Penicillins reaction

In penicillin-allergic patients, oral or parenteral clindamycin may be used. Alternatively, a first-generation cephalosporin such as cefazolin (1 to 2 g IV every 6 to 8 hours) may be used cautiously for patients who have not experienced immediate or anaphylactic penicillin reactions and are penicillin skin test negative. In severe cases in which cephalosporins cannot be used because of documented methicillin resistance or severe allergic reactions to /1-lactam antibiotics, IV vancomycin should be administered. 

A history of a prior penicillin reaction increases the risk of a subsequent exposure. A classic study showed a frequency of allergic reactions to penicillin of 0.62% (155 of 24 906 treatment courses) in patients without a history of penicillin allergy compared with 13% (10 of 78 treatment courses) in patients with a history of penicillin allergy (234). Reaction rates are higher in patients with a history that suggests IgE-mediated reactions (279). 

Rudolph AH, Price EV. Penicillin reactions among patients in venereal disease clinics. A national survey. JAMA 1973 223(5) 499-501. 

Schmitt BD, Krivit W. Benign intracranial hypertension associated with a delayed penicillin reaction. Pediatrics 1969 43(l) 50-3. 

Patients with a history of a mild or a temporally distant penicillin reaction appear to be at low risk of allergic reaction following cephalosporin administration. However, patients who have had a recent severe, immediate reaction to a penicillin should be given a cephalosporin with great caution, if at all. A positive Coombs reaction appears frequently in patients who receive large doses of a cephalosporin, but hemolysis is rare. Cephalosporins rarely have produced bone marrow depression characterized by granulocytopenia. 

Allergic Reactions Penicillin reactions range from skin rashes to anaphylactic shock. The more severe reactions are uncommon, but potentially life-threaten-... 

Allergenicity is less commonly experienced and is less severe with cephalosporins than with penicillins. Cephalosporins frequently are administered to patients who have had a mild or delayed penicillin reaction. Cross-allergenicity is comparatively common, however, and cephalosporins should be administered with caution for patients who have a history of allergies. Patients who have had a rapid and severe reaction to penicillins should not be treated with cephalosporins. 

Kern RA, Wimberley NA Jr (1953) Penicillin reactions their nature, growing importance, recognition, management and prevention. Am J Med Sci 226 357... 

Transformation of Penicillins Reactions of Penam S-Oxides with N-Chloro-N-sodio-carbamates. J. Chem. Soc., Perkin I 1977, 1943. 

Allergy to penicillins is a fairly common phenomenon and is estimated to occur in 2—8% of patients (1, 3 ). Probably due to the repeated and frequent use of penicillins, allergic reactions have become increasingly frequent and severe. It is estimated that approximately 3000 anaphylactic reactions occur annually, of which 10% are fatal (2 ). One reviewer (2 ) has interpreted the evidence to date as suggesting that severe reactions are most likely to occur in patients with a history of atopic asthma, hay fever, or atopic dermatitis. This opinion has also been recently ventured by Parker (5 ). However, the opposite view is put forward by Horowitz (6 ) this author cites a study by Green et al. (1971) on 1027 patients in which it was found that there was no correlation between penicillin reactions (or sensitivity) and a family or personal history of allergy. According to Horowitz this study has since been extended to cover somewhat more than 3000 patients. 

Carbanions stabilized by phosphorus and acyl substituents have also been frequently used in sophisticated cyclization reactions under mild reaction conditions. Perhaps the most spectacular case is the formation of an ylide from the >S-lactam given below using polymeric Hflnig base (diisopropylaminomethylated polystyrene) for removal of protons. The phosphorus ylide in hot toluene then underwent an intramolecular Wlttig reaction with an acetyl-thio group to yield the extremely acid-sensitive penicillin analogue (a penem I. Ernest, 1979). 

A major trend in organic synthesis, however, is the move towards complex systems. It may happen that one needs to combine a steroid and a sugar molecule, a porphyrin and a carotenoid, a penicillin and a peptide. Also the specialists in a field have developed reactions and concepts that may, with or without modifications, be applied in other fields. If one needs to protect an amino group in a steroid, it is advisable not only to search the steroid literature but also to look into publications on peptide synthesis. In the synthesis of corrin chromophores with chiral centres, special knowledge of steroid, porphyrin, and alkaloid chemistry has been very helpful (R.B. Woodward, 1967 A. Eschenmoser, 1970). 

Other Reactions. The reaction of Thydioxybenzaldehyde with sodium cyanide and ammonium chloride, Strecker synthesis, yields /J-hydroxyphenylglycine [938-97-6] a key intermediate in the manufacture of semisynthetic penicillins and cephalosporins (see Antibiotics, p-LACTAMs). 

The P-lactam antibiotics ate produced by secondary metaboHc reactions that differ from those responsible for the growth and reproduction of the microorganism. In order to enhance antibiotic synthesis, nutrients must be diverted from the primary pathways to the antibiotic biosynthetic sequences. Although most media for the production of penicillins and cephalosporins are similar, they ate individually designed for the specific requkements of the high yielding strains and the fermentation equipment used. 

The cephalosporins generally cause few side effects (80,132,219—221). Thrombophlebitis occurs as a result of intravenous administration of all cephalosporins. Hypersensitivity reactions related to the cephalosporins are the most common side effects observed, but these are less common than found with the penicillins. Clinically only about 5—10% of patients with allergic reactions to the penicillins manifest the same reactions to the cephalosporins, and data would contradict any tme cross-reactivity to cephalosporins in patients who have previously reacted to penicillin (80,132,219). 

Penicillins are also degraded by aqueous acids via initial reaction of the sidechain carbonyl group with the P-lactam. PeniciEenic acids (33) are obtained when hydrolysis is carried out at pH 4, penillic acids (34) at pH 2. 

The penicillins in general, ate renowned for their lack of toxicity. The most common adverse effect of the use of penicillins is an allergic reaction which can change from a mild rash to fatal anaphylactic shock in rate cases. AH penicillins cross the placenta and ate excreted in maternal milk. However, the relative freedom from toxicity tenders these compounds valuable agents during pregnancy and lactation. 

Fig. 5. Biosynthesis of penicillins when ACV is aminoadipoly cysteinyl valine and IPNS is isopenicillin N synthase and CgH CH2COSCoA represents benzyl coenzyme A. ACV synthetase is thought to catalyze the first step of this reaction sequence.

Fermentation Processes. The efficient production of penicillin, yeasts, and single-ceUed protein by fermentation requires defoamers to control gas evolution during the reaction. Animal fats such as lard [61789-99-9] were formerly used as a combined defoamer and nutrient, but now more effective proprietary products are usually employed. Defoamer appHcation technology has also improved. For example, in modem yeast production faciHties, the defoamers are introduced by means of automatic electrode-activated devices. One concern in the use of defoamers in fermentation processes is the potential fouHng of membranes during downstream ultrafiltration (qv). SiHcone antifoams (43,44) seem less troubled by this problem than other materials. 

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