zithromax and Acquired-Immunodeficiency-Syndrome

No effective drug and definitive "gold standard" treatment for Toxoplasma gondii (T. gondii) infection has been available so far, though some medicines have been commonly used in the treatment of T. gondii infection, such as spiramycin, azithromycin, traditional Chinese medicine (TCM), pyrimethamine- sulfadiazine (P-S), trimethoprim-sulfamethoxazole (TMP-SMX), and pyrimethamine-clindamycin (P-C). A systematic review and meta-analysis were performed to compare the efficacies of these conventional medicines in the treatment. Cohort studies for the treatment of acute T. gondii infection were searched from PubMed, Google Scholar, ect. All the cases number for different group extracted from each included literature were input to meta-analysis 3.13 software to calculate the pooled negative conversion rate (NCR), cure rate (CR) or vertical transmission rate based on their sample size and weight. The pooled NCR with 95% confidence intervals (CI) was used to evaluate the overall rate of a diagnosis positive result conversion to a negative result after treatment, which of spiramycin, azithromycin and TCM were 83.4% (95%CI, 72.1%-90.8%), 82.5% (95%CI, 75.9%-87.6%), and 85.5% (95%CI, 71.3%-93.3%) respectively, with no statistical difference between them. The pooled CR with 95% CI was used to evaluate the overall rate of complete disappearance of clinical symptoms for toxoplasmic encephalitis after therapy, which of P-S, TMP-SMX, and P-C were 49.8% (95%CI, 38. 8% -60.8%), 59.9% (95%CI, 48.9%-70.0%), and 47.6% (95%CI, 24.8%-71.4%) respectively, with no statistical difference between them. Primary T. gondii infection in pregnancy was treated mainly with spiramycin alone or combined with other drugs, and the pooled rate of vertical transmission was about 9.9% (95%CI, 5.9%-16.2%) after therapy. Toxoplasmic encephalitis in AIDS patients was usually treated with sulfonamides combined with other drugs and the pooled CR was 49.4% (95%CI, 37.9%-60.9%).

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Antiprotozoal Agents; Azithromycin; Clindamycin; Drug Therapy, Combination; Female; Humans; Infectious Disease Transmission, Vertical; Male; Pregnancy; Pyrimethamine; Spiramycin; Sulfadiazine; Toxoplasma; Toxoplasmosis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Polymorphous hemangioendotheliomas (PH) are rare and borderline malignant tumors that are among the wide range of vascular tumors. We report here a 13-year-old male presenting with a history of weight loss, opportunistic infections, and lymphadenopathy. He was determined to be HIV positive and to have acquired immunodeficiency syndrome (AIDS). A biopsy of a femoral node was diagnostic of PH. His systemic lymphadenopathy appeared to resolve with anti-retroviral therapy. This tumor should be considered within the differential diagnoses of pediatric and immunocompromised patients.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Antiretroviral Therapy, Highly Active; Azithromycin; Fever; Hemangioendothelioma; Humans; Lymph Nodes; Male; Trimethoprim, Sulfamethoxazole Drug Combination; Weight Loss

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clarithromycin; Humans; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Azithromycin; Bacterial Infections; Child; Child, Preschool; Clarithromycin; Community-Acquired Infections; Helicobacter Infections; Humans; Malaria; Mycobacterium avium-intracellulare Infection; Pneumonia, Bacterial

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.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Humans; In Vitro Techniques; Macrophages; Mycobacterium avium; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Rats; Tuberculosis

The preferred therapeutic regimen for Toxoplasma encephalitis (TE) is a combination of pyrimethamine and sulfadiazine, and trimethoprim-sulfamethoxazole (TMP-SMX) plus azithromycin is the widespread alternative therapeutic regimen. The synergistic sulfonamides tablet contains TMP, sulfadiazine, and SMX and hypothetically could be used for TE treatment. This study aimed to compare the efficacy and safety of synergistic sulfonamides plus clindamycin (regimen B) with TMP-SMX plus azithromycin (regimen A) for the treatment of human immunodeficiency virus (HIV) associated TE.. This was an open-labeled, multi-center randomized controlled trial recruited from 11 centers. Each recruited patient was randomly assigned to receive regimen A or regimen B for at least 6 weeks. The overall response was evaluated by assessment of the clinical response of TE-associated clinical features and the radiological response of TE-associated radiological findings. The overall response rate, clinical response rate, radiological response rate, and adverse events were assessed at 2, 6, and 12 weeks. Death events were compared between the two regimens at 6, 12, and 24 weeks.. A total of 91 acquired immunodeficiency syndrome (AIDS)/TE patients were included in the final analysis (44 in regimen A vs . 47 in regimen B). The overall response rate, which refers to the combined clinical and radiological response, was 18.2% (8/44) for regimen A and 21.3% (10/47) for regimen B at week 6. The results of clinical response showed that, in comparison with regimen A, regimen B may perform better with regards to its effect on the relief of clinical manifestations (50.0% [22/44] vs . 70.2% [33/47], P = 0.049). However, no significant differences in radiological response, mortality events, and adverse events were found between the two regimens at week 6.. Synergistic sulfonamides plus clindamycin, as a novel treatment regimen, showed no significantly different efficacy and comparable safety in comparison with the TMP-SMX plus azithromycin regimen. In addition, the regimen containing synergistic sulfonamides may exhibit advantages in terms of clinical symptom alleviation.. ChiCTR.org.cn, ChiCTR1900021195.

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clindamycin; Encephalitis; Humans; Sulfadiazine; Sulfanilamide; Sulfonamides; Toxoplasma; Toxoplasmosis, Cerebral; Trimethoprim, Sulfamethoxazole Drug Combination

Immune function was observed for 144 weeks in 643 human immunodeficiency virus (HIV)-infected subjects who (1) had nadir CD4+ cell counts of <50 cells/mm3, followed by a sustained increase to > or =100 cells/mm3 after the initiation of HAART, and (2) were enrolled in a randomized trial of continued azithromycin prophylaxis versus withdrawal for prevention of Mycobacterium avium complex disease. The median CD4+ cell count was 226 cells/mm3 at entry and 358 cells/mm3 at week 144. Anergy (80.2% of patients) and lack of lymphoproliferative response to tetanus toxoid (TT; 73%) after immunization and impaired antibody responses after receipt of hepatitis A (54%) and TT (86%) vaccines were considered to be evidence of impaired immune reconstitution. Receipt of azithromycin did not have an effect on CD4+ cell count but was associated with higher rates of delayed-type hypersensitivity responses to TT (25% of subjects who received azithromycin vs. 15% of those who did not; P=.009) and mumps skin test antigen (29% vs. 17%; P=.001). Although the subjects had only partial responses to immune function testing, the rate of opportunistic infections was very low, and none of the tests was predictive of risk.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Antiretroviral Therapy, Highly Active; Antiviral Agents; Azithromycin; Biomarkers; CD4 Lymphocyte Count; Female; Hepatitis A Antibodies; Hepatitis A Vaccines; HIV Infections; HIV-1; Humans; Longitudinal Studies; Male; Mumps virus; Mycobacterium avium-intracellulare Infection; RNA, Viral; Tetanus Toxoid

To evaluate if atovaquone (ATQ) interacts pharmacokinetically with azithromycin (AZ) in human immunodeficiency virus-infected children, 10 subjects (ages, 4 to 13 years) were randomized in a crossover study to receive AZ (5 mg/kg/day) alone (ALONE) or AZ (5 mg/kg/day) and ATQ (30 mg/kg/day) simultaneously (SIM) prior to receiving AZ and ATQ staggered by 12 h. Despite a lack of significant difference in the mean AZ pharmacokinetic parameters, the steady-state values of AZ's area under the concentration-time curve from 0 to 24 h and maximum concentration in serum were consistently lower (n = 7 of 7) for the SIM regimen than they were for the ALONE regimen. A larger study will be required to determine if ATQ affects AZ pharmacokinetics and efficacy in a clinically significant manner.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; Anti-Bacterial Agents; Antifungal Agents; Atovaquone; Azithromycin; Child; Child, Preschool; Cross-Over Studies; Drug Interactions; HIV-1; Humans; Naphthoquinones

In this study, 30 AIDS patients without Mycobacterium avium infection were randomized to receive treatment with azithromycin (1200 mg), granulocyte-monocyte colony-stimulating factor (GM-CSF; 250 microg/m2/day for 5 days), or both agents. The M. avium killing capacity of neutrophils and monocytes harvested from each patient before intervention and during (day 4), and after therapy (day 8) was assessed. The mean virus load change in the groups receiving GM-CSF was +0.14 log human immunodeficiency virus RNA. After GM-CSF therapy, neither neutrophils nor monocytes could significantly reduce M. avium growth (P=.96 and.31, respectively). Bone pain, myalgia, presyncope, or fever occurred in 55% of patients receiving GM-CSF. Thus, the GM-CSF regimen used in this study did not affect virus load, frequently caused adverse reactions, and did not improve the M. avium killing capacity of neutrophils and monocytes. Future studies using a different GM-CSF regimen are indicated.

Topics: Acquired Immunodeficiency Syndrome; Adult; Azithromycin; Drug Therapy, Combination; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Middle Aged; Monocytes; Mycobacterium avium; Neutrophils

The intracellular dispositions of clarithromycin and azithromycin in AIDS patients requiring Mycobacterium avium complex (MAC) prophylaxis were studied. The dispositions of both drugs in mononuclear and polymorphonuclear leukocytes were markedly different. Our data support the proven efficacy of these agents for MAC prophylaxis since clarithromycin and azithromycin displayed sustained intracellular concentrations which exceeded their MICs for MAC throughout the dosing periods.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Area Under Curve; Azithromycin; Clarithromycin; Cross-Over Studies; Female; Half-Life; Humans; Leukocytes, Mononuclear; Male; Microbial Sensitivity Tests; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Neutrophils

To describe the design and first-round survey results of a trial of intensive sexually transmitted disease (STD) control to reduce HIV-1 incidence.. Randomized, controlled, community-based trial in Rakai District, Uganda.. In this ongoing study, 56 communities were grouped into 10 clusters designed to encompass social/sexual networks; clusters within blocks were randomly assigned to the intervention or control arm. Every 10 months, all consenting resident adults aged 15-59 years are visited in the home for interview and sample collection (serological sample, urine, and, in the case of women, self-administered vaginal swabs). Sera are tested for HIV-1, syphilis, gonorrhea, chlamydia, trichomonas and bacterial vaginosis. Following interview, all consenting adults are offered directly observed, single oral dose treatment (STD treatment in the intervention arm, anthelminthic and iron-folate in the control arm). Treatment is administered irrespective of symptoms or laboratory testing (mass treatment strategy). Both arms receive identical health education, condom and serological counseling services.. In the first home visit round, the study enrolled 5834 intervention and 5784 control arm subjects. Compliance with interview, sample collection and treatment was high in both arms (over 90%). Study arm populations were comparable with respect to sociodemographic and behavioral characteristics, and baseline HIV and STD rates. The latter were high: 16.9% of all subjects were HIV-positive, 10.0% had syphilis, and 23.8% of women had trichomonas and 50.9% had bacterial vaginosis.. Testing the effects of STD control on AIDS prevention is feasible in this Ugandan setting.. An ongoing (1994-98) randomized, community-based trial in Uganda's Rakai District is assessing the assumption that intensive sexually transmitted disease (STD) control efforts result in marked declines in HIV/AIDS prevalence. Described, in this article, are the project design and findings of the first-round baseline survey. 56 communities were grouped into 10 clusters designed to encompass social/sexual networks and clusters within blocks were randomly assigned to the intervention or control arm. All consenting permanent residents of the district are visited in their homes at 10-month intervals where they are administered extensive questionnaires, provide urine and vaginal swab samples, and are offered mass treatment regardless of symptoms or laboratory testing (single oral dose STD treatment in the intervention arm and anthelmintics and iron folate in the control arm). Both groups receive identical health education, condom promotion, and serologic counseling services. In the first round of home visits, 5834 intervention and 5784 control arm subjects were enrolled, representing about 90% of eligible adults. The groups were comparable in terms of sociodemographic and behavioral characteristics and baseline rates of HIV and STDs. 16.9% of subjects were HIV-positive, 10.0% had syphilis, 23.8% of women had trichomonas, and 50.9% had bacterial vaginosis. Detailed STD assessment is expected not only to document the relationship between STD control and HIV, but also to identify which STDs confer the greatest population attributable risk for HIV transmission, facilitating targeted control efforts in the future.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adolescent; Adult; Anti-Infective Agents; Azithromycin; Cefixime; Cefotaxime; Ciprofloxacin; Female; HIV-1; Humans; Incidence; Injections, Intramuscular; Male; Metronidazole; Middle Aged; Penicillin G Benzathine; Prevalence; Sexual Behavior; Sexually Transmitted Diseases; Single-Blind Method; Uganda

Prophylaxis for Mycobacterium avium complex (MAC) should be considered standard treatment for all patients with advanced HIV disease. MAC is the most common bacterial infection that affects AIDS patients. There are three effective agents that significantly reduce the risk of MAC--rifabutin, clarithromycin, and azithromycin. MAC prophylaxis is cost-effective, improves the quality of a patient's life, and improves overall survival by 25 to 32 percent.

Topics: Acquired Immunodeficiency Syndrome; Anti-Infective Agents; Azithromycin; Clarithromycin; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Randomized Controlled Trials as Topic; Rifabutin

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Erythromycin; Humans; Mycobacterium avium-intracellulare Infection

Mycobacterium avium complex infection is common in patients with AIDS. Experimentally infected mice have been treated successfully with azithromycin, a macrolide antibiotic. We report an uncontrolled phase I study in which male homosexuals with AIDS and M avium complex disease were given 500 mg azithromycin per day orally for 10, 20, or 30 days. Quantitative blood cultures showed a mean reduction in mycobacteraemia from 118 colony forming units (cfu)/ml to 43 cfu/ml in 3 patients treated for 10 days, and from 2028 cfu/ml to 136 cfu/ml in 21 patients treated for 20 or 30 days. Of the patients treated for 20 or 30 days, 15 of 21 with fever pretreatment and 12 of 18 with night sweats pretreatment reported resolution of these symptoms. The principal side-effects were loose stools or diarrhoea, but these did not result in cessation of therapy. Azithromycin, as a single oral agent, safely reduced M avium complex bacteraemia and associated symptoms in almost 75% of patients treated for at least 20 days. Further studies are needed to assess emergence of resistance.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Azithromycin; Bacteremia; Drug Administration Schedule; Drug Evaluation; Erythromycin; Follow-Up Studies; Homosexuality; Humans; Male; Mycobacterium avium-intracellulare Infection; Opportunistic Infections

Opportunistic infections, while well studied in the AIDS population, continue to have variable and surprising presentations. Here, we present a case of disseminated histoplasmosis with disseminated nontuberculous mycobacterial infection in a 50 year old man with long standing AIDS living in a non-endemic area.. Patient presented with a constellation of symptoms, and imaging of the chest showed a pulmonary mass with cavitation, multiple nodules, and ground glass opacities. Further investigations revealed granulomatous lung nodules and fungemia consistent with Histoplasma capsulatum, and coinfection with disseminated nontuberculous mycobateria in a nonendemic area.. Immunocompromised patients risk co-inhabitation by multiple infectious organisms. Some of these organisms may preside in the host for years prior to reactivation. Clinicians in non endemic areas should therefore be careful to not overlook specific organisms based on a lack of a recent travel history. Physicians in nonendemic areas should become more familiar with the clinical findings and diagnostic approach of infectious such as Histoplasmosis, to ensure earlier recognition and treatment in immunocompromised individuals.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Amphotericin B; Anti-Bacterial Agents; Anti-HIV Agents; Antifungal Agents; Antitubercular Agents; Azithromycin; Bacteremia; California; Emtricitabine; Ethambutol; Fungemia; Heterocyclic Compounds, 3-Ring; Histoplasmosis; Humans; Lung; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Oxazines; Piperazines; Pyridones; Rifabutin; Tenofovir; Tomography, X-Ray Computed

In order to evaluate the incidence rate and possible risk factors associated with AIDS-related malignancies and infections (ARMI) we performed data analysis of clinical charts of HIV patients in two hospital cohorts, that started high activity antiretroviral therapy (HAART) between July 2003 and October 2007. Trimethoprim-sulfamethoxazole and Azithromycin prophylaxis was provided according to current guidelines. We evaluated development of ARMI six months after-starting HAART and its association with clinical and epidemiological variables. Of 235 patients analyzed -118 women (50.2%) and 117 men (49.8%)- 11 presented ARMI: 3 pulmonary TB and 3 lymph nodes TB cases, 3 cases with meningeal Cryptococcus, one Chagas's disease presenting brain mass and one with non-Hodgkin lymphoma. ARMI incidence: 4.7%. A CD4 cell count < 100/150 was associated with risk of developing ARMI. The mean CD4 cell count was 73 in patients who developed ARMI and 143 in those who did not. No association was found with the other analyzed variables. In the CD4 cell count < 150 group one out of 4 patients with reactive serology presented Chagas's disease causing brain mass; none of the 46 patients with reactive serology presented toxoplasmosis encephalitis. The incidence rate of ARMI was 4.7%. TB in first place and cryptococcosis in second were the AIDS events more frequently observed. A low CD4 cell count was the only observed risk factor statistically associated with development of ARMI. The role of prophylaxis in this population should be re-evaluated.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Antiretroviral Therapy, Highly Active; Argentina; Azithromycin; CD4 Lymphocyte Count; Female; Humans; Male; Neoplasms; Odds Ratio; Retrospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination; Viral Load

Cryptosporydium parvum is an intracellular parasite that infects gastrointestinal epithelium and produces diarrhea that is self-limited in immunocompetent persons but potentially life-threatening in immunocompromised, especially those with the acquired immunodeficiency syndrome (AIDS). C. parvum enteric infection's incidence in a pediatric HIV/AIDS cohort, during a 6 years period, was studied. Clinical and immunologic characteristics of the dual infection were also recorded. Highly active antiretroviral therapy (HAART) was started or continued by all the patients during follow-up. Azithromicyn was used as antiparasitic drug. Cryptosporidiosis incidence was 13.7%; 33 out 240 children showed chronic diarrhea lasting 14 days at least, or recurrent, without dehydration and electrolytic disturbance. Peripheral blood T CD4+ percentage levels of the patients were variable and without relationship with C. parvum presence. Viral load levels in 31 out 33 patients were over cut-off at the enteric episode time. Mild or moderate eosinophilia were recorded in 23% of the patients and other intestinal parasites were present in 11 children. When the number of enteric episodes were compared with the clinical and immunological patient's status, not significant differences were recorded. HAART is the best treatment to improve immune function in HIV patients avoiding potentially fatal complications that accompany acute diarrhea during concomitant infection with C. parvum.

Topics: Acquired Immunodeficiency Syndrome; Adolescent; AIDS-Related Opportunistic Infections; Animals; Anti-HIV Agents; Antiparasitic Agents; Antiretroviral Therapy, Highly Active; Argentina; Azithromycin; CD4-Positive T-Lymphocytes; Child; Child, Preschool; Cryptosporidiosis; Cryptosporidium parvum; Humans; Immunocompromised Host; Incidence

Because most HIV-infected patients die of diseases caused by opportunistic pathogens, the prevention of these infections is an important clinical issue. Cost-containment in the healthcare system is a subject of high priority in public debate. Methods to determine cost-effectiveness of different therapeutic strategies are therefore needed to obtain valid data as the basis for decisions on cost reduction without a decrease in the quality of care. A disease state transition model based on a Markov process was developed to simulate the natural history of HIV infection and the acquired immunodeficiency syndrome (AIDS). Using this model survival time and treatment costs for every patient can be estimated and the results of alternative medications compared. We determined the cost-effectiveness (per life-year saved, LYS) of different strategies for prevention of Mycobacterium avium complex infections in AIDS patients whose treatment regimens include protease inhibitors. The cost-effectiveness ratios for treatment strategies vary from 13,510 euro to 46,152 euro per LYS without protease inhibitors and from 22,309 euro to 51,336 euro with protease inhibitors. When azithromycin, clarithromycin, and rifabutin were compared, azithromycin was the most cost-effective medication for preventing M. avium complex. The results were stable against a wide range of parameter variations concerning costs and incidence rates.

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; Cost-Benefit Analysis; Drug Therapy, Combination; Health Care Costs; Humans; Models, Economic; Mycobacterium avium-intracellulare Infection; Protease Inhibitors; Quality-Adjusted Life Years; Rifabutin

Mycobacterium avium causes disseminated infection in immunosuppressed individuals and lung infection in patients with chronic lung diseases. M. avium forms biofilm in the environment and possibly in human airways. Antibiotics with activity against the bacterium could inhibit biofilm formation. Clarithromycin inhibits biofilm formation but has no activity against established biofilm.

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Aza Compounds; Azithromycin; Biofilms; Clarithromycin; Fluoroquinolones; Humans; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Moxifloxacin; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Quinolines

Topics: Acquired Immunodeficiency Syndrome; Adult; Azithromycin; Colonic Diseases; Diagnosis, Differential; Drug Therapy, Combination; Ethambutol; Fatal Outcome; Granular Cell Tumor; Humans; Immunocompromised Host; Male; Mycobacterium avium Complex; Mycobacterium avium-intracellulare Infection; Mycobacterium Infections; Nucleic Acid Amplification Techniques; Rifabutin; RNA, Bacterial; Whipple Disease

The in vitro anticryptosporidial activities of ranalexin, lasalocid and azithromycin alone and in combination were investigated against four clinical isolates of Cryptosporidium parvum. Susceptibility was tested by inoculating the isolates on to cell monolayers and determining the parasite count after 48 h incubation at 37 degrees C. The culture medium was supplemented with Dulbecco's modified Eagle's medium containing serial dilutions of the above-mentioned compounds. Ranalexin showed moderate anticryptosporidial activity: at a concentration of 64 mg/L it reduced parasite counts by 33.8%. Azithromycin at a concentration of 8 mg/L gave inhibition comparable to that observed with the highest concentration of ranalexin. Lasalocid showed the highest activity, with a 70.3% reduction in parasite counts at 2 mg/L. The combination of ranalexin 64 mg/L and lasalocid 2 mg/L completely suppressed parasite growth without harming the monolayer.

Topics: Acquired Immunodeficiency Syndrome; Animals; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Cells, Cultured; Coccidiostats; Cryptosporidium parvum; Drug Therapy, Combination; Feces; Humans; Lasalocid; Peptides, Cyclic

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.

Topics: Acquired Immunodeficiency Syndrome; Adult; AIDS-Related Opportunistic Infections; Anti-Bacterial Agents; Azithromycin; Female; Humans; Leukocytes; Leukocytes, Mononuclear; Male; Middle Aged; Mycobacterium avium-intracellulare Infection; Neutrophils

Mycobacteria Growth Indicator Tube (MGIT) is a recently introduced rapid growth detection method which uses an oxygen quenched fluorescent indicator. The present study evaluated the ability of this new method to determine the drug susceptibility of Mycobacterium avium complex (MAC). Thirty strains recovered from patients with AIDS were tested for susceptibility to clarithromycin, rifabutin, ciprofloxacin, azithromycin and amikacin using MGIT. Results were compared to susceptibilities determined by the agar dilution method. The results obtained showed a 100% correlation between MGIT and the agar dilution method for rifabutin and clarithromycin. There was a 100% correlation between the two methods for azithromycin against 27 strains. MGIT was well correlated with the agar dilution method for detecting resistance to clarithromycin, rifabutin and azithromycin in 4 days, but the correlation was poor when susceptibilities to ciprofloxacin and amikacin were determined. This rapid method is non-radiometric, noninvasive and does not require any special instruments.

Topics: Acquired Immunodeficiency Syndrome; Agar; Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Clarithromycin; Fluoroimmunoassay; Humans; Microbial Sensitivity Tests; Mycobacterium avium; Nucleic Acid Hybridization; Rifabutin

Nineteen cases of cerebral toxoplasmosis (CTOX) are reported from a group of Edinburgh AIDS patients. All patients were severely immunodeficient at the time of presentation with CD4 count < 50 cells/mm3. Thirteen patients had suffered a previous AIDS-defining illness. In Edinburgh, CTOX has developed in 48% of patients who are seropositive for toxoplasma and have a CD4 count < 50 cells/mm3. It is estimated that at least half of the toxoplasma seropositive patients will develop CTOX if they survive for 21 months after reaching a time in their illness when the CD4 count = 50 cells/mm3. The incidence of CTOX in toxoplasma-seronegative patients with a CD4 count < 50 cells/mm3 is 1.3%. All patients showed improvement on treatment and there was no correlation between clinical or radiological features and patient survival. Those patients unable to tolerate first choice anti-toxoplasma therapy had a significantly shorter survival than the remainder but there was no single therapeutic regimen which conferred a survival advantage. Eighteen patients had died at the time of study and the median survival following diagnosis of cerebral toxoplasmosis was 10 months (range 3-38 months). Postmortem examination of the brain was available in 8, 4 of whom had concomitant cerebral lymphoma. The survival from AIDS or CD4 count = 50 cells/mm3 did not differ significantly between those with treated CTOX and a control group who had no toxoplasma infection, suggesting that treatment is reasonably effective. CTOX is a disease associated with severe HIV-related immunodeficiency and, in those with a CD4 count < 50 cells/mm3, occurs more than 35 times as frequently in toxoplasma-seropositive than toxoplasma-seronegative patients. Treatment is effective but the outcome of treated disease cannot be predicted from presenting clinical or radiological features. Concomitant space-occupying cerebral pathology is evident in 50% of post-mortem examinations.

Topics: Acquired Immunodeficiency Syndrome; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Atovaquone; Autopsy; Azithromycin; Brain; CD4 Lymphocyte Count; Clindamycin; Drug Therapy, Combination; Female; Humans; Incidence; Lymphoma, AIDS-Related; Male; Middle Aged; Naphthoquinones; Pyrimethamine; Retrospective Studies; Sulfadiazine; Toxoplasmosis, Cerebral; United Kingdom

Study efforts are showing progress in the prevention and therapy of Mycobacterium avium complex (MAC) infection. A review of recent study developments highlights clinical findings on prophylactic use of rifabutin, clarithromycin, and azithromycin, used both as monotherapies and as combination therapies. Three tables highlight study results from MAC prophylaxis studies, MAC treatment studies, and candidate regimens for MAC prophylaxis in AIDS. Treatment of disseminated MAC is also addressed. The combination of clarithromycin and clofazimine should not be used as initial therapy. Clofazimine's role in initial therapy is uncertain, and combinations of clarithromycin and ethambutol, with or without rifabutin, appear to be the best current treatment options.

Topics: Acquired Immunodeficiency Syndrome; Antitubercular Agents; Azithromycin; Clarithromycin; Clofazimine; Drug Therapy, Combination; Ethambutol; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin

Mycobacterium avium complex (MAC) infection occurs in 18 to 40 percent of people with AIDS, and most commonly in those with CD4 counts under 50. MAC is a difficult infection to diagnose, as its symptoms mimic many other infections and tumors. MAC infections can occur in the respiratory system or gastrointestinal tract, and the infection may spread through the bloodstream. Clinical trials for MAC prophylaxis include clarithromycin, rifabutin, or a combination of both. The individual drugs and the combination both may cause side effects that would require discontinuation of treatment. Azithromycin administered weekly, compared to rifabutin, or a combination of both, also had some significant adverse effects. The azithromycin/rifabutin combination resulted in the lowest rate of MAC breakthrough. Drug resistance and cross resistance to these drugs exist.

Topics: Acquired Immunodeficiency Syndrome; Azithromycin; CD4 Lymphocyte Count; Clarithromycin; Drug Resistance, Microbial; Drug Therapy, Combination; Humans; Mycobacterium avium-intracellulare Infection; Rifabutin

Topics: Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Anti-Infective Agents; Azithromycin; Ciprofloxacin; Clinical Trials as Topic; Costs and Cost Analysis; Female; Humans; Male; Sexually Transmitted Diseases; Uganda

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Animals; Anti-Bacterial Agents; Azithromycin; Community-Acquired Infections; Cryptosporidiosis; Humans; Injections, Intravenous; Malaria, Falciparum; Mycobacterium avium-intracellulare Infection; Plasmodium falciparum; Pneumonia; Pneumonia, Pneumocystis; Toxoplasmosis, Cerebral

Toxoplasmic encephalitis is one of the leading causes of morbidity in patients with AIDS. Lifelong treatment is needed to prevent relapses, and primary prevention is desirable in high-risk patients, but the available drugs are often poorly tolerated. Azithromycin (AZM) has been considered a drug candidate because of its efficacy in the animal model and its kinetic properties, which would allow intermittent administration. The tolerability and kinetics of AZM and its effect on the disposition of zidovudine (ZVD) were therefore evaluated in a preliminary open study in nine human immunodeficiency virus-infected patients. AZM was administered once weekly for 5 weeks 2 h before the usual morning ZVD dose. The day before and on the first and fifth AZM dosings, blood samples were drawn every 30 min during 5 h for determination of the concentrations of ZVD and its glucuronide metabolite. Blood samples were drawn for AZM measurement over 72 and 360 h on the first and fifth AZM administrations, respectively, as well as before and 3 h after dosing on the second, third, and fourth AZM dosings. After the first and fifth administrations, maximum AZM concentrations in serum were 0.6 +/- 0.1 and 0.8 +/- 0.2 microM (mean +/- standard error of the mean), respectively; times to peak concentration in serum were 3.7 +/- 0.2 and 2.9 +/- 0.4 h, respectively; areas under the plasma concentration-time curves were 9.2 +/- 1.6 and 9.3 +/- 2.0 micrograms.h/ml, respectively; and half-lives were 61.0 +/- 5.4 and 63.8 +/- 6.7 h, respectively. On days -1, 1, and 29, ZVD kinetic parameters were as follows: maximum concentrations in serum, 3.1+/- 0.6, 4.3 +/- 0.6, and 4.2 +/- 0.9 microM, respectively; times to maximum concentrations in serum, 1.1 +/- 0.4, 0.8 +/- 0.2, and 1.2 +/- 0.3 h, respectively: areas under the plasma concentration-time curves, 5.3 +/- 0.9, 5.9 +/- 0.6, and 5.7 +/- 0.8 microgram . h/ml, respectively; and half-lives, 1.3 +/- 0.08, 1.4 +/- 0.04, and 1.3 +/- 0.04 h, respectively. Except for transient mild abdominal cramps that occurred at 2 to 3 h postdose (6 of 45 exposures) and nausea (4 of 45 exposures), neither subjective nor objective side effects were observed. The kinetics of AZM were similar after the first and repeated administrations, and the disposition of ZVD was not altered by this treatment. The efficacy of AZM in preventing cerebral toxoplasmosis can therefore be safely tested in human immunodeficiency virus-infected patients concomitantly treated with zi

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; Adult; Azithromycin; Biotransformation; Drug Administration Schedule; Drug Tolerance; Erythromycin; Female; Humans; Male; Zidovudine

Topics: Acquired Immunodeficiency Syndrome; Adult; Azithromycin; Erythromycin; Humans; Male; Toxoplasmosis, Cerebral

The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infected with the M. avium complex at day 6 of culture. The intracellular CFU was counted 60 min after inoculation. The intracellular and supernatant CFU was counted on days 4 and 7 after inoculation. The concentrations used, which were equal to peak levels in serum, were 10 micrograms of rifapentine per ml (MICs for the two strains, 4 and 16 micrograms/ml), 4 micrograms of clarithromycin per ml (MICs, 8 and 4 micrograms/ml), 1 microgram of azithromycin per ml (MICs, 32 and 16 micrograms/ml), 4 micrograms of temafloxacin per ml (MICs, 2 and 16 micrograms/ml), and 1 microgram of sparfloxacin per ml (MICs, 0.5 and 2 micrograms/ml). Compared with controls on day 7 after inoculation, clarithromycin (P less than 0.001), sparfloxacin (P less than 0.001), and azithromycin (P less than 0.001 for the first strain, P less than 0.02 for the second) slowed intracellular replication. Rifapentine (P less than 0.001) and temafloxacin (P less than 0.001) slowed intracellular replication of the first strain but not of the second strain. Azithromycin plus sparfloxacin was as effective as sparfloxacin alone. In this macrophage model, sparfloxacin or clarithromycin (difference not significant) exhibited a better efficacy than rifapentine, azithromycin, or temafloxacin against intracellular M. avium complex infection.

Topics: 4-Quinolones; Acquired Immunodeficiency Syndrome; Anti-Bacterial Agents; Azithromycin; Cell Division; Clarithromycin; Erythromycin; Fluoroquinolones; Humans; In Vitro Techniques; Leprostatic Agents; Macrophages; Microbial Sensitivity Tests; Mycobacterium avium Complex; Quinolones; Rifampin