title: In vitro studies of the synergism of piperacillin and netilmicin against blood culture isolates.
abstract: The purpose of this study was to evaluate the in vitro synergism between piperacillin and netilmicin against microorganisms isolated from Danish patients with septicemia and to examine the influence of inactivation of piperacillin among these bacteria on the synergy results. A total of 132 stains was examined: Escherichia coli 20, indole-positive Proteus 17, Klebsiella pneumoniae 18, Enterobacter cloacae 20, Pseudomonas aeruginosa 20, Staphylococcus aureus 20, and coagulase-negative staphylococci 17. Synergy testing was performed by checkerboard titration in microtiter trays. The ability of the strains to inactivate piperacillin was examined by the clover-leaf test. Synergism was found for 52% of the strains and partial synergism for 32%. Antagonism was not found. Of the piperacillin-resistant strains synergism could be demonstrated in 80% compared with 33% of the piperacillin-susceptible strains (p less than 0.001). No significant correlation was seen between the results of the synergy test and the results of the susceptibility test to netilmicin. The frequency of piperacillin inactivation according to the clover-leaf test was significantly higher among the strains with synergism than among all the others (p less than 0.02). The combination of piperacillin and netilmicin gave good results concerning the in vitro synergism. This synergism was probably sometimes caused by netilmicin disturbing the bacterial production of piperacillin-inactivating proteins.
authors.forename: M
authors.initials: M
authors.lastname: Arpi
authors.forename: P E
authors.initials: PE
authors.lastname: Jørgensen
authors.forename: H F
authors.initials: HF
authors.lastname: Pedersen
mesh_terms: D001419:Bacteria / Q000187:drug effects* / Q000302:isolation & purification / Q000378:metabolism; D004357:Drug Synergism; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D007709:Klebsiella / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009428:Netilmicin / Q000494:pharmacology*; D010878:Piperacillin / Q000378:metabolism / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D018805:Sepsis / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D009428:Netilmicin; D010878:Piperacillin