Clinical/otologic score before and during treatment of acute otitis media.

OBJECTIVES: To determine clinical characteristics of AOM at presentation and during therapy according to specific etiologies. PATIENTS AND METHODS: 1003 patients studied during 1996-2001 in antibiotic efficacy studies underwent tympanocentesis and middle ear fluid culture at enrollment and on Day 4-6 (in initially culture-positive patients only). We used a clinical/otologic (CO) score for evaluating severity of fever, irritability and tympanic membrane redness and bulging (0-3 each parameter, maximal score=12). RESULTS: Seven hundred sixty-three patients had positive cultures with 392 (39%) Haemophilus influenzae, 198 (20%) Streptococcus pneumoniae and 173 (17%) mixed H. influenzae and S. pneumoniae infection. Mean CO score was higher in culture-positive versus culture-negative patients (8.21+/-2.17 vs. 7.73+/-2.32, p=0.003) regardless of isolated organism. A marked improvement in CO score was observed on Day 4-6 in all patients: 1.83+/-2.18 in children initially culture-positive and 0.9+/-1.67 in those initially culture-negative (p<0.001). The improvement was greater in patients with eradication versus those with bacteriological failure (CO score 1.52+/-1.82 vs. 2.77+/-2.85, p<0.001). CONCLUSIONS: CO score before treatment, after bacterial eradication or in bacteriologic failures are similar in bacterial AOM and are not predictive of the etiology of the disease.

Bacteriologic and clinical efficacy of trimethoprim-sulfamethoxazole for treatment of acute otitis media.

BACKGROUND: Trimethoprim-sulfamethoxazole (T/S) has often been used as first and second line of treatment for acute otitis media (AOM). Because of the increasing resistance of Streptococcus pneumoniae and Haemophilus influenzae to T/S, we undertook the present study to investigate the bacteriologic and clinical efficacy of this drug in AOM. METHODS: Fifty-four culture-positive evaluable patients ages 3 to 32 months with AOM were treated with T/S 4/20 mg/kg in two divided daily doses for 10 days. Middle ear fluid (MEF) was cultured at enrollment (Day 1) and on Days 4 and 5 after initiation of treatment. Additional MEF cultures were obtained if clinical relapse occurred. Clinical failure was determined when the symptoms and signs of AOM did not improve or recurred during therapy. Bacteriologic failure was defined by positive culture on Days 4 and 5, or negative on Days 4 and 5 but positive again before the end of treatment. Patients were followed until Day 28 +/- 2. RESULTS: A total of 67 organisms were isolated from MEF specimens of the 54 study patients: S. pneumoniae, 24; H. influenzae, 40; and Streptococcus pyogenes, 3. Fifteen (63%) of 24 S. pneumoniae were nonsusceptible to T/S (trimethoprim MIC, >0.5 microg/ml), of which 10 (67%) were highly resistant to T/S (trimethoprim MIC, > or = 4.0 microg/ml). Twelve (30%) of 40 H. influenzae and all 3 S. pyogenes isolates were nonsusceptible to T/S (MIC > or = 4.0 microg/ml). Bacteriologic eradication occurred in 9 of 9 (100%) and 27 of 27 (100%) T/S-susceptible S. pneumoniae and H. influenzae, respectively, vs. 4 of 15 (27%) and 6 of 12 (50%) T/S-nonsusceptible S. pneumoniae and H. influenzae, respectively (P < 0.001). The 3 patients with S. pyogenes failed bacteriologically. Nine new organisms, not initially isolated, emerged during treatment, 7 of which (77%) were resistant to T/S. Altogether bacteriologic failure (organisms not eradicated plus newly emerged) occurred in 29 (53%) of 54 patients. Clinical failures occurred in 8 (15%) of 54 patients, and in 7 of these 8 cases the clinical failures occurred in those with bacteriologic failures. Ten patients relapsed clinically after completion of treatment and in 8 of them tympanocentesis for MEF culture was performed. Six of these 8 cultures were positive, and the initial pathogen was isolated in 4 of 6 (67%). CONCLUSIONS: A high bacteriologic failure rate as well as a considerable clinical failure rate occurred among patients with AOM treated with T/S. We believe that T/S is no longer an appropriate empiric choice for the treatment of AOM in regions where high T/S resistance among respiratory pathogens is reported.

Bacteriologic and clinical efficacy of one day vs. three day intramuscular ceftriaxone for treatment of nonresponsive acute otitis media in children.

BACKGROUND: One dose of intramuscular ceftriaxone has been recently licensed in the United States for the treatment of acute otitis media. However, data regarding the bacteriologic and clinical efficacy of this regimen in the treatment of nonresponsive acute otitis media are incomplete. OBJECTIVES: To determine the bacteriologic and clinical efficacy of a 1-day 50-mg/kg vs. a 3-day 50-mg/kg/day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media in children. PATIENTS AND METHODS: In an open, prospective study 109 patients ages 3 to 36 months with culture-proved, nonresponsive acute otitis media were randomized to receive 1 (n = 49) or 3 (n = 60) 50-mg/kg/day intramuscular ceftriaxone doses, respectively. Middle ear fluid was aspirated for culture by tympanocentesis on the day of enrollment (Day 1); a second tympanocentesis with middle ear fluid culture was performed on Days 4 to 5. Additional middle ear fluid cultures were obtained if clinical relapse occurred after completion of therapy. Bacteriologic failure was defined by positive cultures on Days 4 to 5. Patients were followed until Day 28 after completion of therapy. Susceptibility of the middle ear pathogens was measured by E-test. RESULTS: Organisms recovered (n = 133) were Streptococcus pneumoniae (30 and 35 isolates for the 1-day and 3-day treatment group, respectively), Haemophilus influenzae (26 and 38, respectively) and Moraxella catarrhalis (n = 4). Of the 30 S. pneumoniae isolated from the 1-day group, 27 (90%) and 6 (20%) were nonsusceptible to penicillin and ceftriaxone, respectively; 9 of 27 (33%) were fully resistant to penicillin. Thirty-four (97%) and 6 (17%) of the 35 S. pneumoniae isolated from the 3-day group were nonsusceptible to penicillin and ceftriaxone, respectively; 16 of 34 (47%) were fully resistant to penicillin. Bacterial eradication of all H. influenzae and penicillin-susceptible S. pneumoniae was achieved in both treatment groups. Bacterial eradication of 14 of 27 (52%) and 33 of 34 (97%) penicillin-nonsusceptible S. pneumoniae was achieved in the 1-day and 3-day group, respectively. Seven (50%) of the 14 patients from the 2 groups who did not achieve bacterial eradication did not improve clinically on Days 4 to 5 and required additional ceftriaxone treatment. CONCLUSION: The 3-day intramuscular ceftriaxone regimen was significantly superior to the 1-day intramuscular ceftriaxone regimen in the treatment of nonresponsive acute otitis media caused by penicillin-resistant S. pneumoniae.

Oral ciprofloxacin vs. intramuscular ceftriaxone as empiric treatment of acute invasive diarrhea in children.

BACKGROUND: Acute invasive diarrhea is a potentially serious condition in children. Because of the increasing resistance of enteric pathogens to commonly used oral antibiotics, intramuscular ceftriaxone has become the routine drug in the treatment of acute invasive diarrhea requiring an emergency visit in southern Israel. The inconvenience of this parenteral regimen created an increased need for oral pediatric formulations for the treatment of invasive diarrhea. OBJECTIVES: To evaluate the efficacy and safety of a suspension formulation of ciprofloxacin in the treatment of acute invasive diarrhea in infants and children. PATIENTS AND METHODS: From July 1996 through December 1997, 201 evaluable children ages 6 months to 10 years (35% <1 year; 70% <3 years) presenting with acute invasive diarrhea at the Pediatric Emergency Room were randomized to receive either ciprofloxacin suspension (10 mg/kg twice a day + im placebo; n = 95) or im ceftriaxone (50 mg/kg/day + placebo suspension; n = 106) for 3 days in a double blind manner. Stool cultures for Shigella, Salmonella, Campylobacter spp. and diarrheagenic Escherichia coli were obtained on Days 1, 3, 4 to 5 and 21 +/- 5. Clinical response and safety were assessed on Days 1, 2, 3, 4 to 5 and 21 +/- 5. RESULTS: We isolated 127 pathogens from 121 (60%) patients: 73 (57%) Shigella; 23 (18%) Salmonella; 18 (14%) E. coli; and 13 (10%) Campylobacter. Overall bacteriologic eradication on Day 4 to 5 was 99% for Shigella, 77% for Salmonella and 77% for Campylobacter, with no difference between the 2 groups. Clinical cure or improvement was observed in 100 and 99% of the ciprofloxacin and ceftriaxone groups, respectively. Serum ciprofloxacin values determined on Day 3 of the treatment were higher in the majority of patients than were the MIC50 and MIC90 values for the Shigella and Salmonella spp. isolated. Possible drug-related adverse events occurred in 13 patients [ciprofloxacin, 8 (8%); ceftriaxone, 5 (4.7%)] and were mild and transient. Joint examination was normal during and after completion of therapy in all patients. CONCLUSION: Oral ciprofloxacin was as safe and effective as intramuscular ceftriaxone for the empiric treatment of acute invasive diarrhea in ambulatory pediatric patients requiring an emergency room visit.

Predictive value of pneumococcal nasopharyngeal cultures for the assessment of nonresponsive acute otitis media in children.

BACKGROUND: Nonresponsive acute otitis media (NR-AOM) is reported in > 10% of children with AOM treated with antibiotics. Drug-resistant Streptococcus pneumoniae is currently considered the leading cause of antibiotic failures in AOM. Nasopharyngeal colonization with S. pneumoniae was found to increase significantly during episodes of AOM. OBJECTIVES: To investigate the nasopharyngeal colonization with S. pneumoniae during NR-AOM and compare it with that found in AOM not recently treated with antibiotics (NT-AOM); to assess the predictive value of nasopharyngeal pneumococcal cultures results for the bacteriologic assessment of NR-AOM. MATERIALS AND METHODS: Patients age 3 to 48 months with NT-AOM and NR-AOM were prospectively studied. Simultaneous nasopharyngeal cultures for S. pneumoniae and middle ear fluid cultures were obtained at enrollment. Antibiotic susceptibility testing was performed in all S. pneumoniae isolates. Penicillin and ceftriaxone MICs for S. pneumoniae were determined by E-test. The sensitivity, specificity and positive and negative predictive values of positive or negative nasopharyngeal cultures for the presence of S. pneumoniae in middle ear fluid were calculated. RESULTS: We studied 362 and 217 children with NT-AOM and NR-AOM, respectively. Of the children with NT-AOM and NR-AOM, 95 and 97%, respectively, were younger than 2 years of age. S. pneumoniae was isolated in the nasopharynx of 66 and 58% of children with NT-AOM and NR-AOM, respectively. Penicillin-nonsusceptible S. pneumoniae was isolated more frequently from the nasopharynx of patients with NR-AOM than from those with NT-AOM (84% vs. 47%; P < 0.01). Antibiotic susceptibility patterns were similar for S. pneumoniae isolates recovered from the nasopharynx and those from the middle ear fluid in both NT-AOM and NR-AOM. A positive nasopharyngeal culture had only little predictive value for the presence of S. pneumoniae in middle ear fluid (41 and 51% for NT-AOM and NR-AOM, respectively). However, the negative predictive value of nasopharyngeal cultures for recovery of S. pneumoniae in NR-AOM was high and significantly higher in NR-AOM than in NT-AOM (91% vs. 78%, respectively; P = 0.009). The negative predictive value of nasopharyngeal cultures for recovery of antibiotic-resistant S. pneumoniae was 95 and 93% in NT-AOM and NR-AOM, respectively. Conclusions. A significantly higher nasopharyngeal colonization rate with antibiotic-resistant S. pneumoniae was found in patients with NR-AOM than in those with NT-AOM. Negative nasopharyngeal culture for antibiotic-resistant S. pneumoniae practically rules out its presence in middle ear fluid.

Interleukin 8 in middle ear fluid during acute otitis media: correlation with aetiology and bacterial eradication.

OBJECTIVES: To study the concentration of interleukin 8 (IL-8) in the middle ear fluid of children with acute otitis media and the association between IL-8 concentrations, aetiology of acute otitis media, and bacteriological sterilisation. STUDY DESIGN: Middle ear fluid was obtained by tympanocentesis at enrollment (day 1) and on day 4-5 in 81 children aged 3-36 months with acute otitis media who received antibiotic treatment. IL-8 concentrations were measured by enzyme linked immunosorbent assay. RESULTS: 101 samples were obtained on day 1 and 47 samples on day 4-5. 94 pathogens were isolated in 79 of 101 samples obtained on day 1: 56 Haemophilus influenzae, 35 Streptococcus pneumoniae, 2 Moraxella catarrhalis, and 1 Streptococcus pyogenes. Among 40 paired, initially culture positive samples, sterilisation was achieved on day 4-5 in 22 but not in 18 (13 H influenzae, 2 S pneumoniae, and 3 H influenzae and S pneumoniae concomitantly). IL-8 was detected in 96 of 101 and 46 of 47 samples obtained on days 1 and 4-5, respectively. Mean (SD) IL-8 concentration on day 1 was significantly higher in culture positive than in negative samples (12,636 (23,317) v 5,920 (7,080) pg/ml). In paired samples, IL-8 concentration fell in 12 of 22 ears in which sterilisation was achieved and in 9 of 21 ears with persistent or new infection. Mean (SD) IL-8 concentrations on day 4-5 were significantly higher in culture positive than in negative samples (15,420 (15,418) v 6,695 (5,092) pg/ml). CONCLUSIONS: Higher IL-8 concentrations are found in culture positive middle ear fluid in acute otitis media. Bacterial eradication is associated with a fall in these concentrations.

Reactogenicity and immunogenicity of reduced antigen content diphtheria-tetanus-acellular pertussis vaccines as a booster in 4-7-year-old children primed with diphtheria-tetanus-whole cell pertussis vaccine before 2 years of age.

BACKGROUND: The recent introduction of acellular pertussis vaccines (Pa) offers the possibility of booster doses in older children and adults. This can be conveniently accomplished by combining acellular pertussis antigens with diphtheria and tetanus toxoids. However the optimal dosage for the booster injection has not yet been determined. OBJECTIVE: To compare the reactogenicity and immunogenicity of diphtheria-tetanus-acellular pertussis vaccines (DTPa) with lower antigen contents to a licensed DTPa vaccine when given at 4-7 years of age as a booster to DTPw-primed children. METHODS: Two hundred and twenty-six children primed with four doses of DTPw before 2 years of age were enrolled and allocated to three groups to receive one dose of either DTPa (Infanrix, SmithKline Beecham, Biologicals), a reduced antigen formulation of this vaccine (dtpa, SmithKline Beecham Biologicals), or an experimental low dose formulation (dtpa-exp; d and t, Michigan Biologic Products Institute). Reactogenicity was assessed using diary cards for 15 days. Immunogenicity was determined as antibody responses against the vaccine components in pre- and 1 month postvaccination sera. RESULTS: Of the 225 children who completed the study, 60.0-66.7% reported symptoms, with no significant differences in rates between groups. Local, systemic and unsolicited symptoms occurred with similar frequencies in all three groups, the vast majority (> 90%) being considered as mild or moderate. No serious adverse events related to vaccination were reported. After vaccination, all subjects displayed seroprotective concentrations against diphtheria and tetanus, and 98.7-100% had antibodies against the three pertussis component antigens. The group receiving the reduced dose of the licensed vaccine showed antibody concentrations comparable to those of the full dose group. However, the group receiving the experimental low dose formulation had statistically significantly lower antibody concentrations against both diphtheria and tetanus toxoids compared with the two other groups, as well as significantly lower anti FHA antibody concentrations. CONCLUSIONS: Reducing the antigen content of dtpa had no deleterious effect on the immunogenicity of the vaccine when given as a fifth dose at 4-7 years of age in DTPw-primed children. The reactogenicity profile of both the reduced antigen dtpa vaccines and DTPa were acceptable, the vast majority of local and systemic reactions being considered as mild to moderate, with no vaccine-related serious adverse events reported. The use of lower antigen content dtpa vaccine as a booster in children aged 4-7 is safe and immunogenic.

Dynamics of interleukin-1 production in middle ear fluid during acute otitis media treated with antibiotics.

In an ongoing prospective study, IL-1 concentrations were measured in 78 children (aged 3-36 months) with acute otitis media receiving antibiotics. Middle ear fluid IL-1 concentrations were determined using ELISA kits. Ninety-eight middle ear fluid samples were obtained by tympanocentesis at enrollment (day 1) and 43 samples were collected on days 4-5. Ninety-two pathogens were isolated in 77/98 samples obtained on day 1: 55 Haemophilus influenzae, 34 Streptococcus pneumoniae, 2 Moraxella catarrhalis and 1 Streptococcus pyogenes. Among 37 paired samples initially culture-positive, eradication of the pathogen was achieved on day 4-5 in 20 while pathogens were still present in 17. On day 1, IL-1 was detected in 61/77 (79%) culture-positive samples vs 9/21 (43%) culture-negative ones (P = 0.003). The mean +/- SD middle ear fluid concentration of IL-1 on day 1 was significantly higher in culture-positive (316 +/- 508 pg/ml) than in culture-negative samples (111 +/- 245 pg/ml) (P = 0.01). When paired samples were evaluated, IL-1 decreased on days 4-5 in 13/20 (65%) ears where bacterial eradication was achieved, but also in 11/19 (58%) with persistent or new infection. The mean IL-1 concentrations decreased on days 4-5 in the 20 samples from ears where bacterial eradication was achieved (330 +/- 460 vs 118 +/- 294 pg/ml, P = 0.1) but also in the 17 samples where it was not (465 +/- 660 vs 232 +/- 289 pg/ml, P = 0.02). No significant differences were found between day 1 and days 4-5 in the mean IL-1 concentrations measured in patients with H. influenzae vs S. pneumoniae or concomitant H. influenzae and S. pneumoniae. It was concluded that: 1) IL-1 was detected in the middle ear fluid of most patients with acute otitis media; 2) significantly higher IL-1 concentrations were found in patients with culture-positive than in those with culture-negative acute otits media; 3) IL-1 concentrations decreased on days 4-5 of antibiotic therapy, whether the pathogen was eradicated or not.

Resistance pattern of middle ear fluid isolates in acute otitis media recently treated with antibiotics.

BACKGROUND: Little information is available about the effect of antibiotic treatment on the prevalence and MIC of the subsequently isolated pathogens in cases of acute otitis media (AOM) failing a course of antibiotic therapy. This information is important, particularly regarding the effectiveness of the oral antibiotics used in children failing initial therapy. PATIENTS AND METHODS: One hundred eighty-one children with culture-positive AOM were prospectively studied between October, 1995, and July, 1996. Sixty-three (35%) patients received various antibiotics for variable periods during the 14 days preceding enrollment. RESULTS: A total of 94 Streptococcus pneumoniae (Pnc) and 113 Haemophilus influenzae (Hi) were isolated. Thirty-eight Pnc and 35 Hi were isolated in the 63 patients with recently treated AOM. Pnc as a single isolate was more prevalent in patients recently treated with antibiotics (27 of 63, 43%) than among those not recently treated (32 of 118, 27%, P = 0.047). The MIC50 values of penicillin, cefaclor and cefuroxime axetil for Pnc were significantly higher in the pneumococci isolated from patients recently treated than among those isolated from patients not recently treated with antibiotics (0.38, 3 and 0.75 microg/ml vs. 0.094, 0.38 and 0.12 microg/ml, respectively). Seventy-nine percent of Pnc isolates in the recently treated group had MIC for penicillin of >0.1 microg/ml vs. only 47% in those not recently treated (P < 0.05). The respective figures for MIC >0.5 microg/ml of cefaclor were 79% vs. 41% for the recently treated and not recently treated groups (P < 0.001); cefuroxime MIC >0.5 microg/ml was found in 61 and 25%, respectively (P = 0.001). CONCLUSIONS: Pneumococcus is more prevalent in AOM after a recent antibiotic treatment, and the MIC of the commonly used beta-lactam drugs for Pnc is considerably higher in this setting. In view of our data, the use of oral cephalosporins like cefaclor or cefuroxime as second line drugs in the treatment of unresponsive AOM, particularly in regions where resistant PNC is prevalent, should be reconsidered.

Bacteriologic efficacy of a three-day intramuscular ceftriaxone regimen in nonresponsive acute otitis media.

OBJECTIVE: To determine the bacteriologic efficacy of ceftriaxone in nonresponsive acute otitis media in children. METHODS: In a prospective study 92 patients ages 3 to 36 months (median, 11 months) with culture-proved nonresponsive acute otitis media were studied from January, 1995, through August, 1997. The patients were treated with intramuscular ceftriaxone (50 mg/kg/l/day) for 3 days. Middle ear fluid was aspirated for culture by tympanocentesis on day of enrollment (Day 1); a second tap was performed on Days 4 to 10. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive culture on Days 4 to 10. Patients were followed until Day 17+/-2. Susceptibility was measured by E test. RESULTS: The main drugs administered before enrollment were amoxicillin (38%), amoxicillinclavulanate (25%) and cefaclor (20%). Organisms recovered (n=105) were: Haemophilus influenzae, 54; Streptococcus pneumoniae, 47; Moraxella catarrhalis, 2; and Streptococcus pyogenes, 2. Thirty-four (72%) of the 47 S. pneumoniae isolates were intermediately resistant to penicillin (MIC 0.1 to 1.0 microg/ml), but all were susceptible to ceftriaxone (MIC < 0.5 microg/ml). Bacteriologic eradication was achieved in 100 of 105 (95%) cases: 54 of 54 (10O%) H. influenzae, 43 of 47 (92%) S. pneumoniae, 1 of 2 (50%) M. catarrhalis and 2 of 2 (100%) S. pyogenes. Bacteriologic success (with no relapse) occurred in 13 of 13 (100%) penicillin-susceptible S. pneumoniae vs. 28 of 34 (82%) S. pneumoniae intermediately resistant to penicillin (4 cases of bacteriologic failure and 2 cases of relapse). CONCLUSION: A 3-day intramuscular ceftriaxone regimen is efficacious for the treatment of nonresponsive acute otitis media. The optimal duration of treatment in cases of nonresponsive acute otitis media and whether ceftriaxone is efficacious for the treatment of nonresponsive otitis media caused by S. pneumoniae highly resistant to penicillin is yet to be determined.

Safety and immunogenicity of a combined pentavalent diphtheria, tetanus, acellular pertussis, inactivated poliovirus and Haemophilus influenzae type b-tetanus conjugate vaccine in infants, compared with a whole cell pertussis pentavalent vaccine.

BACKGROUND: We compared the safety and immunogenicity of two combined diphtheria-tetanus-pertussis-inactivated poliovirus vaccines containing either acellular (Pa, SmithKline Beecham Biologicals) or whole cell (Pw, Pasteur Merieux Connaught) pertussis components, mixed with a Haemophilus influenzae type b polysaccharide polyribosylribitol phosphate-tetanus conjugate vaccine in an open, randomized study in healthy infants. DESIGN: The combined vaccines were given at 2, 4, 6 and 12 months of age, and serum samples were obtained at ages 2, 6, 7, 12 and 13 months. Adverse events were obtained by diary cards. RESULTS: The Pa group (n = 101) had a clearly lower incidence of both local and systemic adverse events than the Pw group (n = 100). Immunogenicity was comparable for the diphtheria and tetanus components, but significantly superior for pertussis toxin, filamentous hemagglutinin, pertactin and polioviruses 1, 2 and 3 in the Pa group. Both groups had an appropriate response with regard to H. influenzae type b polysaccharide polyribosylribitol phosphate, but the dynamics of the response were significantly different: geometric mean concentrations (micrograms per ml) after the second, third and booster doses were 1.27, 5.06 and 23.12 in the Pa group and 2.72, 6.66 and 13.59 in the Pw group, respectively (P = 0.0002 after second dose; P = 0.0005 after booster). CONCLUSION: The presently studied diphtheria, tetanus, acellular pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination was at least as immunogenic as the diphtheria, tetanus, whole cell pertussis-H. influenzae b vaccine conjugated to tetanus toxoid combination, with a significantly better safety profile. This is of obvious importance in countries where inactivated poliovirus vaccine is part of the routine infant immunization programs.

Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Nasopharyngeal colonization in southern Israel with antibiotic-resistant pneumococci during the first 2 years of life: relation to serotypes likely to be included in pneumococcal conjugate vaccines.

Nasopharyngeal carriage of Streptococcus pneumoniae was studied in 162 healthy infants at ages 2, 4, 6, 7, 12, and 13 months and in an additional 352 healthy children at ages 12, 15, 18, 21, and 24 months. Carriage was 26%, 39%, and 62% at 2, 12, and 24 months, respectively, and the respective resistance to > or = 1 antibiotic was 11%, 19%, and 27%. The presence of an older sibling or antibiotic treatment during the month preceding the culture was associated with carriage of resistant pneumococci in infants, whereas attendance at large day care centers was associated with carriage during the second year of life. Antibiotic resistance was detected in all 7 serotypes included in the candidate pediatric conjugate vaccines and was significantly more prevalent among vaccine-type pneumococci than among non-vaccine-type pneumococci. The use of conjugate vaccines may reduce the spread of resistant pneumococci.