Prophylactic regimens in colorectal surgery: comparisons between metronidazole used alone or with ampicillin for one or three days.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
T Bergan
Publications and source records attributed to T Bergan.
[Pharmacokinetics and tissue penetration of ceftriaxone].
This article describes the pharmacokinetics of ceftriaxone, a new "third generation" cephalosporin. This antibiotic displays two major characteristics: a very long serum half-life and a good tissue penetration. The properties of ceftriaxone should allow its easy clinical handling.
Bile↗
Effect of antibiotics eliminated by first order kinetics.
We wanted to simulate the conditions within the body where bacteria are exposed to antibiotics at concentrations which diminish exponentially and thus do not remain constant as in the usual test systems for determination of the minimum inhibitory or bactericidal concentrations (MIC, MBC). For this purpose we employed a model with a glass chamber containing a constant volume of culture which was supplied continuously with medium at a constant rate. We studied the pattern of bacterial response using a series of bactericidal and bacteriostatic agents added to the system at various multiples of the MIC of several bacterial strains, and using different rates of elimination of the antibacterial agent. Strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes were exposed to amoxicillin, ampicillin, benzylpenicillin, carbenicillin, cefazolin, chloramphenicol, flucloxacillin, gentamicin, or oxytetracyclin. The bacteria were killed or maintained at their initial density depending on the antibiotic and its concentration. The main findings were: for most drugs drop in bacterial number persisted while the concentration of the chamber remained above MIC, a period of time elapsed before recovery and bacterial multiplication resumed at the same rate as in control cultures, the period of antibacterial postantibiotic effect lasted longer with Gram-positive than with Gram-negative species, the point in time when the bacteria resumed multiplication corresponded to the IC50. We observed only minor differences in the pattern of bacteria during exposure to potentially bactericidal agents compared to antibiotics with mainly bacteriostatic effects.
Anti-Bacterial Agents↗
Outer membrane proteins and plasmids in different Yersinia enterocolitica serogroups isolated from man and animals.
Human clinical isolates of Yersinia enterocolitica (serogroups 0:3, 0:8, and 0:9) harboured a 40-45 megadaltons plasmid, which was shared by strains isolated from cases of yersiniosis in animals (0:2 and 0:5) and from healthy swine (0:3 and 0:9). Possession of such plasmids was invariably correlated with expression of three temperature-regulated characteristics related to the bacterial surface: when cultivated at 37 degrees C, all plasmid-bearing strains, unlike their plasmid-cured mutants, (i) underwent autoagglutination, (ii) produced a distinct mannose-resistant haemagglutinin, and (iii) simultaneously synthesized ancillary outer membrane proteins (OMPs). None of these characters was expressed phenotypically at 22 degrees C. Dominant among the plasmid-associated, temperature-regulated OMPs was a high molecular weight protein of approximately 180 kilodaltons, which was found in strains of five different serogroups (0:2, 0:3, 0:5, 0:8, and 0:9) regardless of the source of isolation. Strains isolated from diseased animals and from healthy swine were quite similar, if not identical, to human clinical isolates with respect to these ancillary OMPs. In contrast to the plasmid-associated OMPs expressed only at 37 degrees C, a number of plasmid-independent OMPs were produced mainly at 22 degrees C.
Animals↗
Pharmacokinetics of brodimoprim in serum and skin blister fluid.
Following 400 mg brodimoprim given orally to 8 volunteers, the peaks of the mean concentration curves were 3.2 +/- 1.0 mg/l in serum and 1.0 +/- 0.2 mg/l (+/- SEM) in skin blister fluid. The terminal half-lives were 25.9 +/- 2.2 h and 42.2 +/- 6.5 h in serum and blister fluid, respectively. The area under the concentration-versus-time curve for blister fluid was 73% of serum value, and the mean recovery of bioactive drug in urine during 24 h was 3.4%. Considering the minimal inhibitory concentrations of potential target organisms and the slow elimination, the results suggest that brodimoprim may be useful in the treatment of infections, and that dosage once a day may be sufficient.
Administration, Oral↗
Temocillin penetration of peripheral lymph.
An intravenous dose of temocillin 1g was administered to 5 healthy human volunteers from whom peripheral lymph, serum and urine were monitored for 12 hours. The concentrations after 1 hour were 14.3 mg/L in lymph and 58.1 mg/L in serum. The mean peak concentration in lymph (appearing between 1.5 and 2 hours) was 30.6 mg/L, and the simultaneous serum level was 47.8 mg/L. The lymph concentrations were always below those in serum, and the elimination half-life was 4.4 hours from lymph compared with 4.9 hours from serum. The ratio between the total areas under the concentration curves in lymph and in serum was 0.56, which reflects the ability of temocillin to penetrate to lymph. Serum protein binding appeared to impede the rate of transport from serum to lymph, but when compared with the results of less highly bound penicillins the total penetration of temocillin was better than expected.
Adult↗
Comparative pharmacokinetics of metronidazole and tinidazole and their tissue penetration.
Since metronidazole and tinidazole are used prophylactically against infections after colorectal surgery, their pharmacokinetics and that of hydroxy-metronidazole were compared in 34 such patients. Seventeen patients received a single dose of 1.5 g (50-min infusion) of either agent 1 h before the operation. The concentrations of serum and tissue homogenates (subcutaneous fat, omentum, peritoneum, ileum, appendix, colon) were assayed by high-pressure liquid chromatography. The serum concentrations 1 h after start of infusion were 34.1 +/- 6.7 mg/l of metronidazole, 2.3 +/- 1.2 mg/l of OH-metronidazole, and 35.2 +/- 6.3 mg/l of tinidazole. OH-metronidazole and tinidazole were detectable for 72 h and metronidazole for 48 h. The ranges of serum and tissue concentrations (subcutaneous fat, omentum, peritoneum, ileum, appendix, colon) overlapped (within one single standard deviation). The tissue concentrations were high, particularly in intestinal tissues, except that the levels were low in subcutaneous tissue. The serum half-life of metronidazole was 9.0 +/- 1.6 h, of OH-metronidazole 14.8 +/- 7.4 h, and of tinidazole 16.4 +/- 3.8 h. The terminal-phase distribution volume was 35.8 +/- 10.01 for metronidazole and 40.6 +/- 9.91 for tinidazole, and the total body clearance 2.7 +/- 1.2 l/h and 1.8 +/- 0.5 l/h, respectively. The slower disposition of OH-metronidazole, which inhibits anaerobic bacteria, prolongs the duration of bioactivity in the body after metronidazole to that reached by tinidazole. OH-tinidazole was not detected in patient specimens (assay standards ensured that it could be assayed).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Characterization of enterotoxigenic Escherichia coli. Serotypes, enterotoxins, adhesion fimbriae, and the presence of plasmids.
Enterotoxigenic Escherichia coli of human and procine origin were characterized with respect to their O and H antigens, fimbrial antigens, and type of enterotoxin produced. Enterotoxin production was determined by bioassay (infant mice) and enzyme-linked immunoassay (ELISA). The presence of genes coding for the enterotoxins was determined by DNA-DNA hybridization. The number and molecular size of plasmids in the enterotoxigenic strains were determined by gel electrophoresis. Strains with the same serological pattern showed different plasmid profiles and could thereby easily be separated. One strain of porcine origin possessed only one plasmid, but produced both heat-labile enterotoxin and the F4 antigen (formerly K88), which is an unusual combination.
Animals↗
Penetration of antibiotics into human peripheral lymph.
Explore the source record for details and available documents.
Anti-Bacterial Agents↗
Antibacterial activity and pharmacokinetics of nitroimidazoles. A review.
The antibacterial activity of metronidazole and tinidazole are comparable. The former is subject to biotransformation with the production of both hydroxy-metronidazole and acetylmetronidazole. The hydroxylated moiety has an antibacterial activity and may act either synergistically or additively in combination with metronidazole, thus enhancing the therapeutic activity of the latter. Metronidazole and tinidazole may be given both orally and parenterally. The bioavailability of oral doses of metronidazole is 88-95%, that of tinidazole 90%. Rectal suppositories have a bioavailability of 60-70%. The serum half-life of metronidazole is 6-10 hours, that of hydroxy-metronidazole 9.5-19 hours, and that of tinidazole 9-14 hours. The half-life may be longer in patients who have undergone colorectal surgery. Renal failure enhances the elimination of hydroxy-metronidazole and acetyl-metronidazole, whereas the consequences for unchanged metronidazole are negligible. The effect of reduced renal function on tinidazole is unclear. The extravascular penetration of metronidazole and tinidazole are similar. A single prophylactic intravenous dose of 1500 mg of either drug causes prolonged antibacterial effects which would last 36-48 hours for both drugs.
Bacteria, Anaerobic↗
Initial slope technique for estimation of the apparent volume of distribution during constant-rate intravenous infusion.
A new technique is presented for estimating the apparent volume of distribution of drugs during constant-rate intravenous infusion. It is based on the initial slope of the plasma drug concentration versus time profile during the infusion. Equations are derived to provide estimates of the apparent volume of distribution for a one-compartment drug and for the central compartment of a two-compartment drug. The utility of the technique is illustrated by data obtained during constant-rate infusion of metronidazole in 11 healthy subjects. The average estimated value of the volume of the central compartment of metronidazole was 12% higher than the average value obtained by conventional pharmacokinetic analysis. The systematic error associated with this volume estimation procedure was assessed through the use of dimensionless concentration versus dimensionless time plots. The initial slope technique should prove useful in providing initial estimates of volume terms.
Half-Life↗
Renal biopsies in cystic fibrosis.
Pharmacokinetic studies on antibiotics as well as other studies on renal function indicate renal malfunction in cystic fibrosis. Renal biopsies from two children, and post mortem examination from one child, with this disorder were normal by light microscopy and close to normal by immunofluorescence examination and transmission and scanning electron microscopy, even in cases with advanced disease and marked renal malfunction. Renal biopsy interpretation thus seems to be of little value in the evaluation of renal malfunction in this disorder, and this suggests that the functional abnormalities are caused by metabolic/biochemical defects.
Adolescent↗
The pharmacokinetics of ceftriaxone in serum, skin blister and thread fluid.
Following 4 g of ceftriaxone, given intravenously, to eight volunteers, the antibiotic concentration in serum, suction skin blister fluid and fluid from subcutaneously implanted threads was followed for 28 h. High and sustained levels were found in both serum and extravascular fluids; the mean maximum serum concentration was 448 mg/l, and the mean peak concentrations in blister and thread fluid were 94 mg/l and 63 mg/l, respectively. The terminal, half-lives were: serum 7.2 h, blister fluid 10.3 h and thread fluid 11.3 h. The total area under the concentration versus time curves for serum was 1636 mg X h/l. For blister and thread fluid the areas were 1573 mg X h/l and 808 mg X h/l. The results suggest a twice daily dosage regimen.
Adult↗
Synthesis of analogs of D-Ala-D-Ala as potential inhibitors of bacterial cell wall biosynthesis.
The syntheses of the L,L- and D,D-stereoisomers of N- phenoxyacetyl -X-alanine in which X = Ser, Ala( beta Cl ) or Arg, are described. The antibacterial activity of these peptides and some of their synthetic intermediates has been examined. Four of the intermediates in which X = Ala( beta Cl ) and Arg(NO2), which possess C-terminal benzyl ester groups, were active against viridans streptococci and Streptococcus agalactiae. The D,D-enantiomers were more active than the corresponding L,L-isomers. None of the compounds were active against beta-lactamase producing bacteria or acted as beta-lactamase inhibitors.
Bacteria↗
Synthesis of D-Ala--D-Ala analogues with postulated antibacterial activity.
The syntheses of the L,L- and D,D-stereoisomers of N-phenoxyacetyl-X-alanine in which X=His, Tyr, or Lys, are described. The antibacterial activity of some of the peptide derivatives and their synthetic intermediates have been examined. Some of the intermediates exhibited moderate activity against viridans streptococci, enterococci and Streptococcus agalactiae. None of the compounds were active against beta-lactamase producing bacteria or served as beta-lactamase inhibitors.
Anti-Bacterial Agents↗
Pathogenicity of anaerobic bacteria.
The pathogenicity of anaerobic bacteria has become better understood during the last decade. In addition to the relatively well characterized exotoxins of histotoxic clostridia, a number of factors involved in the production of disease have been described in Bacteroides and other anaerobic bacteria. Important factors are particularly superoxide dismutase, catalase, the abscess inducing capsular polysaccharide of Bacteroides fragilis, proteases, lipases, heparinase, and nucleases. Resistance against phagocytosis has been described in Gram-negative species. Pathogenicity factors like hyaluronidase, haemolysin, lipolysins, and neuraaminidase have been isolated even in species such as the propionibacteria, which are considered to have a low pathogenicity. The ability of different strains to enhance the manifestations of infections when they occur together has pointed to a colloboration between their individual pathogenicity factors in the sense that they enhance the activity of each other. The ability of anaerobes to produce enzymes inactivating antibiotics has become well established and is an important factor in the maintenance of an infection during therapy.
Bacteria, Anaerobic↗
Evaluation of Minitec and API as rapid diagnostic methods for anaerobic bacteria.
The performance of the miniaturized biochemical differentiation systems API 20 anaerobe System and Minitek was compared with pH reactions in PRAS media of 58 anaerobic or capno-aerophilic bacterial strains from recent clinical specimens. The overall correlation of the Minitek reactions was 87% and of the API reactions 85%. The reactions of acid formation from carbohydrates was slightly higher for Minitek. This resulted in a correct diagnosis in 90% after Minitek and 86% after API. If corrected for 3 strains of Clostridium perfringens for which double haemolysis would have prevented reporting of another diagnosis, 95% of the strains would have been correctly identified by Minitek compared to 91% with API. The errors were mostly due to lack of sensitivity of the reactions of the test kits.
Bacteria, Anaerobic↗
Assay of metronidazole by HPLC compared with microbial method.
A high-performance liquid chromatography (HPLC) method for the assay of metronidazole and its 2-hydroxymethyl metabolite in sera was compared with a microbiological method, an agar well diffusion technique with Clostridium perfringens as indicator strain. The HPLC technique involves separation of metronidazole from its two active major metabolites (the 2-hydroxymethyl and the 1-carboxymethyl derivatives) on a mu-Bondapak C18 column and UV detection at 313 nm. The mobile phase was 35% acetonitrile in 0.02 M acetate buffer pH 4 with a low rate 2.0 ml/min. Tinidazole was used as an internal standard and metronidazole and its 2-hydroxymethyl metabolite quantitated by peak height ratios. The 1-carboxymethyl derivative was well separated from the other peaks. The HPLC procedure proved to be superior with respect to sensitivity (detection limits: 0-1 microgram/ml serum for both compounds), speed and precision. It discriminates between metronidazole and its two major active metabolites and quantitates the total amounts present. The microbial technique codetermines all antibacterial active compounds and monitors the free, not protein bound moieties. Published data on the activity of the 2-hydroxymethyl metabolite against Cl. perfringens relative to metronidazole and published results on the protein binding of metronidazole were used to correlate data from the two methods on individual serum samples collected during the early, intermediate and late periods after a single intravenous dose of metronidazole to volunteers.
Bacteriological Techniques↗