erythromycin-estolate and Whooping-Cough

Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit.. To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough.. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007).. All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough.. Three to four review authors independently extracted data and assessed the quality of each trial.. Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis.. Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Topics: Anti-Bacterial Agents; Azithromycin; Bordetella pertussis; Clarithromycin; Contact Tracing; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Humans; Infant; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Whooping Cough

Whooping cough is a highly contagious disease. Infants are the population at highest risk of severe disease and death. Erythromycin for 14 days is recommended for treatment and contact prophylaxis but this regime is considered inconvenient and prolonged. The value of contact prophylaxis is uncertain.. To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough.. The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004); MEDLINE (January 1966 to February 2004); EMBASE (January 1974 to August 2003); conference abstracts and reference lists of articles were searched. Study investigators and pharmaceutical companies were approached for additional information (published or unpublished studies). There were no constraints based on language or publication status.. All randomised and quasi-randomised controlled trials of antibiotics for treatment of and contact prophylaxis against whooping cough were included in the systematic review.. At least three reviewers independently extracted data and assessed the quality of each trial.. Twelve trials with 1,720 participants met the inclusion criteria. Ten trials investigated treatment regimens and two investigated prophylaxis regimens. The quality of the trials was variable. Results showed that short-term antibiotics (azithromycin for three days, clarithromycin for seven days, or erythromycin estolate for seven days) were equally effective with long-term antibiotic treatment (erythromycin estolate or erythromycin for 14 days) in the microbiological eradication of Bordetella pertussis (B. pertussis) from the nasopharynx. The relative risk (RR) was 1.02 (95% confidence interval (CI) 0.98 to 1.05). Side effects were fewer with short-term treatment (RR 0.66; 95% CI 0.52 to 0.83). There were no differences in clinical improvement or microbiological relapse between short and long-term treatment regimens. Contact prophylaxis (of contacts older than six months of age) with antibiotics did not significantly improve clinical symptoms or the number of cases that developed culture positive B. pertussis.. Antibiotics are effective in eliminating B. pertussis from patients with the disease, rendering them non-infectious, but do not alter the subsequent clinical course of the illness. Effective regimens include: three days of azithromycin, seven days of clarithromycin, seven or 14 days of erythromycin estolate, and 14 days of erythromycin ethylsuccinate. Considering microbiological clearance and side effects, three days of azithromycin or seven days of clarithromycin are the best regimens. Seven days of trimethoprim/sulfamethoxazole also appeared to be effective for the eradication of B. pertussis from the nasopharynx and may serve as an alternative antibiotic treatment for patients who cannot tolerate a macrolide. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Topics: Anti-Bacterial Agents; Azithromycin; Bordetella pertussis; Clarithromycin; Contact Tracing; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Humans; Infant; Randomized Controlled Trials as Topic; Trimethoprim, Sulfamethoxazole Drug Combination; Whooping Cough

Although universal immunization against Bordetella pertussis (whooping cough) infection has resulted in dramatic reductions in the incidence of pertussis, outbreaks continue to occur in countries with excellent vaccine coverage. Treatment of infection may ameliorate symptom severity during the catarrhal phase of pertussis but has no effect on established paroxysms, emesis, or apnea if given during the paroxysmal or convalescent phases. Erythromycin, recommended for treatment of pertussis to prevent transmission of infection, is poorly tolerated because of gastrointestinal side effects. We compared the safety and efficacy of erythromycin with azithromycin for treatment of pertussis in a large, randomized, controlled trial that enrolled children from primary care practices in 1 American and 11 Canadian urban centers.. Children who were 6 months to 16 years of age and had cough illness that was suspected to be or was culture confirmed as pertussis were randomized to azithromycin (10 mg/kg on day 1 and 5 mg/kg on days 2-5 as a single dose) or erythromycin estolate (40 mg/kg/day in 3 divided doses for 10 days) with stratification by center. The primary outcome measure was bacteriologic cure of infection as determined by cultures of nasopharyngeal aspirates. Culture-positive participants had a second aspirate collected at the end of therapy (days 5-7 for azithromycin, days 10-12 for erythromycin) and 1 week after therapy. Bacteriologic cure was defined as negative cultures at the end of therapy. Bacteriologic relapse was defined as a positive culture 1 week after completion of therapy and after a negative end-of-therapy culture. Secondary outcomes were pertussis diagnosed by serology and polymerase chain reaction (PCR), treatment-associated adverse events, compliance, and presence of clinical symptoms at the end of the treatment course. Serology was performed using standard enzyme-linked immunosorbent assay methods. A participant was considered to have pertussis when the PCR was positive or a 4-fold increase in pertussis toxin antibody between baseline and follow-up visits was observed. PCR was performed using a 1046-bp ClaI DNA fragment from B pertussis. Adverse events (nausea, vomiting, diarrhea, any gastrointestinal complaint, or other) were determined by a parent-completed diary that was reviewed with study personnel during study visits. Compliance was measured by review of the parent medication diary during study visits and observation of medication containers by the pharmacist at study completion. Symptoms were determined by history collected by study personnel at enrollment and subsequently from the diary. The design of the study was an equivalence trial, aimed at demonstrating that the bacteriologic failure rates with the 2 therapies did not differ by >8%. For the safety analysis, all participants who received at least 1 dose of study drug were included. In the per-protocol efficacy analysis, all culture-positive participants with end-of-treatment cultures were considered.. A total of 477 children were enrolled and randomly assigned to either azithromycin (n = 239) or erythromycin (n = 238). Of these children, 114 (24%) grew B pertussis from nasopharyngeal specimens (azithromycin group: 58 of 239 [24%]; erythromycin group: 56 of 238 [23%]); these children composed the efficacy cohort for the per-protocol and intention-to-treat analyses. Serology and PCR added 52 children to the number considered to have pertussis for a total of 35% (166 of 477) of all children who presented with cough illness. In the safety analysis (antibiotic side effects, compliance) and comparison of cough symptoms after treatment, all randomized children are reported in their assigned treatment group. At end of therapy, bacterial eradication was demonstrated in all 53 patients in the azithromycin group and all 53 patients in the erythromycin group with follow-up cultures available (eradication 100%; 95% confidence interval [CI]: 93.3-100). No bacterial recurrence was demonstrated in children with 1 week posttreatment nasopharyngeal cultures available (51 and 53 participants in the azithromycin and erythromycin arms, respectively [0%, 95% CI: 0-7.0; and 0%, 95% CI: 0-6.7]). No serious adverse events attributable to study drug were observed. Gastrointestinal adverse events were reported less frequently in azithromycin (18.8%; 45 of 239) than in erythromycin estolate (41.2%; 98 of 238) recipients (90% CI on difference: -29.0% to -15.7%) as a result of less nausea (2.9% vs 8.4%; 95% CI: -8.9% to -2.0%), less vomiting (5.0% vs 13.0%; 95% CI: -4.9% to -1.4%), and less diarrhea (7.1% vs 11.8%; 95% CI: -9.0% to -0.3%). Children who were randomized to azithromycin were much more likely to have complied with antimicrobial therapy over the treatment period. In the azithromycin group, 90% of children took 100% of prescribed doses, whereas only 55% of children in the erythromycin group took 100% of prescribed doses.. In this large, multicenter, randomized trial, we found that azithromycin is as effective as erythromycin estolate for the treatment of pertussis in children. Gastrointestinal adverse events were much more common with erythromycin treatment than azithromycin. Compliance with therapy was markedly better with azithromycin than with erythromycin in this study.

Topics: Adolescent; Anti-Bacterial Agents; Azithromycin; Bordetella pertussis; Child; Child, Preschool; Cough; Erythromycin Estolate; Female; Gastrointestinal Diseases; Humans; Infant; Male; Nasopharynx; Patient Compliance; Prevalence; Whooping Cough

Household contacts of patients with pertussis are at increased risk of acquiring infection. Chemoprophylaxis has been recommended to decrease transmission, particularly to young infants who are at increased risk of severe disease. Although epidemiologic investigations of outbreaks have suggested a benefit, there have been no prospective studies evaluating the efficacy of chemoprophylaxis in preventing secondary cases of pertussis.. To determine whether erythromycin estolate chemoprophylaxis is effective in household contacts of children with culture-positive pertussis.. Randomized, double-blind, placebo-controlled study.. Community based.. All household contacts of 152 children with culture-positive pertussis who provided consent (n = 362). After withdrawals, there were 135 households with 310 contacts. Exclusions included pregnancy, age <6 months, already receiving an erythromycin-containing antibiotic, and erythromycin allergy. INTERVENTUINS: Erythromycin estolate (40 mg/kg/day in 3 divided doses; maximum dose 1 g) or placebo for 10 days. Nasopharyngeal cultures, pertussis antibodies, and clinical symptoms were assessed before and after treatment.. Measure efficacy of erythromycin estolate chemoprophylaxis calculated by the proportion of households in each group with a member who developed a nasopharyngeal culture positive for Bordetella pertussis.. There was no difference in the development of respiratory tract symptoms compatible with a case definition of pertussis in the erythromycin- and placebo-treated groups. There were 20 households with secondary culture-positive cases of pertussis; 4 households in the erythromycin-treated group and 15 in the placebo-treated group (efficacy of erythromycin chemoprophylaxis for bacterial eradication 67.5% [95% confidence interval: 7.6-88.7]). However, medication-associated adverse reactions were reported by 34.0% of erythromycin and 15.7% of placebo recipients.. Under the conditions of this study, erythromycin estolate prevented culture-positive pertussis in household contacts of patients with pertussis but did not prevent clinical pertussis.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antibodies, Bacterial; Bordetella pertussis; Child; Child, Preschool; Double-Blind Method; Erythromycin Estolate; Family Health; Female; Humans; Infant; Male; Whooping Cough

Although 14 days of erythromycin is recommended for the treatment of Bordetella pertussis infection, there have been no prospective controlled studies to support the contention that this long course of therapy is required to eradicate the microorganism from the nasopharynx or to prevent bacteriological relapse. We randomly allocated children and adults with culture-positive community-acquired pertussis to either 7 or 14 days of erythromycin estolate treatment (40 mg/kg/d; maximum dose 1 g/d). Nasopharyngeal aspirate cultures were obtained by study nurses during home visits before and at the end of treatment, and 1 week after the completion of treatment. B pertussis-specific antibodies were measured before treatment and 1 month later. Information about clinical symptoms, adverse reactions, and compliance were collected at each scheduled contact.. A total of 168 participants were eligible for analysis (74 treated for 7 days and 94 treated for 14 days). Bacteriological persistence (positive end of therapy culture) occurred once in each group, and bacteriological relapse (positive culture 1 week after completion of treatment) occurred in one participant treated for 7 days. The overall failure rate (persistence plus relapse) of 2.70% in the 7-day group was not different than the rate of 1.06% in the 14-day group. The study had a power of 99.99% at the 5% level to detect a difference in failure rates of 10% and a power of 80% to detect a difference of 5%. We conclude that 7 days of erythromycin estolate is as effective as 14 days for the eradication of B pertussis.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Antibodies, Bacterial; Bordetella pertussis; Child; Child, Preschool; Erythromycin Estolate; Female; Humans; Immunoglobulin A; Immunoglobulin G; Infant; Infant, Newborn; Male; Nasopharynx; Time Factors; Whooping Cough

In an open randomized multicenter study 190 culture-positive pediatric ambulatory pertussis patients were treated for 14 days with either erythromycin estolate (EST) (n = 93; 40 mg/kg/day divided in 2 doses) or erythromycin ethylsuccinate (ETH) (n = 97; 60 mg/kg/day divided in 3 doses). On day 14 Bordetella pertussis was recovered from cultures of 2 patients (2.2%) treated with EST and 1 patient (1.0%) treated with ETH. Despite the fact that 151 patients (79.4%) had reached the early paroxysmal stage at initiation of antimicrobial therapy, clinical improvement was seen in the majority (reduced frequency and severity of coughing: EST, 77.4 and 67.7%; ETH, 74.2 and 63.9%, respectively). Drug-related side effects were noted in 11 patients (11.8%) treated with EST and 16 patients (16.5%) treated with ETH (P greater than 0.05) and consisted mainly of minor gastrointestinal complaints. Erythromycin estolate in a lower dose administered only twice a day was equivalent to erythromycin ethylsuccinate in all aspects and proved to be adequate antimicrobial treatment for pertussis patients.

Topics: Child; Child, Preschool; Erythromycin Estolate; Erythromycin Ethylsuccinate; Female; Humans; Infant; Male; Prospective Studies; Whooping Cough

We studied the pharmacokinetics of erythromycin estolate and ethylsuccinate suspensions in infants under 4 months of age who were being treated for chlamydial infections or pertussis. We conducted our studies after the initial dose of 10 mg/kg and subsequently during steady-state treatment. The estolate preparation resulted in higher peak concentrations in sera, and its absorption and elimination half-lives were longer. Peak concentrations occurred 3 h after a dose with the estolate preparation and 1 h after a dose with the ethylsuccinate preparation. The area under the curve for the estolate preparation was about three times greater than that for the ethylsuccinate preparation. Based on these findings, we recommend that erythromycin estolate suspensions be given to young infants at 8- or 12-h intervals (30 mg/kg per day in three divided doses or 20 mg/kg per day in two divided doses) and that erythromycin ethylsuccinate is best given at 6-h intervals (40 mg/kg per day in four divided doses).

Topics: Chlamydia Infections; Erythromycin; Erythromycin Estolate; Erythromycin Ethylsuccinate; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Tears; Whooping Cough