Nebulized Bacteriophage in a Patient With Refractory Mycobacterium abscessus Lung Disease.
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ABSTRACT:
SUBMITTER: Dedrick RM
PROVIDER: S-EPMC9251665 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Isolation of Mycobacterium abscessus subspecies abscessus (MAA) is common during Mycobacterium avium complex (MAC) lung disease therapy, but there is limited information about the clinical significance of the MAA isolates.We identified 53 of 180 patients (29%) treated for MAC lung disease who had isolation of MAA during MAC lung disease therapy. Patients were divided into those without (group 1) and those with (group 2) MAA lung disease.There were no significant demographic differences between patients with and without MAA isolation or between groups 1 and 2. Group 1 and 2 patients had similar total sputum cultures obtained (P = .7; 95% CI, -13.4 to 8.6) and length of follow-up (P = .8; 95% CI, -21.5 to 16.1). Group 2 patients had significantly more total positive cultures for MAA (mean±SD, 15.0 ± 11.1 vs 1.2 ± 0.4; P < .0001; 95% CI, -17.7 to -9.9), were significantly more likely to develop new or enlarging cavitary lesions while on MAC therapy (P > .0001), and were significantly more likely to meet all three American Thoracic Society diagnostic criteria for nontuberculous mycobacterial disease (21 of 21 [100%] vs 0 of 32 [0%]; P < .0001) compared with group 1 patients. Group 1 patients were significantly more likely to have single, positive MAA cultures than group 2 patients (25 of 31 vs 0 of 21; P < .0001).Microbiologic and clinical follow-up after completion of MAC lung disease therapy is required to determine the significance of MAA isolated during MAC lung disease therapy. Single MAA isolates are not likely to be clinically significant.
| S-EPMC4694086 | biostudies-other
Project description: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.
| S-EPMC7185584 | biostudies-literature
Project description:We report the first Korean case of lung diseases caused by Mycobacterium abscessus subsp. bolletii in a previously healthy male, except for a previous history of pulmonary tuberculosis and bronchiectasis. All serial isolates are identified as M. abscessus subsp. bolletii by multi-locus sequence analysis based on the hsp65, rpoB, and 16S rRNA fragments. At the genetic level, the isolate has the erm(41) gene with a T28 sequevar, associated with clarithromycin resistance, and no rrl mutation. The isolate is resistant to clarithromycin. Although the symptoms and radiographic findings have improved after combination of antibiotics, the follow-up sputum cultures are persistently positive.
| S-EPMC3919962 | biostudies-literature
Project description:An 81-year-old immunocompetent patient with bronchiectasis and refractory Mycobacterium abscessus lung disease was treated for 6 months with a three-phage cocktail active against the strain. In this case study of phage to lower infectious burden, intravenous administration was safe and reduced the M. abscessus sputum load tenfold within one month. However, after two months, M. abscessus counts increased as the patient mounted a robust IgM- and IgG-mediated neutralizing antibody response to the phages, which was associated with limited therapeutic efficacy.
| S-EPMC8571776 | biostudies-literature
Project description:BackgroundLittle is known about the nature of the host immune response to Mycobacterium abscessus complex (MABC) infection. The aim of the present study was to investigate whether alterations in serum immunomolecule levels after treating MABC lung disease patients with antibiotics can reflect the disease-associated characteristics.MethodsA total of 22 immunomolecules in 24 MABC lung disease patients before and after antibiotic therapy were quantitatively analyzed using a multiplex bead-based system.ResultsIn general, the pre-treatment levels of T helper type 1 (Th1)-related cytokines, i.e., interferon (IFN)-? and interleukin (IL)-12, and Th2-related cytokines, i.e., IL-4 and IL-13, were significantly decreased in patients compared with control subjects. In contrast, the pre-treatment levels of Th17-related cytokines, i.e., IL-17 and IL-23, were significantly increased in MABC patients. Interestingly, significantly higher levels of IFN-?-induced protein (IP)-10 and monokine induced by IFN-? protein (MIG) were detected in patients with failure of sputum conversion at post-treatment compared to patients with successful sputum conversion.ConclusionReduced Th1 and Th2 responses and enhanced Th17 responses in patients may perpetuate MABC lung disease, and the immunomolecules IP-10 and MIG, induced through IFN-?, may serve as key markers for indicating the treatment outcome.
| S-EPMC4190320 | biostudies-literature
Project description: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.
| S-EPMC6885786 | biostudies-literature
Project description:In recent years, many novel nontuberculous mycobacterial species have been discovered through genetic analysis. Mycobacterium massiliense and M. bolletii have recently been identified as species separate from M. abscessus. However, little is known regarding their clinical and microbiological differences in Japan. We performed a molecular identification of stored M. abscessus clinical isolates for further identification. We compared clinical characteristics, radiological findings, microbiological findings, and treatment outcomes among patients with M. abscessus and M. massiliense lung diseases. An analysis of 102 previous isolates of M. abscessus identified 72 (71%) M. abscessus, 27 (26%) M. massiliense, and 3 (3%) M. bolletii isolates. Clinical and radiological findings were indistinguishable between the M. abscessus and M. massiliense groups. Forty-two (58%) patients with M. abscessus and 20 (74%) patients with M. massiliense infections received antimicrobial treatment. Both the M. abscessus and M. massiliense groups showed a high level of resistance to all antimicrobials, except for clarithromycin, kanamycin, and amikacin. However, resistance to clarithromycin was more frequently observed in the M. abscessus than in the M. massiliense group (16% and 4%, respectively; P = 0.145). Moreover, the level of resistance to imipenem was significantly lower in M. abscessus isolates than in M. massiliense isolates (19% and 48%, respectively; P = 0.007). The proportions of radiological improvement, sputum smear conversion to negativity, and negative culture conversion during the follow-up period were higher in patients with M. massiliense infections than in those with M. abscessus infections. Patients with M. massiliense infections responded more favorably to antimicrobial therapy than those with M. abscessus infections.
| S-EPMC3486228 | biostudies-literature
Project description:Mycobacterium abscessus accounts for a large proportion of lung disease cases caused by rapidly growing mycobacteria. The association between clarithromycin sensitivity and treatment outcome is clear. However, M. abscessus culture and antibiotic susceptibility testing are time-consuming. Clarithromycin susceptibility genotyping offers an alternate, rapid approach to predicting the efficacy of clarithromycin-based antibiotic therapy. M. abscessus lung disease patients were divided into two groups based upon the clarithromycin susceptibility genotype of the organism isolated. A retrospective analysis was conducted to compare the clinical features, microbiological characteristics, and treatment outcomes of the two groups. Several other potential predictors of the response to treatment were also assessed. Sixty-nine patients were enrolled in the clarithromycin-resistant genotype group, which included 5 infected with rrl 2058-2059 mutants and 64 infected with erm(41)T28-type M. abscessus; 31 were in the clarithromycin-sensitive group, i.e., 6 and 25 patients infected with genotypes erm(41)C28 and erm(41) M type, respectively. The results showed that lung disease patients infected with clarithromycin-sensitive and -resistant M. abscessus genotypes differed significantly in clarithromycin-based combination treatment outcomes. Patients infected with the clarithromycin-sensitive genotype exhibited higher initial and final sputum-negative conversion and radiological improvement rates and better therapeutic outcomes. Multivariate analysis demonstrated that genotyping was a reliable and, more importantly, rapid means of predicting the efficacy of clarithromycin-based antibiotic treatment for M. abscessus lung disease.
| S-EPMC5923093 | biostudies-literature
Project description:The rapidly growing mycobacterium M. abscessus sensu lato is the causative agent of emerging pulmonary and skin diseases and of infections following cosmetic surgery and postsurgical procedures. M. abscessus sensu lato can be divided into at least three subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. Clinical isolates of rapidly growing mycobacteria were previously identified as M. abscessus by DNA-DNA hybridization. More than 30% of these 117 clinical isolates were differentiated as M. abscessus subsp. massiliense using combinations of multilocus genotyping analyses. A much more cost-effective technique to distinguish M. abscessus subsp. massiliense from M. abscessus subsp. abscessus, a multiplex PCR assay, was developed using the whole-genome sequence of M. abscessus subsp. massiliense JCM15300 as a reference. Several primer sets were designed for single PCR to discriminate between the strains based on amplicons of different sizes. Two of these single-PCR target sites were chosen for development of the multiplex PCR assay. Multiplex PCR was successful in distinguishing clinical isolates of M. abscessus subsp. massiliense from samples previously identified as M. abscessus. This approach, which spans whole-genome sequencing and clinical diagnosis, will facilitate the acquisition of more-precise information about bacterial genomes, aid in the choice of more relevant therapies, and promote the advancement of novel discrimination and differential diagnostic assays.
| S-EPMC3911466 | biostudies-literature
Project description:Background:Sitafloxacin (STFX) exhibits potent activity against Mycobacterium avium complex (MAC) in both in vitro and in vivo experiments. However, limited data are available for the clinical efficacy and adverse effects of STFX and the susceptibility of refractory MAC lung disease (MAC-LD) to the drug. Therefore, this study was aimed at evaluating the clinical efficacy and safety of an STFX-containing regimen for the treatment of refractory MAC-LD. Methods:We retrospectively evaluated treatment outcomes of 31 patients with refractory MAC-LD, who received an STFX-containing regimen for ?4 weeks between January 2010 and July 2017. Refractory MAC-LD was defined as persistent positive sputum cultures for >6 months of macrolide-based standard therapy. Results:Clarithromycin resistance (minimum inhibitory concentration [MIC] ?32 ?g/mL) was identified in 15 patients (48%). Twelve months after receiving the STFX-containing regimen, 26% and 19% of patients showed symptomatic and radiological responses, respectively. Although STFX-associated adverse effects were noted in 9 patients, their severity was grade 1 (National Cancer Institute Common Terminology Criteria); only 1 patient discontinued STFX because of suspected gastrointestinal disturbance. Negative sputum culture conversion was achieved in 7 patients (23%). Both univariate and multivariate logistic regression analyses revealed that surgery, low STFX MIC (?1 ?g/mL), and macrolide resistance were significant predictors of negative sputum culture conversion. Conclusions:Our results demonstrate that STFX may be effective in one-fourth of patients with refractory MAC-LD. Prospective larger studies that include the analyses of MAC are needed to determine the clinical efficacy of STFX against refractory MAC-LD.
| S-EPMC6519390 | biostudies-literature