Investigation of Streptococcus pneumoniae and Haemophilus influenzae isolated from pediatric outpatients nationwide with a respiratory tract infection at the first consultation (2002-2003)--proportion of resistant strains and sensitivity to oral antibacterial agents

The propotions of resistant strains and sensitivity to oral antibacterial agents were determined for 468 strains of Streptococcus pneumoniae and 557 strains of Haemophilus influenzae isolated from pediatric outpatients with a respiratory tract infection at the first consultation at 20 medical institutions nationwide in the predefined 4-week period during November 2002 and June 2003. PRSP of the S. pneumoniae strains, accounted for 27%, and BLNAR accounted for 35% of the H. influenzae strains. Against the S. pneumoniae strains, faropenem showed the best MIC90 value, 0.5 microg/mL, of the beta-lactam antibacterial agents, followed by cefditoren-pivoxil, and among the macrolide and ketolide antibacterial agents, telithromycin showed the best MIC90 value, 0.12 microg/mL. Against the H. influenzae strains, cefditoren-pivoxil showed the best MIC90 value, 0.25 microg/mL, among the beta-lactam antibacterial agents, and among the macrolide and ketolide antibacterial agents, azithromycin showed the best activity, followed by telithromycin. It seems necessary to take these results into consideration when choosing drugs for treatment. It will be necessary to survey the trends in resistant strains and the clinical efficacy of various oral antibacterial agents in the future.     

Antimicrobial resistance in Streptococcus pneumoniae and Haemophilus influenzae isolated from nasopharynx in children

The aims of this study are to investigate the antimicrobial susceptibility of bacteria isolated from children and clarify the risk factors for the carriage of the resistant strains. We examined the minimum inhibitory concentrations (MICs) of antimicrobial agents against 949 strains of Streptococcus pneumoniae (S. pneumoniae) and 791 strains of Haemophilus influenzae (H. influenzae) isolated at our department between September, 2001 and May, 2003. Of those, 226 S. pneumoniae strains and 115 H. influenzae strains were analysed for the resistance genes. Also we retrospectively reviewed the profiles of 1,359 patients with either S. pneumoniae, H. influenzae, or both in nasopharynx. From the view point of MICs, PSSP strains were 185 (19%), PISP strains were 443 (47%), and PRSP strains were 321 (34%) in 949 S. pneumoniae strains, and BLNAS strains were 545 (69%), low-BLNAR strains were 104 (13%), BLNAR strains were 81 (11%), and BLPAR strains were 61 (8%) in 791 H. influenzae strains. The results of gene analysis showed that all resistant strains by MICs such as PISP, PRSP, BLNAR, and BLPAR had resistant genes and that 55% of and 21% of susceptible strains of S. pneumoniae (PSSP) and H. influenzae (BLNAS), respectively, had resistant genes. From the investigation for profiles of 1,359 patients, age less than 3 years old, day nursery, and use of antimicrobial agents in last 3 month, seemed to be the risk factors for carriage of resistant strains. To prevent the resistant bacteria from disseminating we should re-consider how to use the antimicobial agents and nurse the young children.     

Trends in pediatric bacterial meningitis in Japan (2003-2004)

We surveyed the epidemiology of pediatric bacterial meningitis between January 2003 and December 2004 in Japan, with the following results: Bacterial meningitis cases numbered 233 (132 boys, 98 girls, and 3 unidentified), equivalent to 1.13-1.6 children of 1000 hospitalized in pediatrics per year. The age distribution for the infections was the highest under 1 year of age, decreasing with increasing age. Haemophilus influenzae was the most common pathogen, followed by Streptococcus pneumoniae, group B streptococcus, and Escherichia coli. The relationship between causactive pathogens and age distribution was as follows: group B. streptococcus and E. coli were major pathogens below 4 months of age and H. influenzae and S. pneumoniae were major pathogens above 4 months of age. Susceptibility tests at each facility demonstrated that 65.0% of H. influenzae isolates and 83.0% of S. pneumoniae isolates in 2004 were drug-resistant. Ampicillin and cephem antibiotics are currently effective against GBS, E. coli and Listeria so a combination of ampicillin and cephem antibiotics is used first line at many facilities for patients below 4 months of age. A combination of carbapenem which showed effective against PRSP and cephem which showed effective against H. influenzae is the first choice in childhood bacterial meningitis for patients above 4 months of age.     

Antimicrobial treatment of otitis media.

The major pathogens causing acute otitis media (AOM) are Streptococcus pneumoniae and Haemophilus influenzae, with Moraxella catarrhalis, Streptococcus pyogenes, and Staphylococcus aureus less frequently isolated. The same organisms and Staphylococcus epidermidis are found in chronic otitis media with effusion. In chronic suppurative otitis media, Pseudomonas aeruginosa and S aureus are most frequently found. Antimicrobial agents found to be most effective in treating AOM are amoxicillin, trimethoprimsulfamethoxazole, erythromycin-sulfisoxazole, amoxicillin-clavulanate, and cefaclor. Cefuroxime axetil and cefixime are alternatives for which there are less data. Currently, about 20% of AOM cases are caused by beta-lactamase-producing strains (usually H influenzae or M catarrhalis) that are resistant to amoxicillin, thus favoring the use of the other agents listed. Concentrations of antibiotics in middle ear infections range from 10% to 76% of peak serum levels for the listed agents and are higher in AOM than in chronic otitis media with effusion, emphasizing the importance of adequate dosing for successful treatment.     

Inhibitory effect of N-acetylcysteine on adherence of Streptococcus pneumoniae and Haemophilus influenzae to human oropharyngeal epithelial cells in vitro

BACKGROUND: Bacterial adherence to mucosal and epithelial cell structures is of importance for the persistence of bacteria in the airways. Cigarette smoking and chronic bronchitis are associated with increased bacterial adherence. N-Acetylcysteine (NAC) medication reduces the number of infectious exacerbations in patients with chronic bronchitis, and NAC medication has been associated with low intrabronchial bacterial numbers. OBJECTIVE: We investigated whether NAC influences bacterial adherence as a possible mechanism behind its clinical effects. METHODS: Highly adhering test strains of Streptococcus pneumoniae and Haemophilus influenzae were used to investigate the influence of four pharmacological compounds on adherence to oropharyngeal epithelial cells in vitro. Adhesion assays were performed both during short-term exposure to, as well as after long-time incubation with, NAC, lidocaine, hydrocortisone and terbutaline at concentrations not inhibiting bacterial growth. RESULTS: Only NAC showed a significant inhibitory effect on adhesion of H. influenzae during short-term incubation. After long-term incubation, both NAC and hydrocortisone inhibited bacterial adhesion for both strains in a dose-dependent manner. When NAC's effect on three different strains of S. pneumoniae and four strains of H. influenzae was studied, inhibition of bacterial adhesion was found for three strains of each species. CONCLUSIONS: NAC lowers bacterial adhesion in vitro to oropharyngeal epithelial cells in doses equivalent to that is being used clinically. This effect might be a contributory mechanism behind the reduction of infectious exacerbations in chronic bronchitis patients.     

Effects of amoxicillin/clavulanate or azithromycin on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae in children with acute otitis media.

The effect of antibiotic therapy on nasopharyngeal colonization by Streptococcus pneumoniae and Haemophilus influenzae was evaluated in children diagnosed with acute otitis media. Children were randomly assigned to receive either amoxicillin/clavulanate or azithromycin therapy, and nasopharyngeal swabs were obtained for culture before and after starting therapy. Amoxicillin/clavulanate therapy eradicated or suppressed all strains of S. pneumoniae susceptible to penicillin, 75% of strains with intermediate resistance, and 40% of strains resistant to penicillin. Azithromycin therapy cleared two-thirds of azithromycin-susceptible strains of S. pneumoniae but none of azithromycin-nonsusceptible strains. Selection for antibiotic-resistant strains in individual children was not observed in children who received amoxicillin/clavulanate therapy but was observed in 2 children who received azithromycin therapy. Carriage of H. influenzae was also reduced by antimicrobial therapy but more so by amoxicillin/clavulanate. Antibiotic therapy does not directly increase the number of resistant strains in the population but, by eradicating susceptible strains, allows greater opportunity for carriage and spread of resistant strains.     

Childhood bacterial meningitis trends in Japan from 2005 to 2006

We surveyed pediatric bacterial meningitis epidemiology from January 2005 to December 2006 in Japan, with the following results. Bacterial meningitis cases numbered 246 -138 boys and 108 girls-, equivalent to 1.7-1.72 children of 1,000 hospitalized in pediatrics per year. The age distribution for infection was highest in those under 1 year of age and decreased with increasing age, Haemophilus influenzae was the most common infection causing the pathogen, followed by Streptococcus pneumoniae, group B streptococcus, and Escherichia coli. The relationship between causative pathogens and age distribution was as follows: group B streptococcus and E. coli were major pathogens in patients under 4 months old and H. influenzae and S. pneumoniae in those over 4 months old. Susceptibility tests at individual facilities showed 59.3% of H. influen- zae isolates and 69.3% of S. pneumoniae isolates in 2004 to be drug-resistant. Ampicillin and cephem antibiotics are effective against GBS, E. coli, and Listeria, so combined of ampicillin and cephem antibiotics are used as first-line antibiotics in many facilities in patients under 4 month old and combined of carbapenem antibiotics effective against PRSP and cephem effective against H. influenzae were the first choice against childhood bacterial meningitis in patients over 4 month old.     

Pathogenic bacteria in the nasal vestivulum of children with acute respiratory tract infection

The isolation frequency of pathogenic bacteria for acute respiratory infection (ARI) in the pharynx and nasal vestivulum was investigated. Age group-matched children with or without ARI including 109 individuals in each group were examined. Any of the organisms, which are widely regarded as the pathogens causing ARI such as Haemophilus influenzae, Streptococcus pneumoniae, beta-haemolytic Streptococcus, Staphylococcus aureus, and Moraxella catarrhalis, were isolated from 91% of the patient group and from 77% of the healthy group. The isolation frequency of S. pneumoniae in the nasal vestivulum of the patient group was outstanding. The healthy carrier rates of S. pneumoniae in the pharynx and nasal vestivulum were 9% and 8%, respectively. Whereas the isolation frequencies from the patient group were 7% and 28%, respectively. alpha-haemolytic Streptococci except S. pneumoniae revealed different tendency from S. pneumoniae. These organisms were almost always isolated from their pharynx but rarely isolated from the nasal vestivulum. The isolation frequency of H. influenzae from the pharynx of the patient group was 41%, which was slightly higher than 34% in the healthy group, but the difference was statistically not significant. H. influenzae was not isolated from the nasal vestivulum of the healthy group, nevertheless it was isolated from 25% of the patient group. The isolation of H. influenzae from the nasal vestivulum may have some important information about ARI. S. aureus was isolated from the pharynx with higher rate than the nasal vestivulum in both groups, and moreover, the isolation frequency of S. aureus in the healthy group was higher than the patient group. It means that the diagnosis of staphylococcal infection should be made very carefully. Considering the results of this study, it could be said that bacteriologic examination of the specimens from nasal vestivulum is valuable to determine S. pneumoniae and H. influenzae as the etiologic agents of ARI.     

下呼吸道感染患儿肺泡灌洗液的病原菌分布及其耐药模式

目的:了解2016年至2018年我国下呼吸道感染患儿的肺泡灌洗液病原菌分布及其对抗菌药物的耐药情况。方法:采集2016年1月至2018年12月10家三级医院收治的年龄<18岁的下呼吸道感染患儿的肺泡灌洗液标本,培养分离获得病原菌。采用纸片扩散法或最低抑菌浓度法对分离菌株进行药物敏感试验,分析病原菌的分布情况,以及菌株来...     

Studies on respiratory infections in primary care clinic (IV). Antibiotic sensitivity of bacteria isolated from patients with respiratory infections visiting 21 private clinics in the Tohoku District of Japan

We determined the MICs of ampicillin, methicillin, cefaclor, cefixime, cefteram, ofloxacin and ciprofloxacin against a total of 1,448 strains from 11 species: 464 strains of Staphylococcus aureus, 306 strains of Streptococcus pneumoniae, 114 strains of Streptococcus pyogenes, 37 strains of Branhamella catarrhalis, 329 strains of Haemophilus influenzae, 32 strains of Escherichia coli, 66 strains of Klebsiella pneumoniae, 26 strains of Enterobacter cloacae, 20 strains of Serratia marcescens, 12 strains of Pseudomonas aeruginosa and 42 strains of Acinetobacter calcoaceticus, isolated from the throat swab and the sputum of 2,539 patients with respiratory infections who visited 21 private clinics in Tohoku district of Japan during the period from January to April in 1989. Ciprofloxacin and ofloxacin were more active against S. aureus, B. catarrhalis, P. aeruginosa and A. calcoaceticus than other antibiotics. Ampicillin and cefteram were more active against S. pneumoniae and S. pyogenes than other antibiotics. New-quinolones and cephems of new-generation were active against H. influenzae, E. coli, K. pneumoniae, E. cloacae and S. marcescens. Of 30 strains of S. aureus which were resistant (MIC greater than or equal to 12.5 micrograms/ml) to ampicillin, only one strain was resistant (MIC greater than or equal to 12.5 micrograms/ml) to methicillin. Twenty strains (6.5%) of S. pneumoniae and 49 strains (14.9%) of H. influenzae were resistant (MIC greater than or equal to 1.56 micrograms/ml) to ampicillin. Of 101 strains of H. influenzae of which their beta-lactamase activity was determined by Nitrocephin-method, 27 (26.7%) were beta-lactamase-positive strains. The above results indicated that MRSA is only rarely found in primary care clinics but the incidence of ampicillin-resistant H. influenzae in primary care clinics is almost the same as that of the intensive care clinic, i.e. medical school-affiliated hospitals. Therefore caution should be exercised as regards antibiotic resistance of the causative organism even in primary care clinics.     

Bacteria isolated from chronic upper and lower respiratory tract infections and the associated therapeutic strategies--in paranasal sinusitis

Nasal sinusitis, tonsillitis, and pharyngolaryngitis typify upper respiratory tract infections, while bronchitis and pneumonia typify lower respiratory tract infections. Cases of paranasal sinusitis with severe suppuration are reportedly becoming less frequent, while those of chronic catarrhal paranasal sinusitis and edematous allergic paranasal sinusitis are becoming more so, The primary factor in paranasal sinusitis, a typical infectious disease encountered in otolaryngology, is bacterial infection. The main causative bacteria are Streptococcus pneumoniae, reported in 13.4% of cases, Haemophilus influenzae in 12.8% Moraxella catarrhalis in 5.5%, Staphylococcus aureus in 26.5%, Pseudomonas aeruginosa in 5.2%, and anaerobes. The incidence of strains resistant to antimicrobial agents has grown for S. pneumoniae, H. influenzae, and M. catarrhalis and decreased for S. aureus and P. aeruginosa. Acute exacerbation or severe suppuration in chronic paranasal sinusitis requires the administration of antimicrobial agents, with the same agent administered 2 weeks for maximal effect. First-line agents are AMPC/CVA, SBTPC, CDTR-PI, CFPN-PI, and GFLX for adults, with ASPC, SBPC, ACPC, CTRX, CMZ, FMOX, PAPM/BP, and MEPM injected in severe cases. Attention must be paid to strains that resist cephems and macrolides, such as PISP, PRSP, and BLNAR. In refractory chronic paranasal sinusitis, attention must also be paid to biofilms produced by S. aureus and P. aeruginosa. Suitable antimicrobial agents should be determined for treating of chronic paranasal sinusitis, in addition to the best procedure to ensure early recovery from inflammation, such as puncturing or irrigating the maxillary sinus, injecting a suitable agent, nebulization, and/or surgically widening the middle meatus.     

Detection of bacterial antigens in body fluids by the Phadebact system

150 infected patients from 2 study centers had body fluids examined for presence of bacterial antigens (group B streptococcus, Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b) using the Pharmacia Phadebact system. The rates of detection of the pneumococcal antigens in the urine or serum of the patients with pneumococcal pneumonia, pneumococcal bacteremia and pneumococcal meningitis were 0.38, 0.47 and 0.5, respectively. The overall detection rate for H. influenzae infections was 0.92 and for group B streptococcal infections 0.87. Serum and urine from 100 non-infected patients were also tested for the presence of group B streptococcus, S. pneumoniae, N. meningitidis and H. influenzae type b antigens with only 1 false positive (H. influenzae type b).     

Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection

The incidence of Haemophilus influenzae and Streptococcus pneumoniae in children with acute respiratory infection (ARI) under 5 years was carried out by throat swab culture, blood culture, body fluid or tissue culture in 688 patients from a community, 744 patients from a teaching hospital in Bangkok, 766 normal children from the community and 303 children from a hospital well baby clinic. H. influenzae was found in the throats of 15-20% of patients and in the throats of 4-6% of normal children (p less than 0.001 for both hospital and community patients). Only 12/332 strains (3.6%) of H. influenzae were type b. The rest of H. influenzae were non type b. The most common biotype of H. influenzae non type b was biotype II. S. pneumoniae was found in hospital patients in highly significant numbers compared to the controls (12% vs 4%). No significant difference was observed in strains from the community patients.     

Relapse of acute purulent otitis media: antibiotic sensitivities of nasopharyngeal pathogens

The present investigation was conducted to find out if a relapse of acute purulent otitis media is associated with a decreased sensitivity of nasopharyngeal pathogens to commonly used antimicrobial agents. All but one of 63 children with relapse included in this study yielded one or more of the classical middle ear pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, S. pyogenes) in their nasopharynx (NPH) secretions. S. pneumoniae was the predominating isolate from NPH (71% of the patients) as well as from middle ear effusion (53%). At a control visit 4 weeks after the start of antibiotic therapy, 91% were NPH carriers of potential pathogens and S. pneumoniae was still the most common isolate (53%). Beta-lactamase was produced by 55% of B. catarrhalis isolates from the NPH specimens on the first visit, but only by 33% of B. catarrhalis isolates on the control visit. Two NPH isolates of H. influenzae produced beta-lactamase. One isolate of S. pneumoniae (serotype 18) was intermediately sensitive to phenoxymethylpenicillin. Generally low MICs were found for erythromycin and cefaclor. H. influenzae isolates were generally sensitive to ampicillin in vitro, but only 1 isolate was fully sensitive to erythromycin. B. catarrhalis isolates were uniformly sensitive to doxycycline and trimethoprim/sulphamethoxazole. No tolerance to penicillin was demonstrated in S. pneumoniae and H. influenzae. The present data indicate that the relapse of acute otitis media is not associated with development of tolerance or resistance to therapeutic antimicrobials commonly used.     

Clinical characteristics of pneumonia caused by beta-lactamase negative ampicillin resistant Haemophilus influenzae (BLNAR)

We wished to assess the clinical differences between beta-lactamase-negative, ampicillin-sensitive and beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae pneumonia. The medical records of 118 patients with H. influenzae pneumonia admitted between March 1998 and March 2003 to Nagasaki University Hospital and affiliated institutions were reviewed. In line with CLSI (Clinical and Laboratory Standards Institute) criteria, we classified H. influenzae according to sensitivity to ampicillin as follows: S (sensitive), minimum inhibitory concentration (MIC) =1; I (intermediate sensitivity), MIC =2; R (resistant), MIC =4. We defined the R strains as the BLNAR group and the S and I strains as the non-BLNAR group. We measured the patient's background, Pneumonia Severity Index (PSI), drug sensitivity of H. influenzae, and evaluation of antibiotic choices. There were no significant clinical differences between the beta-lactamase-negative, ampicillin-susceptible and the beta-lactamase-negative, ampicillin-resistant groups. However, BLNAR pneumonia was more prominent in the younger than the older patients. This study should provide useful information for understanding the clinical characteristics of BLNAR pneumonia.     

Role of Streptococcus pneumoniae and Haemophilus influenzae in the development of acute otitis media and otitis media with effusion in a gerbil model

The efficacy of amoxicillin/clavulanate and cefuroxime was determined in a gerbil model of otitis media with a mixed Streptococcus pneumoniae plus Haemophilus influenzae middle ear (ME) infection. Results were compared with those obtained in a previous single H. influenzae model. All untreated animals inoculated with the mixed inoculum developed acute otitis media (AOM), whereas 86.7% of those inoculated with H. influenzae developed otitis media with effusion (OME). Antibiotics eradicated H. influenzae from the ME more efficiently in AOM than in OME, and this difference was highly significant (P80% of animals developed culture-negative OME.     

Antibody production deficiency with normal IgG levels in bronchiectasis of unknown etiology

BACKGROUND: No defined cause of bronchiectasis is currently found in approximately 50% of cases. Bronchiectasis is a common long-term complication in patients with primary hypogammaglobulinemia. STUDY OBJECTIVES: To ascertain whether antibody production deficiency with normal total serum IgG levels is associated with bronchiectasis. DESIGN: Antibody response to a pneumococcal unconjugate vaccine and an Haemophilus influenzae type b conjugate vaccine was prospectively studied in all consecutive adult patients with bronchiectasis of unknown etiology who were assessed in our chest outpatient clinic from January 1994 to October 2001. Serum-specific antibodies were measured by enzyme-linked immunosorbent assay, and the results were compared with those obtained in a healthy adult control group. Antibody production deficiency was defined as a failure to respond to either vaccine. RESULTS: One hundred seven patients were included in the study (mean age, 46.3 years). Antibody production deficiency was diagnosed in 12 patients (11%). A significantly higher incidence of otitis media, lower serum IgG2 subclass levels, and lower preimmunization antibody levels to Streptococcus pneumoniae and H influenzae type b were observed in patients with antibody production deficiency. The probability of antibody production deficiency in patients with a history of otitis media was 20%, 26% in those with low IgG2 subclass levels, and 58% in those with both a history of otitis media and low IgG2 subclass levels. CONCLUSIONS: Antibody production deficiency with normal IgG levels may be associated with bronchiectasis, making it advisable to evaluate the antibody response to both the H influenzae and pneumococcal vaccines in patients with bronchiectasis of unknown etiology, particularly in those with a history of otitis media, low IgG2 subclass levels, and low levels of baseline specific antibodies.     

Clinical effects of piperacillin and tazobactam/piperacillin on Haemophilus influenzae lower respiratory tract infection in pediatric patients

OBJECTIVE: The prevalence of beta-lactamase-nonproducing ampicillin-resistant (BLNAR) Haemophilus influenzae (H. influenzae) has been increasing in recent years. Piperacillin (PIPC) is one of a few beta-lactams possessing good activity against BLNAR H. influenzae. We studied clinical efficacy of piperacillin and its beta-lactamase inhibitor, tazobactam/piperacillin (TAZ/PIPC) in children with lower respiratory tract infection caused by H. influenzae including resistance strains. METHODS: Subjects were 20 children with lower respiratory tract infection caused by H. influenzae treated with PIPC 100mg/kg/day (7 cases) or TAZ/PIPC 125mg/kg/day (13 cases). We selected cases from which resistant H. influenzae strains might be detected. Patients received prior antimicrobial therapy within two weeks before admission, or with underlying diseases. We examined patient profiles, clinical efficacy, susceptibilities for 6 beta-lactam antibiotics [PIPC, TAZ/PIPC, ampicillin (ABPC), cefotaxime (CTX), ceftriaxone (CTRX), and meropenem (MEPM)] and analyzed 6 genotype patterns of beta-lactam resistant genes by PCR. RESULTS: Efficacy was 7/7 in patients in PIPC group and 12/13 in patients in TAZ/PIPC group. Diminished efficacy was seen in only one case complicated with severe RSV infection. The susceptibility of all strains but one beta-lactamase producing, ABPC resistant (BLP) strain to PIPC and of all to TAZ/ PIPC was below 0.25 microg/mL. The genotype of the 15 strains isolated from the sputum on administration was as follows; beta-lactamase nonproducing, ABPC-susceptible (gBLNAS) strains were 4, gBLP strain was 1, beta-lactamase nonproducing, and ABPC-resistant (gLow-BLNAR) strains were 2, beta-lactamase nonproducing, ABPC resistant (gBLNAR) strains were 8. CONCLUSION: PIPC and TAZ/PIPC were useful against lower respiratory tract infection caused by H. influenzae including BLNAR in children.     

High nasopharyngeal carriage of drug resistant Streptococcus pneumoniae and Haemophilus influenzae in North Indian schoolchildren

OBJECTIVES: To determine the carriage rate of Streptococcus pneumoniae and Haemophilus influenzae in healthy Indian schoolchildren. The prevalence of antibiotic resistant strains in the community may be used to assess the trends of antibiotic resistance in invasive strains. Prevalence of resistance to various antimicrobial drugs among S. pneumoniae and H. influenzae was estimated. METHODS: Two thousand four hundred subjects, aged 5-10 years, were enrolled from 45 rural and 45 urban schools. A nasopharyngeal swab was collected from each child, after taking informed written consent. Swabs were processed to isolate S. pneumoniae and H. influenzae. All isolates were tested for resistance to chloramphenicol, erythromycin and co-trimoxazole. Streptococcus pneumoniae isolates were also tested against tetracycline and oxacillin while H. influenzae isolates were tested against ampicillin. RESULTS: Nasopharyngeal carriage of S. pneumoniae and H. influenzae was high in healthy schoolchildren. Stratified analysis showed that nasal carriage of pneumococci in urban children was significantly lower than in rural children [46.8% vs. 53.2%, P<0.001]. Carriage rates of H. influenzae in male and female populations were significantly different (47.8% vs. 52.3%, P<0.04). Penicillin resistance in S. pneumoniae was found low (3.3%), but 22.9% of H. influenzae isolates were ampicillin resistant. Resistance to co-trimoxazole was very high in both S. pneumoniae (81.8%) and H. influenzae (67.3%). CONCLUSION: There is high nasopharyngeal carriage of drug resistant S. pneumoniae and H. influenzae in schoolchildren of north India. Currently, in India, co-trimoxazole for 5 days is recommended for treatment of non-severe pneumonia and third generation cephalosporins are drug of choice for management of severe pneumococcal/H. influenzae diseases. We found high co-trimoxazole resistance and low penicillin resistance in pneumococcal isolates. This justifies empirical use of penicillin in management of invasive pneumococcal infections in India.