Relationship between clinical efficacy of treatment of pulmonary Mycobacterium avium complex disease and drug-sensitivity testing of Mycobacterium avium complex isolates

We prospectively investigated the relationship between the clinical efficacy of treatment of pulmonary Mycobacterium avium complex (MAC) disease and drug-sensitivity testing of MAC isolates for antituberculous drugs, new quinolone antibiotics, and clarithromycin (CAM). Fifty-two patients who satisfied the diagnostic criteria of the American Thoracic Society (ATS) and who received treatment between April 1998 and December 2005, using combined therapy of rifampicin (RFP), ethambutol (EB), streptomycin (SM), and CAM, were enrolled in this study. The causative microorganisms isolated were Mycobacterium avium in 30 patients and M. intracellulare in 22 patients. Although separation of the two strains showed drug sensitivity testing to have slightly better minimal inhibitory concentrations (MIC) for M. intracellulare than for M. avium, there were no significant differences in the sputum eradication rate or clinical improvement between the two strains. The MICs of various antibiotics for the isolated MAC strains were as follows: RFP, 0.125–8 μg/ml; CAM, 0.25–16 μg/ml; SM, 2–128≦ μg/ml; EB, 128≦ μg/ml; levofloxacin (LVFX), 1–32 μg/ml; sparfloxacin (SPFX), 0.5–16 μg/ml; and gatifloxacin (GFLX), 0.25–8 μg/ml. The isolated MAC strains showed the same excellent drug sensitivity test results for RFP, new quinolones, and CAM, but they showed resistant drug-sensitivity results for EB and SM. Regarding the relationship between clinical efficacy and the MICs of RFP, EB, CAM, and SM, there was a good relationship only for CAM. Although the ATS has not yet recommended routine drug susceptibility testing of CAM, we believe that drug susceptibility testing of CAM should be performed before the initial treatment is undertaken for pulmonary MAC disease.     

Polymerase chain reaction-restriction fragment length polymorphism of the rpoB gene for identification of Mycobacterium avium subsp. paratuberculosis and differentiation of Mycobacterium avium subspecies

Mycobacterial speciation by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis (PRA) of the rpoB gene was evaluated for identification of Mycobacterium avium subsp. paratuberculosis (MAP) and other Mycobacterium avium complex (MAC) members to the species or subspecies level by comparison with conventional methods including hsp65 sequencing, high-performance liquid chromatography, and PCR for accepted species- or subspecies-specific genomic targets. A total of 185 type and clinical mycobacterial strains from humans, animals, and environments were tested. A 360-bp PCR product was subsequently digested with MspI, HaeIII, and SmaI restriction enzymes. The PRA using SmaI restriction showed a unique digestion pattern for MAP distinguishing it from other MAC members and other Mycobacterium spp. Moreover, HaeIII and MspI restriction of the rpoB gene enabled MAC-species and -subspecies discrimination. The rpoB-PRA using SmaI or MspI and HaeIII restriction of the rpoB gene is a simple, convenient, and reliable confirmatory assay for simultaneous identification of MAP and other MAC members.     

Anti-interferon-γ autoantibody in a patient with disseminated Mycobacterium avium complex

We report the case of a 44-year-old woman with disseminated Mycobacterium avium complex (MAC) infection involving multiple bone lesions despite a normal healthy status until 6 months previously. Because she was suspected to have acquired immunodeficiency, we tested interferon (IFN)-γ production by peripheral blood mononuclear cells (PBMC) after phytohemagglutinin (PHA) or anti-CD3 stimulation, and found that these cells produced no, or undetectable, levels of IFN-γ in the presence of the patient’s plasma, but produced nearly normal levels of IFN-γ in the presence of healthy donor plasma. Since the IgG fraction of the patient’s plasma was capable of blocking in vitro responses to IFN-γ, the cause of disseminated MAC infection in this case appeared to be anti-IFN-γ autoantibodies. To reduce the titer of anti-IFN-γ autoantibodies, the patient received intravenous immunoglobulin (IVIG). However, titer of autoantibodies changed little compared to that before IVIG administration. According to our literature search, this is only the second case of disseminated MAC infection associated with anti-IFN-γ autoantibodies in Japan.     

Combined use of clarithromycin and antimycobacterial agents inMycobacterium avium complex chronic pulmonary infection

Clarithromycin, a new macrolide antibacterial agent, is effective against disseminatedMycobacterium avium complex (MAC) infection in AIDS patients. In this study, we evaluated the therapeutic effect of clarithromycin, used in combination with other antimycobacterial drugs, against chronic pulmonary MAC infections in non-AIDS patients. Patients were divided into two groups based on the antimycobacterial drugs used for treatment. Patients of group A (n=5) were recent cases diagnosed to have atypical mycobacteriosis. They were treated on diagnosis, with rifampicin (450 mg q.d.), isoniazid (400 mg q.d.), and clarithromycin (200 mg b.i.d.). Patients of group B (n=23) were treated by adding clarithromycin (200 mg b.i.d.) to an existing therapeutic regimen consisting of several antimycobacterial agents. Clinical improvement was observed in seven (25%) patients, including two (40%) from group A and five (22%) from group B. Treatment was associated with a total mycobacterial eradication rate of 100% (5/5) in group A and 22% (5/23) in group B. Clarithromycin was more effective in patients receiving the drug as the first-line therapy than when used in later therapy. Clarithromycin had a lower efficacy rate in this study compared with the reported effect of clarithromycin in AIDS patients with in disseminated MAC infection. Our results of the first-line use of clarithromycin in combination with other mycobacterial agents for the treatment of chronic pulmonary MAC infections indicate that this agent has a limited but encouraging effect on atypical pulmonary mycobacteriosis.     

Radiological findings of mycobacterial diseases

The diagnosis and treatment of mycobacterial diseases are very important clinical issues. Among mycobacterial diseases, pulmonary tuberculosis remains an important cause of morbidity and mortality throughout the world. Pulmonary tuberculosis demonstrates a variety of clinical and radiological features. In addition, the prevalence of Mycobacterium avium complex (MAC) has increased, especially in elderly women without underlying diseases. Clinically, there is a significant difference between tuberculosis and atypical mycobacterium infection in terms of the infection control measures adopted and the choice of treatment. Therefore, it is very important to know the characteristic radiological findings of mycobacterial diseases. In the present review, key radiological points for diagnosing mycobacterial diseases are discussed.     

A patient with a <Emphasis Type="Italic">Mycobacterium avium</Emphasis> complex infection complicated by systemic lupus erythematosus

A 41-year-old woman was admitted to our hospital because of fever and polyarthralgia. A diagnosis of systemic lupus erythematosus (SLE) was made based on the findings of polyarthritis, leukocytopenia, lymphocytopenia, proteinuria, and positive reactions for antinuclear antibody (ANA) and anti-double strand (ds)DNA antibody. She had also been suffering from a pulmonary Mycobacterium avium complex (MAC) infection with such symptoms as cough and sputum for the past 3 years. Antimicrobial drugs for MAC infection were administered first, and later she was given cyclophosphamide pulse therapy, consisting of methylprednisolone (8mg/day) and mizoribine (100mg/day). Owing to these therapeutic regimens, SLE was successfully treated without an exacerbation of the MAC infection. The risk factors for MAC infection and SLE are also discussed.     

IS6110限制性片段长度多态性和间隔区寡核苷酸分型技术在结核分枝杆菌菌株鉴定中的应用

目的 评价IB6110-限制性片段长度多态性（IS6110-RFLP）和间隔区寡核苷酸分型技术（spoligotyping）两种方法在结核病流行病学上的应用，探讨我国各地区的结核分枝杆菌菌株特点。方法 收集158株结核分枝杆菌临床分离株，分别应用IS6110-RFLP和Spoligotyping两种方法进行鉴定。结果 （1）IS6110-RFLP的分辨力大于spoligotyping分型。（2）将本次试验结果与国际spoligotype数据库进行比较。结果 有14个类型属于共有类型，其中类型1为流行的类型，分布广泛，即所说的北京基因型。（3）广东地区与其他地区成簇率和北京基因型所占比例差异有统计学意义（P〈0．05）。广东地区成簇率和北京基因型所占比例均显著低于其他地区。结论 同时应用IS6110-RFLP分型和Spoligotyping两种方法进行结核病流行病学调查研究非常有效，在中国不同地区的菌株具有不同的特点。     

鸟分枝杆菌复合群肺病死亡率的Meta分析

目的 探究鸟分枝杆菌复合群肺病的死亡率及影响因素.方法 检索Medline、Cochrane、Embase、Web of Science四个数据库,收集1941年1月1日至2020年1月1日有关鸟分枝杆菌复合群(MAC)肺病的全因死亡率的研究,按照纳入和排除标准筛选文献,应用Newcastle-Ottawa scale...     

Use of mefloquine in multidrug-resistant Mycobacterium avium complex pulmonary disease in an HIV-negative patient

Introduction: Mycobacterium avium complex (MAC) is a leading cause of pulmonary disease (PD), even in those with intact immunity, representing about 30% of the cases of pleuropulmonary mycobacterial infection. Based on previous studies, macrolides are the only agents used in the treatment of MAC disease for which there is a correlation between in vitro susceptibility and in vivo (clinical) response. However, resistance develops rapidly if single-agent treatment is used. Data regarding treatment of macrolide-resistant MAC (MRMAC) and multidrug-resistant MAC (MDRMAC) are sparse.Case summary: A 50-year-old, HIV-negative white man, weighing 53.6 kg, with severe chronic obstructive pulmonary disease and bronchiectasis was initially on treatment for MAC-PD and MRMAC. The patient was followed between 1999 and 2006. His treatment history revealed that in addition to the multiple drugs administered during the course of his illness, thalidomide, interferon-γ, and mefloquine were also administered. The patient died ~7 years later due to respiratory failure and overwhelming infectionConclusions: This case report describes the use of mefloquine as adjunct treatment in an HIV-negative patient with MDRMAC-PD and discusses the associated outcomes of drug resistance.     

Absence of Mycobacterium avium subspecies paratuberculosis components from Crohn's disease intestinal biopsy tissues

BACKGROUND: Crohn's disease is a chronic human intestinal inflammatory disorder for which an etiologic agent has not been identified. Johne's disease is a similar chronic enteric granulomatous disease of ruminant species and has been used as a model of Crohn's disease. Johne's disease has been proven to be caused by Mycobacterium avium subspecies paratuberculosis (M. avium ss paratuberculosis). It has been proposed that M. avium ss paratuberculosis may also cause Crohn's disease. This is of particular concern because the organism may be spread to humans through inadequately pasteurized dairy products. OBJECTIVE: We sought to determine whether M. avium ss paratuberculosis could be detected using identical techniques in paraffin-embedded tissue samples of bovine Johne's disease and human Crohn's, ulcerative colitis and diverticular diseases. Samples were obtained for analysis from national tissue banks. DESIGN: Cross-species and cross-disease sample comparisons by multiple detection techniques. METHODS: Histology, immunocytochemistry and polymerase chain reaction (PCR) were utilized to test and compare the presence of M. avium ss paratuberculosis components. Insertion sequence IS900, present in multiple copies and found only in M. avium ss paratuberculosis, was utilized in both PCR and immunocytochemical analyses. RESULTS: The IS900 sequence was demonstrable in all samples of confirmed positive Johne's disease tissue. The sequence was not identified in the 35 Crohn's, 36 ulcerative colitis, and 21 diverticular disease samples. CONCLUSION: M. avium ss paratuberculosis was not associated with the lesions in these Crohn's disease samples, using these methods.     

Microbial substitution of <Emphasis Type="Italic">Mycobacterium avium-intracellulare</Emphasis> to <Emphasis Type="Italic">Mycobacterium abscessus</Emphasis> during clinical course

Mycobacterium avium-intracellulare (MAI) is, among acid-fast bacilli, the most common cause of nontuberculous pulmonary diseases, and MAI infections are often treated according to the guidelines of the American Thoracic Society. However, despite the use of multiple drugs, patients sometimes do not recover with the initial round of treatment. Other kinds of nontuberculous mycobacteria are sometimes found in patients' respiratory samples, even during such treatment for MAI pulmonary disease. We experienced three patients with pulmonary disease due to Mycobacterium abscessus (MA) in whom the disease was difficult to treat because of resistance to all the antituberculous agents used. MA infection had occurred in these patients after long-term treatment with multiple drugs for previous MAI pulmonary disease. We considered that the MA infection in these patients appeared to be the result of insufficient efficacy of the drugs used for MAI and insufficiently aggressive use of antituberculous agents. It thus appeared that MA infection was the result of microbial substitution, and that, if this is the case, the guidelines for the treatment of MAI may need to be modified to eliminate microbial substitution.     

不同类型乙型肝炎患者HBV基因型的分布

目的 探讨乙型肝炎病毒（HBV）各种基因型在不同类型乙型肝炎患者中的分布.方法 用PCR结合限制性片段长度多态性（PCR-RFLP）方法检测56例HBV感染的肝癌、58例肝硬化、60例慢性乙型肝炎患者以及60例HBV无症状携带者血清HBV基因型.结果 无症状携带者中B基因型为46.7%（28/60）,C基因型为33.3%（20/60）,D基因型为20.0%（12/60）;慢性乙型肝炎组B基因型为41.7%（25/60）,C基因型为36.7%（22/60）,D基因型为21.7%（13/60）;肝癌患者中B基因型为33.9%（19/56）、C基因型为60.7%（34/56）、D基因型为5.4%（3/56）;肝硬化患者中B基因型为31.0%（18/58）、C基因型为63.8%（37/58）,D基因型为3.5%（2/58）.结论 在慢性乙型肝炎和无症状携带者中以B基因型为优势感染毒株,而肝硬化和肝癌患者则以C基因型为优势感染毒株.     

First case of nontuberculous mycobacterial lung disease caused by Mycobacterium marseillense in a patient with systemic lupus erythematosus

Mycobacterium marseillense was designated as a new species within Mycobacterium avium complex. We report the first case of M. marseillense lung disease in a patient with systemic lupus erythematosus. All serial isolates were identified as M. marseillense by multilocus sequence analysis, based on hsp65, 16S-23S rRNA internal transcribed spacer, and 16S rRNA fragments.     

Splenic infarction due to Mycobacterium avium complex infection in an HIV-infected patient with immune reconstitution failure: a case report

Splenic infarction is extremely rare in human immunodeficiency virus-infected populations. We report a rare case of splenic infarction involving Mycobacterium avium complex infection in a patient with acquired immune deficiency syndrome with immune reconstitution failure. A young man was initially admitted with cryptococcus meningitis and found to be infected with human immunodeficiency virus. He had anti-cryptococcosis treatment performed in combination with placement of an Ommaya capsule because of persistent intracranial hypertension, and first-line therapy followed by second-line anti-retroviral therapy were performed. Although there was an absence of immune reconstitution, the patient refused to take prophylactic sulfamethoxazole/trimethoprim, isoniazid, and clarithromycin continuously because of gastrointestinal intolerance. Pneumocystis pneumonia then developed. Finally, the patient developed a fever again accompanied by abdominal pain and splenic infarction. M. avium complex infection was verified by a metagenomic next-generation sequencing test using a whole blood sample. M. avium complex infection should be considered as an etiology of splenic infarction in human immunodeficiency virus-infected patients with an extremely low CD₄⁺T-cell count.     

Adult acetonemic vomiting complicated with low body weight in a subject with Mycobacterium avium complex pulmonary disease: a case report

Pulmonary diseases often cause significant health issues and nutritional disorders. Weight loss and malnutrition are related to the severity of obstructive disorders. Therefore, patients with such conditions often experience low nutritional energy. Acetonemic vomiting is caused by acetonemic syndrome. Previously, it was believe that acetonemic vomiting was observed only in childhood. However, it was recently suggested that acetonemic vomiting can also occur in adults. It is also considered that acetonemic vomiting can occur in subjects with low body weight because stored carbohydrate levels are reduced and fats are mainly used for energy. Consequently, large amounts of acetone are produced, ultimately resulting in nausea and vomiting. In this study, we report a case of adult acetonemic vomiting complicated by low body weight in a subject with Mycobacterium avium complex pulmonary disease.     

Detection and characterization of thefimAgene ofEscherichia coliO157:H7

An expected 850-bp DNA fragment containingfimA, the structural gene for type 1 fimbriae, and flanking sequences was amplified from 39 (of 46) pathogenic and commensal strains ofEscherichia coliusing the polymerase chain reaction (PCR). Restriction fragment length polymorphism (RFLP) analysis of the amplified products showed 13HinPI and fourSau96I restriction profiles among these 39E. colistrains, revealing the polymorphic nature of this allele. A unique RFLP pattern was shared byE. coliO157:H7, O157:H^- and a few O55 serotype strains. DNA sequence analysis of thefimAregion demonstrated thatE. coliO157:H7 strain 933 and O157:H⁻strain E32511 contained identical DNA sequences that were distinct from otherE. colistrains, especially a 16-bp sequence 5′ tofimAthat was conspicuously absent only inE. coliO157 strains. Exploiting these differences, a PCR assay was developed that amplifies a 936-bp fragment from allE. coliO157:H7 strains examined to date. This PCR assay offers a simple, rapid, and reliable means to detectE. colistrains of the O157:H7 serotype.     

Pulmonary Mycobacterium intracellulare disease with a solitary pulmonary nodule detected at the onset of pneumothorax

A 61-year-old man with a past history of pulmonary emphysema 6 years earlier was admitted to the emergency department at our hospital because of cough and dyspnea. Left pneumothorax was recognized on a chest radiograph. After his admission to the emergency department, chest drainage was inserted and the left lung was expanded. Afterwards, a nodular shadow (>1.5 cm) was found in the left upper lobe, and differentiation from pulmonary adenocarcinoma was required. As a definite diagnosis could not be made by bronchoscopy, video-assisted thoracoscopic surgery was performed, and a solitary nodule in the left upper lobe was resected. Histologically, a caseating epitheloid granuloma with acid-fast bacilli was found. Regarding the causative pathogen, Mycobacterium intracellulare was identified from the surgically resected specimen. We have reported a peculiar case of pulmonary M. intracellulare disease, detected at the onset of left secondary pneumothorax caused by pulmonary emphysema, which required differentiation from pulmonary adenocarcinoma.     

A PCR-RFLP assay for identification of Anisakis simplex from different geographical regions

Anisakis simplex, a nematode from the family Anisakidae, is a parasite of fish and mammals. It is a casual agent of a human disease called anisakiosis. We found that the assay based on PCR amplification of the ITS-1–5·8 S–ITS-2 fragment of rDNA and subsequent restriction fragment length polymorphism, previously described on the basis of A. simplex isolated solely from one geographical region, can be used as a general test for identification of this worm species. The restriction patterns analysed for four restriction enzymes were found to be identical in the case of allA. simplex individuals isolated from as different geographical regions as Baltic Sea, Norwegian Sea, Bering Sea and Sea of Okchotsk. Moreover, our results support the previously proposed hypothesis, based on the studies of isoenzymes, that there is a remarkable genetic homogeneity within A. simplex from different geographical regions.     

IL-16 rs11556218 gene polymorphism is associated with coronary artery disease in the Chinese Han population

Objective

Our aim was to investigate the association between IL-16 gene polymorphisms (rs4778889 C/T and rs11556218 G/T) and coronary artery disease (CAD).

Design and methods

The initial cohort consisted of 300 CAD patients and 397 controls from the Chinese Han population. Genotyping was performed by using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The positive association between polymorphism and CAD was replicated in another independent cohort, which included 424 CAD cases and 332 controls.

Results

In the initial study, the allele and genotype frequencies of rs4778889 were not different between in CAD and controls (P > 0.05). However, The G allele frequency of rs11556218 was significantly higher in the CAD cases than in the controls (CAD, 46.8% vs. controls, 22.8%, P < 0.001). The risk of CAD was significantly higher in the G allele carriers than in the non-carriers (P < 0.001, adjusted odds ratio = 7.27; 95% confidence interval, 4.13–12.8). In the replication cohort, G carriers of rs11556218 also had a higher risk of CAD (P = 0.005, adjusted OR = 2.33; 95% confidence interval, 1.45–3.74).

Conclusion

Our study suggested that IL-16 rs11556218 G/T polymorphism is significantly associated with the risk of CAD in the Chinese Han population.     

Usefulness of bronchial lavage for the diagnosis of pulmonary disease caused by Mycobacterium avium-intracellulare complex (MAC) infection

To evaluate the usefulness of bronchial lavage for the diagnosis of pulmonary disease due to Mycobacterium avium-intracellulare complex (MAC) infection, we examined the clinical records and bacteriologic findings of patients admitted to our hospital between 1999 and 2002 who fulfilled the 1997 American Thoracic Society (ATS) criteria for MAC pulmonary infection. Bronchoscopic examinations were performed in those patients with MAC pulmonary disease who showed negative sputum smears for mycobacteria on 3 consecutive days (n = 14) or who could not expectorate sputum (n = 2). The bronchial lavage sample was smear-positive for acid-fast bacilli in 8 of the 16 patients (50.0%), polymerase chain reaction (PCR)-positive for MAC in 10 of 15 (66.7%), and culture-positive for MAC in 15 of 16 (93.7%). The brushing sample was positive for MAC in 5 of 14 patients (35.7%), and transbronchial lung biopsy (TBLB)-positive for MAC in 2 of 5 (40.0%). MAC was isolated by culture of bronchial lavage samples in a higher percentage of patients than that in whom MAC was isolated by sputum culture, and we could make an early diagnosis of MAC pulmonary disease based on the smear and PCR results for bronchial lavage samples. Bronchial lavage is useful to screen sputum smear-negative patients suspected of having MAC pulmonary disease.