pleocytosis. CSF cryptococcal antigen is positive in most patients. In a recent series, 83
transplant recipients with cryptococcosis were analyzed. Patients with CNS infection (69% vs.
16%,p<0.001), disseminated infection (82.7% vs. 20%,p<0.001), and fungemia (29% vs. 8%,
p¼0.046) were more likely to receive regimens containing amphotericin B than fluconazole as
primary therapy. Survival at six months tended to be lower in patients whose CSF cultures at
two weeks were positive compared with those whose CSF cultures were negative (50% vs.
91%,p¼0.06) (113). No correlation was found between CSF or serum cryptococcal antigen titer
and evolution or CSF sterilization at two weeks (231).
Focal brain infection (seizures or focal neurological abnormalities) may be caused by
Listeria,T. gondii, fungi (Aspergillus, mucorales, phaeohyphomycetes, or dematiaceous fungi),
posttransplantation lymphoproliferative disease orNocardia. Brain abscesses are relatively
uncommon (0.6%) in SOT patients and most of them (78%) are caused byAspergillus(232),
followed byT. gondiiandN. asteroides. Fever is not common and was documented in only 45%
of the liver transplant recipients with brain abscesses. As discussed herein, the characteristics
that may help in the differential diagnosis are the time of appearance of the lesion and the
presence of concomitant extraneural disease (predominantly pulmonary), which is very
frequent in patients with fungal brain abscesses (70%). Such lesions usually provide an early
clue to the diagnosis. If extraneural involvement is not documented, a brain biopsy should be
performed to establish the etiological diagnosis. Empiric therapy of brain abscesses in SOT
recipients should include antifungal, and not antibacterial or antiviral therapy.
Aspergillusbrain abscesses usually occur in the early posttransplantation period. Most of
the patients present with simultaneous lung lesions that allow an easier diagnostic way.
Overall, disseminatedAspergillusdisease has been described in 9% to 36% of kidney recipients,
15% to 20% of lung recipients, 20% to 35% of heart recipients, and 50% to 60% of liver
recipients with IA (107,233,234). Disseminated infection with CNS involvement occurred in
17% of the cases studied in Spain. Clinical manifestations of CNS aspergillosis include
alteration of mental status, diffuse CNS depression, seizures, evolving cerebrovascular
accidents, and headache (107,235). The CSF fluid is almost always sterile.
Scedosporium, zygomycetes, and other uncommon fungi are being increasingly detected
as significant CNS pathogens in transplant recipients (110,236–238). Brain abscesses due to
dematiaceous fungi are described a median of three months posttransplantation, but may
occur as late as two years later (239). Infections due to the agents of zygomycosis seem to be
increasing in the transplant population and nearly 50% are of the rhinocerebral form (240–242).
Toxoplasmosis was more prevalent when prophylaxis with cotrimoxazole was not
provided (40,243). The incidence is higher in HT recipients. The disease usually occurred
within three months posttransplantation, with fever, neurological disturbances, and pneumo-
nia as the main clinical features. Chorioretinitis may also be found (244,245). Diagnosis was
established by serology and by direct examination, culture, or PCR of biological samples. In
HT recipients, the diagnosis may be provided by the endomyocardial biopsy (246). The lesions
ofT. gondiiare usually multiple, have preferential periventricular localization, and demon-
strate ring enhancement. The donor was the likely source of transmission to most recipients
(247). The mortality rate was high (around 60%). Obstructive urinary tract lithiasis involving
sulfadiazine crystals have been described (248). Disseminated toxoplasmosis should be
considered in the differential diagnosis of immunocompromised patients with culture-
negative sepsis syndrome, particularly if combined with neurological, respiratory, or
unexplained skin lesion (249).
Other parasitic infections such as Chagas disease, neurocysticercosis, schistosomiasis,
and strongyloidiasis are exceedingly less common (250).
Nocardiosis is usually observed between one and six months posttransplantation. The
clinical presentation of nocardiosis includes pneumonia, CNS focal lesions, and cutaneous
involvement (198,251–254). Brain abscesses due toNocardiaare multiple in up to 40% of the
cases and may demonstrate ring enhancement. Diagnosis may be reached by direct
observation of biological samples using modified Ziehl-Neelsen staining or Gram stain. The
mainstays of treatment are sulphonamides or cotrimoxazole, although some authorities
recommend induction therapy with a combination of drugs including carbapenem
derivatives.
402 Mun ̃oz et al.