Nontuberculous Mycobacteria Lung Disease (NTM-LD): Current Recommendations on Diagnosis, Treatment, and Patient Management.

Nontuberculous mycobacteria (NTM) are a group of ubiquitous environmental bacteria that can be found in soil, dust, and water. Mycobacterium avium complex (MAC) is the most common pathogen and the one most associated with chronic pulmonary disease. In recent years, the prevalence of Mycobacterium avium complex-related pulmonary disease (MAC-PD) has increased and is an emerging public health concern. This is due to a combination of environmental and geographic factors, dynamic changes in organism virulence and antimicrobial susceptibility, and evolving host susceptibility. Given the dynamic nature of the disease, management of NTM pulmonary disease (NTM-PD) often includes a multimodal approach including antimicrobial therapy, airway clearance techniques, limiting environmental exposures, and reducing susceptibility to NTM through prevention of reflux and maintenance of body weight. This review will explore the most recent concepts in the diagnosis, treatment, and management of individuals with NTM pulmonary infection.

Critical Upper Airway Edema After a Bee Sting to the Uvula.

Hymenoptera stings of the upper airway are rare events, but can result in rapid, life-threatening airway emergencies. The allergenic and toxic mediators that are released from the stings of bees, wasps, and hornets can cause local tissue inflammation and edema with subsequent upper airway obstruction. We report the case of a 15-y-old girl who suffered a bee sting to the uvula while zip-lining in Costa Rica. Shortly thereafter, she developed a choking sensation with associated dysphonia, odynophagia, drooling, and respiratory distress. She was brought to a rural emergency medical clinic where she was noted to have an erythematous, edematous, boggy uvula, with a black stinger lodged within it, as well as edema of the anterior pillars of the tonsils and soft palate. The stinger was removed with tweezers and she was treated with an intravenous corticosteroid and antihistamine. She had persistence of airway edema and symptoms until the administration of epinephrine, which resulted in clinical improvement shortly thereafter. In our review of this case and the existing literature, we emphasize the importance of early recognition and management of hymenoptera stings of the upper airway, which should always include immediate manual removal of the stinger, and in cases with significant upper airway edema, the administration of epinephrine should be considered.

Immune reconstitution inflammatory syndrome in Mycobacterium chimaera mediastinitis: When clinical judgment trumps imaging.

Mycobacterium chimaera has been described in postoperative cardiovascular procedures in patients after an outbreak of contaminated 3T heater-cooler units. Immune reconstitution inflammatory syndrome (IRIS) has been mostly reported in immunocompromised patients, especially HIV after starting therapy. Our case is a 52-year-old immunocompetent male who was diagnosed with M. chimaera mediastinitis a year after Type A dissection repair and was started on quadruple antimicrobial therapy. He clinically improved but 8 months into therapy he presented with a declining kidney function, pancytopenia, and hypercalcemia which after bone marrow and kidney biopsies were attributed to IRIS. Our patient's diagnosis spared him subsequent surgery. IRIS during the treatment of nontuberculous mycobacteria must be suspected even in immunocompetent patients as reaching the diagnosis is very helpful in preventing additional diagnostic and therapeutic measures.

Mycobacterium avium in Community and Household Water, Suburban Philadelphia, Pennsylvania, USA, 2010-2012.

Attention to environmental sources of Mycobacterium avium complex (MAC) infection is a vital component of disease prevention and control. We investigated MAC colonization of household plumbing in suburban Philadelphia, Pennsylvania, USA. We used variable-number tandem-repeat genotyping and whole-genome sequencing with core genome single-nucleotide variant analysis to compare M. avium from household plumbing biofilms with M. avium isolates from patient respiratory specimens. M. avium was recovered from 30 (81.1%) of 37 households, including 19 (90.5%) of 21 M. avium patient households. For 11 (52.4%) of 21 patients with M. avium disease, isolates recovered from their respiratory and household samples were of the same genotype. Within the same community, 18 (85.7%) of 21 M. avium respiratory isolates genotypically matched household plumbing isolates. Six predominant genotypes were recovered across multiple households and respiratory specimens. M. avium colonizing municipal water and household plumbing may be a substantial source of MAC pulmonary infection.

Mycobacterium avium complex pulmonary disease: new epidemiology and management concepts.

PURPOSE OF REVIEW: The prevalence of Mycobacterium avium complex (MAC)-related pulmonary disease has been increasing because of environmental factors, changes in organism virulence, and evolving host susceptibility. Treatment is often complicated by adverse effects, development of drug resistance, and refractory disease, with recurrence rates as high as 25-45%. RECENT FINDINGS: Aerosolization of water, soil, or dusts are the likely sources of MAC-related pulmonary disease in susceptible individuals. The management of MAC-related pulmonary disease requires a multimodality approach, including antimicrobial therapy in appropriate patients, employment of mucus clearance techniques, instituting changes in the individual's home environment and personal habits to reduce environmental exposure to MAC, prevention of reflux, and maintenance of a healthy body weight. When the standard treatment for MAC-related pulmonary disease is not possible because of drug intolerance, antibiotic resistance, or progression of disease, second-line agents such as inhaled amikacin, clofazimine, bedaquiline, and delamanid must be considered, despite limited experience and few studies to guide their use. SUMMARY: Individuals who have proven to be susceptible to MAC-related pulmonary disease should institute measures to reduce exposure to environmental sources of infection. Further research is needed to assess the impact of such preventive strategies on the incidence of new infection and disease recurrence. The efficacy of new medications for MAC-related pulmonary disease and their use in different combinations also requires further study.

Methylobacterium spp. as an indicator for the presence or absence of Mycobacterium spp.

OBJECTIVE/BACKGROUND: A published survey of bacteria in showerhead biofilm samples revealed that Methylobacterium spp. and Mycobacterium spp. seldom coexisted in biofilms. METHODS: To confirm that information, biofilm samples were collected from household plumbing of Mycobacterium avium patients and Methylobacterium spp. and M. avium numbers were measured by direct colony counts. RESULTS: The results demonstrated that if Methylobacterium spp. were present, Mycobacterium spp. were absent, and the opposite. CONCLUSION: The data demonstrate that microbial populations in biofilms can influence the presence or absence of opportunistic premise plumbing pathogens and, thereby, increase the range of strategies to reduce exposure to waterborne pathogens. Finally, by assessing for the visual presence of methylobacteria as pink pigmentation on showers and shower curtains, homeowners and managers of hospitals and other buildings can quickly determine whether a premise plumbing biofilm sample has mycobacteria with a high degree of assurance.

Variable-Number Tandem-Repeat Analysis of Respiratory and Household Water Biofilm Isolates of "Mycobacterium avium subsp. hominissuis" with Establishment of a PCR Database.

"Mycobacterium aviumsubsp.hominissuis" is an important cause of pulmonary disease. It is acquired from environmental sources, but there is no methodology for large population studies. We evaluated the potential of variable-number tandem-repeat (VNTR) analysis. Clinical and household biofilmM. aviumisolates underwent molecular identification. Testing for IS901was done to separateM. aviumsubsp.aviumfromM. aviumsubsp.hominissuis VNTR types were defined using VNTR loci, and subtyping was performed using 3'hsp65and internal transcribed spacer (ITS) sequencing. Forty-nine VNTR types and eight subtypes ofM. aviumsubsp.hominissuis(IS901negative) were identified among 416 isolates ofM. aviumfrom 121 patients and 80 biofilm sites. Of those types, 67% were found only among patient isolates, 11% only among household water isolates, and 23% among both. Of 13 VNTR types that included ≥4 patients, the majority (61.5%) represented geographic clustering (same city). Most VNTR types with multiple patients belonged to the same 3'hsp65sequence code (sequevar). A total of 44 isolates belonging to fourM. aviumsubsp.hominissuisVNTR types (8%), including three with the rare Mav-F ITS sequence and 0/8 subspecies, produced amplicons with IS901PCR primers. By sequencing, all 44 amplicons were not IS901but ISMav6, which was recently observed in Japan but had not been previously described among U.S. isolates. VNTR analysis ofM. aviumsubsp.hominissuisisolates is easier and faster than pulsed-field gel electrophoresis. Seven VNTR loci separated 417 isolates into 49 types. No isolates ofM. aviumsubsp.aviumwere identified. The distributions of the VNTR copy numbers, the allelic diversity, and the low prevalence of ISMav6 differed from the findings for respiratory isolates reported from Japan.

Normal estrogen, but low dehydroepiandrosterone levels, in women with pulmonary Mycobacterium avium complex. A preliminary study.

RATIONALE: For unclear reasons, the phenotypical hosts for nontuberculous mycobacterial lung infection are often thin, elderly, white women without underlying lung disease. As these women are usually postmenopausal, we hypothesized that a state of relative hormone deficiency may predispose some women to pulmonary nontuberculous mycobacterial infection. OBJECTIVES: To conduct a prospective cross-sectional study to assess for alterations in systemic levels of sex hormones in patients with confirmed pulmonary Mycobacterium avium complex infection compared with healthy control subjects. METHODS: Female patients with pulmonary M. avium complex infection (n = 35) were recruited along with similar-aged control subjects (n = 27) without lung disease from the general population of our institution. Levels of dehydroepiandrosterone-sulfate (DHEA-S), estrone, and ultrasensitive estradiol were measured from sampled blood. MEASUREMENTS AND MAIN RESULTS: DHEA-S levels of patients with M. avium complex infection were significantly lower than control subjects (mean 33 µg/dl vs. 59 µg/dl, P = 0.001). No significant difference was found in the levels of estrone (mean, 27 pg/ml vs. 28 pg/ml, P = 0.665) or ultrasensitive estradiol (mean, 9 pg/ml vs. 9 pg/ml, P = 0.364). Patients with M. avium complex had a lower body mass index (BMI) than control subjects (mean, 22 vs. 26, P = 0.001). There was no association between levels of DHEA-S, estrone, or estradiol, and BMI or age. CONCLUSIONS: Women with M. avium complex infection had lower DHEA-S levels, but not lower estrogen levels, compared with control subjects. There was no relationship between BMI and hormone levels in the study population. Further study of these hormonal effects on immune function in nontuberculous mycobacterial infection is warranted.

Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease.

Recent studies have shown that respiratory isolates from pulmonary disease patients and household water/biofilm isolates of Mycobacterium avium could be matched by DNA fingerprinting. To determine if this is true for Mycobacterium intracellulare, household water sources for 36 patients with Mycobacterium avium complex (MAC) lung disease were evaluated. MAC household water isolates from three published studies that included 37 additional MAC respiratory disease patients were also evaluated. Species identification was done initially using nonsequencing methods with confirmation by internal transcribed spacer (ITS) and/or partial 16S rRNA gene sequencing. M. intracellulare was identified by nonsequencing methods in 54 respiratory cultures and 41 household water/biofilm samples. By ITS sequencing, 49 (90.7%) respiratory isolates were M. intracellulare and 4 (7.4%) were Mycobacterium chimaera. In contrast, 30 (73%) household water samples were M. chimaera, 8 (20%) were other MAC X species (i.e., isolates positive with a MAC probe but negative with species-specific M. avium and M. intracellulare probes), and 3 (7%) were M. avium; none were M. intracellulare. In comparison, M. avium was recovered from 141 water/biofilm samples. These results indicate that M. intracellulare lung disease in the United States is acquired from environmental sources other than household water. Nonsequencing methods for identification of nontuberculous mycobacteria (including those of the MAC) might fail to distinguish closely related species (such as M. intracellulare and M. chimaera). This is the first report of M. chimaera recovery from household water. The study underscores the importance of taxonomy and distinguishing the many species and subspecies of the MAC.

Association between pulmonary mycobacterium avium complex infection and lung cancer.

INTRODUCTION: Patients with lung cancer are sometimes found to have respiratory cultures growing Mycobacterium avium complex (MAC). This study describes the clinical, pathologic, and radiographic -characteristics of individuals who harbor concomitant lung cancer and MAC. METHODS: Retrospective analysis of patients with positive respiratory cultures for MAC (370 men, 475 women) and with newly diagnosed lung cancer (792 men, 840 women) from 1995 to 2010. RESULTS: Of the patients with respiratory cultures growing MAC, 8.6% of men and 6.3% of women had lung cancer. Twenty-five percent of patients with lung cancer and 3% with nonbronchiectatic benign lung disease grew MAC from their respiratory cultures. Significantly fewer women with both MAC and lung cancer were smokers than the control group of women with lung cancer and negative MAC cultures (68% versus 89%, p < 0.01). Squamous cell carcinoma occurred in 40% of women in the MAC/lung cancer group versus 28% of women in the lung cancer control group. Peripherally located squamous cell carcinomas were found in 71% of the MAC/lung cancer group versus 40% of the lung cancer control group (p = 0.01) CONCLUSIONS: The percentage of smokers among women with both MAC and lung cancer was lower than among the lung cancer control group who did not grow MAC. The presence of MAC in respiratory cultures of lung cancer patients was particularly associated with squamous cell carcinomas located in the periphery of the lung. Because MAC typically affects distal airways, this possible association between MAC infection and lung cancer warrants further study.

Primary pericardial mesothelioma unique case and literature review.

A 72-year-old woman, on warfarin therapy and with a remote history of breast cancer and radiation treatment, presented with a 10-day history of nausea, dyspnea, dry cough, and dizziness. An electrocardiogram showed new-onset atrial fibrillation. Computed tomography of the chest revealed multiple pulmonary emboli and a pericardial effusion. Echocardiography showed a pericardial effusion with tamponade characteristics. The patient's condition deteriorated, and a pericardiectomy was performed. Histologic evaluation confirmed primary pericardial mesothelioma. She underwent palliative treatment and died 3 months after discharge from the hospital. We discuss the patient's case and the nature of primary pericardial mesothelioma, a rare oncologic entity.

Reversal of citalopram-induced junctional bradycardia with intravenous sodium bicarbonate.

The cardiotoxicity of tricyclic antidepressants is a well-described phenomenon requiring serious consideration in patients who have taken an overdose. In patients who are at high risk for suicide attempts, selective serotonin reuptake inhibitors (SSRIs) were thought to constitute a safe alternative. However, evidence is accumulating that they, too, possess proarrhythmic properties, which must be reconciled in the setting of an overdose. An 82-year-old woman intentionally ingested citalopram 1.6 g. Several hours after presentation, she developed sinus arrest and junctional bradycardia that resolved after infusion of intravenous sodium bicarbonate solution. Thereafter, she demonstrated no further electrocardiographic abnormalities and was safely transferred to the psychiatry service without the need for a temporary transvenous pacemaker. The dramatic effect of the sodium bicarbonate on the arrhythmia represents a probable event according to the Naranjo probability scale. Intravenous sodium bicarbonate may serve as an effective antidote to SSRI-induced bradyarrhythmias.

Apoptosis induced by Pseudomonas aeruginosa in antigen presenting cells is diminished by genetic modification with CD40 ligand.

Persistent colonization with Pseudomonas aeruginosa (PA) is a hallmark of the lung disease associated with cystic fibrosis (CF). Based on the concept that PA is not cleared from the lung by the host response in individuals with CF, we analyzed the capacity of PA to induce cell death in human alveolar macrophages (AM) and murine dendritic cells (DC), antigen presenting cells that play a central role in the initiation of pulmonary host defenses against pathogens, and evaluated if genetic modification can lead to protection against PA induced cell death. AM and DC were susceptible to cell death induced by the laboratory PA isolates PAO1, PAK and PA103, as well as a mucoid derivative of PAO1 and PA isolates derived from sputum of individuals with CF. Apoptosis, analyzed by TUNEL assay, was detectable in AM and DC as early as 3 h after infection with PA. In contrast, the same strains and doses of PA had little effect on the lung epithelial cell line A549 and primary cultures of human bronchial epithelial cells in vitro. Pretreatment of DC with the caspase inhibitors VAD-fmk and YVAD-cmk reduced PA induced cell death (p < 0.05). Finally, genetic modification of DC to express CD40L using an adenovirus vector decreased the susceptibility of DC to cell death induced by PAO1 compared with DC infected with a control Ad vector (p < 0.01). The data demonstrate that DC and AM are susceptible to apoptosis induced by PA and that this response can be partially reversed by genetic modification with CD40L, a CD4+ T cell molecule that plays a central role in activating antigen presenting cells. These observations suggest a potential mechanism contributing to the persistence of PA in CF and suggest that genetic manipulation of antigen presenting cells with anti-apoptotic genes may be able to strengthen host defenses in CF.

Impact of antiretroviral therapy on decreasing hospitalization rates of HIV-infected patients in 2001.

Effective antiretroviral therapy initially resulted in large decreases in hospitalization rates of HIV-infected patients. The goal of this study was to determine whether these gains were being maintained in 2001. A cross-sectional study of hospital admission characteristics during four time periods was performed. All patients receiving care at the HIV clinics of New York Presbyterian Hospital-Cornell Medical Center (NYPH) in New York City were included. In 1995, 883 outpatients were receiving care for HIV infection at NYPH; this increased to 1990 outpatients by 2001. Demographic and laboratory information was obtained for these outpatients, and diagnoses were recorded for all patients requiring hospitalization on at NYPH during the time periods January 1 through June 30, in 1995, 1997, 1999, and 2001. The incidence of hospital admission declined in all four time periods: 1995 (95 per 100 patient-years [pt-yr]), 1997 (48 per 100 pt-yr), 1999 (38 per 100 pt-yr, p < 0.05), and 2001 (25 per 100 pt-yr). The incidence of bacterial pneumonia and opportunistic infections (OIs) decreased in all four time periods. The median hospitalization were CD4(+) cell count for outpatients increased from 231 (1995) to 364 (2001). Important predictors of hospitalization were CD4(+) < 200, and IVDU as an HIV risk factor. Since 1995 and the introduction of highly active antiretroviral therapy, continuing increases in CD4(+) cell counts of outpatients has been reflected in persistent declines in hospitalization rates. Large decreases in OIs and pneumonia have been minimally offset by stable rates of hospital admissions for diagnoses such as hepatitis, cirrhosis, and cellulitis.