Investigation of the <i>In Vitro</i> Effectiveness of Aztreonam/Avibactam, Colistin/Apramycin, and Meropenem/Apramycin Combinations Against Carbapenemase-Producing, Extensively Drug-Resistant <i>Klebsiella pneumoniae</i> Strains

Kiliç, Ümit; Köroğlu, Mehmet; Olmez, Mehmet; Altındiş, Mustafa

doi:10.1089/mdr.2019.0498

Cited by 10 publications

(11 citation statements)

References 31 publications

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“…While the search for alternative antimicrobial agents that can effectively control the spread of multidrug resistance continues, various temporary measures are been employed for the treatment of infections caused by drug resistant bacterial isolates. Antibiotic combination therapy PLOS ONE is a possible effective option which currently is attracting numerous research attention [34][35][36]. Combinations of antibiotics effectively inhibit microbial proliferation through a multi-target approach resulting in the microbial death.…”

Section: Synergistic Effects Of Colistin-antibiotics Combinationsmentioning

confidence: 99%

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

et al. 2021

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Multidrug resistant Enterobacterales have become a serious global health problem, with extended hospital stay and increased mortality. Antibiotic monotherapy has been reported ineffective against most drug resistant bacteria including Klebsiella pneumoniae, thus encouraging the use of multidrug therapies as an alternative antibacterial strategy. The present works assessed the antibacterial activity of colistin against K. pneumoniae isolates. Resistant isolates were tested against 16 conventional antibiotics alone and in combination with colistin. The results revealed that all colistin resistant isolates demonstrated multidrug resistance against the tested antibiotics except amikacin. At sub-inhibitory concentrations, combinations of colistin with amikacin, or fosfomycin showed synergism against 72.72% (8 of 11 isolates). Colistin with either of gentamicin, meropenem, cefoperazone, cefotaxime, ceftazidime, moxifloxacin, minocycline, or piperacillin exhibited synergism against 81.82% (9 of 11 isolates). Combinations of colistin with either of tobramycin or ciprofloxacin showed synergism against 45.45% (5 in 11 isolates), while combinations of colistin with imipenem or ceftolozane and tazobactam displayed 36.36% (4 of 11 isolates) and 63.64% (7 of 11 isolates) synergism. In addition, combinations of colistin with levofloxacin was synergistic against 90.91% (10 of 11 isolates). The results revealed that combinations of colistin with other antibiotics could effectively inhibit colistin resistant isolates of K. pneumoniae, and thus could be further explore for the treatment of multidrug resistant pathogens.

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Section: Synergistic Effects Of Colistin-antibiotics Combinationsmentioning

confidence: 99%

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

et al. 2021

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“…The alarming rate at which carbapenem resistance is spreading and causing significant clinical and socioeconomic problems worldwide, places this as a major threat to human health (Suay-Garc ıa and P erez-Gracia 2019). As the optimal treatment for infections by Kp-KPC remains undefined, promising substances and combinations are being investigated on an ongoing basis (Reyes et al 2019;Dietl et al 2020;Kilic et al 2020). Along these lines, the current study aimed to evaluate the efficacy of phendione, Cu-phendione and Ag-phendione alone and also when combined with IPM and MEM, in Kp-KPC clinical strains having different levels of carbapenem resistance.…”

Section: Resultsmentioning

confidence: 99%

Antibacterial activity and carbapenem re‐sensitizing ability of 1,10‐phenanthroline‐5,6‐dione and its metal complexes against KPC‐producingKlebsiella pneumoniaeclinical strains

Peregrino

Ventura

Borghi

et al. 2021

Lett Appl Microbiol

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Significance and Impact of the Study: This study shows, for the first time, the promising antimicrobial activity of phenanthroline derivatives against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae clinical strains. It is interesting to highlight that, in addition to a significant antimicrobial effect, studied compounds also showed a strong ability in reduce meropenem minimal inhibitory concentration values of some strains to therapeutic levels (re-sensitization). We believe that we are facing to a group of compounds that should be explored from a therapeutic perspective since they have demonstrated, in previous studies from our research group, low toxicity in vivo and effectiveness against several other microbial species.

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“…In the search of optimal treatments for infections by these carbapenemase-producing strains, combination among antibiotics is being explored (6,7), together with newer options like plazomicin, eravacycline and cefiderocol (8). The most commonly in vitro active and potentially useful drugs remain ceftazidime-avibactam and newer inhibitors combinations, gentamicin, amikacin, colistin, tigecycline, and fosfomycin (9).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Fosfomycin and Its Combination With Aminoglycosides in an Experimental Sepsis Model by Carbapenemase-Producing Klebsiella pneumoniae Clinical Strains

et al. 2021

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Carbapenemase-producing Klebsiella pneumoniae infections are an increasing global threat with scarce and uncertain treatment options. In this context, combination therapies are often used for these infections. The bactericidal and synergistic activity of fosfomycin plus amikacin and gentamicin was studied trough time–kill assays against four clonally unrelated clinical isolates of carbapenemase-producing K. pneumoniae, VIM-1, VIM-1 plus DHA-1, OXA-48 plus CTXM-15, and KPC-3, respectively. The efficacy of antimicrobials that showed synergistic activity in vitro against all the carbapenemase-producing K. pneumoniae were tested in monotherapy and in combination, in a murine peritoneal sepsis model. In vitro, fosfomycin plus amikacin showed synergistic and bactericidal effect against strains producing VIM-1, VIM-1 plus DHA-1, and OXA-48 plus CTX-M-15. Fosfomycin plus gentamicin had in vitro synergistic activity against the strain producing KPC-3. In vivo, fosfomycin and amikacin and its combination reduced the spleen bacterial concentration compared with controls groups in animals infected by K. pneumoniae producing VIM-1 and OXA-48 plus CTX-M-15. Moreover, amikacin alone and its combination with fosfomycin reduced the bacteremia rate against the VIM-1 producer strain. Contrary to the in vitro results, no in vivo efficacy was found with fosfomycin plus amikacin against the VIM-1 plus DHA-1 producer strain. Finally, fosfomycin plus gentamicin reduced the bacterial concentration in spleen against the KPC-3 producer strain. In conclusion, our results suggest that fosfomycin plus aminoglycosides has a dissimilar efficacy in the treatment of this severe experimental infection, when caused by different carbapenemase-producing K. pneumoniae strains. Fosfomycin plus amikacin or plus gentamycin may be useful to treat infections by OXA-48 plus CTX-M-15 or KPC-3 producer strains, respectively.

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Investigation of the In Vitro Effectiveness of Aztreonam/Avibactam, Colistin/Apramycin, and Meropenem/Apramycin Combinations Against Carbapenemase-Producing, Extensively Drug-Resistant Klebsiella pneumoniae Strains

Cited by 10 publications

References 31 publications

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

Synergistic antibacterial effects of colistin in combination with aminoglycoside, carbapenems, cephalosporins, fluoroquinolones, tetracyclines, fosfomycin, and piperacillin on multidrug resistant Klebsiella pneumoniae isolates

Antibacterial activity and carbapenem re‐sensitizing ability of 1,10‐phenanthroline‐5,6‐dione and its metal complexes against KPC‐producingKlebsiella pneumoniaeclinical strains

Efficacy of Fosfomycin and Its Combination With Aminoglycosides in an Experimental Sepsis Model by Carbapenemase-Producing Klebsiella pneumoniae Clinical Strains

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