In vitro synergistic activity of fosfomycin in combination with other antimicrobial agents against carbapenem-resistant Klebsiella pneumoniae isolated from patients in a hospital in Thailand

AbstractThe present study evaluated the carbapenem resistance mechanisms of Klebsiella pneumoniae strains isolated in two Greek tertiary teaching hospitals and their susceptibility to currently used and novel antimicrobial agents.Forty-seven carbapenem resistant K. pneumoniae strains were collected in G. Papanikolaou and Ippokrateio hospital of Thessaloniki between 2016 and 2018. Strain identification and antimicrobial susceptibility was conducted by Vitek 2 system (Biomérieux France). Susceptibility against new antimicrobial agents was examined by disk diffusion method. Polymerase chain reaction (PCR) was used to detect blaKPC, blaVIM, blaNDM and blaOXA-48 genes.The meropenem–EDTA and meropenem–boronic acid synergy test performed on the 24 K. pneumoniae strains demonstrated that 8 (33.3%) yielded positive for metallo-beta-lactamases (MBL) and 16 (66.6%) for K. pneumonia carbapenemases (KPC) production. Colistin demonstrated the highest in vitro activity (87.7%) among the 47 K. pneumoniae strains followed by gentamicin (76.5%) and tigecycline (51%). Among new antibiotics ceftazidime/avibactam showed the highest sensitivity (76.6%) in all strains followed by eravacycline (66.6%). The blaKPC gene was present in 30 strains (63.8%), the blaNDM in 11 (23.4%) and the blaVIM in 6 (12.8%). The blaOXA-48 gene was not detected.Well established antimicrobial agents such as colistin, gentamicin and tigecycline and novel antibiotics like ceftazidime/avibactam and eravacycline can be reliable options for the treatment of invasive infections caused by carbapenem-resistant K. pneumoniae.

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In vitro and in vivo synergistic effects of tigecycline combined with aminoglycosides on carbapenem-resistant Klebsiella pneumoniae

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab122 ◽

2021 ◽

Author(s):

Wentao Ni ◽

Deqing Yang ◽

Jie Guan ◽

Wen Xi ◽

Dexun Zhou ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Synergistic Effects ◽

Molecular Characteristics ◽

Synergistic Activity ◽

Significant Activity ◽

Clinical Pharmacokinetics ◽

Carbapenem Resistant ◽

Time Kill

Abstract Objectives Carbapenem-resistant Klebsiella pneumoniae (CR-KP) infections represent severe threats to public health worldwide. The aim of this study was to assess potential synergistic interaction between tigecycline and aminoglycosides via in vitro and in vivo studies. Methods Antibiotic resistance profiles and molecular characteristics of 168 CR-KP clinical isolates were investigated by susceptibility testing, PCR and MLST. Chequerboard tests and time–kill assays were performed for 20 CR-KP isolates to evaluate in vitro synergistic effects of tigecycline combined with aminoglycosides. A tissue-cage infection model of rats was established to evaluate in vivo synergistic effects. Different doses of tigecycline and aminoglycosides alone or in combination were administered for 7 days via tail vein injection. Antibiotic efficacy was evaluated in tissue-cage fluid and emergence of resistance was screened. Results The chequerboard tests showed that this combination displayed synergistic or partial synergistic activity against CR-KP. The time–kill assays further demonstrated that strong synergistic effects of such a combination existed against isolates that were susceptible to both drugs but for resistant isolates no synergy was observed if clinical pharmacokinetics were taken into consideration. The in vivo study showed that the therapeutic effectiveness of combination therapies was better than that of monotherapy for susceptible isolates, suggesting in vivo synergistic effects. Furthermore, combinations of tigecycline with an aminoglycoside showed significant activity in reducing the occurrence of tigecycline-resistant mutants. Conclusions Compared with single drugs, tigecycline combined with aminoglycosides could exert synergistic effects and reduce the emergence of tigecycline resistance. Such a combination might be an effective alternative when treating CR-KP infections in clinical practice.

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Synergistic activity of fosfomycin–meropenem and fosfomycin–colistin against carbapenem resistant Klebsiella pneumoniae: an in vitro evidence

Future Science OA ◽

10.2144/fsoa-2019-0074 ◽

2020 ◽

pp. FSO461 ◽

Cited By ~ 3

Author(s):

Yamuna Devi Bakthavatchalam ◽

Abirami Shankar ◽

Dhiviya Prabaa Muthuirulandi Sethuvel ◽

Kalaiarasi Asokan ◽

Kalaiarasi Kanthan ◽

...

Keyword(s):

Antibacterial Activity ◽

Klebsiella Pneumoniae ◽

Blood Cultures ◽

Synergistic Activity ◽

Carbapenem Resistant ◽

Resistant Genes ◽

Time Kill ◽

Synergistic Antibacterial Activity

Aim: To evaluate the antibacterial activity of fosfomycin–meropenem and fosfomycin–colistin combinations against carbapenem-resistant Klebsiella pneumoniae (CR-Kp). Methods: A total of 50 CR-Kp isolates recovered from blood cultures were included in this study. All the CR-Kp isolates were screened for the presence of carbapenem resistant genes blaIMP. blaVIM. blaNDM. blaOXA-48 like, blaKPC. blaGES.#x00A0;and blaSPM. Combination testing of fosfomycin–meropenem and fosfomycin–colistin were performed using time-kill assay. Results: Fosfomycin–meropenem combination showed synergy in 20% of the tested CR-Kp isolates. While, fosfomycin–colistin exhibited synergy against 16% of the isolates. A total of 68% (n = 34) of CR-Kp isolates were characterised as OXA-48-like producers and 22% (n = 11) as NDM producers. Synergistic activity of these combinations was observed against OXA-48, NDM and NDM + OXA-48 co-producers. Conclusion: Considerable synergistic antibacterial activity of fosfomycin–meropenem and fosfomycin–colistin was not observed against CR-Kp isolates. Therefore, these combinations may not be promising for infections associated with CR-Kp.

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Combination of Colistin and Azidothymidine Demonstrates Synergistic Activity against Colistin-Resistant, Carbapenem-Resistant Klebsiella pneumoniae

Microorganisms ◽

10.3390/microorganisms8121964 ◽

2020 ◽

Vol 8 (12) ◽

pp. 1964

Author(s):

Ya-Ting Chang ◽

Tsung-Ying Yang ◽

Po-Liang Lu ◽

Shang-Yi Lin ◽

Liang-Chun Wang ◽

...

Keyword(s):

Combination Therapy ◽

Klebsiella Pneumoniae ◽

Therapeutic Option ◽

Rapid Evolution ◽

Toxicity Testing ◽

World Health ◽

Synergistic Activity ◽

Carbapenem Resistant

Carbapenem-resistant Enterobacteriaceae (CRE) is listed as an urgent threat by the World Health Organization because of the limited therapeutic options, rapid evolution of resistance mechanisms, and worldwide dissemination. Colistin is a common backbone agent among the “last-resort” antibiotics for CRE; however, its emerging resistance among CRE has taken the present dilemma to the next level. Azidothymidine (AZT), a thymidine analog used to treat human immunodeficiency virus/acquired immunodeficiency syndrome, has been known to possess antibacterial effects against Enterobacteriaceae. In this study, we investigated the combined effects of AZT and colistin in 40 clinical isolates of colistin-resistant, carbapenem-resistant K. pneumoniae (CCRKP). Eleven of the 40 isolates harbored Klebsiella pneumoniae carbapenemase. The in vitro checkerboard method and in vivo nematode killing assay both revealed synergistic activity between the two agents, with fractional inhibitory concentration indexes of ≤0.5 in every strain. Additionally, a significantly lower hazard ratio was observed for the nematodes treated with combination therapy (0.288; p < 0.0001) compared with either AZT or colistin treatment. Toxicity testing indicated potentially low toxicity of the combination therapy. Thus, the AZT–colistin combination could be a potentially favorable therapeutic option for treating CCRKP.

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In VitroActivity of Polymyxin B plus Imipenem, Meropenem, or Tigecycline against KPC-2-Producing Enterobacteriaceae with High MICs for These Antimicrobials

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00365-15 ◽

2015 ◽

Vol 59 (6) ◽

pp. 3596-3597 ◽

Cited By ~ 9

Author(s):

Natália Barth ◽

Vanessa B. Ribeiro ◽

Alexandre P. Zavascki

Keyword(s):

Klebsiella Pneumoniae ◽

Serratia Marcescens ◽

Antimicrobial Agents ◽

Enterobacter Cloacae ◽

Polymyxin B ◽

Synergistic Activity ◽

Content Type ◽

Time Kill ◽

High Mics

ABSTRACTWe evaluated thein vitroactivity of polymyxin B plus imipenem, meropenem, or tigecycline against six KPC-2-producingEnterobacteriaceaestrains with high MICs for these antimicrobial agents. Polymyxin B with carbapenems, especially meropenem, were the most active combinations forKlebsiella pneumoniaeandEnterobacter cloacaeregardless of the polymyxin B concentration used in the time-kill assay. This combination was also synergistic against twoSerratia marcescensstrains that are intrinsically resistant to polymyxins. Polymyxin B and tigecycline also presented synergistic activity in most experiments.

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Antimicrobial agents active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae isolates in Lebanon

The Journal of Infection in Developing Countries ◽

10.3855/jidc.9729 ◽

2018 ◽

Vol 12 (03) ◽

pp. 164-170 ◽

Cited By ~ 1

Author(s):

George Farah Araj ◽

Aline Z Avedissian ◽

Lina Y Itani ◽

Jowana A Obeid

Keyword(s):

Escherichia Coli ◽

Retrospective Study ◽

Klebsiella Pneumoniae ◽

Antimicrobial Agents ◽

Medical Center ◽

In Vitro Activity ◽

E Coli ◽

Carbapenem Resistant ◽

Promising Treatment

Introduction: It is not yet clear which antimicrobial agents should be used to treat the ominously increasing infections with carbapenem-resistant (CR) bacteria. We therefore investigated the activity of different antimicrobial agents against CR Escherichia coli and Klebsiella pneumoniae in Lebanon. Methodology: This retrospective study assessed the minimum inhibitory concentrations (MICs) of three carbapenems (by Etest), as well as the in vitro activity of eight other antimicrobials (by disk diffusion) against CR E. coli (n = 300) and K. pneumoniae (n = 232) isolates recovered at a major University Medical Center in Lebanon. Results: Higher percentages of isolates showing carbapenem MICs of ≤ 8 µg/mL were noted among the CR E. coli compared to the CR K. pneumoniae for ertapenem (48% vs 27%), imipenem (74 % vs 58%) and meropenem (82% vs 63%). Among the eight other antimicrobials, activity was generally higher when the MICs for the three carbapenems were ≤ 8 µg/mL. Regardless of the MIC level of the three carbapenems, very low susceptibility rates (≤ 33%) were noted for ciprofloxacin, trimethoprim-sulfamethoxazole and aztreonam against both E. coli and K. pneumoniae isolates. With Amikacin, higher susceptibility rates were seen against E. coli isolates (81%-97%) than against K. pneumoniae isolates (55%-86%), also reflecting higher activity than gentamicin (44%-54%). The best activity (66%-100%) was observed for tigecycline, colistin and fosfomycin against both CR species. Conclusions: Based on the in vitro findings in this study, the combination of a carbapenem showing an MIC of ≤ 8 µg/mL together with an active colistin, tigecycline, or fosfomycin, would offer a promising treatment option for patients infected with CR E. coli or K. pneumoniae.

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Retracted: Characterization of carbapenem resistance mechanisms and in vitro synergistic activity of colistin plus meropenem in carbapenem resistant Klebsiella pneumoniae

Microbiology and Immunology ◽

10.1111/1348-0421.12199 ◽

2015 ◽

Vol 59 (3) ◽

pp. 182-182

Keyword(s):

Klebsiella Pneumoniae ◽

Carbapenem Resistance ◽

Resistance Mechanisms ◽

Synergistic Activity ◽

Carbapenem Resistant

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Activity of Imipenem-Relebactam and Comparator Agents against Genetically Characterized Isolates of Carbapenem-Resistant Enterobacteriaceae

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00672-19 ◽

2019 ◽

Vol 63 (9) ◽

Cited By ~ 13

Author(s):

Matthew C. Canver ◽

Michael J. Satlin ◽

Lars F. Westblade ◽

Barry N. Kreiswirth ◽

Liang Chen ◽

...

Keyword(s):

Public Health ◽

Klebsiella Pneumoniae ◽

Antimicrobial Agents ◽

Content Type ◽

Health Threat ◽

Carbapenem Resistant ◽

Public Health Threat ◽

Carbapenem Resistant Enterobacteriaceae

ABSTRACT Carbapenem-resistant Enterobacteriaceae (CRE) strains are an urgent public health threat. We evaluated the in vitro activities of 19 antimicrobial agents, including imipenem-relebactam, against (i) 106 CRE bloodstream isolates that primarily expressed Klebsiella pneumoniae carbapenemase (KPC) and (ii) 20 OXA-48-like-expressing CRE isolates. Ninety-five percent of CRE bloodstream isolates were susceptible to imipenem-relebactam. In contrast to their comparable activities against KPC-producing CRE strains, ceftazidime-avibactam was more active in vitro against OXA-48-like CRE strains than was imipenem-relebactam (90% susceptible versus 15% susceptible).

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Biosynthesis of Zinc Oxide Nanoparticles from Acacia nilotica (L.) Extract to Overcome Carbapenem-Resistant Klebsiella Pneumoniae

Molecules ◽

10.3390/molecules26071919 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1919

Author(s):

Elsayim Rasha ◽

AlOthman Monerah ◽

Alkhulaifi Manal ◽

Ali Rehab ◽

Doud Mohammed ◽

...

Keyword(s):

Electron Microscopy ◽

Zinc Oxide ◽

Klebsiella Pneumoniae ◽

Zinc Oxide Nanoparticles ◽

Acacia Nilotica ◽

Oxide Nanoparticles ◽

Zno Nps ◽

X Ray ◽

Carbapenem Resistant

Recently, concerns have been raised globally about antimicrobial resistance, the prevalence of which has increased significantly. Carbapenem-resistant Klebsiella pneumoniae (KPC) is considered one of the most common resistant bacteria, which has spread to ICUs in Saudi Arabia. This study was established to investigate the antibacterial activity of biosynthesized zinc oxide nanoparticles (ZnO-NPs) against KPC in vitro and in vivo. In this study, we used the aqueous extract of Acacia nilotica (L.) fruits to mediate the synthesis of ZnO-NPs. The nanoparticles produced were characterized by UV-vis spectroscopy, zetasizer and zeta potential analyses, X-ray diffraction (XRD) spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM). The antimicrobial activity of ZnO-NPs against KPC was determined via the well diffusion method, and determining minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), the results showed low MIC and MBC when compared with the MIC and MBC of Imipenem and Meropenem antibiotics. The results of in vitro analysis were supported by the results upon applying ZnO-NP ointment to promote wound closure of rats, which showed better wound healing than the results with imipenem ointment. The biosynthesized ZnO-NPs showed good potential for use against bacteria due to their small size, applicability, and low toxicity to human cells.

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