Staphylococci penicillin, sensitivity

These penicillins resist hydrolysis by staphylococcal penicilhnase. Their appropriate use is restricted to the treatment of infections that are known or suspected to be caused by staphylococci that elaborate the enzyme, including the vast majority of strains that are encountered clinically. These drugs are much less active than penicilhn G against other penicillin-sensitive microorganisms. 

When treatment is initiated before definitive culture and sensitivity results are known, consider that these agents are only effective in the treatment of infections caused by pneumococci, group A beta-hemolytic streptococci, and penicillin G-resistant and penicillin G-sensitive staphylococci. 

Examination of suppurating wound microflora has shown that in both groups the suppuration process was mainly caused by staphylococci which are resistant to or had low sensitivity to penicillin and streptomycin. 

Penicillin, in regard to infections with sensitive microbes, appears to have some advantages over the well-known chemical antiseptics. A good sample will inhibit staphylococci, Streptococcus pyogenes and pneumococcus in a dilution of 1 in 800. It is therefore a more powerful inhibitory agent than is carbolic acid and... it is non-irritant and non-toxic. 

Tyrothricin > 9 is bacteriostatic in concentrations of 0-01 figlml. and less for gram-positive cocci such as pneumococci, streptococci and staphylococci. At concentrations greater than 1 g/ml. it is bactericidal and some species of organisms, e.g. pneumococcus and staphylococcus are lysed. Gramnegative bacteria are much less sensitive. Many penicillin-resistant strains of cocci are sensitive to tyrothricin Table 1.7). 

MECHANISMS OF BACTERIAL RESISTANCE TO PENICILLINS AND CEPHALOSPORINS A sensitive strain may acquire resistance by mutations that decrease the affinity of PBPs for the antibiotic. Because /5-lactam antibiotics inhibit many different PBPs, their affinity for several PBPs must decrease to confer resistance. Methidllin-resistant S. aureus are resistant via acquisition of an additional high-molecular-weight PBP (via a transposon) with a very low affinity for all /5-lactam antibiotics this mechanism is responsible for methicillin resistance in the coagu-lase-negative staphylococci. 

Mechansim of Action. The drug is speeifieally resistant to inactivation by the presenee of the enzyme penicillinase found in staphylococci. It has been observed to induee penicillinase formation which specifically restrains its usage in the control, management and treatment of penicillin G-sensitive infections. 

The biphasic effect is associated primarily with (3-lactam antibiotics. It is a curious phenomenon in which low doses in vitro against certain bacteria (staphylococci and streptococci) produce lysis, whereas higher doses do not. This is believed to result from the differential sensitivity of the penicillin binding proteins (see below for an explanation of this term) in that higher doses of (3-lactams inhibit the autolysins (this term also will be defined later). These are enzymes that also contribute to bacterial lysis. 

Lincomycin is a natural product isolated from fermentations of Streptomyces lincolnensis var. lincolnensis. It is active against Gram-positive organisms, including some anaerobes. It is indicated for the treatment of serious infections caused by sensitive strains of streptococci, pneumococci, and staphylococci. It generally is reserved for patients who are allergic to penicillin because of the increased risk of pseudomembranous colitis (described below). It also serves as the starting material for the synthesis of clindamycin (by a Sn-2 reaction that inverts the R stereochemistry of the C-7 hydroxyl to a C-7 S-chloride). 

In this way Staphylococcus aureus becomes resistant to penicillin in the clinic. Penicillin-resistant strains isolated from patients secrete the enzyme p-lactamase ( penicillinase ). This enzyme hydrolyses the drug to penicil-loic acid, which is biologically inert (see Section 12.i). Penicillinase-producing staphylococci are inherently quite sensitive to penicillin. Hence small inocula can be inhibited by low concentrations of the antibiotic. It is, in effect, a race between the speed with which penicillin can kill the bacteria and the speed with which they can produce enough of the enzyme to destroy the penicillin (Knox, 1962). Actually penicillin can be made to induce some strains of Staph, aureus to produce penicillinase. No permanently resistant population of this bacterium has arisen in this way, and the organisms return fairly rapidly to the uninduced susceptible state when the penicillin is withdrawn. Much of the detail of penicillinase-induction was first worked out in Bacillus cereus (Pollock and Ferret, 1951). 

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