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Purpose : To report a case of endogenous endophthalmitis caused by Haemophilus influenzae in an immunocompetent host. Case report : A 13-year-old male presented with pain, blurriness, and decreased Visual Acuity (VA) of Hand Motion in his right eye. Slit-lamp examination revealed hypopyon. Fundoscopy showed vitritis, vasculitis, and retinal infiltrates. Echography revealed vitreous condensations. Empirical treatment with intravitreal Ganciclovir, oral Valacyclovir, and Dexamethasone was initiated with no improvement. Vitreous culture revealed Haemophilus influenzae growth. Then, intravenous Ciprofloxacin and Cefotaxime and intravitreal Ceftazidime were administered with gradual improvement. Lensectomy with Pars Plana Vitrectomy and intraocular tamponade was performed. Nevertheless, the visual outcome was poor. Conclusion : Pediatric endogenous bacterial endophthalmitis is a rare but potentially devastating infection which is often misdiagnosed. Moreover, we want to highlight the importance of an adequate clinical suspicion in cases of H. influenzae to prevent the serious complications seen in this report.

Haemophilus influenzae is the most common cause of bacterial infection in the lungs of chronic obstructive pulmonary disease (COPD) patients and contributes to episodes of acute exacerbation which are associated with increased hospitalization and mortality. Due to the ability of H. influenzae to adhere to host epithelial cells, initial colonization of the lower airways can progress to a persistent infection and biofilm formation. This is characterized by changes in bacterial behaviour such as reduced cellular metabolism and the production of an obstructive extracellular matrix (ECM). Herein we discuss the multiple mechanisms by which H. influenzae contributes to the pathogenesis of COPD. In particular, mechanisms that facilitate bacterial adherence to host airway epithelial cells, biofilm formation, and microbial persistence through immune system evasion and antibiotic tolerance will be discussed.

Background: We studied Immunoglobulin G (IgG) antibody responses against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in young children with acute viral type respiratory infection and analyzed the findings in a multivariate model including age, nasopharyngeal carriage of the tested bacteria and pneumococcal vaccination., Methods: We included 227 children aged 6-23 months with acute respiratory infection. Nasopharyngeal aspirates were tested for bacterial carriage through detection of messenger RNA (mRNA) transcript with nCounter analysis. Acute and convalescent serum samples were tested for IgG antibody response against eight pneumococcal proteins, three proteins from H. influenzae and five proteins from M. catarrhalis in a fluorescent multiplex immunoassay., Results: A two-fold or greater increase in antibodies to S. pneumoniae, H. influenzae and M. catarrhalis was detected in 27.8, 9.7 and 14.1%, respectively. Nasopharyngeal carriage of each of the studied bacteria was not associated with antibody response detection against each respective bacterium. Furthermore, neither age nor pneumococcal vaccination were independently associated to detection of antibody response against the studied bacteria. Children who carried H. influenzae had higher frequency of colonization by M. catarrhalis (175 [80.3%] vs. 2 [22.2%]; p < .001) than those without H. influenzae. Also, children with acute otitis media tended to have higher frequency of antibody response to S. pneumoniae., Conclusion: Nasopharyngeal colonization by S. pneumoniae, H. influenzae and M. catarrhalis did not induce significant increases in antibody levels to these bacteria. Carriage of pathogenic bacteria in the nasopharynx is not able to elicit antibody responses to protein antigens similar to those caused by symptomatic infections.

Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of morbidity and mortality worldwide. In the lower airways of COPD patients, bacterial infection is a common phenomenon and Haemophilus influenzae is the most commonly identified bacteria. Haemophilus influenzae is divided into typeable and nontypeable (NTHi) strains based on the presence or absence of a polysaccharide capsule. While NTHi is a common commensal in the human nasopharynx, it is associated with considerable inflammation when it is present in the lower airways of COPD patients, resulting in morbidity due to worsening symptoms and increased frequency of COPD exacerbations. Treatment of lower airway NTHi infection with antibiotics, though successful in the short term, does not offer long-term protection against reinfection, nor does it change the course of the disease. Hence, there has been much interest in the development of an effective NTHi vaccine. This review will summarize the current literature concerning the role of NTHi infections in COPD patients and the consequences of using prophylactic antibiotics in patients with COPD. There is particular focus on the rationale, findings of clinical studies and possible future directions of NTHi vaccines in patients with COPD.

Haemophilus influenzae ( H. influenzae ) and Moraxella catarrhalis ( M. catarrhalis ) are associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, their role in the pathogenesis of COPD is unknown. We retrospectively analysed the clinical data of patients with AECOPD (modified British Medical Research Council scale score, Global Initiative for Chronic Obstructive Lung Disease [GOLD] classification, pre-admission antibiotic and inhalant usage, sputum culture and epidemic influenza virus antigen test) for association with admission frequency. Among 169 eligible patients, pathogens were and were not detected in 64 and 105, respectively. The GOLD classification grade was higher in the non-detection group with a prior antimicrobial administration rate of 21.9% than in the detection group. H. influenzae and M. catarrhalis , each identified in 24.6% of the total number of detected pathogens, were the most common infectious bacteria. The GOLD classification grade was higher in the re-hospitalisation group than in the one-time hospitalisation group ( p  < 0.01). Regarding type of pathogen, M. catarrhalis infection ( n  = 16) was more common in the re-hospitalisation group. History of M. catarrhalis,   H. influenzae infection and GOLD grade ≥ III were risk factors for re-hospitalisation, with odds ratios of 92.7 (95% confidence interval [CI]: 3.68-2340.0, p  < 0.01), 20.1 (CI: 1.48-274.0, p  < 0.05) and 9.83 (CI: 2.33-41.4, p  < 0.01), respectively. These bacterial infections and severe airway limitation were associated with increased AECOPD frequency. Routine microbial monitoring may be useful for AECOPD prevention, reducing medical burden and improving prognosis.

Background: The effect of potentially pathogenic bacteria (PPB) on disease severity in patients with bronchiolitis is understudied., Methods: This prospective study was carried out in the Children's Hospital of Soochow University during the 2012-2013 autumn and winter seasons. We enrolled consecutive children < 2 years of age hospitalized with an attending physician's diagnosis of bronchiolitis. Nasopharyngeal aspirate samples were tested for multiple respiratory viruses and cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus., Results: In all, 30% (188 patients) were positive for Strep. pneumoniae, H. influenzae, M. catarrhalis, and Staph. aureus. Length of stay (LOS) for patients with PPB was 4.0 days (interquartile range, IQR, 25th-75th percentile: 3.0-6.0 days) versus 3.0 days (IQR, 3.0-5.0 days) for patients without PPB (p < 0.001). However, requirement and duration of supplemental oxygen were not significantly different between the two groups. H. influenzae was an independent risk factor for hospital LOS ≥ 5.0 days (adjusted odds ratio, 1.75; 95% confidence interval, 1.06-2.91). The presence of PPB was not associated with increased risk of supplemental oxygen requirement., Conclusions: Our study demonstrated that pediatricians should evaluate for PPB in patients with bronchiolitis, especially when they present with RSV infection, fever or percentage of neutrophils > 40%. The presence of H. influenzae in nasal aspirates is associated with longer LOS in patients with bronchiolitis.

Haemophilus influenzae is rarely described as a causative agent of prosthetic joint infections. Here, a case of prosthetic hip joint infection caused by H. influenzae is reported. Treatment was successful, resulting in implant salvage, by debridement and antibiotic treatment with ciprofloxacin as monotherapy for 3 months.

Background: Respiratory tract infections (RTI) are frequently caused by Haemophilus influenzae. Widespread antibacterial resistance among respiratory microorganisms complicates empirical RTI treatment. Therefore, national data on antibiotic resistance for H. influenzae are important for guiding optimal antibiotic choice., Methods: The antibiotic susceptibility of H. influenzae strains isolated from respiratory specimens of patients admitted to the pulmonology services between 2005 and 2010 was assessed. Isolates were collected annually from 13 hospitals in the Netherlands as part of the national intramural antimicrobial resistance surveillance performed by the Dutch Working Group on Antibiotic Policy (SWAB). Breakpoints for resistance were in accordance with the criteria of the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Trend analysis was performed using logistic regression analysis., Results: In total, 1606 H. influenzae strains were analyzed. The prevalence of antibiotic resistance to amoxicillin, co-amoxiclav, doxycycline, co-trimoxazole, and clarithromycin was stable over the 6-y period, and there was a trend towards a decrease in the prevalence of beta-lactamase-producing isolates. Regarding prevalences, no significant trends were observed., Conclusions: Our study showed no significant changes in antibiotic resistance for H. influenzae isolated at different hospitals in the Netherlands over a 6-y period. Regular surveillance remains important in controlling the prevalence of resistance, since actual resistance data should be taken into account when the choice of an empiric antibiotic is made.

Objective: To determine the serotypes, antimicrobial susceptibility, and beta-lactam resistance mechanisms of Haemophilus influenzae strains isolated from invasive and respiratory tract infections (RTIs) prior to the introduction of Haemophilus influenzae type b (Hib) vaccination in Bulgaria., Methods: A total of 259 isolates were serotyped by polymerase chain reaction. Susceptibility to antibiotics and beta-lactamase production were determined, and DNA sequencing of the ftsI gene was performed for ampicillin non-susceptible strains., Results: The invasive H. influenzae infections in children were mainly due to serotype b (94.5% in meningitis and 88.9% in other invasive cases). Non-typeable strains (97.4%) were the most frequently found H. influenzae strains in RTIs both in children and adults. Non-susceptibility to ampicillin occurred in 22% of all strains. Ceftriaxone and levofloxacin were the most active agents tested. Ampicillin resistance occurred in 34.4% of invasive strains, and beta-lactamase production was the only mechanism found. Among respiratory tract isolates, ampicillin non-susceptible strains (18%) were classified into the following groups: beta-lactamase-positive, ampicillin-resistant (BLPAR) strains (7.2%); beta-lactamase-negative, ampicillin-non-susceptible (BLNAR) strains (8.2%); and beta- lactamase-positive, amoxicillin-clavulanate-resistant (BLPACR) strains (2.6%). Among 21 BLNAR and BLPACR strains there were 9 different patterns of multiple-amino acid substitutions in penicillin-binding protein 3. Of these, most isolates (81.0%) belonged to group II, defined by the Asn526Lys substitution., Conclusions: Beta-lactamase production was more common among invasive strains than in respiratory isolates. BLNAR and BLPACR H. influenzae were found only among respiratory tract isolates.

The recovery of potentially pathogenic microorganisms (PPMs) from bronchial secretions is associated with a local inflammatory response in COPD patients. The objective of this study was to determine the relationships between bronchial colonisation and both bronchial and systemic inflammation in stable COPD. In COPD patients recruited on first admission for an exacerbation, bacterial sputum cultures, interleukin (IL)-1β, IL-6 and IL-8 levels, and blood C-reactive protein (CRP) were measured in stable condition. Bronchial colonisation was found in 39 of the 133 (29%) patients and was significantly related to higher sputum IL-1β (median [percentile 25-75]; 462 [121-993] vs. 154 [41-477] pg/ml, p = 0.002), IL-6 (147 [71-424] vs. 109 [50-197] pg/ml, p = 0.047) and IL-8 values (15 [9-19] vs. 8 [3-15] (×10³) pg/ml, p = 0.002). Patients with positive cultures also showed significantly elevated levels of serum CRP (6.5 [2.5-8.5] vs. 3.5 [1.7-5.4] mg/l, p = 0.016). Bronchial colonisation by Haemophilus influenzae was associated with higher levels of IL-1β and IL-8 and clinically significant worse scores on the activity and impact domains of the St. George's Respiratory Questionnaire. In conclusion, bronchial colonisation is associated with bronchial inflammation and high blood CRP levels in stable COPD patients, being Haemophilus influenzae related to a more severe inflammatory response and impairment in health-related quality of life.

An increased incidence of infections by Haemophilus influenzae type f (Hif) has recently been suggested, but such infections have mainly been regarded as opportunistic. We present here a dramatic case of Hif necrotizing myositis and septic shock. A subsequently diagnosed IgG3 and mannose-binding lectin deficiency possibly contributed to the severe outcome.

According to the recommendations of the Swedish Community-Acquired Pneumonia (CAP) guidelines, the selection of empirical antibiotic therapy should be based on the CRB-65 rule. The guidelines recommend empirical therapy directed predominantly against Streptococcus pneumoniae for patients with low CRB-65 scores and broad-spectrum therapy for patients with high CRB-65 scores. In order to study the utility of the recommendations, we analyzed the data from an aetiological study previously performed on 235 hospitalized adult CAP patients at our medical centre. A definite, probable, or possible bacterial aetiology was noted in 194 cases (83%), including 112 cases (48%) with S. pneumoniae aetiology. The following frequencies of definite-probable aetiologies were noted in the patients with CRB-65 score 0-1 (n=155) and CRB-65 score 2-4 (n=80): S. pneumoniae 30% and 35%, Haemophilus influenzae 6.5% and 14% (p=0.063), Mycoplasma pneumoniae 15% and 5.0% (p=0.019), Chlamydophila species 2.6% and 1.2%, Legionella pneumophila 1.9% and 0%, and Staphylococcus aureus 1.3% and 1.2%, respectively. The high frequency of S. pneumoniae in the study supports the recommendations to predominantly cover this bacterium in the empirical therapy of patients with low CRB-65 scores. In the case of treatment failure in these patients, the study indicates that coverage against M. pneumoniae and H. influenzae should be considered.

We investigated the bacterial flora and antimicrobial sensitivity in sputum from patients admitted to hospital with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in order to recommend the best empirical treatment for these patients. The survey was a retrospective study of all patients admitted to Hvidovre hospital with the diagnosis AECOPD during 2004. A total of 118 patients were included. Microscopy, culture and sensitivity testing investigated their sputums. Clinical and paraclinical features were collected from the patients' files. Among the 118 patients, 59 (50%) had a positive sputum culture. The group with positive cultures had a higher blood neutrophil count (p=0.03). There were no other clinical differences between the groups with and without positive sputum culture. The majority of patients with positive sputum cultures were infected with bacteria other than S. pneumonia, mostly H. influenzae and Moraxella catarrhalis. Patients with low FEV(1)<1.0 litre were more likely to be infected with Pseudomonas aeruginosa (p=0.03). The sensitivity patterns of the bacteria showed that the majority were resistant to penicillin. If antibiotics are initiated empirically for AECOPD we recommend either cefuroxime for intravenous treatment or amoxicillin-clavulanate for oral treatment.

Purpose: We hypothesized that observation and analysis of microbiological laboratory statistics from patients with suspected bacterial conjunctivitis should increase our understanding of microbiological epidemiology of the disease in age categories. We further assumed that the statistical data should expose evolution of antimicrobial resistance that may eventually have an influence on clinical decisions., Materials and Methods: We analyzed statistical data of bacterial isolates (1139 strains) and their resistance to common antibiotics from 2494 patients with suspected bacterial conjunctivitis., Results: Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus displayed their presence in 0- to 5-year-old children. Staphylococcus aureus and Pseudomonas aeruginosa were the most common in the elderly (>age 70) among whom a rapid increase in resistance of Staphylococcus aureus to methicillin (MRSA) was recognized., Conclusions: Our study demonstrates that the spectrum of conjunctival bacteria varies among age groups. In addition, our results confirm that a shift in antimicrobial susceptibility can be rapid and age-group specific, thus emphasizing the need for continuous surveillance of bacterial findings.

Background: Haemophilus influenzae is a major respiratory tract pathogen that is becoming increasingly resistant to beta-lactam antibiotics., Materials and Methods: Using a microdilution method performed to Clinical and Laboratory Standards Institute (CLSI) guidelines, we determined the minimal inhibitory concentrations (MICs) of various antibacterial agents against 536 isolates of H. influenzae. The isolates were obtained from patients with respiratory tract infections being treated in 18 European and two Canadian centres between 2006 and 2007., Results: Levofloxacin, moxifloxacin, cefixime and cefpodoxime with MIC(90) values of < or = 0.03, < or = 0.03, 0.03 and 0.06 g/mL, respectively, were the four most active agents tested. Overall, amoxicillin resistance was observed in 25.0% of the strains, but was generally reversed with the addition of clavulanic acid. In 73 strains (13.6%) resistance was due to beta-lactamase (BL) production while the remainder (n = 61; 11.4%) were BL-negative, amoxicillin-resistant (BLNAR) strains. Comparison of penicillin binding protein 3B sequences in BLNAR isolates revealed that only mutations at amino acids 502 (alanine [Ala] --> threonine [Thr]/valine [Val]) and 526 (asparagine [Asn] --> lysine [Lys]) were significantly associated with amoxicillin resistance among European H. influenzae isolates (p < 0.0001 for both)., Conclusions: This surveillance study highlights an increased prevalence of amoxicillin-resistant strains of H. influenzae compared with a previous study that we performed in 2004/2005. The third-generation cephalosporins cefixime and cefpodoxime, as well as amoxicillin plus clavulanic acid, continue to be very active against both BL-positive and BLNAR strains of H. influenzae, and thus remain useful treatment options for patients with respiratory tract infections.

Antimicrobial resistance observed among common respiratory tract pathogens--Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis--may complicate empiric therapeutic selection to treat community-acquired respiratory tract infections. The Tracking Resistance in the United States Today (TRUST) study determined the in vitro activities of frequently prescribed antimicrobial agents against isolates collected from all 50 states from 2001 to 2005. For S pneumoniae (N = 27,781), susceptibility of selected agents in ascending order were penicillin (oral) (65.4%), trimethoprim-sulfamethoxazole (TMP-SMX) (69.5%), erythromycin (72.0%), cefuroxime (oral) (75.9%), tetracycline (85.3%), amoxicillinclavulanate (92.6%), ceftriaxone (nonmeningitis) (96.6%), and levofloxacin (99.0%). Susceptibility to levofloxacin, which was used as a representative of the respiratory fluoroquinolones, was near 99% from 2001 to 2005, and the minimum inhibitory concentration (90%) (MIC(90)) remained unchanged at 1 microg/mL. Levofloxacin and the other respiratory fluoroquinolones remained highly effective against penicillin-resistant S pneumoniae(PRSP) (98%-99% susceptible). However, susceptibility of PRSP to amoxicillin-clavulanate decreased from 62%S in 2003 to 48%S in 2005. Haemophilus influenzae susceptibility to ampicillin averaged near 70%, and near 75% to TMP-SMX. Susceptibility rates to levofloxacin and the other respiratory fluoroquinolones for H influenzae and M catarrhalis remained at or near 100%. Although resistance rates among S pneumoniae have stabilized for penicillin (oral) at elevated levels and increased for macrolides, susceptibility to the respiratory fluoroquinolones has consistently remained high, as they have for H influenzae and M catarrhalis.

Antimicrobial resistance by common respiratory tract pathogens remains a global concern, but surveillance programs allow us to recognize trends in susceptibility that may help guide empiric antimicrobial selection. During 2003 to 2004, the Global Landscape On the Bactericidal Activity of Levofloxacin (GLOBAL) surveillance program collected 9323 isolates of Streptococcus pneumoniae, 5828 isolates of Haemophilus influenzae, and 1878 isolates of Moraxella catarrhalis from 15 countries worldwide, and tested them for susceptibility to commonly used antimicrobial agents at a central laboratory. For S pneumoniae, penicillin (oral) susceptibility ranged from 41.5% (Asia) to 75.3% (Europe), while susceptibility to erythromycin ranged from 23.7% (Asia) to 87.0% (Central and South America). Susceptibility to levofloxacin was > or = 98.0% for each region studied, with the minimum inhibitory concentration (90%) (MIC(90)) = 1 microg/mL. Susceptibility to ciprofloxacin was > or = 81% for each region studied, with the MIC(90) = 2 microg/mL. For H influenzae, resistance to ampicillin ranged from 8.7% (South Africa) to 29.6% (Asia), while resistance to trimethoprimsulfamethoxazole ranged from 15.3% (United States) to 40.3% (Asia). Moraxella catarrhalis isolates from each region were > 95.0% susceptible to all antimicrobials tested. Susceptibility of H influenzae and M catarrhalis to levofloxacin was > 99.0% in each country. In general, S pneumoniae resistance to penicillin and macrolides remains a concern. Although the prevalence of ss-lactamase production by H influenzae and M catarrhalis can be high, these organisms continue to be susceptible to several commonly used antimicrobials. Respiratory fluoroquinolones continue to show high activity against these 3 organisms. There has been no change in the levofloxacin MIC(90) values for S pneumoniae and only rarely have resistant isolates of H influenzae and M catarrhalis been identified worldwide.

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.

Acute bacterial rhinosinusitis is a common infection resulting in substantial morbidity. Cefdinir, an oral cephalosporin, has extended-spectrum, bactericidal activity against common acute bacterial rhinosinusitis pathogens, including Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Cefdinir shows rapid oral absorption and good respiratory tissue penetration, and may be administered once daily. In randomised clinical trials, cefdinir showed efficacy similar to that of other recommended regimens in the treatment of acute bacterial rhinosinusitis, namely amoxicillin/clavulanate and levofloxacin. Cefdinir is well tolerated and has shown a low propensity to suppress the normal commensal flora. Cefdinir oral suspension is rated highly by children in terms of its taste and smell. As the only once-daily beta-lactam currently recommended by acute bacterial rhinosinusitis guidelines (for first-line use in patients with mild acute bacterial rhinosinusitis and no recent antibacterial use), cefdinir offers a convenient and attractive treatment option.

Acute otitis media (AOM) is treated with antibiotics in the United States, but the changing distribution of bacterial pathogens that cause the disorder can present physicians with several challenges. Most physicians treat AOM empirically, and their treatment choice should target Streptococcus pneumonia, nontypeable Haemophilus influenzae, and Moraxella catarrhalis, as those bacteria are most often isolated in AOM. First-line treatment for new onset AOM remains amoxicillin (80-90 mg/kg/d, divided twice daily). For persistent or recurrent AOM, guidelines recommend high-dose amoxicillin-clavulanate, cefdinir, cefprozil, cefpodoxime, cefuroxime, or ceftriaxone. Improved diagnosis and optimizing the choice of therapy by considering in vitro and in vivo efficacy of the different antibiotics will improve patient outcomes. Improved patient outcomes will result in fewer AOM episodes, decreased antibiotic resistance, and reduced direct and indirect health care costs.

Helpful new treatment guidelines offer physicians structure in diagnosing and treating patients who have uncomplicated acute otitis media (AOM). These guidelines should be weighed in light of the evolving microbiology of AOM pathogens. Physicians must be cognizant of the cyclical changes in bacteria as well as new vaccines and antibiotics best suited to address AOM. Although pneumococcal vaccines have helped, serotype shifts and bacterial resistance could work against current treatment practices. Physicians should understand causal organisms and treat patients appropriately to mitigate antibiotic resistance. New vaccines in development may offer additional reduction in AOM and drug resistant pneumococcus in the future.

Azithromycin is a macrolide antibiotic that has been structurally modified from erythromycin with an expanded spectrum of activity and improved tissue pharmacokinetic characteristics relative to erythromycin. This allows once-daily administration for 3-5 days of treatment compared with traditional multi dosing 7-10-day treatment regimens. It has been successfully employed in lower respiratory tract infections. Recent data indicate that azithromycin may exert anti-inflammatory/immunomodulatory effects that may be of use in the treatment of both acute and chronic airway diseases. This review examines the role of azithromycin in lower respiratory tract infections analysing published data on exacerbations of chronic bronchitis, community-acquired pneumonia and cystic fibrosis both in adults and children. In addition, pharmacokinetic and pharmacodynamic properties of the drug are also considered.

To assess resistance rates among respiratory tract pathogens and antimicrobial usage of children in Iceland and Lithuania, and to correlate usage patterns with resistance rates, nasopharyngeal swabs were taken from healthy children attending day-care centres in Reykjavik (n = 6) and Vilnius (n = 13), and cultured for pneumococci, Haemophilus influenzae and Moraxella catarrhalis. Information about recent antimicrobial use was obtained by a questionnaire. 50% and 51% carried pneumococci, 59% and 67% carried H. influenzae and 60% and 46% carried M. catarrhalis, in Reykjavik (n = 297) and Vilnius (n = 508), respectively. The prevalence of penicillin non-susceptible pneumococci was 11% in Reykjavik (mainly serotype 6B) and 5% in Vilnius (mainly 23F). At the time of sampling 3% of the children in Reykjavik and 8% in Vilnius were receiving antimicrobials. Children carrying penicillin non-susceptible pneumococci had used antimicrobials more frequently in the preceding month and this was significant for the Icelandic children (p < 0.0002). Antimicrobial use was more common in Vilnius than in Reykjavik, yet antimicrobial resistance was more common in Reykjavik. Resistance rates cannot be predicted only on the basis of recent antimicrobial use.

We reviewed population-based laboratory reports of invasive meningococcal, pneumococcal, Haemophilus influenzae, Group B Streptococcus (GBS) and Listeria monocytogenes isolates in order to examine the changing epidemiology of meningitis and invasive non-meningitic disease (INMD) caused by these 5 pathogens in the 2 periods before (1983-91) and after (1992-99) routine use of H. influenzae type B conjugate vaccine (Hib) in Scotland. Neissieria meningitidis was the most common cause of meningitis, accounting for 39.2% of cases of meningitis in 1983-91 and 47% of cases in 1992-99, followed by H. influenzae (31%), Streptococcus pneumoniae (22.4%), GBS (3.9%) and L. monocytogenes (3.5%) in 1983-91 and S. pneumoniae (36.3%), H. influenzae (7.8%), GBS (6.1%) and L. monocytogenes (2.8%) in 1992-99. The important epidemiological features of meningitis and INMD caused by these 5 pathogens between 1983-91 and 1992-99 include: 1. The incidence of bacterial meningitis due to S. pneumoniae and GBS was stable; 2. S. pneumoniae was the predominant cause of INMD in both periods; 3. The incidences of INMD caused by N. meningitidis, GBS and S. pneumoniae increased, by 27%, 55% and 56%, respectively; 4. Decreases in the incidences of bacterial meningitis (by 50%) and INMD (by 50%) due to L. monocytogenes were detected; and 5. There were dramatic reductions in the proportions of bacterial meningitis (by 92%) and INMD (by 56%) due to H. influenzae in vaccinated and non-vaccinated individuals. Continued surveillance is necessary to monitor the disease trend, population at risk, serotype distribution and antimicrobial susceptibility in order to implement appropriate public health interventions against invasive bacterial disease.

To investigate the management of patients with community-acquired pneumonia (CAP) treated in hospital in Sweden, a multicentre retrospective cohort study was performed with medical record review of 982 patients (mean age 63 y) at 17 departments of infectious diseases at hospitals in Sweden. Information on antimicrobial therapy, demographic characteristics, comorbid conditions, physical examination findings, and laboratory and microbiological test results were recorded. Outcome measures were in-hospital mortality and length of hospital stay (LOS). Cultures were obtained from blood in 80% and from sputum in 22% of the patients. A microbiological aetiology was determined for 23% of the patients, with Streptococcus pneumoniae as the dominating agent (9%). The initial antibiotic treatment was mostly given intravenously (78%). Penicillin (50%) or a cephalosporin (30%) was the most common choice. Both of these drugs were usually given as a single agent. The overall mortality was 3.5% and the mean LOS was 6.4 d. Thus, the outcome was favourable despite the empirical antibiotic treatment having a narrow spectrum compared with the broader approach recommended in most recent guidelines on the management of CAP. These findings suggest that a majority of patients who are hospitalized with moderately severe pneumonia can be treated initially with penicillin alone.

Non-typable Haemophilus influenzae (NTHI) and Streptococcus pneumoniae are regarded as the main pathogens in patients with humoral immunodeficiency. These patients have been given IgG replacement therapy since the 1950s. However, a number of individuals still suffer from recurrent episodes of respiratory tract infections. Nasopharyngeal cultures were obtained on a regular basis over a 3-6-month period from 11 patients with common variable immunodeficiency disease in 1989 and 1998. The proportion of cultures positive for NTHI decreased from 56% in 1989-90 to 16% in 1998-99 (p < 0.003). After 9 y of IgG therapy, 7 of the 11 patients were free from NTHI in the nasopharynx. Specific NTHI strains were analysed by pulsed-field gel electrophoresis and compared, with regard to genetic relatedness, on an intra-individual basis. In 1 patient the same NTHI strain was found in both 1989 and 1999. The apparent absence of NTHI from the nasopharynx in most of the patients was assumed to be due to subcutaneous IgG treatment, as well as adequate antibiotic treatment.

Sensitivity patterns of Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes were studied prospectively in an outpatient population seeking medical advice for respiratory tract infections (RTI) in the Southern parts of Stockholm. In total, 3,214 nasopharyngeal and 1,907 throat swabs were cultured during January-February 1996. 32% of the patients had received antibiotics during the previous year. Reduced penicillin sensitivity in S. pneumoniae was rare (1.3%) and only seen in patients treated with antibiotics during the previous 4 months. Beta-lactamase production in H. influenzae was found in 13.4% of patients who had been treated with antibiotics during the last 4 months and in 7.9% of the others. No resistance (< 1%) to erythromycin was seen in S. pyogenes. In this population-based surveillance, the levels of resistance in common respiratory tract pathogens were thus low and correlated to previous antibiotic treatment. Strict indications for antibiotic treatment in uncomplicated RTI are advocated to maintain a low resistance rate. Penicillin is still the drug of choice in patients without frequent recurrences of RTI in a setting similar to the one studied.

To determine the prevalence of the asymptomatic carriage of drug-resistant Streptococcus pneumoniae (DRSP) by children attending day-care centres in the Stockholm area, nasopharyngeal swabs were cultured from 1129 children and 308 day-care personnel in 36 day-care centres during a 3-week period, from March to April 1995. Approximately 36% of the children were asymptomatic carriers of S. pneumoniae sensitive to penicillin and other antibiotics. The highest prevalence of nasopharyngeal carriage was found in the 2-year-old group (50%), whereas among the 4-year-old children colonization was observed in 42%, and among the 7-year-old children 21% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. In 2 day-care centres, 4 and 5 children, respectively, were found to have DRSP strains in the nasopharynx. The same serotype of DRSP strain was found among the children attending the same day-care centre. During the same period, none of the staff were found to harbour DRSP in the nasopharynx, but 3% were asymptomatic carriers of penicillin-sensitive S. pneumoniae. The patterns of nasopharyngeal colonization by Haemophilus influenzae, Moraxella catarrhalis and Group A streptococci were also studied in 635 children during the same period. 42% of the nasal cultures yielded Moraxella, 32% H. influenzae and 2% Streptococcus pyogenes.

A retrospective study of the incidence, aetiology and case fatality rate of acute epiglottitis in children and adults was performed. The study covered the whole of Sweden (population 8.4 million) during the years 1987-89, before general vaccination against Haemophilus influenzae (Hi) type b was started. Patients were included if it was documented that they fulfilled all 3 of the following criteria: (a) red and swollen epiglottis visualized by indirect laryngoscopy, (b) inspiratory stridor or difficulties in swallowing, and (c) a temperature > or = 38 degrees C. A total of 306 children and adolescents (0-19 years) and 502 adults (> or = 20 years) were found. The age-specific incidence was highest in children aged 0-4 years, (14.7/100,000 per year). The total incidence was 3.2/100,000 per year. In the age group 0-19 years, blood cultures had been obtained from 195 (64%) and Hi was isolated from 154 (79%). In adults (> or = 20 years), 114 of 298 blood cultures yielded Hi, while pneumococci were isolated from 5 and group A streptococci from 3 patients. A total of 220 children (72%) and 114 adults (23%) needed an artificial airway. Five children and 12 adults died. In conclusion, the incidence of acute epiglottis in Sweden is very high. Compared to a previous country-wide study covering the years 1981-83 that used the same methods for case finding and case definition, the incidence in children had decreased while the incidence in adults had increased.

A polymerase chain reaction (PCR) based diagnostic assay has been developed for the simultaneous detection in cerebrospinal fluid (CSF) of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Listeria monocytogenes and bacteria in general. In the present communication we describe the design of primers for S. pneumoniae, S. agalactiae, and L. monocytogenes, and a general PCR protocol for the assay. The diagnostic outcome is presented for a small collection of CSF specimens including 2 samples from patients with culture-negative purulent meningitis.

In a prospective study between January 1987 and December 1992, 103 patients with invasive Haemophilus influenzae (Hi) infection were identified in a well-defined population before large-scale Haemophilus influenzae type b (Hib) vaccination was introduced. The incidence (case/100,000/year) of invasive Hi infection was 5.9 for the whole population, 55 for children 0-4 years old and as high as 2.8 for adults. Hib was the predominant cause of the infection (83 cases) in children but, in adults, 13/39 (30%) cases were caused by non-typable Hi and 6/39 (19%) by Hi serotype f. Three patients (3%) died and 6 (5.8%) suffered a permanent sequel from the infection. All patients with such a sequel had invasive Hib infection. No significant difference between patients 0-6 years old and matched controls regarding the frequency of subnormal serum levels of immunoglobulins was found.

A nation-wide survey of the prevalence of antimicrobial resistance in Haemophilus influenzae was conducted on isolates collected in 1988-90 from middle ear fluid (MEF), blood, or cerebrospinal fluid (CSF) in infected children or throat samples of healthy children. Altogether 885 strains were examined regarding capsular type b, beta-lactamase production and the minimal inhibitory concentration (MIC) of ampicillin, cefaclor, erythromycin, tetracycline, chloramphenicol, trimethoprim and trimethoprim-sulfamethoxazole for these strains was determined by the agar dilution method. 99% (578/585) of MEF isolates, 93% (112/121) of throat isolates, but only 6% (10/179) of blood/CSF isolates were not of type b (Hib). The rate of beta-lactamase production was 11.4% among Hib strains, 8.0% among non-type b MEF isolates, and 4.5% among non-type b throat isolates. No increase in the prevalence of beta-lactamase production in H. influenzae has taken place in Finland since the early 1980s. Resistance to ampicillin among strains that lacked beta-lactamase activity was rare (0.2%). Of the non-type b MEF and throat isolates, 5.9% and 2.7%, respectively, were resistant to trimethoprim and 3.6% and 2.7%, respectively, to trimethoprim-sulfamethoxazole. Resistance to other drugs was rare (< 2%) in all isolate groups.

In order to evaluate the clinical efficacy and tolerance of cefpodoxime proxetil, compared with that of amoxicillin in the treatment of acute bacterial maxillary sinusitis, a randomized, double-blind, parallel group comparative study was performed. A total of 286 adults patients were included at 12 centres, each treatment group consisting of 143 patients. Each patient was treated for 10 days and observed before and after treatment. The observations included clinical, roentgenological, bacteriological and laboratory examinations. At inclusion, the most common pathogens were Haemophilus influenzae (24%) and Streptococcus pneumoniae (17%). In the per protocol analysis, 117 patients in the cefpodoxime group and 113 in the amoxicillin group were evaluable for clinical efficacy. The clinical response rates were 96% and 91%, respectively. The corresponding figures in the intent-to-treat analysis were 130 and 128 patients, with clinical response rates of 93% and 88%, respectively. Cefpodoxime proxetil proved clinically as effective as amoxicillin in the treatment of acute bacterial maxillary sinusitis. It was more effective in eradicating H. influenzae and was more efficient in improving the radiological score. Adverse events were reported in 20% of cefpodoxime cases and in 16% of amoxicillin cases. There was no statistically significant difference between the groups.

The purpose of the study was to evaluate the history, clinical picture and diagnostic difficulties of acute haematogenous osteomyelitis (AHOM) in children. Forty-seven children under the age of 15 with bacteriologically proven AHOM were collected prospectively in Finland in 1981-93. Staphylococcus aureus was responsible for 89% of the cases. The commonest sites affected were the tibia (25%) and the femur (23%) followed by the pelvis (15%) and the calcaneus (11%). Sites other than the long bones increased in frequency in children over the age of 4 years. Most of the children came with a history of a week or less with classic signs and symptoms of AHOM, increased C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values but negative X-rays. Delay in hospital admission was observed in 19%. In 11% antimicrobial therapy was not instituted within 48 hours on ward. All children were clinically healthy at the 1-year check-up with minor X-ray changes seen in 11 patients. We conclude that children in Finland seek treatment early in the course of AHOM and have a good outcome. S. aureus is the main aetiological agent affecting primarily the long bones, but in older children pelvic and calcaneic sites are also frequent. No significant delays affecting the outcome were noticed in admittance to hospital or in the diagnosis of AHOM.

Six patients with deep obstetrical and gynecological infections due to non-typeable Haemophilus influenzae are presented. 3 patients had tubo-ovarian abscesses, 2 septic abortions and 1 postpartum sepsis. All our patients with tubo-ovarian abscesses had used intra-uterine contraceptive devices until admission and all had a protracted course of illness. Both patients with septic abortion had a severe course, one of them with disseminated intravascular coagulation demanding treatment in the intensive care unit. The patient with postpartum infection had a milder course. The possibility of infection with H. influenzae and the emergence of beta-lactamase producing strains warrant adequate culture procedures in women with obstetrical and gynecological infections in order to ensure proper treatment.

Many immunodeficient patients constantly carry non-typable Hemophilus influenzae (NTHI) in the nasopharynx, despite seemingly adequate antibiotic therapy. We have studied the effect of nasal administration of IgA on nasopharyngeal colonization in 5 patients with hypogammaglobulinemia, with a productive cough, especially in the mornings, who were constant carriers of NTHI in the nasopharynx, and had IgA, 1 ml 6 times/day, given nasally for 14 days. Nasopharyngeal cultures were obtained on days 0, 7, 14 and 28. Two of the patients became culture-negative during the treatment, and the cough was alleviated in all patients.

Non-capsulated Haemophilus influenzae may cause neonatal septicaemia. Genital carriage of this pathogen was studied in 3 mothers of infected neonates and in 2 pregnant women in the first trimester. A carrier state in 2 of the females was terminated by antibiotic therapy after 3 and 7 months, respectively. A previous carrier had no recurrence of H. influenzae in a subsequent pregnancy. A survey of 544 parturient women revealed a carrier rate of 1.8/1,000 (95% confidence limits: 0.1-11). Carriage of non-capsulated H. influenzae is thus rare, and pregnant women may be successfully treated in order to reduce the risk of neonatal infection. There was no evidence of immunodeficiency in women with non-capsulated H. influenzae in the genital tract.

A case of fulminant neonatal Haemophilus influenzae sepsis is presented. A 29-year-old woman presented at 34 weeks gestation with premature labor but with intact membranes. The male infant died 8 h after delivery due to respiratory insufficiency. Ante-mortem blood cultures and post-mortem blood and lung cultures yielded H. influenzae (biotype II) which could not be serotyped. H. influenzae was cultured from the mother's cervix 5 days after delivery. This strain was of the same biotype and also nonserotypable. Serum obtained from the mother exhibited reduced bactericidal activity against the isolates. We suggest the use of selective media in routine cervix cultures from pregnant women to detect H. influenzae, which might be responsible for neonatal septicemia.

Haemophilus influenzae is the aetiological agent in less than 1% of septic arthritis cases in adults and most often serotype b is involved. We report here a case of severe systemic infection due to non-encapsulated H. influenzae biotype III in a 40-year-old man, previously healthy although alcohol abuser. Cholangitis and acute alcoholic hepatitis were diagnosed simultaneously. The organism was grown from blood and from synovial fluid of the left knee, but several other joints were also affected. The close relationship between H. influenzae biotype III and H. aegyptius is mentioned in view of recent reports of fatal childhood illness caused by a special clone of H. aegyptius and the importance of reporting both serotype and biotype in severe H. influenzae induced disease is emphasized.

Specimens from acute otitis media (AOM) examined in the first quarter of the years 1986, 1987, 1988, and 1989 were reviewed in order to point out any changes in the bacteriological etiology. A total of 1,722 specimens were taken in the community and in the hospitals of a county of 500,000 inhabitants in the 4-year-period: 447 (1986), 420 (1987), 388 (1988), 467 (1988). The majority of the specimens came from children less than 10 years of age. The specimen sampling technique differed between the various otologists, but their sampling techniques were constant through the years. Haemophilus influenzae was the most frequent isolate and held a constant incidence of 29.9% with little variation. In 1986-88 Streptococcus pneumoniae was the second (19.8%) and group A streptococci (GAS) the third (9.8%) most common agent in frequency. In 1989 a change in the etiologic agents was seen as GAS increased in frequency to 18.8% (p less than 0.001), while no significant changes occurred in the frequency of H. influenzae and S. pneumoniae. 33% of the specimens were negative in the whole period. It is too early to decide whether a transient epidemic has occurred or whether the findings announce a more constant change in etiology.

The number of patients hospitalized for acute infection in the frontal sinuses at the Department of Oto-Rhino-Laryngology of Turku University Hospital has increased markedly during the last decade. Causes for this increase were evaluated by comparing the backgrounds and medical findings of the 134 patients treated in the years 1977-81 and those of the 421 patients treated in the years 1982-86. Nasal polyps and history of allergic rhinitis were considerably more common in the latter patient group. The disease also seems to recur increasingly in the same patients. Of the aerobic bacteria Streptococcus pneumoniae and Haemophilus influenzae were the most common pathogens and the share of H. influenzae increased slightly, becoming the commonest pathogen in the latter 5-year period. Increasing air pollution in the city area of Turku is worth consideration and should be investigated further.

During a 15-year period Haemophilus species were isolated from unusual anatomical sites in 80 patients, mostly adults. The origin of specimens was pus and swabs from suppurative lesions, fluids from serosal cavities and gall bladder, gut content, and blood in cases with a supposed tissue focus. In 17 patients Haemophilus species were isolated in pure culture, in 63 patients in conjunction with other bacteria. 17 patients had gynaecological complaints: bartholinitis, salpingitis, and vaginal discharge. 22 patients had gastrointestinal complaints, comprising 17 with appendicitis, peritonitis following perforation of gastric ulcer, gall-duct infections, and an abscess in the stomach wall, and 5 patients with colonization of the gut. 41 patients had soft tissue and bone infections.

71 children and adults (median age 7 years) with chronic obstructive pulmonary disease in which ampicillin-sensitive Haemophilus influenzae were isolated from lower airway secretions were included in a single-blind study comparing amoxycillin/clavulanate and amoxycillin alone. The dosage of amoxycillin was 50 mg/kg/day given together with probenecid and divided in 3 doses. Duration of treatment was 14 days. Clinical and bacteriological examinations were performed at study entry and again immediately after the treatment period. A late bacteriological follow-up 1.5 months after entry was performed. 65 patients were eligible for analysis of clinical outcome, and no difference between the groups was found. Side-effects were mild at a frequency of 3% for either preparation. In terms of eradication of the initially isolated H. influenzae amoxycillin/clavulanate tended to be better than amoxycillin, although the difference was not significant (70% and 57%, respectively). In a subset of 33 patients with polymicrobial flora amoxycillin/clavulanate was significantly more effective than amoxycillin. However, amoxycillin/clavulanate did not significantly reduce the emergency of beta-lactamase producing H. influenzae during treatment, and thus offers no advantage over amoxycillin in patients with amoxycillin-sensitive H. influenzae. The combination should be reserved to patients with either polymicrobial flora or ampicillin-resistant H. influenzae.

In a kindergarten with 42 children and 17 female staff members, an epidemic of group B streptococcal carriage in the upper respiratory tract occurred. In the middle of February 1978, 6 children and 5 adults carried type I b streptococci in the throat while only 2 of these 11 were carriers 2 weeks later. Only one other streptococcus, belonging to type II, was found in the throat specimens. Five strains other than type I b were found in the urogenital tract of the staff. Three type I b throat carriers were also urogenital carriers of this type. The spread of type I b streptococci could have resulted from co-spreading with other upper respiratory tract pathogens found, including group A streptococci of type 12. Haemophilus influenzae, Branhamella catarrhalis and pneumococci. Estimation of antibodies with radiolabelled protein A indicated an immune response to type I b, but not to types I a, II or III group B streptococci in the staff compared with healthy blood donors.

In a Swedish nursery 11 of 15 children harboured non-encapsulated Haemophilus influenzae in their nasopharynx. Six children had ampicillin-resistant and beta-lactamase-producing isolates. Five of these children had otitis whereas one was healthy. In order to identify the origin of the H. influenzae isolates their O-antigen determinants were studied by an immunodiffusion technique. 18 different rabbit antisera were used. For each isolate an O-antigen pattern was recorded. Five of the 6 resistant isolates had the same O-antigen pattern, indicating that their origin was one strain. The 6th isolate was from another strain. Different isolates from the same strain were found to be either sensitive or resistant to ampicillin. In one child the H. influenzae lost its resistance during trimethoprim-sulphamethoxazole treatment. It is concluded that an R-factor may have been involved in the distribution of ampicillin resistance in the H. influenzae studied. Previous in-vitro studies have shown that beta-lactamase production can be transmitted by a plasmid among H. influenzae strains.

25 patients, 15 children and 10 adults, with the clinical diagnosis of acute epiglottitis were studied. Patients severely ill on admission, 13 children and 1 adult, were immediately treated with tracheotomy and antibiotics; the remaining patients with antibiotics only. Haemophilus influenzae type b was the causative organism in all children and in 3 adults. One adult had a Diplococcus pneumoniae infection. No pathogens were isolated from the 6 remaining patients. Four of the children developed H. influenzae type b meningitis. All patients recovered. Anti-b antibodies were not demonstrable in any initial serum sample while agglutinating anti-b antibodies were found in subsequent samples (indirect hemagglutination). All patients with a type b infection had already initially precipitating anti-O antibodies against their own strain, and in most cases complement-fixing anti-O antibodies (mixed H. influenzae O antigen) with rising titers in subsequent serum samples. A possible connection between the presence of anti-O antibodies initially and the development of the acute epiglottitis is discussed.

76 patients with acute maxillary sinusitis were treated with oral erythromycin stearate (500 mg twice or 3 times a day for 10 days). The mean concentration of erythromycin in the sinus secretion after 3-5 days' treatment was 0.6 mug/ml with the lower dosage and 1.3 mug/ml with the higher. The concentration of erythromycin in the sinus secretion was, on the average, 10-20 times higher than the minimum inhibitory concentration (MIC) for group A streptococci and pneumococci, and reached MIC values for 15-30% of 100 examined strains of Haemophilus influenzae. 81% of the patients given the smaller and 94% of those given the larger dose improved or recovered. Radiological improvement was demonstrated in both groups. The infections with H. influenzae tended to respond somewhat less to the treatment than those with pneumococci. Comparisons of the roentgen findings and the findings at aspiration showed good agreement. An extra projection taken with the patient recumbent and the affected side downwards gave no information above that obtained from the routine projections. The large dose caused side effects more often (in 17/41 patients) than the smaller one (4/35 patients). In 10 patients treatment was discontinued because of side effects; 8 of them had received the larger dose.

In this study we performed in situ hybridization using biotin-labelled total genomic DNA of Haemophilus influenzae type b as a probe on: (1) smears containing bacteria cultured in vitro: all haemophilus species that can be found in the human respiratory tract appeared to be positive and a large number of other bacterial species appeared to be negative in this in situ hybridization test; (2) sputum smears from 287 patients with bronchitis: the hybridization test was positive on all but 2 of the 44 smears derived from patients whose culture yielded haemophilus and additionally on 12 smears derived from patients, whose culture was negative; and (3) sputum smears from 7 patients suffering from cystic fibrosis (CF): the hybridization test was positive in all these 7 sputum smears, while the culture only yielded haemophilus in 3 cases. The higher sensitivity of the hybridization test compared to culturing could mainly be explained by the failure to detect haemophilus in culture caused by masking due to overgrowth by other bacteria. In conclusion the in situ hybridization test, which can be performed in only 4 h, is a sensitive and specific method for the detection of haemophilus in sputum and is particularly useful in CF patients, where overgrowth by pseudomonas often interferes with diagnosis by culturing.

The occurrence of beta-lactamase production in Haemophilus influenzae, Branhamella catarrhalis and Moraxella nonliquefaciens was compared in 191 healthy children attending day nurseries in 2 municipalities differing with regard to the prescription rate of beta-lactam antibiotics. A significantly higher frequency of beta-lactamase production was recorded in M. nonliquefaciens isolated in the municipality with the higher prescription rate. A corresponding difference was not recorded for H. influenzae or B. catarrhalis. Approximately 75% of the nasopharyngeal pathogens H. influenzae, B. catarrhalis and Streptococcus pneumoniae, as well as the commensal M. nonliquefaciens, were eliminated and often replaced by other strains of either species over a period of one month. Although none of the children were on antibiotics a substantial proportion of the acquired strains produced beta-lactamase. This suggested that the carrier rate of beta-lactamase producing strains of the respiratory tract is not only related to the effect of recent antibiotic treatment but also to the prevalence of such strains in the population.