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phylaxis and include monotherapy and combination regimens.38,39 A recent recommendation is as follows:

a. seropositive recipients receive:

CMV-Ig 150 mg/kg on postoperative day (POD) 1 and 100 mg/kg on PODs 15 and 30

Ganciclovir IV for 30 days Acyclovir 3.2 g/day for 5 months b. CMV donor positive/recipient negative receive: CMV-Ig for seven doses

Ganciclovir for 100 days Acyclovir 3.2 g/day for 3 months

Utilizing this regimen, no evidence of CMV infection was seen in 69% (96 of 140) of patients by the end of the first year post-transplant. The incidence of symptomatic CMV infection was only 20%. The overall mortality rate was 1.4%.

It may be difficult to distinguish CMV pneumonitis from acute rejection in patients who develop cough, fever, and radiographic infiltrates. Bronchoscopy with transbronchial biopsies may be useful in differentiating acute rejection from CMV pneumonitis by providing additional specimens for culture, immunostaining for CMV, and histologic identification of acute rejection or cytomegalic inclusions. Open lung biopsy may be necessary to make the diagnosis in rare cases after failure of empiric therapy.

Standard treatment of CMV disease consists of 2 to 3 weeks of IV ganciclovir at a dose of 5 mg/kg twice daily adjusted for renal function. Although no controlled trials are available for the use of CMV-Ig for therapy, many centers add it to their ganciclovir for the treatment of tissue-invasive CMV pneumonia or colitis.

Resistance of CMV to antiviral agents has been well recognized in the laboratory and clinical setting. The incidence of ganciclovir resistance ranges from 2% to 10%, depending on the intensity of the immunosuppressive regimen and the specific organ transplanted.40 Risk factors for the development of resistance include the intensity of the immunosuppression, particularly the utilization of anti-thymocyte globulin or OKT3 for induction therapy or treatment of rejection episodes, or prolonged exposure to either IV or oral ganciclovir. Furthermore, patients with resistant isolates have decreased overall survival and an earlier onset of BOS. Foscarnet is typically effective for the treatment of ganciclovir-resistant CMV isolates but cross-resistant strains are emerging that may require the use of Cidofovir or a combination of agents.

Fungal

Fungal prophylaxis is not routinely employed. Fungal organisms such as Candida albicans and Aspergillus species may colonize the respiratory tract in lung transplant patients but localized or disseminated disease is uncommon. The diagnosis of infection with these organisms is based on respiratory symptoms, isolation of the organism, and radiographic changes that cannot be explained otherwise. Invasive or disseminated disease should be treated with amphotericin B. To prevent oropharyngeal candidiasis, nystatin 500,000 units in the form of a mouth-wash four times a day can be used.

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