Phenoxymethylpenicillin Research Articles

A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes

OBJECTIVE: Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications. A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported. The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate. STUDY DESIGN: Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery. Latency period, infectious complications, and neonatal outcomes were studied. RESULTS: Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus. CONCLUSION: Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn. (AM J OBSTET GYNECOL 1994;170:516-21.)

Antimicrobial drug suspensions

We conducted a blinded taste test evaluating 12 antimicrobial suspensions by smell, texture, taste, aftertaste and overall acceptance. Drugs received cumulative scores in each category as well as a total score ranking. Overall Lorabid scored highest but not significantly higher than Keflex, Suprax and Ceclor, all of which score higher than the other test drugs. Cefzil and Augmentin scored just below this group of drugs and higher than all other test drugs. Vantin was inferior to these drugs primarily because of its low score in aftertaste. It was ranked along with V-Cillin-K, Veetids, Sulfatrim and Pediazole, the lowest scoring group of drugs other than Dynapen which scored lower than all other test drugs. No difference overall was detected between the two penicillin VK suspensions evaluated, V-Cillin-K and Veetids.

Five Versus Ten Days Treatment of Streptococcal Pharyngotonsillitis: A Randomized Controlled Trial Comparing Cefpodoxime Proxetil and Phenoxymethyl Penicillin

A total of 220 adults and children > 10 years old (mean 29.5 +/- 11.7 years) with pharyngitis/tonsillitis were randomized to receive either cefpodoxime proxetil 100 mg bid for 5 days (n = 113) or phenoxymethyl penicillin, 600 mg tid for 10 days (n = 107). At the end of treatment of the 166 evaluable patients, a satisfactory clinical response was obtained in 85/88 (96.6%) patients treated with cefpodoxime proxetil and in 75/78 (96.1%) treated with phenoxymethyl penicillin. Group A beta-hemolytic streptococci (GABHS) eradication was similar in both groups: 79/82 (96.3%) patients in the cefpodoxime proxetil group and 64/68 (94.1%) patients in the phenoxymethyl penicillin group. At follow-up (20-30 days after the end of treatment) the GABHS eradication persisted in 67/72 (93.1%) patients treated with cefpodoxime proxetil and in 56/61 (91.8%) patients treated with phenoxymethyl penicillin. Significantly better compliance (p < 0.01) was noticed with the cefpodoxime proxetil regimen compared with the phenoxymethyl penicillin regimen, with only 2/110 (2%) poorly compliant patients in the cefpodoxime proxetil group vs 17/104 (16%) in the phenoxymethyl penicillin group. Thus, the shorter duration of therapy, in conjunction with demonstrated clinical and bacteriological efficacy that is equivalent to standard therapy, makes cefpodoxime proxetil an acceptable alternative for the treatment of GABHS pharyngitis/tonsillitis.

Self-Association of Penicillins in Aqueous Solution as Revealed by Gel Filtration Chromatography.

The self-association of penicillin G (PCG) and penicillin V (PCV) in 0.15 M potassium chloride solution has been investigated by frontal gel filtration chromatography (GFC) on Sephadex G-10 columns at 25°C. Analysis of the centroid volume, Vc, of a GFC profile yields the monomer concentration of a penicillin and the weight-average aggregation number, nw. No critical micelle concentration is observed in the Vc vs. concentration profile for PCV. The nw value for PCV is 2 at low concentrations and gradually increases with increasing concentration. PCG forms dimers only below 0.06 M, and provides useful GFC data for the investigation of dimerization. The dimerization constants of PCG and PCV are also evaluated from the concentration dependence of the derivative peak position at the trailing boundary. Stepwise aggregation constants, obtained from non-linear least-squares fitting of the centroid volume data, satisfactorily reproduce observed derivative chromatograms, and are used for calculations of the aggregate size distribution of PCV. The structure-association relationship and the effect of self-association on the bactericidal activity and chemical stability of the penicillins are discussed.

Clarithromycin: where do we go from here?

Clarithromycin is a new macrolide with a broad spectrum of activity against Gram-positive cocci, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma, Chlamydia and selected Mycobacteria, Legionella and protozoa. The drug has a half-life of more than 4 hours and thus can be administered in a twice daily schedule. Clarithromycin is well-tolerated in children and adults and produces fewer gastrointestinal side effects than erythromycin. High concentrations of the drug are achieved in plasma and in cells and tissues including tonsil, lung and middle ear fluids. Clinical efficacy has been demonstrated in randomized multicenter trials of infants and children with acute otitis media, streptococcal pharyngitis and infections of skin and skin structures. Results of these comparative trials with randomized patients receiving clarithromycin or standard drugs identified equivalent clinical and bacteriologic outcomes. A higher rate of eradication of group A Streptococcus from the pharynx was achieved with clarithromycin than with penicillin VK. The potential advantages provided by high concentrations of clarithromycin in cells and tissues such as more rapid clinical improvement or shortened dosage schedules are still to be identified.

Overview of the safety profile of clarithromycin suspension in pediatric patients

Results of preclinical studies conducted to characterize the safety of clarithromycin oral suspension in juvenile mice, rats and dogs as compared with that in adult animals indicate that there is no enhanced risk in younger animals. Adverse events in these preclinical studies mainly involved decreased body and increased liver and kidney weights. The safety profile of clarithromycin suspension also has been evaluated in Phase II (pharmacokinetic) and III (clinical) United States and international clinical trials conducted in pediatric patients. The most frequently reported adverse events occurring among the 1676 patients studied who received clarithromycin suspension in Phase III trials included diarrhea (7%), vomiting (6%), abdominal pain (2%), headache (2%) and nausea (1%). Adverse events were not serious and were usually rapidly reversible. Adverse event rates did not vary with sex or race. Overall adverse event rates were generally similar to those of comparator beta-lactam suspensions (i.e. amoxicillin, amoxicillin/clavulanate, penicillin VK, cefaclor, cefadroxil). With regard to specific gastrointestinal events, however, clarithromycin was better tolerated than amoxicillin/clavulanate whereas penicillin VK showed a lower incidence of gastrointestinal events. Overall clarithromycin oral suspension appears to be safe and well-tolerated, making it suitable for use in the pediatric population.

Efficacy of Muscovy Ducks as an Adjunct for House Fly (Diptera: Muscidae) Control in Swine and Dairy Operations

Field studies were conducted using Muscovy ducks, Cairina moschata L., to control house flies, Musca domestica L., in swine and dairy facilities. In fly-proof calf pens, one Muscovy duck per pen reduced the adult fly numbers by 96.8% when compared with pens without a duck. The maggot population was reduced by 98.7% when compared with pens without a duck. In an enclosed calf room, fly populations on animals were reduced by 84 and 93% when compared with the times when ducks were not present. However, in open areas of the dairy facility which allowed for immigration and emigration of house flies, statistically significant reductions were not observed. Ducks reduced fly populations on animals by 91% in an enclosed swine farrowing room. In an open dry sow facility, ducks reduced the house fly population by up to 86%. Female ducks consumed house flies up to three times faster than the males. During most experiments, duck health was maintained without any supplementary feedings. Ducks had access to flies, water, and spilled (wasted) feed. On conclusion of the studies, the least valuable ducks were sold for twice the invested cost ($2 cost versus $4 sale), yielding a 100% return on investment. Farmer acceptability was good.

Calf Diseases and Mortality in Swedish Dairy Herds

A survey of the mortality and morbidity affecting calves during the first 3 months of life was carried out. Results are reported from 131 herds with altogether 5,050 calvings. These herds kept individual calf cards for all calves born. The incidences of abortions and stillborn calves were 0.6% and 3.6%, respectively. During the period 0-90 days the mortality and morbidity were 2.6% and 11.0%, respectively. The frequencies of enteritis and pneumonia in calves were 7.2% and 0.8%. Mortality and morbidity were influenced by breed, season, age of the dam and time of first colostrum. The frequencies of abortions, stillborn calves, mortality and morbidity varied considerably between herds. Herd factors influencing mortality and morbidity during different periods of time were: herd size, yield, zero-grazing, whether the calf was allowed to feed by suckling, the design of the calf pens, and previous incidence of infectious enteritis in the herd. On average, both mortality and morbidity in calves were low, though in certain herds, temporarily high frequencies were registered.

Clarithromycin: Review of a New Macrolide Antibiotic with Improved Microbiologic Spectrum and Favorable Pharmacokinetic and Adverse Effect Profiles

To compare the new macrolide antibiotic clarithromycin with erythromycin in terms of in vitro activity, pharmacokinetics, pharmacodynamics, clinical efficacy, and toxicity. An English-language literature search employing MEDLINE (1987-91), Index Medicus (1987-91), Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy (1990), Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy (1991), and bibliographic reviews of related textbooks and review articles. Eighty-five articles were selected. Clinical trials with clarithromycin have been limited, and emphasis was placed on trials reported in the Program and Abstracts of the 30th Interscience Conference on Antimicrobial Agents and Chemotherapy and Program and Abstracts of the 31st Interscience Conference on Antimicrobial Agents and Chemotherapy. Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative efficacy and toxicity. A review of 24 human trials suggests that clarithromycin is equally effective as erythromycin, penicillin VK, ampicillin, or amoxicillin for treatment of a variety of upper and lower respiratory tract or skin infections. Clarithromycin also appears to be better tolerated than these agents, with a lower incidence of gastrointestinal adverse effects. Limited clinical studies in patients with Mycobacterium leprae or Mycobacterium avium-intracellulare complex (MAI) suggest that clarithromycin may prove to be efficacious and well tolerated in the treatment of these infections. Clarithromycin is as effective in vivo as erythromycin, with less gastrointestinal irritation. Additionally, clarithromycin appears to expand the traditional spectrum of macrolide antibiotics, with promising activity against M. leprae and MAI.

Loracarbef versus penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in an adult population

Loracarbef, a member of the carbacephem class of β-lactam antibiotics, is a potent antibacterial agent. In a double-blind, randomized clinical trial to assess the efficacy and safety of loracarbef in the treatment of streptococcal pharyngitis and tonsillitis, 107 adult patients were treated with loracarbef (200 mg capsules twice a day or 15 mg/kg/day suspension) and 111 patients were treated with penicillin VK (250 mg capsules four times a day or 20 mg/kg/day suspension) for 10 days. In the loracarbef treatment group, 96.6% of the evaluable patients had a favorable clinical response 3–5 days after therapy, a result that compared favorably with the 93.9% response rate achieved in the penicillin group. The clinical failure/relapse rates were 3.4% for loracarbef-treated patients and 6.1% for patients receiving penicillin. Bacteriologic response data approximated the clinical results, with a successful response in 89.9% of the loracarbef-treated patients and 91.5% of the penicillin recipients. Two (1.9%) loracarbef-treated patients with rash and one (0.9%) penicillin-treated patient with diarrhea discontinued the study early because of these adverse events. The incidence of adverse events was comparable in the two treatment groups except for increased cough, which was reported by 3.7% of the loracarbef-treated patients and none of the penicillin recipients. These data support the conclusion that loracarbef is comparable to penicillin VK in the treatment of streptococcal pharyngitis and tonsillitis in adults.

The effect of respiratory manoeuvres and pharmacological agents on the pharmacokinetics of nedocromil sodium after inhalation.

1. Eight healthy subjects inhaled nedocromil sodium from a metered-dose inhaler using a standardised inspiratory technique. Blood samples were taken for up to 270 min after inhalation for radioimmunoassay of plasma nedocromil sodium concentrations. 2. To investigate the possibility that respiratory manoeuvres can alter the absorption of the drug from the lungs, on the first (control) study day at 70 min after dosing, subjects performed nine forced expiratory manoeuvres over a 3 min period. At 110 min after dosing, subjects took a slow, full inspiration with a 30 s breath-hold, and at 150 min after dosing the subjects performed one single forced expiration. 3. On the second study day, subjects inhaled methoxamine, 0.15 mg kg-1 of a 20 mg ml-1 solution at 60 min after dosing, and the study continued as above. On the third day, subjects repeated the sequence of respiratory manoeuvres, after having taken phenoxymethyl penicillin and probenecid by mouth for 48 h. 4. Both multiple forced expirations and the deep inspiration with breath-hold produced significant increases in the absorption of nedocromil sodium. Inhaled methoxamine did not alter airway calibre or the response to the respiratory manoeuvres. Probenecid, but not penicillin, was detected in the subjects' plasma, and had the effect of increasing the rise in plasma nedocromil sodium concentrations after the multiple forced expirations when compared with the control day. 5. These data suggest that disruption of epithelial tight junctions induced by the respiratory manoeuvres leads to enhanced paracellular transport of nedocromil sodium into the draining circulation of the airways and alveoli.(ABSTRACT TRUNCATED AT 250 WORDS)

Phenoxymethyl penicillin potassium as an in-feed medication for pigs with streptococcal meningitis.

In two separate studies involving 2500 weaner pigs, strategic infeed medication with phenoxymethyl penicillin potassium significantly reduced the incidence of streptococcal meningitis.

Penicillin tolerance in group A streptococci and treatment failure in streptococcal tonsillitis.

Penicillin tolerance in Streptococcus pyogenes has been suggested as a possible cause of therapeutic failure in streptococcal phryngitis treated with penicillin. In 144 patients with acute group A streptococcal tonsillitis treated with phenoxymethyl penicillin 12.5 mg per kg body weight b.i.d. for 10 days the same T-type was recovered after treatment in 21%. The recovery rate was higher for non-tolerant strains, 23%, than for tolerant strains, 10% (p greater than 0.05). Of patients with a non-tolerant strain 17% had both clinical and bacterial treatment failure in comparison with 5% infected with a tolerant strain (p greater than 0.05). Reinfection with a new serotype occurred in altogether 3%. The present data did not indicate that penicillin tolerance in group A streptococci is of significance in acute tonsillitis treated with phenoxymethylpenicillin for 10 days.

Battery-Powered, Electrocuting Trap for Stable Flies (Diptera: Muscidae)

A solar-charged, battery-powered, electrocuting grid was combined with a white plywood base to make a portable, pulsed-current, pest-electrocuting device that attracted and killed stable flies, Stomoxys calcitrans (L.), outdoors. The grid was powered once every 1-2 s by a 0.016-s pulse of 60-Hz alternating current of 4 mA and 9,500 V. Power was turned off at night by a photoresistor. The trap functioned continuously for 14 d with an unrecharged 12-V, 18A/h lawn-tractor battery and killed as many as 4,000 flies per day. Solar cells were used to charge a single 12-V battery continuously that operated 12 grids for a period of 90 d. The grid did not short circuit for any length of time even during heavy rainstorms or when large insects were killed. The incorporation of moiré patterns and the utilization of the correct size, orientation, and placement of wires made the electrocuting grid itself attractive to stable flies. The traps were spaced at distances of up to 120 m from the battery and pulse circuit. The electrocuting traps were more effective than sticky traps and avoided the problems associated with chemicals. They are well suited for use around calf pens, dog kennels, or large animal shelters.

Synthesis and in vitro antibacterial activity of 2β and 2α-(substituted methyl) phenoxymethylpenicillins and an oxidation product

The effect of stereochemical changes on the antibacterial activity of a series of 2-substituted methyl-6β-phenoxyacetamido penams synthesized in our laboratory was studied. The 2α-heteroarylthiomethyl penams were found to be more active than the 2β-substituted derivatives against a range of Gram-positive and Gram-negative microorganisms. Both the isomers of 2-substituted methyl derivatives were found to be less active than the unsubstituted compound, the phenoxymethyl penicillin. The oxidized product of the 2α-isomer was less active than the unoxidized compound.

Effect of Calf Housing on Plasma Ascorbate and Endocrine and Immune Function

The effect of housing calves in indoor metal pens (1.2m × 1.2m) or commercial calf hutches was determined on plasma concentration of cortisol, antibodies, and ascorbate. Six calves per treatment were deprived of colostrum, assigned randomly to treatment, and fed a commercial milk replacer until 56 d of age. Calves housed in hutches had higher plasma IgG concentrations than calves in pens at 42 and 56 d of age. Housing had no effect on plasma IgM concentration. Antibody titers to keyhole limpet hemocyanin injected at 14 and 28 d of age were higher in hutch-housed calves from 21 to 56 d of age. Calves housed in hutches also had lower plasma cortisol concentrations, although cortisol decreased with age in both treatment groups. Plasma ascorbate and ascorbate plus dehydroascorbate were higher in hutch-housed calves. Regression analysis indicated a positive relationship between plasma ascorbate and IgG in metal pen-housed calves and a negative relationship in hutch-housed calves. Housing in 1.2m × 1.2m metal pens decreases cortisol, plasma ascorbate, IgG, and specific antibody titers in dairy calves relative to calves housed in hutches.

Relationship of Microhabitat to Incidence of House Fly (Diptera: Muscidae) Immatures and Their Parasitoids at Dairy Farms in Central New York

Weekly observations were made on the presence of house fly, Musca domestica L., and stable fly, Stomoxys calcitrans (L.), eggs, larvae, and pupae, during 21 wk at nine dairies in Cayuga County, New York. Laboratory-reared fly pupae were exposed at each site to monitor parasitoid activity. Incidence of fly immatures was significantly related to substrate, moisture, and location, but not to indoor or outdoor exposure. Incidence was greatest at wet sites, particularly in manure, bedding, and feed, and lowest at dry sites. Locations with the highest incidence were lean-to, silo, calf pen, outdoor manure pile, outdoor manure ramp, and manure lagoon. Incidence of Muscidifurax raptor Girault and Sanders, Urolepis rufipes (Ashmead), Spalangia cameroni Perkins (Hymenoptera: Pteromalidae) and total parasitism were positively associated with the presence of fly immatures, but Phygadeuon fumator Gravenhorst (Hymenoptera: Ichneumonidae) was independent. With respect to substrate, moisture, and exposure, parasitism was generally distributed in a pattern similar to that of the flies. However, incidence of parasitism was greater, relative to that of fly immatures, in grass and earth substrates, but lower in wet manure and feed. With respect to location, parasitism was high at manure ramps and low in calf pens and in manure sheds, relative to fly immatures. The guild of parasitoids attacking synanthropic muscoid pupae appears to cover all appropriate host microhabitats at dairies in central New York.

Decreased production of para-hydroxypenicillin V in penicillin V fermentations.

Penicillin V (phenoxymethyl penicillin) is produced by industrial strains of Penicillium chrysogenum in the presence of phenoxyacetic acid (POAc), a side-chain precursor for the penicillin V molecule. The wild-type strain of P. chrysogenum produces an undesirable penicillin byproduct, para-hydroxypenicillin V (p-OH penicillin V), in addition to penicillin V, via para-hydroxylation of POAc and subsequent incorporation of the p-OH phenoxyacetic acid into the penicillin molecule. Most of the p-OH penicillin V is produced late in cycle when the POAc concentration in the medium is nearly depleted. The level of p-OH penicillin V produced by the control strain ranges up to 10-15% of the total penicillins produced. 3-Phenoxypropionic acid and p-bromophenylacetic acid partially inhibit the formation of p-OH penicillin V with a minimal effect on penicillin V productivity. Mutants deficient in their ability to hydroxylate POAc were found to produce lower levels of p-OH penicillin V. Multi-step mutation and screening, starting with the wild-type strain, have culminated in isolation of mutants which produce p-OH penicillin V as 1% of the total penicillins with no adverse effect on penicillin V productivity.

Cefalexin and erythromycin are superior to phenoxymethylpenicillin in impetigo

Cefalexin and erythromycin are superior to phenoxymethylpenicillin in impetigo

Delayed allergic reactions to betalactams

We present four cases of delayed allergic skin reactions to amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin. The clinical symptoms reported by the patients, the intradermal skin tests and the controlled challenge results suggested that the mechanism was cellular mediated. In two patients these findings were supported by histopathological studies. Although delayed-type hypersensitivity reactions to beta-lactams with positive skin test seem rare, they can occur to penicillins in allergic patients. The production of these reactions by amoxicillin or ampicillin with good tolerance to benzyl penicillin and phenoxymethyl penicillin emphasizes the role of the side chain in inducing allergic reactions to beta-lactams.