Time-kill kinetics of antibiotics active against rapidly growing mycobacteria

Ferro, Beatriz E.; Ingen, Jakko van; Wattenberg, Melanie; Soolingen, Dick van; Mouton, Johan W.

doi:10.1093/jac/dku431

Cited by 72 publications

(62 citation statements)

References 16 publications

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“…This is in line with our previous studies (10,16) as well as with another recent study assessing the activities of several antibacterial drugs against Mycobacterium abscessus (17). The results of our in vitro study underline the need for potentiation of clarithromycin activity against M. avium.…”

supporting

confidence: 92%

Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro

Bax

Bakker-Woudenberg

Kate

et al. 2016

Antimicrob Agents Chemother

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bThe in vitro activities of clarithromycin and tigecycline alone and in combination against Mycobacterium avium were assessed. The activity of clarithromycin was time dependent, highly variable, and often resulted in clarithromycin resistance. Tigecycline showed concentration-dependent activity, and mycobacterial killing could only be achieved at high concentrations. Tigecycline enhanced clarithromycin activity against M. avium and prevented clarithromycin resistance. Whether there is clinical usefulness of tigecycline in the treatment of M. avium infections needs further study.A lthough the introduction of macrolides improved the success of treatment of Mycobacterium avium infections, the overall prognosis is still poor (1). Therefore, new powerful treatment strategies are needed. Tigecycline has been shown to have good in vitro activity against rapidly growing nontuberculous mycobacteria (NTM) (2-4), and success in clinical use has been reported when the drug is combined with macrolides (5, 6). In contrast, little is known about tigecycline activity against slowly growing NTM, including M. avium, and in vitro activity has not been demonstrated so far (7). In the present study, the bactericidal activities of clarithromycin and tigecycline alone and in combination against M. avium were assessed.Suspensions of the M. avium complex (MAC) 101 strain (kindly provided by L. S. Young, Kuzell Institute for Arthritis and Infectious Diseases, San Francisco, CA) were cultured in Middlebrook 7H9 broth (Difco Laboratories), supplemented with 10% oleic acid-albumin-dextrose-catalase (OADC; Baltimore Biological Laboratories, Baltimore, MD), 0.5% glycerol (Scharlau Chemie SA, Sentmenat, Spain), and 0.02% Tween 20 (Sigma Chemical Co., St. Louis, MO) under shaking conditions at 96 rpm at 37°C. Cultures on solid medium were grown on Middlebrook 7H10 agar (Difco), supplemented with 10% OADC and 0.5% glycerol, for 14 days at 37°C with 5% CO 2 . The susceptibility of the M. avium strain in terms of MICs determined according to the guidelines of the Clinical and Laboratory Standards Institutes (CLSI) (8) was 2 mg/liter for clarithromycin and 16 mg/liter for tigecycline. The concentration-and time-dependent killing capacities of clarithromycin and tigecycline were determined as previously described (9, 10). Briefly, M. avium cultures were exposed to antimicrobial drugs at 4-fold increasing concentrations for 21 days at 37°C under shaking conditions. At days 1, 3, 7, 10, and 21 during exposure, samples were collected, centrifuged at 14,000 ϫ g, and subcultured onto antibiotic-free solid medium. Subculture plates were incubated for 14 days at 37°C with 5% CO 2 to determine the number of CFU. The lower limit of quantification was 5 CFU/ml (log 0.7 ). To assess selection of clarithromycinresistant M. avium, subcultures were also performed on solid medium containing 32 mg/liter clarithromycin. The stabilities of clarithromycin and tigecycline in mycobacterium-free Middlebrook 7H9 broth at 37°C were determined using two test concentrations ...

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supporting

confidence: 92%

Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro

Bax

Bakker-Woudenberg

Kate

et al. 2016

Antimicrob Agents Chemother

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“…16,23,25 In addition, it exhibits more effective bacterial killing after 24 h relative to clarithromycin and cefoxitin. 36 However, the range of MICs of MABSC to amikacin varies widely, and a recent pharmacokinetic/pharmacodynamic model suggested that the current standard amikacin dose does not achieve the target C max /MIC ratio for M. abscessus for more than 75% of patients. 37 Therefore, the bactericidal activity against MABSC of current dosing ranges for amikacin has been questioned.…”

Section: Amikacinmentioning

confidence: 99%

Pulmonary Mycobacterium abscessus complex in children with cystic fibrosis: A practical management guideline

Andrew

Connell

Robinson

et al. 2019

J Paediatrics Child Health

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The treatment of Mycobacterium abscessus complex (MABSC) pulmonary infections is an emerging challenge in patients with cystic fibrosis (CF). Multidrug therapy for prolonged durations is required and carries the significant burden of drug‐related toxicity, cost and selective pressure for multiresistant bacteria. International guidelines acknowledge that clinical and in vitro data to support treatment regimens are limited, particularly in children. As part of a collaboration between the infectious diseases and respiratory units at our institution, we have developed a modified treatment guideline that aims to balance the aims of MABSC eradication and slowing disease progression with minimising drug toxicity and resistance. The outcomes of this treatment approach will be monitored and reported. In this manuscript, we discuss the available evidence for treatment choices and present our treatment guideline for paediatric patients with CF and MABSC infection.

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“…Single exposures of amikacin and clarithromycin were previously described for both M. abscessus (16) and M. avium (17).…”

Section: Susceptibilitymentioning

confidence: 99%

Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin

Ferro

Meletiadis

Wattenberg

et al. 2016

Antimicrob Agents Chemother

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e Multidrug therapy is a standard practice when treating infections by nontuberculous mycobacteria (NTM), but few treatment options exist. We conducted this study to define the drug-drug interaction between clofazimine and both amikacin and clarithromycin and its contribution to NTM treatment. Mycobacterium abscessus and Mycobacterium avium type strains were used. Time-kill assays for clofazimine alone and combined with amikacin or clarithromycin were performed at concentrations of 0.25؋ to 2؋ MIC. Phar- Multidrug therapy is a standard practice when treating mycobacterial infections. However, the pharmacodynamic (PD) interactions among the combined drugs are largely unknown. Understanding these interactions will help to identify synergistic combinations with increased antibacterial killing, which ultimately can result in a better treatment outcome.One of the promising combinations is amikacin and clofazimine, given the key role of amikacin in the treatment of NTM infections (2, 3) and the unique characteristics of clofazimine, like its prolonged half-life, its preferential accumulation inside macrophages (4), and the recently found bactericidal activity only after 2 weeks of treatment in the mouse model of tuberculosis (5).Clarithromycin, on the other hand, has substantial in vitro and clinical activity against Mycobacterium avium complex (MAC), and it has been long considered the cornerstone for Mycobacterium abscessus treatment (3).Hence, the examination of its interaction with clofazimine is interesting.Previous studies showed in vitro synergy between clofazimine and amikacin against both rapidly and slowly growing NTM (1, 6). The combination clarithromycin-clofazimine also showed synergy against MAC strains in checkerboard evaluation (7). These checkerboard titrations offer no information on the mechanism of synergistic activity, the exact killing activity of these combinations, or its concentration dependence. We therefore investigated the pharmacodynamic interactions between clofazimine and amikacin, and clofazimine and clarithromycin, against two key NTM species, using time-kill assays analyzed with two pharmacodynamic drug interaction models: the response surface model of Bliss independence (RSBI) and isobolographic analysis of Loewe additivity (ISLA) (8, 9). MATERIALS AND METHODS Bacterial

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Time-kill kinetics of antibiotics active against rapidly growing mycobacteria

Cited by 72 publications

References 16 publications

Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro

Tigecycline Potentiates Clarithromycin Activity against Mycobacterium avium In Vitro

Pulmonary Mycobacterium abscessus complex in children with cystic fibrosis: A practical management guideline

Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin

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