IN vitro susceptibilities of 98 isolates of Brucella melitensis to N-formimidoyl thienamycin, tetracycline, co-trimoxazole, rifampin, and cefoxitin were determined. N-Formimidoyl thienamycin showed good activity which was similar to those of tetracycline and rifampin and different from that of the other beta-lactam antibiotic tested (cefoxitin), which showed poor activity. Co-trimoxazole showed good activity.

The in vitro synergistic activity of N-formimidoyl thienamycin and amikacin was determined against gentamicin-resistant enterobacteriaceae, Pseudomonas aeruginosa, and Staphylococcus aureus. N-Formimidoyl thienamycin showed synergism with amikacin against 19 of the gentamicin-resistant strains, 14 of the 49 strains of S. aureus, and only 1 strain of the 46 P. aeruginosa isolates.Thienamycin is a P-lactam antibiotic of novel structure produced by Streptomyces cattleya (4). The activity of this compound is characterized by its great intrinsic activity and broad antibacterial spectrum. The stability of thienamycin in the presence of P-lactamases and its activity against Pseudomonas sp. are of particular interest (6), although its potential utility was compromised by its lability in concentrated solutions and as a solid (4). Fortunately, this problem was partly solved with the development of the amidine derivate N-formimidoyl thienamycin (MK0787) (3, 6), a new analog of thienamycin that not only retains its great resistance against P-lactamases but is also capable of inhibiting them (3,7,14). The antibacterial activity of this thienamycin derivative is greater that that of thienamycin, especially against Pseudomonas, Bacteroides, and Enterococcus spp. (6,13). The purpose of this study was to evaluate the combined activity of N-formimidoyl thienamycin and amikacin.All the microorganisms studied, with the exception of Pseudomonas aeruginosa and Staphylococcus aureus isolates, were gentamicin resistant, with a minimum inhibitory concentration (MIC) of >8 ,ug/ml. The total number of isolates was 160; all of them were obtained from clinically significant specimens in a period of 6 months (from July to December 1981 (12). The concentrations used ranged between 0.01 and 32 ,ug/ml for N-formimidoyl thienamycin and between 0.25 and 32 ,ug/ml for amikacin. P-Lactamase activity of staphylococcal isolates was determined by using the Glaxo chromogenic cephalosporin, nitrocefin (9). S. aureus ATCC 25923 and Escherichia coli ATCC 25922 were utilized as control strains. The MICs obtained for these two control strains were 0.01 and 0.125 ,ug/ml with N-formimidoyl thienamycin and 1 and 2 ,ug/ml with amikacin. The evaluation of the N-formimidoyl thienamycin and amikacin combination was carried out in Mueller-Hinton agar by the simplified checkerboard method (5). Methodology and inoculum quantification were as described above. After 24 h of incubation at

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