Microbiological and Clinical Outcomes of Treating Non- Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease

Diel, Roland; Ringshausen, Felix C.; Richter, Elvira; Welker, Lutz; Schmitz, Jochen; Nienhaus, Albert

doi:10.1016/j.chest.2017.04.166

Cited by 142 publications

(111 citation statements)

References 43 publications

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“…Patients with M. abscessus infections are routinely treated with clarithromycin along with two other antibiotics, usually amikacin, imipenem, or tigecycline (8,15). The clinical utility of these antibiotic combinations is limited by the induction of resistance to clarithromycin and by their respective toxicities (16). Our present study confirmed that rifabutin holds promising activity against M. abscessus, and combinations comprising this drug with the core recommended treatment for clarithromycin-resistant M. abscessus are synergistic (10,15).…”

Section: Discussionsupporting

confidence: 74%

In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex

Cheng

Tsai

Chang

et al. 2019

Antimicrob Agents Chemother

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Infections caused by the difficult-to-treat bacterium Mycobacterium abscessus are increasing in frequency. Rifabutin, in contrast to rifampin, appears to be active in vitro against M. abscessus, especially against clarithromycin-resistant strains. However, explorations for potential synergy between rifabutin and available antimicrobials are currently limited. In vitro synergism between rifabutin and 10 antimicrobials was evaluated in 31 mycobacterial strains by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for each rifabutinbased combination. The colony morphology was recorded. Molecular methods for determination of the M. abscessus subspecies and analysis of macrolide resistance were performed by sequencing of the secA1, rpoB, hsp65, erm (41), and rrl genes. Rifabutin yielded an MIC 50 of 16 mg/liter (range, 2 to 32 mg/liter) against 26 clinical M. abscessus isolates (comprising 13 M. abscessus subsp. abscessus and 13 M. abscessus subsp. massiliense isolates) and 5 reference strains, including M. abscessus subsp. abscessus ATCC 19977, M. abscessus subsp. bolletii BCRC 16915, M. abscessus subsp. massiliense BCRC 16916, M. chelonae ATCC 35752, and M. peregrinum ATCC 700686. Significant synergism, classified by an FICI of Յ0.5, was demonstrated for the combinations of rifabutin and imipenem in 100% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates, and significant synergism for rifabutin and tigecycline was demonstrated in 77% of M. abscessus subsp. abscessus and 69% of M. abscessus subsp. massiliense isolates. Among the 6 clarithromycin-resistant (MICs Ն 8 mg/liter) M. abscessus subsp. abscessus isolates, the combination of rifabutin and clarithromycin was 100% synergistic. Rifabutin showed promising in vitro synergism with first-line anti-M. abscessus agents, especially for macrolide-resistant M. abscessus subsp. abscessus isolates.

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Section: Discussionsupporting

confidence: 74%

In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex

Cheng

Tsai

Chang

et al. 2019

Antimicrob Agents Chemother

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“…However, in many NTM species, especially slow-growing NTM (including M. malmoense ), a significant divergence between phenotype in vitro and in vivo has been appreciated [3, 7]. A recent meta-analysis showed a poor treatment response rate, at 54%, with a high all-cause mortality rate (34%–54%) in patients treated for M. Malmoense [8]. The difficulty in determining susceptibility in NTM stems from the lack of a universally accepted laboratory protocol that is optimized for slow-growing organisms.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Cavity From Mycobacterium malmoense in an HIV-Infected Patient: Complicated by Bronchopleural Fistula

Abston

Farber

2018

Open Forum Infectious Diseases

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We present a case of M. malmoense and HIV co-infection complicated by aspergilloma leading to bronchopleural fistula with intractable pneumothorax and pleural aspergillosis, ultimately requiring surgical intervention. Treatment guidelines for M. malmoense are reviewed, literature regarding M. malmoense and HIV co-infection is reviewed, and the epidemiology of M. malmoense in North America is discussed.

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“…Mab is intrinsically resistant to several classes of antibiotics and the percentage of clinical isolates exhibiting resistance to the few drugs currently available to treat this infection is steadily increasing (5–8). Sputum culture conversion rates as low as 25% have been described with antibiotic treatment alone (9) and the cure rate for Mab pulmonary disease is only 30-50% (10).…”

Section: Introductionmentioning

confidence: 99%

Select β-lactam combinations exhibit synergy against Mycobacterium abscessus in vitro

Story-Roller

Maggioncalda

Lamichhane

2019

Preprint

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18Mycobacterium abscessus (Mab) is a nontuberculous mycobacterium that causes 19 invasive pulmonary infections in patients with structural lung disease. Mab is intrinsically 20 resistant to several classes of antibiotics and an increasing number of strains isolated 21 from patients exhibit resistance to most antibiotics considered for treatment of Mab 22 infections. Therefore, there is an unmet need for new regimens with improved efficacy 23 to treat this disease. Synthesis of the essential cell wall peptidoglycan in Mab is 24 achieved via two enzyme classes, L,D-and D-D-transpeptidases, with each class 25 preferentially inhibited by different subclasses of β-lactam antibiotics. We hypothesized 26 that a combination of two β-lactams that comprehensively inhibit the two enzyme 27 classes will exhibit synergy in killing Mab. Paired combinations of antibiotics tested for in 28 vitro synergy against Mab included dual β-lactams, a β-lactam and a β-lactamase 29 inhibitor, and a β-lactam and a rifamycin. Of the initial 206 combinations screened, 24 30 pairs exhibited synergy. 13/24 pairs were combinations of two β-lactams. 12/24 pairs 31 brought the minimum inhibitory concentrations of both drugs to within the therapeutic 32 range. Additionally, synergistic drug pairs significantly reduced the frequency of 33 selection of spontaneous resistant mutants. These novel combinations of currently-34 available antibiotics may offer viable immediate treatment options against highly-35 resistant Mab infections.36Mycobacterium abscessus (Mab) is considered to be among the most virulent of the 38 rapidly-growing nontuberculous mycobacteria (NTM). It may be environmentally or 39 nosocomially acquired (1) and can lead to severe and invasive pulmonary infections in 40 immunocompromised patients or those with structural lung diseases, such as 41 bronchiectasis or cystic fibrosis (CF). In the CF population, invasive Mab infections are 42 associated with rapid lung function decline (2-4), so adequate treatment of these 43 infections is paramount. Mab is intrinsically resistant to several classes of antibiotics 44 and the percentage of clinical isolates exhibiting resistance to the few drugs currently 45 available to treat this infection is steadily increasing (5-8). Sputum culture conversion 46 rates as low as 25% have been described with antibiotic treatment alone (9) and the 47 52 based on empirical evidence, as few systematic clinical trials have been performed to 53 elucidate the optimal therapeutic regimen against Mab. It is also frequently necessary in 54 clinical practice to tailor treatment regimens based on the resistance profiles of 55 individual Mab isolates, as the high degree of variability in antibiotic resistance observed 56 among Mab strains often precludes use of a standardized regimen (10). 58Macrolide antibiotics have historically been considered the backbone of treatment 59 against many NTMs, including Mab (2, 12). However, two of the three Mab subspecies, 60 abscessus and bolletii, harbor a functional erm(41) g...

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Microbiological and Clinical Outcomes of Treating Non- Mycobacterium Avium Complex Nontuberculous Mycobacterial Pulmonary Disease

Cited by 142 publications

References 43 publications

In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex

In Vitro Synergism of Rifabutin with Clarithromycin, Imipenem, and Tigecycline against the Mycobacterium abscessus Complex

Pulmonary Cavity From Mycobacterium malmoense in an HIV-Infected Patient: Complicated by Bronchopleural Fistula

Select β-lactam combinations exhibit synergy against Mycobacterium abscessus in vitro

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