scholarly journals In Vitro Susceptibility Testing of Omadacycline against Nontuberculous Mycobacteria (NTM)

Author(s):  
Barbara A. Brown-Elliott ◽  
Richard J. Wallace

Nontuberculous mycobacteria (NTM) infections are increasing globally. Mycobacterium avium complex (MAC) and M. abscessus complex are the most frequently encountered NTM and oral treatment options are extremely limited for these pathogens, especially for the M. abscessus complex. In this study, the in vitro potency of omadacycline, a new tetracycline derivative, was tested against 111 isolates of NTM. MIC testing was performed as recommended by the Clinical and Laboratory Standards Institute against 70 isolates of rapidly growing mycobacteria (RGM) of which >90% were tetracycline resistant. These included M. abscessus subsp. abscessus (20), M. abscessus subsp. massiliense (3), M. chelonae (15), M. immunogenum (7), the M. fortuitum group including six doxycycline resistant isolates (12), and the M. mucogenicum group including four doxycycline resistant isolates (10). Forty-one isolates of slowly growing mycobacteria (SGM) species including 16 isolates of MAC were also tested. Omadacycline was active against all RGM species with an MIC50 range of 0.004-0.25 and 0.06-1 μg/ml for 80% and 100% inhibition, respectively. For M. abscessus subsp. abscessus, MIC50 values were 0.06 and 0.12 μg/ml with 80% and 100% inhibition respectively. There was considerable trailing of the omadacycline endpoint with the RGM. MICs for tigecycline exhibited no trailing and were generally within 1-2 dilutions of the 100% inhibition omadacycline MIC values. While there was no trailing observed in SGM, omadacycline MICs were higher (MIC range 8->16 μg/ml, N = 41) as previously noted with tigecycline. This study supports further research of omadacycline including clinical trials for the treatment of RGM infections, especially M. abscessus.

Author(s):  
Barbara A. Brown Elliott ◽  
Richard J. Wallace

Nontuberculous mycobacteria (NTM) infections are increasing globally. Mycobacterium avium complex (MAC) and M. abscessus complex are the most commonly reported NTM. Oral treatment options are limited, especially for the M. abscessus. We tested delafloxacin, a new oral fluoroquinolone, against 131 isolates of NTM. Delafloxacin microdilution MICs were performed as recommended by the Clinical and Laboratory Standards Institute using cation adjusted Mueller Hinton broth. The rapidly growing mycobacteria tested included: M. abscessus subsp. abscessus (16) and subsp. massiliense (5), M. chelonae (11), M. immunogenum (5), M. fortuitum group (13), M. porcinum (7), M. senegalense (7), M. mucogenicum group (5), and M. goodii (1). For the slowly growing NTM (SGM), M. avium (16), M. intracellulare (13), M. chimaera (9), M. arupense (5), M. simiae (5), M. lentiflavum (4), M. kansasii (6), and M. marinum (3) were tested. Delafloxacin was most active in vitro against M. fortuitum and M. mucogenicum groups and M. kansasii with MIC50 values of 0.12-0.5 μg/mL (MIC range 0.001-4 μg/mL) compared to ≤0.06->4 μg/mL for ciprofloxacin and ≤0.06->8 μg/mL for moxifloxacin. For other SGM (including MAC), and the M. abscessus/chelonae, the delafloxacin MIC range was 8->16 μg/mL compared to ciprofloxacin and moxifloxacin of 0.5->4 μg/mL and ≤0.06-8 μg/mL, respectively. To our knowledge, this is the first MIC study with delafloxacin to use Clinical and Laboratory Standards Institute (CLSI) recommended methods. This study illustrates the potential utility of delafloxacin in treatment of infections due to some NTM.


1997 ◽  
Vol 41 (7) ◽  
pp. 1558-1561 ◽  
Author(s):  
J E Lutz ◽  
K V Clemons ◽  
B H Aristizabal ◽  
D A Stevens

SCH 56592 (SCH) is a new triazole antifungal with a broad spectrum of activity. In vitro susceptibility testing against five strains of Coccidioides immitis revealed MICs from 0.39 to 3.13 microg/ml and minimal fungicidal concentrations from 1.56 to 3.13 microg/ml. A murine model of systemic coccidioidomycosis was established in female CD-1 mice. Groups received either no treatment or oral therapy with fluconazole at 10 or 100 mg/kg of body weight; itraconazole at 10 or 100 mg/kg; SCH at 0.5, 2, 10, or 25 mg/kg; or its methylcellulose diluent alone. Therapy began 2 days postinfection and continued once daily for 19 days. Surviving mice were euthanized 49 days postinfection, and infectious burdens were determined by culture. All drugs were superior to no-treatment or diluent-treatment controls (P < 0.001) in prolonging survival but were not significantly different from one another. Itraconazole at 100 mg/kg was superior to fluconazole in reduction of CFU in the spleen, liver, and lung (P < 0.01 to 0.001). SCH at 0.5 mg/kg was superior to either fluconazole or itraconazole at 10 mg/kg in reduction of CFU in all three organs (P < 0.05 to 0.001). SCH at 2 mg/kg was not significantly different from itraconazole at 100 mg/kg in all three organs. SCH at 10 and 25 mg/kg was superior to either dose of fluconazole or itraconazole in all three organs (P < 0.05 to 0.001). In terms of reduction of CFU, SCH was > or = 200-fold as potent as fluconazole and > or = 50-fold as potent as itraconazole. There was a clear dose-responsive relationship for SCH in each of the organs. It is noteworthy that SCH effected cures (no detectable C. immitis in any organ) in 1 of 9, 6 of 10, or 9 of 9 surviving mice in animals given 2, 10, or 25 mg/kg, respectively. Neither fluconazole nor itraconazole cured any survivor. SCH has potent, fungicidal activity in vivo against C. immitis. It should be considered for clinical trials in patients with coccidioidomycosis.


2017 ◽  
Vol 55 (6) ◽  
pp. 1747-1754 ◽  
Author(s):  
Barbara A. Brown-Elliott ◽  
Richard J. Wallace

ABSTRACT Tedizolid is a new oxazolidinone with improved in vitro and intracellular potency against Mycobacterium tuberculosis , including multidrug-resistant strains, and some species of nontuberculous mycobacteria (NTM) compared with that of linezolid. Using the current Clinical and Laboratory Standards Institute (CLSI)-recommended method of broth microdilution, susceptibility testing of 170 isolates of rapidly growing mycobacteria showed equivalent or lower (1- to 8-fold) MIC 50 and/or MIC 90 values for tedizolid compared with that for linezolid. The tedizolid MIC 90 values for 81 isolates of M. abscessus subsp. abscessus and 12 isolates of M. abscessus subsp. massiliense were 8 μg/ml and 4 μg/ml, respectively, compared with linezolid MIC 90 values of 32 μg/ml for both. The MIC 90 values for 20 isolates of M. fortuitum were 2 μg/ml for tedizolid and 4 μg/ml for linezolid. Twenty-two isolates of M. chelonae had tedizolid and linezolid MIC 90 s of 2 μg/ml and 16 μg/ml, respectively. One hundred forty-two slowly growing NTM, including 7/7 M. marinum , 7/7 M. kansasii , and 7/11 of other less commonly isolated species, had tedizolid MICs of ≤1 μg/ml and linezolid MICs of ≤4 μg/ml. One hundred isolates of Mycobacterium avium complex and eight M. simiae isolates had tedizolid MIC 50 s of 8 μg/ml and linezolid MIC 50 s 32 and 64 μg/ml, respectively. Nine M. arupense isolates had MIC 50 s of 4 μg/ml and 16 μg/ml for tedizolid and linezolid, respectively. These findings demonstrate a greater in vitro potency of tedizolid than linezolid against NTM and suggest that an evaluation of tedizolid as a potential treatment agent for infections caused by selected NTM is warranted.


2018 ◽  
Vol 6 ◽  
pp. 2050313X1880407 ◽  
Author(s):  
Michael Sander ◽  
Judith L Isaac-Renton ◽  
Megan A Sander

We report a case of cutaneous Mycobacterium marinum infection with the unusual reported features of pruritus and paresthesia. In addition, we report a lack of in-vivo response to antibiotics based on in-vitro susceptibility testing.


1998 ◽  
Vol 42 (2) ◽  
pp. 471-472 ◽  
Author(s):  
M. Hong Nguyen ◽  
Christine Y. Yu

ABSTRACT In vitro susceptibility testing for 50 clinical isolates of fluconazole-susceptible or -resistant Cryptococcus neoformans was performed with itraconazole and voriconazole. Voriconazole was more potent than itraconazole for fluconazole-susceptible isolates and as potent as itraconazole for fluconazole-susceptible dose-dependent isolates and for fluconazole-resistant isolates. For fluconazole-resistant isolates, the voriconazole and itraconazole MICs ranged from 1 to 2 μg/ml.


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