Macrolide resistance rarely occurs in patients also receiving ethambutol and a rifamycin. Macrolide-resistant MAC lung disease requires aggressive drug and surgical therapy for cure.

Current guidelines for macrolide/azalide-based therapies for NB MAC lung disease result in favorable microbiologic outcomes for most patients without promotion of macrolide resistance. Intermittent therapy is effective and significantly better tolerated than daily therapy. Microbiologic recurrences during or after therapy are common and most often due to reinfection MAC genotypes.

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Nontuberculous mycobacteria (NTM) are potential respiratory pathogens in cystic fibrosis (CF). To assess the species-specific prevalence and risk factors for acquisition, we conducted a prospective, cross-sectional study of the prevalence of NTM and clinical features of patients at 21 U.S. centers. Almost 10% of patients with CF who were 10 years or older were included (n = 986). The overall prevalence of NTM in sputum was 13.0% (range by center, 7-24%). Mycobacterium avium complex (72%) and Mycobacterium abscessus (16%) were the most common species. When compared with patients with CF without NTM, culture-positive subjects were older (26 vs. 22 years, p < 0.001), had a higher FEV1 (60 vs. 54%, p < 0.01), higher frequency of Staphylococcus aureus (43 vs. 31%, p < 0.01), and lower frequency of Pseudomonas aeruginosa (71 vs. 82%, p < 0.01). Molecular typing revealed that almost all patients within each center had unique NTM strains. In summary, NTM are common in patients with CF, but neither person-to-person nor nosocomial acquisition explained the high prevalence. Older age was the most significant predictor for isolation of NTM. The clinical significance of NTM in CF is incompletely defined, but patients with these organisms should be monitored with repeat cultures.

We compared the in vitro activity of the glycylcycline tigecycline (formerly GAR-936) with those of tetracycline, doxycycline, and minocycline by broth microdilution against 76 isolates belonging to seven species of rapidly growing mycobacteria (RGM) and 45 isolates belonging to five species of slowly growing nontuberculous mycobacteria (NTM). By using a resistance breakpoint of >4 g/ml for tigecycline and >8 g/ml for tetracycline, all RGM were highly susceptible to tigecycline, with inhibition of 50% of isolates at <0.12 g/ml and inhibition of 90% of isolates at 0.25 g/ml for Mycobacterium abscessus and inhibition of both 50 and 90% of isolates at <0.12 g/ml for M. chelonae and the M. fortuitum group. The MICs of tigecycline were the same for tetracycline-resistant and -susceptible strains, and RGM isolates were 4-to 11-fold more susceptible to tigecycline than to the tetracyclines. In contrast, no slowly growing NTM were susceptible to tigecycline, and isolates of M. marinum and M. kansasii were less susceptible to this agent than to minocycline. This new antimicrobial offers exciting therapeutic potential for the RGM, especially for isolates of the M. chelonae-M. abscessus group, against which the activities of the currently available drugs are limited.Treatment of infections due to rapidly growing mycobacteria (RGM) remains difficult, in part because of resistance to the first-line antituberculous agents and also in part because of resistance to almost all antibacterial agents (3, 21). The only drugs with activity against all three major pathogenic species (Mycobacterium chelonae, M. abscessus, and M. fortuitum) are amikacin (13) and clarithromycin (4). In vitro studies with prior glycylcyclines (N,N-dimethylglycylamido-minocycline ) have shown this class of agents to be extremely active against this group of organisms, including tetracycline-resistant strains (1, 3). The latest glycylcycline, tigecycline (GAR-936), has shown excellent activity against many tetracycline-resistant bacterial species (1, 8, 17; R. N. Jones, A. C. Gales, L. M. Deshpande, D. M. Johnson, and D. J. Biedenbach, poster 407, 39th Intersci. Conf. Antimicrob. Agents Chemother., 1999). With this in mind, we undertook a comparative study of the in vitro susceptibilities of multiple species of nontuberculous mycobacteria (NTM) to tetracycline, minocycline, doxycycline, and tigecycline.(A portion of this study was presented at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy, 16 to 19 December 2001, Chicago, Ill.) MATERIALS AND METHODSOrganisms. Clinical mycobacterial isolates submitted to the Mycobacterial/ Nocardia Laboratory at The University of Texas Health Center for susceptibility testing and selected reference strains were chosen for testing. Clinical isolates were tested upon receipt in the laboratory, while the reference strains were taken from frozen stocks stored at Ϫ70°C in Trypticase soy broth with 15% glycerol. We also tested 45 isolates of slowly growing NTM that included 11 M. avium complex, 10 M. ...

Linezolid is an oxazolidinone available as an oral drug which has activity against most gram-positive bacteria. However, few species of the genus Mycobacterium have been studied. We tested 249 clinical isolates and 10 reference strains of rapidly growing mycobacteria for susceptibility to linezolid by broth microdilution. Clinical species included the Mycobacterium fortuitum group (n ‫؍‬ 74), M. abscessus (n ‫؍‬ 98), M. chelonae (n ‫؍‬ 50), M. mucogenicum (n ‫؍‬ 10), and M. fortuitum third biovariant complex (10). The modal MIC for M. mucogenicum was 1.0 g/ml, and the MIC at which 90% of the isolates tested are inhibited (MIC 90 ) was 4 g/ml; the modal MIC for the M. fortuitum group was 4 g/ml, and the MIC 90 was 16 g/ml; the modal MIC for the M. fortuitum third biovariant complex was 4 g/ml, and the MIC 90 was 8 g/ml; the modal MIC for M. chelonae was 8 g/ml, and the MIC 90 was 16 g/ml; and the modal MIC for M. abscessus was 32 g/ml, and the MIC 90 was 64 g/ml. Based on peak levels of linezolid in serum of 15 to 20 g/ml, we propose the following broth MIC breakpoints for these species: susceptible, < 8 g/ml; moderately susceptible, 16 g/ml; and resistant, >32 g/ml). These studies demonstrate the excellent potential of linezolid for therapy of rapidly growing mycobacteria.Treatment of infections due to nontuberculous mycobacteria remains difficult, in part because they are resistant to many of the first-line tuberculosis agents and in part because so few other agents are available for therapy (21 , abstr. 1098, 1999) which have the potential for activity against nontuberculous mycobacteria, including the rapidly growing mycobacteria (6; M. Wu, P. Aralor, K. Nash, L. E. Bermudez, C. B. Inderlied, and L. S. Young, Abstr. 38th Intersci. Conf. Antimicrob. Agents Chemother., abstr. E-143, 1998; L. E. Bermudez, Abstr. Int. Conf. Macrolides, Azalides, Streptogramins, Ketolides and Oxazolidinone, abstr. 03.16, 2000).We chose to study linezolid, which along with eperezolid is the first of the oxazolidinones to reach clinical testing (4; M. C. Birmingham et al., 39th ICAAC) Linezolid offers special promise, as it is a twice-daily oral drug which is 100% bioavailable (Zyvox package insert, 2000 [Pharmacia & Upjohn, Inc.]; also see reference 8) and appears to be well tolerated (8; N. E. Wilks, Abstr. 39th Intersci. Conf. Antimicrob. Agents Chemother., abstr. 1763Chemother., abstr. , 1999, important features of therapeutic drugs to be used against nontuberculous mycobacteria which cause chronic infections and require long-term therapy (often 6 months or longer) (21). The activities of linezolid against a large number of clinical isolates of rapidly growing mycobacteria, including the common disease-producing species Mycobacterium fortuitum, M. chelonae, and M. abscessus (24), were studied.(This work was presented in part as an abstract at the 100th General Meeting of the American Society for Microbiology, Los Angeles, Calif.) T , and M. abscessus ATCC 19977 T . Susceptibility testing. Susceptibility testing utilized seri...

Mycobacterium avium complex (MAC) isolates among patients with chronic lung disease were studied for their heterogeneity using genetic identification methods, pulsed field gel electrophoresis (PFGE) and seroagglutination. A mean of 7.3 cultures per patient were collected from 17 patients with nodular bronchiectasis who were elderly (mean age 66 yr), predominantly female (76%), had smoked a mean of only 5 pack-years, and had multifocal bronchiectasis. A mean of 7.7 cultures per patient were collected from nine patients with upper lobe cavitary disease who were younger (mean age 52 yr), predominantly male (78%), and heavy smokers (mean 56 pack-yr). A mean of 2.9 PFGE types (genotypes) per patient (range, 1 to 9) were identified in the nodular bronchiectasis group, with 15 of 17 patients (88%) having two or more genotypes and 9 of 17 (53%) having three or more genotypes. In contrast a mean of 1.2 genotypes were identified in the patients with cavitary disease, with only 1 of 9 (11%) having two or more genotypes. Mycobacterium intracellulare was the most frequently recovered genotype in both groups and most isolates were rough or nontypable by seroagglutination. Some genotypes from the same patient considered different by current PFGE criteria had the same serotype and shared 11 to 20 common PFGE bands, suggesting they were related. These data demonstrate that patients with nodular bronchiectasis have multiple and/or repeated infections due to MAC whereas patients with upper lobe cavitary disease are usually infected with only a single strain.

The Mycobacterium fortuitum third biovariant complex (sorbitol-negative and sorbitol-positive) contains unnamed taxa first characterized in 1991. These organisms can cause respiratory infections, a spectrum of soft tissue and skeletal infections, bacteraemia and disseminated disease. To evaluate this group of organisms, clinical reference isolates and the type strains of M. fortuitum third biovariant complex sorbitol-negative (n=21), M. fortuitum third biovariant complex sorbitol-positive (n=3), M. fortuitum (n=3), Mycobacterium peregrinum (pipemidic acid-susceptible) (n=1), Mycobacterium porcinum (n=1), Mycobacterium senegalense (n=2) and Mycobacterium septicum (n=1) were characterized by using conventional phenotypic (morphological, physiological and antimicrobial susceptibilities), chemotaxonomic (HPLC and cellular fatty acids) and genotypic [RFLP of the rRNA gene (ribotyping), PCR-RFLP of a 439 bp segment of the 65 kDa hsp gene (PCR restriction analysis) and 16S rRNA gene sequence] analysis, DNA G+C content and DNA–DNA relatedness analyses. The results of these studies indicated that the strains comprised M. porcinum (n=13), M. septicum (n=1) and four novel closely related genetic groups within the M. fortuitum third biovariant complex: Mycobacterium boenickei sp. nov. (n=6), Mycobacterium houstonense sp. nov. (n=2), Mycobacterium neworleansense sp. nov. (n=1) and Mycobacterium brisbanense sp. nov. (n=1), with type strains ATCC 49935T (=W5998T=DSM 44677T), ATCC 49403T (=W5198T=DSM 44676T) ATCC 49404T (=W6705T=DSM 44679T) and ATCC 49938T (=W6743T=DSM 44680T), respectively.