The pooled recurrence rate from these three studies was 5.4% (7 of 129 patients) [27–29]. Multiple antibiotics are typically required for prolonged periods of time and treatment is frequently poorly tolerated. Although the primary endpoint of reduction in semiquantitative mycobacterial culture growth from baseline was not achieved, significantly more patients who received ALIS achieved culture conversion by day 84 and had greater improvement in distance achieved on 6-minute walk test. J. M. I., E. C., J. An update was performed in May 2016 prior to the final meeting at the ATS International Conference and a final update was performed in June 2018 prior to manuscript submission. Drug susceptibility testing for NTM is useful but only for antibiotics for which correlations between in vitro activity and microbiological response to treatment have been well documented [110, 111]. For cavitary NTM pulmonary disease, sputum samples often suffice for diagnosis [4]. The data reviewed above suggest that treatment outcomes improve if the duration of treatment increases. No studies have specifically addressed this question. However, there is substantial uncertainty regarding best treatment regimens for M. xenopi. Treatment outcomes with intermittent therapy are not as favorable in patients with cavitary pulmonary disease. They … Design of regimens beyond the initial intravenous phase is difficult given the lack of oral antimicrobials with activity against M. abscessus. NTM pulmonary disease has been associated with diminished quality of life that correlates with the severity of lung impairment [106, 107]. Similarly, recent data from randomized clinical trials evaluating ALIS have demonstrated that high MICs of amikacin are associated with poor microbiological response as reported in a previous retrospective analysis of patients treated with parenteral amikacin [19, 20, 87]. Tuberc Respir Dis (Seoul). Remarks: Although no well-designed randomized trials of macrolide therapy have been performed, macrolide susceptibility has been a consistent predictor of treatment success for pulmonary MAC [16–18]. Semiquantitative sputum culture scores from the third month of treatment onwards are predictive of sustained sputum conversion at 12 months of treatment, so regular (e.g., monthly) sputum cultures are recommended during the treatment of MAC pulmonary disease [169]. Infections— Most infections that appear as with pulmonary nodules are relatively indolent and often not active. A case series suggested that intermittent ethambutol administration was less often associated with ethambutol-related ocular toxicity than daily ethambutol administration [165]. We suggest that patients with nodular/bronchiectatic M. kansasii pulmonary disease receive either daily or three times weekly treatment when receiving a macrolide, rifampicin, and ethambutol. One study used intravenously infected mice treated with clarithromycin, ofloxacin plus/minus amikacin [192], and the other study used an inhalational infection model and treatment with either clarithromycin/ethambutol/rifampicin or moxifloxacin/ethambutol/rifampicin plus/minus amikacin [191], and both studies identified microbiologic benefit of the addition of amikacin. Where ALIS is not yet available, addition of inhaled parenteral amikacin is a reasonable alternative. Molecular identification is the preferred method and can be achieved using probes or gene sequencing. The sputum culture conversion rate was significantly higher for patients who received streptomycin than for those who received oral therapy only (71.2% vs 50.7%). Systematic reviews were conducted around each of 22 PICO (Population, Intervention, Comparator, Outcome) questions and the recommendations were formulated, written, and graded using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Nontuberculous mycobacteria (NTM) represent over 190 species and subspecies, some of which can produce disease in humans of all ages and can affect both pulmonary and extrapulmonary sites. In patients with macrolide-susceptible MAC pulmonary disease, we suggest a treatment regimen with at least three drugs (including a macrolide and ethambutol) over a regimen with two drugs (a macrolide and ethambutol alone) (conditional recommendation, very low certainty in estimates of effect). Among patients with pulmonary infection, antimicrobial drug therapy was completely discontinued for 4 because of side effects. As with all patients receiving treatment, frequent sputum cultures should be obtained during the course of therapy to monitor for treatment response and survey for the appearance of other organisms such as M. avium complex. However, the study suffers from serious methodological flaws including lack of randomization, use of the 1997 ATS diagnostic criteria, and methods of determining and interpreting drug susceptibility that are no longer recommended. Dr. Novosad is a medical doctor and Pulmonary/Critical Care Fellow at Oregon Health and Science University. Reported side effects in these series ranged from 8 to 38% and included hoarseness, throat irritation, bitter taste, and thrush. In the Mycobacterial and Bronchiectasis Clinic, pulmonologists are part of a multidisciplinary team … Among those patients who met the 2007 ATS/IDSA criteria for MAC pulmonary disease and in whom treatment was not initiated, 51.6% underwent spontaneous sputum conversion during a median follow-up of 5.6 years [97]. Not surprisingly, there were many gaps and needs identified related to the treatment of NTM pulmonary disease. XIV: In patients with rifampicin susceptible M. kansasii pulmonary disease, should treatment be continued for <12 months or ≥12 months? No isolates in either group developed macrolide resistance, although the study was underpowered to detect a difference. The drugs used to treat NTM pulmonary disease are frequently associated with adverse reactions. Ten (15%) patients had used immunosuppressive medications in the 3 months before diagnosis. 1Members of the study team are listed at the end of this article. abscessus and functional erm(41) gene [40, 124, 125]. The panel members suggest that an expert in the management of patients with M. abscessus pulmonary disease be consulted. XXI: In patients with M. abscessus pulmonary disease, should shorter or longer duration therapy be used for treatment? This is particularly true in the initial months of therapy when bacterial burdens are greater. Most importantly, monotherapy with a single antibiotic or dual therapy with two antibiotics alone are not used for the treatment of mycobacterial pulmonary disease. The methodology team conducted systematic reviews and prepared evidence summaries following the GRADE approach [1, 2]. Our survey revealed that therapeutic regimens for M. abscessus infection vary widely. The decision to initiate antimicrobial therapy for NTM pulmonary disease should be individualized based on a combination of clinical factors, the infecting species, and individual patient priorities. The committee was chaired by C.D. In a retrospective study of 128 patients with M. abscessus, patients with M. abscessus subsp. In a randomized trial comparing intravenous streptomycin with placebo added to a standard 3-drug regimen, there was no association of treatment outcome with MIC to streptomycin; however, exact MIC values were not determined if above 4 μg/mL [121]. For patients with NB MAC lung disease, the priorities are typically to treat the underlying bronchiectasis and determine the course and impact of the MAC infection over time. To better identify treatment approaches and associated toxicities, we collected a series of case reports from the Emerging Infections Network. Postinfection treatment involves a combination of antituberculosis antibiotics, including rifampicin, rifabutin, ciprofloxacin, amikacin, ethambutol, streptomycin, clarithromycin or azithromycin. In a retrospective cohort treated with a standard regimen, the presence of in vitro resistance to clarithromycin was associated with worse outcomes [39]. In patients who fail to convert sputum cultures to negative after six months of treatment or who have extensive disease, expert consultation should be obtained. Two patients who received the shorter course of therapy developed acquired macrolide resistance. However, the latter study applied a drug susceptibility method not recommended for NTM and presented and analyzed only aggregate resistance data for all groups (MAC, M. xenopi, and M. malmoense) utilizing uniform discrete thresholds rather than considering MICs as a continuous variable to be explored for an association across species. Clinical, radiographic, and microbiologic data should be collected in order to assess whether or not a patient is responding to therapy. (ERS), E.C. In addition, the panel members felt that some subgroups of patients should be considered separately in determining the length of therapy such as: patients with nodular/bronchiectatic versus cavitary disease, patients affected by lung disease caused by different M. abscessus subspecies and, importantly, depending on susceptibility to macrolides and amikacin. The pathogenicity of NTM species may differ between geographic areas [9, 10]. 2016 Apr. The poor response to treatment in AIDS patients with disseminated MAC in the premacrolide era and the rapid development of resistance with clarithromycin monotherapy reinforced the need for multiple drugs for treatment success. Experts would consider performing TDM in situations in which drug malabsorption, drug underdosing, or clinically important drug-drug interactions are suspected [227]. (abscessus, bolletii, and massiliense) are rapidly growing mycobacteria that differ in in vitro susceptibility to macrolides based on the functionality of the erm(41) gene [194]. This inducible resistance can be measured in vitro by prolonged (ie, up to 14 days) incubation of microdilution trays [40, 93] or can be investigated by molecular detection and characterization of the erm(41) gene. Patients with M. abscessus pulmonary disease caused by strains without inducible (typically M. massiliense) or mutational macrolide resistance should be treated with a macrolide-containing multidrug regimen that includes at least three active drugs (guided by in vitro susceptibility) in the initial phase of treatment (the phase including intravenous agents) (Tables 3 and 5). Remarks: The optimal duration of therapy for pulmonary MAC disease is not currently known. Host susceptibility to non-tuberculous mycobacterial infections. The clinical laboratory plays a critical role in the diagnosis of NTM pulmonary disease. The relative and absolute effect estimates and 95% CIs for each outcome (Table E3.9) and discussion of value preferences, feasibility, cost, acceptability, and health inequality (Table E4.9) can be found in the supplement. Although some experts would favor 12 months of treatment after culture conversion, there is no evidence that relapses could be prevented with treatment courses longer than 12 months. There is currently not sufficient evidence to support bronchoscopy to obtain specimens for mycobacterial culture to determine the duration of therapy. We suggest that neither parenteral amikacin nor streptomycin be used routinely for treating patients with M. kansasii pulmonary disease (strong recommendation, very low certainty in estimates of effect). , three-, or four-drug regimen be used to generate analytics to improve efficacy and decrease toxicity! 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Patients receiving intermittent azithromycin-containing therapy for MAC pulmonary disease had several limitations, including unknown specific subspecies of M. subsp.

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