A. baumannii isolates.
This study was conducted over a period of three months from September 2019 to December 2019 at the HIPH. It included 30 Acinetobacter isolates that were collected from different clinical microbiology laboratories.
Bacterial isolates that were identified as MDR A. baumannii or Acinetobacter spp. were verified using standard conventional microbiological techniques then they were subjected to antimicrobial susceptibility testing using the Kirby Bauer disc diffusion method on Mueller Hinton agar plates. Isolates that were at least MDR were further identified by VITEK® 2 compact system, then those that were identified as Abc complex were further identified by MALDI-TOF. Colitin MICs were determined using commercial kit (ComASP Colistin) for the 30 confirmed bacterial isolates that were MDR, XDR and/or PDR.
References
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Time–kill assay was performed to test the synergy between colistin and teicoplanin against Acinetobacter spp. following methods published by the CLSI. The results of kill kinetics determination were shown graphically by plotting log10 CFU/ml against time for colistin alone and for colistin-teicoplanin combinations for each tested isolate. Activity was evaluated as follows: Bactericidal was defined as a ≥ 3 log10 CFU/ml decrease in colony count relative to intial inocula. Synergy was defined as a ≥ 2 log10 CFU/ml decrease in colony count at 24 hr when compared to the most active agent used alone.
The results of the present study revealed that:
1. Out the 30 collected Acinetobacter isolates 5 (16.66%) showed resistance to colistin.
2. Colistin resistance was higher in non-baumannii Acinetobacter isolates than in A. baumannii isolates as it was 37.5% versus 9.1% respectively.
3. Sixteen of bacterial isolates of the present study were found to be MDR (53.33%), 11 were XDR (36.67%) and 3 were PDR (10%).4. The combination of 1μg/ml colistin and 10μg/ml teicoplanin showed in vitro synergism against all tested Acinetobacter isolates except one (A. lowffii), however when colistin 1μg/ml was combined with teicoplanin 20μg/ml it was synergistic against it.
5. The combination of 1μg/ml colistin and 10μg/ml teicoplanin was bactericidal at 6 hour against 100% of A. baumannii isolates with no bacterial regrowth at 24 hour.
6. The combination of 1μg/ml colistin and 10μg/ml teicoplanin was bactericidal against 3 out of 8 non-baumannii Acinetobacter isolates, while the combination of 1μg/ml colistin and 20μg/ml teicoplanin was bactericidal against 4 of those isolates.It can be concluded from the present study that:
1. It was concluded from this study that the combination of colistin and teicoplanin was synergistic in vitro.
2. There was a difference between A. baumannii and non-baumannii Acinetobacter isolates in the response to the combination and in the pattern of resistance 3. Colistin resistance rate in A. baumannii was higher than other reported rates in Egypt.
from the results of the present study, the following recommendations are suggested:1. It is recommended that controlled clinical studies to be conducted to clarify the therapeutic potential of the combination of colistin and teicoplanin.
2. Accurate identification of Acinetobacter spp., especially the four interspecies of Abc is very important to appropriate treatment.3. The usage of colistin is needed to be regulated in Egyptian hospitals to prevent the spreading of colistin resistance.