Appropriate use of antibiotics: focus on acute otitis media.
Explore the source record for details and available documents.
Acute Disease↗
Biomedical subjects
Ron Dagan
Publications and source records attributed to Ron Dagan.
Neonatal genital herpes simplex virus type 1 infection after Jewish ritual circumcision: modern medicine and religious tradition.
OBJECTIVE: Genital neonatal herpes simplex virus type 1 (HSV-1) infection was observed in a series of neonates after traditional Jewish ritual circumcision. The objective of this study was to describe neonate genital HSV-1 infection after ritual circumcision and investigate the association between genital HSV-1 after circumcision and the practice of the traditional circumcision. METHODS: Eight neonates with genital HSV-1 infection after ritual circumcision were identified. RESULTS: The average interval from circumcision to clinical manifestations was 7.25 +/- 2.5 days. In all cases, the traditional circumciser (the mohel) had performed the ancient custom of orally suctioning the blood after cutting the foreskin (oral metzitzah), which is currently practiced by only a minority of mohels. Six infants received intravenous acyclovir therapy. Four infants had recurrent episodes of genital HSV infection, and 1 developed HSV encephalitis with neurologic sequelae. All four mohels tested for HSV antibodies were seropositive. CONCLUSION: Ritual Jewish circumcision that includes metzitzah with direct oral-genital contact carries a serious risk for transmission of HSV from mohels to neonates, which can be complicated by protracted or severe infection. Oral metzitzah after ritual circumcision may be hazardous to the neonate.
Circumcision, Male↗
Haemophilus influenzae: a significant pathogen in acute otitis media.
Haemophilus influenzae is a major pathogen in acute otitis media (AOM) causing disease that is not clinically distinguishable from that caused by Streptococcus pneumoniae. AOM caused by H. influenzae is particularly associated with older age and recurrent disease. Antibiotics differ in their ability to eradicate H. influenzae from the middle ear space. In the United States, widespread pneumococcal vaccination has increased the importance of H. influenzae as a major therapeutic challenge in the treatment of AOM.
Acute Disease↗
High seroprevalence of human metapneumovirus among young children in Israel.
Exposure to the newly discovered human metapneumovirus (HMPV) during the first 2 years of life was studied by longitudinal serological analysis in 40 healthy children in southern Israel. The seropositivity rate decreased to a minimum by age 13 months and increased to 52% by age 24 months. Evidence of new infection was detected in 13%, 23%, and 55% of children by ages 7, 13, and 24 months, respectively. The high exposure rates suggest that HMPV may be an important cause of community-acquired respiratory-tract infections in young children.
Adolescent↗
Cytokine mRNA expression in pneumococcal carriage, pneumonia, and sepsis in young mice.
We studied cytokine mRNA expression in Streptococcus pneumoniae carriage, pneumonia, and sepsis in 3-week-old, inbred C57BL/6 and BALB/c mice. Mice were inoculated intranasally with S. pneumoniae serotype 6B, 14, or 3. Survival, bacterial load in the nasopharynx (NP) and lungs, and mRNA levels of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta, interleukin (IL)-10, and IL-12 in the spleen were analyzed. No baseline mRNA expression levels were found, except for TNF-alpha in C57BL/6 mice. Serotype 6B caused NP colonization only, a significant (P<.05) increase in the levels of TNF-alpha, and induction of TGF-beta and IL-12 mRNA. Serotype 14 caused NP and nonlethal lung colonization and induction of TGF-beta, IL-10, and IL-12. Serotype 3 caused NP colonization, pneumonia, 35% mortality, and no alteration in the mRNA expression of tested cytokines. Although activation of the immune system culminated in nonlethal disease, evasion of the immune system was associated with detrimental disease.
Animals↗
Serological criteria for evaluation and licensure of new pneumococcal conjugate vaccine formulations for use in infants.
The World Health Organization (WHO) is undertaking a series of consultations on serological criteria for the evaluation and licensure of new formulations/combinations or different vaccination schedules of pneumococcal conjugate vaccines. The lack of a definitive serological correlate of protection and the multiplicity of antigens involved, especially since the clinical efficacy of most of the individual serotypes represented in the only licensed vaccine has not been established, are hindering the formulation of criteria for licensure of new formulations or combinations of the vaccine. This report analyses the various options with their relative merits and drawbacks and provides preliminary recommendations as guidance to regulatory agencies in evaluating these vaccines for the purposes of licensure. More detailed recommendations for production and control of pneumococcal conjugate vaccines, including criteria for evaluation for licensure, are currently being drafted.
Antibodies, Bacterial↗
The involvement of IL-6 and IL-8 in acute invasive gastroenteritis of children.
The involvement of the proinflammatory cytokines, interleukin 8 (IL-8) and 6 (IL-6), was studied during the first 72 h of acute invasive gastroenteritis. Study population included 33 infants and young children aged six months to six years and seven age-matched controls. As a group, patients with acute invasive gastroenteritis had an increased serum level of IL-8 and IL-6 as compared with healthy controls (p < 0.002 and p < 0.001, respectively). Subjects were then divided into two groups based on stool cultures (proven and non-proven bacterial cultures). Patients with bacterial-proven acute invasive gastroenteritis tended to have increased IL-8 serum concentrations (p < 0.07) as compared with those with non-proven bacterial etiologies and IL-6 levels were only detected in subjects with positive bacterial cultures (p < 0.05). When dividing each sub-group into early and late blood drawing with respect to disease onset, no statistical differences were found in each group but subjects with bacterial-proven etiologies had significant higher IL-6 levels as compared with non-proven etiologies at the two time points (p < 0.019 and p < 0.015, respectively). In conclusion, the proinflammatory cytokines, IL-6 and IL-8, are involved in acute invasive gastroenteritis. The difference in IL-6, and to a lesser degree IL-8, between proven and non-proven bacterial etiologies, needs further investigation.
Child↗
The burden of acute otitis media on the patient and the family.
UNLABELLED: The aim of our study was to determine the burden of acute otitis media (AOM) on patients and their families. Parents of children with AOM were interviewed with regard to the week preceding the AOM diagnosis and every 3 days henceforth for an additional 21 days. The interview included information on loss of workdays, use of health care services and impact on the patient's and family's quality of life. Parents of age- and neighbourhood-matched controls were interviewed in an identical manner. A total of 150 patients and 51 controls were included in the analysis. The following variables differed significantly ( P<0.001) between patients and controls (mean +/- SD): non-routine days 18.5+/-11.0 in patients versus 3.4+/-6.5 in controls; number of visits to primary health centres 2.6+/-1.6 versus 0.4+/-0.6; number of emergency room visits 0.2+/-0.5 versus 0.1+/-0.02 and number of visits to an otolaryngology clinic 0.3+/-0.6 versus 0. Days of antibiotic and over the counter drug use were 9.0+/-5.6 versus 0.3+/- 0.9 and 7.0+/-6.0 versus 4.9+/-6.0, respectively per episode. The mean loss of workdays per child was 1.6+/-1.8 in patients versus 0.25+/-0.6 in controls, for working mothers and 0.6+/-1.1 versus 0.1+/-0.4 for working fathers; duration of absenteeism from day care facilities was 3.5+/-2.5 versus 0.9+/-2.7. CONCLUSION: Acute otitis media significantly reduces the quality of life of both child and parents, causes substantial use of medical services and significant loss of workdays.
Acute Disease↗
The potential indirect effect of conjugate pneumococcal vaccines.
Pneumococcal conjugate vaccines are highly effective in preventing invasive disease in infants and young children, with favorable safety and immunogenicity profiles. These pediatric vaccines have also shown efficacy in reducing cases of non-invasive disease (i.e. otitis media, pneumonia). Recently, pneumococcal conjugate vaccines have demonstrated additional protective qualities that may enhance their use worldwide. For example, they can reduce nasopharyngeal acquisition of vaccine-specific serotypes of Streptococcus pneumoniae, which may in turn reduce the incidence of pneumococcal disease among non-vaccinated individuals; this is termed indirect or herd immunity. Although the emergence of antibiotic-resistant strains has complicated disease management, pneumococcal conjugate vaccines have been shown to protect against pneumococcal disease caused by such strains because most antibiotic-resistant strains are of the serotypes included in these vaccines. Thus, widespread use of these conjugate vaccines may prevent disease by providing both direct and indirect immunity, and may reduce the use of antibiotics and the development of antibiotic resistance worldwide.
Child, Preschool↗
Pneumococcal conjugate vaccines: proceedings from an interactive symposium at the 41st Interscience Conference on Antimicrobial Agents and Chemotherapy.
Globally, Streptococcus pneumoniae is a leading cause of invasive and noninvasive disease in infants and young children. The emergence of antibiotic-resistant strains has increased interest in prevention through immunization. Currently, the only available conjugate pneumococcal vaccine is a seven-valent formulation, PNCRM7. This paper presents excerpts from a symposium that provided an update of ongoing surveillance data and clinical trials evaluating pneumococcal conjugate vaccines. The topics addressed included: (1) PNCRM7 postmarketing safety data; (2) the impact of PNCRM7 in premature infants; (3) the direct and indirect effect of pneumococcal conjugate vaccines on colonization; (4) the effect of pneumococcal conjugate vaccines on replacement disease and the rate of resistance among replacement serotypes; (5) the current recommendations for the use of PNCRM7; and (6) the potential impact of conjugate vaccines in Europe and the Asia-Pacific region.
Anti-Bacterial Agents↗
Accurate diagnosis and appropriate treatment of acute bacterial rhinosinusitis: minimizing bacterial resistance.
BACKGROUND: Antimicrobial resistance in respiratory pathogens has become a common clinical problem that has serious public health implications. Inappropriate use of antibiotics for the treatment of viral upper respiratory tract infections (URTIs) has contributed to the development of resistant microorganisms. Health care providers can help control the spread of resistance by limiting the use of antimicrobial agents to infections that meet clinical guidelines for a bacterial cause. OBJECTIVE: This article examines the means of accurately diagnosing and appropriately treating acute bacterial rhinosinusitis (ABRS) in an effort to control increasing levels of resistance. METHODS: This article discusses current treatment guidelines that provide the evidenced-based rationale for choosing the most appropriate antimicrobial agents for suspected ABRS in adults and children. An evidence-based approach can help minimize the public health threat posed by the continuing increase in microbial resistance. RESULTS: Although definitive clinical criteria that differentiate between ABRS and viral URTI are lacking, careful evaluation of the duration and severity of symptoms provides a rational basis for diagnosing ABRS in primary care settings. CONCLUSIONS: Once a diagnosis of ABRS has been made, empiric antibiotic therapy may be justified. When it is, the first-line agent should be the narrowest spectrum antibiotic that would be expected to eradicate the most common causative organisms. The antibiotic selection process should take into account prevailing patterns of resistance and the presence of risk factors for infection with resistant pathogens, as well as published evidence-based guidelines.
Acute Disease↗
Achieving bacterial eradication using pharmacokinetic/pharmacodynamic principles.
Evidence from studies in otitis media indicates that antimicrobials and dosing regimens that have equivalent bacteriologic efficacy against susceptible pathogens can have significantly different bacteriologic success rates against resistant strains of the same species. Unlike macrolide and fluoroquinolone resistance, penicillin resistance can be overcome in Streptococcus pneumoniae by increasing the dose, and hence increasing the time for which the serum concentrations are above the MIC. The new clinical formulation of extra-strength amoxicillin-clavulanate provides 90 mg/kg per day amoxicillin plus 6.4 mg/kg per day clavulanate (14:1) divided every 12 h, compared with 45/6.4 mg/kg per day b.i.d. with conventional dosing. The pharmacokinetic/pharmacodynamic (PK/PD) profiles of extra-strength amoxicillin-clavulanate predict that the new formulation will be more effective than the conventional formulation against S. pneumoniae with elevated amoxicillin MICs and against Haemophilus influenzae. In an open-label, non-comparative study in children with acute otitis media, the extra-strength formulation had high bacteriologic success rates against the major respiratory pathogens, including penicillin-resistant S. pneumoniae. The development of new antimicrobial agents and formulations should be aimed at meeting PK/PD parameters predictive of bacterial eradication of both susceptible and resistant strains.
Amoxicillin-Potassium Clavulanate Combination↗
Independent risk factors for carriage of penicillin-non-susceptible Streptococcus pneumoniae.
Antibiotic treatment, day-care center (DCC) attendance and young age are associated with penicillin-non-susceptible Streptococcus pneumoniae (PNSSp) carriage. Yet, it is unclear whether each is an independent risk factor for the individual. This cross-sectional surveillance study was designed to answer this question. Nasopharyngeal cultures were obtained from 429 children (< 6 y) during a visit to the pediatrician's office. Two risk rates were calculated: the individual's absolute risk to carry PNSSp [simple odds ratio (ORS)] and the risk of an individual who is already a carrier [conditional odds ratio (ORC)]. Streptococcus pneumoniae was isolated from 52.7% of 401 children. PNSSp was detected in 37.1% of carriers. Independent risk factors were: young age [ORS 2.24, 95% confidence interval (95% CI) 1.2-4.2], DCC attendance (ORS 3.8, 95% CI 1.9-7.5), having young siblings (ORS 2.3, 95% CI 0.95-5.57) and each antibiotic treatment during the previous 3 months (ORS 1.5, 95% CI 1.25-1.85). The only significant risk factor among carriers was prior antibiotic treatment (ORC 2.24, 95% CI 1.64-3.05). Young children, who attended DCC and received 1 antibiotic course (9% of the population) had a risk 12.9 times higher than children without these features.
Age Distribution↗
Greater antibody responses to an eleven valent mixed carrier diphtheria- or tetanus-conjugated pneumococcal vaccine in Filipino than in Finnish or Israeli infants.
BACKGROUND: Antibody responses to pneumococcal conjugate vaccines may vary when administered in different populations or epidemiologic settings. Understanding the causes and significance of this variation could help to determine the number of doses and timing required for protection against pneumococcal diseases in each country. METHODS: This report compares antibody responses to aluminum-adjuvanted and nonadjuvanted mixed carrier 11-valent diphtheria- or tetanus-conjugated pneumococcal vaccine (11-PncTD) formulations when given at 6, 10 and 14 weeks and 9 months of age to Filipino infants (n = 51) and at 2, 4, 6 and 12 months of age to Finnish (n = 127) and Israeli (n = 124) infants. The study populations differ in their natural exposure to pneumococcus and risk factors for pneumococcal carriage and disease. RESULTS: Filipino and Israeli infants had slightly but significantly higher prevaccination geometric mean concentration (GMC) of antibodies than did the Finnish infants. After three doses of aluminum-adjuvanted 11-PncTD vaccine, the Filipino infants had 1.8 to 6.7 and 1.5 to 5.0 times higher GMC than the Finnish and Israeli infants, respectively, against pneumococcal serotypes conjugated to tetanus protein. The GMC of serotypes conjugated to diphtheria toxoid was 1.3 to 3.0 and 0.7 to 2.0 times the GMC in Finnish and Israeli infants, respectively. The nonadjuvanted vaccine formulation induced generally lower GMCs. CONCLUSIONS: The antibody responses to the tetanus-conjugated polysaccharides were considerably higher in the Filipino than in the Finnish or Israeli infants. This may be a result of several factors including the priming effect of tetanus toxoid given to pregnant women, early pneumococcal nasopharyngeal acquisition and genetic differences among populations.
Antibodies, Bacterial↗
Bacteriologic and clinical efficacy of high dose amoxicillin for therapy of acute otitis media in children.
BACKGROUND: High dose (70 to 90 mg/kg/day) amoxicillin is recommended as first line therapy of acute otitis media (AOM) in geographic areas where drug-resistant Streptococcus pneumoniae is prevalent. Information on the bacteriologic efficacy of high dose amoxicillin treatment for AOM is limited. OBJECTIVES: To evaluate the bacteriologic and clinical efficacy of high dose amoxicillin as first line therapy in AOM. METHODS: In a prospective study 50 culture-positive patients ages 3 to 22 months (median, 9 months; 77% <1 year) were treated with high dose amoxicillin (80 mg/kg/day three times a day for 10 days) No antibiotics were administered 72 h before enrollment. Twenty-four (48%) patients presented with their first episode of AOM. Middle ear fluid was cultured by tympanocentesis at enrollment and on Days 4 to 6 of therapy. Additional middle ear fluid cultures were obtained if clinical relapse occurred. Bacteriologic failure was defined by positive cultures on Days 4 to 6 and clinical failure by no change or worsening of AOM signs and symptoms and requirement for additional antibiotics during therapy and/or at end of therapy. Patients were followed until Day 28 +/- 2. Susceptibility to penicillin and amoxicillin was measured by E-test. RESULTS: Sixty-five organisms were recovered at enrollment: Haemophilus influenzae (38), Streptococcus pneumoniae (24), Streptococcus pyogenes (2) and Moraxella catarrhalis (1). Eighteen (75%) S. pneumoniae were nonsusceptible to penicillin (MIC > 0.1 microg/ml). All 24 S. pneumoniae isolates had amoxicillin MIC < or = 2.0 microg/ml. Thirteen (34%) of the 38 H. influenzae were beta-lactamase producers. Eradication was achieved in 41 (82%) patients for 54 of 65 (83%) pathogens: 22 of 24 (92%) S. pneumoniae, 21 of 25 (84%) beta-lactamase-negative H. influenzae, 8 of 13 (62%) beta-lactamase-positive H. influenzae, 2 of 2 S. pyogenes and 1 of 1 M. catarrhalis. Seven organisms not initially present were isolated on Days 4 to 6 in 5 patients: 3 beta-lactamase-positive H. influenzae; 1 beta-lactamase-negative H. influenzae; 2 S. pneumoniae; and 1 M. catarrhalis. In total 14 of 50 (28%) patients failed bacteriologically on Days 4 to 6 (persistence + new infection), of whom 9 (64%) had beta-lactamase-positive H. influenzae. Three (33%) of the 9 patients with bacteriologic failure (2 beta-lactamase-positive H. influenzae, 1 S. pneumoniae) failed also clinically on Days 4 to 6. CONCLUSIONS: The predominant pathogens isolated from children with AOM failing high dose amoxicillin therapy were beta-lactamase-producing organisms. Because its overall clinical efficacy is good, high dose amoxicillin is still an appropriate choice as first line empiric therapy for AOM, followed by a beta-lactamase-stable drug in the event of failure.
Acute Disease↗
Recurrent acute otitis media occurring within one month from completion of antibiotic therapy: relationship to the original pathogen.
OBJECTIVES: (1) To determine the relationship between acute otitis media (AOM) pathogens isolated in cases of early clinical recurrence of AOM (occurring within 1 month from completion of therapy) to the original pathogens causing the initial AOM episode; and (2) To determine whether shorter time intervals between completion of antibiotic therapy and clinical recurrences of AOM are associated with higher rates of true bacteriologic relapse. PATIENTS AND METHODS: From 1995 through 2000, 1077 infants and young children ages 3 to 36 months with AOM were enrolled in double tympanocentesis (performed on Day 1 in all patients and Days 4 to 6 in those initially culture-positive) studies. Of these, 834 (77%) completed successfully the antibiotic treatment [pathogen eradication on Days 4 to 6 of therapy or no pathogen on middle ear fluid (MEF) culture on Day 1 and clinical improvement at end of therapy]. Patients were followed for 3 to 4 weeks after completion of therapy, and additional MEF cultures were obtained if clinical recurrence occurred. True bacteriologic relapse was defined as the presence of a pathogen identical with that isolated before therapy by serotype and pulsed field gel electrophoresis for and by pulsed field gel electrophoresis for Streptococcus pneumoniae and beta-lactamase production for Haemophilus influenzae. RESULTS: MEF cultures were performed in 108 consecutive patients with early recurrent AOM. One hundred pathogens were isolated at recurrence in 88 of 108 (81%) patients: 54 H. influenzae; 45 S. pneumoniae; and 1 Moraxella catarrhalis. Most recurrent AOM episodes developed during the first 2 weeks of follow-up; 39 (36%), 38 (35%), 21 (19%) and 10 (9%) recurrent AOM episodes occurred on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively. In most patients these episodes were caused by a new pathogen. True bacteriologic relapses were found in 30 (28%) of 108 patients whose MEF cultures were positive for 35 pathogens: 13 of 108 (12%) S. pneumoniae; 12 of 108 (11%) H. influenzae; and 5 of 108 (5%) both. When timing of recurrent AOM after completion of therapy was analyzed, true bacteriologic relapses were found in 16 of 39 (41%), 10 of 38 (26%), 3 of 21 (14%) and 1 of 10 (10%) of all episodes on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively (P = 0.01). The respective rates for were 11 of 17 (65%), 3 of 10 (30%), 3 of 13 (23%) and 1 of 5 (20%) (P = 0.02). For H. influenzae the respective rates were 8 of 19 (42%), 9 of 23 (39%), 0 of 8 (0%) and 0 of 4 (0%) (P = 0.02). CONCLUSIONS: Most recurrent AOM episodes occurring within 1 month from completion of antibiotic therapy are in fact new infections. Most of the true bacteriologic AOM relapses occur within 14 days after completion of therapy, but even during this time interval most of the recurrences are caused by new pathogens. H. influenzae is very unlikely to cause true bacteriologic AOM relapses 14 days or later after completion of therapy.
Acute Disease↗
Can acute otitis media caused by Haemophilus influenzae be distinguished from that caused by Streptococcus pneumoniae?
BACKGROUND: Previous limited data suggest that acute otitis media (AOM) caused by Streptococcus pneumoniae can present as a more severe disease than that caused by Haemophilus influenzae or Moraxella catarrhalis, as expressed by both tympanic membrane and systemic findings. OBJECTIVES: To evaluate the severity of disease and impact of various pathogens, age, disease history and previous antibiotic therapy in children with AOM by using a comprehensive clinical/otologic score. PATIENTS AND METHODS: The study group consisted of 372 children ages 3 to 36 months with AOM seen at the pediatric emergency room during 1996 through 2001. All patients had tympanocentesis and middle ear fluid culture performed at enrollment. Clinical status was determined by a clinical/otologic score evaluating severity (0 = absent to 3 = severe) of tympanic membrane findings (redness and bulging) and patient's fever, irritability and ear tugging. Maximal severity score was 15. RESULTS: There were 138 (37%) H. influenzae, 76 (21%) S. pneumoniae, 64 (17%) mixed infections (H. influenzae + S. pneumoniae) and 94 (25%) culture-negative cases. The overall clinical/otologic score was higher in culture-positive than in culture-negative patients (9.27 +/- 2.75 vs.8.38 +/- 3.08, P = 0.01). When analyzed by age groups, this difference was significant only for the youngest age group (3 to 6 months, P = 0.05). The severity scores for AOM caused by H. influenzae and S. pneumoniae were significantly higher than in the culture-negative AOM when tympanic membrane redness and bulging were analyzed separately. No differences were recorded in clinical/otologic scores between different pathogens (9.49 +/- 2.86, 9.03 +/- 2.72 and 9.09 +/- 2.54 for H. influenzae, S. pneumoniae and H. influenzae + S. pneumoniae, respectively). The mean clinical/otologic score was higher in culture-positive than in culture-negative patients without relationship to previous antibiotic treatment or number of previous AOM episodes. CONCLUSIONS: (1) The clinical/otologic score of culture-positive young infants was higher than that of culture-negative infants; (2) the severity of tympanic membrane redness and bulging were the most indicative factors discriminating between a bacterial and nonbacterial etiology of AOM; and (3) the use of a clinical/otologic score could not discriminate among various bacterial etiologies of AOM.
Acute Disease↗
Vaccination of day-care center attendees reduces carriage of Streptococcus pneumoniae among their younger siblings.
AIM: We conducted a study to determine whether administration of a pneumococcal conjugate vaccine to toddlers attending day-care centers (DCCs) could prevent acquisition of Streptococcus pneumoniae of the vaccine serotypes (VT) by their younger siblings. METHODS: In a double blind study, 262 DCC attendees ages 12 to 35 months were randomized to receive a 9-valent pneumococcal conjugate vaccine (PnCRM9; n = 132), or a control vaccine (meningococcus C vaccine; n = 130). It was planned to follow the groups for 2 years with monthly nasopharyngeal pneumococcal cultures during the first follow-up year and every 2 months during the second year. Forty-six younger siblings of the above described children, age <18 months (23 siblings of the PnCRM9 recipients and 23 of the controls), were also enrolled, and nasopharyngeal cultures were obtained monthly until the children reached the age of 18 months or started to attend DCC, if before the age of 18 months. Pneumococcal isolates were serotyped and tested for antibiotic susceptibility. RESULTS: Of the 3748 cultures obtained from the DCC attendees, 2450 (65%) were positive for S. pneumoniae. Of 306 cultures obtained from the younger siblings, 151 (49%) were positive. Among the PnCRM9 recipients, cultures were significantly less frequently positive for the VT S. pneumoniae than among the controls (13% vs. 21%, respectively; P < 0.001). The same pattern was seen in the younger siblings of PnCRM9 recipients vs. the siblings of controls (21% vs. 34%, respectively; P = 0.017). The reverse trend was seen for non-VT strains in both the DCC attendees (44% vs. 34%, respectively; P < 0.001) and their younger siblings (19% vs. 13%, respectively; P = 0.15). There was a significant decrease in the carriage rate of antibiotic-resistant S. pneumoniae in both the PnCRM9 recipients and their younger siblings. The relative risks (and 95% confidence intervals) to carry S. pneumoniae penicillin-nonsusceptible, resistant to > or =1, > or =2 and > or =3 antibiotic categories among younger siblings of PnCRM9 recipients vs. siblings of controls were 0.47 (0.31 to 0.70), 0.49 (0.33 to 0.71), 0.46 (0.30 to 0.73) and 0.49 (0.21 to 1.17), respectively. When acquired, VT and antibiotic-resistant S. pneumoniae were carried for a significantly shorter period of time among siblings of PnCRM9 recipients than in siblings of controls. CONCLUSION: The marked effect of PnCRM9 administration to DCC attendees on carriage of VT and antibiotic-resistant S. pneumoniae among their younger household close contacts demonstrates a herd effect of the vaccine.
Analysis of Variance↗