Synergetic Effects of Combined Treatment of Colistin With Meropenem or Amikacin on Carbapenem-Resistant Klebsiella pneumoniae in vitro

Abstract

The purpose of this study was to investigate the synergistic and bactericidal effects of combinations of colistin with meropenem or amikacin in vitro and provide laboratory data needed for development of therapeutic strategies for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection. We found that minimum inhibitory concentration (MIC) of colistin, meropenem and amikacin were 2∼32, 4∼256, and 1∼16384 µg/ml, respectively. The minimum bactericidal concentration of the antibiotics was either 1× or 2×MIC. Treatments of 6 CRKP isolates at 1 µg/ml colistin completely killed 2 of them and suppressed 4 others growth. 4 CRKP isolates at 16 µg/ml meropenem or amikacin completely killed and suppressed 2 others growth. 2 CRKP isolates showed synergic effects in all colistin combination and 3 CRKP isolates showed synergic effects in part of colistin combination. Our data suggest that colistin in combination with either meropenem or amikacin could be a valid therapeutic option against colistin-resistant CRKP isolates. Moreover, the combination of colistin-amikacin is less expensive to treat CRKP infections in Eastern Heilongjiang Province.

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

“…The antibacterial activities of fosfomycin and meropenem combination and colistin with meropenem combinations effective inhibited NDM and carbapenemase producing K . pneumoniae [ 34 , 39 ]. In addition, relebactam-imipenem combinations showed enhanced antibacterial activity against colistin resistant K .…”

Carbapenems for the Treatment of Pneumonia: A literature review regarding resistance, risk factors, and mortality

“…[58][59][60] Antibiotic Options to Overcome Carbapenem Resistance Other selection of antibiotic therapy as an alternative to overcome resistance to carbapenem antibiotics presented in Table 3. 51,[61][62][63][64][65] The threat of resistance and mortality due to some carbapenems-resistant gramnegative bacteria results in the discovery of monotherapy or combination therapy, such as colistin-tigecycline, colistin-carbapenem. 61 Colistin-tigecycline combination synergized in eight isolates and six isolates had bactericidal activity compared to the less active tigecycline -fosfomycin (only four isolates showed synergy and no bactericidal activity).…”

“…64 Later studies assessed the synergy of the colistin-amikacin/ meropenem combination as a therapeutic option for CRKP (Carbapenem-resistant Klebsiella pneumonia) infection that has been resistant to colistin. 65 Monotherapy regimen or a combination of colistin, cephalosporin, and carbapenems can be other therapeutic options when patients are resistant to carbapenem. According to the IDSA, alternative therapies for carbapenems resistance based on VAP and HAP treatment management, adapt to each hospital's germ sensitivity pattern and the microbial susceptibility associated with the type of pneumonia while considering possible side effects.…”

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“…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.…”

“…While the search for alternative and effective antimicrobial agents continues, various temporary measures are been employed for the treatment of infections caused by drug resistant bacterial isolates. Antibiotic combination therapy 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 effective inactivation of cells and microbial death.…”