Introduction With the emerging potential crisis of untreatable gonorrhoea CDC and WHO have issued a call for new therapeutics options. Hence, this study was conducted to evaluate the in vitro efficacy of 21 dual antibiotic combinations of currently recommended as well as not in-use antibiotics, for treatment of multidrug resistant (MDR) and extensively drug resistant (XDR) Neisseria gonorrhoeae strains.
Methods Minimum inhibitory concentration (MIC) of 83 n. gonorrhoeae strains including 67 MDR and one XDR strain was determined by Etest for cefixime(IX), ceftriaxone(CRO), spectinomycin (SC), azithromycin (AZ), gentamicin (GM), moxifloxacin (MX) and ertapenem (ETP) alone and as 21 antimicrobial combinations by E-test fixed ratio method. Fractional inhibitory concentration index (FICI) was calculated for each combination and geometric means were determined. A FICI value of:≤0.5,>0.5 to≤1.0,>1.0 to≤4.0 and>4.0 denotes synergistic, additive, indifferent and antagonistic effects respectively. Statistical significance was determined by Mann-Whitney’s U-test.
Results The synergy/additive effect without any antagonism was observed in antimicrobial combinations of GM+ETP (34.9%/38.6%), MX+ETP (32.5%/36.2%), AZ+MX (20.5%/25.3%), IX+AZ (9.6%/13.3%) and CRO+AZ (4.8%/30.1%). Geometric mean of FICI for these combinations was 0.57, 0.76, 0.91, 1.0 and 1.15 respectively. Mean MICs of GM+ETP, MX+ETP and AZ+MX was significantly (p value<0.0001) less than that of the individual drugs. The combinations of SC+AZ, GM+MX, TX+GM and AZ+GM revealed 14.4%, 9.5%, 7.2% and 7.2% of antagonism with 0%, 8.4%, 15.7%, and 13.3% of synergistic effect respectively. No significant effects were observed with IX+SC, IX+MX, IX+ETP TX+SC, TX+MX, TX+ETP, SC+GM, SC+MX, SC+ETP and AZ+ETP.
Conclusion The study highlights the higher efficacy of GM+ETP, MX+ETP and AZ+MX combinations for MDR and XDR strains than currently recommended CRO+AZ and IX+AZ combinations. In the context of no new classes of antibiotics available, this presents a glimmer of hope to clinical management of the superbug N. gonorrhoeae.
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