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[The duration of antibacterial treatment following transurethral prostatectomy].

Forty-three cases were studied to determine the most optimal timing to discontinue an oral antibacterial agent for preventing urinary tract infection after transurethral prostatectomy. On the 5th postoperative day intravenous antibiotic treatment was replaced by oral medication of 1.5 g talampicillin hydrochloride (TAPC, Yamacillin), which was tapered and discontinued depending on the urinary findings. Nine out of 15 cases who discontinued the medication within 2 weeks failed to keep the urine sterile. It may be advisable to continue the medication at least 3 weeks and to discontinue thereafter when pyuria has vanished. All 24 cases who followed this principle became sterile within 8 weeks. Medication continued over 8 weeks seemed to have no additional benefit. Four cases dropped out from this treatment mainly because of gastrointestinal symptoms.

Administration, Oral↗

Dose dependence in human absorption of aminopenicillins.

The concentration of antibiotic in a focus of infection depends both on the peak serum concentration and on the area under the serum concentration time curve (AUC). A knowledge of the relationship between increased doses and the corresponding response in serum concentration would be relevant as a basis for determining an adequate clinical dosage. Dose-related changes in the two pharmacokinetic variables, peak serum concentration and AUC, after single doses of bacampicillin are compared with data on different aminopenicillins from other studies. With ampicillin there is a nonlinear relationship between both dose-peak and dose-AUC. The results indicate that the poor absorption of oral ampicillin can only be partially compensated for by increasing the oral dose. But with amoxycillin and the ampicillin esters the absorbed amount (AUC) is a linear function of the dose in the dosage range investigated. The increase in peak serum level with high doses of oral ampicillin is far less than proportional, while this tendency was less pronounced for amoxycillin and still less for pivampicillin, talampicillin and bacampicillin.

Absorption↗

Review of side-effects of aminopenicillins.

Side-effects of aminopenicillin therapy are reviewed on the basis of nine comparative studies of ampicillin and bacampicillin, and available literature data from investigations with talampicillin, pivampicillin, bacampicillin and amoxycillin. Diarrhoea is more common with ampicillin than with newer aminopenicillins. Exanthema do not appear more frequently with newer aminopenicillins. The frequency of upper gastrointestinal complaints in association with some of the newer aminopenicillins (amoxycillin, bacampicillin) is not more frequent than with ampicillin. All current evidence speaks in favour of a change from ampicillin to modern aminopenicillins for oral therapy.

Amoxicillin↗

Studies on aminopenicillin developments. Proceedings of a symposium. Concluding remarks.

This symposium has focused on the bacteriological, pharmacokinetic, therapeutic, and adverse effects of the aminopenicillins. The compounds which are currently being assessed are primarily amoxycillin, ampicillin, bacampicillin, pivampicillin, and talampicillin. The three last mentioned are prodrugs which upon gastrointestinal absorption are rapidly split to yield circulating ampicillin. Pharmacokinetics and side-effects are reasons why one may narrow the selection of most suitable compounds within this group down to three. Ampicillin and amoxycillin are primary choices for parenteral dosage, and amoxycillin and bacampicillin the most suitable for oral therapy.

Administration, Oral↗

Preparation, hydrolysis, and oral absorption of lactonyl esters of penicillins.

Lactonyl esters of ampicillin and other penicillins have been synthesized as prodrugs designed to improve the oral absorption of the parent penicillins. In general, the esters hydrolyzed rapidly in the presence of tissues including blood and certain of the esters were better absorbed than the parent penicillin. The phthalidyl ester of ampicillin [talampicillin (British Pharmacopoeia approved name), BRL 8988] was selected for extended studies. The compound was found to be well absorbed in various animal species and gave ampicillin serum concentrations in fasting human volunteers 2.5-3 times those obtained for ampicillin itself.

Administration, Oral↗

Pelvic tissue and serum concentrations of various antibiotics given as pre-operative medication.

Talampicillin, cephalexin and clindamycin were administered orally, and ampicillin, cephazolin, clindamycin and spectinomycin intramuscularly as preoperative medication to 49 women who were having an abdominal hysterectomy. Antibiotic levels in serum, myometrium or cervix, and Fallopian tube were estimated. Antibiotic absorption from the gastrointestinal tract was delayed, but intramuscular therapy produced serum levels compatible with those reported in ambulant volunteers. None of the antibiotics produced a concentration which inhibited all the potential pathogens causing pelvic inflammatory disease. Inhibitory concentrations were produced by cephazolin except against Bacteroides; by clindamycin except against enterobacteria; by ampicillin except against Bacteroides and enterobacteria; and by spectinomycin except against resistant strains of streptococci. The need for a reassessment of dose regimens and route of administration as well as the possible need for using two antibiotics together for the treatment of pelvic inflammatory disease is suggested.

Anti-Bacterial Agents↗

Susceptibility of Bacteroides from swine abscesses to 13 antibiotics.

The minimal inhibitory concentrations (MIC) of 129 strains of genus Bacteroides, isolated from abscesses in pigs, for 13 different antimicrobial agents were determined by an agar-dilution method under anaerobic conditions. Clindamycin, the most active antibiotic tested, had a median MIC of 0.8 micrograms/ml. Penicillin G, talampicillin, minocycline, chloramphenicol, and cefoxitin also inhibited all isolates at lower concentrations. Some isolates of B pyogenes were susceptible to gentamicin (MIC, 0.4 micrograms/ml), erythromycin (MIC, 0.8 micrograms/ml), cephalexin (MIC, 0.8 micrograms/ml), and cefoxitin (MIC, 3.2 micrograms/ml). Erythromycin, at a concentration of 3.2 micrograms/ml, was active against 70% of B suis tested, but it was less active against the other Bacteroides species. Some strains tested were resistant to streptomycin and neomycin.

Abscess↗

Drug eruptions following treatment with prodrugs: a review of the reported cases in Japan from 1984 to 1989.

A review of 872 cases of drug eruption reported in the Japanese dermatological journals from 1984 to 1989 has revealed a growing subset related to treatment with prodrugs, in which the responsible agent may be the metabolite rather than the prodrug itself. This situation is the result of the presence in tissues and fluids of only the metabolite following absorption and degradation of the prodrug. Because of this condition, patients with drug eruptions after prodrug treatment may develop positive patch test and/or lymphocyte stimulation test reactions not only with the introduced prodrug but also with the metabolite produced in vivo and further with other prodrugs which degrade into the same metabolite.

Adult↗

Liquid chromatographic determination of ampicillin and its metabolites in human urine by postcolumn alkaline degradation.

A high-performance liquid chromatographic method has been developed for the determination of ampicillin (I) and its metabolites [5R,6R)-penicilloate (II), the (5S,6R)-epimer (III), and piperazine-2,5-dione (IV)) in human urine. The assay was based on the measurement of the absorbance at 300 nm following the postcolumn alkaline degradation with 0.75 M sodium hydroxide, 2 X 10(-3) M mercuric chloride, and 1 X 10(-2) M ethylenediaminetetraacetic acid disodium salt in solution. The limits of accurate determination were 0.5 microgram mL-1 for I, 2.0 microgram mL-1 for II and III, and 1.0 microgram mL-1 for IV in neat urine samples with a 10 microL injection. At concentrations of compounds I-IV of 5 micrograms mL-1, within- and between-run precisions were 1.10-4.03% and 0.93-2.34%, respectively. The urinary levels of I and its metabolites were quantified by the proposed method.

Ampicillin↗