Diagnostic Usefulness of Liquid Culture Medium for Mycobacterium avium-intracellulare Complex Lung Disease: A Single-Centre, Retrospective Study.

Background The diagnosis of Mycobacterium avium-intracellulare complex lung disease (MAC-LD) requires two or more positive sputum cultures. Few reports have examined the usefulness of adding liquid culture to conventional solid culture for diagnosing MAC-LD. Methods A retrospective, cohort study of patients examined at Kurashiki Central Hospital in Japan with a confirmed diagnosis of MAC-LD between January 1, 2002, and June 20, 2021, was conducted. The primary endpoint was the culture positivity rate, which was compared between the liquid and Ogawa culture media in patients who underwent sputum culture using both methods. Secondary endpoints were the culture positivity rate in smear-positive specimens and the positivity rate by radiological type. Results The study, which involved 351 patients and 702 specimens, showed a higher positivity rate for liquid culture (n=690, 98.3%) than Ogawa culture (n=315, 44.9%). Overall, 265 patients (75.5%) would have had delayed MAC-LD diagnosis without liquid medium being used. Of the 95 smear-positive specimens, 71 (74.7%) were positive on both cultures, whereas 24 (25.3%) were positive only on liquid culture. The positivity rate of Ogawa culture varied by radiological type. Conclusions Liquid culture is more valuable for the early diagnosis of MAC-LD than Ogawa culture.

Time to diagnosis of nontuberculous mycobacterial pulmonary disease and longitudinal changes on CT before diagnosis.

Background: The healthcare burden of nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing, but the diagnosis remains challenging and sometimes requires considerable time. This nested case-control study aims to clarify the time to diagnosis of NTM-PD, the factors that affect diagnosis and diagnostic delay, and changes in CT findings before diagnosis. Patients and methods: We retrospectively analyzed 187 patients suspected of having NTM-PD based on computed tomography (CT) findings at our institution between January 2019 and September 2020. We investigated the time to diagnosis of NTM-PD for all suspected and diagnosed patients. Multivariate analyses identified the factors affecting diagnosis and diagnostic delay over 6 months. We also evaluated longitudinal changes in CT findings during the observation period using CT scoring system. Results: The median times to diagnosis of NTM-PD were 71.8 months in all suspected patients and 3.2 months in only the diagnosed patients. Multivariable analysis showed that severity of the cavity domain of the CT score and anti-glycopeptidolipid (GPL)-core immunoglobulin A (IgA) antibody positivity were significantly associated with establishing the diagnosis. A low CT score in the cavity domain was a risk factor for delayed diagnosis. In patients with delayed diagnosis, the total CT score was less severe than that in the early diagnosis patients at their first visits; however, it had deteriorated prior to the diagnosis. Conclusion: The diagnosis of NTM-PD sometimes required several years, and the absence or mild cavitation predicted a diagnostic delay. Of concern, a delay in diagnosis can result in a delay in treatment.

A Case of Disseminated Non-tuberculous Mycobacteriosis with a Skull Lesion Controlled by Resection after Exacerbation during Antimicrobial Chemotherapy in a Patient Positive for Anti-IFN-γ-neutralizing Autoantibodies.

A 48-year-old man presented with a fever and back pain and was referred to our hospital with multiple bone destruction and abscess formation. A sputum examination revealed Mycobacterium intracellulare, and pathological findings revealed an indistinct granuloma and acid-fast bacilli, leading to a diagnosis of disseminated nontuberculous mycobacteriosis. Anti-interferon-γ-neutralizing autoantibodies were detected in the serum, and acquired immunodeficiency was suspected to be the etiology. Antimicrobial chemotherapy was initiated, and the lesions generally regressed. However, only the skull lesions worsened, requiring local resection to control the disease. Currently, the patient is continuing to receive drug therapy with good disease control after debridement.

Treatment outcomes and relapse in patients with Mycobacterium avium-intracellulare complex pulmonary disease.

The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. This retrospective study was conducted in Taiwan between 2011 and 2020. A microbiological cure was defined as the requirement for a minimum of three consecutive negative cultures following culture conversion that continued until the completion of anti-MAC treatment. A total of 97 patients with MAC-PD were enrolled in this study. The sputum smear-negative conversion rate was 40% (19/47). Thirty (31%) patients achieved sputum culture-negative conversion rates within 3 years after treatment initiation. All patients with negative sputum culture conversion rates achieved microbiological cure. Patients treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than the other patients (39% vs 17%, P = 0.023). Patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate than those with negative sputum smears (6% vs 44%, P < 0.001). Among 30 patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 (0-483) days, and the 1-year relapse rate was 17%. Treatment with the M + R + EMB-based regimen was associated with a higher microbiological cure rate, and patients with persistently positive sputum smears after 6 months of treatment had a lower microbiological cure rate. IMPORTANCE The treatment responses and outcomes in patients with Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) remain uncertain. In this study, patients with MAC-PD treated with a macrolide + rifamycin + ethambutol (M + R + EMB)-based regimen had a higher microbiological cure rate than those treated with other regimens. After 6 months of treatment, patients with persistently positive sputum smears had a lower microbiological cure rate than those with negative sputum smears. Among patients with microbiological cure, the median time from sputum culture conversion to treatment completion was 221.5 days (range, 0-483), and the 1-year relapse rate was 17%.

Pulmonary Nontuberculous Mycobacteria, Ontario, Canada, 2020.

We measured annual prevalence of microbiologically defined nontuberculous mycobacterial lung disease in Ontario, Canada. Mycobacterium avium prevalence was 13 cases/100,000 persons in 2020, a 2.5-fold increase from 2010, indicating a large increase in true M. avium lung disease. During the same period, M. xenopi decreased nearly 50%, to 0.84 cases/100,000 persons.

Pay attention to the diagnosis and treatment of Mycobacterium avium-intracellulare complex infection / 中华临床感染病杂志

Mycobacterium avium- intracellulare complex is the term of a group of slow growing nontuberculous mycobacterium related to human infections, which has received more and more attention in recent years, and become an important public health issue. This article reviews the progress on clinical diagnosis and treatment of the infections caused by Mycobacterium avium- intracellulare complex.

Effect of sputum quality on Mycobacterium avium-intracellulare complex lung disease diagnosis and treatment initiation according to disease type.

We evaluated sputum quality to establish a diagnostic and treatment strategy for Mycobacterium avium-intracellulare complex lung disease (MAC-LD). Of all 905 MAC-LD patients, 564 (62.3%) had nonpurulent sputum. Furthermore, 88 treated patients were associated with purulent sputum. Therefore, sputum quality may be useful for diagnosing MAC-LD and deciding treatment initiation.

Long-Term Prognosis and Antimycobacterial Glycolipid Antibody as Biomarker in Mycobacterium avium-intracellulare Complex Pulmonary Disease.

Clinical characteristics and outcomes of multidrug chemotherapy have been used as the main prognostic factors for Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) over the last decade; however, no useful prognostic biomarkers have been reported. The aim is to ascertain whether the serum antibody titers could include useful prognostic predictors of MAC-PD. Ninety-four patients with MAC-PD were enrolled and regularly followed up with for more than 5 years or until death. Cox proportional hazard regression and receiver operating characteristic (ROC) curve analyses were used to identify predictors of mortality in this prospective observational study. According to treatment outcomes, 85 patients completed follow-up and were classified into four groups. Seventeen patients (20%) died during follow-up (median, 10.1 years; interquartile range, 8.1 to 12.4 years). All 11 patients with MAC-PD-specific death were included in the 14 patients of the group nonresponsive to the multidrug chemotherapy. They had significantly higher anti-Mycobacterium glycolipid (MBGL) antibody titers than those in the other groups and a significantly (P < 0.0001) poorer survival prognosis. The anti-MBGL antibody titers also served as a negative prognostic factor. A cutoff score of 7, which was calculated by clinical poor prognostic characteristics and anti-MBGL antibody titers, differentiated the nonresponse group and the other groups at baseline (sensitivity, specificity, and area under the curve: 92.9%, 81.7%, and 0.95, respectively). In conclusion, anti-MBGL antibody titers were useful to assess the refractory MAC-PD. The predictions of treatment outcome and mortality become more accurate by using anti-MBGL antibody and clinical poor prognostic characteristics together. IMPORTANCE The natural history of MAC-PD is challenging to predict in immunocompetent patients at diagnosis, and the current multidrug chemotherapy options are not strong enough to eliminate mycobacteria from the lungs. Therefore, the diagnosis of MAC-PD does not necessarily lead to the decision to start chemotherapy. We have also observed refractory patients in clinical practice, who were resistant to multiple-drug chemotherapy and showed persistent excretion of MAC bacilli and progressive worsening of chest radiographic findings until death. We have reported that the measurements of anti-MBGL antibody titers helped assess refractory MAC-PD in this study. Furthermore, the predictions of treatment outcome and mortality become more accurate by using the anti-MBGL antibody in addition to clinical poor prognostic characteristics, which were older age, lower body mass index, the positive results of a smear test for acid-fast bacteria (AFB), and presence of cavitary disease.

Distribution and drug resistance of nontuberculous mycobacteria / 公共卫生与预防医学

Objective To analyze the distribution characteristics and drug resistance of nontuberculous mycobacteria(NTM),and to provide guidance for the selection of targeted agents in clinical treatment. Methods The clinical data of inpatients in our hospital from April 2019 to February 2021 were collected,the culture and strain identification of non tuberculosis mycobacteria were carried out,the drug sensitivity test of anti tuberculosis drugs was carried out,and the drug resistance of non tuberculosis mycobacteria to first-line anti tuberculosis drugs was analyzed. Results A total of 1 326 strains of mycobacterium were isolated,including 1 154(87.03%)strains of mycobacterium tuberculosis and 172(12.97%)strains of non-mycobacterium tuberculosis.Nine species of nontuberculous mycobacteria were detected,including slow-growing mycobacteria such as Mycobacterium kansasii and Mycobacterium avium-intracellulare complex,belonging to Groups I-III,and fast-growing mycobacteria such as Mycobacterium chelonae and Mycobacterium smegmatis,belonging to Group IV. Among them , Mycobacterium avium-intracellulare complex and Mycobacterium chelonae were dominant,accounting for 26.16%and 36.63%,respectively.Drug susceptibility tests showed that the resistance rate of Mycobacterium avium-intracellulare complex to streptomycin was 100.00%,the drug resistance rate of Mycobacterium chelonae to isoniazid,rifampicin and streptomycin was 100.00%,and the drug resistance rate of Mycobacterium smegmatis and Mycobacterium abscessus to most antibacterial drugs was 100.00%.The resistance rate of major NTM bacteria to clarithromycin was relatively low.There was no statistically significant difference in the susceptibility rates of slow and fast-growing mycobacteria to isoniazid and clarithromycin(P>0.05) ; The susceptibility rates of slow-growing mycobacteria to amikacin,clarithromycin and rifambutin were 62.86%,92.86%and 72.86%,all above 50.00%.The susceptibility rate of the fast-growing mycobacteria to clarithromycin was also more than 50.00%,being 87.25%.The susceptibility rate of slow-growing mycobacteria to other antibiotics was higher than that of fast-growing mycobacteria(P<0.05).The drug resistance of Mycobacterium tuberculosis to first-line anti tuberculosis drugs was significantly lower than that of non Mycobacterium tuberculosis(P<0.05). Conclusion Non-tuberculous mycobacteria have high drug resistance,especially fast-growing mycobacteria,so drug susceptibility tests are of great value in clinical treatment.

Mycobacterium Avium Complex Genitourinary Infections: Case Report and Literature Review.

Nontuberculous mycobacterial (NTM) genitourinary (GU) infections are relatively rare, and there is frequently a delay in diagnosis. Mycobacterium avium-intracellulare complex (MAC) cases seem to be less frequent than other NTM as a cause of these infections. In addition, there are no set treatment guidelines for these organisms in the GU tract. Given the limitations of data this review summarizes a case presentation of this infection and the literature available on the topic. Many different antimicrobial regimens and durations have been used in the published literature. While the infrequency of these infections suggests that there will not be randomized controlled trials to determine optimal therapy, our case suggests that a brief course of amikacin may play a useful role in those who cannot tolerate other antibiotics.

Anti-Mycobacterial Drug Resistance in Japan: How to Approach This Problem?

Mycobacteriosis is mainly caused by two groups of species: Mycobacterium tuberculosis and non-tuberculosis mycobacteria (NTM). The pathogens cause not only respiratory infections, but also general diseases. The common problem in these pathogens as of today is drug resistance. Tuberculosis (TB) is a major public health concern. A major challenge in the treatment of TB is anti-mycobacterial drug resistance (AMR), including multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis. Recently, the success rate of the treatment of drug-resistant tuberculosis (DR-TB) has improved significantly with the introduction of new and repurposed drugs, especially in industrialized countries such as Japan. However, long-term treatment and the adverse events associated with the treatment of DR-TB are still problematic. To solve these problems, optimal treatment regimens designed/tailor-made for each patient are necessary, regardless of the location in the world. In contrast to TB, NTM infections are environmentally oriented. Mycobacterium avium-intracellulare complex (MAC) and Mycobacterium abscessus species (MABS) are the major causes of NTM infections in Japan. These bacteria are naturally resistant to a wide variation of antimicrobial agents. Macrolides, represented by clarithromycin (CLR) and amikacin (AMK), show relatively good correlation with treatment success. However, the efficacies of potential drugs for the treatment of macrolide-resistant MAC and MABS are currently under evaluation. Thus, it is particularly difficult to construct an effective treatment regimen for macrolide-resistant MAC and MABS. AMR in NTM infections are rather serious in Japan, even when compared with challenges associated with DR-TB. Given the AMR problems in TB and NTM, the appropriate use of drugs based on accurate drug susceptibility testing and the development of new compounds/regimens that are strongly bactericidal in a short-time course will be highly expected.

[Hot tub lung: A retrospective analysis of 14 cases]. / Poumon de jacuzzi : analyse rétrospective de 14 cas.

INTRODUCTION: Hot tub lung (HTL) is a hypersensitivity pneumonitis (HP) related to inhalation of non-tuberculous mycobacteria (NTM) when exposed to ejected jet droplets from a jacuzzi. The aetiological debate is not completely settled in the literature. METHOD: An observational study of 14 cases of HTL, diagnosed at the University Hospital of Besançon, France, between 2004 and 2018 according to the diagnostic criteria used in the clinic. RESULTS: This cohort corresponds to type I HP (inflammatory), with one case of type II HP. Decrease of lung transfer for carbon monoxide was present in 86% of examinations (n=12/14). In total, 84% of bronchoalveolar lavages showed a lymphocytic cellular pattern≥30% (n=11/13). The environmental survey enabled the identification of NTM in 93% of cases (n=13/14), mainly Mycobacterium avium. Serum precipitins directed against NTM were found in 10% of the cases (n=2/20). Three cases received corticosteroid therapy and none received antibiotics. Antigenic eviction has improved the symptomatology in all cases. CONCLUSIONS: Our cohort supports the hypothesis that HTL is predominantly a type I HP. Avoidance of the agent involved (NTM) is necessary. The diagnosis is difficult because serum precipitins against NTM are not easily demonstrable. An environmental survey could facilitate the identification of the NTM. Prevention of HTL depends on education of the clinician and the patient.

Nontuberculous mycobacterial lung disease epidemiology in Taiwan: A systematic review.

Nontuberculous mycobacteria (NTM) are critical emerging global infectious pathogens. Though NTM can be mere colonizers when isolated from human specimens, NTM are also responsible for diverse human infections. NTM-lung disease (NTM-LD) is the most common human disease entity. The present review aims to provide general insight into NTM-LD epidemiology in Taiwan. In reviewing NTM epidemiology in Taiwan, we discovered three distinguishing features. First, NTM disease incidence has increased in Taiwan over the past decade. Second, the distribution of NTM varies geographically in Taiwan. Mycobacterium avium-intracellulare complex (MAC) is the dominant species in northern Taiwan, whereas Mycobacterium abscessus complex and MAC may be equally dominant in southern Taiwan. Third, researchers in Taiwan have published valuable research investigating NTM among special patient populations, including patients in intensive care units, with ventilator dependency, with pulmonary tuberculosis, and who are infected with specific NTM species. The largest obstacle to clarifying NTM epidemiology in Taiwan may be the lack of routine NTM species identification in laboratories. Increased awareness of NTM diseases and acknowledgment that NTM species identification is crucial and guides clinical management are essential steps for facilitating the identification of NTM species in laboratories.

Different clinical features of patients with pulmonary disease caused by various Mycobacterium avium-intracellulare complex subspecies and antimicrobial susceptibility.

OBJECTIVES: Characteristics of the Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) caused by distinct subspecies remain uncertain. METHODS: This study was conducted from 2013-2015 in three hospitals in Taiwan. RESULTS: Among the 144 patients with MAC-PD, 57 (39.6%), 37 (25.7%), 37 (25.7%), and 13 (9.0%) were infected with Mycobacterium intracellulare subspecies intracellulare (MIsI), Mycobacterium avium subspecies hominissuis (MAsH), Mycobacterium intracellulare subspecies chimaera (MIsC), and others, respectively. Patients with MAsH-PD were younger (p = 0.010) with higher human immunodeficiency virus infection rates (27.0%, 0.0%, 0.0%, and 7.7% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p < 0.001). Twenty-two (15.3%) patients reported spontaneous culture-negative conversion, but 15 (10.4%) and 33 (22.9%) patients developed radiographic progression and unfavorable outcomes, especially MAsH-PD. The susceptibility rates to clarithromycin and inhaled amikacin were both 98.6%. MAsH demonstrated the lowest rate of resistance to moxifloxacin (66.7%, 97.3%, 89.1%, and 92.3% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p = 0.001) and MIsI isolates had the highest rate of resistance to intravenous amikacin (25%, 13.5%, 38.2%, and 15.4% for MAsH-PD, MIsC-PD, MIsI-PD, and others, respectively; p = 0.024). CONCLUSIONS: Pulmonary disease caused by distinct MAC subspecies had different outcomes and drug susceptibility. The local prevalence of species needs to be monitored.

Identificación de especies micobacterianas ambientales u oportunistas en pacientes sintomáticos y con VIH/sida / Identification of environmental or opportunistic mycobacterial species in symptomatic symptomatic and HIV/AIDS patients

El aumento de las infecciones por micobacterias ambientales u oportunistas (MAO) coincide mundialmente con el declive de la infección tuberculosa e incremento de la infección por el virus de inmunodeficiencia humana (VIH). El presente trabajo es un estudio retrospectivo realizado en el Laboratorio Nacional de Referencia-Investigaciones de Tuberculosis/Micobacterias/Lepra (LNRI-TB/Lepra/Micobacterias), del Instituto de Medicina Tropical Pedro Kourí (IPK), La Habana, Cuba, durante el período enero 2014-diciembre 2018. El objetivo de nuestro estudio fue conocer la variabilidad de especies aisladas para establecer un referente actualizado sobre las infecciones causadas por estas. En este trabajo se clasificaron-identificaron 413 cepas procedentes de pacientes sintomáticos; 162 (39.22%) eran aislamientos de pacientes con VIH/sida atendidos en nuestro Hospital Nacional de Referencia a Atención al paciente VIH/sida (IPK), y el resto (n = 251 [60.77%]), procedentes de pacientes inmunocompetentes, incluyendo aislamientos recibidos de los Centros Provinciales de Higiene, Epidemiología, y Microbiología (CPHEM). Las muestras fueron analizadas con las técnicas convencionales establecidas: las pulmonares fueron descontaminadas por el método de Petroff modificado; las extrapulmonares, por el método del ácido sulfúrico al 4%; el cultivo se realizó en medio de Löwenstein-Jensen modificado. Posteriormente se realizó la clasificación-identificación de especies según el esquema fenotípico-bioquímico establecido. Las especies con mayor porcentaje de aislamiento pertenecieron a los Grupos III y IV, complejo Mycobacterium avium-intracellulare (34.14%) y complejo M. fortuitum (20.82%), respectivamente. Estos resultados permitirán conocer la prevalencia de estas especies en nuestro país, reafirmando la importancia diagnóstica de estos microorganismos para aplicar tratamiento específico, sobre todo en pacientes con factores de riesgo, en quienes es más probable la diseminación de la infección.

The increase in infections by environmental or opportunistic mycobacteria (MAO) coincides worldwide with the decline in tuberculosis infection and an increase in infection by the human immunodeficiency virus (HIV). The present work is a retrospective study carried out at the National Reference Laboratory-Tuberculosis/Mycobacterial/Leprosy Research (LNRI-TB / Leprosy / Mycobacteria), of the Pedro Kourí Institute of Tropical Medicine (IPK), La Habana, Cuba, during the period January 2014-December 2018. The objective of our study was to know the variability of isolated species to establish an updated reference on the infections caused by MAO. In this study, 413 strains from symptomatic patients were classified and identified; 162 (39.22%) were isolates from patients with HIV/AIDS treated at our National Hospital of Reference for Attention to HIV/AIDS patients (IPK), and the remaining (n=251 [60.77%]), from immunocompetent patients, including isolates received from the Provincial Centers of Hygiene, Epidemiology, and Microbiology (CPHEM). The samples were analyzed with the established conventional techniques: the lung samples were decontaminated by the modified Petroff method; the extrapulmonary, by the 4% sulfuric acid method; the culture was carried out in modified Löwenstein-Jensen medium. Subsequently, the classification-identification of species was carried out according to the established phenotypic-biochemical scheme. The species with the highest percentage of isolation belonged to Groups III and IV, Mycobacterium avium-intracellulare complex (34.14%), and M. fortuitum complex (20.82%), respectively. These results will allow us to know the prevalence of these species in our country, emphasizing the diagnostic importance of these microorganisms and thus apply a specific treatment, especially in patients with risk factors, in whom the spread of the infection is more likely

Macrolide resistant Mycobacterium avium complex pulmonary disease following clarithromycin and ethambutol combination therapy.

RATIONALE: Whether two-drug therapy (clarithromycin and ethambutol) for Mycobacterium avium complex (MAC) pulmonary disease contributes to the development of macrolide-resistant MAC is unclear. OBJECTIVE: To compare the incidence of macrolide-resistant MAC between patients treated with two-drug therapy (clarithromycin and ethambutol) and the standard three-drug therapy (clarithromycin, ethambutol, and rifampicin) for MAC pulmonary disease. METHODS: We retrospectively reviewed 147 patients with treatment-naive MAC pulmonary disease who had received two-drug therapy (n = 47) or three-drug therapy (n = 100) between 1997 and 2016 at National Hospital Organization, Tenryu Hospital, Hamamatsu, Japan. The risk of development of macrolide-resistant MAC was evaluated by calculating the cumulative incidence rate using Gray's test. RESULTS: The median follow-up period was 74.5 months. During the follow-up period, one of the 47 patients (2.1%) in the two-drug group developed macrolide-resistant MAC, compared to 12 of the 100 patients (12.0%) in the three-drug group. The cumulative incidence rate of macrolide-resistant MAC was lower in the two-drug group than in the three-drug group (0.0023; 95% confidence interval, 0.002 to 0.107 versus 0.200; 95% confidence interval, 0.100 to 0.324, p = 0.0593). CONCLUSIONS: These results suggest that two-drug treatment with clarithromycin and ethambutol for MAC pulmonary disease does not lead to a higher incidence of resistance acquisition to clarithromycin than the standard three-drug treatment.

A survey of clarithromycin monotherapy and long-term administration of ethambutol for patients with MAC lung disease in Japan: A retrospective cohort study using the database of health insurance claims.

BACKGROUND: The number of patients with nontuberculous mycobacteriosis (NTM) has increased exponentially in recent years. In Japan, approximately 88.8% of patients with NTM suffer from Mycobacterium avium-intracellulare complex (MAC) lung disease. Incidence of MAC lung disease is increasing in particularly among the middle-aged and elderly women owing to a rapid increase in nontuberculous mycobacterial infections. General treatment for MAC lung disease is chemotherapy. The type of chemotherapy recommended by specialists to prevent the development of a drug-resistant strain of the bacteria consists of a combination of clarithromycin (CAM), rifampicin, and ethambutol (EB). CAM monotherapy is contraindicated by specialists owing to its high potential to induce drug-resistant bacterial strains in patients with MAC lung disease. In addition, administering EB at doses not less than 1000 mg d-1 is not recommended to avoid adverse drug reactions. However, it is unclear how much such treatment cases exist in real world clinical settings. This is because no long-term investigation has been carried out. MATERIALS AND METHODS: This study investigated treatment with these drugs from 2005 to 2017, by studying 1135 patients with MAC lung disease based on health insurance claims database. RESULTS: Results showed that approximately 9.2% (101 cases) were prescribed long-term CAM monotherapy for 3 months or longer and approximately 3.6% (18 cases) were prescribed high doses of EB. CONCLUSION: CAM monotherapy over a long period of time is potentially detrimental to some patients. Better awareness of the types of treatments and their potential negative effects will be beneficial to clinical practitioners.

Effect of rifampicin and clarithromycin on the CYP3A activity in patients with Mycobacterium avium complex.

BACKGROUND: The prevalence of pulmonary infections caused by nontuberculous mycobacteria (NTM) is increasing worldwide. Furthermore, the treatment of infections caused by the Mycobacterium avium-intracellulare complex (MAC) remains challenging. The cytochrome P450 (CYP) enzyme inducer, rifampicin, and the CYP inhibitor, clarithromycin, have clinical activity against MAC and key drugs in the treatment of MAC infection. The interaction of rifampicin and clarithromycin may influence the therapeutic process. METHODS: Thirty-one Japanese chemo-naïve patients with pulmonary MAC infection were included in the study. Before and after 7-day administration of rifampicin and clarithromycin, the pharmacokinetics of midazolam, a CYP3A-specific probe, were analyzed. The concentrations of midazolam were determined by liquid chromatography-tandem mass spectrometry. None of the patients were receiving any other medications that might affect CYP3A activity. RESULTS: Of the patients, 24 (77.4%) were infected with Mycobacterium avium (M. avium) and 7 (22.6%) were infected with Mycobacterium intracellulare (M. intracellulare). The concentrations of midazolam were significantly reduced with administration of rifampicin and clarithromycin [the median (range) was 1.75 (0.70-8.22) to 1.04 (0.30-2.63) ng/mL, P<0.0001]. The differences in midazolam levels were not correlated with clinical characteristics. CONCLUSIONS: Coadministration of rifampicin and clarithromycin may increase CYP3A enzymatic activity.

DIAGNOSIS AND MANAGEMENT OF MYCOBACTERIOSIS IN A COLONY OF LITTLE PENGUINS (EUDYPTULA MINOR).

A group of zoo-housed little penguins (Eudyptula minor) was diagnosed with mycobacteriosis. While undergoing multidetector computed tomography (MDCT) imaging for an unrelated research project, pulmonary lesions were detected in multiple individuals. In general, birds appeared healthy and free of outward signs of disease. After the loss of three individuals, polyclonal mycobacterial disease due to Mycobacterium avium-intracellulare complex was confirmed. Surviving birds were treated with rifampin (45 mg/kg), ethambutol (30 mg/kg), clarithromycin (10 mg/kg), and enrofloxacin (30 mg/kg) compounded into a single capsule administered once a day in food. After 3 mo of therapy, MDCT imaging documented a decrease in nodule size and number in all remaining birds, with further improvement documented after 13 mo of treatment. MDCT imaging was invaluable for diagnosing disease, documenting disease progression over time, and assessing response to therapy. Early initiation of therapy before the development of outward signs of disease led to resolution of mycobacterial pulmonary lesions in multiple penguins. Mycobacterial disease in this group of little penguins, as well as previously published reports, suggests that the species is at increased risk for developing mycobacteriosis.

Disseminated Mycobacterium avium-Intracellulare Complex Infection Presenting With Disseminated Intravascular Coagulation in an AIDS Patient.

Disseminated Mycobacterium avium-intracellulare complex (MAC) infection is one of the relatively common opportunistic infections seen in severely immunocompromised AIDS patients. A constellation of clinical, laboratory, and pathological features involving multiple organ systems are often present in disseminated MAC infection but disseminated intravascular coagulation (DIC) has not been previously described in association with this condition. To our knowledge, this is the first reported case of DIC complicating disseminated MAC infection in an AIDS patient. In this article, we present the case of a 33-year-old AIDS patient with high viral load, CD4 lymphocyte count of 1/mm3, who presented with nonspecific symptoms, anemia, thrombocytopenia, and increased lactate dehydrogenase, alkaline phosphatase, and ferritin. She also had abnormal coagulation parameters and features compatible with chronic DIC. Bone marrow biopsy assisted in making the correct diagnosis. She also later grew MAC from blood and sputum cultures. There were no other factors identified after a complete workup to explain DIC in this patient. After commencement of appropriate MAC therapy, she initially had a good response with some improvement of her coagulation parameters. Few months later, however, probably attributable to poor medication compliance, her condition deteriorated with development of thromboembolism, full-fledged DIC, sepsis, and an eventual fatal outcome. This case illustrates the importance of including disseminated MAC in the differential diagnosis of DIC in an AIDS patient.