ABSTRACT
Title
Therapeutic drug monitoring (TDM)-guided therapy in three-times weekly teicoplanin treatment for chronic infections
Authors
PG. Cojutti1, F. Pea1, B. Del Pin2, B. Cadeo2, M. Furlanut1
1 Institute of Clinical Pharmacology and Toxicology, Dpt. of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy
2 Clinic of Infectious Diseases, Dpt. of Medical and Morphological Research, Medical School, University of Udine, Udine, Italy
1 Institute of Clinical Pharmacology and Toxicology, Dpt. of Experimental and Clinical Pathology and Medicine, Medical School, University of Udine, Udine, Italy
2 Clinic of Infectious Diseases, Dpt. of Medical and Morphological Research, Medical School, University of Udine, Udine, Italy
Abstract
Introduction: The long elimination half-life of teicoplanin enables a three-times weekly dosing administration as outpatient parenteral antibiotic therapy (OPAT), a useful approach in the treatment of chronic infections requiring a lengthy antimicrobial course.
The aim of this study is to investigate the feasibility, tolerability and the pharmacodynamic target attainment of this drug administration schedule.
Methods: After a period of daily dosing with teicoplanin, patients were arranged to receive their dose on Mondays, Wednesdays and Fridays, according to a thrice-weekly dosing regimen. Teicoplanin trough concentrations (Cmin) determined in the context of a therapeutic drug monitoring (TDM) programme along with liver, renal and haematological parameters were measured each Monday morning and doses consequently adjusted to maintain Cmin between 20 and 30 mg/L.
Results: 46 patients were enrolled in this study: 27 prosthetic joint infections, 7 osteomyelitis, 5 skin structure infections, 4 spondylodiscitis, 2 arthritis, 1 endocarditis. There were 29 males and 17 females, with median age of 68 years, weight of 80 kg and estimated creatinine clearance (CLCr) at baseline of 87.9 mL/min. Teicoplanin was administered empirically in 31 patients, for methicillin-resistant coagulase-negative staphylococci (MR-CNS) in 11 patients, for methicillin-resistant Staphylococcus aureus (MRSA) in 2 patients, for Enterococcus sp. in 2 patients.
During the three-times weekly administration a total of 568 teicoplanin Cmin were analysed, with a median per patient determinations of 12 (range: 4-27). The median drug dose was 12.57 mg/kg (range:1.75-37.74) on Mondays and Wednesdays and 19.05 mg/kg (range:1.75-52.83) on Fridays. 9%, 71% and 20% of observed Cmin resulted <20 mg/dL, between 20-30 mg/dL and >30 mg/dL respectively. The median number of changes in dose during therapy was 2 (range: 0-9). The median duration of treatment was 94 days (range 31-259).
As far as adverse effects are concerned, a reduction of more than 30% from baseline in platelet count and estimated CLCr was observed in 36% (only in 3 cases platelets halved) and 8.6% of patients respectively, but in none of these cases did it cause discontinuation of treatment.
Cure was obtained in 40 subjects (91%), improvement and no change in 2 cases each (4% each), failure in 1 case; 1 patient dead for other reasons.
Conclusions: Three-times weekly teicoplanin administration coupled with a regular therapeutic drug monitoring support seems a valuable pharmacological strategy in order to both guarantee a high likelihood of target attainment and a good safety profile.
The aim of this study is to investigate the feasibility, tolerability and the pharmacodynamic target attainment of this drug administration schedule.
Methods: After a period of daily dosing with teicoplanin, patients were arranged to receive their dose on Mondays, Wednesdays and Fridays, according to a thrice-weekly dosing regimen. Teicoplanin trough concentrations (Cmin) determined in the context of a therapeutic drug monitoring (TDM) programme along with liver, renal and haematological parameters were measured each Monday morning and doses consequently adjusted to maintain Cmin between 20 and 30 mg/L.
Results: 46 patients were enrolled in this study: 27 prosthetic joint infections, 7 osteomyelitis, 5 skin structure infections, 4 spondylodiscitis, 2 arthritis, 1 endocarditis. There were 29 males and 17 females, with median age of 68 years, weight of 80 kg and estimated creatinine clearance (CLCr) at baseline of 87.9 mL/min. Teicoplanin was administered empirically in 31 patients, for methicillin-resistant coagulase-negative staphylococci (MR-CNS) in 11 patients, for methicillin-resistant Staphylococcus aureus (MRSA) in 2 patients, for Enterococcus sp. in 2 patients.
During the three-times weekly administration a total of 568 teicoplanin Cmin were analysed, with a median per patient determinations of 12 (range: 4-27). The median drug dose was 12.57 mg/kg (range:1.75-37.74) on Mondays and Wednesdays and 19.05 mg/kg (range:1.75-52.83) on Fridays. 9%, 71% and 20% of observed Cmin resulted <20 mg/dL, between 20-30 mg/dL and >30 mg/dL respectively. The median number of changes in dose during therapy was 2 (range: 0-9). The median duration of treatment was 94 days (range 31-259).
As far as adverse effects are concerned, a reduction of more than 30% from baseline in platelet count and estimated CLCr was observed in 36% (only in 3 cases platelets halved) and 8.6% of patients respectively, but in none of these cases did it cause discontinuation of treatment.
Cure was obtained in 40 subjects (91%), improvement and no change in 2 cases each (4% each), failure in 1 case; 1 patient dead for other reasons.
Conclusions: Three-times weekly teicoplanin administration coupled with a regular therapeutic drug monitoring support seems a valuable pharmacological strategy in order to both guarantee a high likelihood of target attainment and a good safety profile.