A prospective observational study of 5-, 7-, and 10-day antibiotic treatment for acute otitis media.

OBJECTIVE: To compare 5-, 7- and 10-day duration of antibiotic therapy for acute otitis media (AOM) in children. STUDY DESIGN AND SETTING: Prospective nonrandomized 1-year evaluation of 3 treatment durations for AOM in a private pediatric setting. Outcomes assessed at 14 +/- 4 days after start of therapy with clinical response categorized as cure, improvement, or failure. RESULTS: A total of 2172 children were studied; 46.4% were < or =2-years-old. Antibiotics used were amoxicillin (61.9% of patients), trimethoprim/sulfamethoxazole (11.7%), cephalosporins (14.2%), amoxicillin/clavulanate (5.2%), and macrolides/azalides (4.8%). No overall difference in outcome was observed comparing the 5-day (n = 707), 7-day (n = 423), or 10-day (n = 1042) treatments, including children < or =2-years-old. However, in the subset who had an episode of AOM in the preceding month, outcome differed; 5-day treatment was followed by more frequent failure than 10-day treatment (P < 0.001). In logistic regression analysis, variables identified as contributing to a cure were: >2-years-old (P < 0.0001), no AOM in the preceding month (P = 0.07), or preceding 12 months (P = 0.03). CONCLUSIONS: Our study supports the transition from 10 to 5 days for standard AOM antibiotic treatment duration in most patients. A 10-day regimen may be superior in children who have experienced an episode of AOM within the preceding month, a known risk factor for resistant bacterial infection in the otitis-prone patient.

Penicillin failure in streptococcal tonsillopharyngitis: causes and remedies.

UNLABELLED: 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.

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.

Variables influencing penicillin treatment outcome in streptococcal tonsillopharyngitis.

OBJECTIVE: To examine whether penicillin treatment success for group A beta-hemolytic streptococcal tonsillopharyngitis is influenced by patient age, number of days ill prior to initiation of treatment, number of prior episodes, season, total dosage (milligrams per kilogram), and frequency of administration (2 vs 3 times daily). METHODS: Four hundred seventy-eight children, adolescents, and young adults aged 2 to 21 years with acute symptoms compatible with the clinical diagnosis of group A beta-hemolytic streptococcal tonsillopharyngitis and a positive streptococcus rapid antigen detection test result were enrolled (intent-to-treat group). Patients were randomly assigned to receive penicillin V potassium, 250 mg 3 times daily (n = 239) or 500 mg 2 times daily (n = 239). Randomization was independent of patient body weight and treatment was for 10 days with both regimens. Follow-up examinations occurred, and cultures were obtained at 14 to 21 days after the initiation of antibiotic therapy; those with group A beta-hemolytic streptococcus isolated from a throat culture and who returned for follow-up were assessed for outcome (n = 359). RESULTS: Using a logistic regression analysis with a stepwise variable selection, we found the major variables associated with penicillin treatment success to be the number of days ill prior to initiation of treatment (P = .001; odds ratio, 1.55 [95% confidence interval, 1.2-2.1]) and the age of the child when infected (P = .004; odds ratio, 1.14 [95% confidence interval, 1.05-1.25]). The number of prior episodes within the preceding year, the season, the total daily penicillin dose (range, 8-76 mg/kg), and 2 vs 3 times daily dosing did not significantly alter treatment outcome. CONCLUSION: Treatment after 2 days of illness and of adolescent patients increases penicillin treatment success for group A beta-hemolytic streptococcal tonsillopharyngitis.

Incidence of streptococcal carriers in private pediatric practice.

OBJECTIVE: To determine the incidence of group A beta-hemolytic streptococcus (GABHS) carriers in children who are well, in children seen with presumed and documented viral illnesses with sore throat, and in children after treatment of acute GABHS tonsillopharyngitis with 10 days of oral penicillin V potassium, oral cephalosporins, or macrolides. METHODS: Prospective collection of clinical and microbiologic data from October 1996 to June 1997 in a private pediatric practice were obtained from children who were asymptomatic and well, from children with both presumed (and documented) viral sore throats, and from children who had completed a full antibiotic treatment course for acute GABHS throat infections. RESULTS: The incidence of GABHS carriers was 2.5% among well children (n = 227), 4.4% among children with upper respiratory tract infections including sore throat of presumed viral etiology (n= 296), and 6.9% among children with upper respiratory tract infections including sore throat from whom viruses were isolated (n = 87). Following 10 days' treatment of acute GABHS tonsillopharyngitis, 81 (11.3%) of 718 children treated with penicillin, 22 (4.3%) of 508 children treated with an oral cephalosporin, and 10 (7.1%) of 140 children treated with a macrolide were GABHS carriers (P<.001). CONCLUSIONS: A small percentage of children seen in private pediatric practices who are well or who have apparent viral upper respiratory tract infections with sore throat are GABHS carriers. Penicillin treatment of acute GABHS tonsillopharyngitis results in a higher GABHS carriage rate than occurs following treatment with cephalosporins and macrolides.

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.

Antibody response and reactions to completion of a four-dose series with a two- or three-component acellular pertussis vaccine compared to whole cell pertussis vaccine.

We compared the reactions and immunogenicity of DT acellular pertussis (DTaP) vaccines containing pertussis toxoid (PT) and filamentous haemagglutinin (FHA) (2-component DTaP) or PT, FHA and pertactin (PRN) (3-component DTaP vaccine) with a whole cell (DTwP) vaccine as a fourth-dose booster in 158 children (15-20 months old) who had received 3 primary vaccine doses with the same vaccines at 2, 4 and 6 months of age. Randomization was 3:1 for DTaP:DTwP and all children received concomitant oral polio vaccine (OPV). Fever (> 38 degrees C), irritability, local injection site erythema (> 10 mm), swelling (> 10 mm), and pain (moderate or more) were assessed for 72 h after booster vaccination. DTwP vaccinees had a higher incidence of fever (29.4%) and injection-site pain (45.7%) than 3-component DTaP vaccinees (fever, 9.6%, p < 0.02; injection-site pain, 3.8%, p < 0.01); 2-component DTaP vaccinees had less injection-site pain (8.3%, p < 0.01). Pre- and post-vaccination immunoglobulin G (IgG) antibody was measured by enzyme-linked immunosorbent assay (ELISA). Pre- and post anti-PT levels were similar for all 3 vaccine groups. Anti-FHA antibody was higher pre- and post-vaccination for both DTaP vaccine groups compared with the DTwP vaccinees (p < 0.01 for all comparisons). For 3-component DTaP vaccinees, anti-PRN antibody was higher pre- and post-vaccination compared to DTwP vaccinees (p < 0.01 for both comparisons). Tetanus antibody was higher pre- and post-vaccination for DTwP versus both DTaP vaccine groups, and diphtheria antibody was similar pre- and post-vaccination for all 3 groups. These 2- and 3-component DTaP vaccines produce less common reactions and comparable or higher antibody to the components they contain (except tetanus) than DTwP vaccine when given as a booster to 15- to 20-month-old children previously primed with the same vaccine.

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.

Safety and immunogenicity of an acellular pertussis vaccine booster in 15- to 20-month-old children previously immunized with acellular or whole-cell pertussis vaccine as infants.

The objective of this study was to evaluate reactogenicity and immunogenicity of the recently US-licensed Connaught/BIKEN (C/B) acellular DTP (ADTP) vaccine as a booster for children aged 15 to 20 months after they had received either the C/B ADTP or the US-licensed Connaught whole-cell DTP (WDTP) vaccine as infants. After infants had received either three doses of C/B ADTP (n = 109) or three doses of WDTP vaccine (n = 30) at 2, 4, and 6 months of age according to a 3:1, randomized, prospective design, they all received booster doses at 15 to 20 months of age with C/B ADTP. Fever > 101 degrees F (38.3 degrees C), irritability, injection site redness > or = 1 inch, injection site swelling, and injection site pain, among other reactions, were monitored for 14 days after vaccination. IgG antibody to pertussis toxin (PT) and filamentous hemagglutinin were analyzed by enzyme-linked immunosorbent assay and neutralizing antibody to PT was measured by Chinese hamster ovary (CHO) cell assay. No significant differences were observed between the WDTP- and ADTP-primed infants following their ADTP booster for any of the monitored reactions within 72 hours of vaccine administration or in the 4 to 14 days after vaccination. Prior to the ADTP booster, antibody levels were higher in children who had received ADTP compared with those who had received WDTP vaccine as infants for PT antibody as measured by enzyme-linked immunosorbent assay and CHO cell assay. Higher levels of IgG antibody following the ADTP booster were observed to filamentous hemagglutinin and to PT in ADTP-primed compared with WDTP-primed children.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of a diphtheria and tetanus toxoids and bicomponent acellular pertussis vaccine with diphtheria and tetanus toxoids and whole-cell pertussis vaccine in infants.

OBJECTIVE: To compare the reactogenicity and immunogenicity of a diphtheria and tetanus toxoids and two-component acellular pertussis (ADTP) vaccine with a US-licensed whole-cell (WDTP) vaccine. SETTING: General pediatric practice in suburban Rochester, NY. DESIGN: Prospective, double-blind, randomized study. PARTICIPANTS: One hundred ten infants were studied; 88 (80%) received ADTP and 22 (20%) received WDTP at ages 2, 4, and 6 months. INTERVENTION: Vaccination. MEASUREMENTS/MAIN RESULTS: Temperature of 38.3 degrees C or higher (P = .03) and moderate or severe injection-site pain (P = .02) occurred less frequently in infants receiving ADTP than those receiving WDTP for the combined three doses. Following the third dose, ADTP vaccination produced higher antibody responses than WDTP to pertussis toxin (geometric mean enzyme-linked immunosorbent assay IgG was 52.2 vs 12.5; P < .001) and to filamentous hemagglutinin (geometric mean IgG was 182.8 vs 3.5; P < .001). No interference in the diphtheria or tetanus antibody responses was observed in recipients of the ADTP vaccine. CONCLUSIONS: This two-component ADTP vaccine, when given as a primary infant series, produces fewer adverse effects and greater immunogenicity to the two pertussis components that it contains than US-licensed WDTP vaccine.

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)

Acellular pertussis vaccination of 2-month-old infants in the United States.

This is the first study in children from the United States that evaluates the immunogenicity of and adverse reactions to the Connaught/Biken two-component acellular pertussis vaccine compared with whole-cell pertussis vaccine when given as a primary immunization series at 2, 4, and 6 months of age. Three hundred eighty infants were studied; 285 received acellular diphtheria-tetanus toxoids-pertussis (DTP (ADTP)) and 95 received whole-cell DTP (WDTP). Following the third dose, ADTP vaccination produced higher antibody responses than WDTP to lymphocytosis-promoting factor (enzyme-linked immunosorbent assay IgG geometric mean titer (GMT) = 131 vs 9 and Chinese hamster ovary cell assay GMT = 273 vs 16) and to filamentous hemagglutinin (IgG GMT = 73 vs 10) (all P less than .0001). Agglutinin responses were higher in WDTP compared with ADTP recipients (GMT = 50 vs 37; P = .02). Local reactions were fewer for all three doses following ADTP vaccination. Fever, irritability, drowsiness, anorexia, vomiting, and unusual crying all occurred less frequently in ADTP compared with WDTP recipients for one or more of the three doses. We conclude that this two-component ADTP vaccine when given as a primary series produces greater immunogenicity and fewer adverse effects than the currently licensed WDTP vaccine.

Clinical reactions and immunogenicity of the BIKEN acellular diphtheria and tetanus toxoids and pertussis vaccine in 4- through 6-year-old US children.

OBJECTIVE--To compare the immunogenicity and reactogenicity of a two-component acellular pertussis vaccine with a whole-cell diphtheria and tetanus toxoids and pertussis vaccine (W-DTP) when administered as a booster to children 4 through 6 years of age. DESIGN--This was a randomized, double-blind study. SETTING--Children in this study were from three general pediatric practices (two were private, one was university-affiliated). PARTICIPANTS--Three hundred and sixteen 4- through 6-year-old children who had received four previous W-DTP immunizations at the recommended times were studied. SELECTION PROCEDURES AND INTERVENTIONS--Children were randomly assigned in a 1:3 ratio to receive either W-DTP or one of three lots of acellular diphtheria and tetanus toxoids and pertussis vaccine (A-DTP). The A-DTPs contained 3.75 micrograms each of lymphocytosis promoting factor and filamentous hemagglutinin protein nitrogen per 0.5 mL and the same concentrations of diphtheria and tetanus toxoids as W-DTP. Serum samples were obtained on the day of immunization and 4 to 6 weeks later. Adverse reactions were recorded by parents at 6, 24, 48, and 72 hours. MEASUREMENTS AND RESULTS--An indirect enzyme-linked immunosorbent assay (ELISA) method determined IgG antibody response to lymphocytosis promoting factor, filamentous hemagglutinin, and tetanus toxoid; a CHO cell assay measured neutralizing antibodies to pertussis toxin; and serum neutralization on VERO cells assayed diphtheria antitoxin. One month after booster doses were administered, the geometric mean antibody levels for A-DTP vs W-DTP were IgG filamentous hemagglutinin, 362 vs 104 ELISA U/mL; IgG lymphocytosis promoting factor, 408 vs 81 ELISA U/mL; CHO cell, 210 vs 107; diphtheria, 21.7 vs 12.1 U/mL; and tetanus, 2.86 vs 2.04 Eq/mL. Following immunization with A-DTP, local and systemic adverse experiences were 30% to 50% and 20% to 30% fewer, respectively, as compared with W-DTP. CONCLUSIONS--The BIKEN A-DTP vaccine used in this study demonstrates enhanced immunogenicity to lymphocytosis promoting factor, filamentous hemagglutinin, and other measured antigens and less reactogenicity compared with licensed W-DTP [corrected].

Effect of dose and a comparison of measures of vaccine take for oral rhesus rotavirus vaccine. The Maryland Clinical Studies Group.

Ninety-six healthy infants ages 2 to 5 months received rhesus rotavirus vaccine serotype 3 (RRV) as a single dose of 10(3), 10(4) or 10(5) plaque-forming units (pfu) in this double-blinded, placebo-controlled study. Half of the infants in each dose group were also randomized to receive either 30 ml of infant formula as buffer before vaccination or were vaccinated on an empty stomach. The incidence of fever, increased stool frequency and decreased activity level was consistently higher among infants who received RRV than those who received placebo. There was no consistent increase in incidence of symptoms as the dose of RRV was increased. Possible vaccine-related side effects were increased in older vaccinees and in those with higher pre-vaccination antibody titers. The seroconversion rate and pre to postvaccination antibody rise, evaluated by enzyme-linked immunosorbent assay and by plaque reduction neutralization, correlated well. The 10(5) and 10(4) pfu RRV dose produced significantly higher rates of seroconversion and higher antibody rises than did placebo (P less than 0.001 for 10(5) and P = 0.005 for 10(4]. The 10(3) pfu dose was no more immunogenic than placebo. In the 10(4) pfu dose group 73% of infants receiving formula as a "buffer" seroconverted compared with 36% of those not receiving formula; 63% of infants partially breast-fed or formula-fed seroconverted compared with 17% of those exclusively breast-fed. These differences in seroconversion rate were largely overcome by increasing the RRV dose to 10(5) pfu. Stool (copro IgA) antibody responses were examined; of six infants showing a copro IgA response only one had seroconverted based on enzyme-linked immunosorbent assay or plaque reduction neutralization. RRV was recovered by tissue culture more frequently from the stool in those infants who received RRV 10(5) and 10(4) pfu than among those receiving 10(3) pfu or placebo (P less than 0.001).