Up to a third of febrile neutropenic patients unresponsive to empirical antibiotics have systemic infections with either Candida or Aspergillus. Serious fungal infections also occur in patients undergoing bone marrow transplantation and organ transplantation, and in those who have received high-dose corticosteroid therapy. The mortalities from these infections are in excess of 35 per cent and 80 per cent respectively. This provides the rationale for administering empirical systemic antifungal drugs in patients with a persistent culture-negative fever 72 to 96 h after the commencement of empirical antimicrobial therapy or in the presence of pulmonary infiltrates.
The newer imidazoles, such as fluconazole and itraconazole, have been extremely useful in the treatment of Candida, Cryptococcus, and Coccidiomycosis but have little activity against Aspergillus. Amphotericin B still remains the gold standard for the treatment of most fungal infections in immunocompromised hosts. The problems with amphotericin B are that it must be given intravenously, preferably through central venous access, and it is associated with severe side-effects which include fever, rigor, hypotension, and renal toxicity. Concomitant use of antibiotics such as gentamicin and vancomycin may exacerbate renal toxicity in patients receiving amphotericin. Lipid-based amphotericin compounds have been developed in an effort to reduce toxicity and improve efficacy.
Viral infections such as herpes simplex, varicella zoster, cytomegalovirus, and adenoviruses frequently occur in neutropenic patients, particularly those with impaired cell-mediated immunity. These infections can be primary, for example when a renal transplant patient who is seronegative for cytomegalovirus is grafted with a kidney from a seropositive donor. More often they result from reactivation of latent virus, as when a patient with Hodgkin's disease develops varicella zoster following irradiation or chemotherapy.
Herpes simplex virus infection usually presents as a mucocutaneous infection which is easy to diagnose except in patients with mucocutaneous bleeding. Acyclovir (aciclovir) is the treatment of choice and is relatively free from toxicity as it can only be converted into its active form by herpes viruses and not by the host cells. It is excreted by the kidneys and the dose should be reduced according to creatinine clearance. Because of poor bioavailability of orally administered acyclovir, the intravenous route is recommended for neutropenic patients with severe infection.
Varicella infection is not uncommon in children with malignancy (e.g. acute lymphocytic leukemia) who are receiving chemotherapy. As a preventive measure, immunocompromised children with no immunity against varicella should receive varicella zoster immune globulin (VZIG) as soon as possible if exposed to either chickenpox or varicella zoster. Those with active infection should be treated with intravenous acyclovir. Foscarnet is usually effective in patients with acyclovir resistance.
Cytomegalovirus is an important opportunistic pathogen following organ transplantation. It is associated with a variety of clinical syndromes including pneumonitis, colitis, hepatitis, mononucleosis, retinitis, and encephalitis. In bone marrow transplant patients, the risk of cytomegalovirus pneumonitis is further increased in patients with graft versus host disease. Mortality from cytomegalovirus infections is high, particularly in patients with pneumonitis. Two agents, ganciclovir and foscarnet, are currently available for the treatment of cytomegalovirus. Major side-effects of these drugs include bone marrow and renal toxicity.
In the neutropenic host, infection with Mycobacterium tuberculosis usually results from reactivation of latent infection and is more common in conditions such as myelodysplasia, chronic lymphocytic leukemia, and hairy cell leukemia. These patients are prone to atypical presentations, rapid progression, and extrapulmonary and disseminated mycobacteriosis. Infections with non-tuberculous mycobacteria (e.g. Mycobacterium avium complex and Mycobacterium kansasii) are more common in patients with HIV infection. Treatment of tuberculosis should be with multiple drugs (three or four drugs), and should be individualized on the basis of sensitivity testing, degree of immunodeficiency, and adverse effects. The non-tuberculous mycobacteria have heterogeneous in vitro antibiotic susceptibility patterns, and treatment regimens must be designed on a species-specific basis.
P. carinii is a ubiquitous extracellular organism that causes asymptomatic latent infection in normal hosts but rarely causes disease. However, 85 per cent of patients with AIDS develop P. carinii pneumonia, which may also be seen in bone marrow and solid organ transplant patients as well as in patients with leukemia, lymphoma, and primary immune deficiency. Drugs such as fludarabine are increasingly being used in the treatment of low-grade lymphomas. By their action on adenosine deaminase they cause a reduction in CD4 T-lymphocyte count and therefore predispose patients treated with these agents to infection with P. carinii.
The standard treatment of P. carinii pneumonia is with trimethoprim plus sulfamethoxazole (co-trimoxazole) or parenteral pentamidine. Other drugs that have been used include dapsone, atovaquone, clindamycin, and primaquine. Other life-threatening parasitic infections such as malaria and babesiosis, and infections with Strongyloides species, can also occur in the neutropenic patient. These infections can sometimes emerge decades after a forgotten exposure in an endemic area.
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The term vaginitis is one that is applied to any inflammation or infection of the vagina, and there are many different conditions that are categorized together under this ‘broad’ heading, including bacterial vaginosis, trichomoniasis and non-infectious vaginitis.