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.

Late Onset Hypercalcemia in an HIV Patient as a Manifestation of Immune Reconstitution Inflammatory Syndrome (IRIS).

Hypercalcemia in human immunodeficiency virus (HIV) patients can be challenging due to various underlying mechanisms. 1,25- dihydroxycholecalciferol (1,25 (OH)2 vitamin D)-mediated hypercalcemia due to increased activity of extrarenal 1-alpha hydroxylase is one of the well-known mechanisms of hypercalcemia described in HIV patients. Mycobacterium avium-intracellulare (MAI) is a granulomatous disease that can cause hypercalcemia due to ectopic production of alpha -1 hydroxylase and result in increased levels of 1,25 (OH)2 vitamin D. Herein, we present a case of "late-onset" hypercalcemia in a patient with HIV/AIDS and MAI infection in the setting of suspected immune reconstitution inflammatory syndrome (IRIS). The hypercalcemia workup showed an inappropriately average level of 1,25 (OH)2 vitamin D while the rest of the workup was unrevealing. Unusually normal levels of vitamin D metabolites were the driving mechanism of hypercalcemia in this case. The late presentation of hypercalcemia was likely due to IRIS unmasking an underlying granulomatous infection, and this consideration led to the successful treatment of the patient with steroid administration. This case emphasizes the importance of considering IRIS in evaluating hypercalcemia that presents late in the course of granulomatous infections in HIV patients.

Hypercalcemia as a rare manifestation of immune reconstitution inflammatory syndrome (IRIS) in a person living with Human Immunodeficiency Virus (HIV) with disseminated nontuberculous mycobacteriosis.

INTRODUCTION: Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV). CASE PRESENTATION: A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18Fluoro-D-glucose positron emission computed tomography (18FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered. CONCLUSION: Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment.

Cutaneous Mycobacterium avium-intracellulare infection masquerading as sarcoidosis.

Mycobacterium avium-intracellulare (MAC) infection may have different skin manifestations, including cutaneous granulomas. Granulomatous skin reactions have distinct morphologic and histopathologic appearances. We present the case of an adolescent male with cutaneous MAC, misdiagnosed as sarcoidosis after initial biopsy results, demonstrated preservation of reticulin fibers and absence of organisms within granulomas. Sarcoidal granulomas often stain positive for reticulin fibers, which could be used to distinguish them from the infectious kind. This case should alert clinicians to the fact that the presence or quantity of intact reticular fibers may not be a reliable tool to differentiate between a sarcoidal and an infectious granuloma. Our case also highlights the diagnostic challenge of cutaneous MAC infection.

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.

Septic Mycobacterium Avium Intracellulare Extensor Tenosynovitis of the Wrist.

Mycobacterium avium intracellulare (MAI) infections of the hand, wrist, and upper extremity are rare, but potentially devastating atypical mycobacterial infections that can affect tendon, bone, and other soft tissues of the musculoskeletal system. We present an immunocompromised patient presenting with acute swelling and pain in the dorsum of the hand and wrist that underwent a wrist extensor tenosynovectomy with intraoperative cultures revealing infection with MAI. The patient developed severe progression of the infection with osteomyelitis of the distal forearm and carpal bones, multiple subsequent extensor tendon ruptures, and dorsal skin necrosis. The infection was eradicated with a combination of surgical treatment and antibiotic therapy. The case is discussed in context of the prior scant literature of infectious tenosynovitis of the hand, wrist, and upper extremity caused by MAI. This case report and literature review outline recommendations for diagnosis and effective treatment of MAI.

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.

A Patient With Mycobacteremia Due to Two Different Nontuberculous Mycobacteria.

Disseminated nontuberculous mycobacterial infections are most common in patients with severe immunosuppression, such as people with human immunodeficiency virus (HIV) and low CD4+ T-cell counts. In this report, we present a rare case of a person with HIV who was hospitalized for mycobacteremia due to 2 different nontuberculous mycobacteria. We also provide a comprehensive summary of published case reports describing nontuberculous mycobacterial coinfections.

Miliary Tuberculosis: A Case Report Highlighting the Diagnostic Challenges Associated With the Condition.

End-stage renal disease requiring chronic dialysis is an immunocompromised state which increases the risk of tuberculosis development and its spread. Due to the high frequency of non-specific or "decoy" symptoms at presentation and frequent extrapulmonary involvement, diagnosis of tuberculosis is a significant challenge. Therefore, it is correctly labeled as 'Tuberculosis; the great imitator' as it can mimic various other disease processes, causing confusion and testing of subsystems involved in the disease process, which come back as abnormal, leading to a vicious cycle. Missing the diagnosis leads to grave consequences, especially in a patient with a miliary form of tuberculosis, as the prognosis with any delay in treatment is poor. High diagnostic suspicion is required to promptly diagnose and treat the condition, especially in a resource-rich setting where tuberculosis is uncommon. Here, we report a patient with miliary tuberculosis who presented with a chief complaint of chronic diarrhea and fecal continence, with prior recent negative interferon-gamma release assay testing. Due to every organ system involved, multiple subspecialties were on board, with a broad differential in mind, including malabsorption syndromes, neoplasia, infections, amyloidosis, and autoimmune disorders, and therefore, numerous tests were performed. However, despite all efforts, the diagnosis was delayed significantly, leading to the unfortunate demise of the patient. The case report sheds light on unique clinical features of miliary tuberculosis, diagnostic findings, and a reminder to always keep tuberculosis high in the differential in an appropriate clinical setting.

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.

Florid Pulmonary Mycobacterium avium-intracellulare Infection in a Patient With Large Granular Lymphocytic (LGL) Leukemia on Chronic Cyclophosphamide.

Large granular lymphocytic (LGL) leukemia is a rare form of incurable chronic leukemia frequently complicated by life-threatening cytopenias. The less common NK-cell variant of this disorder poses a diagnostic challenge and its etiologic basis is poorly understood. Here we present the case of an elderly man diagnosed with LGL leukemia after presenting with severe Coombs-negative hemolytic anemia, who had a robust durable response to oral cyclophosphamide. Close to two years after initial diagnosis, he developed a florid Mycobacterium avium-intracellulare (MAI) infection of the lungs. We discuss the clinical and pathologic features of this case, highlighting aspects common to this disorder and areas of clinical uncertainty. We hope to both raise awareness of the risk for pulmonary MAI infection in patients treated with lymphodepleting drugs and to motivate the prospective evaluation of strategies to prevent opportunistic infections in LGL leukemia.

Hypercalcemia Secondary to Immune Reconstitution Inflammatory Syndrome in an HIV-Infected Individual With Mycobacterium avium Complex.

Immune reconstitution inflammatory syndrome (IRIS) is an uncommon cause of hypercalcemia in HIV-infected patients recently started on highly active antiretroviral therapy (HAART). It is hypothesized that increased granulomatous formation due to IRIS leads to an overproduction of calcitriol. High levels of calcitriol, then, can lead to significant hypercalcemia. We present the case of a 63-year-old male with HIV off HAART presented to the emergency room for confusion, frequent falls, and cough. His CD-4 count was noted to be below 35 cells/µL (255-2,496). Over the course of the hospitalization, the patient was found to have disseminated Mycobacterium avium complex (MAC) infection and was initiated on HAART. Initiation of HAART was followed by an increase in calcium up to 14.1 mg/dL. The hypercalcemia did not respond to either Calcitonin or Pamidronate. Consideration was then given to IRIS in the setting of MAC infection leading to increased granulomatous formation. Calcium levels normalized within three days of therapy after initiation of prednisone for the treatment of IRIS.  It is thought that an increase in CD-4 counts leads to the recovery of an immune response. This can lead to granulomatous inflammation. An increase in granuloma formation can cause hypercalcemia due to overproduction of calcitriol via increased 1𝛼-hydroxylase activity from macrophages. Our case report describes IRIS-mediated hypercalcemia in an HIV-infected individual with MAC infection. This unusual cause of severe hypercalcemia should be considered in differential diagnoses for immunocompromised patients in the appropriate setting. Prompt treatment of IRIS with glucocorticoids can lead to the resolution of hypercalcemia.

Septic Arthritis of the Right Wrist Due to Mycobacterium avium Complex in an Immunocompetent Patient.

Septic arthritis due to Mycobacterium avium complex (MAC) is extremely rare. While MAC infection is classically associated with HIV/AIDS and immunosuppressed states, it may occur in immunocompetent individuals. We report a case of MAC septic arthritis of a native wrist joint in an immunocompetent host. The diagnosis of septic arthritis due to MAC is commonly delayed and initially misdiagnosed, warranting a high level of suspicion to make an accurate and timely diagnosis. Suspecting the diagnosis when there are atypical features present in the clinical history may be crucial in identifying affected patients.

Nontuberculous Mycobacterial Infection Predisposing to Chronic Cavitary Pulmonary Aspergillosis.

Aspergillus is a large group of spore-forming fungi in the phylum Ascomycota. Aspergillus infections more frequently occur in individuals with pre-existing lung conditions such as cystic fibrosis and asthma and immunosuppressed individuals, and less frequently in the immunocompetent population. Pulmonary aspergillosis can be subdivided into three categories: allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, and invasive pulmonary aspergillosis. We present a rare case of a 57-year-old male with a previously known diagnosis of pancreatic adenocarcinoma on chemotherapy who was found to have a co-infection of the respiratory tract by Aspergillus flavus and Mycobacterium avium intracellulare.