Abscessus Lung Disease Research Articles

Durlobactam to boost the clinical utility of standard of care β-lactams against Mycobacterium abscessus lung disease.

β-Lactams present several desirable pharmacodynamic features leading to the rapid eradication of many bacterial pathogens. Imipenem (IPM) and cefoxitin (FOX) are injectable β-lactams recommended during the intensive treatment phase of pulmonary infections caused by Mycobacterium abscessus (Mab). However, their potency against Mab is many-fold lower than against Gram-positive and Gram-negative pathogens for which they were optimized, putting into question their clinical utility. Here, we show that adding the recently approved durlobactam-sulbactam (DUR-SUL) pair to either IPM or FOX achieves growth inhibition, bactericidal, and cytolytic activity at concentrations that are within those achieved in patients and below the clinical breakpoints established for each agent. Synergies between DUR-SUL and IPM or FOX were confirmed across a large panel of clinical isolates. Through in vitro resistant mutant selection, we also show that adding DUR-SUL abrogates acquired resistance to IPM and FOX. Since the use of β-lactam injectables is firmly grounded in clinical practice during the intensive treatment phase of Mab pulmonary disease, their potentiation by FDA-approved DUR-SUL to bring minimum inhibitory concentration distributions within achievable concentration ranges could offer significant short-term benefits to patients, while novel β-lactam combinations are optimized specifically against Mab pulmonary infections, for which no reliable cure exists.

Amikacin Liposomal Inhalation Suspension for Non-Tuberculous Mycobacteria Lung Infection: A Greek Observational Study.

Background and Objectives: Intravenous amikacin, recommended for severe or recurrent M. avium complex (MAC) infections and as initial treatment for M. abscessus lung disease, is often limited by serious adverse effects such as renal and auditory toxicities. Inhaled Amikacin Liposome Inhalation Suspension (ALIS) enhances pulmonary drug deposition while minimizing systemic adverse effects, and it has recently been introduced as an add-on therapy for refractory MAC infections or when other standard treatments are inadequate. This study aims to retrospectively describe the outcomes of Greek patients with difficult-to-treat non-tuberculous mycobacterial (NTM) lung disease following the addition of ALIS to guideline-based therapy. Materials and Methods: Seventeen consecutive patients (median age: 66 years) treated with ALIS as an add-on therapy to a standard regimen at "Sotiria" General Hospital of Chest Diseases (Athens, Greece) from 2020 to 2023 were enrolled in this study. These patients had recurrent or refractory NTM lung disease and/or limited treatment options due to prior treatment-related adverse effects. Clinical, radiological, and microbiological data on treatment response and overall outcomes after ALIS initiation were recorded for each patient. Results: By the end of 2023, 14 out of 17 patients had either successfully completed or were continuing their ALIS therapy. At 6 months, 85.7% (12/14) showed clinical, microbiological, and radiological improvement. However, 25% (3/12) of treated patients, primarily those with monomicrobial or combined M. abscessus lung disease, experienced disease relapse after therapy completion. The most frequent adverse effects related to ALIS were mild and localized to the respiratory tract, with only one patient discontinuing therapy due to hypersensitivity pneumonitis. Conclusions: Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease, particularly those who had discontinued intravenous aminoglycosides due to significant adverse effects, with notable responses observed in MAC lung disease. Further research is needed to validate these findings in clinical practice and to investigate ALIS's role in NTM lung disease caused by other species.

Toward better cures for Mycobacterium abscessus lung disease.

SUMMARYThe opportunistic pathogen Mycobacterium abscessus (Mab) causes fatal lung infections that bear similarities-and notable differences-with tuberculosis (TB) pulmonary disease. In contrast to TB, no antibiotic is formally approved to treat Mab disease, there is no reliable cure, and the discovery and development pipeline is incredibly thin. Here, we discuss the factors behind the unsatisfactory cure rates of Mab disease, namely intrinsic resistance and persistence of the pathogen, and the use of underperforming, often parenteral and toxic, repurposed drugs. We propose preclinical strategies to build injectable-free sterilizing and safe regimens: (i) prioritize oral bactericidal antibiotic classes, with an initial focus on approved agents or advanced clinical candidates to provide immediate options for desperate patients, (ii) test drug combinations early, (iii) optimize novel leads specifically for M. abscessus, and (iv) consider pharmacokinetic-pharmacodynamic targets at the site of disease, the lung lesions in which drug tolerant bacterial populations reside. Knowledge and tool gaps in the preclinical drug discovery process are identified, including validated mouse models and computational platforms to enable in vitro mouse-human translation. We briefly discuss recent advances in clinical development, the need for readouts and biomarkers that correlate with cure, and clinical trial concepts adapted to the uniqueness of Mab patient populations for new regimen development. In an era when most pharmaceutical firms have withdrawn from antimicrobial drug discovery, the breakthroughs needed to fill the regimen development pipeline will likely come from partnerships between academia, biotech, pharma, non-profit organizations, and governments, with incentives that reward cooperation.

Efficacies of omadacycline + amikacin + imipenem and an all-oral regimen omadacycline + clofazimine + linezolid in a mouse model of M. abscessus lung disease.

Treatment outcomes for Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab. Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen's effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCEMycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus. Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.

Case Commentary: Dual β-lactam as part of regimen to treat Mycobacterium abscessus lung disease.

Individuals with compromised lung function and immunity are susceptible to developing chronic Mycobacterium abscessus infection. Current treatment recommendations typically involve using one β-lactam antibiotic in combination with non-β-lactam antibiotics. However, a recent case study (B. Becken, K. M. Dousa, J. L. Johnson, S. M. Holland, and R. A. Bonomo, Antimicrob Agents Chemother 68:e00319-24, 2024, https://doi.org/10.1128/aac.00319-24) demonstrated successful treatment of chronic M. abscessus lung disease in a child using two β-lactam antibiotics simultaneously. This commentary reviews the emerging evidence and outstanding questions regarding dual β-lactam therapy for M. abscessus infections.

Geographic Variation and Environmental Predictors of Nontuberculous Mycobacteria in Laboratory Surveillance, Virginia, USA, 2021-20231.

Because epidemiologic and environmental risk factors for nontuberculous mycobacteria (NTM) have been reported only infrequently, little information exists about those factors. The state of Virginia, USA, requires certain ecologic features to be included in reports to the Virginia Department of Health, presenting a unique opportunity to study those variables. We analyzed laboratory reports of Mycobacterium avium complex (MAC) and M. abscessus infections in Virginia during 2021-2023. MAC/M. abscessus was isolated from 6.19/100,000 persons, and 2.37/100,000 persons had MAC/M. abscessus lung disease. M. abscessus accounted for 17.4% and MAC for 82.6% of cases. Saturated vapor pressure was associated with MAC/M. abscessus prevalence (prevalence ratio 1.414, 95% CI 1.011-1.980; p = 0.043). Self-supplied water use was a protective factor (incidence rate ratio 0.304, 95% CI 0.098-0.950; p = 0.041). Our findings suggest that a better understanding of geographic clustering and environmental water exposures could help develop future targeted prevention and control efforts.

Efficacy of Omadacycline-Containing Regimen in a Mouse Model of Pulmonary Mycobacteroides abscessus Disease.

Mycobacteroides abscessus is an opportunistic pathogen in people with structural lung conditions such as bronchiectasis, chronic obstructive pulmonary disease, and cystic fibrosis. Pulmonary M. abscessus infection causes progressive symptomatic and functional decline as well as diminished lung function and is often incurable with existing antibiotics. We investigated the efficacy of a new tetracycline, omadacycline, in combination with existing antibiotics recommended to treat this indication, in a mouse model of M. abscessus lung disease. Amikacin, azithromycin, bedaquiline, biapenem, cefoxitin, clofazimine, imipenem, linezolid, and rifabutin were selected as companions to omadacycline. M. abscessus burden in the lungs of mice over a 4-week treatment duration was considered the endpoint. Omadacycline in combination with linezolid, imipenem, cefoxitin, biapenem, or rifabutin exhibited early bactericidal activity compared to any single drug. Using three M. abscessus isolates, we also determined the in vitro frequency of spontaneous resistance against omadacycline to be between 1.9 × 10-10 and 6.2 × 10-10 and the frequency of persistence against omadacycline to be between 5.3 × 10-6 and 1.3 × 10-5. Based on these findings, the combination of omadacycline and select drugs that are included in the recent treatment guidelines may exhibit improved potency to treat M. abscessus lung disease. IMPORTANCE M. abscessus disease incidence is increasing in the United States. This disease is difficult to cure with existing antibiotics. In this study, we describe the efficacy of a new tetracycline antibiotic, omadacycline, in combination with an existing antibiotic to treat this disease. A mouse model of M. abscessus lung disease was used to assess the efficacies of these experimental treatment regimens. Omadacycline in combination with select existing antibiotics exhibited bactericidal activity during the early phase of treatment.

Preclinical murine models to study lung infection with Mycobacterium abscessus complex

Mycobacterium abscessus is a non-tuberculous mycobacterium (NTM) able to cause invasive pulmonary infections, named NTM pulmonary disease. The therapeutic approaches are limited, and infections are difficult to treat due to antibiotic resistance conferred by an impermeable cell wall, drug efflux pumps, or drug-modifying enzymes. The development of new therapeutics, intended as antimicrobials or drug limiting immunopathology, is urgently necessary. In this context, the preclinical murine models of M. abscessus represent a useful tool to validate and translate in vitro-proofed concepts. These in vivo models are essential for developing new targets and drugs, ameliorating our knowledge in combinatorial regimens of current existing antibiotic treatments, and repurposing existing drugs for new therapeutic options against M. abscessus infection. Thus, this review aims at providing an overview of the current state of the art of preclinical murine models to study M. abscessus lung infection and its exploitation for new therapeutic approaches.This review discusses the murine models available focusing on the different bacterial challenges (aerosol, intranasal, intratracheal, and intravenous administrations), murine genetic background, and additional bacterial related factors. Then, we discuss the successful preclinical models for M. abscessus respiratory infection exploited to study the efficacy and safety of new antimicrobials or to determine the best dosage and route of administration of existing drugs. Finally, we present the current murine models exploited to develop new therapeutic approaches to modulate the host immune response and limit immunopathological damage during M. abscessus lung disease. In conclusion, our review article provides an overview of current and available murine models to characterize acute or chronic infections and to study the outcome of new therapeutic strategies against M. abscessus lung infection.

Why Matter Matters: Fast-Tracking Mycobacterium abscessus Drug Discovery.

Unlike Tuberculosis (TB), Mycobacterium abscessus lung disease is a highly drug-resistant bacterial infection with no reliable treatment options. De novo M. abscessus drug discovery is urgently needed but is hampered by the bacterium’s extreme drug resistance profile, leaving the current drug pipeline underpopulated. One proposed strategy to accelerate de novo M. abscessus drug discovery is to prioritize screening of advanced TB-active compounds for anti-M. abscessus activity. This approach would take advantage of the greater chance of homologous drug targets between mycobacterial species, increasing hit rates. Furthermore, the screening of compound series with established structure–activity-relationship, pharmacokinetic, and tolerability properties should fast-track the development of in vitro anti-M. abscessus hits into lead compounds with in vivo efficacy. In this review, we evaluated the effectiveness of this strategy by examining the literature. We found several examples where the screening of advanced TB chemical matter resulted in the identification of anti-M. abscessus compounds with in vivo proof-of-concept, effectively populating the M. abscessus drug pipeline with promising new candidates. These reports validate the screening of advanced TB chemical matter as an effective means of fast-tracking M. abscessus drug discovery.

Amikacin Liposomal Inhalation Suspension in the Treatment of Mycobacterium abscessus Lung Infection: A French Observational Experience.

Background Mycobacterium abscessus infections remain difficult to manage in both cystic fibrosis (CF) and non-CF patients and reported clinical outcomes are largely unsatisfactory. Clinical trial data are limited and no approved therapies are currently available for the management of M abscessus lung diseases. As an alternative, cohort studies may provide insightful information into the management of M abscessus pulmonary disease.MethodsBased on a retrospective observational cohort study, we investigated the safety and efficacy of amikacin liposome inhaled suspension (ALIS) as an adjunct to a standard antibiotic regimen for M abscessus lung infection in both CF and non-CF patients. We also assessed the association of patient drug compliance with culture conversion and clinical outcomes.ResultsTwenty-six patients had long-term follow-up data available. Culture conversion was achieved in 54% (14/26) of the patients with no difference between CF and non-CF patients after an average treatment duration of 10 months. Patient treatment compliance was significantly better in the converter group compared to nonconverters with an odds ratio of 44.78 associated with good compared to poor patient compliance. Overall, 9 patients (35%) experienced an adverse event that led to treatment discontinuation.ConclusionsALIS appears beneficial in both CF and non-CF populations with M abscessus lung disease.

Strongly Bactericidal All-Oral β-Lactam Combinations for the Treatment of Mycobacterium abscessus Lung Disease.

ABSTRACTBioactive forms of oral β-lactams were screened in vitro against Mycobacterium abscessus with and without the bioactive form of the oral β-lactamase inhibitor avibactam ARX1796. Sulopenem was equally active without avibactam, while tebipenem, cefuroxime, and amoxicillin required avibactam for optimal activity. Systematic pairwise combination of the four β-lactams revealed strong bactericidal synergy for each of sulopenem, tebipenem, and cefuroxime combined with amoxicillin in the presence of avibactam. These all-oral β-lactam combinations warrant clinical evaluation.

Nebulized Bacteriophage in a Patient With Refractory Mycobacterium abscessus Lung Disease.

An elderly man with refractory Mycobacterium abscessus lung disease previously developed anti-phage neutralizing antibodies while receiving intravenous phage therapy. Subsequent phage nebulization resulted in transient weight gain, decreased C-reactive protein, and reduced Mycobacterium burden. Weak sputum neutralization may have limited the outcomes, but phage resistance was not a contributing factor.

In Vitro Activity of Bedaquiline and Imipenem against Actively Growing, Nutrient-Starved, and Intracellular Mycobacterium abscessus.

Mycobacterium abscessus lung disease is difficult to treat due to intrinsic drug resistance and the persistence of drug-tolerant bacteria. Currently, the standard of care is a multidrug regimen with at least 3 active drugs, preferably including a β-lactam (imipenem or cefoxitin). These regimens are lengthy and toxic and have limited efficacy. The search for more efficacious regimens led us to evaluate bedaquiline, a diarylquinoline licensed for treatment of multidrug-resistant tuberculosis. We performed in vitro time-kill experiments to evaluate the activity of bedaquiline alone and in combination with the first-line drug imipenem against M. abscessus under various conditions. Against actively growing bacteria, bedaquiline was largely bacteriostatic and antagonized the bactericidal activity of imipenem. Contrarily, against nutrient-starved persisters, bedaquiline was bactericidal, while imipenem was not, and bedaquiline drove the activity of the combination. In an intracellular infection model, bedaquiline and imipenem had additive bactericidal effects. Correlations between ATP levels and the bactericidal activity of imipenem and its antagonism by bedaquiline were observed. Interestingly, the presence of Tween 80 in the media affected the activity of both drugs, enhancing the activity of imipenem and reducing that of bedaquiline. Overall, these results show that bedaquiline and imipenem interact differently depending on culture conditions. Previously reported antagonistic effects of bedaquiline on imipenem were limited to conditions with actively multiplying bacteria and/or the presence of Tween 80, whereas the combination was additive or indifferent against nutrient-starved and intracellular M. abscessus, where promising bactericidal activity of the combination suggests it may have a role in future treatment regimens.

Epetraborole Is Active against Mycobacterium abscessus.

ABSTRACTBenzoxaboroles are a new class of leucyl-tRNA synthetase inhibitors. We recently reported that the antitubercular 4-halogenated benzoxaboroles are active against Mycobacterium abscessus. Here, we find that the nonhalogenated benzoxaborole epetraborole, a clinical candidate developed for Gram-negative infections, is also active against M. abscessus in vitro and in a mouse model of infection. This expands the repertoire of advanced lead compounds for the discovery of a benzoxaborole-based candidate to treat M. abscessus lung disease.

Serological diagnosis of Mycobacterium avium complex lung diseases by enzyme immunoassay of IgA antibodies against MAC-specific glycopeptidolipid core antigen

IntroductionThere is an increasing trend worldwide in the incidence of Mycobacterium avium complex pulmonary diseases (MAC-PD) and the diagnosis is sometimes complicated. Recently, an enzyme immunoassay (EIA) kit that detects serum IgA antibody against MAC-specific glycopeptidolipid (GPL) core antigen had been developed and found to be useful in discriminating MAC-PD from other lung diseases. The antibody was subsequently also found to be elevated in patients suffering Mycobacterium abscessus pulmonary diseases (MAB-PD). This study is to evaluate this EIA kit in the serological diagnosis of MAC-PD in Hong Kong Chinese patients. MethodsThe study was conducted in Grantham Hospital, Hong Kong between July 2017 and July 2018. Assay of the IgA antibody level using the EIA kit was done on blood samples collected from patients suffering from MAC-PD, MAB-PD, pulmonary tuberculosis and other lung diseases. ResultsThere were 100 subjects recruited into the study, among which 11 were excluded. By using the cut-off value 0.7 U/mL provided by the manufacturer, the sensitivity and specificity for diagnosis were 73.7% and 77.6% for MAC-PD; 50% and 77.6% for MAB-PD. By receiver operating characteristic curves analysis, new cut-off for MAC-PD and MAB-PD were calculated as 1.771 U/mL and 0.172 U/m, respectively. The sensitivity and specificity were 68.4% and 86.2% for MAC-PD, whereas 66.7% and 72.4% for MAB-PD. ConclusionsOur study showed that the enzyme immunoassay of IgA antibodies against MAC-specific glycopeptidolipid core antigen could help to distinguishing MAC and M. abscessus pulmonary diseases from pulmonary tuberculosis and other lung diseases among Hong Kong Chinese patients. Further larger scale studies in our local population for the usefulness of this antibody test in the diagnosis and monitoring of MAC and M. abscessus lung diseases might be warranted.

Clinical risk factors related to treatment failure in Mycobacterium abscessus lung disease.

The clinical importance of Mycobacterium abscessus subsp. abscessus (M. abscessus) lung disease has been increasing, but few studies have assessed the clinical characteristics associated with the treatment outcome. We retrospectively analyzed 75 consecutive patients with M. abscessus lung disease diagnosed at a tertiary hospital from January 2004 to April 2018. Among 52 patients with sufficient clinical data, 19 patients (42.2%) achieved treatment success. Compared with 26 (57.8%) patients in the treatment failure group, body mass index (BMI) (19.8 vs 17.5kg/m2, P = 0.022), previous nontuberculous mycobacterial (NTM) lung disease (26.3% vs 61.5%, P = 0.034), the presence of cavitary lesions (31.6% vs 69.2%, P = 0.017), and the bronchiectasis score (3.0 vs 5.0, P = 0.003) were significantly different in the treatment success group. Multivariate analysis showed that age (adjusted hazard ratio (aHR), 0.94; 95% confidence interval (CI), 0.90 to 0.99; P = 0.010), the presence of cavitary lesions (aHR, 0.34; 95% CI, 0.12 to 0.94; P = 0.039), and previous NTM lung disease (aHR, 0.28; 95% CI, 0.09 to 0.86; P = 0.026) were negatively associated with treatment success. This is the first study to show that previous NTM lung disease might be a clinically important factor related to unfavorable treatment outcomes in M. abscessus lung disease patients. To increase our understanding the characteristics of M. abscessus lung disease, this factor should be independently analyzed in future research.

Spontaneous sputum conversion and reversion in Mycobacterium abscessus complex lung disease.

BackgroundWe aim to investigate the rate of spontaneous sputum conversion and reversion in patients with Mycobacterium abscessus complex (MABC) lung disease.MethodsAmong 241 patients diagnosed with MABC lung disease between July 2012 and December 2018, 126 patients with persistent sputum positivity for ≥ 6 months without treatment were enrolled at a tertiary referral center in South Korea. Patients were subdivided into two groups, depending on whether or not treatment was initiated within 2 years of diagnosis. The rates of spontaneous sputum culture conversion and reversion was investigated in patients who did not receive treatment within 2 years.ResultsThe mean age of 126 patients was 62.9 years. During a mean follow-up duration of 3.2 years, 33 (26.2%) patients received treatment within 2 years of diagnosis. Among the remaining 93 patients not receiving treatment within 2 years, spontaneous sputum conversion occurred in 24 (25.8%) patients during a mean follow-up duration of 3.7 years after diagnosis. No significant differences were observed in time to conversion between Mycobacterium abscessus and Mycobacterium massiliense lung diseases. The Cox regression analysis showed that malignancy as a comorbid disease and the lower number of lobes involved were independent predictors of spontaneous sputum conversion. After spontaneous sputum conversion, reversion occurred in 27.8% patients at a median of 18.2 months after conversion.ConclusionsAmong patients with MABC lung disease who did not receive treatment for at least 2 years after diagnosis, approximately one-fourth experienced spontaneous conversion. However, not a few patients experienced reversion after spontaneous conversion.

Glycopeptidolipid Genotype Correlates With the Severity of Mycobacterium abscessus Lung Disease.

Smooth and rough colony morphotypes of Mycobacterium abscessus are associated with virulence, but some isolates form both smooth and rough colonies, impeding successful morphotype identification. Reportedly, smooth/rough morphotypes are also related to the glycopeptidolipid (GPL) genotype. However, the accuracy of GPL genotyping to discriminate morphotypes and the relationship between GPL genotype and clinical characteristics of M abscessus lung disease have not been verified. A retrospective analysis of colony morphology, GPL genotype, and clinical data from 182 patients with M abscessus lung disease was conducted. Of 194 clinical isolates, 126 (65.0%), 15 (7.7%), and 53 (27.3%) exhibited rough, smooth, and mixed colony morphotypes, respectively. Glycopeptidolipid genotyping indicated that 86.7% (13 of 15) of smooth isolates belonged to the GPL-wild type (WT) group, whereas 98.4% (124 of 126) of rough isolates belonged to the GPL-mutant type (MUT) group. Therefore, GPL genotyping accurately distinguished between smooth and rough morphotypes. Mixed colony morphotypes were also divided into GPL-WT (18.9%) and GPL-MUT (81.1%) groups. Further analysis revealed that patients infected with the GPL-MUT group presented with significantly worse baseline clinical characteristics and exacerbated episodes of lung disease. Glycopeptidolipid genotyping accurately distinguishes smooth and rough colony morphotypes. Patients infected with the GPL-MUT genotype exhibit worse clinical characteristics and are at a higher risk of exacerbated lung disease.

Rifabutin Is Active against Mycobacterium abscessus in Mice.

There is no reliable cure for Mycobacterium abscessus lung disease. Rifampin is not used clinically due to poor in vitro potency. In contrast, we have shown that rifabutin, another approved rifamycin used to treat tuberculosis, is potent in vitro against M. abscessus Here, we report that rifabutin is as active as clarithromycin against M. abscessus K21 in NOD.CB17-Prkdcscid/NCrCrl mice. This suggests that rifabutin should be considered a repurposing candidate for patients with M. abscessus disease.

An Intensified Regimen Containing Linezolid Could Improve Treatment Response in Mycobacterium abscessus Lung Disease.

Background Treatment response for the Mycobacterium abscessus (M. abscessus) lung disease remains far from satisfying. An effective regimen is needed to solve the problem. Methods We retrospectively reviewed the medical records of all patients with M. abscessus lung disease who received antibiotics regimen at Beijing Chest Hospital Affiliated to Capital Medical University between July 1, 2010, and February 1, 2018. Patients were administered a conventional antibiotics regimen (including macrolide and moxifloxacin, along with an initial 12-week course of low-dose cefoxitin and amikacin) or intensified regimen (including a higher dosage of cefoxitin and linezolid besides conventional drugs), respectively. The time to sputum-culture conversion and proportion of sputum-culture conversion in liquid broth were investigated to evaluate the efficacy and evaluation of safety by performing the classification of adverse events according to the Division of AIDS, National Institute of Allergy and Infectious Disease. Patients were followed for 18 months from baseline. Results In the conventional regimen group, the sputum conversion rate at 18 months was 29.4% (10/34), and the median time until sputum conversion was 2 months (IQR, 1-2 mo). Furthermore, in the intensified regimen group, the sputum conversion rate was 81.3% (13/16), and the median time until sputum conversion was 1 month (IQR, 1-1 mo). Leukopenia and drug-induced hepatotoxicity occurred more frequently in the intensified regimen group in contrast with the conventional regimen group patients. However, only 1 adverse event in the intensified regimen group was classified as severe adverse event. Conclusions The intensified regimen could improve sputum conversion of M. abscessus lung disease compared with conventional regimen, but close safety surveillance is necessary to monitor adverse events.