Infective endocarditisis a rare event in SOT population (1.7–6%), but it may be an
underappreciated sequela of hospital-acquired infection in transplant patients (56). The
spectrum of organisms causing infective endocarditis was clearly different in transplant
recipients than in the general population; 50% of the infections were due toAspergillus
fumigatusorS. aureus, but only 4% were due to viridans streptococci. Fungal infections
predominated early (accounting for 6 of 10 cases of endocarditis within 30 days of
transplantation), while bacterial infections caused most cases (80%) after this time. In 80%
(37) of the 46 cases in transplant recipients, there was no underlying valvular disease. Seventy-
four percent (34) of the 46 cases were associated with previous hospital-acquired infection,
notably venous access device and wound infections. Three patients withS. aureusendocarditis
had had an episode ofS. aureusbacteremia more than three weeks prior to the diagnosis of
endocarditis and had received treatment for the initial bacteremia of less than 14 days’
duration. The overall mortality rate was 57% (26 of 46 patients died), with 58% (15) of the
26 fatal cases not being suspected during life (56). CMV,Toxoplasma, and parvovirus B19 may
cause myocarditis in this population. Therapy of established infections is similar to that of
other immunosuppressed patients.
Fever of Unknown Origin
Undoubtedly, the most common alarm sign suggesting infection is fever. In transplant
recipients, fever has been defined as an oral temperature of 37.8 8 C on at least two occasions
during a 24-hour period (9). Antimetabolite immunosuppressive drugs, mycophenolate mofetil
and azathioprine, are associated with significantly lower maximum temperatures and
leukocyte counts (10). However, it is important to remember that fever and infections do not
always come together. The absence of fever does not exclude infection. In fact, 40% of the liver
recipients with documented infection (mainly fungal) were afebrile in a recent series (41). In
fact, absence of febrile response has been found to be a predictor of poor outcome in liver
transplant recipients with bacteremia (260). In that series, the independent factors predictive of
greater mortality were ICU stay at the time of bacteremia (100% vs. 47%;p¼0.005), absence
of chills (0% vs. 53%;p¼0.005), lower temperature at the onset of bacteremia (99.2 8 F vs. 101.5 8 F;
p¼0.009), lower maximum temperature during the course of bacteremia (99.3 8 F vs. 102 8 F,p¼
0.008), greater serum bilirubin level (7.6 vs. 1.5 mg/dL;p¼0.024), abnormal blood pressure
(80% vs. 16%;p¼0.001), and greater prothrombin time (15.6 vs. 13.3 seconds;p¼0.013).
A major difference with immunocompetent critical patients is that the list of potential
etiological agents is much longer and is influenced by time elapsed from transplantation. CMV
(as main offender or as copathogen) should be considered in practically all-infectious
complications in this population. Accordingly, a sample for CMV antigenemia (or PCR if
available) should always be obtained. Other viruses such as adenovirus, influenza A, or HHV-6
may also cause severe infections after SOT and can be recovered from respiratory samples or
blood. If indicated, invasive diagnostic procedures should be performed rapidly and a serum
sample stored.
Bacterial infections must always be considered and urine and blood cultures obtained
before starting therapy. Diagnosis of catheter-related infections without removing the devices
may be attempted in stable patients. Lysis centrifugation blood cultures as well and hub
and skin cultures have a high negative predictive value (264). The first steps for diagnosis
of pneumonia should include a chest X ray and culture of expectorated sputum or
bronchoaspirate (submitted for virus, bacteria, mycobacteria, and fungus). A CT scan or
ultrasonography may also be ordered to exclude the presence of collections in the proximity of
the surgical area. Lumbar puncture and cranial CT (including the paranasal sinus) must be
performed if neurological symptoms or signs are detected. In case of diarrhea,C. difficile
should be investigated. Cultures and PCR for detection ofM. tuberculosisshould be ordered for
all transplant recipients with suspicion of infection.
Fungal infections should be aggressively pursued in colonized patients and in patients
with risk factors. Early stages of fungal infection may be very difficult to detect (107,265).
Isolation of Candidaor Aspergillusfrom superficial sites may indicate infection. Fundus
examination, blood and respiratory cultures, and Aspergillus and Cryptococcus antigen
detection tests must be performed.
404 Mun ̃oz et al.