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The incidence of penicillin- and erythromycin-resistant strains of Streptococcus pneumoniae has increased considerably in Belgium. The medical charts of all patients with pneumococcal bacteraemia who were admitted to hospital over a period of 3 years (n = 136) were reviewed to identify treatment failure of outpatient antibiotic therapy. Twelve patients had received antibiotics for at least 48 h prior to admission. Four treatment failures received clarithromycin as pre-hospitalization therapy, and S. pneumoniae from all four patients were highly resistant to macrolides. Five patients failed on co-amoxiclav, whereas their S. pneumoniae were susceptible to penicillin and amoxicillin. This observation suggests that macrolide resistance is clinically relevant and leads to treatment failure, whereas suboptimal dosing may explain breakthrough pneumococcal bacteraemia in beta-lactam-treated patients.

The genetic basis of macrolide resistance was characterized in 59 Streptococcus pneumoniae isolates. All isolates were collected in 1995 and 1997 and were from invasive infections. The majority of the isolates (54 of 59 isolates) were erythromycin and clindamycin resistant (MLS(B)-phenotype) and carried the ermAM gene. Five isolates were erythromycin resistant but clindamycin susceptible (M-phenotype). Using PCR the mefE gene was detected in these five isolates. Contrary to the situation found in Canada and the USA, mefE-mediated erythromycin resistance in S. pneumoniae is uncommon in Belgium.

MICs of 16 non-beta-lactams were determined by agar dilution for 283 penicillin-susceptible, 122 intermediate and 23 fully penicillin-resistant isolates of pneumococci. Penicillin-resistant pneumococci were more likely to be resistant to tetracyclines, macrolides and related compounds. In the latter group, quinupristin/dalfopristin was the only compound whose activity was not influenced by penicillin resistance. Among the fluoroquinolones, clinafloxacin and trovafloxacin showed excellent activity. Strains resistant to macrolides, tetracycline and penicillin were concentrated in serogroups 6, 9, 14, 19 and 23.

MICs of 21 beta-lactams were determined by agar dilution against 283 penicillin-susceptible (pen-S), 122 intermediate (pen-I) and 23 fully penicillin-resistant (pen-R) pneumococci. MICs of all beta-lactams increased with increasing MICs of penicillin. Clometocillin was the most active penicillin against pen-I or pen-R pneumococci. All oral cephalosporins except cefuroxime and cefpodoxime were less active than penicillin and none was satisfactory against pen-I or pen-R pneumococci. The parenteral third- and fourth-generation cephalosporins (except ceftazidime) were similar in activity to penicillin against pen-S isolates. Cefpirome showed the lowest mean MICs against pen-I and pen-R strains.

Between 1991 and 1995 the Belgian National Program for Surveillance of Hospital Infections (NSIH) collected data on perioperative antibiotic prophylaxis in 72 acute care hospitals. From the costs of prophylactic antibiotics for six categories of surgical procedure and from discharge summaries for hospitalization episodes nationwide, annual drug costs were estimated for 73% of Belgian surgical activity. Costs of antibiotics used in these surgical activities were estimated at 386-410 million Belgian francs (Bf) per year (US$12.1-12.9 million). After agreeing recommendations for best practice, the hypothetical costs of 'optimal' antimicrobial prophylaxis were calculated for the same selection of surgical procedures. It was calculated that savings of at least 194 million Bf (US$6.1 million) could be made if recommendations were followed closely. Only the costs borne by the National Health Insurance Institute for reimbursement of the dispensed drugs were considered in this study. Other direct costs, such as those related to drug storage, dispensing and administration, were not included.

The in-vitro activity of ampicillin, of mecillinam and of combinations of ampicillin with mecillinam, clavulanic acid or 6 beta-bromopenicillanic acid has been studied against 126 Enterobacteriaceae resistant to ampicillin. The combination of ampicillin with mecillinam showed synergy or addition in 60% of the combinations tested. Synergy was seen especially when the strains were resistant to mecillinam, indifference when they were susceptible to mecillinam. The combination of ampicillin with mecillinam was more active than the combination with clavulanic acid against Escherichia coli, Klebsiella and Enterobacter, but not against Proteus, Morganella and Providencia. The combination of ampicillin with clavulanic acid was more active than the combination with 6 beta-bromopenicillanic acid in E. coli, Klebsiella and Enterobacter strains.

The in-vitro activity of BRL-36650, a novel beta-lactamase-stable penicillin was tested in comparison with that of cefotaxime, ceftazidime, aztreonam and imipenem against 559 multiply resistant Gram-negative organisms, some of which were also resistant to third generation cephalosporins. BRL-36650 and imipenem were the most active antibiotics. Against 342 Enterobacteriaceae the MICs90 were: imipenem 2 mg/l, BRL-36650 4 mg/l, aztreonam 8 mg/l and cefotaxime 32 mg/l. Against 122 Pseudomonas aeruginosa the MICs90 were: BRL-36650 4 mg/l, imipenem 8 mg/l, aztreonam and ceftazidime 64 mg/l.

In a large multicentre study, the susceptibility of 2171 bacterial isolates to ofloxacin and other antibiotics has been examined by the Kirby-Bauer method. Susceptibility to ofloxacin (breakpoint less than or equal to 2 mg/l) was observed in 99.2% of 1104 strains Enterobacteriaceae, 88.9% of 217 Pseudomonas aeruginosa, 93.6% of 31 other Pseudomonas spp., 96.3% of 27 Acinetobacter calcoaceticus, 99.2% of 118 Haemophilus influenzae, 97.4% of 423 staphylococci, 79.4% of 107 Streptococcus faecalis and 98.7% of 142 other streptococci. There was no relationship between resistance to ofloxacin and resistance to beta-lactam antibiotics, aminoglycosides or other antibiotics tested within the same bacterial species.

The in-vitro activity of pefloxacin was evaluated against 360 Enterobacteriaceae, 143 Pseudomonas aeruginosa and 124 staphylococci, selected for multiply resistance to different beta-lactam antibiotics and aminoglycosides. The MIC90 of pefloxacin against staphylococci and most Enterobacteriaceae was 0.5 mg/l or less. The MIC90 against Serratia marcescens and P. aeruginosa varied between 4 and 8 mg/l. Time-killing curves showed that pefloxacin at concentrations of four times the MIC decreased the viable counts by 3 logs or more within 1-8 h.