Optimal teicoplanin loading regimen to rapidly achieve target trough plasma concentration in critically ill patients

Abstract

Teicoplanin is used for the treatment of Methicillin‐resistant Staphylococcus aureus infection. It has been demonstrated that conventional loading regimen was insufficient for teicoplanin to achieve target trough plasma concentration (Cmin > 10 mg/L). Therefore, a Chinese expert group recommended an optimal loading dose regimen of teicoplanin to treat severe Gram‐positive infection. However, there was no report about the teicoplanin concentration, and the safety and efficacy of teicoplanin therapy in Chinese patients since the consensus was published. The objective of this study was to compare the teicoplanin Cmin and clinical response in critically ill Chinese patients after the administration of conventional or optimal loading regimen, and to reveal the potential factors that may affect teicoplanin Cmin in addition to loading regimen. Fifty‐five patients were retrospectively divided into two groups based on teicoplanin loading regimen: (a) CD group (conventional loading dose group, n = 18, loading dose was 400 mg); (b) OD group (optimal loading dose group, n = 37, loading dose was 800 mg). Initially, three loading doses were administered every 12 hours, while the fourth loading dose was injected 24 hours after the third dose. The maintenance dose was 400 mg (CD group) or 800 mg (OD group), respectively. The mean teicoplanin Cmin on day 2 and day 4 in the OD group was significantly higher than those in the CD group, which were 14.75 ± 5.93 mg/L vs 8.26 ± 4.87 mg/L (P < .001) and 14.90 ± 5.20 mg/L vs 9.13 ± 4.75 mg/L (P = .019), respectively. The percentages of patients in the OD group achieving the target teicoplanin Cmin on day 2 and day 4 were also significantly higher than those in the CD group, which were 83.7% vs 33.3% (P < .001) and 82.4% vs 28.6% (P = .0013), respectively. Furthermore, multivariate linear regression analysis showed that body‐weight exerted significant effect on teicoplanin Cmin in the OD group. The percentage of favourable clinical response in the OD group was significantly higher than that in the CD group (83.8% vs 55.6%, P = .025). There was no difference between teicoplanin adverse effects in the two groups. The study demonstrated that the optimal loading dose regimen of teicoplanin can rapidly reach target Cmin, and result in a good clinical efficacy and low adverse effect in critically ill Chinese patients.

Voriconazole therapeutic drug monitoring in critically ill patients improves efficacy and safety of antifungal therapy

“…Critically ill patients often received multiple extracorporeal support therapy, including CRRT and extracorporeal membrane oxygenation (ECMO), which may change the pharmacokinetic characteristics of voriconazole and affect the VPC. 32,33 We have listed the main research results about the pharmacokinetic parameters of voriconazole in critically ill patients with extracorporeal support therapy in Table S3. 18,[34][35][36][37][38][39] Most of these studies agreed with our results that CRRT did not exert an effect on VPC, and there was no need to adjust voriconazole dosage during CRRT.…”

“…This finding may be caused by the inconsistent CRRT protocol and the high rate of utilization of CRRT (34.4%) in our study, and almost half of the patients in the TDM group were treated by CRRT. Critically ill patients often received multiple extracorporeal support therapy, including CRRT and extracorporeal membrane oxygenation (ECMO), which may change the pharmacokinetic characteristics of voriconazole and affect the VPC 32,33 . We have listed the main research results about the pharmacokinetic parameters of voriconazole in critically ill patients with extracorporeal support therapy in Table S3 18,34‐39 .…”

Optimal Teicoplanin Dosage Regimens in Critically Ill Patients: Population Pharmacokinetics and Dosing Simulations Based on Renal Function and Infection Type

“… 4 , 5 The loading dose of teicoplanin during the first few days of treatment was necessary to attain target trough concentration (C min ) and optimal loading dose was associated with higher cure rate. 6 , 7 At the same time, maintenance dose should not be overlooked. 8 The standard dose [loading dose of 400 mg (6 mg/kg) every 12 hours for the first three doses followed by maintenance dose of 400 mg once daily (400mg q12h×3, 400mg qd)] was used to keep C min ≥ 10 mg/L for the treatment of most infections caused by Gram-positive bacteria such as skin and soft tissue infection, pneumonia, intra-abdominal infection and urinary tract infection.…”

Teicoplanin versus β-lactam for febrile patients with Staphylococcus-like bacteremia: focus on methicillin-susceptible Staphylococcus aureus bacteremia

“…Variations in the source of MSSA bacteremia and the small number of patients with endocarditis precludes us from making comparisons the outcomes of endocarditis with those of other more common sources of MSSA bacteremia. We did not analyze serum teicoplanin levels in the present study and all patients received teicoplanin treatment with a maintenance dose of 6 mg/kg every 12 h but they did not receive higher loading dosage (12 mg/kg every 12 h), which was suggested in the recent studies to rapidly achieve target trough plasma concentration in critically ill patients [ 36 , 37 ]. However, our previous experience has shown that this maintenance dosage will produce favorable outcomes in patients with MRSA bacteremia irrespective of the teicoplanin MIC [ 32 ].…”