85 INFECTIONS IN THE IMMUNOCOMPROMISED HOST
Harrison’s Manual of Medicine
INFECTIONS IN THE IMMUNOCOMPROMISED HOST
The immunocompromised pt is at increased risk for infection with both common and opportunistic pathogens and may have a blunted clinical response that challenges diagnosis. Acquired disease, loss of physical barriers, or an inborn immune defect may lower a person’s immunity. Table 85-1 summarizes infections associated with acquired or inborn defects in immune response.
Table 85-1 Infections Associated with Selected Defects in Immunity
In addition, infections are a common cause of death and an even more common cause of morbidity in pts with a wide variety of neoplasms (Table 85-2). Pts undergoing intensive chemotherapy for any form of cancer will have defects due not only to granulocytopenia but also to lymphocyte dysfunction. Neutropenic febrile pts should receive empirical antibiotic treatment to prevent death. Several general guidelines are useful in the initial treatment of neutropenic pts (Fig. 85-1). Prophylaxis for Pneumocystis carinii is mandatory for pts with acute lymphocytic leukemia and for all cancer pts receiving glucocorticoid-containing chemotherapy regimens.
Table 85-2 Infections and Cancer
FIGURE 85-1. Diagnosis and treatment of febrile neutropenic pts: an algorithm. Several general guidelines are useful in the initial treatment of these pts: (1) It is necessary to use antibiotics active against both gram-negative and gram-positive bacteria in the initial regimen. (2) An aminoglycoside or an antibiotic without good activity against gram-positive organisms (e.g., ciprofloxacin) alone is not adequate in this setting. (3) The agents used should reflect both the epidemiology and the antibiotic resistance pattern of the hospital. For example, in hospitals where there is gentamicin resistance, amikacin-containing regimens should be considered; in hospitals with frequent P. aeruginosa infections, a regimen with the highest level of activity against this pathogen (such as tobramycin plus a semisynthetic penicillin) would be reasonable for initial therapy. (4) A single third-generation cephalosporin constitutes an appropriate initial regimen in many hospitals (if the pattern of resistance justifies its use). (5) Most standard regimens are designed for pts who have not previously received prophylactic antibiotics. The development of fever in a pt receiving antibiotics affects the choice of subsequent therapy (which should target resistant organisms and organisms known to cause infections in pts being treated with the antibiotics already administered). (6) Randomized trials have indicated that it is safe to use oral antibiotic regimens to treat “low-risk” pts with fever and neutropenia. Outpatients who are expected to remain neutropenic for <10 days and who have no concurrent medical problems (such as hypotension, pulmonary compromise, or abdominal pain) can be classified as low risk and treated with a broad-spectrum oral regimen. On the basis of large studies, it can be concluded that this therapy is safe and effective, at least when delivered in the inpatient setting. Outpatient treatment has been assessed in small studies, but data from large randomized trials demonstrating the safety of outpatient treatment of fever and neutropenia are not yet available. (Adapted from R Finberg: HPIM-15, p. 552.)
Infections in pts during the first month after bone marrow transplantation (BMT) are similar to those in leukemia pts who are granulocytopenic as a result of chemotherapy. Prophylactic trimethoprim-sulfamethoxazole or ciprofloxacin decreases the incidence of gram-negative bacteremia in these pts. Cytomegalovirus (CMV) disease is the major concern in the second through fourth months after BMT. In addition, most pts should receive prophylaxis for P. carinii starting 1 month after engraftment and continuing for at least 1 year.
The organisms that cause infections in recipients of solid organ transplants are different from those that infect bone marrow transplant recipients because solid organ recipients do not go through a period of neutropenia. However, they are immunosuppressed for longer periods than bone marrow recipients (often permanently), and they are susceptible to infections with the same organisms as pts with chronically impaired T cell immunity. During the first month after transplantation, infections of wound or anastamotic sites prevail. CMV is most often a problem in the first 6 months as a consequence of the administration of agents that suppress cell-mediated immunity and of the acquisition or reactivation of viruses. Beyond 6 months after transplantation, infections characteristic of pts with defects in cell-mediated immunity may be a problem (Table 85-2).
For a more detailed discussion, see Finberg R: Infections in Patients with Cancer, Chap. 85, p. 547; and Finberg R, Fingeroth J: Infections in Transplant Recipients, Chap. 136, p. 860, in HPIM-15.