Phenoxymethylpenicillin Research Articles

Spectrophotometric determination of some penicillins with ammonium vanadate

A spectrophotometric method for determining some penicillins has been developed. A known volume of the penicillin solution—in phosphate buffer of pH 6.8 is boiled with ammonium vanadate solution—in sulphuric acid medium—for 10 min and the absorbance of the colour formed is measured at 750 nm. The excess of vanadate can also be determined volumetrically. The method has been successfully applied for the determination of penicillin G sodium, phenoxymethyl penicillin, ampicillin sodium, phenethicillin potassium, cloxacillin sodium and methicillin sodium. The procedure is also used for analysing some pharmaceutical preparations of these drugs, e.g., injections. The results obtained are in agreement with those of the B P 1973 methods.

Effects of supplements of phosphorus or phosphorus and protein on the ovarian activity of cows fed native pasture hay

Eight cows with calves in pens were fed native tropical pasture hay harvested at intervals throughout the wet season. Four of the cows were supplemented with phosphorus. When pastures matured and declined in quality, calves were weaned and their dams were firstly group-fed hay in yards and later allowed to graze native pasture. One group continued to receive phosphorus supplement and both groups were supplied with protein supplement to offset possible deficiency. During the pen feeding period, none of the cows exhibited oestrus and plasma progesterone declined as the quality of the hay fell; the cows were refractory to treatment with luteolytic prostaglandin. Some four months after the commencement of protein supplementation, two cows from the group receiving phosphorus supplement exhibited oestrus. Three cows from each group had elevated plasma progesterone levels, and these animals all exhibited oestrus following treatment with prostaglandin. Phosphorus supplementation had no significant effect on feed intake, liveweight change or milk production. Blood inorganic phosphorus was significantly increased by treatment but bone phosphorus was not. It was concluded that phosphorus supplementation alone had no significant effect on reproductive activity. If cows received adequate protein, however, oestrus activity was markedly increased whether phosphorus was supplemented or not.

Overwhelming postsplenectomy infection

One of the more intriguing aspects of the spleen is the protection against certain bacterial infections afforded by its unique vascular and immune function. There have been extensive clinical surveys which indicate an incidence of overwhelming postsplenectomy infection (OPSI) above that of the disease for which the splenectomy was done. In the absence of the spleen, either congenital or subsequent to surgical removal, this overwhelming sepsis has a 50% case fatality rate. The most common infective organism has been Diplococcus (tstreptococcus) pneumoniae (D. pneumoniae). Intensive investigations indicated loss of phagocytic function of the spleen, depression of serum IgM levels, a possible suppression of the lymphocyte responsiveness, and changes in opsonin-alternative complement system as potential causes of OPSI. Preventive measures against OPSI include trials of prophylactic Phenoxymethyl Penicillin (penicillin) and pneumococcal vaccine.

A Simplified Apparatus for the Microbiological Isolation of Calves

SUMMARY An isolator has been developed for rearing gnotobiotic and specific pathogen free (SPF) calves. The isolator consisted of relatively cheap components which could be rapidly assembled; the upper half being a flexible polyvinyl chloride (PVC) canopy clamped to a glass fibre tank. This formed the lower half of the microbiological barrier, and also served as the calf pen. The assembled isolator could be sterilized with peracetic acid. Over fifty gnotobiotic calves have been reared successfully in this type of isolator. Some calves were kept for up to five months, though the average time within the isolator was one month. Ten cases of contamination were thought to be attributable to faults in the rearing isolator. No cases of cross contamination of experimental agents from one isolator to another were discovered in either gnotobiotic or SPF animals.

Susceptibility of Staphylococcus aureus and Staphylococcus epidermidis to 65 antibiotics.

The susceptibilities of 36 recent isolates of Staphylococcus aureus and 35 recent isolates of Staphylococcus epidermidis were determined against each of 65 antimicrobial agents and against two of them in combination. Rifampin was the most active of all the agents tested against both S. aureus and S. epidermidis. Among the penicillins, cloxacillin, dicloxacillin, and nafcillin were most active, although benzylpenicillin and phenoxymethyl penicillin were more active against susceptible strains. Cephaloridine was the most active of the cephalosporins, and sisomicin was the most active aminoglycoside. Minocycline was more active than the other tetracycline analogues tested. Among the macrolide-lincomycin compounds in clinical use, clindamycin was more active, and lincomycin was less active than erythromycin. The synergy of trimethoprim-sulfamethoxazole was more striking against S. aureus than against S. epidermidis. The median minimal inhibitory concentrations of the penicillins, cephalosporins, and aminoglycosides were lower against S. aureus, whereas the minimal inhibitory concentrations of the tetracyclines were lower against S. epidermidis.

Binding of Antibiotics to Dry Udder Secretion and to Udder Tissue Homogenates

SUMMARY Several antibiotics were infused into the udders of cows at drying-off. Two weeks later, the cows were slaughtered, the udders were removed and the extent of antibiotic binding to the secretions and to 25% udder tissue homogenates was determined by equilibrium dialysis. Antibiotics which were more than 50% bound to the secretion of the dry udder were cloxacillin, novobiocin, and phenoxymethyl penicillin, whereas neomycin, dihydrostreptomycin, spiramycin and polymyxin B were more than 50% bound to udder tissue homogenates. Benzylpenicillin, ampicillin, cephaloridine, erythromycin and chloramphenicol were less than 50% bound to both dry udder secretion and udder tissue homogenates. Results are discussed in relation to the persistence of antibiotics in the udder of the dry cow.

Synthesis of pivaloyloxymethyl esters of penicillins and their conversion to deacetoxycephalosporins

The chemical transformation of penicillins is an important method of obtaining compounds of the cephalosporin series, and has already found practical use in the production of cephalosporin preparations such as cephalexin and cephradin [i, 2]. The method of transformation which has received the most attention uses the trichloroethyl [I] and p-nitrobenzyl [3] esters of benzyl and phenoxymethyl penicillin sulfoxides. One of the defects of these methods is the difficulty of removing the ester-protecting groups from the carboxyl group in the final product. Hence, it was of interest to investigate the use of other peniCillin esters for the transformation, esters which would either split more readily or would give a preparation suitable for use as an ester. The acyloxymethyl esters of penicilfins [4] are compounds of this type. The possibility of using cephalosporin acyloxymethyl esters is also indicated in the literature [5].

Chemotherapy of experimental streptococcal endocarditis. IV. Further observations on prophylaxis.

The ability of antibiotics to prevent Streptococcus sanguis endocarditis was tested in rabbits. Only vancomycin or a combination of penicillin G plus streptomycin always prevented infection when administered as a single dose. A loading dose of 30 mg/kg of phenoxymethyl penicillin (penicillin V) followed by additional 7.5 mg/kg doses for 48 h proved to be the only successful prophylactic program that could be given orally to man. Cefazolin alone or with streptomycin in multiple doses was also an effective alternative to penicillin or penicillin derivatives. Erythromycin uniformly failed to protect animals from bacterial endocarditis but showed greater prophylactic efficacy when a low inoculum of streptococci was used.

Carfecillin

Carfecillin (Uticillin - Beecham), the phenyl ester of carbenicillin (Pyopen - Beecham), shares many of the properties of carbenicillin but can be taken by mouth. It should not be confused with a brand of phenoxymethyl penicillin sold in the USA as ‘Uticillin V.K’.1 Published information on carfecillin is sparse but a similar drug, carbenicillin indanyl sodium, which is not available in Britain, has been studied in the USA,2 and first reports on carfecillin3 4 suggest that their pharmacology and clinical actions are similar.

Synthesis of unsaturated analogs of phenoxy methylpenicillin

Some unsaturated acylaminophenoxymethylpenicillins and their methyl esters were synthesized and characterized. The antimicrobial properties of these compounds and their sensitivity toward penicillinase depend on the position of the unsaturated acylamino group in the benzene ring.

CLINDAMYCIN EFFECTIVE IN THERAPY OF STREPTOCOCCAL PHARYNGITIS

Benzathine penicillin (BP) is considered to be the most effective therapy for removal of Streptococcus (S.) pyogenes from the pharynx. The following study was undertaken to determine whether oral clindamycin (CL) was equally effective for this purpose. This possibility was suggested by published observations made in private practice in which CL was compared with other oral antibiotics. 939 clinic patients with throat cultures positive for S. pyogenes were randomly selected for treatment with intramuscular BP, oral CL or oral phenoxymethyl penicillin (PMP). 621 returned for a follow-up culture and brief history on at least one scheduled visit. 307 returned for all scheduled visits at 1, 2, and 4 weeks after initiation of therapy. Data from the first 2 follow-up cultures indicate that CL and BP had similar failure rates (8% and 9% resp.) and that PMP was less efficacious than either of the other 2 antibiotics (p<.01). Late cultures indicate that CL is not as efficient as BP or PMP in preventing recurrences. This latter finding differs from all others in the literature, is not due to age, sex, weight, quantity of S. pyogenes in original culture or dosage of CL, and is unexplained. Oral CL is effective in removing S. pyogenes from the pharynx and may be as effective as BP.

The configuration of phenoxymethyl- and 6-epiphenoxymethylpenicillin sulfoxides.

The configuration of phenoxymethyl- and 6-epiphenoxymethylpenicillin sulfoxides.

Penicillin and Erythromycin Concentrations in Tonsils

Penicillin and erythromycin concentrations were measured in sera and tonsils of children undergoing tonsillectomy. For two hours after the intramuscular administration of potassium penicillin G (5,000 units/kg), the levels of penicillin in tonsil were consistently greater than the minimal inhibitory concentrations (MIC) of most group-A, β hemolytic streptococci. Antibiotic was not detected in six of ten specimens obtained four to six hours after single or multiple doses of orally administered phenoxymethyl penicillin. Tonsillar levels of erythromycin were greater than the MIC for group-A, β hemolytic streptococci in eight of ten specimens obtained four to seven hours after single or multiple doses of orally administered erythromycin estolate. Data correlating tonsillar antibiotic levels, MIC values, and in vitro streptococcal kill curves may have relevance to relapse and treatment failures in streptococcal pharyngitis.

In vitro activity of cephalothin and three penicillins against Escherichia coli and Proteus species.

The susceptibility of clinical isolates of Escherichia coli (67) and Proteus species (58) to cephalothin, ampicillin, benzyl penicillin, and phenoxymethyl penicillin was determined in vitro by using broth dilution and disk diffusion tests. The data were correlated by using a four-category scheme for interpreting minimal inhibitory concentrations (groups 1 to 4) as recommended by a subcommittee of an international collaborative study of susceptibility testing. With cephalothin and ampicillin, groups 1 (susceptible) and 2 (moderately susceptible) were susceptible by the disk test, and with benzyl penicillin, similar results were observed when the interpretive zone standards were changed. Strains categorized as group 4 (very resistant) were resistant by the disk method, but group 3 (moderately resistant) strains were not adequately distinguished by disk testing. Group 3 susceptibility to benzyl and phenoxymethyl penicillins can be predicted by extrapolating results from tests with ampicillin disks.

Metabolism of penicillins to penicilloic acids and 6-aminopenicillanic acid in man and its significance in assessing penicillin absorption.

Penicillins can be metabolized to penicilloic acids in man, the extent being dependent on the penicillin structure. In the phenoxy penicillin series, phenoxymethyl penicillin was found to be particularly unstable, but the higher homologues were more stable. In the isoxazolyl series, oxacillin was unstable, and progressive insertion of halogen in the phenyl ring increased stability. Ampicillin and amoxycillin showed some instability, ampicillin possibly being the more stable. After intramuscular administration, carbenicillin was very stable in the body, ampicillin was fairly stable, and benzyl penicillin was unstable. It is important to take into account the penicilloic acid content of urine when estimating total absorption of a penicillin. Increased stability in the body as well as slower renal clearance can lead to high concentrations in the serum. Penicilloic acids seemed to be more slowly cleared from the body than penicillins. The liver is probably the site of inactivation.

Kinetic Analysis of Complex Formation between Penicillin and Sucrose

The formation of 1:1 molar complexes between sucrose and the following penicillins was studied: potassium penicillin G USP; potassium phenoxymethyl penicillin USP; sodium dicloxacillin, monohydrate; and ampicillin, anhydrous. Kinetic parameters, based on a model system, are presented for each interaction. The degree of complexation was greatest with sodium dicloxacillin and least with ampicillin. The rate of degradation of complexed penicillin was 5-6 times the rate for the uncomplexed penicillin. The relatively high equilibrium constant obtained for sodium dicloxacillin was consistent with the strong effect of sucrose on the observed rate constant. Ampicillin, whose observed rate constant was only slightly affected, had a very low equilibrium constant. Complexation involves the intact penicillin and accelerates the degradation of penicillin but does not appear to change the degradation pathway.

Measurement of β-Lactamase Activity and Rate of Inactivation of Penicillins by a pH-Stat Alkalimetric Titration Method

The pH-stat alkalimetric titration method was shown to be applicable and superior to other chemical methods in the investigation of β-lactamase activity as well as in kinetic studies. For both staphylococcal and bacillary β-lactamases, the pH optimums depended not only on bacterial strain and temperature but also on the substrate. Of all the compounds studied, 6-[2-amino-(3-trienyl)acetamido]penicillanic acid, 6-[2-(1-aminocyclohexyl)acetamido]penicillanic acid, 6-(2-amino-2-methylpropionamido)penicillanic acid, and ampicillin were the least stable toward Staphylococcus aureus Tex-2 β-lactamase. Penicillin G, phenoxymethyl penicillin, phenethicillin, 6-(1-amino-3-cyclopentene-1-carboxamido)-penicillanic acid, 6-(2-amino-2-indancarboxamido)penicillanic acid, and carbenicillin were about twice as stable as ampicillin, and 6-(1-aminocyclopentanecarboxamido)penicillanic acid, 6-[2-(1,4-cyclohexadien-1-yl)acetamido]penicillanic acid, and cyclacillin were about four times as stable. N-Sulfonylation of cyclacillin gave a product, 6-[1-(2-mesitylenesulfonamido)cyclohexanecarboxamido]-penicillanic acid, that was about 10 times as stable as the parent compound. The nature of the penicillin side chain, particularly the stereospecificity, plays a significant role in the stability of this molecule toward the β-lactamases.

Abbreviated case report: Actinomycosis of the tongue

A painful enlargement of the tongue in a 43-year-old farmer was found to be due to actinomycosis. Treatment with potassium phenoxymethyl penicillin over a period of several months resulted in remission of the disease.

Penicillin V concentration in dental alveolar blood after tooth extraction.

abstract – The penicillin V concentration in the blood flow from extraction wounds was assayed after oral administration of phenoxymethyl penicillin. The penicillin concentration in cubital vein blood was determined for comparison. In addition, the effect of various local anesthetics on the alveolar penicillin concentration was studied in connection with oral administration. The concentration of penicillin in the blood flow from the extraction wound was usually lower than the concentration in cubital vein blood. This tendency seemed to persist also when the interval between the intake of penicillin and the withdrawal of blood was prolonged. When a vasoconstrictor‐free agent (Carbocain Dental® 3 %) was used, attention was drawn to the strikingly high alveolar penicillin concentration. No differences between different groups of teeth in the mandible were observed. A peak in the penicillin concentrations was attained in the cubital vein blood and alveolar blood within 20–30 min from oral intake.

Determination of p-Hydroxyphenoxyacetic Acid in Phenoxymethyl Penicillin Fermentations

A method based on TLC separation and subsequent colorimetric determination was developed for the determination of p-hydroxyphenoxyacetic acid in phenoxymethyl penicillin (penicillin V) fermentation samples. The p-hydroxyphenoxyacetic acid is extracted from penicillin culture fluid into amyl acetate. A portion of the extract is dried and then dissolved in acetone. An aliquot is chromatographed on a silica gel thin-layer plate by ethyl acetate-chloroform-acetic acid (9:1:0.15 v/v). The zones are located by spraying with an aqueous mixture of equal volumes of 1% ferric chloride and 1% potassium ferricyanide. The zones are transferred into glass tubes, treated by sodium nitrite in dilute sulfuric acid, and neutralized by ammonia. The absorbance of the orange supernate, which is proportional to the concentration of p-hydroxyphenoxyacetic acid, is measured spectrophotometrically at 478 nm.