The effect of antistaphylococcal agents used alone and in combinations on the survival of Staphylococcus aureus ingested by human polymorphonuclear leukocytes

The intracellular activity of a number of drugs used alone and in combinations against Staphylococcus aureus was investigated using an experimental design which imitates the clinical situation and differs from other published methods. Staphylococci were phagocytosed by human polymorphonuclear leukocytes and, after differential centrifugation and washing, the granulocytes were incubated in 90% pooled human serum with clinically relevant drug concentrations. When exposed to antibiotics, more than 40 50% of the bacteria were located intracellularly. Fusidic acid (100 mg/1), erythromycin (20 mg/1), and clindamycin (20 mg/1) all had a bacteriostatic effect during the first 6 h of incubation, whereas rifampicin (1 and 5 mg/1), vancomycin (5 and 20 mg/1), and ciprofloxacin (2 mg/1) all acted bactericidally with decreases in viable counts between 1.3–1.9 log₁₀. The greatest bactericidal effect was achieved with tobramycin (10 mg/1), which produced more than a 4 log₁₀ decrease in viable counts at 6 h. Combinations of fusidic acid with other antibiotics all resulted in killing kinetics different from those achieved with the drugs used individually. The bactericidal effect of ciprofloxacin and dicloxacillin during the first 6 h was abolished when these drugs were combined with fusidic acid. However, at 24 h no significant difference was found between the effect of dicloxacillin alone versus the combination dicloxacillin and fusidic acid. The combination of fusidic acid and rifampicin resulted in a killing identical to that achieved with rifampicin used alone during the first 6 h, but at 24 h the killing by the combination was significantly greater. The bactericidal effect of the combination dicloxacillin (20 mg/1) and tobramycin (10 mg/1) equalled that obtained with tobramycin (10 mg/1) used alone. Rifampicin (5 mg/1) antagonized the bactericidal effect of ciprofloxacin (2 mg/1) during the first 6 h of incubation but at 24 h the combination acted synergistically. The results obtained are partly in agreement and partly in conflict with previous results.