Antibacterial activity of mecillinam.
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Biomedical subjects
Publications and source records attributed to D S Reeves.
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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.
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Talampicillin is a thiazolide carboxylic ester of ampicillin and is hydrolysed in the intestinal mucosa to release free ampicillin. The mean peak serum concentration of ampicillin occurred one hour after a dose of talampicillin and was about twice that attained by an equivalent dose of ampicillin. The presence of food in the stomach reduced and delayed the peak blood levels but did not affect the total amount of antibiotic absorbed or the urinary recovery. Talampicillin had less effect on the faecal flora in volunteers than ampicillin, and no overgrowth with Candida spp or Staphylococcus aureus was seen. Thirty-eight out of 47 urinary infections were eradicated by a seven-day course of talampicillin.
A Staphylococcus aureus strain, resistant to aminoglycosides, including gentamicin and tobramycin, and to penicillin, lincomycin, and other antibiotics, caused an outbreak of hospital infection in a surgical ward which spread to the intensive-therapy unit and to two other hospitals. 21 patients were colonised and 9 of these had overt clinical infection. Administration of antibiotics to which the staphylococcus was resistant was associated with colonisation. The use of gentamicin, tobramycin, and lincomycin in these hospitals has increased as has the occurrence of bacterial resistance to these agents. An antibiotic policy to control their use is essential to preserve their value in life-threatening infections by bacteria resistant to other agents.
Carbenicillin or ticarcillin were incubated individually with each of the following antibiotics: gentamicin, tobramycin, sisomicin, amikacin. The residual activity of each aminoglycoside in this mixture was assayed enzymatically. Amikacin was inactivated the least of the aminoglycosides. Both penicillins inactivated each aminoglycoside to a similar extent by a degree which varied according to the medium of incubaiton, the least inactivation being seen in pooled human serum and the most in phosphate buffer at pH 7.4.
Pivmecillinam (FL 1039) is the pivaloyloxymethyl ester of mecillinam (FL 1060) which has considerable in vitro activity against Enterobacteriaceae. 38 hospital inpatients who had proven urinary tract infections were treated with 400 mg pivmecillinam four times daily for 5-7 days. The MIC of mecillinam to the infecting organisms was determined as were the serum and urinary concentrations of the antibiotic. The patients were followed up for 4-6 weeks after the end of treatment. Three patients were lost to follow-up. Of the 35 patients who were adequately followed up, 29 (83%) were classified as cured and there were 6 failures. Reported side effects were of a minor nature.
A total of 2,031 clinical isolates of Gram negative bacilli was obtained from hospitals in 4 centres and these cultures were tested for resistance to ampicillin, cephazolin and sulphonamide. Ampicillin and sulphonamide resistance in outpatients ranged from 15 to 28 per cent of E. coli strains and 4 to 11 per cent of Proteus mirabilis strains. Resistance to cephazolin in outpatients ranged from 0 to 3 per cent of E. coli and 0 to 6 per cent of Proteus mirabilis. Resistance patterns for E. coli, Proteus mirabilis and Klebsiella strains isolated from inpatients were much higher and varied widely. These patterns are presented and the reasons for these variations discussed.
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Blood and urine levels of carbenicillin were measured in 10 healthy volunteers and four patients with renal failure after single and multiple oral dose of carfecillin. Urinary levels after 1000-mg doses in healthy subjects were considered sufficient for treatment of Pseudomonas aeruginosa urinary infections, but the serum levels were too low for chemotherapy of systemic infections with this organism even in severe renal failure. Urinary infections were treated in 35 inpatients with a seven-day course of carfecillin. The infection was eradicated in 21 cases (60%). In 12 cases the pathogen was Ps. aeruginosa, which was eradicated from eight patients (67%). Many patients had severe urinary tract disease. Side effects were virtually absent.
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The acetyltransferase technique of serum gentamicin assay was demonstrated to be specific for aminoglycoside antibiotics. The enzyme involved was isolated and stabilized by lyophilization.
The adenylytransferase/acetyltransferase methods of gentamicin assay have been evaluated for accuracy, speed, and cost. For a comparable cost of materials the latter method is more accurate than that using the adenylytransferase enzyme. The acetyltransferase method is much quicker than the adenyltransferase due to the shorter time necessary for radioactive counting. Sonication is an easier method of enzyme preparation than the previously used osmotic shock technique. The acetyltransferase method is reproducible and there was a very good correlation between it and a microbiological agar-plate diffusion method.
The use of high-voltage electrophoresis and bioautography for the separation mixtures of antibiotics received in clinical serum samples is described. The electrophoretic characteristics of 39 antibiotics are given as is the accuracy of the method for quantitating three antibiotics. In screening 189 consecutive serum samples submitted for routine antibiotic assay, undisclosed antibiotics were revealed by the technique in 35.