[Synergy between sulbactam and ampicillin or cefoperazone in antimicrobial activity against beta-lactamase producing microorganisms. Results with the use of microdilution broth method]

Abstract

Antimicrobial activities of sulbactam (SBT) with ampicillin (ABPC) or with cefoperazone (CPZ), in other words, the effects of SBT, an beta-lactamase inhibitor, against beta-lactamase producing strains of clinical isolates, were studied using microdilution broth method. 1. beta-Lactamase producing strains such as Staphylococcus aureus, Branhamella catarrhalis, Haemophilus influenzae, Escherichia coli and Klebsiella pneumoniae decompose benzylpenicillin (PCG) which is one of substrates of the acid-metry disc method and show a strong reaction, while they do not decompose cefazolin (CEZ), another substrate, showing no or weak reaction. Thus, it is suspected that beta-lactamases produced by these organisms are mainly penicillinase (PCase). MIC-distributions of ABPC and CPZ against these clinical isolates which seemed to produce PCase shifted to lower MIC ranges with MIC's reduced to 1/4 or below when 0.025 to 0.39 microgram/ml of SBT was added. 2. It appears that beta-lactamase produced by Proteus vulgaris may be oxyiminocephalosporinase (CXase), because P. vulgaris showed strong reaction on CEZ, but moderate reaction on PCG in the acid-metry disc method. MIC-distribution of ABPC and CPZ against P. vulgaris shifted to a lower range with MIC's of 1/4 or below when 0.20 to 0.39 microgram/ml of SBT was added. 3. All the test strains of Pseudomonas aeruginosa showed strong reaction on CEZ but only 56% of the test strains showed reaction on PCG. It appears that the beta-lactamases which showed strong reaction on CEZ is cephalosporinase and is encoded in chromosome, while those beta-lactamase that showed strong reaction on PCG is encoded in a plasmid which was acquired secondarily by P. aeruginosa. MIC-distribution of CPZ against P. aeruginosa shifted to a lower range with MIC values of 1/2 or below with the addition of SBT at 1.56 micrograms/ml. 4. It appears that the synergy of SBT with ABPC or with CPZ against the PCase or CXase producing strains may occur in the presence of SBT at a concentration far less than that reported previously.