scholarly journals HIỆU QUẢ PHỐI HỢP KHÁNG SINH IN VITRO TRÊN VI KHUẨN GRAM ÂM KHÁNG CARBAPENEM

2022 ◽  
Vol 508 (2) ◽  
Author(s):  
Ngô Hoàng Ngọc Thanh ◽  
Phạm Thái Bình ◽  
Cao Minh Nga

Đặt vấn đề: Theo Tổ chức Y tế thế giới (WHO), vi khuẩn (VK) Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae kháng carbapenem (APK-CR) là những vi khuẩn (VK) có mức cảnh báo cao nhất, cần ưu tiên phát triển các loại kháng sinh (KS) mới do tình trạng kháng thuốc đáng báo động [7]. Mục tiêu: Khảo sát MIC và hiệu quả phối hợp KS in vitro của meropenem (ME) - colistin (COL) và meropenem - ciprofloxacin (CIP) trên các chủng VK APK-CR. Phương pháp: Nghiên cứu mô tả cắt ngang. Các chủng APK-CR được phân lập tại Bệnh viện Đại học Y Dược TP. HCM từ tháng 12/2020 đến tháng 06/2021. Kết quả: Có 151 chủng gồm 51 chủng A. baumannii, 50 chủng P. aeruginosa và 50 chủng K. pneumoniae. MIC của ME và CIP trên các chủng APK-CR đều cao (chiếm 92-100%); có 6% chủng P. aeruginosa và 10% chủng K. pneumoniae là có MIC kháng COL. Hiệu quả hiệp đồng và cộng hợp trong phối hợp KS in vitro của ME-COL trên APK-CR có tỷ lệ lần lượt là 58,8% và 41,2%, 32% và 60%, 20% và 60%. Hiệu quả hiệp đồng và cộng hợp trong phối hợp KS in vitro của ME-CIP trên APK-CR có tỷ lệ lần lượt là 33,3% và 45,1%, 30% và 60%, 42% và 44%. Kết luận: APK-CR đề kháng với ME, CIP với tỷ lệ rất cao. Phối hợp ME-COL và ME-CIP trên APK-CR có kết quả hiệp đồng và cộng hợp làm giảm tỷ lệ đề kháng KS của APK-CR.

2019 ◽  
Author(s):  
L. Blasco ◽  
A. Ambroa ◽  
R. Trastoy ◽  
E. Perez-Nadales ◽  
F. Fernández-Cuenca ◽  
...  

ABSTRACTThe multidrug resistance (MDR) among pathogenic bacteria is jeopardizing the worth of antimicrobials, which had previously changed medical sciences. In this study, we used bioinformatic tools to identify the endolysins ElyA1 and ElyA2 (GH108-PG3 family) present in the genome of bacteriophages Ab1051Φ and Ab1052Φ, respectively. The muralytic activity of these endolysins over MDR clinical isolates (Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae) was tested using the turbidity reduction assay. The minimal inhibitory concentrations (MICs) of endolysin, colistin and their combination were determined using the microdilution checkerboard method. The antimicrobial activity of the combinations was confirmed by time kill curves and in vivo assays in larvae of Galleria mellonella. Our results showed that ElyA1 displayed activity against all 25 strains of A. baumannii and P. aeruginosa tested and against 13 out of 17 strains of K. pneumoniae. No activity was detected when assays were done with endolysin ElyA2. The combined antimicrobial activity of colistin and endolysin ElyA1 yielded a reduction in the colistin MIC for all strains studied, except K. pneumoniae. These results were confirmed in vivo in G. mellonella survival assays. In conclusion, the combination of colistin with new endolysins such as ElyA1 could increase the bactericidal activity and reduce the MIC of the antibiotic, thus also reducing the associated toxicity.IMPORTANCEThe development of multiresistance by pathogen bacteria increases the necessity of the development of new antimicrobial strategies. In this work, we combined the effect of the colistin with a new endolysin, ElyA1, from a bacteriophage present in the clinical strain of Acinetobacter baumannii Ab105. ElyA1 is a lysozyme-like family (GH108-GP3), whose antimicrobial activity was described for first time in this work. Also, another endolysin, ElyA2, with the same origin and family, was characterized but in this case no activity was detected. ElyA1 presented lytic activity over a broad spectrum of strains from A. baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae. When colistin was combined with ElyA1 an increase of the antimicrobial activity was observed with a reduced concentration of colistin, and this observation was also confirmed in vivo in Galleria mellonella larvae. The combination of colistin with new endolysins as ElyA1 could increase the bactericidal activity and lowering the MIC of the antibiotic, thus also reducing the associated toxicity.


2021 ◽  
Vol 14 (4) ◽  
pp. 370
Author(s):  
Le Phuong Nguyen ◽  
Chul Soon Park ◽  
Naina Adren Pinto ◽  
Hyunsook Lee ◽  
Hyun Soo Seo ◽  
...  

The siderophore–antibiotic conjugate LCB10-0200 (a.k.a. GT-1) has been developed to combat multidrug-resistant Gram-negative bacteria. In this study, the in vitro activity of LCB10-0200 and LCB10-0200/avibactam (AVI) has been investigated against carbapenem-resistant Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. Minimal inhibitory concentrations (MICs) of LCB10-0200, LCB10-0200/AVI, aztreonam, aztreonam/AVI, ceftazidime, ceftazidime/AVI, and meropenem were measured using the agar dilution method. Whole genome sequencing was performed using Illumina and the resistome was analyzed. LCB10-0200 displayed stronger activity than the comparator drugs in meropenem-resistant E. coli and K. pneumoniae, and the addition of AVI enhanced the LCB10-0200 activity to MIC ≤ 0.12 mg/L for 90.5% of isolates. In contrast, whereas LCB10-0200 alone showed potent activity against meropenem-resistant A. baumannii and P. aeruginosa at MIC ≤ 4 mg/L for 84.3% of isolates, the combination with AVI did not improve its activity. LCB10-0200/AVI was active against CTX-M-, SHV-, CMY-, and KPC- producing E. coli and K. pneumoniae, while LCB10-0200 alone was active against ADC-, OXA-, and VIM- producing A. baumannii and P. aeruginosa. Both LCB10-0200 and LCB10-0200/AVI displayed low activity against IMP- and NDM- producing strains. LCB10-0200 alone exhibited strong activity against selected strains. The addition of AVI significantly increased LCB10-0200 activity against carbapenem-resistant E. coli, K. pneumoniae.


2010 ◽  
Vol 54 (6) ◽  
pp. 2732-2734 ◽  
Author(s):  
Carl Urban ◽  
Noriel Mariano ◽  
James J. Rahal

ABSTRACT In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin were assessed against 20 carbapenem-resistant clinical isolates with different mechanisms of carbapenem resistance. Bactericidal activity was achieved in 90% of all bacteria assayed using combinations of polymyxin B, doripenem, and rifampin against five each of the carbapenem-resistant Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli isolates studied. Combinations with these antibacterials may provide a strategy for treatment of patients infected with such organisms.


Author(s):  
Tonny Loho ◽  
Ninik Sukartini ◽  
Dalima A. W. Astrawinata ◽  
Suzanna Immanuel ◽  
Diana Aulia ◽  
...  

Evaluation of the in vitro interaction of doripenem and amikacin against Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae was done by classifying them into four groups: doripenem and amikacin sensitive (DOR-S/AMK-S), doripenem sensitive and amikacin resistant (DOR-S/AMK-R), doripenem resistant and amikacin sensitive (DOR-R/AMK-S), and both doripenem and amikacin resistant (DOR-R/AMK-R). The MIC of each antibiotic and their combination was obtained using the Etest method. The fractional inhibitory concentration index was calculated to classify the results as synergistic, additive, indifferent, or antagonistic interaction. In the DOR-S/AMK-S class, 1 isolate of A. baumannii showed synergy and the other 5 showed additive results, 5 isolates of P. aeruginosa showed additive and 1 isolate showed indifferent result, and 2 isolates of K. pneumoniae showed additive and the other 4 showed indifferent results. In the DOR-S/AMK-R class, 3 isolates of A. baumannii showed additive and the other 3 showed indifferent results, 2 isolates of P. aeruginosa showed indifferent results, and 1 isolate of K. pneumoniae showed additive and the other 5 showed indifferent results. In the DOR-R/AMK-S class, 1 isolate of A. baumannii showed additive and the other 5 showed indifferent results, 1 isolate of P. aeruginosa showed additive and the other 5 showed indifferent results, and 4 isolates of K. pneumoniae showed additive and the other 2 showed indifferent results. In the DOR-R/AMK-R class, 6 isolates of A. baumannii showed indifferent results, 1 isolate of P. aeruginosa showed additive and the other 5 showed indifferent results, and 1 isolate of K. pneumoniae showed additive and the other 5 showed indifferent results. Synergy occurred in only 1 (1.5%) isolate. Additive interaction occurred in 24 (35.3%) isolates, and indifferent interaction occurred in 43 (63.2%) isolates. Doripenem sensitive combined with amikacin sensitive reduced MIC significantly in all bacterial isolates when compared to single MIC of each antibiotic.


2012 ◽  
Vol 56 (9) ◽  
pp. 4856-4861 ◽  
Author(s):  
Céline Vidaillac ◽  
Lothaire Benichou ◽  
Raphaël E. Duval

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 (1/19) were ≥128, 4 to ≥128, and 2/38 to >128/2,432 μg/ml, respectively. Colistin resistance demonstrated little impact on vancomycin, trimethoprim, or trimethoprim-sulfamethoxazole MIC values. Isolates with subpopulations heterogeneously resistant to colistin were observed to various degrees in all tested isolates. In time-kill assays, all tested combinations were synergistic against KPm1 at 0.25× MIC and 0.5× MIC and ABm1 and PAm1 at 0.5× MIC. In contrast, none of the tested combinations demonstrated synergy against any colistin-susceptibleP. aeruginosaisolates and clinical strains ofK. pneumoniaeisolates. Only colistin plus trimethoprim or trimethoprim-sulfamethoxazole was synergistic and bactericidal at 0.5× MIC againstK. pneumoniaeATCC 700603. Colistin resistance seems to promote thein vitroactivity of unconventional colistin combinations. Additional experiments are warranted to understand the clinical significance of these observations.


2019 ◽  
Vol 17 (3) ◽  
pp. 140-148 ◽  
Author(s):  
A. Ouelhadj ◽  
L. Ait Salem ◽  
D. Djenane

Ce travail vise l’étude de l’activité antibactérienne de l’huile essentielle (HE) de Pelargoniumx asperum et de la bactériocine, la nisine seul et en combinaison vis-à-vis de six bactéries dont quatre sont multirésistantes d’origine clinique. L’activité antibactérienne in vitro a été évaluée par la méthode de diffusion sur gélose. La concentration minimale inhibitrice (CMI) est aussi déterminée pour HE. Les résultats ont révélé une activité antibactérienne significative exercée par HE visà-vis de Staphylococcus aureus (ATCC 43300), Staphylococcus aureus et Escherichia coli avec des diamètres d’inhibition de 36,00 ; 22,50 et 40,00 mm, respectivement. Cependant, l’HE de Pelargonium asperum a montré une activité antibactérienne supérieure par rapport à la nisine. Les valeurs des CMI rapportées dans cette étude sont comprises entre 1,98–3,96 μl/ml. Les combinaisons réalisées entre HE et la nisine ont montré un effet additif vis-à-vis de Escherichia coli (ATCC 25922) avec (50 % HE Pelargonium asperum + 50 % nisine). Par contre, nous avons enregistré une synergie vis-à-vis de Klebsiella pneumoniae avec (75 % HE Pelargonium asperum + 25 % nisine) et contre Pseudomonas aeruginosa avec les trois combinaisons testées. Les résultats obtenus permettent de dire que l’HE de Pelargonium asperum possède une activité antibactérienne ainsi que sa combinaison avec la nisine pourrait représenter une bonne alternative pour la lutte contre l’antibiorésistance.


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