To gain greater insight into the optimal therapeutic strategy for M. abscessus lung disease, we retrospectively assessed the efficacy of a combination antibiotic therapy, which included a clarithromycin-containing three-drug regimen along with an initial 4-week course of intravenous cefoxitin and amikacin. Antimicrobial susceptibility testing was performed at the Korean Institute of Tuberculosis. In a large study of 154 patients with RGM-associated lung disease, in which more than 80% of patients were infected by M. abscessus, Griffith and colleagues concluded that M. abscessus was extremely difficult to eradicate by antibiotic therapy (6). Of the oral antibiotics, clarithromycin showed moderate in vitro activity against the isolates (73%, 33/45), but demonstrated better in vitro activity than ciprofloxacin (47%, 21/45). Wallace RJ Jr, Brown-Elliott BA, Ward SC, Crist CJ, Mann LB, Wilson RW. Pulmonary TB and NTM lung disease: comparison of characteristics in patients with AFB smear-positive sputum. During this period, 188 patients were newly diagnosed with M. abscessus lung disease. With this in mind, in this issue of the European Respiratory Journal, Kwak et al. Koh WJ, Kwon OJ, Lee KS. The most common are Mycobacterium avium complex or MAC. Our treatment strategy for patients with M. abscessus lung disease is divided into two paths: reservation of antibiotic therapy for patients with mild forms of the disease and initiation of aggressive antibiotic therapy with standardized regimens for patients with severe or progressive forms of the disease. If an adverse reaction associated with cefoxitin occurred, imipenem (750 mg, three times a day) (3) was substituted for cefoxitin. M. abscessus is distantly related to tuberculosis and can cause lung infections in people with cystic fibrosis. The challenge is amplified by the fact that the incidence of MAB-PD may also be increasing [6], possibly as a result of ageing populations with pre-existing lung disease, alongside increasing use of immunosuppressant drugs, and increased environmental exposure. Out of 188 patients with M. abscessus lung disease, 102 (54%) patients did not receive antibiotic therapy for the following reasons: mild symptoms and no clear evidence of disease progression during the observation period (n = 83; median follow-up duration, 20.5 mo; interquartile range [IQR, 25th and 75th percentiles] 12.8–38.0 mo); lost to follow-up (n = 8; median follow-up duration, 17.7 mo; IQR 4.3–39.3 mo); transfer to another hospital after diagnosis of M. abscessus lung disease (n = 6; median follow-up duration, 11.2 mo; IQR 8.2–54.5 mo); or death due to another disease (n = 5; median follow-up duration, 24.5 mo; IQR 13.3–51.2 mo). Definition of abbreviations: AFB = acid-fast bacilli; IQR = interquartile range. The diagnosis was based on repeated sputum culture positivity in 167 patients (89%) and on bronchial washing or bronchoalveolar lavage fluid culture positivity in the remaining 21 patients (11%) who were either unable to produce sputum or had negative sputum cultures. Furthermore, of these nine patients, sputum relapse occurred during antibiotic treatment in five patients and after completion of treatment in four patients (5, 6, 7, and 40 mo after treatment completion, respectively). Has anyone ever been cured from this? Adekambi T, Berger P, Raoult D, Drancourt M. Kim HY, Kook Y, Yun YJ, Park CG, Lee NY, Shim TS, Kim BJ, Kook YH. Introduction. Treatment guidelines for NTM depend upon the type and extent of the infection, … In contrast to clarithromycin, no such relationship was found for amikacin, cefoxitin, ciprofloxacin, or doxycycline in this study. Published by John Wiley & Sons Ltd. Our study found that a combination antibiotic therapy is modestly effective in producing a favorable microbiologic response. This is an open-label study of efficacy, safety and tolerability of once daily dosing of Liposomal-Amikacin for Inhalation (LAI), in addition to a standard multi-drug antibiotic therapy in accordance with the 2007 ATS/ IDSA guidelines, in patients with Mycobacterium abscessus lung disease. COMPARISON OF THE CLINICAL AND RADIOGRAPHIC CHARACTERISTICS OF PATIENTS WITH MYCOBACTERIUM ABSCESSUS LUNG DISEASE WHO RECEIVED ANTIBIOTIC THERAPY WITH THOSE WHO DID NOT RECEIVE ANTIBIOTIC THERAPY. ATS/IDSA recommendations suggest that susceptibility to some agents, such as amikacin, cefoxitin, clarithromycin, ciprofloxacin, and doxycycline, should be reported and used to guide treatment (1, 2). In recent years, Mycobacterium massiliense and Mycobacterium bolletii have been newly identified within the M. abscessus group (35, 36). Clinical significance of nontuberculous mycobacteria isolated from respiratory specimens in Korea. abscessus (where treatment success was found in only 33% of cases), the use of azithromycin (but not clarithromycin), and parenteral amikacin was also related to treatment success; cefoxitin was not associated with treatment success. Mycobacterium abscessus complex is an ubiquitous, rapidly growing mycobacterium.1,2 The lungs are the most frequent site of infection, and M. abscessus infections progress slowly if left untreated.1,4 A history of chronic cough is often present initially, whereas fever and constitutional symptoms are seen with Forty-eight (74%) patients had the nodular bronchiectatic form, 15 (23%) had the upper lobe cavitary form, and 2 (3%) had unclassifiable variants. Spectrum of disease due to rapidly growing mycobacteria. Additionally, if we are to better understand which treatment regimens offer the greatest chance of success, there is a need for consistency in approach to defining the end-points by which we measure treatment success. Categorical variables were analyzed using the Pearson χ2-test or Fisher exact test. Copyright © 1987-2020 American Thoracic Society, All Rights Reserved. en pacientes con fibrosis quística. Because of these adverse reactions, cefoxitin was discontinued in 39 (60%) patients after treatment for a median of 22 days. Pulmonary resections included lobectomy in six patients, pneumonectomy in three patients, bilobectomy in two patients, segmentectomy in one patient, and lobectomy plus segmentectomy in two patients. None of the examined isolates was susceptible to doxycycline (Table 3). Isolates are usually susceptible only in vitro to the parenteral agents amikacin, cefoxitin, and imipenem, and to oral macrolides (clarithromycin and azithromycin) (1, 2 Es un grupo de micobacterias no tuberculosas … We do not capture any email address. The present study has several limitations. Looking to the future, this could include development of a tool combining measures of quality of life, and symptomatic and radiographic improvement, alongside sputum culture conversion. Additional detail on the method is provided in the online supplement. CHARACTERISTICS OF 65 PATIENTS WITH MYCOBACTERIUM ABSCESSUS LUNG DISEASE WHO RECEIVED COMBINATION ANTIBIOTIC THERAPY FOR MORE THAN 12 MONTHS. [9] present a timely, and welcome, individual patient data meta-analysis of outcomes in MAB-PD. Nucleotide-binding oligomerization domain (NOD) 2 is a cytosolic receptor which senses a bacterial peptidoglycan component, muramyl dipeptide (MDP). Infections with Mycobacterium abscessus can often cause serious symptoms. Isolates were considered resistant if the MIC of clarithromycin was 8 μg/ml or greater and susceptible if the MIC of clarithromycin was 2 μg/ml or less (14). Identificación rápida de . TABLE 5. Nam HS, Koh WJ, Kwon OJ, Cho SN, Shim TS. Conflict of interest: M. Wilkie has nothing to disclose. the site you are agreeing to our use of cookies. Surprisingly, limited data are available in the literature regarding the clinical efficacy of this combination antibiotic therapy for M. abscessus lung disease. The guidelines state that administration of this combination therapy for 2 to 4 weeks (1) or 2 to 4 months (2) usually produces clinical and microbiologic improvement; however, cost and morbidity are significant impediments to a curative course of therapy (likely 4–6 mo). Mycobacterium abscessus is closely related to the bacteria that causes tuberculosis. Having said that, this important paper makes two key contributions to this field of research. To better identify treatment ap-proaches and associated toxicities, we collected a series of case reports from the Emerging Infections Network. The initial sputum conversion rate was 72% (47/65), and the median time until sputum conversion was 1 month (IQR, 1–1 mo). The other 18 (28%) patients, including 2 patients who died of disease progression, failed to achieve sputum conversion. The broth microdilution MIC determination was not established in Korea during the early study period. However, the patients did not receive the currently recommended combination of antibiotics, which includes newer macrolides such as clarithromycin. National Committee for Clinical Laboratory Standards. Combination therapy of intravenous amikacin with cefoxitin or imipenem and an oral macrolide have been recommended by the American Thoracic Society (ATS)/Infectious Diseases Society of America (IDSA) and many other experts (1–4). This challenge starts from a poorly understood pathogenesis, continues with complicated subspecies variation in treatment response, and extends to the multidrug-resistant nature of these organisms. Therefore, 38 (58%) of the 65 patients' sputum converted and remained culture negative until the end of December 2008. Wallace RJ Jr, Meier A, Brown BA, Zhang Y, Sander P, Onyi GO, Bottger EC. Mycobacterium abscessus in both adults and children has been associated with a wide variety of clinical manifestations including the following: pulmonary infections; chronic otitis media; lymphadenitis; central line-associated blood stream infections, especially in oncology and hematopoietic stem cell transplant patients; and skin and soft tissue infections in both immune compromised and normal host children [20, 21, 47–49]. CONCLUSIONS: Mycobacterium abscessus infection in LTR is rare and can lead to severe complications. Finally, as the authors illustrate, this is the first individual patient data meta-analysis in the NTM-PD field, but was ultimately only able to include 303 patients. This site uses cookies. Adverse reactions associated with cefoxitin occurred frequently. Methods: Sixty-five patients (11 males, 55 females, median age 55 yr) with M. abscessus lung disease were treated with clarithromycin, ciprofloxacin, and doxycycline, together with an initial regimen of amikacin and cefoxitin for the first 4 weeks of hospitalization. Moreover, a study showed that moxifloxacin has a good activity against M. abscessus and combinations of clarithromycin and moxifloxacin were effective against M. abscessus strains in in vitro models (25). Cremades R, Santos A, Rodriguez JC, Garcia-Pachon E, Ruiz M, Escribano I, Royo G. Screening for sterilizing activity of antibiotic combinations in an acid model of rapidly growing mycobacteria during the stationary phase of growth. TREATMENT RESPONSES OF 65 PATIENTS WITH MYCOBACTERIUM ABSCESSUS LUNG DISEASE. Mycobacterium tuberculosis was not isolated. Additional detail on the method is provided in an online data supplement. This approach usually requires placement of a long-term indwelling intravenous access with the potential for morbidity. M. abscessus is resistant to many antibiotics and thus is very difficult to treat. Kobashi Y, Matsushima T, Oka M. A double-blind randomized study of aminoglycoside infusion with combined therapy for pulmonary. The rate of infected patients is rapidly growing, and so is the proportion of Myco Ab patients within the NTM community. Sputum conversion rates were lower in patients whose isolates were resistant to clarithromycin (42%, 5/12) compared with those whose isolates were susceptible or intermediate to clarithromycin (76%, 25/33). Al paciente se le indicó . MAC encompasses three mycobacterial species known as M. avium,M. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. Mycobacterium abscessus is often resistant to multiple an-timicrobial drugs, and data supporting effective drugs or dosing regimens are limited. Three patients were able to continue antibiotic therapy after reduction of the clarithromycin dosage (500 mg/d). The frequently changing nomenclature to describe RGM is a source of confusion for clinicians. However, frequent adverse reactions and the potential for long-duration hospitalization are important problems that remain to be solved. Mycobacterium abscessus lung disease recurred in 5 (15%) patients after successful completion of antibiotic therapy. Activities of linezolid against rapidly growing mycobacteria. Six patients underwent treatment for 19.2 months (IQR, 16.8–21.1 mo). For instance, M. abscessus has been labeled as Mycobacterium cheloneii subspecies abscessus, Mycobacterium chelonae subspecies abscessus, and finally, in 1992, as M. abscessus (34). Therefore, the microbiologic response rate, which was defined as sputum conversion and the maintenance of negative sputum cultures for more than 12 months, was significantly lower in patients infected with clarithromycin-resistant isolates (17%, 2/12) compared with patients infected with clarithromycin-susceptible or intermediate isolates (64%, 21/33; P = 0.007) (Table 6). First, our study is a retrospective case study that was conducted at a single center. American Thoracic Society. Definition of abbreviation: MICS = minimum inhibitory concentrations. aureus, Haemophilus influenzae, Pseudomonas aeruginosa, Strep. Sputum relapse was defined as two consecutive positive cultures after sputum conversion (18). Thus, we are not sure whether the recurrence was due to relapse with the original strain or reinfection with a genetically different strain (40, 41). Gastrointestinal symptoms (e.g., anorexia, nausea, or diarrhea) associated with oral antibiotic usage after discharge from the hospital occurred in 14 (22%) patients. Pulmonary Mycobacterium abscessus: can we identify the road to improved outcomes. MINIMUM INHIBITORY CONCENTRATIONS BREAKPOINTS AND IN VITRO SUSCEPTIBILITY OF MYCOBACTERIUM ABSCESSUS (N = 45). Drug-induced hepatotoxicity (aspartate aminotransferase or alanine aminotransferase levels ≥ 120 IU/L) occurred in 10 (15%) patients. Follow-up HRCT scans were performed at a median 12.2 months (IQR, 11.9–12.5 mo) after the start of antibiotic therapy. Interestingly, for M. abscessus subsp. Of the 38 patients who achieved culture-negative sputum for more than 12 months, 32 patients completed their antibiotic therapy and were followed up for only a median of 12 months. As shown in Table 5, response rates were 83% based on symptoms and 74% based on HRCT findings. Complete blood cell counts, serum creatinine, and liver function test results were monitored twice a week during hospitalization. ESR levels decreased to a median of 26.0 mm/h (IQR, 16.3–46.5 mm/h) after an initial 4 weeks of treatments and further decreased to a median of 17.5 mm/h (IQR, 12.0–42.0 mm/h) after 12 months of treatment (P < 0.001). Permission was obtained from the institutional review board of Samsung Medical Center to review and publish information from the patients' records. However, the relationship between in vitro susceptibility results for M. abscessus and clinical responses to these agents has not been established., Refused further therapy before treatment completion, Death due to disease progression during the treatment, Initial sputum conversion and maintenance of conversion, Initial sputum conversion, with sputum relapse. Common symptoms of NTM are chronic, dry cough, and shortness of breath. All patients met the diagnostic criteria for NTM lung disease, according to the ATS guidelines in 1997 (1). The recent demonstration that bacteriophage therapy may offer an alternative treatment approach is one such direction [10], but others may include a better-defined role for improved mucociliary clearance, to help augment antibiotic therapy in MAB-PD, for example. Although M. abscessus complex most commonly causes chronic lung infection and skin and soft tissue infection (SSTI), the complex can also cause infection in almost all human organs, mostly in patients with … Two patients died due to disease progression at 18 and 30 months, respectively. Sputum smears and mycobacterial cultures were performed with standard methods (13). When and how to treat pulmonary non-tuberculous mycobacterial diseases. M. abscessus can also be acquired from contaminated medical equipment, although most of these nosocomial infections in-volve the skin and soft tissues [2]. Olaison L, Belin L, Hogevik H, Alestig K. Incidence of β-lactam-induced delayed hypersensitivity and neutropenia during treatment of infective endocarditis. M. abscessus was the most commonly NTM species cultured, representing 298 (55.6%) of the isolates; Mycobacterium avium complex was second with 190 (35.4%) isolates (Fig. Residual bias, and the dangers of multiple testing in small cohorts, mean that one must still interpret these findings with a degree of caution. Of those, Mycobacterium abscessus appears in 16 to 68 percent of cases. Close observation is indicated if the decision is made not to treat. One patient, whose sputum cultures had converted to negative for 18 months, refused further therapy at 19 months.