Steven M. Marsocci

Penicillin failure in streptococcal tonsillopharyngitis: causes and remedies.

Synopsis. Penicillin administered for 10 days has been the treatment of choice for group A beta-hemolytic streptococcal tonsillopharyngitis since the 1950s. The bacteriologic failure rate of 10 days of penicillin therapy ranged from approximately 2 to 10% until the early 1970s. Beginning in the late 1970s bacteriologic and clinical failure rates with penicillin therapy began to increase steadily over time and are now reported to be approximately 30%. The primary cause of penicillin treatment failure in streptococcal tonsillopharyngitis may be lack of compliance with the 10-day therapeutic regimen. Other causes of penicillin treatment failure include reexposure to Streptococcus-infected family members or peers; copathogenicity, in which bacteria susceptible to a class of drugs are protected by other, colocalized bacterial strains that lack the same susceptibility; antibiotic-associated eradication of normal protective pharyngeal flora; and penicillin tolerance, whereby streptococcal bacteria repeatedly or continuously exposed to sublethal concentrations of antibiotic become increasingly resistant to eradication. Although 10 days of penicillin therapy is effective in the management of tonsillopharyngitis for many patients, multiple factors may, singly or together, cause treatment failure. A number of antibiotics, particularly the cephalosporins, have been demonstrated to be superior to penicillin at eradicating group A beta-hemolytic Streptococcus, and several are effective when administered for 4 to 5 days. Conclusions. Ten days of penicillin therapy may not be the best therapeutic choice for all pediatric patients. Other antibiotics, shortened courses of the cephalosporins in particular, may be preferable in some cases.

Recurrent group A streptococcal tonsillopharyngitis.

OBJECTIVE To examine the epidemiology and treatment of group A beta-hemolytic streptococcal (GABHS) recurrent tonsillopharyngitis in private pediatric practice. METHODS This was a retrospective chart review study covering the time span 1975 to 1996 involving 2140 GABHS episodes. Diagnosis was based on acute clinical symptoms and laboratory confirmation (throat culture or positive rapid antigen detection test) of GABHS. RESULTS Eighty percent (n=1721) of the episodes evaluated were treated with penicillin or amoxicillin; 352 (20.5%) of these were followed by a recurrence within 30 days and 519 (30.2%) within 60 days. GABHS recurrences within 30 days after penicillin/amoxicillin treatment rose from 9% in 1975 to 1979 to 25.9% in 1980 to 1984, 24.2% in 1985 to 1989, 22.4% in 1990 to 1994 and 25.9% in 1995 to 1996 (P < 0.02); 53.4% of the recurrences were associated with symptoms and signs of GABHS tonsillopharyngitis, 9.9% were asymptomatic and 36.7% could not be classified. Recurrences within 60 days after penicillin/ amoxicillin treatment rose from 10.7% in 1975 to 1979 to 38.7% in 1980 to 1984, 39.0% in 1985 to 1989, 31.7% in 1990 to 1994 and 37.5% in 1995 to 1996 (P < 0.001). Recurrent GABHS infections occurred more frequently in younger children (1 to 8 years of age, 21.3% recurrence rate) than in adolescents (13 to 19 years, 5% recurrence rate; P=0.002). Recurrences within 30 days occurred more often after therapy with penicillin (21.8% of 1581 episodes) than with cephalosporins (8.6% of 254 episodes) (P < 0.0001) or with macrolides (14.0% of 143 episodes, P=0.04). Recurrence rates were unaffected by patient gender or season of the year. CONCLUSIONS Recurrent GABHS infections occur more frequently in the 1990s than the 1970s, occur more frequently in children younger than 8 years of age than in adolescents and occur more frequently after penicillin treatment than with alternative antibiotic therapy.

Outcomes After Judicious Antibiotic Use for Respiratory Tract Infections Seen in a Private Pediatric Practice

Background. Most respiratory tract infections (RTIs) in children have a viral cause, they resolve on their own, and antibiotics need not be prescribed. Objective. We sought to provide evidence that judicious antibiotic use can be accomplished in private pediatric practice without observing an increase in return office visits or in the rate of bacterial infections that may follow. Study Design. This was a prospective 12-month study from July 1, 1996 through June 30, 1997. On the same 1 day each week, a representative convenience sample of acute respiratory tract illness patients was enrolled, and laboratory studies performed as appropriate, including viral cultures on all. Children were then followed for 30 days to ascertain the outcomes of not prescribing antibiotics except when specific bacterial infections were present at the initial visit. Results. Three hundred eighty-three children were enrolled; 293 (77%) did not receive antibiotics at the enrollment visit. Ninety children (23%) received antibiotics based on a diagnosis of acute otitis media (n = 53), acute streptococcal tonsillopharyngitis (n = 18), or other presumed or documented bacterial infections (n = 19). An unscheduled return visit related to the initial visit occurred for 86 (29%) of the 293 children not receiving antibiotics initially and in 40 (44%) of 90 children receiving antibiotics initially. Eighty-seven children (23%) had positive viral culture results. The most frequently isolated viruses were adenovirus, enterovirus, parainfluenzae virus, and influenza virus. Conclusion. Children with RTIs without a concomitant presumed or proven bacterial infection do not require antibiotics. In this busy office practice, >75% of the children presenting with an RTI did not have a presumed or proven bacterial infection. These children did not have a higher rate of return office visits or an increase in bacterial infections. This reinforces the judicious use of antibiotics in managing children with RTIs. outcomes, antibiotic, respiratory infections.

Comparison of a three-component acellular pertussis vaccine with whole cell pertussis vaccine in two-month-old children.

An acellular pertussis vaccine (DTaP) containing pertussis toxoid, filamentous hemagglutinin and the 69-kDa outer membrane protein (pertactin) was compared with United States-licensed whole cell pertussis vaccine (DTwP) as a three dose sequence at 2, 4 and 6 months of age. Eighty infants were enrolled; 62 received DTaP and 18 received DTwP. Sixty-two infants had preimmunization and 1 month postimmunization sera available for pertussis antibodies. No infant experienced a serious adverse reaction. Significantly fewer infants in the DTaP group experienced irritability (P < 0.001) and moderate to severe injection site pain and redness (P < 0.001, and P = 0.03, respectively). The DTaP group also had significantly greater increases in geometric mean titers of antibodies against filamentous hemagglutinin (P < 0.001) and pertactin (P = 0.006). This three-component DTaP vaccine induced an antibody response to pertussis toxin, filamentous hemagglutinin and pertactin but caused fewer adverse reactions than DTwP when administered as a primary series of immunization to 2-month-old infants.

Efficacy of Penicillin vs. Amoxicillin in Children with Group A Beta Hemolytic Streptococcal Tonsillopharyngitis

The purpose of this study was to compare the bacteriologic and clinical efficacy of oral penicillin versus amoxicillin as first-line therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis. The prospective observational study was conducted over 18 months (January 2000-June 2001). Children enrolled had acute onset of symptoms and signs and a laboratory-documented GABHS tonsillopharyngitis illness. Follow-up examination and laboratory testing occurred 10 ± 4 days following completion of treatment. In total, 389 patients were enrolled (intent-to-treat group): 195 received penicillin V and 194 received amoxicillin. Fifty-six of the penicillin-treated and 57 amoxicillin-treated patients refused to take the drug, or were noncompliant, or did not return for the follow-up visit, leaving 276 patients in the per-protocol group: 139 penicillin-treated and 137 amoxicillin-treated. Bacteriologic cure for amoxicillin-treated children occurred in 76% versus 64% in the penicillin-treated children (p=0.04). The clinical cure rate for amoxicillin-treated children was 84% compared to 73% in the penicillin-treated children (p=0.03). Since treatment allocation was not randomized, logistic regression analysis was used to adjust for treatment group differences. The odds ratio (OR) estimate for cure for patients in the amoxicillin versus penicillin V treatment group remained significant (OR=1.84, 95% confidence interval 1.02-3.29); the same was true for clinical cure (OR=1.99, 95% CI=1.02-3.87). Amoxicillin may be superior to penicillin for bacteriologic and clinical cure of GABHS tonsillopharyngitis.

Acellular Pertussis Vaccine Boosters Combined With Diphtheria and Tetanus Toxoid Boosters for Adolescents: Safety and Immunogenicity Assessment When Preceded by Different 5-Dose DTaP/DTwP Schedules

A sixth dose of tetanus, diphtheria, acellular pertussis (Tdap) vaccine in adolescents might produce a differing reactogenicity and/or immunogenicity response depending on the composition of the 5 prior doses of DTaP or DT-whole cell pertussis (DTwP) vaccine. Reactions and immune responses following receipt of the Sanofi Pasteur (Adacel) and GlaxoSmithKline (Boostrix) Tdap vaccines were assessed in 229 adolescents. No differences were observed for reactions to either Tdap vaccine regardless of the prior DTaP/DTwP vaccination history. Seroprotective levels and antibody concentrations were comparable regardless of prior DTaP/DTwP vaccine history. A sixth sequential dose of Tdap after 5 doses of DTaP appears safe and immunogenic.

A comparative evaluation of the safety and immunogenicity of a single dose of unbuffered oral rhesus rotavirus serotype 3, rhesus/human reassortant serotypes 1, 2 and 4 and combined (tetravalent) vaccines in healthy infants

To assess safety and immunogenicity, 213 healthy infants aged 6 weeks to 4 months were randomized to receive a single dose of placebo, a 10(4) or 10(5) p.f.u. dose of rhesus rotavirus (RRV) serotype 3, human-RRV reassortant (VP-7 serotypes 1, 2 or 4) or a 10(4) or 10(5) p.f.u. dose of tetravalent rotavirus vaccine (containing equal parts of serotype 1, 2, 3 and 4 strains). The infants were fed ad libitum before and after vaccination; no buffer was used. For 7 days after vaccination, potential vaccine side effects were monitored, and no significant differences were noted for any symptom evaluated among the single serotype, tetravalent or placebo groups. Sera, obtained before and 28 days after vaccination, were measured for antibody to rotavirus by IgG, IgA and IgM enzyme-linked immunosorbent assay in all subjects, and by neutralizing antibody to the individual serotypes by plaque reduction in placebo and tetravalent vaccinees. The serological response rates for serotypes 1, 2, 3, 4 and the tetravalent vaccine were 25, 12, 19, 11 and 22%, respectively, at 10(4) p.f.u.; 47, 50, 35, 29 and 61%, respectively, at 10(5) p.f.u.; and 37% for placebo. The tetravalent vaccine was more immunogenic at 10(5) than at 10(4) p.f.u. (p = 0.04). Grouped together, the vaccines at 10(5) p.f.u. (single serotype and tetravalent) were more immunogenic than the vaccines at 10(4) p.f.u. (38 of 85 versus 17 of 94 seroresponders; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

White Blood Cell Count Can Aid Judicious Antibiotic Prescribing in Acute Upper Respiratory Infections in Children

Fifty percent or more of children with upper respiratory infections (URIs) and nonspecific febrile illnesses (e.g., children febrile, anorexic, decreased activity, irritable) receive unnecessary antibiotics from community-based physicians. This study was undertaken to show that white blood cell (WBC) count testing can aid physicians in avoiding antibiotic prescribing when managing children with URIs, and nonspecific febrile illnesses. A prospective, 3-year study was conducted in a community-based pediatric practice. A weekly convenience sample (Tuesdays) of acute URI and febrile patients ages 3 months to 21 years was studied. Data collected on enrollment included: age, gender, duration of illness, recent/current antibiotic use, temperature, symptoms, signs, laboratory testing (WBC count, cultures), diagnosis and treatment. Similar data on any illness visits in the previous 2 weeks and the subsequent 2 weeks after enrollment were collected. Viral culture specimens were obtained on a subset. The use of the WBC count was assessed, including obviating antibiotic prescription, frequency of related follow-up visits, and the occurrence of subsequent bacterial infections. Of 1,956 patients with respiratory or febrile illness enrolled, 1,219 (62%) had a diagnosis established by history and examination (e.g., acute otitis media) and 737 (38%) did not. Of the 737 patients without an established diagnosis, 386 (52%) did not receive an antibiotic because they did not appear particularly ill, their temperature was less than 101 °F, and parents were not demanding antibiotics, leaving 351 (48%) patients who appeared ill, had a temperature greater than 101 °F, and parents were demanding an antibiotic or physicians were inclined to give an antibiotic. A WBC count was performed on these 351 children; 337 children (96%) had a WBC count less than 15,000/mm3, and 14 (4%) had a W1BC 15,000/mm3 or greater. An antibiotic was prescribed for 13 of the 14 children with a WBC count greater than 15,000/mm3. With this approach, return office visits in the following 2 weeks were infrequent (13% of 737 patients), and no child had significant bacterial illness that was missed. With selective use of WBC count testing near-complete avoidance of unnecessary antibiotic use can be achieved in caring for children with URI and nonspecific febrile illness without adverse outcomes.

Efficacy of Cephalexin Two vs. Three Times Daily vs. Cefadroxil Once Daily for Streptococcal Tonsillopharyngitis

The purpose of this study was to compare the bacteriologic and clinical efficacy of oral cephalexin twice vs. three times daily vs. cefadroxil once daily as therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis. A prospective open-label, observational cohort study was conducted over 18 months (January 2000-June 2001). Children enrolled had an acute onset of symptoms and signs of a tonsillopharyngeal illness and a laboratory-documented GABHS infection. Follow-up examination and laboratory testing occurred 21 ± 4 days following enrollment. Two hundred seventy-one patients were enrolled (intent to treat group): 63 received cephalexin twice daily, 124 received cephalexin three times daily, and 84 received cefadroxil once daily. Fifty-three children did not return for the follow-up visit, leaving 218 patients in the per-protocol group: 54 cephalexin twice daily treated, 94 cephalexin 3-times daily treated, and 70 cefadroxil once-daily treated. In the per-protocol group, bacteriologic cure for those treated with cephalexin twice daily was 87%, for cephalexin 3 times daily, it was 81% and for cefadroxil once daily it was 81% (p=0.61). The clinical cure rate for cephalexin twice-daily treatment was 91%; for three-times daily, it was 86%; and for cefadroxil once daily, it was 84% (p=0.56). Because treatment allocation was not randomized, logistic regression analysis was used to adjust for treatment group differences. Younger age of patient was significantly associated with bacteriologic (p=0.04) and clinical (p=0.01) failure independent of treatment group but in the adjusted logistic model no differences were found among the 3 treatment regimens. Cephalexin dosed twice daily or three times daily and cefadroxil dosed once daily appear equivalent in bacteriologic and clinical cure of GABHS tonsillopharyngitis.