Pleuritis Caused by <i>Mycobacterium kyorinense</i> without Pulmonary Involvement
Tatsuyoshi IkeueHiroshi YoshidaEiichiro TanakaIssei OhiSusumu NoguchiAkari FukaoSatoshi TerashitaSadao HorikawaTakakazu Sugita
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Abstract:
We herein describe the first known case of pleuritis caused by Mycobacterium kyorinense without pulmonary involvement. A 48-year-old man undergoing immunosuppressant therapy presented with cough and dyspnea. An accumulation of pleural fluid was noted; however, computed tomography revealed no pulmonary lesions. Cultures of the fluid yielded non-tuberculous mycobacteria, which was identified as Mycobacterium kyorinense. The patient recovered after 6 months of therapy with clarithromycin and moxifloxacin. Clinicians should be aware that Mycobacterium kyorinense can cause pleuritis without pulmonary involvement. When mycobacterial species are isolated from the pleural fluid, precise identification and drug susceptibility testing are warranted.Keywords:
Mycobacterium avium complex
Mycobacterium abscessus
Mycobacterium abscessus
Mycobacterium chelonae
Mycobacterium fortuitum
Nontuberculous Mycobacteria
Regimen
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The differentiation between Mycobacterium abscessus subspecies abscessus (M. abscessus) and Mycobacterium abscessus subspecies massiliense (M. massiliense) and determination of the presence of inducible resistance to macrolide antibiotics are important factors in the management of patients with Mycobacterium abscessus complex (MABC) infections. Unlike pulmonary MABC infections, little information on extrapulmonary MABC infections is available.The molecular identification of clinical isolates was performed, and the clinical characteristics and treatment outcomes of 20 consecutive patients with extrapulmonary MABC infections were assessed.M. abscessus and M. massiliense each caused 10 (50%) of the cases. Eight (80%) M. abscessus isolates that had inducible resistance to clarithromycin harbored an intact erm(41) gene of the T28 variant, whereas two (20%) M. abscessus isolates had the C28 erm(41) variant and were susceptible to clarithromycin. All M. massiliense isolates had a truncated erm(41) gene and were susceptible to clarithromycin. The drug susceptibility profiles other than clarithromycin were similar for the M. abscessus and M. massiliense isolates. Of the 20 patients, 17 (85%) showed a favorable outcome, including all patients with M. massiliense infection and 70% (7/10) of patients with M. abscessus infection. Favorable outcomes were associated with M. massiliense and M. abscessus isolates with a non-functional erm(41) gene (p=0.049).Precise species and subspecies identification and the determination of macrolide susceptibility are recommended for the optimal treatment of extrapulmonary MABC infections.
Mycobacterium abscessus
Subspecies
Nontuberculous Mycobacteria
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Objectives . Clarithromycin is recommended as the core agent for treating M. abscessus infections, which usually calls for at least one year of treatment course, facilitating the development of resistance. This study aimed to identify the underlying mechanism of in vivo development of clarithromycin resistance in M. abscessus clinical isolates. Methods . M. abscessus isolates from patients with lung infections during long-term antibiotic therapy were longitudinally collected and sequenced. PFGE DNA fingerprinting was used to confirm the genetic relationships of the isolates. Whole genome comparative analysis was performed to identify the genetic determinants that confer the clarithromycin resistance. Results . Three pairs of initially clarithromycin-susceptible and subsequently clarithromycin-resistant M. abscessus isolates were obtained. We found that the clarithromycin-resistant isolates emerged relatively rapidly, after 4–16 months of antibiotic therapy. PFGE DNA fingerprinting showed that the clarithromycin-resistant isolates were identical to the initial clarithromycin-susceptible ones. Whole genome sequencing and bioinformatics analysis identified several genetic alternations in clarithromycin-resistant isolates, including genes encoding efflux pump/transporter, integral component of membrane, and the tetR and lysR family transcriptional regulators. Conclusion . We identified genes likely encoding new factors contributing to clarithromycin-resistance phenotype of M. abscessus , which can be useful in prediction of clarithromycin resistance in M. abscessus .
Mycobacterium abscessus
TetR
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Background: Mycobacterium abscessus is the most pathogenic and drug-resistant rapid-growing mycobacterium.Clarithromycin or azithromycin are the only regular oral antimycobacterial agents that have an effect on M. abscessus.We tried to detect the clarithromycin-resistant strains from the clinical isolates of M. abscessus.Methods: We tried to isolate the clarithromycin-resistant strains from 220 clinical isolates of M. abscessus by performing using reverse hybridization assay (RHA) and the broth microdilution test (BMT).Results: Seven resistant strains (3.2%) from all the tested clinical isolates were detected by BMT.Three of these resistant strains were also detected by RHA and it was confirmed that they had point mutants.Conclusion: These results showed that clarithromycin resistance in M. abscessus clinical isolates is related to a point mutation and other unknown mechanisms.(
Mycobacterium abscessus
Broth microdilution
Antimycobacterial
Nontuberculous Mycobacteria
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Objective To compare the efficacy of clarithromycin with moxifloxacin in treatment of light and moderate community acquired pneumonia patients. Methods 78 CAP patients were randomly divided into two groups, clarithromycin group consisted of 38 patients and treated with clarithromycin 250mg bid and moxifloxacin group consisted of 40 patients treated with moxifloxacin 400mg,qd. Both for a course of 2～4 weeks. Results 23 patients in clarithromycin group were cured,12 markedly improved,2 improved,1 not improved, with a cure rate of 60.5% and an effective rate of 92.1%. 25 patients in the moxifloxacin group were cured, 11 markedly improved, 3 improved,1 not improved , with a cure rate of 62.5% and an effective rate of 90%. 3 patients (7.9%) in the clarithromycin group and 4 patients(10%) in the moxifloxacin group had gastrointestinal reaction. There no significant differences in cure rates, effective rate and gastrointestinal reaction rate between the two groups were observed (P 0.05). Conclusion The effect and side-effects of orally clarithromycin and moxifloxacin on light and moderate community acquired pneumonia patients are similar. Clarithromycin is recommended for use in hospitals as it is cheaper and convenient.
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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.
Mycobacterium abscessus
Nontuberculous Mycobacteria
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Purpose: Clarithromycin is a 14-membered ring macrolide antibiotic with anti-inflammatory as well as antibacterial activity, and has been used worldwide. Moxifloxacin is a leading fourth generation quinolone antibiotic that has been used worldwide perioperatively. We intended to evaluate whether clarithromycin can suppress angiogenesis and inflammation in the cornea, and to compare the anti-inflammatory and anti-angiogenic effects of the two antibiotics, clarithromycin and moxifloxacin.Methods: We made a murine corneal suture model and tested the anti-inflammatory and anti-angiogenic effects of clarithromycin (5 mg/ml) and moxifloxacin (5 mg/ml) in two randomly divided groups. Dexamethasone (5 mg/ml) was used as a positive control. After making two sutures on the cornea, we performed subconjunctival injections (10 μl) on each group on the day of suture, and every day thereafter until the 8th day post-suture. After harvesting corneas on the 8th post-suture day for immunohistochemical staining, we compared neovascularization (NV), lymphangiogenesis (LY) and inflammatory cell infiltration among the groups.Results: Clarithromycin suppressed NV, LY and inflammatory infiltration, compared with phosphate-buffered saline (PBS). However, moxifloxacin did not suppress NV, LY, or inflammatory infiltration, compared with PBS. Comparison between clarithromycin and moxifloxacin, clarithromycin showed a tendency of decreasing LY (p = 0.063) and had less inflammatory cell infiltration (p < 0.05) than did the moxifloxacin group. The anti-(lymph)angiogenic and anti-inflammatory effects of clarithromycin were as high as those of dexamethasone.Conclusion: Clarithromycin suppressed LY and inflammation in the cornea, and its anti-inflammatory effect was significantly superior to that of moxifloxacin.
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Medical records of 77 patients with Q fever pneumonia that was serologically confirmed by enzyme-linked immunosorbent assay were studied to compare the clinical efficacy of doxycycline, clarithromycin, and moxifloxacin. The mean times to defervescence were 2.4 days for those receiving doxycycline, 1.9 days for those receiving clarithromycin, and 2.2 days for those receiving moxifloxacin. There were no interruptions of the regimens in any groups because of side effects, and outcome was favorable in all patients with no complications or relapses during follow-up. This efficacy of clarithromycin and moxifloxacin, together with their safety profiles, suggest that these alternative agents in the treatment of Q fever pneumonia could also be used as the first-line therapy.
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Abstract Background Mycobacterium abscessus group belongs to a group of rapidly growing mycobacteria (RGM) and, following Mycobacterium avium complex, is the second most common pathogen responsible for lung disease caused by nontuberculous mycobacteria (NTM). Clarithromycin is known to be the key drug in the treatment of M. abscessus group disease, but a high failure rate of treatment response is reported due to clarithromycin inducible resistance. Methods Using the results from a clarithromycin susceptibility test we examined the proportion of clarithromycin inducible resistant M. abscessus (sensu stricto; hereafter referred to as M. abscessus) clinical strains. Also, we attempted to detect the clarithromycin resistant strains, using the amplification refractory mutation system-PCR (ARMS-PCR) and real-time PCR methods for rapid detection of single-nucleotide polymorphisms (SNPs) at position 28 (T or C) of the erm(41) gene of M. abscessus leading to resistance to clarithromycin. Results Of the 157 M. abscessus clinical strains, clarithromycin susceptible, resistant, and inducible resistant strains accounted for 10.83% (n = 17), 22.29% (n = 35), and 66.88% (n = 105), respectively. Clarithromycin resistant strains were able to separate from clarithromycin susceptible strains by ARMS-PCR and real-time PCR identical to DNA sequence analysis. Conclusion Most M. abscessus clinical strains in Korea are resistant to clarithromycin, and ARMS-PCR and real-time PCR are useful tools for the rapid detection of single-nucleotide polymorphisms (SNPs) at position 28 of the erm(41) gene.
Mycobacterium abscessus
Nontuberculous Mycobacteria
23S ribosomal RNA
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The ribosomal methylase Erm(41) confers inducible resistance to macrolides in Mycobacterium abscessus. The aim of this work was to systematically study and compare drug susceptibility to clarithromycin and azithromycin in M. abscessus and Mycobacterium chelonae clinical isolates with a particular focus on inducible drug resistance. Clinical isolates of M. abscessus subsp. abscessus (n = 21), M. abscessus subsp. bolletii (n = 16), M. abscessus subsp. massiliense (n = 10) and M. chelonae (n = 22) were characterized regarding their erm(41) and rrl genotypes and subjected to drug susceptibility testing (DST) for clarithromycin and azithromycin. Microdilution DST was performed in cation-adjusted Mueller–Hinton broth (pH 7.4) with readings at days 3, 7 and 12 and with pre-incubation at subinhibitory macrolide concentrations for erm(41) induction. In addition, the influence of variations in pH and growth medium on DST results was examined. MICs of azithromycin were consistently higher than those of clarithromycin. In strains with an inducible erm(41) gene, high median MICs of ≥256 mg/L on day 12 were observed for both clarithromycin and azithromycin. Inducible resistance was at least as pronounced for azithromycin as for clarithromycin. Our findings do not support the suggestion of a preferential use of azithromycin over clarithromycin in order to limit inducible macrolide resistance. Both compounds provoked a comparable resistance phenotype in M. abscessus. Caution is needed when using either azithromycin or clarithromycin for treatment of M. abscessus infections.
Mycobacterium abscessus
Mycobacterium chelonae
Broth microdilution
23S ribosomal RNA
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