Pharmacodynamic analysis and clinical trial of amoxicillin sprinkle administered once daily for 7 days compared to penicillin V potassium administered four times daily for 10 days in the treatment of tonsillopharyngitis due to Streptococcus pyogenes in children.

An a priori pharmacokinetic/pharmacodynamic (PK/PD) target of 40% daily time above the MIC (T >MIC; based on the MIC(90) of 0.06 microg/ml for Streptococcus pyogenes reported in the literature) was shown to be achievable in a phase 1 study of 23 children with a once-daily (QD) modified-release, multiparticulate formulation of amoxicillin (amoxicillin sprinkle). The daily T >MIC achieved with the QD amoxicillin sprinkle formulation was comparable to that achieved with a four-times-daily (QID) penicillin VK suspension. An investigator-blinded, randomized, parallel-group, multicenter study involving 579 children 6 months to 12 years old with acute streptococcal tonsillopharyngitis was then undertaken. Children were randomly assigned 1:1 to receive either the amoxicillin sprinkle (475 mg for ages 6 months to 4 years, 775 mg for ages 5 to 12 years) QD for 7 days or 10 mg/kg of body weight of penicillin VK QID for 10 days (up to the maximum dose of 250 mg QID). Unexpectedly, the rates of bacteriological eradication at the test of cure were 65.3% (132/202) for the amoxicillin sprinkle and 68.0% (132/194) for penicillin VK (95% confidence interval, -12.0% to 6.6%). Thus, neither antibiotic regimen met the minimum criterion of > or =85% eradication ordinarily required by the U.S. FDA for first-line treatment of tonsillopharyngitis due to S. pyogenes. The results of subgroup analyses across demographic characteristics and current infection characteristics and by age/weight categories were consistent with the primary-efficacy result. The clinical cure rates for amoxicillin sprinkle and penicillin VK were 86.1% (216/251) and 91.9% (204/222), respectively (95% confidence interval, -11.6% to -0.4%). The results of a post hoc PD analysis suggested that a requirement for 60% daily T >MIC(90) more accurately predicted the observed high failure rates for bacteriologic eradication with the amoxicillin sprinkle and penicillin VK suspension studied. Based on the association between longer treatment courses and maximal bacterial eradication rates reported in the literature, an alternative composite PK/PD target taking into consideration the duration of therapy, or total T >MIC, was considered and provides an alternative explanation for the observed failure rate of amoxicillin sprinkle.

Causative pathogens, antibiotic resistance and therapeutic considerations in acute otitis media.

Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are the most frequently isolated pathogens in patients with acute otitis media (AOM). Other potential causative pathogens include Streptococcus pyogenes in older children and Chlamydia pneumoniae in younger children. The recent emergence of penicillin-resistant S. pneumoniae and the increasing frequency of beta-lactamase-producing strains of M. catarrhalis and H. influenzae are creating concerns regarding the use of amoxicillin as traditional first line empiric therapy for AOM in younger children. Both the in vitro antibiotic activity against these more resistant causative pathogens and the antibiotic concentrations achieved in middle ear fluid must be considered when selecting antibiotics for treatment of refractory AOM. The newer macrolides, azithromycin and clarithromycin, provide reasonable in vitro coverage against penicillin-resistant S. pneumoniae and beta-lactamase-producing H. influenzae, although azithromycin is more active against the latter. Both drugs also achieve notably higher, sustained concentrations in middle ear fluid than do beta-lactam antibiotics. Thus the newer macrolides represent important new rational alternatives for the management of AOM.

Comparative study of the effectiveness of cefixime and penicillin V for the treatment of streptococcal pharyngitis in children and adolescents.

An open label randomized trial conducted in rural Kentucky compared the efficacy and safety of cefixime (CFX), 8 mg/kg once daily, with those of penicillin V (PEN), 250 mg 3 times daily, in 110 pediatric patients with Group A beta-hemolytic streptococcal pharyngitis. Forty-eight CFX and 47 PEN patients were evaluable for efficacy. At the end of therapy bacteriologic eradication was 45 of 48 (94%) and 36 of 47 (77%) in the CFX and PEN V groups, respectively (P < 0.05). Up to 6 weeks posttherapy 10 (21%) CFX patients and 21 (45%) PEN patients had positive Group A beta-hemolytic Streptococcus cultures (P < 0.05). Concordant serotypes were identified from 4 of 7 CFX and 15 of 17 PEN patients with positive repeat cultures. All discordant serotypes (5 of 31) were identified at greater than 19 days posttherapy. Symptomatic treatment failures (concordant serotypes) occurred in 1 (2%) CFX and 8 (17%) PEN patients (P < 0.05). Drug-related adverse experiences consisted of 2 cases of mild diarrhea and loose stools in the CFX group and none in the PEN group. No clinically significant laboratory test abnormalities occurred in either group. CFX, once daily, was as safe as and significantly more effective than PEN given 3 times daily for the treatment of Group A beta-hemolytic streptococcal pharyngitis.

Five-day cefdinir course vs. ten-day cefprozil course for treatment of acute otitis media.

OBJECTIVE: To compare the clinical efficacy of a 5-day cefdinir course with a 10-day cefprozil course in the treatment of pediatric acute otitis media (AOM). DESIGN: Comparative, investigator-blinded multicenter trial. SETTING: Primary care, ambulatory. PATIENTS: Children ages 6 months through 12 years with clinical symptoms and tympanic membrane signs of AOM, plus tympanometric-confirmed middle ear effusion in at least 1 ear. Of the 435 patients enrolled in the study, 373 were evaluable. INTERVENTION: Patients received cefdinir 14 mg/ kg/day divided twice a day for 5 days or cefprozil 30 mg/kg/day divided twice a day for 10 days. MAIN OUTCOME MEASURES: Clinical resolution of tympanic membrane signs and symptoms of AOM determined at end of therapy on Study Days 9 to 11. RESULTS: The clinical cure rate at end of therapy was 80% (152 of 190) for cefdinir-treated patients and 82.5% (151 of 183) for cefprozil-treated patients (95% confidence interval, 10.43% to 5.4%). Diarrhea and overall adverse reactions, respectively, occurred in 7.8 and 13% of cefdinir-treated patients and in 4.2 and 12% of cefprozil-treated patients. CONCLUSIONS: A short course 5-day regimen of cefdinir was as clinically effective and well-tolerated as a 10-day regimen of cefprozil in the treatment of nonrefractory AOM.

Future indications for macrolides.

The antimicrobial spectrum of azithromycin and clarithromycin suggests a number of further uses for these newer macrolides. Favorable clinical and bacteriologic responses have been reported with both antibiotics in children with community-acquired pneumonia. Response rates were high for overall patient populations and for subgroups with infection caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. Treatment with azithromycin or clarithromycin has resulted in a reduction in mycobacteremia and an improvement in clinical symptoms in adult AIDS patients with disseminated Mycobacterium avium-intracellulare complex. Prophylactic treatment with azithromycin may prevent M. avium-intracellulare complex, especially when combined with rifabutin. Preliminary evidence suggests that both azithromycin and clarithromycin in multidrug combinations may effectively eradicate Helicobacter pylori and that azithromycin may be useful in treating bacterial gastritis caused by Campylobacter species. Trachoma and infections caused by Bordetella pertussis and Ureaplasma urealyticum are other possible future indications for the newer macrolides. Limited clinical evidence also suggests that azithromycin may be effective in the prevention and treatment of malaria.

Microbiology of acute otitis media recently treated with aminopenicillins.

INTRODUCTION: Sparse recent data are available in the United States regarding the pathogens of acute otitis media (AOM) most likely to be recovered from children recently treated with the two most frequently prescribed antibiotics, amoxicillin or amoxicillin/clavulanate (AMC). METHODS: Of the 704 rural Kentucky children with culture-positive AOM who underwent a single tympanocentesis or culture of otorrhea between 1992 and 1998, 96 pathogens were recovered from 90 children during therapy or within 7 days posttherapy with an aminopenicillin. Identification and susceptibility testing of AOM pathogens were performed by routine National Committee for Clinical Laboratory Standards methods. RESULTS: Pathogens recovered from children with AOM recently treated (0 to 7 days) with amoxicillin (n = 38) and AMC (n = 58), respectively, were as follows: Haemophilus influenzae (beta-lactamase-negative), 16 and 29%; H. influenzae (beta-lactamase-positive), 11 and 22%; penicillin-susceptible Streptococcus pneumoniae, 26 and 12%; intermediately penicillin-nonsusceptible S. pneumoniae (PNSP), 20 and 10%; resistant PNSP 13 and 17%; Moraxella catarrhalis (beta-lactamase-positive), 13 and 7%; and Streptococcus pyogenes, 3 and 2%. H. influenzae was also isolated from 8 (75%) of 12 children treated with high dose AMC ( approximately 80 mg/kg/day amoxicillin component). Significantly fewer children recently treated with amoxicillin were otitis-prone than those given AMC (24% vs. 74%, P < 0.0001). CONCLUSIONS: The predominant pathogen recovered from children with AOM recently treated with amoxicillin was S. pneumoniae (59%) rather than beta-lactamase-producing organisms (24%). H. influenzae was the predominant (51%) pathogen, rather than PNSP (27%), recovered from children recently treated with AMC.

Five-day twice daily cefdinir therapy for acute otitis media: microbiologic and clinical efficacy.

OBJECTIVE: To examine the microbiologic and clinical efficacy of a 5-day course of cefdinir in the treatment of tympanocentesis-documented acute otitis media (AOM). DESIGN: Open label noncomparative trial. SETTING: Primary care, ambulatory. PATIENTS: Children ages 6 months through 12 years with signs of AOM and middle ear effusion confirmed by tympanometry in at least one ear. INTERVENTION: Patients underwent tympanocentesis at baseline and received cefdinir 7 mg/kg twice a day for 5 days. MAIN OUTCOME MEASURES: Presumptive eradication of middle ear pathogens determined by clinical cure of signs and symptoms of AOM at end of therapy (Study Days 7 to 9) and Visit 3 (Study Days 16 to 21). RESULTS: A total of 125 of 177 enrolled children had 134 pathogens isolated by tympanocentesis: Streptococcus pneumoniae, 69 (51.5%); Haemophilus influenzae 44 (32.8%; beta-lactamase-positive in 18 of 44 strains); beta-lactamase-positive Moraxella catarrhalis, 15 (11.2%); and Streptococcus pyogenes, 6 (4.5%). The clinical cure rates by patient in the microbiologically and overall clinically evaluable groups, respectively, were 73% (84 of 115) and 77.4% (130 of 168) at the end of therapy visit and 57.4% (66 of 115) and 61.9% (104 of 168) at Visit 3. Presumptive eradication rates at end of therapy were 8 of 11 (72.7%) and 4 of 8 (50%) for patients with penicillin-intermediate and -resistant S. pneumoniae isolates, respectively. Adverse reactions occurred in 16% of patients, with diarrhea (11%) occurring most frequently. CONCLUSIONS: A 5-day regimen of cefdinir was effective in the eradication of the common causative pathogens of nonrefractory AOM, including intermediate penicillin-resistant S. pneumoniae and beta-lactamase-producing organisms. Cefdinir should be considered a suitable second line antibiotic for AOM.

Relation of the outcome of conjunctivitis and the conjunctivitis-otitis syndrome to identifiable risk factors and oral antimicrobial therapy.

The epidemiology, microbiology and clinical outcome of the conjunctivitis-otitis syndrome (CJ-AOM) was investigated in a rural private practice concurrent to a double blind placebo-controlled study of orally administered amoxicillin for prevention of acute otitis media (AOM) secondary to conjunctivitis. Bacterial pathogens were isolated when greater than 15 polymorphonuclear leukocytes/high power field were observed on Gram-stained smear of conjunctival secretions. Nontypable Haemophilus influenzae biotype 2 predominated in CJ-AOM; however, Streptococcus pneumoniae was isolated nearly as frequently as H. influenzae in conjunctivitis without AOM. Younger age (P = 0.001) and more episodes of AOM in the previous year (P = 0.006) were risk factors for CJ-AOM. Persistence of AOM was frequently observed in CJ-AOM. The frequency of AOM secondary to conjunctivitis was reduced (P = .01) in amoxicillin recipients (2 of 41) compared with placebo (11 of 42), but amoxicillin failed to eradicate nasopharyngeal carriage of H. influenzae. More episodes of AOM per year (P less than 0.001) and day care (P less than 0.001) were found to be risk factors for AOM secondary to conjunctivitis.

Safety, tolerability and immunogenicity of a formalin-inactivated hepatitis A vaccine (VAQTA) in rural Kentucky children.

This study evaluated the immunogenicity and safety/tolerability profile of an investigational formalin-inactivated hepatitis A virus vaccine (VAQTA; Merck Research Laboratories) in 150 seronegative healthy children, 4 to 12 years old. The vaccine was derived from virus grown in infected MRC-5 cells in either roller bottles or Nunc cell factories (Nunc, Denmark). Subjects were vaccinated intramuscularly in a two dose regimen initially and at 24 weeks: Group A (n = 50) with a 12-unit dose from a roller bottle lot; Group B (n = 50) with a 25-unit dose from another roller bottle lot; and Group C (n = 50) with a 25-unit dose from a Nunc cell lot. Sera for anti-hepatitis A virus antibodies were drawn 3 weeks before vaccination and 4, 24 and 28 weeks after the first dose. Seroconversion from < 10 mIU/ml to > or = 10 mIU/ml by modified HAVAB (Abbott Laboratories) was observed in 99% of subjects at week 4 and persisted in 100% of subjects at week 28 (4 weeks after the second dose). The ranges of geometric mean titers of anti-HAV for all subjects at weeks 4, 24 and 28 were 31 to 49, 51 to 79 and 7059 to 29,609 mIU/ml, respectively. The 12- and 25-unit dose levels of roller bottle yielded similar geometric mean titers. The rise in geometric mean titers after the booster dose was > 120-fold and was highest in the recipients of the 25-unit Nunc cell lot (P < 0.05 for Group C vs. B).(ABSTRACT TRUNCATED AT 250 WORDS)

High prevalence of multidrug-resistant Streptococcus pneumoniae among children in a rural Kentucky community.

In 1992 drug-resistant Streptococcus pneumoniae was cultured with increasing frequency from aspirates of middle ear fluid from children with acute otitis media in a rural Kentucky community. To determine the prevalence of carriage of drug-resistant S. pneumoniae in the community, we obtained nasopharyngeal swabs from 158 (70%) of 227 children attending a child daycare center and from 82 children attending the county health center. S. pneumoniae was isolated from 126 children. Among 123 isolates tested 65 (53%) were penicillin-resistant, including 41 (33%) strains that were highly resistant; 61 (50%) were multidrug-resistant. Serotypes 19F, 6B, 23F and 6A comprised 89% of the penicillin-resistant isolates. Detection of a variety of serotypes and drug resistance patterns among nasopharyngeal isolates of S. pneumoniae suggests that multidrug-resistant pneumococcal strains are endemic in this community. Surveillance for drug-resistant pneumococci with the use of respiratory secretions obtained by nasopharyngeal swab may provide useful information on the prevalence of drug-resistant strains causing invasive disease and otitis media. Such information could be used to guide empiric therapy of pneumococcal infections.

Penicillin-resistant Streptococcus pneumoniae in acute otitis media: risk factors, susceptibility patterns and antimicrobial management.

From January, 1992, to January, 1994, penicillin-resistant (minimal inhibition concentration (MIC) > 0.06 microgram/ml) Streptococcus pneumoniae (PRSP) isolates accounted for 48 (17%) of 283 isolates from acute otitis media (AOM) or recurrent AOM in 246 ambulatory patients in rural Kentucky. By broth microdilution, relatively penicillin-resistant (MIC > 0.06 to 1.0 microgram/ml) and highly penicillin-resistant (MIC > or = 2.0 micrograms/ml) strains were detected in 25 (16%) and 23 (15%), respectively, of 157 pneumococcal middle ear isolates. Using 1994 National Committee for Clinical Laboratory Standards breakpoints for pneumococci (unavailable for oral cephalosporins except cefuroxime), highly PRSP strains were almost uniformly susceptible to clindamycin and vancomycin. In contrast highly PRSP strains were resistant to most oral antimicrobials customarily used for AOM with one-third of strains highly resistant (MIC > or = 2.0 micrograms/ml) to ceftriaxone. Serotypes 6B, 19F and 23F accounted for 95% of highly PRSP strains and serotype 9V for 48% of relatively PRSP strains. By multivariate analysis, otitis-prone condition (P = 0.0008) and number of antibiotic courses before day of culture (P < 0.0001) were independently predictive of PRSP. Highly PRSP isolates were more commonly isolated from patients recently treated within 3 days (30%) vs. those who completed therapy more than 3 days earlier (2%) (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative safety and efficacy of cefdinir vs amoxicillin/clavulanate for treatment of suppurative acute otitis media in children.

OBJECTIVE: Two dosage regimens of cefdinir were compared with amoxicillin/clavulanate for the treatment of suppurative acute otitis media (AOM) in children. METHODS: This was an investigator-blinded, randomized, comparative, multicenter trial, in which tympanocentesis was performed in 384 patients, ages 6 months to 12 years, who had nonrefractory AOM. Patients were randomized to receive one of three 10-day treatment regimens: cefdinir 14 mg/kg daily (QD; n = 128); cefdinir 7 mg/kg twice a day (BID; n = 128); or amoxicillin/clavulanate 40/10 mg/kg/day divided for use three times a day (TID; n = 128). RESULTS: Of the 384 enrolled patients 303 were evaluable for clinical efficacy. Clinical success rates were statistically equivalent for the 3 treatment groups at the end of therapy: 85 of 102 (83.3%) for cefdinir QD; 81 of 101 (80.2%) for cefdinir BID; 86 of 100 (86%) for amoxicillin/clavulanate. Of the 197 evaluable patients from whom a susceptible pathogen was recovered, presumptive eradication rates at end of therapy were equivalent: 55 of 65 (84.6%), 54 of 66 (81.8%) and 55 of 66 (83.3%) for cefdinir QD-, cefdinir BID- and amoxicillin/clavulanate-treated patients, respectively. However, presumptive eradication rates for Streptococcus pneumoniae were significantly lower for cefdinir BID (55.2%) than for amoxicillin/clavulanate (89.5%; P = 0.0019) and marginally lower than for cefdinir QD (80%; P = 0.054). Diarrhea was the most common treatment-associated adverse reaction in all groups but was significantly more common in amoxicillin/clavulanate-treated patients (35%) than in patients who had been treated with cefdinir QD (10%, P<0.001) or cefdinir BID (13%, P<0.001). CONCLUSIONS: A 10-day regimen of cefdinir 14 mg/kg QD or 7 mg/kg BID was as clinically effective overall as a 10-day regimen of amoxicillin/ clavulanate 40/10 mg/kg/day divided TID in the treatment of tympanocentesis-confirmed, nonrefractory AOM in children. These data suggest that cefdinir QD may be a better alternative than cefdinir BID for refractory AOM. Both dosing regimens of cefdinir were associated with significantly fewer gastrointestinal adverse reactions than was amoxicillin/clavulanate.

Chlamydia pneumoniae in acute otitis media.

BACKGROUND: Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. METHODS: We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. RESULTS: C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. CONCLUSIONS: This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.

Management of acute otitis media in the 1990s: the decade of resistant pneumococcus.

Acute otitis media (AOM) has become increasingly difficult to treat in the 1990s, the decade of drug-resistant pneumococcus. Throughout the world, drug-resistant strains of this pathogen are being recovered from 20 to 50% of cases of initial untreated AOM, and from 45 to 90% of refractory AOM. Almost as alarming is that beta-lactamase-producing strains of Haemophilus influenzae are currently being isolated in 40 to 50% of cases of AOM in the US. Clinicians can no longer expect 'Pollyanna-like' high rates of clinical resolution for this disease. It is now imperative that they become aware of the regional prevalence of these drug-resistant bacteria and, just as importantly, their patterns of antibacterial resistance. Although some authors would hold that any antibacterial, or even placebo, should be adequate for most cases of AOM, clinical practice appears to suggest otherwise. Amoxicillin, still the first-line therapeutic choice for initial nonrefractory AOM, will often fail. The real dilemma begins when clinicians search for clinical data to select an antibacterial for therapeutic failures--few data are available. Thus, to give optimal treatment to a child who has failed antibacterial therapy--the true actual indication for all second-line antibacterials--they must instead become familiar with the following in vivo and in vitro data: 1. 'In vivo sensitivity data': otherwise known as bacteriological efficacy, in which repeat tympanocentesis is performed in mid-therapy. This reveals the bacterial 'Achilles heel' or weakness for the individual antibacterial agents. 2. Clinical efficacy data: analysis of rates of clinical resolution after therapy in comparative trials which use a single tympanocentesis initially and a 'gold standard' comparator antibacterial. 3. 'Bug to drug' data: comparison of reported middle ear concentrations for each individual antibacterial agent relative to the respective minimum inhibitory concentrations of isolates, particularly drug-resistant pneumococcus and H. influenzae (if possible, obtained from the paediatric respiratory tract). The selection of an antibacterial agent for AOM in any particular case should not be merely a random process. It involves awareness of the pathogens most likely to be observed: with co-infections; after failure with a particular antibacterial (the bacterial 'Achilles heel' of the drug); and at different points in time, whether initially or after therapeutic failures (e.g. first-line versus fourth-line failure).

Attention-deficit disorder. A paradigm for psychotropic medication intervention in pediatrics.

Pediatricians frequently encounter patients with behavioral or academic problems in clinical practice. Assessing and managing these patients requires awareness of the numerous physical, emotional, and psychological causes. Because of their limited contact with these patients during a routine visit, pediatricians as a minimum, should rely on careful parental and social history, teachers' evaluations by checklist, achievement test scores and grades, and the clinicians' own gestalt regarding patients' behavior. This article provides a framework that practitioners can incorporate into their routine office practices. Practitioners must also be knowledgeable about different forms of ADD and learning disabilities, differential diagnosis, and frequently encountered comorbidities. A modest armamentarium of psychotropic drugs potentially useful in the treatment of ADD are available; however, they must be aware of indications, subtle differences in pharmacokinetics, rates of efficacy, and adverse effects for these medications. Appropriate behavioral intervention, educational assessment, and placement when necessary are also essential for optimal management. Enabling the child or adolescent to achieve successfully in school, to experience positive social interactions, and to regain self-esteem are the more rewarding facets of pediatric care.

Primary pneumococcal peritonitis complicated by exudative pleural effusion in an adolescent girl.

A healthy, young adolescent girl developed primary pneumococcal peritonitis, an infection rarely reported in this age group in North America. Her course was further complicated by exudative pleural effusion and pneumonia despite receiving 10 days of clindamycin therapy. Laparascopy proved useful in making the initial diagnosis, but may have contributed to the pathogenesis of the pulmonary process. Case presentation, management, and etiology are discussed.

Restricted use of antibiotic prophylaxis for recurrent acute otitis media in the era of penicillin non-susceptible Streptococcus pneumoniae.

OBJECTIVE/INTERVENTION: To compare the annual rates of acute otitis media (AOM) episodes, antibiotic days, and ventilating tube insertion during the first 3 years of life before and after a practice change to restrict use of antibiotic chemoprophylaxis for recurrent AOM. METHODS SETTING: The sole pediatric private practice in a rural Kentucky community. PATIENTS: Population-based sample of all children born consecutively in two different 13 month intervals. Cohort 1 (n=251) was born before and Cohort 2 (n=274) was born after restricted use of chemoprophylaxis and documented emergence of widespread penicillin non-susceptible Streptococcus pneumoniae (PNSP). DESIGN: Retrospective case cohort comparison. MAIN OUTCOME MEASURES: Suppurative AOM diagnosed by validated experienced otoscopists using stringent tympanic membrane criteria. RESULTS: Children were mostly white with the majority (50-65%) enrolled in daycare during each year. The first episode of AOM was experienced by 6 and 12 months of age in 64 and 86%, respectively. Rates of children with recurrent AOM in Cohorts 1 and 2 were 28 and 31% in Year 1, 17 and 23% in Year 2, and 7 and 10% in Year 3, respectively. Rates of new onset AOM and persistent AOM episodes were similar between cohorts in the first 2 years. Number of days of antibiotic prophylaxis were reduced from 11.2 to 3.4 days in Year 1, from 11.9 to 2.6 days in Year 2, and from 6.9 to 0.7 days in Year 3, respectively (P<0.0001 for each year). Total antibiotic days for Years 1, 2 and 3 were reduced commensurately with prophylactic days from 61.7 to 55.5 days (nonsignificant), from 56.3 to 45.8 days (P=0.047), and from 38.7 to 25.7 days (P<0.0001), respectively. For each year a non-significant trend for increased ventilating tube placement from Cohort 1 to Cohort 2, respectively, was observed, 2 versus 2.2%, 4 versus 5.8%, and 0.8 versus 2.6%. Daycare attendance and white race were consistently significant risk factors for AOM and recurrent AOM. CONCLUSIONS: In the era of PNSP, restricted use of antibiotic chemoprophylaxis for recurrent AOM was not associated with significantly increased rates of new onset AOM episodes or tube placement in the first 24 months of life. Total antibiotic days were also significantly reduced in Cohort 2 during Years 2 and 3.