Synergy between cefuroxime and ticarcillin against Providencia, and the activity of cefuroxime against Streptococcus faecalis and gram-negative bacteria

Abstract

The combination of a cephalosporin and a penicillin has previously not been considered to be useful, but cefuroxime and cefamandole have a wider spectrum than older cephalosporins, and ticarcillin is active against Strep. faecalis, Bacteroides and Pseudomonas. If a non-toxic combination such as cefuroxime and ticarcillin could act synergistically to lower bactericidal concentrations these drugs could have a wide clinical application. Six strains of Providencia stuarti were isolated from paraplegics with urinary tract infection. When tested separately the MICs and MBCs of cefuroxime were 64 and 512 mg/l respectively, and of ticarcillin 2 and 512 mg/l. However, the organisms were inhibited by cefuroxime 1 mg/l with ticarcillin 4 mg/1. and killed by cefuroxime 2 mg/1 and ticarcillin 4 mg/l. The patients were treated intramuscularly with ticarcillin 1.5 g b.d. and cefuroxime 750 mg in the morning. and 1 1/2 h after the morning combination the serum was bactericidal to the Providencia at dilutions of 1 in 4 to 1 in 16, and the organisms were eradicated. Cefuroxime and ticarcillin have been found to act synergistically also against some strains of Klebsiella, Enterobacter, Acinetobacter and Strep. faecalis. The MIC of cefuroxime for Strep. faecalis can be mis-read if the inoculum is too small. Repeated studies showed that in 50 isolates of Strep. faecalis the MIC of cefuroxime was 256 mg/l for 12 strains, 512 mg/l for another 31 strains, and 1024 mg/l for the other 5 strains. Although 87 of 100 strains of Strep. faecalis were inhibited by ticarcillin 32 mg/l, the MBC was usually 512 mg/l. At a concentration of cefuroxime of 16 mg/l none of 300 strains of E. coli were resistant to cefuroxime. and of 132 strains of Klebsiella only 3 were resistant, whereas 6 were resistant to cefoxitin. Of 56 strains of Enterobacter 47 were sensitive to cefuroxime but only 6 to cefoxitin. Cefuroxime is also more active than cefoxitin against Acinetobacter, 15 of 27 strains being sensitive, but is less active than cefoxitin against indole-positive Proteus species, Citrobacter and Serratia. The combination of a cephalosporin and a penicillin has previously not been considered to be useful, but cefuroxime and cefamandole have a wider spectrum than older cephalosporins, and ticarcillin is active against Strep. faecalis, Bacteroides and Pseudomonas. If a non-toxic combination such as cefuroxime and ticarcillin could act synergistically to lower bactericidal concentrations these drugs could have a wide clinical application. Six strains of Providencia stuarti were isolated from paraplegics with urinary tract infection. When tested separately the MICs and MBCs of cefuroxime were 64 and 512 mg/l respectively, and of ticarcillin 2 and 512 mg/l. However, the organisms were inhibited by cefuroxime 1 mg/l with ticarcillin 4 mg/1. and killed by cefuroxime 2 mg/1 and ticarcillin 4 mg/l. The patients were treated intramuscularly with ticarcillin 1.5 g b.d. and cefuroxime 750 mg in the morning. and 1 1/2 h after the morning combination the serum was bactericidal to the Providencia at dilutions of 1 in 4 to 1 in 16, and the organisms were eradicated. Cefuroxime and ticarcillin have been found to act synergistically also against some strains of Klebsiella, Enterobacter, Acinetobacter and Strep. faecalis. The MIC of cefuroxime for Strep. faecalis can be mis-read if the inoculum is too small. Repeated studies showed that in 50 isolates of Strep. faecalis the MIC of cefuroxime was 256 mg/l for 12 strains, 512 mg/l for another 31 strains, and 1024 mg/l for the other 5 strains. Although 87 of 100 strains of Strep. faecalis were inhibited by ticarcillin 32 mg/l, the MBC was usually 512 mg/l. At a concentration of cefuroxime of 16 mg/l none of 300 strains of E. coli were resistant to cefuroxime. and of 132 strains of Klebsiella only 3 were resistant, whereas 6 were resistant to cefoxitin. Of 56 strains of Enterobacter 47 were sensitive to cefuroxime but only 6 to cefoxitin. Cefuroxime is also more active than cefoxitin against Acinetobacter, 15 of 27 strains being sensitive, but is less active than cefoxitin against indole-positive Proteus species, Citrobacter and Serratia.