Antimicrobial Susceptibility of Rapidly Growing Mycobacteria
The Clinical Microbiology Laboratory isolates rapidly growing mycobacteria at the rate of about five per month from clinical specimens, primarily sputum. Often contaminants, these mycobacteria can also cause serious disease, with some species more likely than others to cause disease. The three most common isolates are M. abscessus ssp abscessus, M. chelonae, and M. fortuitum; of these M. abscessus ssp abscessus is the one that most commonly causes disease. Clinically relevant isolates are tested at HUP, using CLSI guidelines . The clinical validity of these results has not been determined in prospective studies, making it unclear how the results should be applied to treatment decisions. The interpretive guidelines ("sensitive, intermediate, resistant") have never been validated, and are borrowed from those used for other organisms. Regardless such results are often used for treatment decisons.
Taxonomic changes, and the description of tens of novel rapidly growing mycobacteria over the last ten years, have made it challenging for non-mycobacteriologists to keep all the players straight. Molecular methods for bacterial identification, especially sequencing of variable genes, have shown that some older species can now be divided into multiple new species. This has made identification of the bacteria by phenotypic means nearly impossible, requiring molecular-based identification imperative. The HUP laboratory uses sequence analysis of hsp65 to identify most mycobacteria, and may use rpoB sequencing at times as well. Partial 16S rDNA sequence analysis is insufficiently discriminating for distinguishing between many mycobacterial species, and even full length sequence analysis may not allow adequate discrimination between species. For example, partial 16S rDNA sequencing can not distinguish between M. abscessus and M. chelonae, let alone between M. abscessus ssp abscessus and M. abscessus ssp bolletii. What used to be called M. abscessus is now recognized as two different subspecies, M. abscessus ssp abscessus and M. abscessus spp bolletii (which I am sorry to tell you used to be itself two different species, M. bolletii and M. massiliense). Unusual antibiotic susceptibility phenotypes may lead to discovery of novel species, for example, M. franklinii masquerading as M. abscessus ssp abscessus; separting these species may require multiple target sequencing.
M. abscessus ssp abscessus is the "bad boy" of rapid growers because of its high level of in vitro and in vivo resistance, whereas M. fortuitum is much more susceptible to many drugs. M. abscessus ssp abscessus and M. fortuitum are both inducibly resistant to macrolide antibiotics, with only very rare isolates of M. abscessus ssp abscessus being macrolide susceptible. The HUP lab routinely tests for inducible macrolide resistance in these species. In contrast, M. chelonae, and some strains of M. abscessus ssp bolletii (ones that used to be called M. massiliense) are macrolide susceptible. Although only limited anecdotal data exist, it appears as if inducible macrolide resistance is the major reason why macrolide therapy fails for M. abscessus ssp abscessus infections, sometimes after an initial response to macrolide therapy.
Tigecycline susceptibility breakpoints for mycobacteria have not been established. Only MICs are reported for this drug. For perspective, the tigecycline US FDA-defined susceptibility breakpoints are 0.25, 0.5, 2 and 4 mg/L for streptococci and enterococci, S. aureus, Enterobacteriaceae and anaerobic bacteria, respectively. There are no CLSI tigecycline breakpoints. EUCAST-defined tigecycline breakpoints are 0.25, 0.5 and 1 mg/L for pk/pd (organism idependent but not specifically adressing mycobacteria), staphylococci and Enterobacteriaceae, respectively. Tigecycline Cmax is around 0.6 mg/L and Cmin around 0.1 mg/L, with steady state dosing at 50 mg IV q 12 hrs. Tigecycline lung concentrations are around 0.4 mg/L (ELF) and 15 mg/L (alveolar macrophages).
More information: ATS guideline on diagnosis and treatment of non-tuberculous mycobacterial diseases
archived susceptibility data for rapidly growing mycobacteria 2010-2013
P Edelstein 12/15/14
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