Pulmonary co-infection with nocardia species and nontuberculous mycobacteria mimicking miliary tuberculosis in a patient with Crohn's disease under combined immunosuppressive therapy.

Nocardiosis is a rare infection caused by ubiquitous soil-born, acid-resistant, Gram-positive bacteria that can be life-threatening in immunocompromised patients. Originally usually diagnosed in HIV-positive patients, only few cases have been reported in patients on immunosuppressive therapy for inflammatory bowel disease or rheumatologic disorders. We present a case of a 32-year-old man who was treated with infliximab, prednisolone, and azathioprine for severe terminal ileitis. Although the clinical status improved under triple immunosuppressive therapy, weight loss, weakness, and fatigue persisted. Laboratory studies revealed iron deficiency anemia, hypalbuminemia and raised inflammatory markers. Chest computed tomography scan showed multiple pulmonary nodules and a large cavity in the left upper lobe (segment 3a). Empiric tuberculostatic therapy was introduced for suspected miliary tuberculosis but stopped for lack of clinical improvement and negative tuberculosis tests (interferon-gamma release assay, microscopy, polymerase chain reaction). Finally, the diagnosis of pulmonary nocardiosis with concomitant pulmonary Mycobacterium avium infection was confirmed microbiologically, and the patient was treated with high-dose co-trimoxazole, clarithromycin, ethambutol, and rifampicin for 12 months.This case report underlines the increased risk of severe and rare infections like nocardiosis with combination immunosuppressive therapy and the necessity for thorough diagnostic screening for opportunistic infection. Although long-term antibiotic treatment for nocardiosis is mandatory, the optimal timing to restart immunosuppressive therapy remains ambiguous.

[Case of hot tub lung with confirmation of exacerbation following jet bath use].

A 49-year-old woman presented with exertional dyspnea. Chest CT revealed patchy areas of ground-glass attenuation and ill-defined centrilobular nodules scattered in both lungs. Bronchoalveolar lavage (BAL) fluid showed lymphocytosis. Transbronchial lung biopsy revealed bronchiolocentric alveolitis and well-formed non-necrotizing granulomas were present. She had used a jet bath before the onset of symptoms and mycobacterial culture revealed the presence of Mycobacterium avium complex (MAC) in sputum sample, BAL samples and jet bath water. Restriction fragment length polymorphism (RFLP) analysis revealed that the isolated MAC were essentially clonal. She had used the jet bath for the inhalation provocation study, and after the challenge she complained of dyspnea and have body temperature increased. We diagnosed hot tub lung due to Mycobacterium avium complex. Because avoidance of the jet bath caused improvement of her symptoms and reduced her fever and PaO2 increased by 10 Torr but did not improve the CT findings, antimycobacterial drugs were prescribed. The patient recovered fully. This case proves that the cause of hot tub lung is the use of jet bath through the inhalation provocation study.

Hot tub lung: presenting features and clinical course of 21 patients.

BACKGROUND: Hot tub lung is an emerging lung disorder associated with exposure to Mycobacterium avium complex organisms contaminating hot tub water. OBJECTIVES: To define the clinical characteristics and outcome of patients with hot tub lung. METHODS: Retrospective review of 21 patients diagnosed with hot tub lung at a tertiary medical center over a 7-year period. RESULTS: The mean (+/-sd) age at presentation was 46 (+/- 15) years; 9 patients were men (43%). All patients described ongoing exposure to hot tubs. The most common referral diagnoses were sarcoidosis, bronchitis, and asthma. Dyspnea and cough were present in all patients, hypoxemia was noted in 10 patients (48%). High-resolution computed tomography of the chest had been performed in 20 patients and demonstrated diffuse centrilobular nodules and/or ground-glass opacities in all patients. M. avium complex was isolated from the hot tub water, respiratory secretions and/or lung tissue in all patients. Bronchoscopic or surgical lung biopsy was obtained in 18 patients and demonstrated bronchiolocentric granulomatous inflammation. With avoidance of exposure, clinical and radiologic improvement was observed in all patients. Additionally, 13 patients (62%) received corticosteroid therapy, 1 (5%) antimycobacterial therapy, 2 (10%) received both, and 5 patients (24%) received no pharmacologic therapy. CONCLUSIONS: Hot tub lung likely represents hypersensitivity pneumonitis due to inhalational exposure to M. avium complex. Antimycobacterial therapy does not appear to be required in the management of this disease. Although corticosteroids may be helpful in the treatment of severely affected patients, others can be managed by avoidance of additional exposure alone.

Hypersensitivity pneumonitis reaction to Mycobacterium avium in household water.

BACKGROUND: Hypersensitivity pneumonitis has been described with exposure to aerosolized Mycobacterium avium complex (MAC) in indoor hot tubs (hot tub lung). OBJECTIVES: To describe a case of MAC-associated hypersensitivity pneumonitis-like reaction possibly from showering and review previous hot tub lung reports. METHODS: For the case report, we investigated a patient with histologically diagnosed hypersensitivity pneumonitis and MAC-positive sputum culture findings. Mycobacterial cultures were obtained from his home and workplace. Isolates were typed using pulsed-field gel electrophoresis. For the review, MEDLINE and EMBASE were searched for hot tub lung reports, which were reviewed and summarized. RESULTS: A 50-year-old man had progressive dyspnea and episodic fever and myalgias. Pulmonary function testing results revealed obstruction and impaired diffusion; a chest CT scan found diffuse, centrilobular, ground-glass nodules, and air trapping, and a lymphocytic alveolitis with an elevated CD4/CD8 ratio. Transbronchial biopsy showed multiple well-formed nonnecrotizing granulomas. Multiple respiratory samples and shower and bathtub specimens grew MAC, with matching pulsed-field gel electrophoresis patterns. The patient changed from showering to tub bathing. Prednisone and antimycobacterial drugs were administered for approximately 1 year. His symptoms, pulmonary function abnormalities, and CT scan findings resolved. The literature review yielded 36 cases of hot tub lung. Clinical features included dyspnea (97%), cough (78%), and fever (58%). Pulmonary function testing showed obstruction (67%), restriction (55%), and impaired diffusion (75%). A chest CT scan showed ground-glass opacification (95%) and nodules (67%). Granulomas were well-formed in 95%. Treatments included discontinuation of hot tub use and prednisone, antimycobacterial drugs, or both. Outcomes were favorable. CONCLUSIONS: A hypersensitivity pneumonitis-like reaction to mycobacteria can occur from exposures other than hot tubs. There are key differences between classic hypersensitivity pneumonitis and MAC-associated hypersensitivity pneumonitis. Antimycobacterial therapy may be required. The possibility of MAC hypersensitivity pneumonitis from showering raises potential implications in the investigation of patients with hypersensitivity pneumonitis.

Hot tub lung: infection, inflammation, or both?

Increasing numbers of patients have presented with a hypersensitivity pneumonitis-type course in association with hot tub exposure. Mycobacterium avium complex (MAC) organisms have been isolated from both patient specimens and hot tub water with matching fingerprints by restricted fragment length polymorphism and electrophoresis when performed. Review of the clinical, microbiologic, and radiographic presentations of 9 patients to the Mayo Clinic with this diagnosis are compared with 32 patients in the published literature. The diagnosis, treatment, and prognosis of MAC hot tub lung are reviewed.

Treatment of Mycobacterium avium complex bacteremia in AIDS with a four-drug oral regimen. Rifampin, ethambutol, clofazimine, and ciprofloxacin. The California Collaborative Treatment Group.

OBJECTIVE: To determine the quantitative microbiologic response and the clinical response of patients with Mycobacterium avium complex bacteremia and AIDS to an oral antimycobacterial regimen. DESIGN: A phase II, multicenter clinical trial. SETTING: Four university-affiliated medical centers. PATIENTS: Forty-one patients with HIV infection who had at least two consecutive blood cultures positive for M. avium complex and who had not received previous antimycobacterial therapy were enrolled in the study. Thirty-one patients were evaluable with regard to the efficacy of the oral regimen. INTERVENTIONS: Patients received a combination of orally administered rifampin (600 mg), ethambutol (15 mg/kg body weight), clofazimine (100 mg once daily), and ciprofloxacin (750 mg twice daily) for 12 weeks. Parenterally administered amikacin, 7.5 mg/kg daily for 4 weeks after the first 4 weeks of oral therapy, was used at the discretion of the individual investigator. MEASUREMENTS: Clinical symptoms, Karnofsky scores, and adverse events were monitored. Colony counts for M. avium complex were determined. MAIN RESULTS: The mean logarithmic (log) baseline colony count decreased from 2.1 to 0.7 after 4 weeks of oral therapy (P less than 0.001). Suppression of bacteremia was sustained throughout therapy. Thirteen patients (42%) became culture negative during therapy. The mean duration of treatment was 9.7 weeks. Nineteen evaluable patients (61%) completed 12 weeks of therapy. Adverse reactions to one or more agents were common. CONCLUSIONS: A rapid reduction in symptoms and bacteremia can be achieved as early as week 2 of therapy using an oral regimen of rifampin, ethambutol, clofazimine, and ciprofloxacin. Colony counts rose dramatically after therapy was discontinued, suggesting that more prolonged periods of therapy are necessary to eradicate systemic infection.

Current and investigational therapies for AIDS-associated Mycobacterium avium complex disease.

The epidemiology, pathogenesis, clinical manifestations, and treatment of Mycobacterium avium complex (MAC) infection are reviewed. MAC infection is one of the most common infections in AIDS patients. Its pathogenesis is poorly understood, but it is believed to develop by gastrointestinal colonization followed by systemic invasion. The relatively poor response to treatment may be partly accounted for by the tremendous mycobacterial load present by the time patients develop systemic symptoms. Clinically, MAC infection is difficult to differentiate from the signs and symptoms of AIDS or from other opportunistic infections. Signs and symptoms include fever, malaise, anorexia, night sweats, and weight loss; diarrhea and abdominal pain may also be present. There is no established therapy for MAC infection, although combinations of three to five antimicrobial agents are typically used. There has been consistently poor correlation between in vitro results and in vivo outcomes in the treatment of MAC infection. Currently, the role of treatment is mainly to suppress the progression of infection and to relieve symptoms. Recent in vitro studies and animal studies have revealed possible alternative agents and combinations of agents (e.g., macrolide antibiotics, quinolones, amikacin, cytokines) that may influence therapy of MAC infection. No known therapy for MAC has been shown to prolong survival in AIDS patients, possibly because of the high organism load that exists once patients become symptomatic. Research is needed to find improved methods for earlier detection of MAC infection, determine optimal dosage regimens of current antimycobacterial agents, develop better antimycobacterial drug-delivery systems (e.g., liposomes), and discover new antimicrobials with better activity against MAC and methods of immune modulation that will overcome immune system defects.