Bactericidal effect of combinations of antibiotic and antineoplastic agents against Staphylococcus aureus and Escherichia coli.
BACKGROUND
The bactericidal effect of some antibiotic and antineoplastic agents commonly used in clinical practice was investigated to analyse whether the combinations act synergistically, have indifferent or antagonistic antibacterial effects compared to the effect of the antibiotics alone.


METHODS
The rate of killing of meropenem, ceftazidime and tobramycin was studied against six different strains of Staphylococcus aureus and Escherichia coli, and the results were compared to the rate of killing of the antibiotics in combination with the cytostatic drugs doxorubicin, etoposide and 5-fluorouracil (5-FU).


RESULTS
Tobramycin showed synergy against two strains of S. aureus after 3 h in the presence of 5-FU and against one strain of S. aureus in the presence of doxorubicin. Meropenem induced an antagonistic bactericidal effect against one isolate of S. aureus after 24 h. Ceftazidime expressed an indifferent bactericidal effect together with the cytostatic agents. The antineoplastic agents had no impact on the bacterial killing of any of the antibiotics against E. coli.


CONCLUSIONS
Tobramycin expressed a significantly better bactericidal effect against S. aureus after 3 h in the presence of doxorubicin and 5-FU than tobramycin alone. Meropenem expressed antagonism against one clinical strain of S. aureus, but the cytostatic drugs did not affect the killing of other strains tested. Ceftazidime expressed indifferent bactericidal activity together with the antineoplastic agents.
Nyhlén
A
A
Department of Infectious Diseases, University Hospital of Lund, Sweden. Bengt.Ljungberg@infek.lu.se
Ljungberg
B
B
Nilsson-Ehle
I
I
Odenholt
I
I
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004926:Escherichia coli / Q000187:drug effects* / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy*; D005047:Etoposide / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000472:pathogenicity; D013845:Thienamycins / Q000494:pharmacology*; D014031:Tobramycin / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D002511:Cephalosporins; D013845:Thienamycins; D005047:Etoposide; D004317:Doxorubicin; D002442:Ceftazidime; D000077731:Meropenem; D005472:Fluorouracil; D014031:Tobramycin