Once-daily therapy for streptococcal pharyngitis with amoxicillin.

OBJECTIVE: An orally administered antimicrobial regimen for the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis given once rather than multiple times each day would be more convenient and might result in improved patient compliance. The purpose of this study was to evaluate the effectiveness of once-daily amoxicillin in the treatment of GABHS pharyngitis. PATIENTS: Children presenting to a private pediatric office with GABHS pharyngitis. DESIGN: Patients were randomly assigned to receive orally either amoxicillin (750 mg once daily) or penicillin V (250 mg three times a day) for 10 days. Compliance was monitored by urine antimicrobial activity. OUTCOMES: Outcomes were measured by impact on the clinical course, eradication of GABHS within 18 to 24 hours, and bacteriologic treatment failure rate as determined by follow-up throat cultures 4 to 6 and 14 to 21 days after completing therapy. GABHS isolates were serotyped to distinguish bacteriologic treatment failures (same serotype as initial throat culture) from new acquisitions (different serotypes). RESULTS: During the 16 months of this study, 152 children between 4 and 18 years of age (mean, 9.9 years) were enrolled; 79 children were randomly assigned to receive once-daily amoxicillin and 73 were assigned to receive penicillin V three times a day. The children in the two treatment groups were comparable with respect to age, duration of illness before initiation of therapy, compliance, and signs and symptoms at presentation. There was no significant difference in the clinical or bacteriologic responses of the patients in the two treatment groups at the 18- to 24-hour follow-up visit. Bacteriologic treatment failures occurred in 4 (5%) of the 79 patients in the amoxicillin group and in 8 (11%) of the 73 patients in the penicillin V group. CONCLUSIONS: These data demonstrate that once-daily amoxicillin therapy is as effective as penicillin V therapy given three times a day for the treatment of GABHS pharyngitis, and if confirmed by additional investigations, once-daily amoxicillin therapy could become an alternative regimen for the treatment of this disease.

Community-wide outbreak of group G streptococcal pharyngitis.

Although several outbreaks of group G beta-hemolytic streptococcal (GGBHS) pharyngitis have been described, doubt still remains regarding the etiologic role of GGBHS in acute pharyngitis beyond a limited number of situations. In the winter/spring of 1986/87, throat cultures were obtained from 222 consecutive children seen at a private pediatric office with acute pharyngitis and group A beta-hemolytic streptococci (GABHS) were recovered from 91 children (41%) and GGBHS from 56 children (25%). One patient had both GABHS and GGBHS isolated. This isolation rate of GGBHS was dramatically greater than in previous and subsequent years, and 67% of the GGBHS isolates occurred during an 8-week period. Results of DNA fingerprinting of the 57 isolates of GGBHS demonstrated that 43 (75%) appeared to be the same strain. The patients with GGBHS were comparable to those with GABHS with respect to clinical findings, antistreptolysin-O titer response, and clinical response to antibiotic therapy. However, patients with GGBHS were significantly older (P less than .05). This is the first well-documented, community-wide outbreak of GGBHS pharyngitis and the first respiratory outbreak of GGBHS pharyngitis in a pediatric population. GGBHS may be a more important cause of acute, treatable pharyngitis than had been previously recognized.

Lack of impact of early antibiotic therapy for streptococcal pharyngitis on recurrence rates.

To determine whether recurrence rates for group A beta-hemolytic streptococcal (GABHS) pharyngitis are related to the time of initiation of antibiotic therapy, we randomly assigned 113 patients with GABHS pharyngitis either to a group that began a 10-day course of penicillin V at the time of diagnosis or to a group that began the same antibiotic regimen after a dealy of 48 hours. Follow-up throat culture specimens were obtained 4 days, 2 months, and 4 months after the completion of antibiotic therapy, as well as during any interim episodes of acute pharyngitis. Serotyping of all GABHS isolates was performed to distinguish between recurrences with homologous serotypes and new acquisitions with heterologous serotypes. There was no significant difference between the two treatment groups in age, gender, duration of illness before enrollment in the study, initial clinical presentation, or compliance. Of the 50 patients in the immediate-treatment group, 6 (12%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. Of the 63 patients in the delayed-treatment group, 9 (14%) had homologous serotypes of GABHS isolated on one of the follow-up throat cultures. These data indicate that a 48-hour delay in the initiation of penicillin therapy for GABHS pharyngitis does not reduce the recurrence rate.

Liposome immunoassay for rapid identification of group A streptococci directly from throat swabs.

The Q Test Strep (Becton Dickinson and Co., Franklin Lakes, N.J.) is a new solid-phase liposome immunoassay for the rapid diagnosis of group A beta-hemolytic streptococcal pharyngitis. Compared with blood agar plate cultures, the Q Test Strep had a sensitivity of 91%, a specificity of 83%, a positive predictive value of 88%, and a negative predictive value of 87%. Liposome technology can be used to facilitate the rapid diagnosis of group A beta-hemolytic streptococcal pharyngitis.

Evaluation of a new latex agglutination test for detection of streptolysin O antibodies.

Acute- and convalescent-phase serum specimens were collected from 50 patients with group A streptococcal pharyngitis. The anti-streptolysin O (ASO) titer for each serum specimen was determined by using both the standard neutralization assay and the latex agglutination (LA) test (Rheumagen ASO; Biokit Inc., New Britain, Conn.). When the ASO titers derived by the two methods were compared, the correlation coefficient was 0.93. When the ability of the LA test to demonstrate a significant ASO titer rise (greater than or equal to 2 dilutions) was compared with that of the standard neutralization assay, the LA test had a sensitivity of 91%, a specificity of 86%, a positive predictive value of 83%, and a negative predictive value of 92%. Triplicate LA test determinations were performed on a subset of 31 serum specimens, and for 29 (94%), the repeated ASO titers were all within 1 dilution of each other; the width of the 95% confidence interval for the triplicate measurements of each serum specimen was +/- 32.8 IU. We found the Rheumagen ASO to be a simple, rapid LA procedure for measuring ASO titers that produces results that are highly reproducible, show little lot-to-lot variability, and are comparable to the ASO titers obtained with the standard neutralization assay.

Failure of once-daily penicillin V therapy for streptococcal pharyngitis.

To determine if a single daily dose of penicillin V would be effective in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis, 154 patients with GABHS pharyngitis were randomly assigned to receive 750 mg of penicillin V once daily for ten days or 250 mg of penicillin V three times daily for ten days. The two regimens were comparable in their ability to eradicate GABHS from the upper respiratory tract in 18 to 24 hours and in their impact on the clinical course of the disease. However, a bacteriologic treatment failure occurred in six (8%) of the 76 patients in the three-times-daily group and in 16 (22%) of the 74 patients in the once-daily group. These findings support the current recommendation that penicillin V be given in two or more divided doses for a full ten days for the treatment of GABHS pharyngitis.

The group A streptococcal carrier state. A reexamination.

Streptococcal infection usually is defined as a positive throat culture with a serologic response to group A beta-hemolytic streptococci, and a patient with a positive throat culture and no serologic response is a streptococcal carrier. Studies suggest that streptococcal carriers should show little clinical response to antibiotic therapy when compared with patients with true streptococcal infections. Patients with acute pharyngitis were divided into three groups: group 1--38 patients with negative throat cultures; group 2--72 patients with a positive throat culture and a significant rise in streptococcal antibody titers; and group 3--77 patients with positive throat cultures and no significant rise in streptococcal antibody titers. Patients in group 2 and group 3 had a comparable and dramatic clinical response to antibiotic therapy that was considerably greater than the clinical response in the patients in group 1. These findings raise questions about the appropriateness of using streptococcal antibody responses to distinguish between the streptococcal carrier state and a true streptococcal infection.

Clinical comparison of once-daily cefadroxil and thrice-daily cefaclor in the treatment of streptococcal pharyngitis.

The efficacy of cefadroxil once daily and cefaclor given 3 times daily was compared in 250 pediatric patients with group A beta-hemolytic streptococcal pharyngitis. The duration of the therapy was 10 days. Therapeutic response was based on clinical responses at 24 h and 10 days and throat cultures on days 14, and 21 or 28. Five (5%) cefadroxil-treated patients and 12 (12%) cefaclor-treated patients were still culture-positive on day 14. When the patients were stratified according to major differences between treatment groups observed at baseline, a significant difference between the treatment groups in favor of cefadroxil was found on day 14 (p = 0.020) and days 21-28 (p = 0.043). These data were confirmed by the clinical findings; failure or clinical recurrence occurred in 4.6% of cefadroxil-treated patients versus 22.1% of cefaclor-treated patients. The patients complied with the recommended drug regimen, and none experienced any significant drug-related adverse reactions. The results of this study indicate that cefadroxil given once daily for streptococcal pharyngitis is an effective and well-tolerated antimicrobial agent, and suggest that the desirable pharmacokinetic properties of cefadroxil contribute to this efficacy.

Role of Chlamydia trachomatis and Mycoplasma pneumoniae in acute pharyngitis in children.

In a group of children with acute, nonstreptococcal pharyngitis, only one (2%) of the 44 children tested showed serologic or direct-immunofluorescence evidence of a recent Chlamydia trachomatis infection. Only two (5%) of the 43 children tested showed serologic evidence of a recent Mycoplasma pneumoniae infection. Neither C. trachomatis nor M. pneumoniae appears to be an important cause of acute pharyngitis in children.

Five vs ten days of penicillin V therapy for streptococcal pharyngitis.

To determine the effectiveness of a short (five-day) course of penicillin V potassium therapy, 172 patients with group A beta-hemolytic streptococcal (GABHS) pharyngitis were randomly assigned to receive 250 mg of penicillin V potassium three times daily for either five or ten days. The patients in the two treatment groups were comparable with respect to clinical findings, compliance, and serologic response to GABHS. A bacteriologic treatment failure was defined as the presence of the same serotype of GABHS in the follow-up as in the initial throat culture and occurred in 13 (18%) of the 73 patients in the five-day treatment group and in six (6%) of the 99 patients in the ten-day treatment group. These findings support the current recommendation for a full ten days of oral penicillin V therapy for the treatment of GABHS pharyngitis.

Streptozyme test for antibodies to group A streptococcal antigens.

The ability of the Streptozyme test to identify significant antibody rises in 46 patients with streptococcal pharyngitis was comparable to, but no greater than, that of the antistreptolysin O or antideoxyribonuclease B test and inferior to that of the combined use of both the antistreptolysin O and antideoxyribonuclease B tests. Serum specimens were also simultaneously analyzed with three different lots of Streptozyme reagent. Lot-to-lot variation in the reagent resulted in a significant difference in antibody titer for 18 (19%) of the 92 sera tested. Differences among the three lots also produced variation in determining whether a significant rise in titer had occurred from the acute phase to the convalescent phase serum for a given patient. These observations raise concerns about the standardization of the Streptozyme reagent and document the need for precise identification and quantitation of the streptococcal antigens used in this product.

Once daily therapy for streptococcal pharyngitis with cefadroxil.

To determine if a single daily dose of cefadroxil would be effective in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis, 196 patients with GABHS pharyngitis were randomly assigned to receive either penicillin V 250 mg three times daily or cefadroxil 30 mg/kg once daily, for 10 days. Outcome was measured by the ability to isolate GABHS from the upper respiratory tract 18 to 24 hours after the onset of therapy, the impact on the clinical course, and the bacteriologic treatment failure rate. There was no significant difference in the number of patients in the cefadroxil and penicillin V treatment groups with throat cultures positive for GABHS at the 18 to 24-hour follow-up visit (0% and 2%, respectively), and the clinical responses of the patients in the two treatment groups were similar. Of the 99 patients in the three times daily penicillin V group, six (6%) had strains of GABHS isolated on one of the follow-up cultures that were identical to the strains isolated from their initial throat cultures and were considered to have bacteriologic treatment failures. Of the 96 patients in the once daily cefadroxil group, two (2%) were considered to have bacteriologic treatment failures. A single daily dose of cefadroxil appears to be as effective in the treatment of GABHS pharyngitis in this population as penicillin V given three times daily.

Antigen detection test for streptococcal pharyngitis: evaluation of sensitivity with respect to true infections.

The clinical significance of false-negative results on antigen detection tests for group A beta-hemolytic streptococcal (GABHS) pharyngitis (negative test results and positive culture) has yet to be determined. We recently compared the Culturette Brand Ten-Minute Group A Strep ID Kit with blood agar cultures in 313 patients with pharyngitis, 257 (82%) of whom had positive throat cultures for GABHS. The Culturette Brand test had a sensitivity of 88%, specificity of 96%, a positive predictive value of 99%, and negative predictive value of 64%. More than half of the false-negative Culturette Brand test results occurred in children with less than 10 GABHS colonies on throat culture (1+ culture). When these 1+ cultures were not considered positive, the sensitivity of the Culturette Brand test was 93%. The sensitivity of the Culturette Brand test increased with an increased degree of positivity of the corresponding throat culture. Of the 31 children with false-negative Culturette Brand test results, 14 (45%) had a significant streptococcal antibody response; of the 224 children with true-positive Culturette Brand test results (positive test results and positive culture) from whom serologic data were available, 114 (51%) had a significant streptococcal antibody response. This difference is not statistically significant. These findings suggest that almost half of patients with false-negative results on antigen detection tests for GABHS pharyngitis have true infections (positive culture and antibody rise) and are not merely streptococcal carriers.

Effect of antibiotic therapy on the clinical course of streptococcal pharyngitis.

We examined the effect of antibiotic therapy on the clinical course of group A beta-hemolytic streptococcal (GABHS) pharyngitis in 260 children. After a throat culture had been obtained, each child was evaluated for the presence of predetermined signs and symptoms, and was then randomized in a double-blind manner to receive penicillin V, cefadroxil, or placebo. Of the 194 children with throat cultures positive for GABHS, 68 received penicillin V, 70 received cefadroxil, and 56 received placebo. Approximately 18 to 24 hours later, each patient returned for reevaluation. Significantly fewer children who had received either penicillin or cefadroxil had persistence of each of the three objective signs and each of the three subjective symptoms than did children who had received placebo. In addition, the evaluating physician, parents, and patients all believed that significantly fewer of the patients given antibiotic failed to demonstrate overall clinical improvement.