An electronic surveillance network for monitoring antibiotic resistance in The Netherlands has been in operation since 1989. Seven public health laboratories participate and the system covers about 25% of all bacteriological determinations in The Netherlands. This paper reports the results of staphylococci isolated in the period 1989-1995. About 0.3% of the Staphylococcus aureus isolates in the study period were resistant to methicillin. This low percentage may be due to the restrictive use of antibiotics and to strict isolation measures aimed at eradicating methicillin-resistant S. aureus. Low frequencies of resistance among methicillin-resistant S. aureus were found for vancomycin (0%), chloramphenicol (11%), cotrimoxazole (11%), mupirocin (3% low-level resistance) and fusidic acid (7%). Twenty-one percent of the coagulase-negative staphylococci were resistant to methicillin. Low frequencies of resistance among these methicillin-resistant coagulase-negative staphylococci were those to vancomycin (0.4%), nitrofurantoin (2%), doxycycline (20%) and amikacin (20%). Coagulase-negative staphylococci from cerebrospinal fluid, blood and skin were less often resistant to quinolones than isolates from respiratory tract, faeces and urine. A significant increase in resistance of coagulase-negative staphylococci to methicillin, erythromycin, gentamicin and ciprofloxacin was observed in the investigated period but the resistance to doxycycline and co-trimoxazole decreased in the last few years. To confirm the determination of methicillin resistance and coagulase production, a PCR method was developed which detects both the mecA and the coagulase gene. The results of the PCR method correlated well with the methicillin MIC as determined by an agar-dilution method.

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The bioavailability of penicillin and dihydrostreptomycin from three penicillin/ aminoglycoside fixed combination products for intramuscular injection was investigated in a four-way, randomized, crossover experiment in rabbits. Attention is focused on bioequivalence based on plasma concentration vs. time profiles to study whether the rabbit is a good model to detect differences in in vivo delivery of penicillin and/or dihydrostreptomycin after intramuscular administration of different products. In all products, penicillin was present as a suspension. Although the extent of absorption of penicillin did not differ between the three products, large differences in the rates of absorption were observed. With respect to dihydrostreptomycin, no significant differences were observed between the products. The results from this study demonstrate that the rabbit is a good model to detect differences in bioavailability of suspended penicillin from penicillin /dihydrostreptomycin fixed combination products for intramuscular injection. A study with the same products is presently being carried out in calves to investigate whether bioequivalence studies in rabbits could replace studies in the target animals.