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; Bala, Manju; Bhargava, Aradhana; Kakran, Monika; Bhatnagar, Ravi

doi:10.1371/journal.pone.0193678

Cited by 26 publications

(32 citation statements)

References 24 publications

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“…Minimum FICI values can be found in Table S3 in the supplemental material. Our cutoff values were designed as follows: an FICI value of <0.8 represents synergy, FICI values between 0.8 and 2 represent additive interactions, FICI values between 1 and 2 represent independent interactions, and an FICI value of ≥2 represents antagonism ( 63 – 66 ). Isobolograms were generated by plotting the FIC A and FIC B values as x , y coordinates.…”

Section: Methodsmentioning

confidence: 99%

Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community

Adamowicz

Harcombe

2020

Antimicrob Agents Chemother

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With the growing global threat of antimicrobial resistance, novel strategies are required for combatting resistant pathogens. Combination therapy, wherein multiple drugs are used to treat an infection, has proven highly successful in the treatment of cancer and HIV. However, this practice has proven challenging for the treatment of bacterial infections due to difficulties in selecting the correct combinations and dosages. An additional challenge in infection treatment is the polymicrobial nature of many infections, which may respond to antibiotics differently than a monoculture pathogen. This study tests whether patterns of antibiotic interactions (synergy, antagonism, or independence/additivity) in monoculture can be used to predict antibiotic interactions in an obligate cross-feeding co-culture. Using our previously described weakest link hypothesis, we hypothesized antibiotic interactions in co-culture based on the interactions we observed in monoculture. We then compared our predictions to observed antibiotic interactions in co-culture. We tested the interactions between ten previously identified antibiotic combinations using checkerboard assays. Although our antibiotic combinations interacted differently than predicted in our monocultures, our monoculture results were generally sufficient to predict co-culture patterns based solely on the weakest link hypothesis. These results suggest that combination therapy for cross-feeding multispecies infections may be successfully designed based on antibiotic interaction patterns for their component species.

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Section: Methodsmentioning

confidence: 99%

Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community

Adamowicz

Harcombe

2020

Antimicrob Agents Chemother

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“…25 Within the microbiology laboratory, studies have also examined the synergistic effect of various multi-drug combinations; for example, one such study recently evaluated 21 antimicrobial combinations and suggested five potential new dual candidate combinations, containing either gentamicin or ertapenem, for treatment of MDR and XDR N. gonorrhoeae infections. 26 Attention has once again focussed on ciprofloxacin as a potential agent for the treatment of gonorrhoea in settings where the prevalence of fluoroquinolone resistance is lower than 50%. Ciprofloxacin has the advantage that it can be prescribed as a single-dose oral regimen and it is highly efficacious in treating fluoroquinolone-susceptible gonococci in the oropharynx.…”

Section: Current Treatment Options For Gonorrhoeamentioning

confidence: 99%

New treatment options for Neisseria gonorrhoeae in the era of emerging antimicrobial resistance

Lewis¹

2019

Sex. Health

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Neisseria gonorrhoeae, the causative agent of gonorrhoea, has rapidly evolved from an exquisitely susceptible pathogen into a ‘superbug’ with the capacity to exhibit an extensively drug resistant (XDR) phenotype. The threat of untreatable gonorrhoea now looms on the horizon while the arsenal of effective antimicrobial agents diminishes with time. Ceftriaxone remains the mainstay of first-line therapy as a single agent or as the backbone of a dual therapy regimen. The implementation of new assays to facilitate ‘precision’ treatment, based on the prediction of N. gonorrhoeae susceptibility to old anti-gonococcal drugs, may enable sparing use of ceftriaxone in those countries that can afford this technology. A few existing drugs, such as ertapenem, can be repositioned to help manage multi-drug resistant and XDR gonorrhoea. Recent clinical trials involving solithromycin and delafloxacin have generated disappointing results in that both agents failed to show non-inferiority to conventional ceftriaxone-based regimens. At present, zoliflodacin and gepotidacin appear to be the most promising antimicrobial agents in clinical development. Both drugs performed well in eradicating urogenital gonorrhoea in recent Phase 2 trials; however, treatment failures were reported at the oropharyngeal site, which is an important site of infection in men who have sex with men and sex workers. Given this observation, it is unlikely that either of these new agents could be promoted for monotherapy of gonorrhoea. The pre-clinical pipeline remains relatively empty of agents likely to progress to clinical development for gonorrhoea treatment and increased investment into gonorrhoea-specific drug discovery is recommended.

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“…On a similar note, Singh et al assayed the potent utility of in vitro interactions of 21 dual therapy combinations against 95 N. gonorrhoeae strains [ 23 ]. Of these 21 combinations, five were novel introductions that are not included in any existing guidelines: gentamicin + ertapenem, moxifloxacin + ertapenem, spectinomycin + ertapenem, azithromycin + moxifloxacin, and cefixime + gentamicin.…”

Section: Future Perspectivesmentioning

confidence: 99%

Future Prospects for Neisseria gonorrhoeae Treatment

Suay-García

Pérez‐Gracia

2018

Antibiotics

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Gonorrhea is a sexually transmitted disease with a high morbidity burden. Incidence of this disease is rising due to the increasing number of antibiotic-resistant strains. Neisseria gonorrhoeae has shown an extraordinary ability to develop resistance to all antimicrobials introduced for its treatment. In fact, it was recently classified as a “Priority 2” microorganism in the World Health Organization (WHO) Global Priority List of Antibiotic-Resistant Bacteria to Guide Research, Discovery and Development of New Antibiotics. Seeing as there is no gonococcal vaccine, control of the disease relies entirely on prevention, diagnosis, and, especially, antibiotic treatment. Different health organizations worldwide have established treatment guidelines against gonorrhea, mostly consisting of dual therapy with a single oral or intramuscular dose. However, gonococci continue to develop resistances to all antibiotics introduced for treatment. In fact, the first strain of super-resistant N. gonorrhoeae was recently detected in the United Kingdom, which was resistant to ceftriaxone and azithromycin. The increase in the detection of resistant gonococci may lead to a situation where gonorrhea becomes untreatable. Seeing as drug resistance appears to be unstoppable, new treatment options are necessary in order to control the disease. Three approaches are currently being followed for the development of new therapies against drug-resistant gonococci: (1) novel combinations of already existing antibiotics; (2) development of new antibiotics; and (3) development of alternative therapies which might slow down the appearance of resistances. N. gonorrhoeae is a public health threat due to the increasing number of antibiotic-resistant strains. Current treatment guidelines are already being challenged by this superbug. This has led the scientific community to develop new antibiotics and alternative therapies in order to control this disease.

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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

Cited by 26 publications

References 24 publications

Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community

Weakest-Link Dynamics Predict Apparent Antibiotic Interactions in a Model Cross-Feeding Community

New treatment options for Neisseria gonorrhoeae in the era of emerging antimicrobial resistance

Future Prospects for Neisseria gonorrhoeae Treatment

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