Plasma Antibiotic Concentrations Research Articles

Single Dose Oral Ciprofloxacin for Perioperative Antibiotic Prophylaxis in Lung Surgery

The need for antimicrobial prophylaxis in lung surgery has been well documented. Ciprofloxacin, an antimicrobial agent with a very broad spectrum of antibacterial activity, is rapidly absorbed after oral administration, leading to a bioavailability of nearly 85%. Its good tissue penetration, good safety record, and its extremely good chemical stability make this drug a potentially useful agent for perioperative antibiotic prophylaxis. In perioperative antibiotic prophylaxis, it is desirable to achieve the highest possible antibiotic concentrations in plasma and tissues during the surgical procedure' in order to extend the inhibitory concentration to as many potential pathogens as possible. In the present study, the efficacy of a single dose of oral ciprofloxacin 750mg in elective lung surgery was investigated. 1. Materials and Methods

Penetration of erythromycin into periapical lesions after repeated doses of erythromycin acistrate and erythromycin stearate: A pilot study

In 26 patients who had undergone apicectomy and extirpation of granulomas ( n = 9) or radicular cysts ( n = 17), concentrations of erythromycin, 2′-acetyl erythromycin, and their anhydro forms were determined with a novel chemical method in plasma and periapical lesions after at least 2 days of treatment with erythromycin acistrate (EA) (400 mg three times daily, n = 11) or erythromycin stearate (ES) (500 mg three times daily, n = 15). Oral surgery was performed 2 1 2 to 3 hours after the last dose. Blood samples were collected at the time of operation, and immediately before antibiotic treatment, and 1, 2, and 6 hours after treatment. At all time points EA produced at least twice the total antibiotic (2′-acetyl erythromycin plus erythromycin) concentrations in plasma as ES. Erythromycin levels in plasma were at least as high after EA treatment as after ES. In periapical lesions erythromycin concentration after EA was three times higher (1.34 ± 0.28 μg/gm) than after ES treatment (0.40 ± 0.17 μg/gm). Although the total drug concentration in periapical lesions was about the same after EA (2.64 μg/ml) and ES (3.41 μg/ml), most of the drug recovered after ES was antimicrobially inactive anhydroerythromycin (3.01 μg/gm). The concentration of anhydroerythromycin in plasma was approximately the same as that of erythromycin after ES throughout the dose interval. After EA treatment both plasma and the peripical lesion samples contained hardly detectable amounts of anhydroerythromycin. Hence EA has a good bioavailability essential for treatment and prophylaxis of bacterial infections in dentistry.

Impact of dosage schedule of antibiotics on the treatment of serious infections

Experimental studies suggest that the importance of the antibiotic dosage schedule for therapeutic efficacy in severe infection and when host defences are impaired is related to the class of antibiotic. The efficacy of beta-lactams is mainly dependent on the maintenance of adequate antibiotic concentrations in plasma during the entire treatment interval, and not on high peak concentrations. The efficacy of aminoglycosides is related to the total dose administered, i.e., the area under the concentration-time curve, irrespective of the frequency of administration. This difference in efficacy between beta-lactams and aminoglycosides in relation to the dosage schedule correlate well with differences between both classes of antibiotics in kinetics of antibacterial activity in vitro and in vivo. Another factor relevant in this respect is the post-antibiotic effect (PAE) which means the suppression of bacterial regrowth at the end of the period of exposure to antibiotic.

Altered pharmacokinetics of antibiotics during vascular surgery

Prophylactic antibiotics significantly decrease the incidence of infection in various surgical procedures. Although antibiotics must be administered preoperatively to be effective, it is unknown whether therapeutic concentrations are necessary throughout the operation to prevent infection. Furthermore, the pharmacokinetics of antibiotics during surgical procedures is not well understood. Several factors, including blood loss, fluid redistribution, and changes in renal blood flow may alter the pharmacokinetic disposition of the antibiotic. In a controlled investigation of intraoperative antibiotic pharmacokinetics, cefamandole was studied in eight patients undergoing elective surgery of the abdominal aorta and peripheral vasculature. Both elimination half-life (67 ± 19 minutes versus 93 ± 23 minutes) and the volume of distribution (16.8 ± 5.3 liters versus 25.2 ± 11.9 liters) increased when compared with the preoperative state. The increased volume may be due, in part, to redistribution of fluid. Plasma concentrations of antibiotic were low at the time of graft placement in those patients with normal renal function. Additional antibiotic dosing may be warranted prior to prosthesis insertion in these patients.

Concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms in plasma and tonsillar tissue after repeated dosage of erythromycin stearate and erythromycin acistrate.

The concentrations of erythromycin, 2'-acetylerythromycin (2'-AE) and their anhydro forms in plasma and tonsillar tissue were analyzed after a 3-day repeated-dosage regimen of erythromycin stearate (ES; 500 mg twice a day [b.i.d]) and erythromycin acistrate (EA), a new erythromycin prodrug, at two doses (400 and 500 mg b.i.d.). The tonsils of 40 patients were removed at 112 to 329 min after intake of the last dose. Blood samples were collected at the time of tonsillectomy and at 0, 2, and 6 h after the last dose. At all time points, EA produced severalfold more total antibiotic (erythromycin + 2'-AE) concentrations in plasma compared with ES. There were two nonabsorbers in the ES group, but none in the two EA groups. The mean total antibiotic levels in tonsillar tissue after EA treatment exceeded the levels after treatment with ES by a factor of 3 (for EA at 400 mg b.i.d.) and 4.5 (for EA at 500 mg b.i.d.). The ratios of erythromycin concentration in tonsil to that in plasma at the time of tissue removal were quite similar for all groups (means, 0.51 to 0.54). In the EA groups, 2 of 26 (8%) patients had no measurable erythromycin in the tonsillar tissue samples, whereas in the ES group, 3 of 14 (21%) patients had no measurable erythromycin in the same tissue. The degree of hydrolysis of 2'-AE to erythromycin was about 25% in plasma at the time of tonsillectomy for both EA groups and about 40% in tonsillar tissue. There were negligible amounts of anhydro forms in plasma after EA administration, whereas in the ES group, anhydroerythromycin levels were, from time to time, even higher than erythromycin levels. Very high levels of anhydro forms were detected in tonsillar tissue after ES treatment, whereas only low levels were found after EA administration.

Cefoxitin pharmacokinetics: relation to three different renal clearance studies in patients with various degrees of renal insufficiency.

The pharmacokinetics of cefoxitin were examined in 4 healthy volunteers, 6 patients with normal renal function (inulin clearance, greater than 80 ml/min per 1.73 m2), and 35 patients with various degrees of renal insufficiency (inulin clearance, 80 to less than 5 ml/min per 1.73 m2). A single dose of 30 mg of cefoxitin per kg of body weight was injected intravenously over 3 min. Antibiotic concentrations in plasma were determined by the agar diffusion technique. The cefoxitin half-life increased progressively from 39 min in subjects with normal renal function to 23.5 h in oligoanuric patients. Correspondingly, total body clearance decreased from 340 to 13 ml/min per 1.73 m2. In addition to the study of cefoxitin kinetics, in 29 of the 41 patients, three different renal clearance tests were performed (inulin, p-aminohippurate, and creatinine clearances). Of these, p-aminohippurate clearance showed the best correlation with the elimination rate constant beta as well as total body clearance of cefoxitin; but with respect to beta, the differences between the p-aminohippurate and creatinine clearances were quantitatively negligible. Therefore, even in substances which are eliminated predominantly by active tubular secretion, creatinine clearance could be recommended for dosage adjustments.

Effects of impaired renal function, hemodialysis, and peritoneal dialysis on the pharmacokinetics of mezlocillin

The pharmacokinetics of mezlocillin were examined in 8 patients with normal renal function (inulin clearance, > 80 ml/min per 1.73 m2), 32 patients with moderately reduced renal function (inulin clearances, 80 to 5 ml/min per 1.73 m2), and 12 patients maintained by hemodialysis or peritoneal dialysis because of severely impaired renal function. A single dose of 60 mg of mezlocillin per kg of body weight was infused intravenously over 30 min. Antibiotic concentrations in plasma, urine, and dialysate were determined by the agar diffusion technique. The half-life of mezlocillin increased with decreasing renal function from an average of 53 min in subjects with normal function to 165 min in oligoanuric patients. The urinary recovery of this drug in 24 h decreased from 65% at a glomerular filtration rate of 92 ml/min to 7.6% at a glomerular filtration rate of 6.7 ml/min. Volume of distribution was not changed by the renal insufficiency, amounting on the average to 22.5% of body weight. Intermittent hemodialysis or peritoneal dialysis contributed to only a minor degree to the 24-h mezlocillin kinetics. The pharmacokinetic properties of mezlocillin permit a normal dosage over wide ranges of renal insufficiency; however, when the glomerular filtration rate is below 10 ml/min, the dosage interval should be increased from 8 to 12 h.

The pharmacokinetic studies of cephalothin, cefazolin and cefmetazole in the neonates and the premature babies.

The pharmacokinetic study of antibiotics provides essential information for the rational antibiotic therapy of infections in children and especially in neonates. It is therfore necessary to establish techniques to measure the plasma concentrations of antibiotics, using small volumes. Preliminary studies in rabbits and the further studies in the neonates and in older children showed excellent correlation between the concentration of plasma antibiotics in venous and capillary blood, as measured by High Pressure Liquid Chromatography (HPLC) and by the bioassay. We confirmed that the HPLC is more useful for assays, in neonates and children for the following reasons; the volume of the plasma is less than standard bioassay (50 μl vs 200 μl); less time is required (20 min vs 18-20 hrs) ; the method can detect the metabolites; multiple antibiotics can be assayed simultaneously. Pharmacokinetic studies for cephalothin (CET), cef azolin and cef metazole in neonates (2-21 days) and in older children (9-12 years) using bioassay and HPLC showed that these antibiotics had more prolonged half-lives and delayed urinary excretion in neonates than in older children. Desacetylcephalothin (DACET), the metabolite of CET, was detected in both plasma and urine in neonates as well as in older children. The amount of urinary DACET, however, was larger in neonates than in older children, and the half-life of DACET was longer in neonates than in older children.

Effect of ingesta on systemic availability of chloramphenicol from two oral preparations in cats

On five separate occasions, five adult cats were dosed orally with 100 mg chloramphenicol tablets or chloramphenicol palmitate suspension. Each preparation was given once when the cats were fasted and once when fed ad lib. In addition, fasted cats were given the tablet preparation on one occasion with 10 ml water orally immediately afterwards. Chloramphenicol concentrations were determined at intervals after dosing, and all urine passed in 24 h after dosing was collected for chloramphenicol assay. The initial plasma antibiotic concentrations were lower with chloramphenicol palmitate suspension than with chloramphenicol tablets, and the bioavailability of chloramphenicol from the palmitate ester was especially poor in starved cats. Chloramphenicol palmitate may thus be undesirable for antimicrobial therapy in inappetent cats. Food and fluid did not appear to influence the availability of chloramphenicol from the tablet preparation, although effects on plasma drug concentrations within 1.5 h of dosing would have been missed in this study. A relatively large proportion of an oral dose of chloramphenicol is excreted unchanged in feline urine. Because of the potential toxicity of the drug, chloramphenicol dose rates should be restricted in cats with renal insufficiency or another antibiotic used.

Letter to the Editor

Journal of Small Animal PracticeVolume 20, Issue 3 p. 195-196 Free Access Letter to the Editor R.J. Bywater, R.J. Bywater Beecham Pharmaceuticals Research Division, Walton Oaks, Dorking Road, Tadworth, Surrey.Search for more papers by this authorJ.F. Buswell, J.F. Buswell Beecham Pharmaceuticals Research Division, Walton Oaks, Dorking Road, Tadworth, Surrey.Search for more papers by this authorS. Lay, S. Lay Beecham Pharmaceuticals Research Division, Walton Oaks, Dorking Road, Tadworth, Surrey.Search for more papers by this author R.J. Bywater, R.J. Bywater Beecham Pharmaceuticals Research Division, Walton Oaks, Dorking Road, Tadworth, Surrey.Search for more papers by this authorJ.F. Buswell, J.F. Buswell Beecham Pharmaceuticals Research Division, Walton Oaks, Dorking Road, Tadworth, Surrey.Search for more papers by this authorS. Lay, S. Lay Beecham Pharmaceuticals Research Division, Walton Oaks, Dorking Road, Tadworth, Surrey.Search for more papers by this author First published: March 1979 https://doi.org/10.1111/j.1748-5827.1979.tb07032.xCitations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. REFERENCES Acred, P., Hunter, PA., Mizen, L. & Rolinson. G.N. (1970) α-Amino-P-hydroxybenzylpenicillin (BRL 2333), a new broad spectrum semi-synthetic penicillin: in vivo evaluation. Antimicrobial Agents and Chemotherapy 1, 416. Palmer, G.H., Buswell, J.F., Dowrick, J.S. & Yeoman, G.H. (1976) Amoxycillin, a new veterinary penicillin. Vet. Rec. 99, 84. Siwak, A.D. (1978) The influence of the time of treatment in relation to feeding on the efficacy of amoxycillin therapy in dogs and cats. 54, 342. Watson, A.D.J. & Egerton, J.R. (1977) Effect of feeding on plasma antibiotic concentrations in greyhounds given ampicillin and amoxycillin by mouth. J. small Anim. Prac., 18, 779. Citing Literature Volume20, Issue3March 1979Pages 195-196 ReferencesRelatedInformation

Comparison of Cephalothin and Cefamandole Prophylaxis During Insertion of Prosthetic Heart Valves

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 mug/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (P<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.

Effect of feeding on plasma antibiotic concentrations in greyhounds given ampicillin and amoxycillin by mouth.

ABSTRACTIn a cross‐over study, six Greyhounds were dosed by mouth with ampicillin and amoxycillin at 20 mg/kg, using three different feeding regimens (no food, canned food prior to dosing, and dry food ad lib) with each drug. Antibiotic levels in plasma were determined by microbiological assay at intervals after dosing.Plasma ampicillin concentrations tended to be lower in fed than in starved Greyhounds, but amoxycillin levels were relatively unaffected by feeding. In starved Greyhounds, ampicillin gave higher early levels than amoxycillin.

Evaluation of a micromethod for determination of antibiotic concentrations in plasma.

The various steps of a paper disc micromethod for quantitative determination of plasma concentrations of antibiotics is described. Only 10 µl of plasma is needed for a single determination, allowing easy and repeated capillary sampling. Separate assay was attempted of three antibiotics in a mixture (streptomycin, cloxacillin and ampicillin), both by use of selective inhibitors (semicarbazide, penicillinase) in the culture medium and by choosing suitable strains of bacteria. In this way, it was possible to determine streptomycin and cloxacillin separately when all three antibiotics were present simultaneously in the plasma. The assay of ampicillin, however, was always influenced by the presence of even small concentrations of cloxacillin. The 95% confidence intervals of the standard curves for the three antibiotics are presented. — The method is suitable both for pharmacokinetic studies and for routine clinical control of plasma antibiotic levels, even in premature children.

A comparison of antibiotic concentrations in plasma and muscle

Plasma and muscle levels of various antibiotics were compared at hourly intervals after administration in rabbits. The levels of aureomycin, chloramphenicol and terramycin in muscle were found to be approximately two-thirds of the plasma levels. The penicillin levels in muscle were less than one-third of the plasma levels.