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In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era.

ABSTRACT: Recent WHO guidelines recommend dual therapy with ceftriaxone or cefixime plus azithromycin for gonorrhea. Azithromycin in combination with gentamicin or spectinomycin has been recommended in treatment failure cases. Due to emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) Neisseria gonorrhoeae strains, it is important to look for efficacy of these combinations and also of others that might be used in future. Therefore, we aimed to evaluate in vitro synergy of 21 dual combinations including current and alternative WHO recommended treatment regimens and other dual combinations.The potential utility of in-vitro interactions of 21 combinations was investigated against 95 N. gonorrhoeae strains including 79 MDR and one XDR strain collected during March 2013 to July 2017 and fractional inhibitory concentration index (FICI) was calculated. These 21 combinations comprised of two WHO currently recommended (cefixime+azithromycin, ceftriaxone+azithromycin); two WHO recommended in treatment failure cases (azithromycin+gentamicin, spectinomycin+azithromycin) and other 17 combinations.FICI of the four WHO recommended antimicrobial combinations were higher (>1.0) than the five novel combinationbreeds (FICI range 0.603-0.951) in the study i.e. gentamicin+ertapenem, moxifloxacin+ertapenem, spectinomycin+ertapenem, azithromycin+ moxifloxacin, cefixime+gentamicin. No antagonistic effect of the above four WHO recommended combinations except spectinomycin+azithromycin (FICI = 4.25) was observed for the XDR strain. Out of above five novel combinations, four combinations produced high synergistic effects in overall 95 strains and also for the XDR strain with FICI of 0.13 to 0.38. Antagonistic effects varying from 3.2 to 12.6% were observed for 10 out of 21 tested combinations (azithromycin in combination with gentamicin and spectinomycin; ceftriaxone with moxifloxacin, gentamicin, spectinomycin and ertapenem; spectinomycin with moxifloxacin and gentamicin; cefixime and gentamicin combination with moxifloxacin).WHO recommended cefixime+azithromycin, ceftriaxone+azithromycin combinations having no antagonism indicates their continuing clinical utility. Highest antagonism without any synergistic effect for the WHO recommended spectinomycin+azithromycin in treatment failure cases suggests that this combination should be evaluated further both in vitro and in vivo. Highest synergistic or additive effect without any antagonistic effect of the above five novel combinations suggests that these may be recommended for treatment in future.

SUBMITTER: Singh V

PROVIDER: S-EPMC5839552 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era.

Singh Vikram V Bala Manju M Bhargava Aradhana A Kakran Monika M Bhatnagar Ravi R

PloS one 20180306 3

<h4>Background</h4>Recent WHO guidelines recommend dual therapy with ceftriaxone or cefixime plus azithromycin for gonorrhea. Azithromycin in combination with gentamicin or spectinomycin has been recommended in treatment failure cases. Due to emergence of multi-drug resistant (MDR) and extensively-drug resistant (XDR) Neisseria gonorrhoeae strains, it is important to look for efficacy of these combinations and also of others that might be used in future. Therefore, we aimed to evaluate in vitro ...[more]

PMID: 29509792

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Project description:BackgroundFixed-dose combinations (FDC) are medicine formulations that combine two or more ingredients in fixed ratios in a single dose form. Although advantageous in tuberculosis and malaria (efficacy, adherence, protection against resistance), only a few antibiotic FDC (FDC-AB) have been developed along full microbiological, pharmacological and clinical validation and safety studies. The World Health Organization (WHO) database of Access, Watch and Reserve (AWaRe) antibiotics contains, since 2021, a list of "Not Recommended" FDC-AB (n = 103) which are rejected for use in clinical practice. BODY: The share of non-recommended FDC-AB in global antimicrobial use (2000-2015) was < 3% but substantially higher in middle income countries. The share increases over time, but recent data particular concerning sub-Saharan Africa are rare. Along three non-recommended FDC-AB listed in the Tanzanian National Essential Medicine List (ampicillin-cloxacillin, flucloxacillin-amoxicillin and ceftriaxone-sulbactam) we discuss the concerns and reasons behind use of these products. Non-recommended FDC-AB have poor rationale (ratios of both ingredients), lack evidence of efficacy (pharmacological, microbiological and clinical), have difficulties in dosing (underdosing of the single ingredients, absence of pediatric dosing) and risks of safety (additive toxicity). They are expected to fuel antimicrobial resistance (unnecessary broad spectrum coverage) and are incompatible with antimicrobial stewardship. The specific context of low- and middle-income countries contributes to their increased use: at the side of prescriber and supplier are the lack of diagnostics, poor training in antibiotic prescribing, patients' preferences, role-model of senior prescribers and pharmaceutical promotion. International market mechanisms include economic motivation for development, branding and promotion, poor access to the single antibiotic forms and weak national regulatory capacity.Conclusion and implicationsThere is an urgent need for monitoring consumption of non-recommended FDC-AB in low- and middle-income countries, particular in Sub-Saharan Africa. A multinational and multisectoral antimicrobial stewardship strategy is needed in order to abolish the use of non-recommended FDC-AB.

Dataset Information

In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era.

Publications

In vitro efficacy of 21 dual antimicrobial combinations comprising novel and currently recommended combinations for treatment of drug resistant gonorrhoea in future era.

Similar Datasets

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