A contrivance for bacteriocine typing.
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Bacteriocins↗
Biomedical subjects
T Bergan
Publications and source records attributed to T Bergan.
Typing of Pseudomonas aeruginosa by pyocine production.
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Bacteriocins↗
A new species, Sphaerophorus intermedius, isolated from empyema.
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Bacteriological Techniques↗
Antibacterial activity and kill kinetics of ampicillin/sulbactam (CP-45899) combinations against Escherichia coli and Klebsiella aerogenes.
Combinations of ampicillin and sulbactam (CP-45899) were tested against 11 strains of Escherichia coli and five strains of Klebsiella aerogenes. With the exception of one E. coli, strain, the strains were all highly resistant to ampicillin. Synergy was demonstrated by agar dilution in six of the ten resistant E. coli strains and in three of the five K. aerogenes strains. At simulated in vivo conditions with constantly decreasing concentrations mimicking in vivo pharmacokinetics, synergy was detected against the beta-lactamase-producing strains tested, although the activity against the more resistant K. aerogenes strains was low. The correlation between antibacterial activity as determined by minimum inhibitory concentrations and the bacterial kill kinetics exhibited in the in vivo simulation model was acceptable for E. coli. The relationship was less predictable for K. aerogenes, however.
Ampicillin↗
Antibacterial activity and kill kinetics of amoxicillin-clavulanic acid combinations against Escherichia coli and Klebsiella aerogenes.
Combinations of amoxicillin and clavulanic acid were tested against 11 Escherichia coli strains and five Klebsiella aerogenes strains. Apart from one E. coli, the strains were highly resistant to amoxicillin due to beta-lactamase production. Synergy was demonstrated in all strains by agar dilution. Synergy was detected against the beta-lactamase-producing strains under simulated in vivo conditions with constantly decreasing concentrations simulating in vivo pharmacokinetics. The correlation between antibacterial activity determined by minimum inhibitory concentrations and bacterial kill kinetics in the in vivo simulation model was acceptable. A higher bacterial kill rate was observed when the antibiotic dosage was increased beyond the minimum concentration where an antibacterial effect was seen; this was not demonstrable by traditional agar dilution tests. In combination, a greater relative amount of amoxicillin compared to clavulanic acid allows a reduction in the total amount of antimicrobial agents with the same degree of antibacterial activity.
Amoxicillin↗
Induced abortion: microbiological screening and medical complications.
Preoperative cervical screening of 1,193 women undergoing first-trimester induced abortions yielded Chlamydia trachomatis in 11.7%, Neisseria gonorrhoeae in 0.8%, Mycoplasma hominis in 22.1%, Ureaplasma urealyticum in 10.1%, herpes simplex virus in 0.9% and Group B streptococci (GBS) in 2.9%. C. trachomatis and N. gonorrhoeae were especially frequent among teenagers. A total of 2.2% (26 women) developed postoperative pelvic inflammatory disease (PID) and 0.9% (13 women) endometritis. PID developed significantly more often in untreated chlamydia-positive (22.7%), M. hominis-positive (8.1%) and GBS-positive (6.1%) women than in women without these microbes (0.5%) (p less than 0.05). Prompt treatment of the chlamydia infection before or in connection with the abortion procedure significantly decreased the likelihood of developing chlamydial PID from 22.7% to 2.1% (p less than 0.001). The study confirms the importance of preoperative screening for chlamydia and suggests screening for M. hominis and GBS as well. The results of screening should be available before the abortion, allowing patients to be treated pre- or peroperatively.
Abortion, Induced↗
Extravascular penetration of ciprofloxacin. A review.
The pharmacokinetics of ciprofloxacin after oral and intravenous administration have been studied extensively, and the results have been published worldwide. This paper serves as a review of the pharmacokinetics of ciprofloxacin, with specific reference to its penetration into body fluids and tissues. Ciprofloxacin has a protein binding of approximately 30% and penetrates well into tissues. For instance, the total concentration (area under the serum concentration-time curve) in peripheral human lymph is 70% of the serum values, and the peak level in lymph appears with 1-2 hr. The corresponding value for suction skin blisters is 60% and for inflammatory blisters 120%. Ciprofloxacin is concentrated in white blood cells, lung, prostate, and kidney and reaches concentrations above serum in many other tissues as well. Urine concentrations are up to 100 times those in serum. The levels in bile are comparable or only slightly higher (less than or equal to x 10) than serum levels. The penetration into cerebrospinal fluid (CSF) is low; the CSF levels are 4-10% of the serum levels in noninflammatory CSF and 30-50% in CSF from patients with meningitis.
Administration, Oral↗
Transintestinal elimination of ciprofloxacin.
This study identified the routes of elimination of ciprofloxacin in two groups of five subjects each: one of healthy volunteers; the other of patients with severe renal failure having mean creatinine clearance of 12 ml/min (range, 8-16 ml/min). Each subject received one dose of 200 mg ciprofloxacin infused intravenously (IV) over 30 min. In an effort to recover the total drug administered, all urine and feces were collected for 7 days following dosing. Blood samples were drawn at set intervals. Serum, urine, and feces were assayed for ciprofloxacin and metabolites by high-pressure liquid chromatography. The ciprofloxacin elimination half-life was 3.9 +/- 0.4 hr in the healthy volunteers and 11.2 +/- 2.5 hr in the patients with severe renal failure. The total 7-day recovery of ciprofloxacin and its metabolites in urine and feces ranged from 74.0% to 114.7% of the dose (mean, 96.3 +/- 14.1%) in normal subjects and from 48.5% to 109.1% (mean, 88.1 +/- 20.9%) in patients. The dose of ciprofloxacin recovered in urine was 65.3 +/- 10.7% in healthy subjects and 19.0 +/- 15.9% in impaired patients (reduction factor, 3.4). In contrast, the dose recovered in feces was 11.4 +/- 2.6% in the group of normal subjects and 37.2 +/- 12.5% in the group of patients with impaired renal function in a 3.3-fold increase.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Safety of intravenous ciprofloxacin in healthy volunteers after multiple dosing. A review.
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Ciprofloxacin↗
Pharmacokinetics of ampicillin in serum and in dermal suction blisters after oral administration of bacampicillin.
After oral administration of 0.8 g of bacampicillin, the median concentration of ampicillin in serum peaked at 1-2 hr and reached 8.4 and 12.3 micrograms/ml in two groups of 13 and four healthy volunteers, respectively. In the fluid of dermal blisters produced by suction, the peak values were 2.6 and 2.7 micrograms/ml, respectively. After oral administration of 1.6 g of bacampicillin to four healthy individuals, the median peak concentrations were 15.5 micrograms/ml in serum and 3.8 micrograms/ml in blister fluid. The rate of penetration of ampicillin into the blister fluid was lower than the rate of gastrointestinal absorption of bacampicillin, and the elimination of ampicillin from the blister fluid was slower than from serum; the half-life in blister fluid was approximately twice that in serum. Concentrations of ampicillin in the blister fluid exceeded those in serum at greater than or equal to 3 hr. Concentrations of less than 0.7 micrograms/ml were observed in blister fluid 11 hr after administration of the dose. The bioavailability of ampicillin was relatively greater after a 1.6-g dose of bacampicillin than after a 0.8-g dose. Inflammation in the blister fluid that was induced by endotoxin, which provoked a strong cellular response but cased no increase in the concentration of protein in the fluid, did not significantly influence the pharmacokinetics of ampicillin. The results suggest that the pharmacokinetics of antimicrobial agents in serum and in extravascular foci may be relevant to the setting of breakpoints between sensitivity and resistance of pathogens of antimicrobial agents.
Administration, Oral↗
Pharmacokinetics of tissue penetration of antibiotics.
Past efforts to characterize the ability of antibiotics to penetrate into tissues is reviewed, particularly the results of models that reflect the concentration of antibiotics in interstitial fluid (i.e., skin blisters, tissue chambers, skin chambers, wound exudates, implanted fibrin clots, and peripheral lymph). The preferable sources of such fluid appear to be skin chambers, suction-induced skin blisters, and peripheral lymph. Extent of penetration of antibiotics into tissue fluid is related to the amount of antibiotic not bound to protein. Protein binding is particularly inhibitory to penetration when greater than 80% of the antibiotic is bound. It is preferable to follow the extravascular concentrations of antibiotic for longer periods than is usually done. The ability of antibiotics to penetrate is best evaluated by use of the ratio of the area under the concentration curve (AUC) for antibiotic in the peripheral locus to the AUC for serum. Pharmacokinetic analysis should be done with data from each individual, not with data derived from curves using mean values. Penetration into fibrin, lymph, and chambers implanted in tissues follows Fick's law of diffusion. Lag times indicate the interval before penetration of antibiotic in serum to the peripheral locus may be observed. First-order, one-compartment, open models are applicable to the characterization of extravascular concentrations of antibiotics. The AUC for antibiotic in serum during a time interval is the factor determining the amount of agent that passes into an extravascular focus. Concentrations of drug in tissues are lower than those in serum; the peaks occur simultaneously or shortly after the maximal levels are reached in serum, and for most antibiotics the elimination of antibiotics from extravascular parts of the body is slower than from serum, particularly for agents with a half-life in serum of less than 4-5 hr.
Animals↗
Requirements for pharmacokinetic evaluation of antibiotics in phase I studies.
Initial pharmacokinetic studies usually include healthy volunteers to minimize variation generated by diseases. Ethical aspects of initial studies are paramount. The guidelines of the Helsinki Declaration should be followed or even extended. Thorough toxicologic screening in animals is a prerequisite. The use of radioisotopes for pharmacokinetic studies should be limited. The basic design of studies includes cross-over administration of intravenous and oral doses of several sizes. Bioavailability, total area under the serum concentration curve, serum half-life, amount eliminated in urine as active drug, and metabolism are the most important data. The fate of the parent compound and of its possible metabolites in both healthy persons and ill individuals (including those with renal or hepatic dysfunction) should be monitored. Diet may have consequences with regard to recommended dosage schedules. When possible, tissue penetration of antibiotics should be assessed, preferably through the analysis of peripheral human lymph and of suction-blister and peritoneal fluids. Theoretical dosage schedules based on pharmacokinetic assessments in healthy persons should be tested in patients with infectious disease, particularly in those with reduced renal and/or hepatic function.
Administration, Oral↗
Does serum protein binding inhibit tissue penetration of antibiotics?
Accumulated data on the penetration of 15 antibacterial agents into peripheral human lymph are reviewed. The major factor determining extravascular penetration is the level of serum protein binding. The penetration ratios of extravascular and serum levels diminish gradually as the level of protein binding increases. However, even at the highest protein-binding levels, distinct lymph concentrations are observed. The degree of penetration ranges from 100% for the antibiotic with the lowest level of serum protein binding (gentamicin, no drug bound) to 20% for that with the highest level of protein binding (flucloxacillin, 96% bound).
Anti-Bacterial Agents↗
Renal excretion of gentamycin in chronic pyelonephritis.
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Absorption↗
Chelating agents.
The antibacterial activity of metal ions, metal chelates, and molecules with chelating ability for polyvalent cations have been evaluated. The chelator N, N'-ethylenebis[2-(2-hydroxyphenyl)-glycine] (EHPG) exerted moderate-to-good activity against isolates of pathogenic bacteria and fungi. Other chelating agents such as ethylenediamine-tetraacetic acid (EDTA) and diethylene-triamine-pentaacetic acid (DTPA) revealed weak-to-moderate activity. Metal chelation of ligands reduced the activity of EDTA and DTPA.
Anti-Bacterial Agents↗
Pharmacokinetic evaluation of imipenem combined with cilastatin in cystic fibrosis.
The pharmacokinetics of imipenem (MK-787) and cilastatin (MK-791) were studied in 30 patients with cystic fibrosis (CF) receiving the drug for therapeutic purposes at doses of 11 mg/kg given as a 30-min infusion. The serum concentrations and urine elimination were studied after the first dose and during steady state. The concentrations were assayed by high-pressure liquid chromatography. The total areas under the imipenem serum concentration curves (AUCs) to infinity were 30.4 +/- 6.8 mg.h/l after the first dose compared with 29.1 +/- 7.1 mg.h/l during steady state (NS). The cilastatin AUCs on the 2 days were 40.3 +/- 9.3 and 38.3 +/- 0.4 mg.h/l (NS), respectively. The urinary recovery of imipenem was 47.8 +/- 17.8% after the first dose and 57.8 +/- 24.2% during steady state (NS). The amounts of cilastatin eliminated in the urine during 6 h were 6/7.3 +/- 22.9% after the first dose and 60.5 +/- 17.0% of the dose during steady state (NS). The mean half-life of imipenem in these CF patients was 1.2 +/- 0.4 h on the first day of the examination and within the same range during steady state. The distribution volume (Vd beta) was in the range of 28 liters, the total body clearance was 16.3 liters/h (285 ml/min) on the first day. The t1/2 of cilastatin was 0.59 +/- 0.14 h after the first dose and 0.61 +/- 0.14 h during steady state. Thus patients with CF eliminated cilastatin more quickly than imipenem.
Adolescent↗
Antibacterial activity of cefcanel.
The minimum inhibitory concentration of cefcanel, a new oral cephalosporin, has been determined for 182 clinical isolates, of which 84 were from the family Enterobacteriaceae, 45 were from the genus Streptococcus, 18 were nonfermentative rods, 25 were Haemophilus influenzae and 10 were Branhamella catarrhalis. In general, cefcanel was more active than the other cephalosporins against the species Escherichia coli, Klebsiella aerogenes and Proteus mirabilis. Among the genus Streptococcus only the enterococci were resistant to cefcanel. H. influenzae and B. catarrhalis showed also a reasonable susceptibility towards cefcanel. Oxidative rods were highly resistant to cefcanel.
Bacteria↗
Pharmacokinetic profile of fosfomycin trometamol.
The pharmacokinetics of fosfomycin trometamol has been assessed in 12 healthy volunteers given oral doses of 2, 3, and 4 g of fosfomycin and 3 g intravenously of fosfomycin as fosfomycin sodium, all in the fasting state. The assay was microbiological (Proteus mirabilis ATCC 21100). There was a gradual rise in both peak serum concentrations and total area under the curve by rising oral doses, from 16.0 mg/l and 106.7 mg x h/l, after 2 g to 30.9 mg/l and 189.7 mg x h/l after 4 g respectively. The serum half-life was 4 h after the oral doses and 2.1 h after the intravenous dose. After the oral doses, the amounts excreted in urine in the active form ranged from 36 to 40% compared to 93% after the intravenous dose. The bioavailability was slightly below 40%. Concentrations in urine covers the usual urinary tract pathogens after oral doses of 2, 3, and 4 g.
Administration, Oral↗