Antibiotic Levels in the Human Serum, Pericardial Fluid and Heart Tissues

Kišš, Ján; Faragó, E; Békássy, S; Gömöry, Ágnes

doi:10.1007/978-3-642-68172-1_59

Cited by 5 publications

(6 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Serum samples taken at the beginning (a mean of 90 min) and the end (a mean of 148 min) of bypass surgery revealed mean concentrations of 10.9 ± 0.5 and 9.5 ± 0.2 ,ug/ml after a dose of 6 mg/kg and 44.6 _ 1.5 and 23.4 ± 0.6 ,ug/ml after a dose of 12 mg/kg, respectively. Teicoplanin could still be detected in serum 8,16,24, and 48 h after administration of both dosages; and levels at those times were 4.8 ± 0.1 and 9.6 + 0.2, 3.7 ± 0.1 and 6.6 ± 0.1, 2.8 ± 0.1 and 5.5 ± 0.1, and 1.5 ± 0.1 and 3.4 ± 0.1 ,ug/ml for the 6-and 12-mg/kg doses, respectively. Tables 1 and 2 summarize the data for the concentration of teicoplanin in atrial appendages and in serum samples taken from the 32 patients who received the 6-mg/kg dose and the 17 patients who were given the 12-mg/kg dose.…”

Section: Resultsmentioning

confidence: 99%

Concentrations of teicoplanin in serum and atrial appendages of patients undergoing cardiac surgery

Bergeron

Saginur

Desaulniers

et al. 1990

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The concentrations of teicoplanin in sera and heart tissues of 49 patients undergoing coronary bypass were measured. Each patient received a 6-or 12-mg/kg dose of teicoplanin administered in a slow intravenous bolus injection over 3 to 5 min beginning at the time of induction of anesthesia. Mean ± standard error of the mean concentrations in serum were, for the two doses, respectively, 58.1 ± 1.7 and 123.3 ± 7.4 ,g/ml 5 min after administration and 22.2 ± 0.7 and 56.5 ± 2.8 pg/mi at the time of removal of atrial appendages. Mean ± standard error of the mean concentrations in tissue were 70.6 ± 1.7 and 139.8 ± 2.2 ,g/g, respectively, giving mean tissue/serum ratios of 3.7 ± 0.3 and 2.8 ± 0.2, respectively. Teicoplanin penetrates heart tissue readily and reaches levels in the serum far in excess of the MICs for most pathogens that have been found to cause infections following open heart surgery.The incidence of infection following cardiac surgery caused by multiresistant Staphylococcus aureus, Staphylococcus epidermidis, and group JK diphtheroids is increasing (12,15,16). Thus far, vancomycin has been a valid alternative to standard antibiotic prophylaxis; but complications may occur if it is administered by rapid injection, and major side effects have restricted its use. Teicoplanin, a new glycopeptide antibiotic that is chemically related to the vancomycin-ristocetin group, has in vitro activity similar to that of vancomycin and seems to be less toxic (4, 7, 10, , abstr. no. 597, 1989). Moreover, its pharmacokinetic properties allow for single-daily-dose therapy (5, 6). If used as a prophylactic agent in cardiac surgery, it might be a practical alternative to standard antibiotics, including cefazolin, cefamandole, semisynthetic penicillins given alone or in combination with aminoglycosides, or vancomycin, which is occasionally used when methicillin-resistant staphylococcal contamination is a concern. In the present study, we evaluated the penetration of teicoplanin into the heart tissues of patients undergoing cardiopulmonary bypass surgery. MATERIALS AND METHODSA total of 32 patients (16 from Quebec, Quebec, Canada, and 16 from Ottawa, Ontario, Canada) who were about to undergo cardiopulmonary bypass surgery were studied initially. They all gave written informed consent to take part in the study. They received a 6-mg/kg dose of teicoplanin administered in a slow bolus injection over 3 to 5 min through a peripheral vein beginning at the time of induction of anesthesia. Following this initial study, a second group of 17 patients operated on in Quebec City were studied and were given a 12-mg/kg dose that was administered in a similar fashion. All the assays and analysis of data were done * Corresponding author.at the Infectious Disease Research Laboratory, Centre Hospitalier de l'Universitd Laval, Quebec City. The group that received the 6-mg/kg dose was composed of 24 males and 8 females, and the group that received the 12-mg/kg dose was composed of 16 males and 1 female. The ages of the two groups of patient...

show abstract

Section: Resultsmentioning

confidence: 99%

Concentrations of teicoplanin in serum and atrial appendages of patients undergoing cardiac surgery

Bergeron

Saginur

Desaulniers

et al. 1990

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…Although there are no reported data for cloxacillin levels in the heart, Kiss et al (13), using another isoxazolyl penicillin, flucloxacillin, at a dose of 500 mg intramuscularly could detect low concentrations of antibiotic in cardiac tissue. The concentrations varied from 2.3 to 3.5 ,ug/g in the auricle and from 1.1 to 2.5 ,ug/g in the mitral valve.…”

Section: Discussionmentioning

confidence: 99%

Concentrations of fusidic acid, cloxacillin, and cefamandole in sera and atrial appendages of patients undergoing cardiac surgery

Bergeron¹,

Desaulniers²,

Lessard³

et al. 1985

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The concentrations of cefamandole, cloxaciDin and fusicid acid were measured in the serum and heart tissue of 100 recipients of these drugs before cardiac surgery. During cardiopulmonary bypass, mean (± standard deviation) peak concentrations in serum of all patients were 63.0 ± 34.0 Lg of cefamandole per ml, 30.8 17.7 ,ug of cloxacillin per ml, and 32.4 ± 10.8 Fg of fusidic acid per ml. Mean (± standard deviation) concentrations in atrial appendages taken 1 h (±15 mi) after infusion were 21.3 ±11.0 ,ug of cefamandole per g, 23.8 ± 17.3 ,ug of cloxaciDin per g, and 10.7 ± 4.2 ,ug of fusidic acid per g. No cloxacillin coild be detected in 5 of 39 heart specimens. Mean tissue-to-serum ratios at 1 h for cefamandole, cloxacillin, and fusidic acid were respectively 0.35, 0.73, and 0.33. Fusidic acid, a drug which is highly effective in vitro against both methicillin-resistant Staphylococcus aureus and .taphylococcus epidermidis, was detectable in heart tissue in concentrations which were 12 times higher than the MICs of this agent against these resistant microorganisms.There are several published reports on the penetration of cefamandole in human heart but none on either cloxacillin, a drug which in several countries of the world is used as a prophylactic agent in cardiac surgery (3, 9), or fusidic acid, an agent of some promise because of activity in vitro against both methicillin-resistant and -susceptible Staphylococcus aureus and Staphylococcus epidermidis (4,20). The increasing incidence of severe infection due to those latter microorganisms (9,12,15) has stimulated us to compare the penetration of these three antibiotics in human heart. MATERIALS AND METHODSPatients. A total of 100 patients (69 males and 31 females) about to undergo cardiac surgery were admitted into this study. They ranged in age from 21 to 84 years old (mean, 55 years). Men constituted 65% and 55% of the cefamandoleand cloxacillin-treated groups, respectively. They accounted for 90o of the fusidic acid group. Surgeries consisted of coronory bypass (CPB) (66%) and valve replacement (32%) for the cefamandole and cloxacillin groups and CPB for the fusidic acid group. Duration of surgery varied from 3 to 5 h. Extracorporeal circulation lasted 1 to 3 h. Drug administration. Cefamandole (Eli Lilly, Canada) was administered to 37 patients, and cloxacillin (Ayerst, Canada) was administered to 34 patients. At induction of anesthesia, both drugs were infused intravenously (i.v.) at a dose of 1 g over 5 min. Fusidate diethanolamine (Leo Laboratories, Canada) was administered to 29 patients i.v. at a dose of 580 mg over 2 h before surgery. After the first dose, cefamandole and cloxacillin were continued every 4 h for 24 h, and fusidic acid was continued every 8 h. Each patient received a total of six injections of either drug.Sample collection. Blood samples were collected 1, 2, 3, and 4 h after administration of either cefamandole, cloxacillin, or fusidate diethanolamine. Additional samples were collected at 5, 6, and 8 h from patients receiving fusi...

show abstract

“…Antimicrobials were evaluated in separate mixed/competition C. difficile studies alongside controls in which NTCD-E4 or RT027 were singly inoculated, with dosing regimens following standard clinical dosing (frequency and duration) at gut-reflective antimicrobial concentrations. Concentrations of antimicrobials were DA, clindamycin 33.9 mg/L 6-hourly; CFX, cefotaxime 20 mg/L 12-hourly; CIP, ciprofloxacin 139 mg/L 12-hourly, AMP, ampicillin 8 mg/L 8-hourly [ 32 , 33 , 34 , 35 ]. Antimicrobial agents were evaluated over a 7-day instillation period ( Figure 1 ).…”

Section: Methodsmentioning

confidence: 99%

“…* Antimicrobial agents were evaluated individually over 7 days in competition C. difficile studies (gut models pre-inoculated with NTCD-E4) alongside controls of singly inoculated NTCD-E4 and RT027, with dosing regimens following standard clinical dosing (frequency and duration) at gut-reflective antimicrobial concentrations. DA, clindamycin 33.9 mg/L 6-hourly; CFX, cefotaxime 20 mg/L 12-hourly; CIP, ciprofloxacin 139 mg/L 12-hourly, AMP, ampicillin 8 mg/L 8-hourly [ 32 , 33 , 34 , 35 ]. ** CIP experiment was terminated after 56 days.…”

Section: Figurementioning

confidence: 99%

Non-Toxigenic Clostridioides difficile Strain E4 (NTCD-E4) Prevents Establishment of Primary C. difficile Infection by Epidemic PCR Ribotype 027 in an In Vitro Human Gut Model

et al. 2023

View full text Add to dashboard Cite

Clostridioides difficile infection (CDI) remains a significant healthcare burden. Non-toxigenic C. difficile (NTCD) strains have shown a benefit in preventing porcine enteritis and in human recurrent CDI. In this study, we evaluated the efficacy of metronidazole-resistant NTCD-E4 in preventing CDI facilitated by a range of antimicrobials in an in vitro human gut model. NTCD-E4 spores (at a dose of 107) were instilled 7 days before a clinical ribotype (RT) 027 (at the same dose) strain (210). In separate experiments, four different antimicrobials were used to perturb gut microbiotas; bacterial populations and cytotoxin production were determined using viable counting and Vero cell cytotoxicity, respectively. RT027 and NTCD-E4 proliferated in the in vitro model when inoculated singly, with RT027 demonstrating high-level cytotoxin (3-5-log10-relative units) production. In experiments where the gut model was pre-inoculated with NTCD-E4, RT027 was remained quiescent and failed to produce cytotoxins. NTCD-E4 showed mutations in hsmA and a gene homologous to CD196-1331, previously linked to medium-dependent metronidazole resistance, but lacked other metronidazole resistance determinants. This study showed that RT027 was unable to elicit simulated infection in the presence of NTCD-E4 following stimulation by four different antimicrobials. These data complement animal and clinical studies in suggesting NTCD offer prophylactic potential in the management of human CDI.

show abstract

Antibiotic Levels in the Human Serum, Pericardial Fluid and Heart Tissues

Cited by 5 publications

References 4 publications

Concentrations of teicoplanin in serum and atrial appendages of patients undergoing cardiac surgery

Concentrations of teicoplanin in serum and atrial appendages of patients undergoing cardiac surgery

Concentrations of fusidic acid, cloxacillin, and cefamandole in sera and atrial appendages of patients undergoing cardiac surgery

Non-Toxigenic Clostridioides difficile Strain E4 (NTCD-E4) Prevents Establishment of Primary C. difficile Infection by Epidemic PCR Ribotype 027 in an In Vitro Human Gut Model

Contact Info

Product

Resources

About