Simultaneous respiratory tract colonization by multiple strains of nontypeable haemophilus influenzae in chronic obstructive pulmonary disease: implications for antibiotic therapy.

Nontypeable Haemophilus influenzae often causes exacerbations of chronic obstructive pulmonary disease (COPD), and these exacerbations are frequently treated with oral antibiotics. The goals of this study were to determine the frequency of the simultaneous presence of multiple strains of H. influenzae in sputum and to measure the MICs of antibiotics for the isolates. In a prospective study, adults with COPD were seen monthly. Sputum cultures were obtained, and individual colonies were subjected to genomic DNA typing and MIC determinations. Multiple strains of H. influenzae were present simultaneously in the sputum of 26.3% of adults with COPD. In 64.5% of these, MICs of >/=1 antibiotic varied by >/=4-fold among the strains. Therefore, multiple strains of H. influenzae are frequently present simultaneously in the sputum of adults with COPD, and the antimicrobial susceptibility of different strains in the same sputum sometimes differs.     

Strain-specific immune response to Haemophilus influenzae in chronic obstructive pulmonary disease

Previous studies of immune response to Haemophilus influenzae after exacerbations of chronic obstructive pulmonary disease (COPD) have yielded contradictory results. Using homologous (infecting) strains and immunoassays to surface-exposed epitopes, we tested the hypothesis that adults with COPD make new antibodies to strain-specific, surface-exposed epitopes on H. influenzae after exacerbations. We collected clinical information, sputum, and serum monthly and during exacerbations from 81 patients with COPD over 56 months. Serum antibodies to H. influenzae after exacerbations associated with H. influenzae in sputum were detected with whole bacterial cell ELISA and bactericidal assays. An immune response to homologous H. influenzae occurred after 22 of 36 (61.1%) exacerbations with newly acquired strains compared with 7 of 33 (21.2%) exacerbations with preexisting strains (odds ratio [OR] = 4.4; 95%, 1.8 to 10.8; p = 0.001). An absence of an immune response was strongly associated with complement sensitivity (OR = 0.03; 95% confidence interval, 0.003 to 0.22; p = 0.001). New bactericidal antibodies developed after exacerbations were highly strain specific, showing bactericidal activity for only 11 of 90 (12.2%) heterologous strains. Development of an immune response to H. influenzae supports its role in causing exacerbations. The strain specificity of the immune response likely represents a mechanism of recurrent exacerbations.     

Persistent colonization by Haemophilus influenzae in chronic obstructive pulmonary disease

Nontypeable Haemophilus influenzae colonizes the respiratory tract of adults with chronic obstructive pulmonary disease (COPD) and causes intermittent exacerbations. Isolates of H. influenzae collected monthly in a prospective study were subjected to molecular typing. During a 7-year study spanning 345 patient-months of observation, 122 episodes of negative cultures lasting 1 month or more, and that were preceded and followed by isolation of an apparently identical strain of H. influenzae, were found. Seventeen such episodes of negative cultures, lasting 6 months or more and spanning 203 patient-months, were studied in detail to test the hypothesis that these periods of negative cultures represented continuous colonization by the same strain of H. influenzae. Molecular typing by three independent methods established that the strains preceding and following the episodes of negative cultures were indeed identical. Strain-specific H. influenzae DNA was detected in some of the sputum samples that had yielded negative cultures. These results indicate that some patients with COPD are persistently colonized with H. influenzae and that sputum cultures underestimate the frequency of colonization of the respiratory tract by H. influenzae in COPD. This observation has a significant impact on understanding bacterial colonization in COPD.     

Haemophilus influenzae from patients with chronic obstructive pulmonary disease exacerbation induce more inflammation than colonizers

RATIONALE: Airway infection with Haemophilus influenzae causes airway inflammation, and isolation of new strains of this bacteria is associated with increased risk of exacerbations in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To determine whether strains of H. influenzae associated with exacerbations cause more inflammation than strains that colonize the airways of patients with COPD. METHODS: Exacerbation strains of H. influenzae were isolated from patients during exacerbation of clinical symptoms with subsequent development of a homologous serum antibody response and were compared with colonization strains that were not associated with symptom worsening or an antibody response. Bacterial strains were compared using an in vivo mouse model of airway infection and in vitro cell culture model of bacterial adherence and defense gene and signaling pathway activation in primary human airway epithelial cells. RESULTS: H. influenzae associated with exacerbations caused more airway neutrophil recruitment compared with colonization strains in the mouse model of airway bacterial infection. Furthermore, exacerbation strains adhered to epithelial cells in significantly higher numbers and induced more interleukin-8 release after interaction with airway epithelial cells. This effect was likely mediated by increased activation of the nuclear factor-kappaB and p38 mitogen-activated protein kinase signaling pathways. CONCLUSIONS: The results indicate that H. influenzae strains isolated from patients during COPD exacerbations often induce more airway inflammation and likely have differences in virulence compared with colonizing strains. These findings support the concept that bacteria infecting the airway during COPD exacerbations mediate increased airway inflammation and contribute to decreased airway function.     

Airway bacterial concentrations and exacerbations of chronic obstructive pulmonary disease

RATIONALE: Increased bacterial concentration (load) in the lower airways and new bacterial strain acquisition have been posited as mechanisms for chronic obstructive pulmonary disease (COPD) exacerbations. Bacterial concentrations are higher during exacerbation than during stable disease; however, these studies are cross sectional and devoid of strain typing. OBJECTIVES: To determine if the increased bacterial concentrations function as a separate mechanism for exacerbation induction independent of new strain acquisition. METHODS: In a prospective, longitudinal cohort of patients with COPD, the relationship between exacerbation occurrence, sputum bacterial concentrations, and new strain acquisition was examined. MEASUREMENTS AND MAIN RESULTS: Clinical information, quantitative sputum cultures, and molecular typing of potential bacterial pathogen isolates. Over 81 months, 104 subjects completed 3,009 clinic visits, 560 (19.6%) during exacerbations and 2,449 (80.4%) during stable disease. Among preexisting strains, sputum concentrations of Nontypeable Haemophilus influenzae and Haemophilus haemolyticus were not different in exacerbation versus stable disease. Moraxella catarrhalis (stable, 10(8.38 +/- 0.13) [mean +/- SEM] vs. exacerbation, 10(7.78 +/- 0.26); p = 0.02) and Streptococcus pneumoniae (stable, 10(8.42 +/- 0.21) vs. exacerbation, 10(7.76 +/- 0.52); p = 0.07) concentrations were lower during exacerbations compared with stable periods. Concentrations of new strains of H. influenzae (stable, 10(7.28 +/- 0.15) vs. exacerbation, 10(7.76 +/- 0.17); p = 0.04) and M. catarrhalis (stable, 10(7.85 +/- 0.15) vs. exacerbation, 10(8.37 +/- 0.14); p = 0.02), were increased during exacerbations; however, the differences were small. CONCLUSIONS: Change in bacterial load is unlikely to be an important mechanism for exacerbations. Better understanding of the host-pathogen interaction, rather than enumerating bacteria in respiratory samples, is required to provide new insights into bacterial infection in COPD.     

Endogenous and exogenous reinfections by Haemophilus influenzae in patients with chronic obstructive pulmonary disease: the effect of antibiotic treatment on persistence

To analyze whether exacerbations in chronic obstructive pulmonary disease (COPD) coincide with reinfection by Haemophilus influenzae, 16 COPD patients were studied longitudinally for 3 years. Exacerbations coincided with reinfection by H. influenzae, either endogenous, by a strain with a DNA fingerprint indistinguishable from the strain previously present but with another major outer membrane protein (MOMP) pattern (2 patients), or exogenous, by a strain with a different DNA fingerprint and MOMP pattern (3 patients). The other patients, remaining in an infectious state without clear exacerbations for longer periods, were persistently infected by a particular H. influenzae strain (median persistence time, 5.5 months; range, 2-23 months). Of 8 antibiotic-treated patients, 7 remained infected by H. influenzae with the same DNA fingerprint, although all strains were sensitive to the antibiotics prescribed. Results of the study suggested that exacerbations in COPD patients coincide with endogenous or exogenous reinfection by H. influenzae, persistently infected patients keep the same H. influenzae strain for longer periods, and antibiotic treatment was not effective in eradicating H. influenzae.     

Identification of strains on recurrent Haemophilus influenzae infections in patients with chronic respiratory tract infections]

Nontypable Haemophilus influenzae is one of the most important pathogenic bacteria in respiratory tract infections. H. influenzae is most frequently associated with recurrent infections in chronic respiratory tract infections (CRTIs). It is known that H. influenzae often reemerges after the antibiotic treatment has been stopped. We analyzed serotype, biotype, and the OMP patterns of H. influenzae isolates from sputum of CRTIs patients to determine whether an exacerbation is caused by an identical H. influenzae strain, or by a new H. influenzae strain. One hundred eighty nine strains of H. influenzae were obtained from 124 exacerbation from 24 patients. The first and second isolates were identical in 23 out of 33 exacerbations (< or = 15-days interval between each exacerbation) and also in 22 out of 34 exacerbations (15 < days but < or = 30-days interval between each exacerbation). This is called early recurrence. In contrast, the first and second isolates were different in 28 out of 34 exacerbations (> 30-days interval between each exacerbation). This is called late recurrence. These results suggest that early recurrence and late recurrence of recurrent H. influenzae infections occur in a different mechanism.     

Antimicrobial resistance of Haemophilus species in patients with chronic bronchitis.

Haemophilus influenzae strains resistant to ampicillin have become an important cause of disease in pediatric patients. Because many adults with chronic bronchitis carry Haemophilus organisms in their tracheobronchial tree and because antimicrobial agents are used commonly in these patients, we assessed the prevalence of resistance to ampicillin and other antimicrobial agents in this population. We studied 150 Haemophilus isolates (73 H. influenzae, 69 H. parainfluenzae, 6 H. parahemolyticus, and 2 H. hemolyticus) obtained from 138 patients with chronic bronchitis from January 1978 through March 1979. Ampicillin resistance due to production of beta-lactamase was found in 7 of the 150 isolates (4.7 %)-2 H. influenzae, 4 H. parainfluenzae and 1 H. parahemolyticus. Resistance to tetracycline was found in 9 strains (6 %), but all strains were susceptible to chloramphenicol.     

Antimicrobial susceptibilities of Haemophilus species in Hong Kong

Altogether 403 Haemophilus spp. were isolated in seven hospital laboratories in Hong Kong during June 1986, mostly from sputum. Of these 73% were Haemophilus influenzae and 27% Haemophilus parainfluenzae. All the isolates of H. influenzae were non-capsulated; Haemophilus spp. were not isolated from blood or cerebrospinal fluid (CSF) during the period of the study. Antimicrobial resistance, including multiple resistance, was common. Of all the strains of H. influenzae, 20% were resistant to 1 mg/l ampicillin, (all except one by production of TEM-1 beta-lactamase), 65% were resistant to 0.5 mg/l erythromycin, 25% to 1 mg/l tetracycline, 14% to 1 mg/l chloramphenicol (mediated by the production of a chloramphenicol-destroying enzyme) and less than 1% to 8 mg/l cefaclor and 0.5 mg/l trimethoprim. All isolates were susceptible to cephamandole and cefuroxime. Haemophilus parainfluenzae showed similar susceptibilities, except that a greater proportion of strains was sensitive to erythromycin and chloramphenicol. Only 50% of the ampicillin-resistant strains of H. influenzae and H. parainfluenzae contained detectable plasmids of 2-55 Mdal arranged in six to nine different plasmid profiles. Resistance to ampicillin and chloramphenicol has increased markedly in isolates of H. influenzae in Hong Kong over the last 5 years. This resistance may be associated with transposable genes.     

临床分离流感嗜血杆菌和副流感嗜血杆菌的耐药性研究

目的 了解上海部分医院分离的流感和副流感嗜血杆菌对常用抗菌药物的敏感性、对β内酰胺类和喹诺酮类药物的耐药机制以及耐药菌株的克隆传播情况.方法 以琼脂稀释法测定氨苄西林等13种抗菌药物对2006年上海5所医院临床分离的156株嗜血杆菌属细菌的体外抗菌活性,头孢硝噻吩纸片法检测β-内酰胺酶,PCR扩增检测TEM和ROB型β-内酰胺酶基因和喹诺酮类耐药株的喹诺酮耐药决定区,以肠杆菌科基因间重复序列聚合酶链反应(ERIC-PCR)比较细菌的同源性.药物敏感性试验结果采用χ2检验,ERIC-PCR条带模型转换数据进行聚类分析.结果 109株流感嗜血杆菌对氨苄西林敏感率为74.3%,而对氨苄西林舒巴坦、头孢菌素类、氟喹诺酮类等敏感率为100.0%.109株流感嗜血杆菌和47株副流感嗜血杆菌β-内酰胺酶产酶率分别为25.7%和19.1%(χ2=0.776,P=0.378),产酶株均检测到TEM基因.109株流感嗜血杆菌中仅1株对环丙沙星耐药,其gyrA基因存在84位丝氨酸突变为亮氨酸,parC基因存在206位甘氨酸突变为精氨酸.ERIC-PCR结果显示,106株流感嗜血杆菌在85%相似度水平可被分为73型.结论 上海地区流感嗜血杆菌临床菌株对除氨苄西林外的其他常用抗菌药物仍保持很高的敏感率.受试流感嗜血杆菌对氨苄西林耐药的主要机制均为产TEM型β-内酰胺酶.在包括氨苄西林耐药株在内的流感嗜血杆菌中,克隆传播尚不普遍.     

Invasive Haemophilus influenzae disease in adults. A prospective, population-based surveillance. CDC Meningitis Surveillance Group.

OBJECTIVE: To define the incidence of and possible risk factors for invasive Haemophilus influenzae disease in adults. DESIGN: Prospective, population-based surveillance of hospital and referral bacteriology laboratories. SETTING: Metropolitan Atlanta, Georgia community. PATIENTS: All patients with H. influenzae isolated from normally sterile sites (blood, cerebrospinal fluid, joint, pleura) from 1 December 1988 through 31 May 1990. MEASUREMENTS: Isolates of H. influenzae were analyzed for serotype and biotype status, outer membrane proteins, lipooligosaccharide phenotypes, ribotyping patterns and beta-lactamase production. RESULTS: A total of 194 cases of invasive H. influenzae occurred (annual incidence of 5.6 cases/100,000 population), of which 47 (24%) were in adults 18 years old or older (annual incidence 1.7 cases/100,000 adults). Adults with invasive H. influenzae ranged from 18 to 96 years; 79% were women. Bacteremic pneumonia accounted for 70% of the adult cases. Other sources for invasive H. influenzae in adults were obstetric infections, epiglottitis, and tracheobronchitis; one patient had meningitis. Underlying conditions were noted in 92% of the patients. Chronic lung disease was the most common risk factor, but pregnancy (annual incidence, 4.9/100,000 pregnant women), HIV infection (annual incidence, 41/100,000 known HIV-infected adults), and malignancy were also important. Overall mortality was 28% in adults, and over half of pregnancy-related infections resulted in fetal death. Fifty percent of the 40 isolates available for testing were serotype b; 47.5%, nontypable; and 2.5%, serotype f. Sixteen of the 45 isolates (36%) were ampicillin-resistant. Based on biotypes, outer membrane protein profiles, lipooligosaccharide phenotypes, and ribotyping patterns, the type b isolates showed less heterogeneity than the nontypable isolates but were distinguishable from one another. CONCLUSIONS: Adult cases currently represent one quarter of all cases of invasive H. influenzae disease. Half of the reported adult cases were caused by type b H. influenzae, and the rate of ampicillin resistance in H. influenzae isolates from adults was higher than previously reported. Haemophilus influenzae is an important cause of bacteremia in compromised adults.     

Respiratory infections caused by non-typeable Haemophilus influenzae

PURPOSE OF REVIEW: This review will consider recent developments in the clinical aspects of infections due to non-typeable Haemophilus influenzae. In addition, newer developments in the areas of mechanisms of pathogenesis, host pathogen interaction, immune responses and efforts toward vaccine development will be reviewed briefly. RECENT FINDINGS: Non-typeable H. influenzae continues to be a common cause of otitis media in infants and children, sinusitis in children and adults, pneumonia in adults, and lower respiratory tract infection in adults with chronic obstructive pulmonary disease. While the rate of beta-lactamase production by isolates of H. influenzae varies geographically, most regions show a rate of 20-35% of isolates producing beta-lactamase. Recent studies have highlighted the possible role of bacterial biofilms formed by H. influenzae as a cause of otitis media. Several lines of evidence indicate that H. influenzae causes intracellular infection in the lower respiratory tract in chronic obstructive pulmonary disease and this observation has important implications in understanding the human immune response to the bacterium. Lipooligosaccharide is an important virulence factor for H. influenzae and research is generating new information on the complex role of this molecule in colonization and infection of the respiratory tract. Several surface molecules are under active evaluation as vaccine antigens. SUMMARY: Non-typeable H. influenzae is an important cause of respiratory tract infections in children and adults. Most strains are susceptible to amoxicillin/clavulanate, fluoroquinolones and the newer macrolides. Research in the next decade promises substantial progress in the challenge of developing vaccines for nontypeable H. influenzae.     

Changes in outer membrane proteins of nontypable Haemophilus influenzae in patients with chronic obstructive pulmonary disease

Five individual colonies of Haemophilus influenzae were isolated from each of one to three cultures of sputum collected from 18 patients with chronic obstructive pulmonary disease (COPD). The isolates were studied to investigate whether the major outer membrane proteins (MOMPs) changed during persistence. The relationship between isolates was analyzed by fingerprinting their chromosomal DNA. The fingerprints of eight strains (isolated from eight patients) with various MOMP compositions were different, whereas fingerprints of isolates with identical MOMP compositions were indistinguishable. In 12 patients, two or more strains with different MOMP compositions were found; one strain was isolated from the sputum samples of each of the six remaining patients. In seven of the 12 patients, strains with different MOMPs but with indistinguishable fingerprints were found. The differences were found in proteins b,c (five patients) and d (five patients). In patients with COPD, the MOMPs of H. influenzae are subject to changes that may enable this bacterium to escape immunological defense mechanisms.     

Molecular epidemiology of Haemophilus influenzae within families in Santiago, Chile

Thirty-six consecutive patients with invasive Haemophilus influenzae type b (Hib) infections at Roberto del Rio Children's Hospital, Santiago, Chile, were enrolled in a prospective study. Throat cultures were obtained from household contacts of each index case, adjacent neighbors, and matched community control households. Colonization rates for H. influenzae were comparable among groups; however, among household contacts 18% of colonizing isolates were Hib, compared with 2% and 3% among neighbor and community controls. When selected isolates were evaluated further by outer membrane protein (OMP) profiles and multilocus enzyme electrophoresis, only one of the four Hib isolates from household members matched the corresponding index case isolate. One serologically nontypeable isolate from a household contact had an OMP profile and electrophoretic type identical to that of the corresponding Hib index case isolate; hybridization studies with a 9-kb capsular gene probe showed a profile consistent with a capsule-deficient mutant. Hib strains were isolated more frequently from household contacts than from control persons living in Santiago, but colonizing Hib strains were often unrelated to the index case strain.     

Fundamental studies on rapid detection of Haemophilus influenzae by enzyme-linked immunosorbent assay (ELISA)

To establish a rapid method for detection of Haemophilus influenzae, an antiserum against H. influenzae (Anti-HibOMP) was prepared by immunization of rabbits with crude outer membrane proteins (OMP) of H. influenzae type b. Various isolates of H. influenzae including typable and nontypable strains and other species were tested by ELISA and Western blot assay with Anti-HibOMP. The results are as follows: 1. Anti-HibOMP reacted to all of the OMPs from 18 H. influenzae isolates which contained typable and nontypable strains by Western blot assay. Molecular weights of these OMPs were about 24, 27, 31, 34, 39 and 45 kilo-dalton. This result suggests that all H. influenzae isolates have identical antigenic proteins on their outer membranes. 2. It was found that 172 out of 179 (96%) culture suspensions of H. influenzae isolates including 66 typable and 113 nontypable showed positive result by ELISA with Anti-HibOMP. 3. To define the cross-reactivity of Anti-HibOMP, 20 species (111 isolates) other than H. influenzae were tested by the ELISA. All isolates were negative with exception of a portion of H. parainfluenzae and Staphylococcus aureus producing Protein A. The cross-reactions to H. parainfluenzae and S. aureus were removed by absorption of Anti-HibOMP with formalinized cells of H. parainfluenzae and reduction of the antibody to F(ab)2 with pepsin digestion respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spectrum of invasive Haemophilus influenzae type b disease in adults

A prospective nationwide surveillance of invasive Haemophilus influenzae type b disease among adults (greater than or equal to 16 years old) was conducted in Finland during 1985 through 1988. Thirty-one cases were identified (annual incidence, 0.22/100,000). Of these infections, 71% occurred in patients with severe underlying conditions. The overall case fatality rate was 26%. Septicemia (13 patients) and pneumonia (seven patients) were the most common clinical manifestations of H influenzae type b infection; the others were epiglottitis (six patients), meningitis (three patients), and arthritis (two patients). Epiglottitis occurred in significantly younger patients, all of whom were women and four of whom were previously healthy. Subtyping of the H influenzae type b isolates according to the major outer membrane protein subtype, biotype, and lipopolysaccharide serotype showed that patterns that were uncommon (14%) among children were more common (27%) in the adults.     

Poor clinical outcome for meningitis caused by Haemophilus influenzae serotype A strains containing the IS1016-bexA deletion

Since the introduction of Haemophilus influenzae type b (Hib) conjugate vaccines, meningitis caused by serotypes other than Hib has gained in importance. We conducted active hospital-based surveillance for meningitis over an 11-year period in Salvador, Brazil. H. influenzae isolates were serotyped and analyzed by polymerase chain reaction, pulsed-field gel electrophoresis, and DNA sequencing to identify strains with a specific deletion (IS1016) in the bexA gene (IS1016-bexA). We identified 43 meningitis cases caused by non-type b H. influenzae: 28 (65%) were caused by type a (Hia), 9 (21%) were caused by noncapsulated strains, and 3 (7%) each were caused by types e and f. Hia isolates clustered in 2 clonal groups; clonal group A strains (n = 9) had the IS1016-bexA deletion. Among children <5 years of age, meningitis caused by Hia from clonal group A had higher case-fatality than meningitis caused by clonal group B. Despite small numbers, these results indicate that the presence of the IS1016-bexA deletion is associated with enhanced virulence in non-type b H. influenzae.     

Airway inflammation and etiology of acute exacerbations of chronic bronchitis

STUDY OBJECTIVES: The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations. DESIGN: This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n = 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared. SETTING: An outpatient research clinic at a Veterans Affairs Medical Center. PATIENTS: These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB. INTERVENTIONS: None. Measurements and results: H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations. H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB. CONCLUSIONS: Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB.     

Pneumococcal and Haemophilus influenzae meningitis in a children's hospital in Ethiopia: serotypes and susceptibility patterns

Streptococcus pneumoniae and Haemophilus influenzae are responsible for most pyogenic meningitis cases in children in Ethiopia. Resistance of S. pneumoniae and H. influenzae to penicillin and chloramphenicol respectively has been reported globally. Resistance has been related to specific serotypes of S. pneumoniae or to beta-lactamase-producing H. influenzae strains. This study describes the serotypes/ serogroups and susceptibility pattern of the two organisms causing meningitis in Ethiopian children. There were 120 cases of meningitis caused by S. pneumoniae (46) and H. influenzae (74) over a period of 3 years (1993-95). Nineteen children died from pneumococcal and 28 from haemophilus meningitis. Penicillin-resistant pneumococcal meningitis (4/8 = 50%) caused a greater mortality rate than penicillin-susceptible pneumococcal meningitis (15/38 = 39%). Common serotypes accounting for 76% of S. pneumoniae were type 14, 19F, 20, 1, 18 and 5; and serotypes 14, 19F and 7 (accounting for 17% of strains) showed intermediate resistance to penicillin G. 97% of the H. influenzae isolates were type b, and in only two cases beta-lactamase-producing. 72% of isolates of the S. pneumoniae we identified belong to serotypes preventable by a 9-valent vaccine. Our study highlights the possibility of resistant pyogenic meningitis in children in Ethiopia due to emerging resistant strains of S. pneumoniae and H. influenzae isolates.     

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.