Community-Acquired Infections in Solid Organ Transplant Recipients

Tue H. Ngo

The risk of infection in solid organ transplant (SOT) recipients changes over time. More than 6 months after transplantation, the intensity of immunosuppression is decreased in recipients who have a good functioning allograft.¹ Their risk for most opportunistic infections declines in this late posttransplant period, and thus, other typical community-acquired infections predominate. SOT recipients may have manifestations from reactivated or chronic viral infections, such as varicella-zoster virus (VZV), hepatitis C virus (HCV), and hepatitis B virus (HBV).¹^,²^,³ A small group of patients who experience recurrent episodes of acute or chronic rejection, and thus require higher doses of immunosuppression, remain at high risk for opportunistic infections.³

Patients in the late posttransplant period usually reside in their home and are predisposed to community-acquired infections found in the general population, such as community-acquired bacterial pneumonia, urinary tract infection, and community respiratory viral infection. These infections may be more severe in the transplant population due to immunosuppression.¹^,²^,³ Organisms commonly identified in community-acquired bacterial pneumonia include Streptococcus pneumoniae, Haemophilus influenzae, and Legionella species. However, microorganisms may not be isolated from cultures in bacterial pneumonia.²^,⁴ The incidence of invasive pneumococcal disease is 12.8-fold greater among SOT recipients compared to the general population with 90% of infections associated with bacteremia.⁵

SOT recipients are at risk for illnesses due to community-acquired respiratory viruses such as rhinovirus, coronavirus, respiratory syncytial virus, influenza, parainfluenza, human metapneumovirus, and adenovirus. Common presenting symptoms include coryza, cough, sore throat, dyspnea, and fever.⁶^,⁷ A high rate of progression to lower respiratory tract infection has been reported, with 26% of patients with influenza and parainfluenza infection progressed to viral pneumonia in one study.⁷ Community respiratory viruses can also have an indirect effect on the graft as well, possibly leading to increased risk for graft rejection.⁶^,⁷^,⁸ Among 21 SOT recipients with influenza at the University of Pittsburgh who had a biopsy performed on their transplanted organs, 62% showed acute rejection in their lung or kidney grafts.⁸

Reactivation of latent infections can also occur during this period. Mycobacterium tuberculosis infection after transplantation is typically due to reactivation of a latent infection, although donor transmission, community acquisition, and nosocomial acquisition have been described. The incidence of tuberculosis (TB) varies from 0.35% to 15% among SOT recipients worldwide⁹ and occurs at a median of 6 to 9 months posttransplant, with the majority (63% to 95%) of cases diagnosed within the first year after transplantation.⁹^,¹⁰ TB most commonly involves the lungs (>70%)⁹^,¹⁰;
however, extrapulmonary TB (16%) and disseminated infection (33%) have been described. Radiographic pulmonary presentation is variable, ranging from focal infiltrate to a miliary pattern, nodules, pleural effusions, diffuse interstitial infiltrates, and cavitary disease.⁹ TB-attributable mortality remains high with a reported incidence of 9.5%.¹⁰ The recommended initial phase of treatment for active TB includes isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB) for the first 2 months. If the TB isolate is sensitive to INH, RIF, and PZA, then EMB can be discontinued. Then, treatment is tapered generally to INH and RIF in the continuation phase. Treatment regimen and duration should be guided by an expert in treating these patients.¹¹ Drug-drug interactions occur between RIF and the immunosuppressant medications with RIF significantly reducing the serum concentrations of cyclosporine, tacrolimus, sirolimus, and everolimus. Graft rejection has been reported with subtherapeutic immunosuppressant levels due to interactions with RIF, and thus, close monitoring of drug levels is warranted. Rifabutin, a weaker inducer of cytochrome P3A4, may have less drug interactions and result in more manageable immunosuppressant levels and thus, provides an alternative to RIF.¹¹ Hepatotoxicity due to INH is a concern in particular among liver transplant recipients, and hepatotoxicity can be increased in conjunction with RIF. Close monitoring of liver function tests is needed.⁹^,¹¹

Infections in the late posttransplant period usually occur as a result of reactivated or chronic viral infections.¹^,²^,³ VZV in SOT recipients typically manifests as herpes zoster (HZ), representing predominantly reactivation disease, but cases of primary community-acquired infection have been reported.¹² HZ is characterized by a painful, vesicular rash in a dermatomal distribution, which can involve one or two adjacent dermatomes, and can be associated with risk for cutaneous and visceral dissemination. Patients may experience pain and paresthesia a few days prior to the development of rash.¹² The overall incidence of HZ is 8.6% among SOT recipients, and the median time to development of disease is 9 months, with 63% of recipients experiencing HZ by 12 months after transplantation. Postherpetic neuralgia developed in 43% of patients in one study.¹³

Primary infection with JC virus (JCV), a polyomavirus, typically occurs at a young age with establishment of a latent infection. Reactivation of JCV can induce progressive multifocal leukoencephalopathy (PML), which is a demyelinating disease of the central nervous system. Neurologic deficit is the hallmark of PML, characterized by motor, sensory, visual deficit, ataxia, cognitive, or behavioral changes.¹⁴ Disease develops at a median of 17 months posttransplantation with 71% of cases diagnosed within 24 months after transplantation.¹⁵ MRI of the brain demonstrates T1 hypointense, T2 hyperintense lesions in the subcortical areas, cerebellum, and brain stem without enhancement or mass effect.¹⁶ Brain biopsy is needed for definitive diagnosis. If a tissue sample cannot be obtained, then the diagnosis can be suggested by the constellation of compatible clinical history, characteristic MRI findings, and JCV DNA in the cerebrospinal fluid.¹⁴ Treatment for PML in transplant recipients involves decreasing immunosuppression. There is no effective antiviral agent for treatment of PML.¹⁴^,¹⁵

Only gold members can continue reading. Log In or Register to continue