Herbert W. Clegg

Treatment of streptococcal pharyngitis with once-daily compared with twice-daily amoxicillin : A noninferiority trial

Background: Two relatively small previous studies comparing once-daily amoxicillin with conventional therapy for group A streptococcal (GAS) pharyngitis reported similar rates of bacteriologic success for each treatment group. The purpose of this study was to further evaluate once-daily amoxicillin for GAS pharyngitis in a larger study. Methods: In a single pediatric practice, from October through May for 2 consecutive years (2001–2003), we recruited children 3 to 18 years of age who had symptoms and signs suggestive of GAS pharyngitis. Patients with a positive rapid test for GAS were stratified by weight (<40 kg or ≥40 kg) and then randomly assigned to receive once-daily (750 mg or 1000 mg) or twice-daily (2 doses of 375 mg or 500 mg) amoxicillin for 10 days. We determined bacteriologic failure rates for GAS in the pharynx from subsequent swabs taken at 14 to 21 (visit 2) and 28 to 35 (visit 3) days after treatment initiation. We conducted a randomized, controlled, investigator-blinded, noninferiority trial to evaluate whether amoxicillin given once daily would have a bacteriologic failure rate no worse than that of amoxicillin given twice daily within a prespecified margin of 10%. GAS isolates were characterized to distinguish bacteriologic failures from new acquisitions. Adverse events were described and adherence was evaluated by review of returned daily logs and dosage bottles. Results: Of 2139 potential study patients during the 2-year period, we enrolled 652 patients, 326 into each treatment group. Children in the 2 groups were comparable with respect to all demographic and clinical characteristics except that children <40 kg more often presented with rash in each treatment group. At visit 2, failure rates were 20.1% (59 of 294) for the once-daily group and 15.5% (46 of 296) for the twice-daily group (difference, 4.53%; 90% confidence interval [CI], −0.6 to 9.7). At visit 3, failure rates were 2.8% (6 of 216) for the once-daily group and 7.1% (16 of 225) for the twice-daily group (difference, −4.33; 90% CI, −7.7 to −1.0). Gastrointestinal and other adverse events occurred in the once-daily treatment group with a frequency comparable to that in the twice-daily treatment group. Presumed allergic reactions occurred in 0.9% (6 of 635). More than 95% (516 of 541) of patients complied with 10 days of therapy with no significant differences between groups. Conclusions: We conclude that amoxicillin given once daily is not inferior to amoxicillin given twice daily. Gastrointestinal and other events did not occur significantly more often in the once-daily treatment group. From the data in this large, investigator-blinded, controlled study, once-daily amoxicillin appears to be a suitable regimen for treatment of GAS pharyngitis.

Comparison of a latex agglutination test and four culture methods for identification of group A streptococci in a pediatric office laboratory

A latex agglutination test and four culture methods for the detection of group A hemolytic streptococci were compared in a pediatric office laboratory. The anaerobic (GasPak) and Detekta-Kit methods produced the highest recovery rates, but aerobic incubation of 5% blood agar plates gave very acceptable results (sensitivity 92%, or 98% if the 1+ positive cultures were eliminated; specificity 100%), and had fewer disadvantages. Delaying inoculation of plates for 2 to 6 hours resulted in significantly greater numbers of strongly positive (3+ and 4+) cultures. The group A selective sheep blood agar media as used in this study offered no advantage. The Culturette test had a sensitivity of 72% and specificity of 98%, compared with the GasPak method, and 77% and 97%, respectively, compared with standard aerobic cultures. Thus it appears too insensitive to be used alone, but might complement culture methods in selected patients.

Comparison of an optical immunoassay technique with two culture methods for the detection of group A streptococci in a pediatric office

For detecting group A beta-hemolytic streptococci in an office setting, an optical immunoassay method was compared with two culture methods. The sensitivity and specificity of OIA as compared with 5% sheep blood agar cultures were 91.4% and 95.6%, and as compared with a Todd-Hewitt broth method were 90.4% and 94.1%, respectively.

Extrapharyngeal group A streptococcus infection: diagnostic accuracy and utility of rapid antigen testing

Background. Antigen tests have been well-studied and are widely used in pediatric practice for rapid detection of group A Streptococcus (GAS) infections in the throat, but they have not been examined sufficiently for the detection of infection of skin sites, such as the perineal region or impetiginous lesions. Methods. During the 3-year period 1999 to 2002, we evaluated 239 patients with suspected GAS skin infection, in 5 pediatric practices, using 3 Dacron swabs for each site. The first swab was tested in the pediatric office laboratory with an antigen detection kit. For the first 91 patients, the Abbott Test Pack Plus antigen detection test (ADT) was used. The Abbott Signify Strep A ADT was used to test subsequent patients. The second swab was tested with BD Directigen 1-2-3 ADT in the hospital laboratory. The third swab was placed in modified Stuart’s transport medium for comparison of recovery of GAS from culture in broth or on agar. A positive culture served as the reference standard. Test performance and test accuracy were determined for each ADT. Results. Of the 247 ADTs and cultures performed on 239 patients, 91 with suspected skin infection were tested with the Test Pack Plus test, 149 with the Signify Strep A test and 247 with the Directigen test. Eighty-six (35%) cultures were positive, 73 from perineal sites (54 rectal, 13 vaginal, 6 penile) and 13 from impetiginous lesions. There was 100% concordance for the 86 cultures positive for GAS in a comparison between dry Dacron swabs and swabs that had been placed in modified Stuart’s transport medium. Test Pack Plus and Signify Strep A ADTs had similar performance characteristics for skin infections: sensitivity, 92 and 88%; specificity, 99 and 97%; positive predictive value, 96 and 94%; and negative predictive value, 97 and 93%. Directigen ADT had sensitivity 78%, specificity 100%, positive predictive value 100% and negative predictive value 89%. Accuracy for the tests varied from 92 to 97%. Conclusion. Tests designed to detect GAS carbohydrate antigen in patients with pharyngitis can be used rapidly and accurately to detect GAS antigen in patients with cutaneous lesions suspected of GAS infection.

Nail Dystrophy in Congenital Cutaneous Candidiasis

Abstract: Congenital cutaneous candidiasis (CCC) is usually a benign condition characterized by various skin manifestations and is rarely associated with nail changes. We report a premature infant with CCC who developed dystrophy of all 20 nails at about 1 month of age. Nail dystrophy due to Candida albicans in the young infant may be differentiated from other congenital or hereditary nail malformations by appearance, recovery of the organism in nail culture, and complete resolution over a period of several months.

Furosemide-associated fever

We describe a 5-month-old infant who had fever of unknown origin leading to an exhaustive evaluation during a 7-week period. Fever caused by the use of furosemide was proved; the fever resolved after discontinuation of this medication and recurred after its reintroduction.

Comparison of immediate and delayed culture methods for isolation of group A streptococci.

Recovery rates of Group A beta-hemolytic streptococci in throat cultures from 300 children were studied using three different methods. The swabs were streaked onto plates immediately, streaked from the same dry swabs held at room temperature for 3 to 6 hours and streaked from swabs held in transport media at room temperature for 3 to 6 hours. The cultures were processed in a pediatric office and interpreted by a microbiologist. The recovery rates were similar for the three methods, but the cultures were easier to interpret when the swzabs had been allowed to dry before streaking as a result of a decrease in the normal flora on these plates. In a separate study the recovery of Group A beta-hemolytic streptococci from 187 swabs was identical whether the swabs were streaked at 3 to 6 hours or at 18 to 24 hours.