Slowly growing mycobacteria (SGM) species are ubiquitous organisms that are widely distributed in the environment [
At present, standard therapeutic strategies to treat SGM infections are lacking. In this study, 19 new antimicrobial agents were tested against 33 reference SGM pathogens using a modified broth microdilution method with the aim of identifying optimal schemes according to the Clinical Laboratory Standards Institute (CLSI) (USA) [
Thirty-three international reference SGM strains were purchased from Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ) and the American Type Culture Collection (ATCC), including
The MIC (
Sp. (international code) | FOX | CFP | CMZ | FEP | RPT | RBT | AZM | CLR | ROX | THI |
---|---|---|---|---|---|---|---|---|---|---|
|
>256 | 128 | >256 | >256 | 4 |
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>256 |
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>256 | 2 |
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>256 |
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>256 | 256 | 256 | 128 | 16 | 4 |
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256 |
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4 |
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256 |
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256 | 16 | 32 | 32 | 32 | 32 | >256 |
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1 |
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256 |
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32 |
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>256 |
|
128 | 128 |
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32 |
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128 |
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16 | 16 |
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64 |
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>256 |
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256 | >32 | 32 |
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>256 |
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8 |
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256 |
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8 | 2 |
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32 |
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128 | >256 |
|
256 | 32 |
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>256 |
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64 |
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4 | 1 |
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256 |
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64 | >32 | 32 |
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64 |
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64 | >32 |
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256 |
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>32 |
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32 | >256 |
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32 | >32 |
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64 |
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1 | >32 |
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>32 |
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8 |
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64 |
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32 |
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>32 |
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32 |
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128 |
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2 | >32 |
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4 | >32 |
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>32 |
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64 |
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256 |
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>32 |
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1 | >32 |
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128 |
Sp. (international code) | DOX | MIN | TIG | MEM | CLO | SMZ | PASI | LNZ | DAP |
---|---|---|---|---|---|---|---|---|---|
|
>256 | 64 | 32 | >256 | 16 |
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32 | 32 | >256 |
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256 | 64 |
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>256 |
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64 |
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8 |
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16 |
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4 |
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>256 | 16 | 16 | >256 |
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16 | 32 | 16 |
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2 |
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32 |
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8 |
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32 | 256 | >256 |
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4 |
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32 |
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8 |
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64 |
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64 |
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8 | 32 |
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32 |
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64 | >256 |
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64 |
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128 |
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32 | 256 | >256 | 32 | 256 |
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16 |
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1 |
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8 |
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8 |
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256 |
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8 |
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16 |
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8 |
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8 |
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4 |
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64 | 64 | 16 |
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32 | 256 | 64 | 32 | 256 |
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>256 | 16 |
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32 | >256 | 16 | 32 | >256 |
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>256 | 128 |
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4 | 128 | 128 |
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128 |
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>256 | 128 | 8 |
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32 |
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128 | 32 | 8 |
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128 | 128 | 16 |
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2 |
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128 |
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4 |
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32 |
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32 |
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8 |
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64 | 32 |
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2 |
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32 |
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32 |
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4 |
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4 |
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128 | 8 |
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4 |
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128 |
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8 |
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256 | 256 |
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1 |
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256 |
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8 |
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256 |
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8 |
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8 |
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2 |
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4 |
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4 |
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256 | 16 |
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16 |
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8 |
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>256 | 16 | 16 |
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256 | 16 |
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256 |
Nineteen chemicals were purchased from Sigma-Aldrich Company: cefoxitin (FOX), cefoperazone (CFP), cefmetazole (CMZ), cefepime (FEP), rifapentine (RPT), rifabutin (RBT), azithromycin (AZM), clarithromycin (CLR), roxithromycin (ROX), thioacetazone (THI), doxycycline (DOX), minocycline (MIN), tigecycline (TIG), meropenem (MEM), clofazimine (CLO), sulfamethoxazole (SMZ), pasiniazid (PASI), linezolid (LNZ), and dapsone (DAP). All of the antituberculous agents were freshly prepared.
SGM strains were incubated using Difco Middlebrook 7H10 Agar (BD company) with 5% oleic acid-albumin-dextrose-catalase (OADC) [
The MIC (
Susceptibility | Intermediate susceptibility | Resistance | |
---|---|---|---|
Cefoxitin | ≤16 | 32–64 | ≥128 |
Cefoperazone | ≤16 | 32–64 | ≥128 |
Cefmetazole | ≤16 | 32–64 | ≥128 |
Cefepime | ≤16 | 32–64 | ≥128 |
Rifapentine | — | — | >1 |
Rifabutin | — | — | >2 |
Azithromycin | ≤8 | 16 | ≥32 |
Clarithromycin | ≤8 | 16 | ≥32 |
Roxithromycin | ≤8 | 16 | ≥32 |
Thioacetazone | — | — | ≥8 |
Doxycycline | ≤1 | 2–4 | ≥8 |
Meropenem | ≤4 | 8–16 | ≥32 |
Clofazimine | — | — | ≥1 |
Sulfamethoxazole | ≤38 | — | ≥76 |
Pasiniazid | — | — | ≥2 |
Minocycline | ≤1 | 2–4 | ≥8 |
Linezolid | ≤8 | 16 | ≥32 |
Dapsone | — | — | ≥4 |
Tigecycline | ≤1 | 2–4 | ≥8 |
The antimicrobial susceptibility profiles of the 33 SGM reference species to 19 antibacterial agents are presented in Table
The drug susceptibility profiles of the tested organisms revealed that
Susceptibility of 33 international standard slowly growing mycobacterial strains to 19 antibacterial agents.
Sp. (international code) | FOX | CFP | CMZ | FEP | RPT | RBT | AZM | CLR | ROX | THI | DOX | MIN | TIG | MEM | CLO | SMZ | PASI | LNZ | DAP | Susceptibility rate (%) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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26.32 |
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94.74 |
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63.16 |
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84.21 |
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26.32 |
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94.74 |
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94.74 |
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94.74 |
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52.63 |
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78.95 |
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94.74 |
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78.95 |
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63.16 |
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52.63 |
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78.95 |
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89.47 |
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57.89 |
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78.95 |
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94.74 |
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47.37 |
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52.63 |
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52.63 |
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52.63 |
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68.42 |
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84.21 |
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68.42 |
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89.47 |
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57.89 |
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68.42 |
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89.47 |
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63.16 |
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73.68 |
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57.89 |
The sensitivity profiles of 33 reference slowly growing mycobacteria to 19 antimicrobial agents.
The sensitivity profiles of the
In this study, 19 antimicrobial susceptibility tests were performed against 33 SGM organisms by a Microplate Alamar Blue Assay. The current first-line drugs for the treatment of nontuberculous mycobacteria are capreomycin, clarithromycin, and rifampin. And the current second-line drugs for the treatment of nontuberculous mycobacteria are moxifloxacin, linezolid, amikacin, ciprofloxacin, ethambutol, isoniazid, rifabutin, streptomycin, and trimethoprim-sulfamethoxazole [
In recent studies [
Our findings present the drug susceptibility profiles of representative SGM species to a range of antimicrobial agents and provide insight into potentially effective therapeutic strategies. In the future, susceptibility testing of clinical isolates may help to tailor therapeutic strategies to individual patients. Combination therapy should also be explored as a means to increase the efficacy of drug treatment against SGM pathogens. Furthermore, the synergistic activity of some drugs will be analyzed, and drug susceptibility in vivo response must be performed in our recent research.
The authors have declared that no conflicts of interest exist.
This paper is financially supported by the Project of the National Key Program of Mega Infectious Diseases (no. 2013ZX10004-101), the Key Project of the State Key Laboratory for Infectious Disease Prevention and Control (no. 2014SKLID104), Science and Technology of Shanxi Province for Youth Science Foundation (no. 2016021161), a Science and Technology Innovation Team support project (no. CX201412) from Changzhi Medical College, and innovation project of university students in Shanxi Province (no. 2016303). The authors thank the staffs of National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention.