Candida Albicans Microbe - Article Example

Candida Albicans Candida albicans is an oval budding yeast that produces pseudohyphae both in culture and and in tissues and in exu s and is a member of the normal flora of the mucous membranes in the respiratory, gastrointestinal, and femal genital tracts where it gains dominance and is associated with pathologic conditions. Sometimes it produces progressive systemic disease in debilitated or immunosuppressed patients, particularly if cell mediated immunity is impaired. Candida may produce blood strem invasion, thrombophlebitis, endocarditis, or infection of the eyes and virtually any organ or tissue when introduced intravenously. Morphology In smears of exudates, Candida appears as a gram positive, oval budding yeast, 2-3 x 4-6 micrometer, gram positive, elongated budding cells in chains, or true hyphae. On Sabouraud’s agar incubated at room temperature, soft, cream-colored colonies with a yeasty odor develop. The surface growth consists of oval budding cells. The submerged growth consists of pseudomycelium. This is composed of pseudohyphae that form blastoconidia at the nodes and sometimes chlamydoconidia terminally. Clinical Presentation Among the principal predisposing factors to Candida infection are the following: diabetes mellitus, general debility, immunodeficiency, indwelling urinary or intravenous catheters, intravenous opioid abuse, administration of antimicrobials, and corticosteroids. A. Mouth: Infection of the mouth (thrush) occurs-mainly in infants and in AIDS patients-on the Buccal mucous membranes and appears as white adherent patches consisting largely of pseudomycelium and desquamated epithelium, with only minimal erosion of the membrane. Growth of Candida in the mouth is enhanced by corticosteroids, antibiotics, high levels of glucose, and immunodeficiency. B. Female Genitalia: Vulvovaginitis resembles thrush but produces irritation, intense itching, and discharge. Loss of an acid pH in the vagina predisposes to candidal vulvovaginitis. Acid pH is normally maintained by the bacterial flora in the vagina. Diabetes, pregnancy, progesterone, and antibiotic therapy predispose to disease. C. Skin: Infection of the skin occurs principally in moist, warm parts of the body, such as the axilla, intergluteal folds, groin, or inframammary folds; it is most common in obese and diabetic individuals. The infected areas become red and weeping and may develop vesicles. D. Nails: Pinful, reddened swalling of the nail fold, resembling a pyogenic paronychia, may lead to thickening and transverse grooving of the nails and eventually loss of the nail. E. Lungs and other organs: Candida infection may be a secondary invader of lungs, kidneys and other organs where a preexisting disease is present (eg, tuberculosis or cancer) E. Lungs and other organs: Candida infections may be a secondary invader of lungs, kidneys, and other organs where a preexisting disease is present (eg, tuberculosis or cancer). In uncontrolled leukemia and in immunocompromised surgical patients, candidal lesions may occur in many organs. Candida endocarditis occurs particularly in narcotics addicts or on prosthetic valves. Candiduria sometimes develops after urinary catheterization, but it tends to subside spontaneously. F. Chronic Mucocutaneous Candidiasis: This disorder is a sign of cellular immunity in children. Diagnostic Laboratory Tests (Definitive diagnosis) A. Specimens: Specimens consists of swabs and scrapings from surface lesions, sputum, exudates, and materials from removed intravenous catheters. B. Microscopic Examination: Sputum, exudates, thrombi, etc, may be examined in Gram-stained smears for psedohyphae and budding cells. Scrapings are first placed in a drop of 10% potassium hydroxide. C. Culture: All specimens are cultured on Sabouraud’s agar at room temperature and at 37 ° C; typical colonies are examined for cells and budding pseudomycelia. Chlamydoconidia production by C albicans on cornmeal-polysorbate 80 agar is an important differential test (Brooks, 1989). Amphotericin B Amphotericin A and B are antifungal antibiotics produced by Streptomyces nodosus. Amphotericin A is not in clinical use. Mechanism of action Amphotericin B is selective in its fungicidal effect because it exploits the difference in lipid composition of fungal and mammalian cell membranes. Ergosterol, a cell membrane sterol, is found in the cell membrane of fungi, whereas the predominant sterol of bacteria and human cells is cholesterol. Amphotericin B binds to ergosterol and alters the permeability of the cell by forming Amphotericin B-associated pores in the cell membrane. Amphotericin B combines avidly with lipids (ergosterol) along the double bond-rich side of its structure and associates with water molecules along the hydroxyl-rich side. This amphipathic characteristic facilitates pore formation by multiple Amphotericin molecules, with the lipophillic portions around the outside of the pore and the hydrophilic regions lining the inside. The pore allows the leakage of intracellular ions and macromolecules, eventually leading to cell death. Some binding to human membrane sterols does occur, probably accounting for the drug’s prominent toxicity (Katzung, 2003). Indications: Mycotic infections; treatment of cutaneous and mucocutaneous mycotic infections caused by Candida (Monilia) species. Contraindications: Hypersensitivity to any of the product component (Kastrup, 2003). Pharmacokinetics: Amphotericin B is poorly absorbed from the gastrointestinal tract. Oral Amphotericin B is thus effective only on fungi within the luman of the tract and cannot be used for the treatment of systemic disease. The intravenous injection of 0.6 mg/ kg/d of Amphotericin B results in average blood levels of 0.3-1 mcg/ml and is more than 90% bound by serum proteins. While it is mostly metabolized, some Amphotericin B is excreted slowly in the urine over a period of several days. Hepatic impairment, renal impairment and dialysis have little impact on drug concentrations and therefore no dosage adjustment is required. The drug is widely distributed in tissues, but only 2-3% of the blood level is reached in cerebrospinal fluid, thus occasionally necessitating intrathecal therapy for certain types of fungal meningitis. Adverse effects The toxicity of Amphotericin B can be divided into two broad categories: immediate reactions, related to the infusion of the drug, and those occurring more slowly. A. Infusion-Related Toxicity: These reactions are nearly universal and consist of fever, chills, muscle spasms, vomiting, headache, and hypotension. B. Slower Toxicity: Renal damage is the most significant toxic reaction. Renal impairment occurs in nearly all patients treated with clinically significant doses of Amphotericin. The degree of azotemia is variable and often stabilizes during therapy, but can be serious enough to necessitate dialysis. A reversible component is associated with decreased renal perfusion and represents a form of prerenal renal failure. An irreversible component results from renal tubular injury and subsequent dysfunction. The irreversible form of Amphotericin nephrotoxicity usually occurs in the setting of prolonged administration (> 4 g cumulative dose). Renal toxicity commonly presents with renal tubular acidosis and severe potassium and magnesium wasting. Abnormalities of liver function tests are occasionally seen, as is a varying degree of anemia due to reduced erythropoietin production by damaged renal tubular cells. After intrathecal therapy with Amphotericin, seizures and a chemical arachnoiditis may develop, often with serious neurologic sequele (Katzung 2003). Alexander and Wingard (2005) investigated the renal safety of 3514 patients with fungal infections treated with amphotericin B lipid complex (ABLC). They reported that in ABLC-treated patients, concomitant treatment with potentially nephrotoxic agents and a baseline S-Cr level of 65 years of age and those < or = 65 years of age was similar. Despite higher median pretreatment serum creatinine (S-Cr) among patients >65 years of age (1.7 mg/dl vs. 1.4 mg/dl, respectively), both groups showed only a 0.1 mg/dl median S-Cr change from baseline by the end of therapy (P = 0.525). Clinical response was 56 and 51%, respectively, in patients >65 years of age and patients 65 years of age or younger (P = 0.04). Ponikau et al (2005) tested the hypothesis that intranasal antifungal treatment improved the objective computed tomography (CT) findings (inflammatory mucosal thickening), nasal endoscopy stages, and symptoms of CRS. Twenty-four patients after completing 6 months of treatment with amphotericin B achieved a relative reduction in the percentage of mucosal thickening on CT scans (n = 10; -8.8%) compared with placebo (n = 14; +2.5%; P = .030). They concluded that intranasal amphotericin B reduced inflammatory mucosal thickening on both CT scan and nasal endoscopy and decreased the levels of intranasal markers for eosinophilic inflammation in patients with CRS. In an earlier study, Hooshmand-Rad et al, (2004) compared the renal effects of high-dosage/long-duration (HDos/LDur) ABLC therapy (>5 mg/kg.d for >12 days) with those of low-dosage/short-duration (LDos/SDur) ABLC therapy (< or = 5 mg/kg.d for < or = 12 days). A total of 1726 patients were studied. Data suggested that higher ABLC dosages appear to be as well tolerated as lower dosages, warranting further study of ABLC dosages >5 mg/kg.d for >12 days in the treatment of systemic fungal infections. The incidence of invasive fungal infections in patients receiving aerosolized amphotericin B formulations as sole prophylaxis was determined by Drew et al., (2004). In their study, both aerosol AmBd and ABLC appeared to be associated with a low rate of invasive pulmonary fungal infection in the early post transplant period. Patients receiving ABLC were less likely to experience a treatment-related adverse event. Netea et al., (1999) investigated the effect of reconstituted high-density lipoproteins (rHDL) infusion into volunteers on the growth of Candida albicans. Infusion of reconstituted high-density lipoproteins (rHDL) is being studied in clinical trials as an adjunctive therapy for gram-negative sepsis. C. albicans growth was 10- to 100-fold higher in the plasma of volunteers infused with 80 or 100 mg/kg rHDL than in plasma collected before infusion; administration of 60 mg/kg rHDL had marginal effects. In vitro, the isolated lipoprotein subfractions had a growth-promoting effect on C. albicans. These data suggested the potential adverse effects of rHDL if infused into patients with systemic candidiasis. Thus, rHDL infusion into patients with sepsis caused by an unknown microorganism may be contraindicated. REFERENCES Alexander, B. D. & Wingard, J. R. (2005). Study of renal safety in Amphotericin B in lipid complex-treated patients. Clin. Infect. Dis, vol 40, iss S6, p S414-S421. Kastrup, E.K., Teri, H.B., Renee, E.W., Kirsten, K.N., Lindsay, D.H., Sara, L.S., Sharon, M.M & Susan, H.S (2003), Drug Facts and Comparisons, Missouri, A Walters Kluwer Company, 1822. Hooshmand-Rad, R, Chu, A, Gotz, V, Morris, J,et al. (2005). Use of Amphotericin B lipid complex in elderly patients. J INFECT, vol 50, iss 4, 277-287 Ponikau, J. U, Sherris, D. A, Weaver, A & Kita, H (2005).Treatment of chronic rhinositis with intanasal amphotericin B: A randomized, placebo-controlled, double blind pilot trial. J Allergy Clin Immunol, vol 115, iss 1, 125-131. Hooshmand-Rad, R, Reed, M. D, Chu, A, Gotz, V; et al(2004). Retrospective study of the renal effects of amphotericin b lipid complex when used at higher-than-recommended dosages & longer durations compared with lower dosages and shorter durations in patients with systemic fungal infections. Clin Ther, vol 26, iss 10, 1652-1662. Drew, R. H., Elizabeth, D.A., Daniel, K, B., R. Duane. D., Scott, M.P & John, R.P (2004).Comparative safety of Amphotericin B lipid complex and Amphotericin B deoxycholate as aerosolized antifungal prophylaxis in lung-transplant recipients. Transplantation, vol 77, iss 2, 232-237. : Netea, M. G, Curfs, J. H. A, Demacker, P. N. M, Meis, J. F. G et al (1999). Infusion of lipoproteins into volunteers enhances the growth of Candida albicans. Clin Infect Dis, vol 28, iss 5, 1148-1151. Katzung, B.G. (2003). Basic and Clinical Pharmacology. 8th edn, New York, McGraw-Hill Medical Publishing Division, 814-816. Brooks, G.F., Janet, S.B & L. Nicholas, O. (1989). Jawetz, Melnicks & Adelberg’s Medical Microbiology. 12th edn, Norwalk ,Appleton & Lange, 545-547. TET-TOX A c t i v e   I n g r e d i e n t   An adsorbed tetanus vaccine. I n d i c a t i o n s   Active immunisation. M a n u f a c t u r e r   CSL, Austral. CSL Ltd 45 Poplar Road Parkville VIC 3052 Australia (Thompson Micromedex 2007). Gentamicin/gentamycin? As per the sources (Craig, 1997 and Mycek 2000), the correct spelling of gentamicin is ‘GENTAMICIN’. References Sweetman, S.C ( ) Martindale: The Complete Drug Reference, 33rd edn, London,Pharmaceutical Press, 2125. Craig, C.R & Robert, E.S. (1997), Modern Pharmacology with clinical applications,New York, Little Brown and Company, 575. Mycec, M.J., Richard, A.H & Pamela, C.C. (2000), Lippincott’s illustrated reviews: Pharmacology, 2nd edn, New York, Lippincott Williams & Wilkins, 315. Micromedex ® Healthcare Series, Vol.132. Thompson Micromedex, 1974-2007. Read More