Ampicillin in Treatment of Certain Gram-negative Bacterial Infections

Abstract

Ampicillin, the first semisynthetic penicillin active against Gram-negative pathogens, is bactericidal in vitro to Escherichia coli, certain Proteus spp., some Klebsiella strains, salmonellae, and shigellae. The susceptible range of Gram-positive organisms is the same for ampicillin as for benzylpenicillin, although ampicillin is much less potent, weight for weight. Ampicillin is also destroyed by penicillinase, and is therefore inactivated by many strains of Staphylococcus aureus and by certain penicillinase-producing strains of Proteus and Klebsiella (Rolinson and Stevens, 1961 ; Acred et al, 1962). Ampicillin is acid-stable and is well absorbed from the gastro-intestinal tract. Maximum serum concentrations are reached after one and a half to three hours, falling to lower but still significant levels in four to six hours (Knudsen et ai, 1961 ; Stewart et al., 1961). Renal excretion of ampicillin produces very high concentrations in the urine (Brown and Acred, 1961 ; Acred et al., 1962). The levels attained are very much higher in bile than in serum, and as the drug is not detoxicated in the liver its bactericidal activity is unaffected (Stewart and Harrison, 1961 ; Acred et ai, 1962). Biliary concentrations of ampicillin are much greater than those of chloramphenicol, streptomycin, or neomycin (Harrison and Stewart, 1961). In experimental animals it is evenly distributed through out the body, except for the kidneys and liver, where tissue concentrations are high (Brown and Acred, 1961). Diffu sion into the cerebrospinal fluid is poor (Stewart et al., 1961 ; Acred et al., 1962). The present investigation is an attempt to assess the therapeutic effect of ampicillin in certain infections of the urinary tract and various types of salmonellosis.