In vitro interaction of some drug combinations to inhibit rapidly growing mycobacteria isolates from cats and dogs and these isolates' susceptibility to cefovecin and clofazimine

Bennie, C J M; To, Joyce; Martin, P; Govendir, Merran

doi:10.1111/avj.12279

Cited by 9 publications

(12 citation statements)

References 29 publications

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“…Our data for the MIC of each individual drug against MAP were comparable to previous studies that reported the MIC for CLA in the range between 0.25 and 0.5 μg/mL, CLO at 0.5–1 μg/mL, and RIF at 0.3–0.5 μg/mL [ 28 – 31 ]. Non-MAP strains such as M. smegmatis , M. intracellulare and M. avium strains were susceptible at higher dosages of >4 to 20 μg/mL of CLA, CLO, and RIF which confirmed previous studies [ 32 , 33 ].…”

Section: Discussionsupporting

confidence: 89%

RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis

2016

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BackgroundMycobacterium avium subspecies paratuberculosis (MAP) has been implicated as an etiological agent of Crohn’s disease (CD), a debilitating chronic inflammatory bowel disease. Clarithromycin (CLA), clofazimine (CLO), rifabutin (RIF) and other antibiotics have been used individually or in combinations with other drugs to treat mycobacterial diseases including CD. The treatment has varied by regimen, dosage, and duration, resulting in conflicting outcomes and additional suffering to the patients. RHB-104, a drug formula with active ingredients composed of (63.3 %) CLA, (6.7 %) CLO, and (30 %) RIF, has been recently subjected to investigation in an FDA approved Phase III clinical trial to treat patients with moderate to severe CD. In this study, we determined the efficacy of RHB-104 active ingredients against MAP strains isolated from the blood, tissue, and milk of CD patients. Based on fluorescence quenching technology using the Bactec MGIT Para-TB medium, we determined the minimum inhibitory concentration (MIC) of CLA, CLO, RIF individually and in dual and triple combinations against 16 MAP clinical strains and 19 other mycobacteria.ResultsThe MIC of all drugs against 35 different mycobacteria ranged between 0.25–20 μg/mL. However, the MIC of RHB-104 active ingredients regimen was the lowest at 0.25–10 μg/mL compared to the MIC of the other drugs at 0.5–20 μg/mL. The components of RHB-104 active ingredients at their individual concentrations or in dual combinations were not effective against all microorganisms compared to the triple combinations at MIC level. The MIC of CLA–CLO, CLA–RIF, and CLO–RIF regimens ranged between 0.5–1.25 μg/mL compared to 0.25 μg/mL of bactericidal effect of the triple combination.ConclusionThe data clearly demonstrated that lower concentrations of the triple combination of RHB-104 active ingredients provided synergistic anti-MAP growth activity compared to individual or dual combinations of the drugs. Consequently, this is favorable and should lead to tolerable dosage that is desirable for long-term treatment of CD and Mycobacterium avium complex disease.

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Section: Discussionsupporting

confidence: 89%

RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis

2016

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“…smegmatis) and slow-growing bacilli [Mtb, M. avium intracellulare complex (MAC) and M. leprae]. 54,[56][57][58][59] In addition, clofazimine acts synergistically with other antimicrobial agents, such as amikacin and clarithromycin, against several mycobacterial species, including M. avium and M. abscessus in vitro. 57 In the case of Mtb, clofazimine, at low concentrations, is active against both DS-and DR-TB strains in vitro and in vivo, exhibiting differential activities against Mtb populations according to the stage of growth.…”

Section: Antimicrobial Activity Of Clofaziminementioning

confidence: 99%

Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline

Cholo

Mothiba

Fourie

et al. 2016

J. Antimicrob. Chemother.

115

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Drug-resistant (DR)-TB is the major challenge confronting the global TB control programme, necessitating treatment with second-line anti-TB drugs, often with limited therapeutic efficacy. This scenario has resulted in the inclusion of Group 5 antibiotics in various therapeutic regimens, two of which promise to impact significantly on the outcome of the therapy of DR-TB. These are the 're-purposed' riminophenazine, clofazimine, and the recently approved diarylquinoline, bedaquiline. Although they differ structurally, both of these lipophilic agents possess cationic amphiphilic properties that enable them to target and inactivate essential ion transporters in the outer membrane of Mycobacterium tuberculosis. In the case of bedaquiline, the primary target is the key respiratory chain enzyme F/F-ATPase, whereas clofazimine is less selective, apparently inhibiting several targets, which may underpin the extremely low level of resistance to this agent. This review is focused on similarities and differences between clofazimine and bedaquiline, specifically in respect of molecular mechanisms of antimycobacterial action, targeting of quiescent and metabolically active organisms, therapeutic efficacy in the clinical setting of DR-TB, resistance mechanisms, pharmacodynamics, pharmacokinetics and adverse events.

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“…This drug is reported to be one of the more commonly used antimicrobials in veterinary medicine due to its broad spectrum and length of efficacy 54–56 . There are minimal data in the veterinary literature regarding cefovecin‐resistant bacteria in dogs, with the most recent study reporting in vitro mycobacteria isolate resistance in Australia 57 . With this new knowledge of cefovecin resistance seen in orbital abscesses, it is not recommended to give a subcutaneous injection of cefovecin for retrobulbar cellulitis.…”

Section: Discussionmentioning

confidence: 99%

Canine Retrobulbar Cellulitis and Abscessation in the Southeastern United States: A review of case management, diagnostic imaging, bacterial isolates, and susceptibility patterns

Herrmann

Hamor

Plummer

2021

Veterinary Ophthalmology

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Objective To describe common bacterial organisms cultured from retrobulbar cellulitis and abscess lesions, in vitro susceptibility patterns, common diagnostic techniques utilized, etiologies encountered, and prevalence of blindness. Animals studied Thirty‐eight dogs diagnosed with retrobulbar cellulitis or abscessation from 2007 to 2017. Procedure For cases of orbital cellulitis or abscess, signalment, orbital imaging, cytology, histopathology, bacterial culture and susceptibility testing, presence of vision at the initial examination and resolution, and presumed cellulitis/abscess etiology were recorded. Results Most cases were medically (78.9%) versus surgically managed (18.4%). Most common form of orbital imaging was computed tomography (48.5%) followed by ocular ultrasound (18.2%). Fifteen of eighteen cultures (83.3%) showed growth of aerobic bacterial organisms, anaerobic bacterial organisms, or both. Most common aerobic bacteria were gram‐negative bacilli (40.0%) followed by Corynebacterium sp. (26.7%) and α‐hemolytic Streptococci sp. (26.7%) but Micrococcus and Bacillus spp. were also identified. Most common anaerobic bacteria were gram‐negative bacilli (40.0%). Antibiotics with highest susceptibility patterns included gentamicin, followed equally by amoxicillin/clavulanic acid, cephalothin, chloramphenicol, and imipenem. No bacteria were susceptible to cefovecin. Six cases presented with vision loss due to retrobulbar disease (15.8%). Idiopathic (50%) disease and tooth root abscessation (23.7%) were most commonly diagnosed cause of orbital disease. Conclusion Retrobulbar cellulitis/abscess is a serious and vision‐threatening process, which can be effectively managed by broad‐spectrum antibiotics such as gentamicin or amoxicillin/clavulanic acid, but not cefovecin. This study identified three organisms that have not been previously reported to be associated with orbital cellulitis (Corynebacterium sp., Bacillus sp. and Micrococcus sp.).

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In vitro interaction of some drug combinations to inhibit rapidly growing mycobacteria isolates from cats and dogs and these isolates' susceptibility to cefovecin and clofazimine

Abstract: Drugs commonly used for treatment of RGM, when tested as combinations, do not appear to antagonise one another in vitro. Cefovecin is not efficacious for treatment of RGM infections.

Cited by 9 publications

References 29 publications

RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis

RHB-104 triple antibiotics combination in culture is bactericidal and should be effective for treatment of Crohn’s disease associated with Mycobacterium paratuberculosis

Mechanisms of action and therapeutic efficacies of the lipophilic antimycobacterial agents clofazimine and bedaquiline

Canine Retrobulbar Cellulitis and Abscessation in the Southeastern United States: A review of case management, diagnostic imaging, bacterial isolates, and susceptibility patterns

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