- Clarithromycin Or Azithromycin For Macbook Pro
- Clarithromycin Or Azithromycin For Macrolide Antibiotics
If disseminated MAC develops, a treatment regimen containing clarithromycin or azithromycin and at least one other agent is recommended. Diagnosis, therapy, and prophylaxis for HIV-infected children follow similar guidelines. Both azithromycin and clarithromycin are active agents for MAC prophylaxis in patients with late-stage acquired immunodeficiency syndrome (AIDS), although azithromycin may be the preferable agent because of fewer drug-drug interactions.
Abstract Context.— Cryptosporidium parvum infection, a common cause of diarrhea in persons infected with the human immunodeficiency virus (HIV), is difficult to treat or prevent. Objective.— To evaluate relative rates of cryptosporidiosis in HIV-infected patients who were either receiving or not receiving chemoprophylaxis or treatment for Mycobacterium avium complex. Design.— Analysis of prospectively collected data from HIV-infected patients' visits to their physicians since 1992. Setting.— Ten (8 private, 2 publicly funded) HIV clinics in 9 US cities. Patients.— A total of 1019 HIV-infected patients with CD4 + cell counts less than 0.075×10 9/L. Main Outcome Measures.— Incidence of clinical cryptosporidiosis during treatment with clarithromycin, rifabutin, and azithromycin. Results.— Five of the 312 patients reportedly taking clarithromycin developed cryptosporidiosis vs 30 of the 707 patients not taking clarithromycin (relative hazard RH, 0.25 95% confidence interval (CI), 0.10-0.67; P =.004).Two of the 214 patients taking rifabutin developed cryptosporidiosis vs 33 of the 805 not taking rifabutin (RH, 0.15 95% CI, 0.04-0.62; P=.01).
Prophylactic efficacy of either drug was 75% or greater. No protective effect was seen in the 54 patients reportedly taking azithromycin (RH, 1.48 95% CI, 0.44-5.04; P=.46). Conclusions.— Clarithromycin and rifabutin were highly protective against development of cryptosporidiosis in immune-suppressed HIV-infected persons in this analysis; further study is warranted. Methods HOPS is an actively recruiting cohort that now includes over 2800 HIV-infected out-of-hospital patients seen in about 30000 symptom-driven visits since 1992.
Study sites include 10 (8 private and 2 public) clinics caring for HIV-infected patients. HOPS physicians are almost all board certified in both internal medicine and infectious disease and care for HIV-infected patients only.
Information in 5 categories—demographics and risk behaviors for HIV infection; symptoms; diagnosed diseases ('definitive' and 'presumptive'); medications taken (dose and duration); and laboratory test results—is abstracted at each visit, electronically entered at each site using a common form, collected centrally, and reviewed and corrected before entry in the Centers for Disease Control and Prevention database. This analysis includes patients seen up to April 1996. Much effort has been applied to the correctness and completeness of HOPS data, including standardized training and extensive verifying of data. Because we aimed to investigate those receiving clarithromycin and other MAC prophylaxis (azithromycin or rifabutin) who were also at risk for clinical cryptosporidiosis, we limited this analysis to HOPS patients with CD4 + cell counts less than 0.075×10 9/L. We considered that a person had taken 1 of the 3 drugs if reportedly taking it for at least 3 months continuously.
The period of patient observation was time between first clinic visit when CD4 + cell count was less than 0.075×10 9/L until last clinic visit (before April 1996) or development of cryptosporidiosis. Outcome measure was clinical cryptosporidiosis, defined as diarrhea and other gastrointestinal symptoms, leading to a physician visit, with a positive stool examination for C parvum oocysts (acid-fast staining of unconcentrated fecal smears). We analyzed effects of drugs of interest, demographic and socioeconomic variables, and other factors, notably observation duration and most recent CD4 + cell count, on outcome. Data were analyzed with Statistical Analysis Software (SAS Institute Inc, Cary, NC), version 6.11. Incidence density of cryptosporidiosis, incidence relative risk, confidence intervals, and P values were calculated using maximum likelihood (likelihood ratio) tests. Potentially confounding variables were analyzed by continuity-adjusted χ 2, Wilcoxon rank sum, and Fisher exact (2-tailed) tests. A time-dependent accelerated failure time analysis, using SAS PROC LIFEREG, version 6.11, was done to assess relative contributions of individual drugs and independent (demographic and immunologic) variables to the likelihood of developing disease.
A change-in-estimate forward stepwise method was used to assess importance and order of independent variables entered into the final model. A variable that changed the estimate of association between a MAC drug and cryptosporidiosis by 5% or more was considered a potential confounder. The variable that changed the association the most, and by at least 5%, was put in the model, and remaining variables were added one at a time. When no new variable changed the association estimate by more than 5%, the model was considered complete.
Results We identified 535 HIV-infected patients who had taken clarithromycin, azithromycin, or rifabutin for 5546 patient-months of observation and 484 patients not receiving these drugs and who were followed up for 4510 patient-months ; all patients had CD4 + cell counts less than 0.075×10 9/L. Patients taking these drugs had a mean of 13.6 (range, 2-66) visits and those not taking them had a mean of 7.9 (range, 2-46) visits. Those taking any of the 3 drugs usually did so for prophylaxis (77%) vs therapy for MAC (17%); 6% took any drug or a combination for both prophylaxis and treatment of MAC. The 535 patients reportedly taking MAC drugs and the 484 persons not taking them were comparable in many ways. Men who have sex with men were better educated, more likely to have a private medical payment source, and more likely to receive drugs (and earlier) than other groups. These variables, among others, were considered potentially confounding and so included in the final statistical model. We evaluated outcomes after and histories of cryptosporidiosis and diarrhea before each patient observation.
The 1019 patients had the following dispositions over about 312 years of data collection: 458 (45%) were still actively being followed by April 1, 1996; 353 (35%) died—without cryptosporidiosis diagnosis—while under care; 76 (8%) were transferred; 74 (7.3%) were 'inactive'; 38 (3.7%) had no clinic visit for more than 6 months as of April 1, 1996; and 20 (2%) could not be located. Prior to the censoring date of observation (first CD4 + cell count.
Clarithromycin Or Azithromycin For Macbook Pro
Comment This analysis indicates that those reportedly on MAC prophylaxis with clarithromycin or rifabutin also had a several-fold decreased risk of developing cryptosporidiosis, a statistically robust effect in regression analyses controlling for observation duration and many demographic (age, sex, race, transmission risk group, main source of medical payment) and immunologic (CD4 + cell count) variables. We did not find statistically significant differences in several possible confounders, such as geographic site (municipal water source ) and drugs considered unrelated to development of cryptosporidiosis (acyclovir and trimethoprim-sulfamethoxazole), that might be indexes of access to medical care (data not shown). There are unavoidable limitations; these data were derived from an observed cohort, not a controlled clinical trial, and unmeasured factors may confound associations. The 3 drugs, recommended in HIV patients only for prevention and treatment of MAC, may have been differentially prescribed and used by HIV patients in this study. However, patients who did and did not receive MAC drugs did not differ markedly in demographic or immunologic profiles , and our analyses controlled for these variables and others. Because we lacked an absolute standard or another commonly used test for Cryptosporidium infection, we do not know if some patients taking macrolides had suppressed and undetectable stool organisms, yet suffered from cryptosporidiosis. Still, only a high rate of 'false-negative' stool examination results—and that occurring in persons suffering from disease despite undetectable stool C parvum oocytes—would negate the large and robust prophylactic efficacy of clarithromycin and rifabutin seen.
Of factors possibly confounding the observed protective effect, host immunologic function is putatively most important. Cryptosporidial diarrhea is less likely in those with high or increasing CD4 + cell counts., Besides limiting our analyses to those with a CD4 + cell count of less than 0.075×10 9/L, the time-dependent regression model controlled for this factor. Also, means of most recent CD4 + cell counts of those with or without MAC prophylaxis or treatment were both about 0.040×10 9/L. Thus, no confounding variable—such as combination antiretroviral or protease inhibitor use (not approved for use or available generally until after periods of observation in this analysis)—was detected that would enhance immunologic protection. Data regarding biologic mechanisms and efficacy of these drugs are relatively scant and inconclusive. Some semisynthetic macrolides may reduce cryptosporidial oocyst load in stools of infected persons,: clarithromycin and azithromycin activity against Cryptosporidium has been seen in vitro and in experimental models. Lower activity of clarithromycin vs azithromycin in animal models, may result from animal inability to produce the active 14-hydroxy-metabolite seen in humans receiving clarithromycin.
A few controlled trials of clarithromycin and azithromycin in treating cryptosporidiosis in about 90 patients have shown decreased stool oocytes and some clinical benefit. Anecdotal reports of success with spiramycin, another macrolide antibiotic, indicate possible benefit in placebo-controlled trials in 54 patients with acquired immunodeficiency syndrome., We are unaware of animal models or human trials of rifabutin anticryptosporidial activity, a semisynthetic ansamycin antibiotic with a mechanism of action distinct from that of macrolides. Although there may be few or no published studies of rifabutin in treating cryptosporidiosis, a possible protective effect should be considered. The lack of protective effect in those taking azithromycin is confusing, since it is similar in structure and action to clarithromycin and spiramycin, which seem to have some therapeutic efficacy in animals and humans.
Clarithromycin Or Azithromycin For Macrolide Antibiotics
Therapeutic efficacy of a 500-mg daily dose of azithromycin, however, was not seen in a recent study. The lack of prophylactic efficacy seen in our data may partly be attributable to small numbers of patients receiving azithromycin (54 persons), of whom only 2 developed cryptosporidiosis and who may not have been adherent. The small numbers preclude a definitive conclusion about its potential utility. Randomized clinical trials of this issue will be difficult, as study participants with low CD4 + cell counts cannot ethically be randomized for MAC chemoprophylaxis, and newer antiretroviral therapy will confound the analysis. We found robust and statistically significant protective effects of clarithromycin and rifabutin, used for MAC prophylaxis and treatment, in preventing cryptosporidiosis. These data, primarily involving chemoprophylaxis, cannot necessarily be extended to treatment of HIV-infected persons with cryptosporidiosis. We conclude that similar analyses of other data sets and expanded trials of new macrolide and other agents for preventing cryptosporidiosis in HIV-infected persons are warranted.