title: Challenges in the diagnosis and management of Nocardia infections in lung transplant recipients.
abstract: BACKGROUND
  Nocardia infection occurs in 2.1-3.5% of lung transplant recipients, and may involve cavitary nodular pulmonary lesions, soft tissue infection, or other sites of dissemination. Nocardiosis can pose challenging clinical problems in the areas of diagnosis and treatment. Diagnostic delays may occur, and adverse reactions to therapy are common. This study reviews clinical and epidemiological aspects of nocardiosis in lung transplant recipients, with special attention to pitfalls in management. Clinicians should be alert for these possibilities in order to institute prompt therapy and to achieve successful outcomes.
  
  
  METHODS
  A retrospective cohort study was conducted of 577 lung transplant recipients from January 1991 to May 2007. Demographics, reason for transplant, recent rejection, time from transplantation, site of infection, hypogammaglobulinemia, and/or neutropenia shortly before onset, Pneumocystis jiroveci prophylaxis, Nocardia species, radiographic findings, extrapulmonary lesions, nature and duration of treatment, adverse reactions, and outcomes were recorded.
  
  
  RESULTS
  Nocardia infection occurred in 1.9% (11/577). Mean onset was 14.3 months after transplant (range 1.5-39 months). N. asteroides was isolated in 55% (6/11). Emphysema was the most common reason for transplant (7/11, 64%). Six patients were receiving trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis at the time of diagnosis. Three patients had immune globulin G levels <400 mg/dL and 2 were neutropenic in the 3 months preceding diagnosis. Diagnosis was made by bronchoalveolar lavage (55%), skin abscess culture (18%), open lung biopsy (9%), pleural fluid (9%), and sputum culture (9%). Definitive diagnosis required a median of 9 days and a mean of 13.6 days (range 3-35 days) from the time of diagnostic sampling. Soft tissue lesions occurred in 3 and central nervous system involvement in 1 patient. Adverse reactions to therapy occurred in 9/10 (90%) of patients for whom information was available. Nocardia-related mortality occurred in 2/11 patients (18%).
  
  
  CONCLUSIONS
  Nocardiosis occurred in 1.9% of lung transplant recipients and was associated with a mean of nearly 2 weeks to diagnosis and frequent adverse effects on therapy. TMP-SMX prophylaxis on a thrice weekly basis did not prevent all episodes of nocardiosis. Despite utilization of protocol bronchoscopies with cultures for Nocardia, this organism remains a source of clinical complexity in the lung transplant population.
authors.affiliation: Department of Internal Medicine, The Cleveland Clinic, Cleveland, Ohio 44195, USA. kristypoonya@yahoo.com
authors.forename: H K
authors.initials: HK
authors.lastname: Poonyagariyagorn
authors.forename: A
authors.initials: A
authors.lastname: Gershman
authors.forename: R
authors.initials: R
authors.lastname: Avery
authors.forename: O
authors.initials: O
authors.lastname: Minai
authors.forename: H
authors.initials: H
authors.lastname: Blazey
authors.forename: K
authors.initials: K
authors.lastname: Asamoto
authors.forename: J
authors.initials: J
authors.lastname: Alster
authors.forename: S
authors.initials: S
authors.lastname: Murthy
authors.forename: A
authors.initials: A
authors.lastname: Mehta
authors.forename: G
authors.initials: G
authors.lastname: Pettersson
authors.forename: D P
authors.initials: DP
authors.lastname: Mason
authors.forename: M
authors.initials: M
authors.lastname: Budev
mesh_terms: D000038:Abscess / Q000175:diagnosis / Q000453:epidemiology / Q000382:microbiology; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001706:Biopsy; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology / Q000473:pathology; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009617:Nocardia Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology*; D009616:Nocardia asteroides / Q000302:isolation & purification; D009820:Ohio / Q000453:epidemiology; D035422:Pleural Cavity / Q000378:metabolism / Q000382:microbiology; D011183:Postoperative Complications / Q000175:diagnosis* / Q000188:drug therapy / Q000453:epidemiology*; D012189:Retrospective Studies; D012867:Skin / Q000473:pathology; D013183:Sputum / Q000382:microbiology; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use
chemical_list: D000890:Anti-Infective Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination