Penicillinase action

Beta-lactam ring (site of penicillinase action)... 

Indicate from the diagram below the site of action of penicillinase. 

The conventional bioassays based on methodology developed by FDA and expanded by FSIS use four extractant buffers, five test organisms, five growth media, two incubation temperatures, and penicillinase to detect, identify, and/or quantify antibiotics such as the penicillins, streptomycins, tetracyclines, neomycins, erythromycin, tylosin, etc. Bioassay laboratory results are used by FSIS to take regulatory action and by FDA to prosecute farmers with histories of improperly withdrawing antibiotics before marketing their herds or flocks. 

In terms of the spectrum of antimicrobial action, oxacillin is analogous to benzylpenicillin. However, it combines the resistance to penicillinase with durability in an acidic medium, which allows it to be used not only intramuscularly, but also orally. It is used for infections caused by... 

Moxalactam is resistant to the action of beta-lactamase, penicillinase, and cephalospori-nase, which are produced by Gram-negative and Gram-positive bacteria. Many strains of... 

All -lactam antibiotics are bactericidal. They interfere with the synthesis of the bacterial wall by inhibiting the bacterial ftanspeptidase enzymes essential for the construction of peptidoglycan of the wall. Some -lactams may be inactivated by the -lactamases (penicillinases) produced by bacteria and, thus, the activity of both penicillins and cephalosporins can be determined by their ability to withstand the destructive action of -lactamases also produced by the organism for its optimal protection. Bacterial resistance caused by -lactamase production... 

Rx of pneumonia, skin, soft tissue Infxns, osteomyelitis caused by penicillinase-producing staphylococci Action Bactericidal X cell wall synth Dose Adults. 250-500 mg qid Feds <40 kg, 12.5-100 mg/kg/d - qid take on empty stomach Caution [B, ] Contra Component orPCN sensitivity Disp Caps 125, 250, 500 mg soln 62.5 mg/5 mL SE N/D, abd pain Interactions T Effects W/ disulfiram, probenecid T effects OF MRX, X effects W/ macrolides, tetracyclines, food X effects OF OCPs, warfarin EMS Monitor for signs of electrolyte disturbances and hypovolemia d/t D OD May cause N/V/D, behavior changes, urinary retention, skin rash and Szs symptomatic and supportive... 

Stability of the penicillins to acid or the action of penicillinase [Note Penicillin G is largely inactived by stomach acid, but doses can be adjusted so that adequate serum levels are achieved.]... 

Gutnick MJ, Prince DA. Penicillinase and the convulsant action of penicillin. Neurology 1971 21(7) 759-64. 

RECEPTOR ANTAGONIST reported to have little sedative action, tazifylline hydrochloride tazifyUine. tazobactam (inn] (tazobactam sodium [usan]) is an ENZYME INHIBITOR active against the P-lactamase ( penicillinase ) enzymes produced by Gram-positive and -negative bacteria. Clinically, it can be used co-administered with -lactamase susceptible penicillins and cephalosporins, enhancing their antibacterial actions, tazobactam sodium tazobactam. 

Later, his research topics included carbohydrate-amino acid relationship in nervous tissue, a study of the mode of action of insulin, fermentation technology, 6-aminopenicillanic acid and penicillinase-stable penicillins, lysergic acid production in submerged culture, and the isolation of new fungal metabolites. 

A number of buffers are reported to catalyze the degradation of phenoxymethyl penicillin in aqueous solutions at 8CP 49 In Qther studies 50, 51 the presence of pharmaceutical excipients, surfactants, preservatives and. suspending and thickening agents reduced the stability of penicillin V in aqueous solutions. Amino alkylcatechols have been studied as model compounds that simulate the action of penicillinase... 

This situation changed when an efficient chemical method was developed at Eli Lilly in Indianapolis, which would remove the side-chain of cephalosporin C to produce a bare cephalosporin nucleus, the so-called 7-aminocephalosporanic acid, from which a whole range of semi-synthetic cephalosporins could be produced. Of these, cephaloridine and cephalothin were the most widely used. Of even greater significance was the invention of some very clever chemistry, also by the Lilly group, which involved the conversion of the penicillin nucleus into the cephalosporin nucleus in a short sequence of chemical transformations (Fig. 2.2). This meant that the very cheap penicillin G could be converted into what became the best-selling cephalopsorin cephalexin (Keflex). This had excellent oral bioavailability, was very stable to metabolism, and resisted the actions of penicillinases. The other semi-synthetic cephalosporin that came to be widely used was cefaclor... 

I I Site of action of penicillinase H Site of action of amidase... 

Clavulanic acid is a chemical similar in structure to penicillin, which acts as a substrate for penicillinase, thus inhibiting its action on penicillin. This agent is added to penicillin preparations to decrease the manifestation of bacterial resistance. 

Bacteria also can destroy /5-lactam antibiotics enzymatically via the actions of /5-lactamases (Figures 44-1 and 44-3). The substrate specificities of some of these enzymes are relatively narrow such enzymes are sometimes referred to as penicillinases or cephalosporinases. Other extended-spectrum enzymes can hydrolyze a variety of /5-lactam antibiotics. 

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. 

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