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L D Sabath

Publications and source records attributed to L D Sabath.

97 records · Page 6Linked to original sources
PubMed1965

Cephalosporinase and penicillinase activities of a beta-lactamase from Pseudomonas pyocyanea.

1. Pseudomonas pyocyanea N.C.T.C. 8203 produces a beta-lactamase that is inducible by high concentrations of benzylpenicillin or cephalosporin C. Methicillin appeared to be a relatively poor inducer, but this could be attributed in part to its ability to mask the enzyme produced. Much of the enzyme is normally cell-bound. 2. No evidence was obtained that the crude enzyme preparation consisted of more than one beta-lactamase and the preparation appeared to contain no significant amount of benzylpenicillin amidase or of an acetyl esterase. 3. The maximum rate of hydrolysis of cephalosporin C and several other derivatives of 7-aminocephalosporanic acid by the crude enzyme was more than five times that of benzylpenicillin. Methicillin, cloxacillin, 6-aminopenicillanic acid and 7-aminocephalosporanic acid were resistant to hydrolysis, and methicillin and cloxacillin were powerful competitive inhibitors of the action of the enzyme on easily hydrolysable substrates. 4. Cephalosporin C, cephalothin and cephaloridine yielded 2 equiv. of acid/mole on enzymic hydrolysis, and deacetylcephalorsporin C yielded 1 equiv./mole. Evidence was obtained that the opening of the beta-lactam ring of cephalosporin C and cephalothin is accompanied by the spontaneous expulsion of an acetoxy group and that of cephaloridine by the expulsion of pyridine. 5. A marked decrease in the minimum inhibitory concentration of benzylpenicillin and several hydrolysable derivatives of 7-aminocephalosporanic acid was observed when the size of the inoculum was decreased. This suggested that the production of a beta-lactamase contributed to the factors responsible for the very high resistance of Ps. pyocyanea to these substances. It was therefore concluded that the latter might show synergism with the enzyme inhibitors, methicillin and cloxacillin, against this organism.

Cephalosporins↗
PubMedDate not supplied

Biochemical and physiologic basis for susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents.

The mechanisms involved in the susceptibility and resistance of Pseudomonas aeruginosa to antimicrobial agents are varied. For the beta-lactam agents, susceptibility of the organism is dependent on penetration of the outer membrane, binding to target proteins, absence of significant beta-lactamases, and, possibly, the initiation of cell wall lysis. Susceptibility to aminoglycosides is based on membrane permeation and transport and specific binding to the 30S ribosomal subunit. Antipseudomonal activity of the polymyxins is related to their binding to membrane phospholipids, with subsequent disruption of the membrane; and activity of tetracycline and erythromycin, which is pH-dependent, affects protein synthesis. Resistance to beta-lactam agents is mediated through beta-lactamases, the Id and V enzymes being especially important in P. aeruginosa. Other postulated mechanisms of resistance include the presence of a permeability barrier, insensitivity of target sites, decreased binding, and "trapping." Decreased binding to the S12 protein (often termed the P10 protein in references to streptomycin), decreased active transport, and enzyme-mediated modification are the major mechanisms responsible for resistance to aminoglycosides. The factors involved in resistance to tetracycline and erythromycin remain unclear. The emergence of resistance during a single course of beta-lactam therapy is a special problem with P. aeruginosa and may be due to acquisition of resistance genes, cross-infection, selection or induction of resistance in some variants, or mutation.

Aminoglycosides↗
PubMedDate not supplied

The outlook for prevention and treatment of infections due to Pseudomonas aeruginosa.

Control measures based on careful hospital surveillance are aimed primarily at minimizing environmental sources of Pseudomonas aeruginosa. Other important aspects of epidemiologic control include aggressive evaluation of outbreaks and limitation of antimicrobial use. Potent new antimicrobial chemotherapy has been developed, with most new agents of the beta-lactam and aminoglycoside classes. In spite of these developments, the likelihood of drug resistance seems great and the search for novel compounds continues. Of greatest appeal are approaches that augment host defences. Replacement or supplementation of circulating phagocytic cells is conceptually attractive, but this approach has encountered major technical problems and complications. More recently, there has been important progress in developing immunologic approaches aimed at augmenting circulating antibodies. Development of monoclonal antibodies and new methods for preparing hyperimmune globulins has produced forms of intervention that must be tested by clinical trials, but not all patients may benefit from augmentation of circulating antibodies to P. aeruginosa.

Anti-Bacterial Agents↗