| dc.description.abstract | This research was prompted by concerns of Tallaght Hospital, a major teaching hospital in Dublin, Ireland, that the dosage regimen for teicoplanin in patients with haematological malignancy was suboptimal. Three studies were conducted to investigate this issue. Study 1: A survey of teicoplanin usage in adult patients with haematological malignancy in the UK and Ireland. Objective: To investigate current practices with teicoplanin use in patients with haematological malignancy in centres throughout the UK and Ireland. Methods: An on-line survey was distributed to 598 haematology and oncology pharmacists. Survey questions were aimed at identifying typical hospital practices for teicoplanin use in patients with haematological malignancy. Results: 51 responses were received. Responses indicated that teicoplanin is widely used but evidence-practice gaps for empiric use strategies in febrile neutropaenia were noted. For dose selection, the manufacturer’s Summary of Product Characteristics (SmPC) was heavily relied upon, rather than therapeutic drug monitoring (TDM), as an indicator of therapeutic dosing. Conclusions: Despite emerging evidence to support targeted prescribing, aggressive dosing and routine TDM, findings suggested that many centres do not use teicoplanin in this way. Study 2: A retrospective study of teicoplanin use in adult patients with haematological malignancy: exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity. Objective: In 2010, Tallaght Hospital introduced higher doses and a higher target trough concentration for teicoplanin for haematological malignancy patients. This study aimed to explore whether target trough concentrations were achieved, to identify factors associated with trough concentrations attained, and to assess clinical efficacy with teicoplanin treatments and nephrotoxicity. Methods: This was a retrospective, single-centre, cohort study of 172 teicoplanin treatments in 104 adults with haematological malignancy. Mixed-effects regression was used to evaluate factors affecting trough concentrations, and logistic regression was used to assess the relationship between trough concentrations and treatment outcomes. Nephrotoxicity was assessed using the RIFLE criteria. Results: Considerable variability in trough concentrations was observed, with trough concentrations ≥20 mg/L rarely achieved early in therapy. A mixed-effects regression model explaining 52% of the variation in trough concentrations was developed. Results suggested a positive relationship between trough concentration and the likelihood of a favourable outcome for coagulase-negative staphylococcal (CoNS) central line-associated blood stream infection (CLABSI). Teicoplanin was well tolerated renally. Conclusions: Findings suggested a risk of underexposure if conventional teicoplanin doses are used in haematological malignancy patients. Given the variability in trough concentrations observed and the suggested link with clinical outcome, individualised initial dosing followed by TDM appears to be the optimal approach. Study 3: A prospective study to determine the pharmacokinetic parameters and attainment of pharmacokinetic/pharmacodynamic targets of teicoplanin in adult patients with haematological malignancy. Objective: The objective of this study was to describe the population pharmacokinetics (PK) of total and unbound teicoplanin in adult patients with haematological malignancy and to provide dosing recommendations that result in a high likelihood of achieving optimal teicoplanin concentrations. Methods: This was a prospective, hospital-based, PK study. We recruited 30 patients and collected serial total and unbound serum teicoplanin concentrations. Population PK analyses of total and unbound teicoplanin were undertaken using Pmetrics. Monte Carlo simulations were conducted to determine the probability of target attainment (PTA) for various dosing regimens.
Results: Three- and four-compartment linear population PK models were most appropriate for describing total and unbound teicoplanin data, respectively. High interpatient variability in PK parameters was observed. Covariates for total teicoplanin included creatinine clearance (CLcr) for clearance (CL), and total body weight (TBW) for volume of the central compartment (Vc). Covariates for unbound teicoplanin included CLcr for CL, and TBW and serum albumin concentration for the volume of the unbound central compartment (Vuc). Dosing simulations showed that administering five loading doses 12-h, stratified by TBW and CLcr, was associated with an increased likelihood of achieving optimal teicoplanin concentrations early in therapy. Teicoplanin was well tolerated in the study cohort. Conclusions: More aggressive loading dose regimens require serious consideration. Clinicians should be mindful of the effects of enhanced renal function on dosing requirements. Routine TDM should be mandatory for this vulnerable patient group.
This research was prompted by concerns of Tallaght Hospital, a major teaching hospital in Dublin, Ireland, that the dosage regimen for teicoplanin in patients with haematological malignancy was suboptimal. Three studies were conducted to investigate this issue. Study 1: A survey of teicoplanin usage in adult patients with haematological malignancy in the UK and Ireland. Objective: To investigate current practices with teicoplanin use in patients with haematological malignancy in centres throughout the UK and Ireland. Methods: An on-line survey was distributed to 598 haematology and oncology pharmacists. Survey questions were aimed at identifying typical hospital practices for teicoplanin use in patients with haematological malignancy. Results: 51 responses were received. Responses indicated that teicoplanin is widely used but evidence-practice gaps for empiric use strategies in febrile neutropaenia were noted. For dose selection, the manufacturer’s Summary of Product Characteristics (SmPC) was heavily relied upon, rather than therapeutic drug monitoring (TDM), as an indicator of therapeutic dosing. Conclusions: Despite emerging evidence to support targeted prescribing, aggressive dosing and routine TDM, findings suggested that many centres do not use teicoplanin in this way. Study 2: A retrospective study of teicoplanin use in adult patients with haematological malignancy: exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity. Objective: In 2010, Tallaght Hospital introduced higher doses and a higher target trough concentration for teicoplanin for haematological malignancy patients. This study aimed to explore whether target trough concentrations were achieved, to identify factors associated with trough concentrations attained, and to assess clinical efficacy with teicoplanin treatments and nephrotoxicity. Methods: This was a retrospective, single-centre, cohort study of 172 teicoplanin treatments in 104 adults with haematological malignancy. Mixed-effects regression was used to evaluate factors affecting trough concentrations, and logistic regression was used to assess the relationship between trough concentrations and treatment outcomes. Nephrotoxicity was assessed using the RIFLE criteria. Results: Considerable variability in trough concentrations was observed, with trough concentrations ≥20 mg/L rarely achieved early in therapy. A mixed-effects regression model explaining 52% of the variation in trough concentrations was developed. Results suggested a positive relationship between trough concentration and the likelihood of a favourable outcome for coagulase-negative staphylococcal (CoNS) central line-associated blood stream infection (CLABSI). Teicoplanin was well tolerated renally. Conclusions: Findings suggested a risk of underexposure if conventional teicoplanin doses are used in haematological malignancy patients. Given the variability in trough concentrations observed and the suggested link with clinical outcome, individualised initial dosing followed by TDM appears to be the optimal approach. Study 3: A prospective study to determine the pharmacokinetic parameters and attainment of pharmacokinetic/pharmacodynamic targets of teicoplanin in adult patients with haematological malignancy. Objective: The objective of this study was to describe the population pharmacokinetics (PK) of total and unbound teicoplanin in adult patients with haematological malignancy and to provide dosing recommendations that result in a high likelihood of achieving optimal teicoplanin concentrations. Methods: This was a prospective, hospital-based, PK study. We recruited 30 patients and collected serial total and unbound serum teicoplanin concentrations. Population PK analyses of total and unbound teicoplanin were undertaken using Pmetrics. Monte Carlo simulations were conducted to determine the probability of target attainment (PTA) for various dosing regimens.
Results: Three- and four-compartment linear population PK models were most appropriate for describing total and unbound teicoplanin data, respectively. High interpatient variability in PK parameters was observed. Covariates for total teicoplanin included creatinine clearance (CLcr) for clearance (CL), and total body weight (TBW) for volume of the central compartment (Vc). Covariates for unbound teicoplanin included CLcr for CL, and TBW and serum albumin concentration for the volume of the unbound central compartment (Vuc). Dosing simulations showed that administering five loading doses 12-h, stratified by TBW and CLcr, was associated with an increased likelihood of achieving optimal teicoplanin concentrations early in therapy. Teicoplanin was well tolerated in the study cohort. Conclusions: More aggressive loading dose regimens require serious consideration. Clinicians should be mindful of the effects of enhanced renal function on dosing requirements. Routine TDM should be mandatory for this vulnerable patient group.
This research was prompted by concerns of Tallaght Hospital, a major teaching hospital in Dublin, Ireland, that the dosage regimen for teicoplanin in patients with haematological malignancy was suboptimal. Three studies were conducted to investigate this issue. Study 1: A survey of teicoplanin usage in adult patients with haematological malignancy in the UK and Ireland. Objective: To investigate current practices with teicoplanin use in patients with haematological malignancy in centres throughout the UK and Ireland. Methods: An on-line survey was distributed to 598 haematology and oncology pharmacists. Survey questions were aimed at identifying typical hospital practices for teicoplanin use in patients with haematological malignancy. Results: 51 responses were received. Responses indicated that teicoplanin is widely used but evidence-practice gaps for empiric use strategies in febrile neutropaenia were noted. For dose selection, the manufacturer’s Summary of Product Characteristics (SmPC) was heavily relied upon, rather than therapeutic drug monitoring (TDM), as an indicator of therapeutic dosing. Conclusions: Despite emerging evidence to support targeted prescribing, aggressive dosing and routine TDM, findings suggested that many centres do not use teicoplanin in this way. Study 2: A retrospective study of teicoplanin use in adult patients with haematological malignancy: exploring relationships between dose, trough concentrations, efficacy and nephrotoxicity. Objective: In 2010, Tallaght Hospital introduced higher doses and a higher target trough concentration for teicoplanin for haematological malignancy patients. This study aimed to explore whether target trough concentrations were achieved, to identify factors associated with trough concentrations attained, and to assess clinical efficacy with teicoplanin treatments and nephrotoxicity. Methods: This was a retrospective, single-centre, cohort study of 172 teicoplanin treatments in 104 adults with haematological malignancy. Mixed-effects regression was used to evaluate factors affecting trough concentrations, and logistic regression was used to assess the relationship between trough concentrations and treatment outcomes. Nephrotoxicity was assessed using the RIFLE criteria. Results: Considerable variability in trough concentrations was observed, with trough concentrations ≥20 mg/L rarely achieved early in therapy. A mixed-effects regression model explaining 52% of the variation in trough concentrations was developed. Results suggested a positive relationship between trough concentration and the likelihood of a favourable outcome for coagulase-negative staphylococcal (CoNS) central line-associated blood stream infection (CLABSI). Teicoplanin was well tolerated renally. Conclusions: Findings suggested a risk of underexposure if conventional teicoplanin doses are used in haematological malignancy patients. Given the variability in trough concentrations observed and the suggested link with clinical outcome, individualised initial dosing followed by TDM appears to be the optimal approach. Study 3: A prospective study to determine the pharmacokinetic parameters and attainment of pharmacokinetic/pharmacodynamic targets of teicoplanin in adult patients with haematological malignancy. Objective: The objective of this study was to describe the population pharmacokinetics (PK) of total and unbound teicoplanin in adult patients with haematological malignancy and to provide dosing recommendations that result in a high likelihood of achieving optimal teicoplanin concentrations. Methods: This was a prospective, hospital-based, PK study. We recruited 30 patients and collected serial total and unbound serum teicoplanin concentrations. Population PK analyses of total and unbound teicoplanin were undertaken using Pmetrics. Monte Carlo simulations were conducted to determine the probability of target attainment (PTA) for various dosing regimens.
Results: Three- and four-compartment linear population PK models were most appropriate for describing total and unbound teicoplanin data, respectively. High interpatient variability in PK parameters was observed. Covariates for total teicoplanin included creatinine clearance (CLcr) for clearance (CL), and total body weight (TBW) for volume of the central compartment (Vc). Covariates for unbound teicoplanin included CLcr for CL, and TBW and serum albumin concentration for the volume of the unbound central compartment (Vuc). Dosing simulations showed that administering five loading doses 12-h, stratified by TBW and CLcr, was associated with an increased likelihood of achieving optimal teicoplanin concentrations early in therapy. Teicoplanin was well tolerated in the study cohort. Conclusions: More aggressive loading dose regimens require serious consideration. Clinicians should be mindful of the effects of enhanced renal function on dosing requirements. Routine TDM should be mandatory for this vulnerable patient group. | |
