Bactericidal activity and killing rate of serum against Gram-positive cocci in volunteers receiving imipenem, oxacillin, vancomycin or ampicillin plus gentamicin

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Abstract
The serum bactericidal activity and rate of killing of serum was studied in two groups of ten volunteers receiving imipenem 500 mg, oxacillin 3 g and vancomycin 1 g given iv (Group 1) or imipenem 500 mg, vancomycin 1 g, and ampicillin 3 g plus gentamicin 80 mg iv (Group 2). Serum samples collected 30 min, 1 h and 6 h after the start of a 15 min infusion were tested against Staphylococcus aureus susceptible (five strains) or resistant (five strains) to oxacillin, Staphylococcus epidermidis susceptible to (five strains) or resistant (five strains) to oxacillin (Group 1), and against Streptococcus faecalis (four strains), Streptococcus spp. (six strains). All strains of streptococci had been isolated from patients with endocarditis. Imipenem produced the highest bactericidal titres against susceptible staphylococci whereas vancomycin produced the highest titres against oxacillin-resistant staphylococci. Against “non faecalis” streptococci, imipenem was equivalent to ampicillin plus gentamicin, whereas ampicillin plus gentamicin was the most active regimen against Str. faecalis. The study of the rate of killing of serum showed that imipenem was able to kill initially 1-5 log cfu/ml of Str. faecalis but this was followed by regrowth. A similar regrowth was observed with oxacillin-resistant straphylococci. Killing curves in broth were studied with imipenem at two temperatures (30 and 37°C) and two initial inocula (105 and 106 cfu/ml) for 48 h of incubation against oxacillin-resistant staphylococci; regrowth occurred more rapidly with a high initial inoculum and low temperature of incubation despite a rapid initial killing. Gentamicin was found significantly to increase the rate of killing of imipenem against Str. faecalis in killing curves in broth. In conclusion, imipenem showed excellent activity, as assessed by the measure of the bactericidal titres and rate of killing in serum, against the studied strains with the exception of oxacillin-resistant staphylococci and Str. faecalis.

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