Recommendations for first-line and second-line drug testing and organism group, specific methodologies, and reporting recommendations have been addressed by the Clinical and Laboratory Standards ...Institute (CLSI) and are important in the selection of appropriate antimicrobial treatment regimens for nontuberculous mycobacteria (NTM) disease. This review also includes recent information on new antimicrobials proposed for the treatment of NTM but not yet addressed by the CLSI and molecular (gene sequencing) methods associated with the detection of antimicrobial resistance of two major therapeutic antimicrobials, clarithromycin and amikacin.
species are a complex group of organisms considered to belong to the aerobic actinomycetes. Of the validly described species, many have been implicated as the cause of serious human infections, ...especially in immunocompromised patients. The genus has a complicated taxonomic history; this is especially true for
, the type species of the genus and previously the most frequently reported nocardial taxon from human specimens. We provide background on the current taxonomy of
, with a focus on clinically relevant species, and discuss the currently available methods used to accurately identify isolates to the species, complex, or group level.
BACKGROUND There is no large study validating the appropriateness of current treatment guidelines for Mycobacterium avium complex (MAC) lung disease. This is a retrospective single-center review ...evaluating the efficacy of macrolide/azalide-containing regimens for nodular/bronchiectatic (NB) MAC lung disease. METHODS Patients were treated according to contemporary guidelines with evaluation of microbiologic responses. Macrolide susceptibility of MAC isolates was done at initiation of therapy, 6 to 12 months during therapy, and on the first microbiologic recurrence isolate. Microbiologic recurrence isolates also underwent genotyping for comparison with the original isolates. RESULTS One hundred eighty patients completed > 12 months of macrolide/azalide multidrug therapy. Sputum conversion to culture negative occurred in 154 of 180 patients (86%). There were no differences in response between clarithromycin or azithromycin regimens. Treatment regimen modification occurred more frequently with daily (24 of 30 80%) vs intermittent (2 of 180 1%) therapy ( P = .0001). No patient developed macrolide resistance during treatment. Microbiologic recurrences during therapy occurred in 14% of patients: 73% with reinfection MAC isolates, 27% with true relapse isolates ( P = .03). Overall, treatment success (ie, sputum conversion without true microbiologic relapse) was achieved in 84% of patients. Microbiologic recurrences occurred in 74 of 155 patients (48%) after completion of therapy: 75% reinfection isolates, 25% true relapse isolates. CONCLUSIONS 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.
This multicenter study was designed to assess the accuracy and reproducibility of the Vitek MS v3.0 matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry system for ...identification of
and
species compared to DNA sequencing. A total of 963 clinical isolates representing 51 taxa were evaluated. In all, 663 isolates were correctly identified to the species level (69%), with another 231 (24%) correctly identified to the complex or group level. Fifty-five isolates (6%) could not be identified despite repeat testing. All of the tuberculous mycobacteria (45/45; 100%) and most of the nontuberculous mycobacteria (569/606; 94%) were correctly identified at least to the group or complex level. However, not all species or subspecies within the
,
, and
complexes and within the
and
groups could be differentiated. Among the 312
isolates tested, 236 (76%) were correctly identified to the species level, with an additional 44 (14%) correctly identified to the complex level. Species within the
and
complexes could not always be differentiated. Eleven percent of the isolates (103/963) underwent repeat testing in order to get a final result. Identification of a representative set of
and
species was highly reproducible, with 297 of 300 (99%) replicates correctly identified using multiple kit lots, instruments, analysts, and sites. These findings demonstrate that the system is robust and has utility for the routine identification of mycobacteria and
in clinical practice.
Infections caused by nontuberculous mycobacteria (NTM) are increasing globally.
complex (MAC) and
complex are the most frequently encountered NTM, and oral treatment options are extremely limited for ...these pathogens, especially for the
complex. In this study, the
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
subsp.
(20 isolates),
subsp.
(3),
(15 isolates),
(7 isolates), the
group, including six doxycycline-resistant isolates (12 isolates), and the
group, including four doxycycline-resistant isolates (10 isolates). Forty-one isolates of slowly growing mycobacteria (SGM), including 16 isolates of MAC, were also tested. Omadacycline was active against all RGM species, with MIC
ranges of 0.004 to 0.25 and 0.06 to 1 μg/ml for 80% and 100% inhibition, respectively. For
subsp.
, MIC
s 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 of tigecycline exhibited no trailing and were generally within 1 to 2 dilutions of the 100% inhibition omadacycline MICs. While there was no trailing observed in SGM, omadacycline MICs were higher (MIC range, 8 to >16 μg/ml;
= 41), as previously noted with tigecycline. This study supports further research of omadacycline, including clinical trials, for the treatment of RGM infections, especially
.
Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease.
In this phase II study, we investigated the efficacy and safety of liposomal ...amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex MAC or Mycobacterium abscessus) disease.
During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events.
The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 32% of 44 vs. 4 9% of 45; P = 0.006) and improvement in 6-minute-walk test (+20.6 m vs. -25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation.
Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6-minute-walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).
Nontuberculous mycobacterial (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 complex. 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.
(
= 16) and subsp.
(
= 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
against the M. fortuitum and M. mucogenicum groups and M. kansasii, with MIC
values of 0.12 to 0.5 μg/ml (MIC range, 0.001 to 4 μg/ml) compared to ≤0.06 to >4 μg/ml for ciprofloxacin and ≤0.06 to >8 μg/ml for moxifloxacin. For other SGM (including MAC), and the M. abscessus/M. chelonae, the delafloxacin MIC range was 8 to >16 μg/ml compared to ciprofloxacin and moxifloxacin of 0.5 to >4 μg/ml and ≤0.06 to 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.
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