These findings reveal the importance of iga gene variability and expression levels in the establishment of disease phenotype. They identify nontypeable H influenzae IgA1 protease as a virulence factor and as a potential target for the development of new strategies to fight these important pathogens.

SUMMARYAn investigation was undertaken to determine the isolation rate and antibiotic resistance ofHaemophilus influenzae from the nasopharynx of young children. The 996 subjects studied were up to 6 years of age. H. influenzae was isolated from 304 (30 5 %) and strains of capsular type b from 11 (1 1 %). Age, sibling status, season, respiratory infection and antibiotic therapy all influenced isolation rates. The overall prevalence of antibiotic resistance in the strains isolated was ampicillin 5-4% (all fl-lactamase producers), cefaclor 0-3 %, chloramphenicol 1-3%, erythromycin 38-2 %, tetracycline 1 3 %, trimethoprim 5-4 % and sulphamethoxazole 0%. Ampicillin resistance was more common in type b than non-capsulated strains.

Objective-To investigate the epidemiology of invasive disease due to Haemophilus influenzae type b, the clones responsible, and the antibiotic resistance of the isolates.

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The in-vitro activity of a new macrolide antibiotic CP-62,993 (Pfizer Ltd) was determined for 420 bacterial isolates, comprising 150 Haemophilus influenzae, 48 Branhamella catarrhalis, 50 Staphylococcus aureus, 50 coagulase negative staphylococci, 50 beta-haemolytic streptococci, 50 Streptococcus pneumoniae and 22 oral streptococci. CP-62,993 was compared with erythromycin and penicillin (ampicillin in the case of H. influenzae). The MICs of CP-62,993 were found to be lower than those of erythromycin for the two Gram-negative species tested: this was particularly marked in the case of H. influenzae where a ten-fold difference in the MIC50 was observed (CP-62,993, 0.25 mg/l, erythromycin 2 mg/l). In general MICs of CP-62,993 were two-fold higher than those of erythromycin for the Gram-positive species studied, with the exception of the oral streptococci which were equally susceptible (MIC50 0.03 mg/l) to both macrolides. Activity similar to that of erythromycin was observed against Str. pneumoniae (MIC values 0.015-0.12 mg/l), Staph. aureus (MIC 0.12-1 mg/l) and beta-haemolytic streptococci (MIC 0.06-4 mg/l). Incubation in a CO2 enriched atmosphere decreased activity of both erythromycin and CP-62,993. The effect was more marked for CP-62,993, the MIC50s of all groups of organisms being increased four-fold when they were incubated in the presence of 5 or 10% CO2.

A study was undertaken to evaluate the prevalence and antibiotic susceptibility of bacteria present in the middle ear of patients with otitis media with effusion. Middle ear effusions (MEE), nasopharyngeal and throat swabs were obtained at operation and cultured for aerobic and anaerobic bacteria. Two hundred and fifty-nine effusions were obtained from 152 subjects examined.Haemophilus influenzaewas isolated from 32 (12.3 per cent) effusions.Streptococcus pneumoniaefrom seven (2.7 per cent),Staphylococcus aureusfrom seven (2.7 per cent), Branhamella catarrhalis from one (0.4 per cent)—Group A β haemolytic streptococci from one (0.4 per cent) andStaphylcoccus epidermidisfrom three (1.9 per cent). The occurrence of respiratory pathogens in MEE reflected their prevalence in the upper respiratory tract. Significantly fewer children who had received antibiotics prior to surgery had organisms present in the MEE. Eight and a half per cent ofH. influenzaeand 64 per cent ofB. catarrhaliswere resistant to ampicillin. The present study confirms that bacteria are present in the middle ear in a significant number of patients with otitis media with effusion.

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The in-vitro activity of a new oral carbacephem, LY163892, was compared with cefaclor, cephalexin, cephradine, cefadroxil and selected penicillins against 529 bacterial isolates. LY163892 exhibited greater activity in vitro than all four cephalosporins against Haemophilus influenzae, beta-lactamase producing Branhamella catarrhalis, Escherichia coli, Klebsiella spp. and Proteus mirabilis. LY163892 had equivalent potency to cefaclor against non-beta-lactamase producing B. catarrhalis, streptococci and Staphylococcus aureus. Group D beta-haemolytic streptococci, Proteus vulgaris, and methicillin-resistant staphylococci were universally resistant to LY163892 and the four cephalosporins. Broth dilution experiments indicated that LY163892 was bactericidal against a range of Gram-positive and Gram-negative organisms and suggested that the antibiotic had a similar degree of stability to the beta-lactamases of H. influenzae, B. catarrhalis and Staph. aureus as did cefaclor. The susceptibility of 16 strains of H. influenzae to LY163892 and cefaclor were equivalent when estimated using three different commercially available agar media. Addition of carbon dioxide to the incubation atmosphere significantly reduced the potency of both drugs.