In the second European survey of the prevalence of antimicrobial resistance in Haemophilus influenzae, 2529 clinical isolates collected in 1988/89 from 78 laboratories in nine countries (Austria, Belgium, Federal Republic of Germany, France, Italy, The Netherlands, Spain, Switzerland, United Kingdom) were examined. Of these, 23.8% were type b strains. The overall rate of beta-lactamase production was 9.1%, being slightly higher in type b isolates (10.5%) compared to non-type b isolates (8.6%). The MICs of six antimicrobials (ampicillin, cefaclor, chloramphenicol, erythromycin, tetracycline, and cotrimoxazole) were determined by an agar dilution procedure at a single central laboratory. The proportion of isolates resistant to the antimicrobials varied considerably amongst the individual countries. The highest incidence of resistance to all six drugs was observed in strains collected in Spain, whereas resistance was rarely encountered among strains isolated in Austria and the FRG. Resistance to ampicillin (MIC greater than or equal to 4 mg/l) among strains that lacked beta-lactamase activity was uncommon (0.3%). Based on the NCCLS Haemophilus influenzae breakpoints, the rates of susceptibility and resistance to cefaclor, chloramphenicol, tetracycline, and cotrimoxazole were 96.4/1.5, 96.2/2.8, 92.4/4.7, and 87.9/7.3%, respectively. The rate of susceptibility and resistance to erythromycin was 2.3/19.9. Multiple resistance to ampicillin, chloramphenicol, tetracycline, and cotrimoxazole was observed in 15 isolates (0.6%), and resistance to three drugs simultaneously in 72 (1.5%). The incidence of beta-lactamase producing strains was similar to that seen in the first European study performed in 1986 (9.1% vs. 10.9%), and was half that observed in US isolates collected in 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

A new carbapenem antibiotic, meropenem, was shown to be active against a large number of Gram-positive bacteria. The drug inhibited penicillinase-positive and -negative, methicillin-susceptible staphylococti equally well. Among the comparative antimicrobials examined, only Af-formimidoyl-thienamycin (imipenem) was two to four times more active than meropenem. Compared with vancomycin or methicillin, meropenem was 10-20 times more active. Strains of 11 species of streptococci were highly susceptible to meropenem; the geometric mean MICs of the drug for these species ranged from 0-01 to 0-04 mg/1. The agent, however, only had moderate activity against Enterococcus faecalis (mean MIC 5 mg/1) and Ent.faecium (mean MIC 11-6 mg/1). Among Corynebacterium jeikeium, strains were encountered that showed susceptibility to meropenem but resistance to imipenem and other /Jlactams. Strains of other corynebacteria, Rhodococcus equi, Erysopelothrix rhusiopathiae, Listeria monocytogenes, and Bacillus spp. all were highly susceptible to meropenem (mean MICs 0-04-0-17 mg/1). Although methicillin-resistant staphylococci were inhibited by concentrations of 1-2 mg/1 of meropenem in agar dilution tests, such strains showed heteroresistance in population studies, as is typical for all /J-lactam antibiotics. In addition, the biochemical correlate of methicillin-resistance, penicillin-binding protein 2', showed low affinity for meropenem, similar to that for imipenem. Meropenem was as bactericidal as imipenem and comparative bactericidal antimicrobials in killing-curve experiments. Strains of Ent.faecium, C. jeikeium, and L. monocytogenes were killed at a slower rate than streptococci or staphylococci.

Examination of the activity of cefoperazone against ampicillin-resistant, gramnegative bacteria in agar dilution and simultaneously in broth dilution revealed that strains could be divided into three classes: class I strains were susceptible in agar (mean minimal inhibitory concentration [MIC], 0.5 mg/liter) as well as in broth dilution (mean MIC, 1.5 mg/liter), class II strains were susceptible in agar (MIC, 0.9 mg/liter), but resistant in broth dilution (MIC, 182 mg/liter); and class III strains were highly resistant in both test systems. Among 100 randomly selected ampicillin-resistant Escherichia coli cultures, 51 belonged to class I and 49 belonged to class II. Class III E. coli strains were much rarer. Similar results were obtained with cefamandole and cephalothin, but not with six other secondand third-generation cephalosporins. MICs of cefoperazone against cultures of all three classes were influenced by initial inoculum size. The inoculum effect was greatest with class IX strains. Examination of bactericidal activity by cefoperazone showed killing of class I and class II E. coli strains and of class III strains of other genera during the first hours of incubation and regrowth after the drug was destroyed by the action of TEM P-lactamase (penicillinase). Representative class I bacteria produced 10 to 100 times less TEM 1-lactamase than did class II strains. It appeared that the quantitative difference in TEM production was the reason for the different resistance phenotypes in class I and class II strains. Salmonella and Klebsiella strains of class III produced the same amounts of TEM ,-lactamase as did class II E. coli strains. Probably, some factors other than P-lactamase contributed to the class III phenotype in these species.

Between 40 and 43 Haemophilus influenzae isolates obtained from Greece, Lebanon, Israel and Morocco respectively (a total of 167 strains) were analysed for prevalence of resistance to six different drugs. Of these isolates 12.6% produced beta-lactamase and were resistant to ampicillin. All isolates, except a single strain from Greece, were susceptible to cefaclor. The frequency of resistance to chloramphenicol and tetracycline was below 2%. The frequency of isolates susceptible and resistant to erythromycin and cotrimoxazole varied from country to country.

Page 20, column 1, lines 8 to 10:. .. categorized as resistant in agar dilution and susceptible in broth dilution tests" should read ... categorized as susceptible in agar dilution and resistant in broth dilution tests." 933