Penicillin determination

Desensitization Patients with a positive skin test to one of the penicillin determinants can be desensitized, a relatively safe procedure. This is recommended in instances when penicillin must be given where no proven alternatives exist. 

There was a high degree of cross-reactivity between imipenem determinants, analogous to the penicillin determinants in penicillin-allergic patients. Nine of twenty patients with positive penicillin skin tests had positive skin reactions to analogous imipenem determinants (40). In view of this appreciable cross-reactivity, imipenem should not be given to patients with penicillin allergy. 

Silviu-Dan F, McPhiUips S, Warrington RJ. The frequency of skin test reactions to side-chain penicillin determinants. 

Decristoforo and Danielsson (1984) designed an enzyme thermistor for penicillin determination based on (3-lactamase immobilized on porous... 

Oh, D. M., Sinko, P. J., and Amidon, G. L., 1989, Characterization of oral absorption of some penicillins Determination of inhinsic membrane absorption parameters in the intestine in... 

In an evaluation of 276 patients who had a reaction attributed to amoxicUlin-clavulanic acid, 55 patients (19.9 %) reacted positively to different penicillin determinants. Of the 221 with negative skin tests, 15 were positive to amoxicillin and seven were judged to be allergic to clavulanic acid on the basis of tolerance to benzylpenicillin and amoxicillin and an immediate reaction to clavulanic acid following challenges. In the skin test-positive group, skin and... 

Mifflin, T. E. Andriano, K. M. Robbins, W. B. Determination of Penicillin Using an Immobilized Enzyme Electrode, /. Chem. Educ. 1984, 61, 638-639. 

Duarte and colleagues used a factorial design to optimize a flow injection analysis method for determining penicillin potentiometricallyd Three factors were studied—reactor length, carrier flow rate, and sample volume, with the high and low values summarized in the following table. 

An optimum response was defined as the greatest sensitivity, as determined by the measured potential for a standard solution of penicillin, and the largest sampling rate. The results of the optimization studies are shown in the following... 

In the case of thienamycin (Fig. lb) the absolute stereochemistry at C-5 was unambiguously deterrnined from the ene-lactam (16). The resultant (R)-aspartic acid (17) demonstrated that the absolute stereochemistry at C-5 of thienamycin is (R), corresponding to that found in the C-5 position of both penicillins and cephalosporins. Confirmation of the stereochemical assignments in both thienamycin (2) and the olivanic acid MM 13902 (3, n = 0) has been confirmed by x-ray crystallography (19,21,22). The stmctural determination of the nonsulfated derivatives from S. olivaceus (23), PS-5 (5) (5), the carpetimycins (6), and the asparenomycins (7) followed a similar pattern. 

One approach to combating antibiotic resistance caused by P-lactamase is to inhibit the enzyme (see Enzyme inhibition). Effective combinations of enzyme inhibitors with P-lactam antibiotics such as penicillins or cephalosporins, result in a synergistic response, lowering the minimal inhibitory concentration (MIC) by a factor of four or more for each component. However, inhibition of P-lactamases alone is not sufficient. Pharmacokinetics, stability, ability to penetrate bacteria, cost, and other factors are also important in determining whether an inhibitor is suitable for therapeutic use. Almost any class of P-lactam is capable of producing P-lactamase inhibitors. Several reviews have been pubUshed on P-lactamase inhibitors, detection, and properties (8—15). 

The role of IR spectroscopy in the early penicillin structure studies has been described (B-49MI51103) and the results of more recent work have been summarized (B-72MI51101). The most noteworthy aspect of a penicillin IR spectrum is the stretching frequency of the /3-lactam carbonyl, which comes at approximately 1780 cm" This is in contrast to a linear tertiary amide which absorbs at approximately 1650 cm and a /3-lactam which is not fused to another ring (e.g. benzyldethiopenicillin), which absorbs at approximately 1740 cm (the exact absorption frequency will, of course, depend upon the specific compound and technique of spectrum determination). The /3-lactam carbonyl absorptions of penicillin sulfoxides and sulfones occur at approximately 1805 and 1810 cm respectively. The high absorption frequency of the penicillin /3-lactam carbonyl is interpreted in terms of the increased double bond character of that bond as a consequence of decreased amide resonance, as discussed in the X-ray crystallographic section. Other aspects of the penicillin IR spectrum, e.g. the side chain amide absorptions at approximately 1680 and 1510 cm and the carboxylate absorption at approximately 1610 cm are as expected. 

In spite of the slow development of crystal structure analysis, once it did take olT it involved a huge number of investigators tens of thousands of crystal structures were determined, and as experimental and interpretational techniques became more sophisticated, the technique was extended to extremely complex biological molecules. The most notable early achievement was the structure analysis, in 1949, of crystalline penicillin by Dorothy Crowfoot-Hodgkin and Charles Bunn this analysis achieved something that traditional chemical examination had not been able to do. By this time, the crystal structure, and crystal chemistry, of a huge variety of inorganic compounds had been established, and that was most certainly a prerequisite for the creation of modern materials science. 

The pH of the mixture was adjusted to 7.5 by adding a saturated sodium bicarbonate solution. After being washed twice with diethyl ether, the reaction solution was acidified to pH 2 with dilute hydrochloric acid and extracted with ether. The ether solution containing the free penicillin was washed twice with water and then extracted with 50 ml of N potassium bicarbonate solution. After freeze drying of the obtained neutral solution, the potassium salt of o-azidobenzylpenicillin was obtained as a slightly colored powder (11.2 grams, 54% yield) with a purity of 55% as determined by the hydroxylamine method (the potassium salt of penicillin G being used as a standard). 

A suspension of 6-aminopenicillanic acid (36.4 grams) in water was adjusted to pH 7.2 by the addition of N aqueous sodium hydroxide and the resulting solution was treated with a solution of 3-(2-chloro-6-fluorophenyl)-5-methylisoxazole-4-carbonyl chloride (46.1 grams) in isobutyl methyl ketone. The mixture was stirred vigorously for hours and then filtered through Dicalite. The layers were separated and the isobutyl methyl ketone layer was shaken with saturated brine. Then, precipitation of the sodium salt only took place after dilution of the mixture with ether. In this way there was obtained 60.7 grams of the penicillin sodium salt having a purity of 88% as determined by alkalimetric assay. 

Penicillin can likewise be determined by using the enzyme penicillinase to destroy the penicillin with production of hydrogen ions which can be determined using a normal glass pH electrode. Many other organic materials can be determined by similar procedures.34,35... 

To determine if a specific type of bacteria is sensitive to penicillin, culture and sensitivity tests are performed. A culture is performed by placing infectious material obtained from areas such as the skin, respiratory tract, and blood on a culture plate that contains a special growing medium. This growing medium is food for the bacteria After a specified time, the bacteria are examined under a microscope and identified. The sensitivity test involves placing the infectious material on a separate... 

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