Fungal infections chemotherapy

Griseofulvin is adminisfered orally in the form of tablets. It is not totally absorbed when given orally, and one method of increasing absorption is to reduce the particle size of the drug. Griseofulvin is deposited in the deeper layers of the skin and in hair keratin, and is therefore employed in chemotherapy of fungal infections of these areas caused by susceptible organisms. 

Neutrophil Segs 40%-60% Bands 3%-5% Phagocytic Leukocytosis Bacterial infections Fungal infections Physiologic stress Tissue injury (e.g. myocardial Infarction) Medications (e.g. corticosteroids) Leukopenia Long-standing infection Cancer Medications (e.g., chemotherapy)... 

Autologous bone marrow transplant Neutropenia resulting from chemotherapy Allogeneic bone marrow transplant Peripheral blood progenitor cell mobilization Leukemias (leukopenias and fungal infection) March 1991 Sept. 1995 Nov. 1995 Dec. 1995 Nov. 1996... 

Infections Corticosteroids may mask signs of infection, and new infections may appear during their use. There may be decreased resistance and inability of the host defense mechanisms to prevent dissemination of the infection. Restrict use in active tuberculosis to cases of fulminating or disseminated disease in which the corticosteroid is used for disease management with appropriate chemotherapy. Corticosteroids may exacerbate systemic fungal infections and may activate latent amebiasis. 

In recent years, the incidence and severity of human fungal infections have increased dramatically. The use of powerful immunosuppressive agents for cancer chemotherapy and for organ transplant, combined with the AIDS epidemic, has led to this significant increase. However, in healthy individuals, a normally functioning immune system tends to ward off fungal infections. 

It is indicated in mucosal candidiasis, systemic candidiasis, crypttococcosis, prophylaxis of fungal infections following cytotoxic chemotherapy or radiotherapy maintenance to prevent relapse of cryptococcal meningitis in patients with AIDS sporotrichosis, histoplasmosis and vaginal candidiasis. 

Echinacea has been used investigationally to enhance hematologic recovery following chemotherapy. It has also been used as an adjunct in the treatment of urinary tract and vaginal fungal infections. These indications require further research before they can be accepted in clinical practice. E purpurea is ineffective in treating recurrent genital herpes. 

L.S. Young, Current needs in chemotherapy for bacterial and fungal infections, Rev. Infect. Dis., 7 (Suppl. 3) S380, 1985. 

A major cause of morbidity and mortality in patients who receive cytotoxic treatment or radiotherapy for cancer is bacterial and fungal infections. Intensive chemotherapy is associated with fever and infection, and the development of neutropenia further increases this risk of infection. Consequently, maximum doses of some cytotoxic drugs are limited due to bone marrow toxicity. Higher doses of chemotherapy and radiation therapy have become possible due to a reduction in bone marrow damage with the availability of the CSFs for clinical use. 

Chapter 11. Chemotherapy of infections Chapter 12. Antibacterial drugs Chapter 13. Chemotherapy of bacterial infections Chapter 14. Viral, fungal, protozoal and helminthic infections... 

Schaffner A, Schaffner M. Effect of prophylactic fluconazole on the frequency of fungal infections, amphotericin B use, and health care costs in patients undergoing intensive chemotherapy for hematologic neoplasias. J Infect Dis 1995 172(4) 1035-41. 

Studies in patients undergoing allogeneic bone marrow transplantation have revealed that oral fluconazole, 400mg d" , is effective in reducing the severity of invasive fungal infections and subsequent mortality. The evidence of fluconazole effectiveness is less clear in patients with bone marrow suppression secondary to chemotherapy. 

Leukocytosis is a normal host defense to infection and is an important adjunct to antimicrobial therapy. Unfortunately, bacterial infection is a common complication of neutropenia from cancer chemotherapy. These patients are incapable of increasing their WBCs in response to infection. In fact, susceptibility to infection in these patients is highly dependent on their WBC status. Patients with neutrophil counts of less than 500 cells/mm are at high risk for the development of bacterial or fungal infections. The absence of leukocytosis also occurs in the elderly and in severe cases of sepsis. ... 

Advances in medical technology, including organ and bone marrow transplantation, cytotoxic chemotherapy, the widespread use of indwelling intravenous (IV) catheters, and the increased use of potent broad-spectrum antimicrobial agents all have contributed to the dramatic increase in the incidence of fungal infections worldwide. 

Flucytosine is a powerful antifungal agent used in the treatment of serious systemic fungal infections, such as Cryptococcus neoformans and Candida spp (Table 40.2). Flucytosine itself is not cytotoxic but, rather, is a pro-drug that is taken up by fungi and metabolized to 5-fluorouracil (5-FU) by fungal cytidine deaminase (Fig. 40.11) (51). Then, 5-FU is converted to 5-fluorodeoxyuridine, which as a thymidylate synthase inhibitor interferes with both protein and RNA biosynthesis. 5-Fluorouracil is cytotoxic and is employed in cancer chemotherapy (see Chapter 42). Human cells do not contain cytosine deaminase and, therefore, do not convert flucytosine to 5-FU. Some intestinal flora, however, do convert the drug to 5-FU, so human toxicity does result from this metabolism. Resistance rapidly develops to flucytosine when used alone, so it is almost always used in conjunction with amphotericin B. Use of flucytosine has declined since the discovery of fluconazole. 

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