Infections Pneumocystis carinii

AIDS (acquired immunodeficiency syndrome) is the final stage of disease caused by infection with HIV. In this stage, the vims infection has severely affected the immune system, causing a depletion of CD4+ T-helper cells. AIDS is characterized by the manifestation of typical diseases caused by opportunistic infections (Pneumocystis carinii pneumonia, CMV retinitis, candidiasis of the esophagus, cerebral toxoplasmosis), neurological manifestations, cachexia, or certain tumors (Kaposi sarcoma of the skin, B-cell lymphoma). 

Purine analogues usually do not cause nausea and vomiting or hair loss, but they are associated with cumulative and prolonged myelosuppression and profound immunosuppression, which increases the risk of opportunistic infections such as fungal infections, Pneumocystis carinii pneumonia, and viral infections. 

Human immunodeficiency virus, AIDS Mycobacterial, cytomegaloviral, and Pneumocystis carinii (P. jiroveci) infection... 

AIDSTRIALS (AIDS Clinical Trials). The AIDSTRIALS database [80] provides information about AIDS-related studies of experimental treatments conducted under the FDA s investigational new drug (IND) regulations. AIDSTRIALS contains information about clinical trials of agents undergoing evaluation for use against AIDS, HIV infection, and AIDS-related opportunistic diseases such as Pneumocystis carinii pneumonia (PCP). Detailed information is supplied... 

It was found that the HIV envelope glycoprotein in vitro increases the production of NO by human monocyte-derived macrophages [114]. NO production is increased in patients who have AIDS [115], and the increased concentrations of nitrite in AIDS patients with opportunistic infections is caused by T gondii, Pneumocystis carinii, Mycobacterium tuberculosis, and Mycobacterium avium, whereas nitrite concentrations are normal in symptom-free patients. It was also confirmed that there was increased production of NO in the sera of children with HIV-1 infection, and of circulating cytokines, such as interleukin lp, tumor necrosis factor a, and interferon y. It is postulated that rises in the concentrations of these cytokines may represent a substantial stimulation of NO production [116]. In contrast, it has been shown that there was no altered endogenous nitrate formation in eight patients with AIDS, most of whom had opportunistic infections [117]. It has also been noted that there were high... 

IMMUNODEFICIENCY WITH HYPER-IGM (HIGMl), AN IMMUNOGLOBULIN ISOTYPE SWITCH DEFECT CHARACTERIZED BY ELEVATED CONCENTRATIONS OF SERUM IGM AND DECREASED AMOUNTS OF ALL OTHER ISOTYPES. AFFECTED MALES PRESENT AT AN EARLY AGE (USUALLY WITHIN THE FIRST YEAR OF LIFE) RECURRENT BACTERIAL AND OPPORTUNISTIC INFECTIONS, INCLUDING PNEUMOCYSTIS CARINII PNEUMONIA AND INTRACTABLE DIARRHEA DUE TO CRYPTOSPORIDIUM INFECTION. DESPITE SUBSTITUTION TREATMENT WITH INTRAVENOUS IMMUNOGLOBULIN, THE OVERALL PROGNOSIS IS RATHER POOR, WITH A DEATH RATE OF ABOUT 10% BEFORE ADOLESCENCE. 

Adenosine deaminase (ADA) deficiency, an autosomal recessive disorder, produces severe combined immunodeficiency (SCID). Lacking both B-cell and T-cell function, children are multiply infected with many organisms Pneumocystis carinii, Candida) and do not survive without treatment. Enzyme replacement therapy and bone marrow transplantation may be used. Experimental gene therapy trials have not yet yielded completely successfiil cures. 

A 12-week-old infant with a history of persistent diarrhea and candidiasis is seen for a respiratory tract infection with Pneumocystis carinii. A chest x-ray confirms pneumonia and reveals absence of a thymic shadow. Trace IgG is present in his serum, but IgA and IgM are absent. His red blood cells completely lack an essential enzyme in purine degradation. The product normally formed by this enzyme is... 

In combination with pyrimethamine or trimethoprim, sulfanilamides are active with respect to a few protozoal infections, including Toxoplasma, Plasmodium falciparum, and Pneumocystis carinii. 

Potentially fatal opportunistic infections Potentially fatal opportunistic infections, especially Pneumocystis carinii pneumonia, may occur with methotrexate therapy. Radiotherapy Methotrexate given concomitantly with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis. 

Dapsone, combined with other antUeprosy agents like rifampin and clofazimine, is used in the treatment of both multibacillary and paucibacillary M. leprae infections. Dapsone is also used in the treatment and prevention of Pneumocystis carinii pneumonia in AIDS patients who are allergic to or intolerant of trimethoprim-sulfamethoxazole. 

Pentamidine is active against Pneumocystis carinii, trypanosomes, and leishmaniasis unresponsive to pentavalent antimonials. It is an alternative agent for the treatment of P. carinii pneumonia. Although it is more toxic than trimethoprim-sulfamethoxazole, it has been widely used in patients with acquired immunodeficiency syndrome (AIDS), in whom P. carinii infection is common. 

Individuals with defects in cellular immunity are prone to fungal, protozoal, and viral infections, such as Candida albicans, cytomegalovirus, and Pneumocystis carinii, since cell-mediated immune responses are the primary defenses against these types of infection. Because of the role of cell-mediated immunity in tumor surveillance, these individuals will also demonstrate an increased incidence of malignancy if they survive long enough. 

Glucocorticoids are also used in the treatment of a number of HIV-related disorders, including Pneumocystis carinii pneumonia, demyelinating peripheral neuropathies, tuberculous meningitis, and nephropathy. Glucocorticoids are used as adjunctive therapy in Pneumo cystitis carinii pneumonia to decrease the inflammatory response and allow time for antimicrobial agents to exert their effects. In patients who are immunocompromised because of HIV infection, adjunctive steroids may be less beneficial in promoting survival. 

Used in all types of infection caused by Salmonella typhi, Klebsiella, Enterobacter, Pneumocystis carinii etc. and many other sulfonamide resistant stains of S. aureus, Strep, pyogenes, Shigella, E. coli, H. influenzae, meningococci and gonococci etc. It is particularly effective as a second line agent in penicillin allergic patients and also in patients where newer antibiotics are contraindicated or can t be used. 

It is used in the treatment of severe anaerobic infections caused by bacteroides and other anaerobes. It is also used in combination with aminoglycoside in the treatment of abdomen and GIT wounds, infections of female genital tract, pelvic abscesses, aspiration pneumonia and septic abortion. It is also used for prophylaxis of endocarditis. It is also used along with primaquine in Pneumocystis carinii pneumonia in AIDS patients and with pyrimethamine for toxoplasmosis. 

Infants with SCID have profound immunodehciency and present with frequent episodes of diarrhea, pneumonia, otitis, sepsis, and cutaneous infections. Persistent infections with opportunistic organisms such as Pneumocystis carinii, Epstein-Barr virus, Candida albicans, cytomegalovirus, parainhuenzae 3 virus, respiratory syncitial virus, adenovirus, varicella, and bacille Calmette-Guerin (BCG) lead to death within the hrst or second year of life. ADA dehciency also occurs in adults, but with a much later onset and nhlder, but clinically discernible, immunodehciency [3,5]. 

The main folate antagonist is methotrexate, an analogue of folic acid. Methotrexate competitively inhibits dihydrofolate reductase, the enzyme responsible for the synthesis of purine and pyramidine from folic acid. Trimetrexate, a methotrexate analogue, is useful in treating methotrexate-resistant tumours. It is also used to treat Pneumocystis carinii infections. Methotrexate is usually given orally, but may also be given intravenously or intrathecally. In addition to its use in cancer therapy, it is used in the treatment of psoriasis. Methotrexate can cause an obstructive nephropathy due to its precipitation in the renal calyx. 

Infection with herpes simplex virus, cytomegalovirus, Staphylococcus epidermidis, Pneumocystis carinii, Legionella, Cryptococcus, Serratia, and gram-negative bacteria... 

Indications IV Infusion Prophylaxis and treatment of Pneumocystis car/n/ pneumonia Shigellosis Severe or complicated urinary tract infections Tablets Prophylaxis and treatment of Pneumocystis carinii pneumonia Acute exacerbation of chronic bronchitis Urinary tract infections Travelers diarrhea in adults Shigellosis Acute otitis media ... 

Within the last few years, some new sulfa drugs have been introduced, including tnmethoprim-sulfamethoxazole. This drug has broadened the scope in treatment of urinary tract infections derived from species in addition to E. coli, namely, Klebsiella, Enterobacter, and Porteus species. This drug also is used for the treatment of acute otitis media in children, particularly those instances where strains uf H. influenzae and streptococcus pneumoniae may be suspected. The drug is also used to treat systemic infections that may arise from chloramphenicol- and ampicillin-rcsistant Salmonella as well as infections attributed to Pneumocystis carinii. 

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