Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Azithromycin and clarithromycin are structural analogues of erythromycin that have similar mechanisms of action. The newer macrolides have several distinct advantages over erythromycin, including improved oral bioavailability; longer half-life, allowing once or twice daily administration; higher tissue concentrations; and fewer gastrointestinal adverse effects. Clarithromycin and azithromycin also have enhanced antimicrobial activity. The clinical efficacy of the newer macrolides has been similar to erythromycin for the treatment of upper and lower respiratory tract and skin and soft tissue infections. New therapeutic roles include the use of azithromycin for C. trachomatis infections and the inclusion of clarithromycin or azithromycin as part of therapeutic regimens for disseminated MAC infections in HIV-infected patients. Further clinical trials are needed to determine the optimal roles for and uses of these new macrolides.
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PMID:The newer macrolides. Azithromycin and clarithromycin. 749 Apr 41

In June 1993, the United States Public Health Service (USPHS) made recommendations for treatment of disseminated Mycobacterium avium complex (MAC) in patients infected with the human immunodeficiency syndrome (HIV). It was suggested that every treatment regimen include either azithromycin or clarithromycin plus one or more of the following drugs: ethambutol, clofazimine, rifabutin, rifampin, ciprofloxacin, or amikacin. This study compares the effect of multiple drug therapy regimens on the survival of patients of the HIV outpatient department of the Medical Center of New Orleans, Louisiana. A retrospective chart review of 122 confirmed cases of MAC was conducted. Three treatment groups were considered: no/monotreatment (n = 40), multitreatment without clarithromycin (n = 32), and multitreatment with clarithromycin (n = 50). Azithromycin, amikacin, and rifabutin were not used in this clinic during the study period. Both multitreatment without clarithromycin (p < 0.03) and multitreatment with clarithromycin (p < 0.005) were significantly protective for survival after adjusting for CD4 cell count at time of diagnosis, nonadherence to treatment, number of concomitant opportunistic infections at diagnosis, and weight loss > 10%. Neither of the groups that received multidrug therapy were significantly less likely to have MAC-related symptoms than the no/mono group at 3 and 6 months postdiagnosis. These findings support the USPHS recommendation for multiple drug treatment either with or without clarithromycin. Prospective controlled clinical trials will clarify the optimal regimen for disseminated MAC disease.
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PMID:Comparison of multiple drug therapy regimens for HIV-related disseminated Mycobacterium avium complex disease. 774 89

Mycobacterium avium infection is a frequent complication during the late stage of AIDS. M. avium is resistant or poorly susceptible to classical antituberculosis drugs. Some new macrolide antibiotics such as clarithromycin or azithromycin are bactericidal against M. avium, and their use has dramatically improved the prognosis of this infection. In vitro, azithromycin has MICs against M. avium ranging from 4 to 64 MIC50 being 16 mg/l and a MIC90 being 32 mg/l. Despite low concentrations in serum, close to 0.4 mg/l, very high intracellular concentrations of azithromycin, above the MIC, may be achieved. Azithromycin is active in vitro in the model of macrophage infection. Furthermore, azithromycin is active against murine experimental infection with M. avium. Clinical studies conducted among patients with AIDS have shown that azithromycin was active against disseminated M. avium infection, with a dose of 600 mg/d. Ongoing studies are designed to better determine the ideal dose, to compare its activity with that of clarithromycin and to determine the antibiotics that could be combined to prevent the selection of resistant mutants. Other ongoing studies are evaluating the efficacy of azithromycin for the chemoprophylaxis of M. avium infection in HIV infected patients with a CD4T lymphocyte concentration lower than 100/mm3.
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PMID:[Azithromycin and Mycobacterium avium infection]. 853 84

Azithromycin is an azalide antibiotic with important properties which allow it to be used as a single-dose treatment for genital Chlamydia trachomatic infections. A single 1 g dose is as effective as a standard seven-day course of doxycycline. Ofloxacin 400 mg bid for seven days is also effective against Chlamydia trachomatis. Both azithromycin 2 g and ofloxacin are also effective against uncomplicated gonorrhoea. Neisseria gonorrhoeae continues to be sensitive to third generation cephalosporins, e.g. ceftriaxone 125 mg. Oral single dose cephalosporins offer ease of administration and safety, e.g. cefixime (400 mg), cefuroxime axetil (1 g) and cefpodoxime proxetil (200 mg). The fluoroquinolones, e.g. ciprofloxacin (500 mg) and ofloxacin (400 mg), are being increasingly used as first-line medications, however, caution is recommended as the development of resistance is anticipated and already being detected in many areas. Syphilis continues to be sensitive to penicillin. This should be administered parenterally. Coexistent human immunodeficiency virus infection may make standard therapy inadequate, and closer follow-up is recommended. Therapy with non-penicillin antibiotics is still inadequately studied. Chancroid is treated with ceftriaxone, ciprofloxacin, azithromycin, or erythromycin. In some areas, resistance to tetracyclines and TMP-SMX has made these drugs ineffective as first-line treatments. Bacterial vaginosis is effectively treated with a single dose of metronidazole 1 g or 500 mg bid over seven days. Similar regimens are also effective against trichomoniasis. Vulvovaginal candidiasis can be treated with topical imidazole preparations or oral antifungal medications.
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PMID:Antimicrobial therapy of non-viral sexually transmitted diseases--an update. 884 92

Testing for and treating sexually transmitted diseases (STDs) in pregnant women deserves special attention. Treatment possibilities are limited because of potential risks for the developing fetus, and because effects can differ in pregnant compared with non-pregnant women, re-infection may be missed because of the intrinsic delicacy of contact-tracing during pregnancy and because pregnant women are more reluctant to take the prescribed medication in its full dose, if at all. However, the devastating effects of some of these genital infections far outweigh any potential adverse effects of treatment. Although active syphilis has become a rarity in most Western countries, it is still prevalent in South America, Africa and South-East Asia. Benzathine benzylpenicillin (2.4 million units once or, safer, twice 7 days apart) is the treatment of choice, although patients with syphilis of longer standing require 3 weekly injections as well as extensive investigation into whether there has been any damage due to tertiary syphilis. Despite declining rates of gonorrhea, the relative rate of penicillinase-producing strains is increasing, especially in South-East Asia. The recommended treatment is intramuscular ceftriaxone (125 or 250 mg) or oral cefixime 400 mg. Despite good safety records after accidental use, fluoroquinolones are contraindicated during pregnancy. An alternative to a fluoroquinolone in pregnant women with combined gonorrhea and chlamydial infection is oral azithromycin 1 or 2 g. Azithromycin as a single 1 g dose is also preferable to a 7 day course of erythromycin 500 mg 4 times a day for patients with chlamydial infection. Eradication of Haemophilus ducreyi in patients with chancroid can also be achieved with these regimens or intramuscular ceftriaxone 250 mg. Trichomonas vaginalis, which is often seen as a co-infection, has been linked to an increased risk of preterm birth. Patients infected with this parasite should therefore received metronidazole 500 mg twice daily for 7 days as earlier fears of teratogenesis in humans have not been confirmed by recent data. Bacterial vaginosis is also associated with preterm delivery in certain risk groups, such as women with a history of preterm birth or of low maternal weight. Such an association is yet to be convincingly proven in other women. The current advice is to treat only women diagnosed with bacterial vaginosis who also present other risk factors for preterm delivery. The treatment of choice is oral metronidazole 1 g/day for 5 days. The possible reduction of preterm birth by vaginally applied metronidazole or clindamycin is still under investigation. In general, both test of cure and re-testing after several weeks are advisable in most pregnant patients with STDs, because partner notification and treatment are likely to be less efficient than outside pregnancy and the impact of inadequately treated or recurrent disease is greater because of the added risk to the fetus. Every diagnosis of an STD warrants a full screen for concomitant genital disease. Most ulcerative genital infections, as well as abnormal vaginal flora and bacterial vaginosis, increase the sexual transmission efficiency of HIV, necessitating even more stringent screening for and treating of STD during pregnancy.
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PMID:Treatment of sexually transmitted bacterial diseases in pregnant women. 1077 30

Cisapride, a prokinetic agent, has been used for the treatment of a number of gastrointestinal disorders, particularly gastro-oesophageal reflux disease in adults and children. Since 1993, 341 cases of ventricular arrhythmias, including 80 deaths, have been reported to the US Food and Drug Administration. Marketing of the drug has now been discontinued in the US; however, it is still available under a limited-access protocol. Knowledge of the risk factors for cisapride-associated arrhythmias will be essential for its continued use in those patients who meet the eligibility criteria. This review summarises the published literature on the pharmacokinetic and pharmacodynamic interactions of cisapride with concomitantly administered drugs, providing clinicians with practical recommendations for avoiding these potentially fatal events. Pharmacokinetic interactions with cisapride involve inhibition of cytochrome P450 (CYP) 3A4, the primary mode of elimination of cisapride, thereby increasing plasma concentrations of the drug. The macrolide antibacterials clarithromycin, erythromycin and troleandomycin are inhibitors of CYP3A4 and should not be used in conjunction with cisapride. Azithromycin is an alternative. Similarly, azole antifungal agents such as fluconazole, itraconazole and ketoconazole are CYP3A4 inhibitors and their concomitant use with cisapride should be avoided. Of the antidepressants nefazodone and fluvoxamine should be avoided with cisapride. Data with fluoxetine is controversial, we favour the avoidance of its use. Citalopram, paroxetine and sertraline are alternatives. The HIV protease inhibitors amprenavir, indinavir, nelfinavir, ritonavir and saquinavir inhibit CYP3A4. Clinical experience with cisapride is lacking but avoidance with all protease inhibitors is recommended, although saquinavir is thought to have clinically insignificant effects on CYP3A4. Delavirdine is also a CYP3A4 inhibitor and should be avoided with cisapride. We also recommend avoiding coadministration of cisapride with amiodarone, cimetidine (alternatives are famotidine, nizatidine, ranitidine or one of the proton pump inhibitors), diltiazem and verapamil (the dihydropyridine calcium antagonists are alternatives), grapefruit juice, isoniazid, metronidazole, quinine, quinupristin/dalfopristin and zileuton (montelukast is an alternative). Pharmacodynamic interactions with cisapride involve drugs that have the potential to have additive effects on the QT interval. We do not recommend use of cisapride with class Ia and III antiarrhythmic drugs or with adenosine, bepridil, cyclobenzaprine, droperidol, haloperidol, nifedipine (immediate release), phenothiazine antipsychotics, tricyclic and tetracyclic antidepressants or vasopressin. Vigilance is advised if anthracyclines, cotrimoxazole (trimethoprim-sulfamethoxazole), enflurane, halothane, isoflurane, pentamidine or probucol are used with cisapride. In addition, uncorrected electrolyte disturbances induced by diuretics may increase the risk of torsade de pointes. Patients receiving cisapride should be promptly treated for electrolyte disturbances.
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PMID:Drug interactions with cisapride: clinical implications. 1092 50

Azithromycin, has been proved to be effective in the treatment and prophylaxis of a wide variety of infections. While the penetration of azithromycin into a number of types of mammalian cells has been well characterized, the influence of HIV infection on the intracellular disposition of this agent has not been studied. We therefore studied the disposition of azithromycin in polymorphonuclear (PMN) and mononuclear (MONO) leukocytes from six healthy volunteers and six volunteers with AIDS. After oral administration of a single 1200-mg dose of azithromycin (two 600-mg tablets), blood samples were collected over 6 days and intracellular azithromycin concentrations in MONOs and PMNs were measured. Analysis of the intracellular pharmacokinetics revealed an apparent difference in the MONO and PMN profile; this profile was similar for both groups. Intracellular concentrations of azithromycin remained high throughout the study period. Furthermore, no statistically significant differences in the intracellular area under the curve (11309+/-2543 vs. 16650+/-6254 for PMN; 14180+/-3802 vs. 21211+/-10001 for MONO) were observed between the healthy and AIDS populations, respectively. Our data confirm the extensive uptake of azithromycin by white blood cells both in healthy volunteers and in AIDS patients.
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PMID:Comparison of azithromycin leukocyte disposition in healthy volunteers and volunteers with AIDS. 1118 11

Two studies were conducted in HIV-infected subjects to assess the potential for azithromycin to interact with zidovudine and dideoxyinosine. Both studies used 12 subjects. The zidovudine study dosed subjects with 1200 mg/day of azithromycin (n = 7) (later changed to 600 mg/day [n = 5]) for Days 8 to 21 of a 21-day course of 100 mg, five times/day of zidovudine. Subjects treated with 200 mg of dideoxyinosine twice daily for 21 days received 1200 mg of azithromycin or an equivalent amount of placebo/day for Days 8 to 21. Antiretroviral plasma and urine sampling were conducted on Days 1, 7, and 21 for zidovudine and on Days 7 and 21 for dideoxyinosine. Peripheral mononuclear cells were also collected for quantitation of phosphorylated zidovudine. Azithromycin had no significant impact on the Cmax and AUC of zidovudine, although it significantly decreased the zidovudine tmax by 44% and increased the intracellular exposure to phosphorylated zidovudine by 110%. Azithromycin had no significant effect on dideoxyinosine pharmacokinetics. Based on the results of these studies, it is concluded that azithromycin may be safely coadministered with both zidovudine and dideoxyinosine.
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PMID:Lack of an effect of azithromycin on the disposition of zidovudine and dideoxyinosine in HIV-infected patients. 1121 Apr 4

Cryptosporidiosis is a protozoal infection that can come from water, or be spread from person to person. Individual protozoa are very resistant to the environment and disinfectants. How cryptosporidium causes infection is unknown, but it is known that large adult animals that commonly become infected do not get sick; small animals such as mice do not get symptomatic infection so there are no disease models to study in the lab. It is not known how many people are carrying the organism, however, in people with AIDS, 10 to 20 percent appear to be infected and testing for cryptosporidiosis is nearly impossible. It is also unknown what the immune system responds to in order to make antibodies to cryptosporidium. There have been outbreaks of cryptosporidiosis in the water supply of cities with public water filtering systems, such as Milwaukee in 1993. Boiling water for at least 1 minute kills the cryptosporidial oocysts if any exist, and while some bottled water claims to be cryptosporidium free, no data exist to prove it. No really good treatment exists for cryptosporidiosis, but Azithromycin is better absorbed than other drugs studied; it can be obtained directly from Pfizer through their compassionate use program. A new study using IGX is being conducted using chicken immunoglobulins which fight cryptosporidiosis. Participants drink irradiated eggnog five times per day. Participants must be HIV positive, have cryptosporidiosis, and not have other intestinal infection. The Network can be contacted for more information on this study.
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PMID:What's in the water? 1136 99

Research results reported at the Inter-Science Conference on Antimicrobial Agents and Chemotherapy (ICAAC) which may benefit both physicians and patients are summarized. Researchers from the University or Miami and the University of California in Los Angeles created a model of the blood-brain barrier and found conditions that may enhance HIV penetration of the central nervous system. The National Institutes of Health's (NIH) researchers reported that N-acetyl-L-cisteine (NAC) could become an adjunctive treatment for aspergillus infections. Toronto researchers reported that the antimicrobial, Azithromycin, is capable of causing hearing and balance deficits. Researchers from Johns Hopkins found an association between improved survival and use of rifabutin. According to Madrid physicians, patients treated with intravenous cytarabine, the only drug seriously considered for treatment of progressive multifocal leukoencephalopathy (PML), have shown modest improvements. Other abstracts mention new antifungals, higher CD8 cell counts and fewer opportunistic diseases, and immune globulins and prevention of infections in children with HIV.
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PMID:ICAAC's small advances. 1136 79


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