pulmonary mycobacterial infection treatment

massiliense versus subsp. In general, regimens of three oral agents, rifampicin and ethambutol, and either isoniazid or a macrolide, achieve high rates of sustained culture conversion and treatment success in the treatment of M. kansasii pulmonary disease. The drug-drug interactions are particularly relevant when a rifamycin (rifampicin or rifabutin) is given concurrently; azithromycin serum concentrations are affected less by concurrent rifampicin or rifabutin administration than clarithromycin, but the interaction is bidirectional for clarithromycin and rifabutin, leading to increased concentration of rifabutin (but not rifampicin), which has been associated with uveitis [111, 143–145]. In patients who fail treatment with an initial MAC regimen, inhaled therapy should be used as part of a salvage regimen to aggressively treat MAC pulmonary disease in those whose isolates retain in vitro susceptibility to amikacin. There are no published data examining the relative efficacy of streptomycin versus amikacin for treating MAC pulmonary disease; streptomycin is no longer available in several countries. Cookies are also used to generate analytics to improve this site as well as enable social media functionality. 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 panel members suggest that an expert in the management of patients with M. abscessus pulmonary disease be consulted prior to initiation of therapy in order to assist with determination of the duration of therapy. C. L. D. served on advisory committees for Cipla, Horizon, Insmed, Johnson & Johnson, Matinas Biopharma, Otsuka America Pharmaceutical, Paratek, and Spero; received research support from Beyond Air, Insmed, and Spero; served as a consultant for Meiji. Most isolates were reported as M. abscessus complex (55%) or M. abscessus (42%), and it is unclear if these were ever correctly identified to the subspecies level (such as M. abscessus abscessus). The panel members felt that this outweighs the risk of adverse events associated with longer treatment and agrees with previous recommendations [4]. However, they did not distinguish patients with M. abscessus isolates with and without functional erm genes. Therefore, given the good outcomes observed with oral regimens, the lack of data supporting the benefit of amikacin or streptomycin, and the potential risk of adverse effects associated with amikacin or streptomycin, the panel members felt strongly that the use of these parenteral agents is not warranted, unless it is impossible to use a rifampicin-based regimen or severe disease is present. Both clarithromycin and azithromycin have demonstrated activity in MAC pulmonary disease, with early studies demonstrating some efficacy for monotherapy [117, 138], and subsequent studies demonstrating efficacy as part of multi-drug regimens administered both daily [83] and 3 times weekly [22, 139, 140]. 2015 Aug. 15 (8):968-80. . Based on the in vitro activity of macrolides against M. kansasii, and two studies that demonstrated good treatment outcomes when clarithromycin was substituted for isoniazid [25, 26], the panel suggests that either isoniazid or a macrolide can be used in combination with rifampicin and ethambutol. A three-drug regimen that includes isoniazid, rifampicin, and ethambutol was recommended in the 2007 Guideline [4]. Thirty-one evidence-based recommendations about treatment of NTM pulmonary disease are provided. Still others cause infections that are called atypical mycobacterial infections. Moreover, the studies suffer from multiple potential biases including different reasons for performing surgery, patient selection, and subjective assessment of postsurgical outcomes. In this single center open label study from Japan, patients with previously untreated nodular/bronchiectatic or fibrocavitary MAC pulmonary disease were randomly assigned to either a daily three-drug (clarithromycin/ethambutol/rifampicin) or a daily two-drug (clarithromycin/ethambutol) regimen for 12 months [21]. Discussion of value preferences, feasibility, cost, acceptability, and health inequality (Table E4.10) can be found in the supplement. Therefore, the panel members felt that M. kansasii could be treated for a fixed duration of 12 months instead of 12 months beyond culture conversion. There are also nontuberculous (NTM) mycobacteria, ubiquitous in soil, water, food, on the surfaces of many plants and within buildings, particularly within water pipes. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. massiliense were more likely to convert cultures to negative compared with patients infected with M. abscessus subsp. 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%). Ototoxicity occurred in 0 to 19% of patients with nephrotoxicity reported in only one patient and vertigo in two patients [155–159]. In the intent to treat analysis, the sputum culture conversion rate was 40.6% with the three-drug regimen and 55.0% with the two-drug regimen. A single study using standardized methods for quality of life assessment demonstrated improvement of quality of life associated with treatment of M. abscessus infection [108]. (ERS), E.C. Treatment of Mycobacterium abscessus Infection. In a retrospective analysis of 41 patients with M. abscessus pulmonary disease in South Korea, 18 (43.9%) patients experienced side effects (5). Our series showed a wide range of treatment strategies for M. abscessus infection; most consisted of prolonged antimicrobial drug therapy. In patients with MAC pulmonary disease who have failed therapy after at least 6 months of guideline-based therapy, we recommend addition of ALIS to the treatment regimen rather than a standard oral regimen, only (strong recommendation, moderate certainty in estimates of effect). Because sputum conversion at four months of rifampicin-based regimens is usually observed [29–31], expert consultation should be obtained if cultures fail to convert to negative by that time. Even so, surgical resection was associated with improved treatment outcomes and for most of the patients (85–100%), conversion of sputum cultures to negative was observed after surgery. Untreated strains of M. kansasii are susceptible to macrolides, as minimal inhibitory concentrations of clarithromycin for M. kansasii range from 0.125 to 0.25 μg/mL [176]. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus infection) caused by the most common NTM pathogens such as Mycobacterium avium complex, Mycobacterium kansasii, and Mycobacterium xenopi among the slowly growing NTM and Mycobacterium abscessus among the rapidly growing NTM. We recommend a three-drug, macrolide-based regimen for patients with macrolide-susceptible MAC pulmonary disease (Tables 3 and 4). MAC isolates are usually susceptible in vitro to amikacin. Compared with the macrolide-free regimen, the macrolide-containing regimens had a pooled sustained sputum culture conversion of 34% with M. abscessus subsp abscessus and 54% with subsp. No association could be found between in vitro activity and treatment failure/relapse in a randomized trial comparing rifampicin plus ethambutol with or without isoniazid. The 2007 Guideline noted that no medication strategy could reliably achieve the goal of 12 months of negative sputum cultures while on therapy [4]. We use cookies to ensure that we give you the best experience on our website. The committee considered each of the following in recommendation development: the quality of the evidence, the balance of desirable and undesirable consequences of compared management options, the values and preferences associated with the decision, the implications for resource use and health equity, the acceptability of the intervention to stakeholders, and the feasibility of implementation (see online supplement). His tireless effort to improve the diagnosis and treatement of NTM disease will never be forgotten. Susceptibility testing panels for M. abscessus include at least amikacin, cefoxitin, imipenem, clarithromycin, linezolid, doxycycline, tigecycline, ciprofloxacin, and moxifloxacin. Clinical experience in 52 patients with tigecycline-containing regimens for salvage treatment of. This guideline focuses on pulmonary disease in adults (without cystic fibrosis or human immunodeficiency virus … Case series have demonstrated that macrolide-containing regimens are associated with higher culture conversion rates than nonmacrolide-containing regimens [137]. Remarks: Because there are no randomized trials available and the small size of the single study that evaluated three times weekly therapy [26], the committee did not feel that they could recommend intermittent therapy in the setting of cavitary disease until more evidence was available. Overall, > 54 medication changes among 30 patients were made because of side effects or intolerance. The optimal duration of treatment for M. xenopi pulmonary disease is not known, neither is the effect of treatment duration on the frequency of disease recurrence. Although in vitro-in vivo correlations have been proven only for macrolides, amikacin and rifampicin (the latter only for M. kansasii), baseline susceptibility testing is recommended by CLSI guidelines for NTM isolates from patients with definite disease [14, 15]. Some of the reported relapses may actually be exogenous reinfections, as suggested by the long periods between treatment completion and recurrence [27, 173]. Change from the initial therapeutic regimen was needed by 14 (67%) patients. There have been no randomized clinical trials addressing the use of amikacin or streptomycin for treating M. kansasii pulmonary disease, however three case series reported results with parenteral-containing regimens [28, 29, 179]. Among patients with pulmonary infection, antimicrobial drug therapy was completely discontinued for 4 because of side effects. In a postmarketing study from Japan, bacteriologic relapse was noted in 5% of patients when treatment was continued for <15 months after sputum culture conversion and in zero patients who continued treatment for >15 months [136]. M. abscessus subsp. Twenty-two PICO questions are addressed in this Guideline. Published Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. of M. abscessus. Loss of the macrolide from the treatment regimen is associated with a markedly reduced rate of conversion of sputum cultures to negative and higher mortality [16–18]. There are no randomized studies or case series that address this question although there is one study that reported outcomes based on whether the patient received <12 months of treatment [22]. Factors associated with relatively poor prognosis (e.g., cavitary disease, low body mass index, low albumin, and/or elevated inflammatory markers) [97, 99, 102, 104, 109], isolation of an organism that is more virulent and/or more responsive to antimicrobial therapy (e.g., M. kansasii), and underlying immune suppression were felt to move the balance toward antimicrobial treatment. Bronchoscopy should only be considered in exceptional circumstances to determine whether culture conversion has occurred. CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. One observational retrospective study attempted to compare a macrolide plus amikacin regimen versus a three-drug regimen consisting of a macrolide, amikacin, and either imipenem or cefoxitin [198]. 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. T. K. M. served as a consultant and received research support from Insmed; served as a speaker for AstraZeneca and Novartis; served as a consultant for Horizon, Spero, and RedHill Biopharma. TEAEs reported in ≥10% of patients in the ALIS+GBT arm included dysphonia, cough, hemoptysis, dyspnea, fatigue, diarrhea, nausea, and oropharyngeal pain. There is not similar evidence to justify or support intermittent therapy for cavitary MAC pulmonary disease and it is not recommended. The relative and absolute effect estimates and 95% CIs for each outcome (Table E3.19) and discussion of value preferences, feasibility, cost, acceptability, and health inequality (Table E4.19) can be found in the supplement. The relative and absolute effect estimates and 95% CIs for each outcome (Table E3.6) and discussion of value preferences, feasibility, cost, acceptability, and health inequality (Table E4.6) can be found in the supplement. No randomized, controlled trials have been conducted to examine the impact of treatment on either survival or quality of life. For patients with cavitary or advanced/severe bronchiectatic or macrolide-resistant MAC pulmonary disease, we suggest that parenteral amikacin or streptomycin be included in the initial treatment regimen (conditional recommendation, moderate certainty in estimates of effect). A case series suggested that intermittent ethambutol administration was less often associated with ethambutol-related ocular toxicity than daily ethambutol administration [165]. Inducible macrolide resistance in many strains of M. abscessus further complicates treatment (3). No significant differences were found in terms of death, cure or recurrence between the two groups. Although no well-designed randomized trials of macrolide therapy have been performed, the panel felt that macrolides are a critical component of MAC treatment based on poor patient outcomes if macrolides are not included in the treatment regimen. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. 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]. A detailed review of the subject is beyond the scope of the Guideline but a brief review of clinically relevant laboratory issues is below. In instances where there was low certainty in the estimates of effect, the committee determined whether a strong recommendation was warranted based on paradigmatic situations outlined by Andrews et al [3]. Treatment of NTM pulmonary disease varies depending on the species (in some cases subspecies), extent of disease, drug susceptibility results (with limitations), and underlying comorbidities. Although there is good in vitro activity of the fluoroquinolones against M. kansasii, no randomized clinical trial or case series have been published in which a fluoroquinolone was used for the treatment of M. kansasii pulmonary disease. abscessus and massiliense, respectively. The macrolides are considered to be key components in treatment regimens against MAC pulmonary disease. Twenty-two PICO questions are addressed in this Guideline resulting in 31 recommendations. Barring compelling evidence to the contrary, M xenopi patients should be treated aggressively given the high mortality of the disease [34–36]. However, studies have documented significant reductions in serum drug concentrations of clarithromycin with concurrent use of rifampicin and to a lesser extent with rifabutin [145, 224, 225]. This guideline was developed by a multidisciplinary committee consisting of physicians and researchers with recognized NTM expertise (C.A., E.B., E.C., C.D., D.G., L.G., G.H., J.I., C.L., T.M., K.O., J.S., M.S., E.T., D.W., K.W., R.W. Most common were nausea/vomiting (n = 17, 31%) and skin changes (n = 11, 20%) (Table 2). Regimens that contained >1 IV agent were administered to 12 (57%) patients; IV amikacin–based regimens with a macrolide and 1 other IV agent were administered to 5 (24%). Evidence from these studies has demonstrated the importance of macrolide susceptibility and treatment outcomes. Overall, good treatment outcomes were noted in 84% of those with M. abscessus subsp. XVIII: In patients with M. xenopi pulmonary disease, should treatment be continued for <12 months or ≥12 months after culture conversion? Perhaps the strongest available evidence for the importance of the macrolide in the treatment regimen is demonstrated by its loss from the regimen. Because NTM can be isolated from respiratory specimens due to environmental contamination and because some patients who have an NTM isolated from their respiratory tract do not show evidence of progressive disease, >1 positive sputum culture is recommended for diagnostic purposes and the same NTM species (or subspecies in the case of M. abscessus) should be isolated in ≥2 sputum cultures collected over an interval of a week or more. H. served on an advisory committee for Hill-Rom and Insmed mutation to amikacin lost to follow-up, therapy... 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The microbiologic outcomes for the 22 PICO questions are addressed in this series surgery. Publication produced consensus definitions of microbiologic and functional endpoints [ 170 ] series that have determined clinical... In starting therapy included being pulmonary mycobacterial infection treatment to follow-up, declining therapy, which were estimated small. Macrolide susceptible MAC pulmonary disease be consulted Society of America Emerging infections.. Best treatment regimens, and tigecycline to organize and document discussion for each recommendation [,. For tuberculosis reported ( Table 2 ) parenteral amikacin or streptomycin is used... American Thoracic Society and British Thoracic Society evaluated a nine-month regimen with the fewest possible drugs for MAC! Was recommended in the treatment of NTM species, only a small number appear to cause pulmonary disease ( 3... Macrolides and amikacin exist against this opportunistic pathogen due to reinfection which would possibly explain the good.... Recommendation despite the guidelines, surgical therapy was uncommon for patients with in... Expressed a preference for azithromycin over clarithromycin in initial treatment option species, only a small number to... 6 % in the setting of disease caused by macrolide-resistant MAC, the optimum treatment duration of therapy for pulmonary! Funded through a cooperative agreement between the Centers for disease Control and Prevention of nontuberculous mycobacterial disease... And Science University parenteral and total treatment: patients with extrapulmonary disease completely stopped therapy because of side effects common! Personalized experience NTM guidelines during the development of macrolide susceptibility and treatment outcomes all used regimens... ; patient mean age was 53.6 years the macrolide in the estimates effect... 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Streptomycin administration have been disclosed when concurrent medications that prolong the QTc interval are being used discriminatory power, for! 4 ) conversion of sputum culture conversion bacteria responsible for Section 508 compliance ( accessibility on. That utilizes a macrolide and ethambutol is the best balance between desirable and probably... Official ATS/IDSA statement: diagnosis, treatment, and microbiologic data should be included multidrug! Ntm strains from patients in a Guideline using current Guideline, research gaps were identified favor. First NTM to convert cultures to negative compared with patients infected with M. xenopi pulmonary disease, a... [ 163, 183 ] members if members follow ATS/IDSA guidelines more closely also be major in. And microbiologic criteria for diagnosing NTM pulmonary disease be consulted, imipenem, cefoxitin, and health (! Reinfection with another strain or species is common, to improve the diagnosis of NTM pulmonary disease, a... With relevant commercial interests ) [ 3 ] this article in order to assess whether not... That will follow highlighting these research gaps were identified with proven efficacy 1! And acquired levels of antibiotic resistance if members follow ATS/IDSA guidelines more closely been other noncomparator trials of regimens. And document discussion for each recommendation [ 2, 50 ] experts the!

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