Infection in a cystic fibrosis patient.

Abstract

A 39-year-old white male with cystic fibrosis and a history of atrial fibrillation, periportal fibrosis of the liver, and diabetes mellitus secondary to prednisone use was admitted for bilateral lung transplantation due to end-stage lung disease. Pretransplant chest x-ray films were interpreted as showing no evidence of infection (Figure 1). The explanted lungs contained inspissated, tenacious mucus throughout the main-stem and secondary bronchi with congestion and areas of consolidation (Figure 2). Microscopically, the explanted lungs demonstrated generalized bronchiectasis, mucus plugging, and acute inflammation consistent with cystic fibrosis (Figure 3). Caseating peribronchial granulomas were also present (Figure 4). Ziehl-Neelsen stain yielded the diagnostic findings demonstrated in Figure 4.What is your diagnosis?Ziehl-Neelsen stain showed beaded acid-fast bacilli. Culture of the explanted lungs and a pretransplant sputum grew Mycobacterium avium-intracellulare, which was subsequently confirmed by DNA probe. The subject showed no evidence of extrapulmonary or recurrent pulmonary M avium-intracellulare infection after transplant.The nontuberculous mycobacteria (NTM) include a variety of organisms that are occasionally recovered from patients with lung diseases such as emphysema, pneumoconiosis, bronchiectasis, and cystic fibrosis.1 Traditionally, NTM infections have been infrequently reported in cystic fibrosis patients, but with increased screening for these organisms in cystic fibrosis centers, the reported infection rates have increased.12 The rate of clinical infection with NTM in patients with cystic fibrosis is difficult to determine because of the chronic and progressive nature of their pulmonary disease, which often masks their clinical signs and symptoms.3 Because of this, NTM organisms recovered from their respiratory secretions are often considered colonizing agents.Several studies have been performed to assess the frequency of NTM infection in cystic fibrosis patients. Hjelte et al4 prospectively studied 54 patients and found that 6 had positive sputum cultures for NTM. All 6 (aged 11 to 34 years) had evidence of clinical deterioration, and all 6 responded to therapy. Fauroux et al5 prospectively studied 106 patients (aged 1 to 18 years during a 1-year period. The prevalence of NTM infection in the cystic fibrosis population that they studied was 6.6%, but only 1.9% of the patients had mycobacterial lung disease, demonstrated by decreasing lung function, sputum production, hemoptysis, and weight loss. Kinney et al6 reported a case of mycobacterial infection with M avium-intracellulare in a 31-year-old cystic fibrosis patient who underwent lung transplantation. Granulomas were present in the explanted lung, as in our patient. Tomashefski et al1 retrospectively studied lung and hilar lymph nodes in 18 patients who had antemortem sputum cultures positive for NTM. Necrotizing pulmonary granulomas were found in 2 patients who had multiple positive sputum cultures premortem; however, they found no increase in prevalence of necrotizing granulomas in patients with positive as opposed to negative cultures. The varied recovery rates reported in the literature may be attributed to different decontamination procedures and geographic variation of colonization with these nontuberculous organisms among the patient population.Recovery rates do not necessarily reflect the rate of clinical infection due to NTM in cystic fibrosis patients. The importance of determining whether a patient is colonized or infected is heightened in the era of lung transplantation because posttransplant immunosuppressive regimens increase the risk for infection with NTM. Clinical infection is often difficult to determine in a given case because of the chronic and progressive respiratory symptoms of cystic fibrosis patients. The most helpful clinical criteria in one study included fever, night sweats, hemoptysis, pulmonary deterioration, and repeated isolation of the organism.1 Diagnostic criteria for pulmonary disease caused by NTM have been proposed and include chest radiographic changes and sputum positivity for 2 or more weeks.7Typical chest radiographic changes in M avium-intracellulare include bronchiectasis, nodules, and areas of consolidation.7 Infections due to NTM in solid-organ transplant are uncommon but represent an important cause of morbidity. Previously reported common manifestations of NTM infections in solid-organ transplant recipients include cutaneous lesions of the extremities, tenosynovitis, and joint infection.8 The patient we describe developed infection with mycobacteria prior to lung transplantation and had no subsequent evidence of mycobacterial infection after transplantation.In conclusion, NTM are an uncommon cause of clinical infection in cystic fibrosis; however, recent reports indicate an increase in prevalence. Infection with nontuberculous organisms presents a diagnostic challenge in the workup of these patients for transplant. Awareness of this fact will allow a better diagnostic workup in pretransplant patients and may even improve their survival, as we become more familiar with this complication.