Six antineoplastic antibiotics showed little antibacterial activity against 28 strains of four species of gram-negative enteric bacteria. By using the cellophane transfer technique, combinations of these agents with 16 antibacterial drugs usually showed indifference. However, combinations of mitomycin C, especially with the aminoglycosides, were synergistic on strains of Escherichia coli, Proteus, and Klebsiella pneumoniae. Bleomycin, on the other hand, often showed antagonism on strains of E. coli and K. pneumoniae with the ,B-lactams, aminoglycosides, and other antibacterial agents. Checkerboard titrations and kinetic killing curves confirmed these findings.We have recently described (14) both synergism and antagonism with combinations of each of six antineoplastic antibiotics and each of 16 antibacterial drugs when tested against 10 strains of Staphylococcus aureus. The present paper records the bactericidal activity of the same drug combinations on four species ofgramnegative bacilli which are commonly implicated in infections occurring in patients with malignant neoplastic disease (2,10,12).(This work will be submitted to the Hebrew University of Jerusalem by J. Y. J. in partial fulfillment of the requirements for a Ph.D. degree.)MATERIALS AND METHODSThe 28 strains of gram-negative bacilli used were isolated from blood, urine, and pus samples in the Department of Clinical Microbiology of the Hadassah University Hospital and consisted of 6 strains of Escherichia coli, 3 strains ofProteus mirabilis, 2 ofProteus morganii, 1 of Proteus rettgeri, 6 of Kkbsiella pneumoniae and 10 strains of Pseudomonas aeruginosa.The combinations of antibacterial and antineoplastic agents were initially screened by the cellophane transfer technique (3-5, 7). Details of this method and the other methods used to determine minimal inhibitory concentrations and minimal bactericidal concentrations (MBCs) and for the quantitative evaluation of combined activity were described in our previous paper (14).The antibacterial drugs, antineoplastic antibiotics, and the concentrations of the drugs employed to impregnate the test strips used in the cellophane transfer technique were identical to those described by Jacobs et al. (14) except for penicillin G (600 tg/ml) and rifampin (1,000 ,g/ml). The results of cellophane transfer screening were classified as synergism, indifference, or antagonism by two of the authors independently according to published criteria (4, 11). Doubtful results were duplicated or triplicated.Checkerboard titrations (14) were used to confirm the synergistic and antagonistic combinations indicated by the cellophane transfer technique.Fractional bactericidal concentrations (FBCs) of each drug were calculated by dividing the MBC of the drug in combination by the MBC of the drug alone. The total of the FBCs of the two drugs tested is the FBC index (XFBC) (14). Kinetic killing curves were prepared after following the action of the drug combination during 24 h, in examples selected according to results of the cellophane tra...