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Metabolism: Clinical and Experimental Dec 1996To study the effect of carnitine depletion on physical working capacity, healthy subjects were administered pivaloyl-conjugated antibiotics for 54 days. The mean...
To study the effect of carnitine depletion on physical working capacity, healthy subjects were administered pivaloyl-conjugated antibiotics for 54 days. The mean carnitine concentration in serum decreased from 35.0 to 3.5 mmicromol/L, and in muscle from 10 to 4.3 micromol/g noncollagen protein (NCP). Exercise tests were performed before and after 54 days' administration of the drug. At submaximal exercise, there was a slight increase in the concentration of 3-hydroxybutyrate in serum, presumably caused by decreased fatty acid oxidation in the liver. There was also a decreased consumption of muscle glycogen, indicating decreased glycolysis in the skeletal muscle. The muscle presumably had enough energy available, since there was no significant decrease in the concentration of adenosine triphosphate (ATP) and creatine phosphate during exercise. The work at maximal oxygen uptake (VO2max) and the maximal heart rate were reduced. Since VO2max is considered dependent on heart function, carnitine depletion seemed to affect cardiac function.
Topics: Adolescent; Adult; Amdinocillin Pivoxil; Blood Glucose; Carnitine; Exercise; Fatty Acids, Nonesterified; Female; Glycogen; Humans; Male; Middle Aged; Pentanoic Acids; Pivampicillin; Triglycerides
PubMed: 8969283
DOI: 10.1016/s0026-0495(96)90179-1 -
Ugeskrift For Laeger Oct 1996A case of Listeria monocytogenes septicaemia and infection of a prosthetic hip joint is presented in a patient with non-insulin-dependent diabetes mellitus. The patient...
A case of Listeria monocytogenes septicaemia and infection of a prosthetic hip joint is presented in a patient with non-insulin-dependent diabetes mellitus. The patient developed the infection five and a half years after primary alloplastic operation. The prosthesis was removed and a temporary prosthesis with gentamicin was placed ("spacer"). The antibiotic treatment included ampicillin, pivampicillin and sulfamethoxazole-trimetroprim. Six weeks after removal of the prosthesis an un-cemented prosthesis was placed, and the patient had a full functional recovery.
Topics: Aged; Anti-Bacterial Agents; Hip Prosthesis; Humans; Listeriosis; Male; Prosthesis-Related Infections; Reoperation
PubMed: 8928284
DOI: No ID Found -
American Journal of Veterinary Research Jul 1996To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro...
OBJECTIVES
To determine the oral bioavailabilities of 3 ampicillin esters (pivampicillin, bacampicillin, and talampicillin) and ampicillin sodium, and to determine in vitro stability of the ampicillin esters in ileal contents (pH 8.3 to 8.5).
DESIGN
A crossover design to administer the 4 drugs orally, and ampicillin i.v. to all horses in the study.
ANIMALS
4 healthy adult horses.
PROCEDURE
The drugs were administered intragastrically to the horses at a dosage equimolar to 15 mg of ampicillin/kg of body weight. Also, ampicillin sodium was administered i.v. at the same dosage. Blood samples were taken up to 12 hours after drug administration, and ampicillin concentrations in plasma were determined. For the in vitro study, the ampicillin esters were incubated at 37 C in ileal contents obtained from ponies with cecal fistulas. After incubation, the remaining intact ester and the formed ampicillin were measured.
RESULTS
Absolute oral bioavailability was 31, 39, 23, and 2% for pivampicillin, bacampicillin, talampicillin, and ampicillin sodium, respectively. In the in vitro study, 90% decomposition of the ester took place in 30, 60, and 5 minutes, for pivampicillin, bacampicillin, and talampicillin, respectively.
CONCLUSIONS
Pivampicillin and bacampicillin are promising candidates for oral antibiotic treatment of horses. The rapid decomposition of ampicillin esters is caused by chemical hydrolysis at the high pH of equine ileal contents.
Topics: Administration, Oral; Ampicillin; Animals; Biological Availability; Cross-Over Studies; Drug Stability; Female; Half-Life; Horses; Intestinal Absorption; Male; Metabolic Clearance Rate; Orchiectomy; Penicillins; Pivampicillin; Talampicillin
PubMed: 8807014
DOI: No ID Found -
Contact Dermatitis Apr 1996
Topics: Air Pollutants, Occupational; Dermatitis, Allergic Contact; Dermatitis, Occupational; Geobacillus stearothermophilus; Humans; Microbial Sensitivity Tests; Penicillins; Pivampicillin
PubMed: 8730176
DOI: 10.1111/j.1600-0536.1996.tb02209.x -
The Veterinary Record Mar 1996To evaluate the side effects of oral pivampicillin and trimethoprim/ sulphadiazine, 200 horses receiving these antimicrobial agents were studied. The horses received... (Comparative Study)
Comparative Study
To evaluate the side effects of oral pivampicillin and trimethoprim/ sulphadiazine, 200 horses receiving these antimicrobial agents were studied. The horses received either trimethoprim/ sulphadiazine (30 mg/kg twice daily) or pivampicillin (25 mg/kg twice daily) for three or more days. No adverse effects other than loose faeces and diarrhoea were detected. The risk of diarrhoea was significantly less after the oral administration of pivampicillin (3 per cent) than after trimethoprim/ sulphadiazine (7 per cent). Horses whose appetite was reduced appeared to be predisposed to develop diarrhoea after the administration of either oral antimicrobial agent.
Topics: Administration, Oral; Animals; Anti-Infective Agents; Diarrhea; Drug Combinations; Female; Horse Diseases; Horses; Incidence; Male; Pivampicillin; Sulfadiazine; Trimethoprim
PubMed: 8734507
DOI: 10.1136/vr.138.11.253 -
The Veterinary Quarterly 1996Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses.... (Comparative Study)
Comparative Study
Pivampicillin was administered as an oral paste to five healthy adult horses, and an oral paste with ampicillin trihydrate was administered to three horses. Pivampicillin was administered to both starved and fed horses, ampicillin trihydrate was administered to fed horses only. The dose of pivampicillin was 19.9 mg/kg, and the dose of ampicillin trihydrate was 17 mg/kg. Both doses are equivalent on a molecular basis to 15 mg/kg ampicillin. Ampicillin concentrations in plasma were determined up to 24 hours after administration. After administration of pivampicillin to starved and fed horses the mean areas under the plasma concentration-time curve (AUCs) were 23.0 and 19.3 micrograms.h.ml-1, respectively. After administration of ampicillin trihydrate to fed horses the mean AUC was 0.7 microgram.h.ml-1. The peak plasma concentrations were 4.8, 6.7, and 0.1 microgram/ml, after administration of pivampicillin to starved and fed horses and of ampicillin trihydrate to fed horses, respectively. There was no statistically significant difference in peak plasma concentration or AUC between pivampicillin administered to starved or fed horses. It is concluded that pivampicillin administered as an oral paste at a dose of 19.9 mg/kg gives satisfactory plasma concentrations in both starved and fed horses, whereas ampicillin trihydrate produces negligible plasma concentrations. Pivampicillin binds to feedstuffs at the pH found in the horse's stomach and small intestine. After incubation for 6 h at pH 6, approximately 15% remains in solution, and after incubation for 3 h at pH 1.9, approximately 40% remains in solution. Ampicillin, which binds to feedstuffs to a lesser extent, has a lower bioavailability than pivampicillin. Therefore, binding to feedstuffs does not seem to be a critical factor in the absorption of aminopenicillins.
Topics: Administration, Oral; Ampicillin; Animals; Anti-Bacterial Agents; Female; Horses; Hydrogen-Ion Concentration; In Vitro Techniques; Intestine, Small; Male; Ointments; Penicillins; Pivampicillin; Stomach
PubMed: 8933688
DOI: No ID Found -
Biochimica Et Biophysica Acta Nov 1995Pivaloyl-containing antibiotics and pivalic acid in man or rat have been reported to cause increased urinary carnitine loss secondary to pivaloylcarnitine generation....
Pivaloyl-containing antibiotics and pivalic acid in man or rat have been reported to cause increased urinary carnitine loss secondary to pivaloylcarnitine generation. Pivaloylcarnitine concentration was especially high in heart after administration of pivalic acid or pivampicillin in vivo. Formation of pivaloylcarnitine was therefore studied in isolated rat heart cells in the presence of sodium pivalate. Formation of pivaloylcarnitine in rat heart cells increased with incubation time, after a lag time from 0 to 2 h and linearly up to 6 h. The formation increased with increasing concentration of sodium pivalate, followed Michaelis-Menten kinetics with an apparent Km = 348 +/- 10 microM and Vmax = 116 +/- 20 pmol.mg protein-1.h-1. Bromoacetylcarnitine inhibited the pivaloylcarnitine formation to Ki = 116 +/- 43 microM and Vmax = 107 +/- 14 pmol.mg protein-1.h-1. The uptake of carnitine in heart cells was suppressed 62-74% by deoxycarnitine (40 microM) and D-carnitine (200 microM), and 95% by NaF (5 mM), NaN3 (500 microM) or at temperature 4 degrees C. Pivaloylcarnitine inhibited carnitine uptake to 33-35% of the controls, while sodium pivalate did not. More than 90% of intracellular pivaloylcarnitine was released from the heart cells after 18 h of incubation in the absence of sodium pivalate and L-carnitine. These data show that pivalate is readily converted to pivaloylcarnitine in heart cells, in contrast to the limited conversion in hepatocytes.
Topics: Acetylcarnitine; Animals; Betaine; Carnitine; Cells, Cultured; Kinetics; Myocardium; Pentanoic Acids; Pivampicillin; Rats; Rats, Wistar
PubMed: 7488636
DOI: 10.1016/0005-2760(95)00151-2 -
Biochimica Et Biophysica Acta Jan 1995Both pivaloylesterified antibiotics and pivalic acid cause pivaloylcarnitine excretion into urine in the rat and human. In the present study, the formation of... (Comparative Study)
Comparative Study
Both pivaloylesterified antibiotics and pivalic acid cause pivaloylcarnitine excretion into urine in the rat and human. In the present study, the formation of pivaloylcarnitine, expressed as short-chain acylcarnitines has been observed in rats. The carnitine pool of the rats was radiolabeled by injection of L-[3H]butyrobetaine 24 h prior to exposure to pivalic acid injected i.p. or pivampicillin administered orally. The presence of pivaloylcarnitine in liver, heart, kidney, stomach, small intestine, testis, muscle, brown fat, white fat and serum was determined at zero time, 0.5, 2, 8 and 24 h after exposure to pivalic acid. After injection of pivalic acid, pivaloylcarnitine calculated as percent of free carnitine and short-chain acylcarnitines amounted to (mean +/- SD) 1.1 +/- 0, 15.4 +/- 2.5, 33.4 +/- 0.7 and 37.5 +/- 1.5% in the heart and 1.2 +/- 0.2, 20.6 +/- 9.5, 29.8 +/- 7.6 and 22.5 +/- 1.6% in brown fat after 0, 0.5, 2 and 8 h, respectively. 2 h after administration, pivaloylcarnitine calculated as percent of free carnitine and short-chain acylcarnitines was highest in the heart (20.9 +/- 7.6%) and brown fat (19.0 +/- 8.5%) in the pivalic acid-treated rat, and highest in the kidney (12.4 +/- 3.1%) and brown fat (10.2 +/- 2.8%) in the pivampicillin-treated rat. Pivaloylcarnitine percent in the liver was 2.8 +/- 0.6 in the pivalic acid-treated rat, 3.5 +/- 1.2 in the pivampicillin-treated rat and 1.3 +/- 0.4 in the control group. Pivaloylcarnitine concentration, nmol/g and nmol/organ, was highest in the heart and brown fat in both treatment groups. The present study suggests that the heart and the brown fat, but not the liver, play important roles in pivaloylcarnitine formation in the rat.
Topics: Adipose Tissue, Brown; Animals; Carbon Radioisotopes; Carnitine; Chromatography, Gas; Isotope Labeling; Male; Myocardium; Pentanoic Acids; Rats; Rats, Wistar; Tissue Distribution
PubMed: 7827109
DOI: 10.1016/0304-4165(94)00129-l -
Scandinavian Journal of Infectious... 1995In this double-blind multicentre study, using the intention-to-treat approach, a total of 293 patients with fever (> or = 38.5 degrees C), symptoms of sepsis and signs... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Ampicillin plus mecillinam vs. cefotaxime/cefadroxil treatment of patients with severe pneumonia or pyelonephritis: a double-blind multicentre study evaluated by intention-to-treat analysis.
In this double-blind multicentre study, using the intention-to-treat approach, a total of 293 patients with fever (> or = 38.5 degrees C), symptoms of sepsis and signs of pneumonia or pyelonephritis were randomly assigned to treatment with ampicillin and mecillinam (A+M) or cefotaxime followed by cefadroxil. In the febrile phase, treatment was given intravenously twice daily, either with 1,200 mg ampicillin together with 600 mg mecillinam or with 2 g cefotaxime alone. When the patients stayed afebrile, the intravenous administration was replaced by oral treatment twice daily for 14 days, either with 500 mg pivampicillin and 400 mg pivmecillinam or 1 g cefadroxil. In the A+M group, 33% (48/144) of the patients did not complete the full course of treatment as compared with 32% (47/149) in the cephalosporin group, the reasons being treatment failure in 27 and 29, respectively, or adverse effects (n = 16 in both groups). The median duration of fever was 47 h in the A + M group and 50 h in the cephalosporin group. Of 135 patients with pneumonia, 68% were completely cured in the A + M group, and 65% in the cephalosporin group, the main reasons for treatment failure being Mycoplasma pneumonia or ornithosis. Of 136 patients with pyelonephritis, 63% were cured in each group. The main reason for failure was bacteriological relapse. Side-effects were reported by 32 patients (22%) of the A+M group, as compared with 41 (28%) of the cephalosporin group. Epigastric complaints were equally frequent in both groups, but there was a tendency for a higher frequency of exanthema in the A+M group, and for antibiotic-associated diarrhoea and fungal superinfections in the cephalosporin group.
Topics: Amdinocillin; Ampicillin; Cefadroxil; Cefotaxime; Cephalosporins; Double-Blind Method; Drug Therapy, Combination; Escherichia coli Infections; Female; Fever; Humans; Male; Middle Aged; Penicillins; Pneumonia, Bacterial; Pyelonephritis
PubMed: 8588136
DOI: 10.3109/00365549509047047 -
Nordisk Medicin 1995An enquiry into the use of antibiotic prophylaxis in conjunction with diagnostic or therapeutic urological procedures at hospitals in four Scandinavian countries showed... (Comparative Study)
Comparative Study
An enquiry into the use of antibiotic prophylaxis in conjunction with diagnostic or therapeutic urological procedures at hospitals in four Scandinavian countries showed manifest national differences to exist for most procedures. In transurethral resection, for instance, antibiotic cover was used at 79 percent of Finnish hospitals, but at only nine percent of Danish hospitals. Not only were dosage regimens characterized by wide national variation, but also the spectrum of antibiotics used, quinolones being most frequently used in Sweden, but ampicillin and pivampicillin in Denmark. For some procedures policy was more uniform in all countries, antibiotic cover rarely being used in connection with ureterocystoscopy (5 percent of hospitals), but often in conjunction with percutaneous stone surgery (72 per cent). In certain procedures where there is strong evidence suggesting the necessity of antibiotic prophylaxis, it was not always used-e.g., in transrectal prostate biopsy where it was used at only 62 per cent of hospitals. The interpretation of published findings and clinical experience would appear to differ markedly, and local traditions would seem to be strong determinants of clinical routines. The wide variation suggests that all patients do not receive optimal treatment. To improve routines, our knowledge of antibiotic preparations needs to be expanded by well executed studies, followed by general implementation of the results at the various centres. A series of consensus conferences should be arranged and the recommendations published as a first step toward a more uniform and probably better use of antibiotic prophylaxis in conjunction with diagnostic and therapeutic urological procedures.
Topics: Anti-Bacterial Agents; Cystoscopy; Denmark; Female; Finland; Humans; Male; Nephrostomy, Percutaneous; Norway; Premedication; Prostatectomy; Sweden; Ureteroscopy; Urologic Diseases
PubMed: 7831109
DOI: No ID Found