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Published on: April 18, 2019
In Vitro Synergistic Effect of Colistin with Fosfomycin Against Carbapenem-Resistant Klebsiella pneumoniae
Chethankumar P1, Tejashree A1, Neetha S Murthy1
1Microbiology, JSS Medical College and Hospital, JSS Academy of Higher Education and Research (JSSAHER), Mysore, IND.
Background:
The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae, a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method.
Methods:
A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method.
Results:
Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001).
Conclusion:
This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.
Insights
This study found that combining fosfomycin with colistin shows promising in-vitro synergy against carbapenem-resistant Klebsiella pneumoniae (CRKP). This combination therapy may help overcome resistance and reduce mortality rates associated with CRKP infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Rising antimicrobial resistance, particularly carbapenem-resistant Klebsiella pneumoniae (CRKP), poses a significant global health threat.
- CRKP infections present treatment challenges due to multidrug resistance, necessitating novel therapeutic strategies.
- Colistin is a critical reserve antibiotic for CRKP, but monotherapy risks resistance development and toxicity.
Purpose of the Study:
- To evaluate the in-vitro synergistic effect of fosfomycin when combined with colistin against CRKP isolates.
- To determine the potential of fosfomycin-colistin combination therapy in combating CRKP infections.
Main Methods:
- A prospective laboratory study was conducted over one year.
- Carbapenem resistance in Klebsiella pneumoniae isolates was confirmed using the VITEK-2 compact system.
- Minimum Inhibitory Concentrations (MICs) of colistin and fosfomycin were determined by broth microdilution (BMD).
- Synergistic activity was assessed using the BMD-based Checkerboard method.
Main Results:
- Out of 50 CRKP isolates, 72% demonstrated synergism with the fosfomycin-colistin combination.
- Partial synergism was observed in 12% of isolates, while 16% showed indifference.
- No antagonism or additivity was noted, with statistically significant results (p < 0.00001).
Conclusions:
- The study demonstrates promising in-vitro synergy between fosfomycin and colistin against CRKP.
- Combination therapy with fosfomycin and colistin may mitigate resistance and toxicity associated with colistin monotherapy.
- This approach offers potential benefits in reducing CRKP-associated mortality and improving patient outcomes.
