After obtaining the previously mentioned samples, empiric antibiotics should be
promptly started in all transplant patients with suspicion of infection and toxic or unstable
situation. They are also recommended if a focus of infection is apparent, in the early
posttransplant setting in which nosocomial infection is very common, or when there has been a
recent increase of immunosuppression. In a stable patient without a clear source of infections,
further diagnostic testing should be carried out and noninfectious causes be considered.
We have recently demonstrated that only 58.5% of patients with BSI received appropriate
empirical antimicrobial therapy. Inadequate treatment was related to a longer hospital stay, a
higher mean risk of CDAD, a higher mean overall mortality rate, and a higher risk of infection-
related mortality (288). So once blood cultures are obtained, empirical broad-spectrum
antimicrobials guided by the clinical condition of the patient and the presumed origin should
be promptly started. When results of blood cultures are available, antibiotics should be
adjusted according to susceptibility patterns of the isolates. This antibacterial de-escalation
strategy attempts to balance the need to provide appropriate, initial antibacterial treatment
while limiting the emergence of antibacterial resistance.
The selection of the antimicrobial should be based on the likely origin of the infection,
prevalent bacterial flora, rate of antimicrobial resistance, and previous use of antimicrobials by
the patient. In our series of bacteremia in HT recipients, gram-negative microorganisms
predominated (55.3%), followed by gram-positive microorganisms (44.6%). Gram-negatives
accounted for 54% of infections in the first month, 50% during months 2 to 6, and 72% of
infections occurring afterward (p¼0.3) (34).
The possibility of drug interactions, mainly with cyclosporine and tacrolimus, is very real
and impacts significantly on the choice of antimicrobial. There are three categories of
antimicrobial interaction with cyclosporine and tacrolimus. First, the antimicrobial agent (e.g.,
rifampin, isoniazid, and nafcillin) upregulates the metabolism of the immunosuppressive drugs,
resulting in decreased blood levels and an increased possibility of allograft rejection. Second, the
antimicrobial agents (e.g., the macrolides erythromycin, clarithromycin, and to a lesser extent
azithromycin or the azoles ketoconazole, itraconazole, and to a lesser extent fluconazole)
downregulate the metabolism of the immunosuppressive drugs, resulting in increased blood
levels and an increased possibility of nephrotoxicity and overimmunosuppression. And finally,
there may be synergistic nephrotoxicity, when therapeutic levels of the immunosuppressive
agents are combined with therapeutic levels of aminoglycosides, amphotericin, and
vancomycin, and high therapeutic doses of cotrimoxazole and fluoroquinolones.
Outcome of Febrile Processes of SOT Recipients in the ICU
SOT patients have higher risk of dying after an ICU admission than the general population,
and in most series it is a poor prognostic factor (289,290). However, the overall prognosis is
better than that of bone marrow recipients (291–293). The overall ICU mortality of SOT patients
was 18% in a recent series and infection was the major cause of death (disseminated mycoses,
HCV, multiorganic failure, hepatic artery thrombosis with sepsis, and primary nonfunction of
the graft).
Mortality of febrile liver recipients at 14 days (24% vs. 0%,p¼0.001) and at 30 days (34%
vs. 5%,p¼0.001) was significantly higher in the ICU, as compared with non-ICU patients (9).
Mortality of OLT with lung infiltrates in the ICU was 28%. Pneumonia, creatinine level>1.5 mg/dL,
higher blood urea nitrogen, and worse APACHE (Acute Physiology and Chronic Health
Evaluation) neurological score were predictors of poor outcome (41). The need for mechanical
ventilation was an independently significant predictor of mortality (7). Infection was a risk
factor for early renal dysfunction (294). Need for preoperative ICU care was predictive of an
increased risk of death in OLT patients waiting for retransplantation (290).
Infection is also a leading cause of death in heart recipients (30% of early deaths, 45% of
deaths from 1 to 3 m, and 9.7% thereafter) (295). Overall, 31% of the patients with pneumonia
died (Aspergillus62%; CMV 13%; nosocomial bacteria 26%). Mortality was 100% in patients
requiring mechanical ventilation (7/13Aspergillus, 5/11P. jiroveci, 1/8 CMV) (64). Infectious
complications including pneumonia, bacteremia, and sepsis are significant predictors of
overall mortality in extended criteria HT recipients [pneumonia hazard ratio (HR) 4.2 (95%
CI 2.5–7.0), bacteremia HR 3.0 (95% CI 1.9–4.9), sepsis HR 6.0 (95% CI 3.6–10.2)] (296).
Infections in Organ Transplants in Critical Care 407