metronidazole or vancomycin. Oral metronidazole (500 mg t.i.d. or 250 mg every 6 hours) and
oral vancomycin (125 mg every 6 hours) administered for 10 to 14 days have similar
therapeutic efficacy, with response rates near 90% to 97%. When oral administration is not
feasible, IV metronidazole should be used, since IV vancomycin is not effective. Nearly, all
patients respond to treatment in about five days. Comparison of metronidazole’s activity with
that of vancomycin in patients with moderately severe disease shows similar response rates.
The former is preferred because of its reduced risk of vancomycin-resistance induction and
lower cost. However, recent reports of severe clinical forms suggest that vancomycin may be
preferable for these especially virulent strains.
C. difficile strains resistant to metronidazole and with intermediate resistance to
vancomycin have been described. The administration of probiotics such asSaccharomyces
boulardiiorLactobacillusspp. for prophylaxis of CDAD remains controversial, and we do not
recommend it in critical patients since the occurrence of severe invasive disease byS. boulardii
has been described (185).
As mentioned, a substantial proportion of patients (10–25%) have a relapse usually
3–10 days after treatment has been discontinued, even with no further antibiotic therapy.
Relapse usually results from either a failure to eradicateC. difficilespores from the colon or due
to reinfection from the environment. Nearly all patients respond to another course of
antibiotics if given early. The frequency of relapses does not seem to be affected by the
antibiotic selected for treatment, the dose of these drugs, or the duration of treatment.
Multiple relapses may be difficult to manage. Several measures have been suggested:
gradual tapering of the dosage of vancomycin over one to two months, administration of
“pulse-dose” vancomycin, use of anion-exchange resins to absorb C. difficile toxin A,
administration of vancomycin plus rifampin or administration of immunoglobulins.
Infectious enteritis is especially frequent in intestinal transplant recipients (39%). Viral
agents are the cause in two-thirds of the cases. In a recent series, there were 14 viral enteritis
(one CMV, 8 rotavirus, 4 adenovirus, 1 EBV), 3 bacterial (C. difficile), and 3 protozoal infections
(1Giardia lamblia, 2 Cryptosporidium). The bacterial infections tended to present earlier than the
viral infections, and the most frequent presenting symptom was diarrhea (186).
Immunosuppressive drugs such as mycophenolate mofetil, cyclosporine A, tacrolimus,
and sirolimus are all known to be associated with diarrhea. The incidence of diarrhea ranged
from 13% to 38% for regimens containing CSA and MMF and 29% to 64% for regimens with
tacrolimus and MMF (187). Rarely, graft-versus-host disease (GVHD), lymphoproliferative
disorder, de novo inflammatory bowel disease (IBD), or colon cancer may present as diarrhea.
Flare-up of preexisting IBD is also not uncommon after liver transplantation.
CMV andC. difficileare the most common causes of proven infectious diarrhea in SOT
patients in the developed world (178,188–190). Accordingly, the first step of the management
of a patient with fever and diarrhea or abdominal pain should be directed to exclude these
pathogens. If clinical manifestations persist despite exclusion of these, a wider differential
diagnosis and more sophisticated diagnostic techniques should be considered since there are
reports of SOT recipients with infections caused by Norwalk virus (191), rotavirus (192),
adenovirus (193), EBV (194), Cryptosporidium parvum (195), Isospora belli (196,197), etc.
However, the cause of acute diarrhea remains unidentified in one of three patients (188).
Neurological Focality
The detection of CNS symptoms in an SOT recipient should immediately arise the suspicion of
an infection (198). Fever, headache, altered mental status, seizures, focal neurological deficit, or
a combination of them should prompt a neuroimaging study (135). Noninfectious causes
include immunosuppressive-associated leukoencephalopathy (199), toxic and metabolic
etiologies, stroke, and malignancies (200). Therapy with OKT3 monoclonal antibody has
been related to the production of acute aseptic meningitis (CSF pleocytosis with negative
cultures, fever, and transient cognitive dysfunction). Infectious progressive dementia has been
related to JC virus, herpes simplex, CMV, and EBV.
Most common cause of meningoencephalitis in organ transplant recipients are herpes
viruses, followed byL. monocytogenes, C. neoformans, andT. gondii.HHV-6 is a neurotropic
400 Mun ̃oz et al.