Correspondence
risk of morbidity and mortality from bacterial infection, it makes sense to obtain appropriately timed measurements and serum concentrations during the first dose (no need to obtain true peak or trough concentrations because the computer program can calculate the true maximum and minimum serum concentrations) with prompt individualised dose adjustment. For vancomycin, this will obviate the need to use trough concentrations to estimate the area under the curve (AUC), which has been shown to be inaccurate.4 Two serum concentrations can be used to calculate an appropriate AUC. In most institutions, there should be no problem with providing this type of service 24 h a day year round. For vancomycin and aminoglycosides, first-dose pharmacokinetic monitoring in critically ill patients with stable renal function should be the standard. Additional consideration should be given to doing first-dose pharmacokinetics for rapid dose adjustment in patients who are not in the intensive care unit. I declare no competing interests.
Joseph S Bertino Jr [email protected] Bertino Consulting, Schenectady, NY 12303, USA 1
2
3
4
Roberts JA, Abdul-Aziz M, Lipman J, et al, on behalf of The International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14: 498–509. Martinez MN, Papich MG, Drusano GL. Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target. Antimicrob Agents Chemo 2012; 56: 2795–805. Kashuba ADM, Nafziger AN, Drusano GL, Bertino JS Jr. Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram negative bacteria. Antimicrob Agents Chemother 1999; 43: 623–29. Neely MN, Youn G, Jones B, et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother 2014; 58: 309–16.
Author’s reply Timely administration of effective antibiotic therapy can increase the likelihood of treatment success for critically ill patients. However, optimised dosing is challenging in these patients because of various pharmacokinetic and pharmacodynamic factors. 1 Although therapeutic exposures are associated with clinical cure,2 preclinical infection model data show that higher antibiotic exposures can also suppress the emergence of antibiotic resistance.3 Therefore, low antibiotic concentrations need to be minimised, and use of therapeutic drug monitoring (TDM) can rapidly ensure achievement of target exposures. To this end, Joseph Bertino’s comments represent the ideal for TDM, in which initial measurement of antibiotic concentrations occurs during the first dosing interval and are used for early dose optimisation. In our collaborative review,4 we emphasised this point by stating “During the first or a subsequent dosage interval, one or more blood samples could be taken to estimate the patient’s individual PK parameters for the antibiotic”. This wording was used to allow for practicalities associated with blood sampling, such that if TDM was to be done in a clinical unit where it is done infrequently, or out of hours, then accurate TDM could be done when an appropriate member of the clinical team can supervise the process. Particularly, for antibiotics with short half-lives, such as β lactams, which might have a dosing interval of every 4 h, or for vancomycin, for which a unit might use a 6 h dosing interval, accurate timing of sampling and coordination with the pathology laboratory might not be possible during the first dose. In fact, since antibiotics are often commenced during the night shift in intensive care units, this situation is common. However, for antibiotics with a longer dosing interval, such as once-daily aminoglycosides, or vancomycin when administered every 12 h, TDM sampling should be possible in most cases during the first dosing interval because of a
www.thelancet.com/infection Vol 14 December 2014
wider sampling window. Despite these practical issues, we support Bertino’s comments that accurate TDM should be undertaken as early a possible in the treatment course and preferably during the first dosing interval. Regular TDM should subsequently occur to ensure therapeutic concentrations are maintained throughout the entire course of therapy. I declare no competing interests. I am funded by a Career Development Fellowship from the National Health and Medical Research Council of Australia (APP1048652).
Jason A Roberts, on behalf of The International Society of Anti-Infective Pharmacology (ISAP) and the PK/PD Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) [email protected] Burns, Trauma, and Critical Care Research Centre, University of Queensland, Herston, Brisbane, QLD 4029, Australia; Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia; and Institute of Translational Medicine, University of Liverpool, Liverpool, UK 1
2
3
4
Lipman J, Udy AA, Roberts JA. Do we understand the impact of altered physiology, consequent interventions and resultant clinical scenarios in the intensive care unit? The antibiotic story. Anaesth Intensive Care 2011; 39: 999–1000. Muller AE, Punt N, Mouton JW. Optimal exposures of ceftazidime predict the probability of microbiological and clinical outcome in the treatment of nosocomial pneumonia. J Antimicrob Chemother 2013; 68: 900–06. Vanscoy B, Mendes RE, Castanheira M, et al. Relationship between ceftolozane-tazobactam exposure and drug resistance amplification in a hollow-fiber infection model. Antimicrob Agents Chemother 2013; 57: 4134–38. Roberts JA, Abdul-Aziz MH, Lipman J, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14: 498–509.
1181
risk of morbidity and mortality from bacterial infection, it makes sense to obtain appropriately timed measurements and serum concentrations during the first dose (no need to obtain true peak or trough concentrations because the computer program can calculate the true maximum and minimum serum concentrations) with prompt individualised dose adjustment. For vancomycin, this will obviate the need to use trough concentrations to estimate the area under the curve (AUC), which has been shown to be inaccurate.4 Two serum concentrations can be used to calculate an appropriate AUC. In most institutions, there should be no problem with providing this type of service 24 h a day year round. For vancomycin and aminoglycosides, first-dose pharmacokinetic monitoring in critically ill patients with stable renal function should be the standard. Additional consideration should be given to doing first-dose pharmacokinetics for rapid dose adjustment in patients who are not in the intensive care unit. I declare no competing interests.
Joseph S Bertino Jr [email protected] Bertino Consulting, Schenectady, NY 12303, USA 1
2
3
4
Roberts JA, Abdul-Aziz M, Lipman J, et al, on behalf of The International Society of Anti-Infective Pharmacology and the Pharmacokinetics and Pharmacodynamics Study Group of the European Society of Clinical Microbiology and Infectious Diseases. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14: 498–509. Martinez MN, Papich MG, Drusano GL. Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target. Antimicrob Agents Chemo 2012; 56: 2795–805. Kashuba ADM, Nafziger AN, Drusano GL, Bertino JS Jr. Optimizing aminoglycoside therapy for nosocomial pneumonia caused by gram negative bacteria. Antimicrob Agents Chemother 1999; 43: 623–29. Neely MN, Youn G, Jones B, et al. Are vancomycin trough concentrations adequate for optimal dosing? Antimicrob Agents Chemother 2014; 58: 309–16.
Author’s reply Timely administration of effective antibiotic therapy can increase the likelihood of treatment success for critically ill patients. However, optimised dosing is challenging in these patients because of various pharmacokinetic and pharmacodynamic factors. 1 Although therapeutic exposures are associated with clinical cure,2 preclinical infection model data show that higher antibiotic exposures can also suppress the emergence of antibiotic resistance.3 Therefore, low antibiotic concentrations need to be minimised, and use of therapeutic drug monitoring (TDM) can rapidly ensure achievement of target exposures. To this end, Joseph Bertino’s comments represent the ideal for TDM, in which initial measurement of antibiotic concentrations occurs during the first dosing interval and are used for early dose optimisation. In our collaborative review,4 we emphasised this point by stating “During the first or a subsequent dosage interval, one or more blood samples could be taken to estimate the patient’s individual PK parameters for the antibiotic”. This wording was used to allow for practicalities associated with blood sampling, such that if TDM was to be done in a clinical unit where it is done infrequently, or out of hours, then accurate TDM could be done when an appropriate member of the clinical team can supervise the process. Particularly, for antibiotics with short half-lives, such as β lactams, which might have a dosing interval of every 4 h, or for vancomycin, for which a unit might use a 6 h dosing interval, accurate timing of sampling and coordination with the pathology laboratory might not be possible during the first dose. In fact, since antibiotics are often commenced during the night shift in intensive care units, this situation is common. However, for antibiotics with a longer dosing interval, such as once-daily aminoglycosides, or vancomycin when administered every 12 h, TDM sampling should be possible in most cases during the first dosing interval because of a
www.thelancet.com/infection Vol 14 December 2014
wider sampling window. Despite these practical issues, we support Bertino’s comments that accurate TDM should be undertaken as early a possible in the treatment course and preferably during the first dosing interval. Regular TDM should subsequently occur to ensure therapeutic concentrations are maintained throughout the entire course of therapy. I declare no competing interests. I am funded by a Career Development Fellowship from the National Health and Medical Research Council of Australia (APP1048652).
Jason A Roberts, on behalf of The International Society of Anti-Infective Pharmacology (ISAP) and the PK/PD Study Group of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) [email protected] Burns, Trauma, and Critical Care Research Centre, University of Queensland, Herston, Brisbane, QLD 4029, Australia; Royal Brisbane and Women’s Hospital, Brisbane, QLD, Australia; and Institute of Translational Medicine, University of Liverpool, Liverpool, UK 1
2
3
4
Lipman J, Udy AA, Roberts JA. Do we understand the impact of altered physiology, consequent interventions and resultant clinical scenarios in the intensive care unit? The antibiotic story. Anaesth Intensive Care 2011; 39: 999–1000. Muller AE, Punt N, Mouton JW. Optimal exposures of ceftazidime predict the probability of microbiological and clinical outcome in the treatment of nosocomial pneumonia. J Antimicrob Chemother 2013; 68: 900–06. Vanscoy B, Mendes RE, Castanheira M, et al. Relationship between ceftolozane-tazobactam exposure and drug resistance amplification in a hollow-fiber infection model. Antimicrob Agents Chemother 2013; 57: 4134–38. Roberts JA, Abdul-Aziz MH, Lipman J, et al. Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions. Lancet Infect Dis 2014; 14: 498–509.
1181
