Pharmacokinetics of Teicoplanin in An ICU Population of Children and Infants (original) (raw)
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International Journal of Antimicrobial Agents, 2008
The optimum teicoplanin loading dose and duration of therapy required for rapid attainment of a therapeutic trough plasma concentration (C min ) (≥10 mg/L for serious Gram-positive infections and ≥20 mg/L for deep-seated infections) are not known. In this open-label, multicentre, observational study, teicoplanin levels were determined following administration of loading doses of 6 mg/kg every 12 h on Day 1 followed by 6 mg/kg once or twice daily to hospitalised patients with suspected or diagnosed Gram-positive infections. C min levels for the first 4 days of treatment were collected 15 min prior to drug administration. Levels were determined with an Abbott TDx ® /FLx ® Analyzer and Seradyn Teicoplanin Innofluor Assay Kit. The two target trough values (≥10 mg/L and ≥20 mg/L) were only achieved by Day 4 in the once-daily group (n = 34; mean 9.55 mg/L, 95% confidence interval (CI) 8.17-10.94 mg/L) and in the twice-daily group (n = 40; mean 21.8 mg/L, 95% CI 17.21-26.39 mg/L), respectively. However, the mean C min in the twice-daily group was ≥10 mg/L (11.03 mg/L) by Day 2. To achieve rapid therapeutic C min concentrations targeted for the majority of serious Gram-positive infections, we recommend teicoplanin loading doses of 6 mg/kg every 12 h for 48 h followed by once-daily for infections other than infective endocarditis, septic arthritis and osteomyelitis. Regarding the latter infections, higher loading doses might be warranted to reach rapid steady-state concentrations.
Age- and gender-related differences in teicoplanin levels in paediatric patients
Journal of Antimicrobial Chemotherapy, 2013
Teicoplanin is a glycopeptide antibiotic active against Gram-positive bacteria, including methicillinresistant staphylococci. While teicoplanin trough levels (TTLs) .10 mg/L are commonly considered appropriate, levels .20 mg/L are aimed for in the treatment of severe infections. Due to toxicity, it is recommended to avoid levels .60 mg/L. Patients and methods: In our institution, the initial dosing schedule of teicoplanin (10-15 mg/kg every 12 h for three loading doses and every 24 h thereafter) is adapted according to TTLs analysed by a fluorescence polarization immunoassay on treatment days 2 to 4. Teicoplanin peak levels (TPLs) are analysed in selected cases 30 min after the end of infusion. In a retrospective analysis we evaluated 1357 TTLs and 333 TPLs from 410 treatment episodes from 2005 to 2011. Results: Initial TTLs were ,10 mg/L in 14.1% and ,20 mg/L in 72.6% of episodes. Toddlers had significantly lower TTLs, with a 2-fold and 2.5-fold increased risk of having levels ,10 mg/L (24.6%) and ,20 mg/L (82.6%), respectively. For the entire cohort, follow-up TTLs were less likely to be ,10 mg/L and more likely to be .20 mg/L when compared with initial TTLs (P,0.001, each). Adolescent girls had significantly higher initial TPLs (P ¼0.001) and significantly higher follow-up TTLs (P¼ 0.016) than adolescent boys. In parallel, adolescent girls had initial TPLs .60 mg/L significantly more frequently (P ¼ 0.012) and follow-up TTLs ,10 mg/L significantly less frequently (P ¼0.005). Conclusions: More tailored dosing regimens with higher loading doses, especially for toddlers, should be considered. While further pharmacokinetic data in paediatric patients are pending, therapeutic drug monitoring is mandatory.
Data obtained as part of our routine drug monitoring of teicoplanin therapy (therapeutic drug monitoring, TDM) in adult critically ill patients being treated for suspected or documented Grampositive multiresistant infections were assessed, retrospectively. Data were available for 202 patients (146 male, 56 female; age 58 ± 16 years) with a total number of 829 teicoplanin trough plasma levels (C min ) assessed. The percentage of patients with adequate teicoplanin concentrations (C min ≥ 10 mg/L) during the treatment period substantially increased from 3.2% on day 2, to 35%, 70%, 90% and ∼95% on days 4, 7, 11 and 15, respectively. The findings suggest that optimal teicoplanin therapy was achieved only after at least 4, and probably 7, days of therapy in most cases, mainly because of a failure to use an appropriate loading dose. Among the possible causes for the reluctance to use a loading dose, concern over the potential nephrotoxicity of teicoplanin was a major factor. We conclude that loading doses of teicoplanin (6 mg/kg every 12 h for at least three doses) must be considered mandatory in all patients, regardless of their renal function, to enable optimal drug concentrations to be achieved early in the treatment period. Subsequently, TDM is important to ensure that dose regimens are optimized to the individual requirements of the patients.
Critical Care, 2008
all 10 cities including the rural areas of the province of Kerman. All data were finally analyzed by SPSS software (version 11.5). Results On the basis of recorded statistical analysis, the mortality cases of human rabies in the province of Kerman during one decade was 10 persons (eight males and two females). One-half of them (50%) were bitten by dogs and the others (50%) by foxes. Among the reported deaths, 40% were from Kahnooj county (Jiroft region). The reported data indicated that 21,546 persons were bitten by animals during 10 years in the province of Kerman. The mean of age of the people who were bitten by dogs was 24.80 years (SD = ±14.6), while the mean age of the people who were bitten by foxes was 57.25 years (SD = ±1.50). There was a significant difference between the mean age of these two groups of the people (P < 0.05). The most frequent rate of injured people was reported in the age group 10-19 years old and the frequency rate of males (76.00%) was more than females (24.00%). Therefore, there was a statistically significant difference between males and females in this study (P < 0.01). About 60% of all persons that were bitten by animals were from rural areas and 40% of them were from urban areas (P < 0.05). Among the people who were bitten and injured by animals during one decade in the province of Kerman, 85.70% of them were not treated by the rabies prophylaxis treatment regimen. Among all of them who were bitten by animals, 50% were injured through hands and feet, 40%
Pharmacokinetics of teicoplanin in critically ill patients with various degrees of renal impairment
Antimicrobial Agents and Chemotherapy, 1987
The pharmacokinetics of teicoplanin were studied in 15 adult patients in the acute phase of severe infections caused by gram-positive cocci. All the subjects were given a daily intravenous bolus dose of 6 mg of teicoplanin kg-l (body weight). The pharmacokinetic study was performed over a 48-h period after injection 4. The subjects were categorized according to their mean creatinine clearances (ml min-1 kg-') during the study period: group 1 (n = 3), >1.6; group 2 (n = 6), 0.8 to 1.6; and group 3 (n = 6), 0.15 to 0.8. Mean concentrations of teicoplanin in serum at 1, 24, and 48 h were 33 8, 9 + 3, and 6 2.5 ,ug ml-l, respectively. The mean half-lives of the concentration-time curve from 12 to 48 h were 28 4, 44 ± 24, and 48 ± 14 h in groups 1, 2, and 3, respectively (group 3 versus group 1: P < 0.05). The mean area under the serum concentration-time curve from time zero to 24 h was 344 ± 92 mg. h-liter-', and the mean hybrid volume of distribution was 1.09 ± 0.46 liter. kg-'. These values were similar for the three groups, with a trend for larger areas under the curve in group 3. Creatinine clearance correlated directly with the total body clearance of teicoplanin (r = 0.70) and with the renal clearance of teicoplanin (r = 0.82). However, in critically ill patients, the wide interindividual variations in pharmacokinetic parameters are more relevant than those related to the variations in renal function when creatinine clearance is above 0.30 ml min-' kg-'. We concluded that, in such conditions, monitoring of concentrations of teicoplanin in serum is mandatory.
Antimicrobial Agents and Chemotherapy, 2020
Objective: Serum cystatin C (CysC) has recently been proposed as an alternative marker to serum creatinine (SCR) for estimating renal clearance. In the present study, we performed a population pharmacokinetic analysis of teicoplanin (TEIC), which is mainly eliminated through the kidneys, using CysC as a predictor for renal clearance. Methods: Thirty-six patients with MRSA infections who were administrated to the National Hospital Organization Beppu Medical Center between January 2012 and December 2013 were enrolled and gave 123 sets of blood TEIC concentration data. Renal clearance was estimated by the Hoek equation using CysC, by creatinine clearance predicted by the Cockcroft-Gault equation using SCR, or directly by CysC. One compartment open model with inter-individual variabilities for renal clearance and the volume of distribution as well as an additional residual error model was used to estimate population pharmacokinetic parameters for TEIC. Results: The model with the best predictability was that with CysC as a predictor for renal clearance; it showed better significance than the models using estimated the glomerular filtration rate by the Hoek equation or CLcr. The final model was as follows: CL (L/hr) ¼ 0.510 Â (CysC/1.4) À0.68 Â Total body weight/ 60 0.81 , omega (CL) ¼ 19.8% CV, VC (L) ¼ 78.1, omega (V) ¼ 42.7% CV. Conclusion: The present results show the usefulness of CysC to more accurately predict the pharmacokinetics of drugs mainly eliminated through the kidneys, such as TEIC. However, since the sample size in this study was relatively small, further investigations on renal clearance predictability using CysC are needed.
Intensive Care Medicine, 2003
Objective: To compare the pharmacokinetic parameters of sequential intravenous and subcutaneous teicoplanin in the plasma of surgical intensive care unit patients. Design and setting: Prospective, randomized, crossover study in the surgical ICU of a university hospital. Patients: Twelve patients with a suspected nosocomial infection, a serum albumin level higher than 10 g/l, body mass index less than 28 kg/m 2 , and estimated creatinine clearance higher than 70 ml/min. Interventions: Teicoplanin was first administered intravenously as a loading dose of 6 mg/kg per 12 h for 48 h and then continued at a daily dose of 6 mg/kg. On the fourth day patients were randomized in two groups according to the order of the pharmacokinetic studies. Measurements and results: Serial plasma samples were obtained to measure teicoplanin levels. Compared with a 30-min intravenous infusion the peak concentration of teicoplanin after a 30-min subcutaneous administration occurred later (median 7 h, range 5-18) and was lower (16 µg/ml, 9-31; vs. 73, 53-106). Despite large and unpredictable interindividual differences no significant differences between subcutaneous and intravenous administration were observed in: trough antibiotic concentrations (10 µg/ml, 6-24; vs. 9, 5-30), the area under the teicoplanin plasma concentration vs. time curves from 0 to 24 h (AUC 0-24h ; 309 µg/ml per minute, 180-640; vs. 369, 171-955), the proportion of the dosing interval during which the plasma teicoplanin concentration exceeded 10 µg/ml (96%, 0-100%; vs. 79%, 13-100%), and the ratio of AUC 0-24h to 10 (77, 45-160; vs. 92, 43-239). Conclusions: In critically ill patients without vasopressors a switch to the subcutaneous teicoplanin after an initial intravenous therapy seems to give comparable pharmacodynamic indexes of therapeutic success.
Renal Tolerability of Teicoplanin in a Case of Neonatal Overdose
Journal of Chemotherapy, 1998
The literature does not contain reports regarding teicoplanin overdose in newborns. In a neonate with a history of recent postasphyctic acute renal failure which recovered within 7 days of life, antibiotic therapy with teicoplanin was started for sepsis due to Staphylococcus hominis. However, for 5 days the dosage was excessive (20 mg/kg twice daily instead of an initial dose of 16 mg/kg and then doses of 8 mg/kg once daily). Once this error had been noted, therapy was immediately suspended. Clinically the newborn had improved and blood culture at the end of the therapy was negative. Biohumoral tests revealed constantly normal levels of serum creatinine, serum cystatin C and blood nitrogen. Urinary parameters of tubulotoxicity were also within normal values. Urinary epidermal growth factor was increased. Teicoplanin was well tolerated at the renal level in the newborn even in this case of excessive dosage.
Pharmacokinetic Profile of Two Different Administration Schemes of Teicoplanin
Clinical Drug Investigation, 1999
Objective: To evaluate the pharmacokinetic appropriateness of a possible switch in dosing schedule for outpatients after hospital discharge, i.e. the bioequivalence of a single 400mg intravenous daily dose versus double-refracted 200mg intramuscular doses. Subjects and Methods: This study was conducted in 10 normal healthy volunteers using a two-way randomised, open-label, two-period crossover design. Each subject received two different drug regimens of teicoplanin: a single 400mg intravenous daily dose versus double daily refracted 200mg intramuscular doses. Teicoplanin serum concentrations were analysed by means of a fluorescence polarisation immunoassay system in samples collected for up to 72 hours after each regimen. Pharmacokinetic evaluations were performed by means of a 3compartment open model with first-order elimination using the WinNonlin pharmacokinetic software package. Results: Teicoplanin peak serum concentrations were 97.96 ± 23.49 mg/L, 3.47 ± 1.00 mg/L and 6.99 ± 1.52 mg/L after a single 400mg intravenous dose, and after the first and second intramuscular administrations, respectively. The trough level at 24 hours (C24)was 4.55 ± 1.04 mg/L after the 400mg intravenous dose, and 6.67 ± 1.75 mg/L after double 200mg intramuscular doses. The ratio between C24 intramuscular and intravenous treatment was 1.46 ± 0.17. Total body exposure (AUC0-∞) was 474.22 ± 111.77 mg/L • h post-intravenous dose, and 424.84 ± 113.53 mg/L • h post-intramuscular doses. Intramuscular bioavailability suggested substantial bioequivalence with intravenous administration (89.58 ± 14.35%). Dose-normalised data indicated that the intersubject variability was mainly related to interindividual differences in bodyweight. Conclusion: These findings indicated that a total daily dosage of teicoplanin 400mg administered in two refracted doses by the intramuscular route could produce steady-state trough levels that are even higher than those achievable after once-daily intravenous administration during maintenance treatment. Since the time during which the serum concentration persists above MIC is actually thought to be a possible major determinant for the outcome of treatment with glycopeptides, this intramuscular schedule could enhance the pharmacokinetic exposure CLINICAL PHARMACOKINETICS
International Journal of Antimicrobial Agents, 2014
The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (= 0.79, P = 0.0021) and trough (= 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.