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Lewis SJ, Jang SM, Mueller BA. Vancomycin and daptomycin dosing recommendations in patients receiving home hemodialysis using Monte Carlo simulation. BMC Nephrol 2023; 24:270. [PMID: 37710245 PMCID: PMC10500909 DOI: 10.1186/s12882-023-03314-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2023] [Accepted: 08/29/2023] [Indexed: 09/16/2023] Open
Abstract
BACKGROUND Few drug dosing recommendations for patients receiving home hemodialysis (HHD) have been published which has hindered the adoption of HHD. HHD regimens vary widely and differ considerably from conventional, thrice weekly, in-center hemodialysis in terms of treatment frequency, duration and blood and dialysate flow rates. Consequently, vancomycin and daptomycin clearances in HHD are also likely to be different, consequently HHD dosing regimens must be developed to ensure efficacy and minimize toxicity when these antibiotics are used. Many HHD regimens are used clinically, this study modeled ten common HHD regimens and determined optimal vancomycin and daptomycin dosing for each HHD regimen. METHODS Monte Carlo simulations using pharmacokinetic data derived from the literature and demographic data from a large HHD program treating patients with end stage kidney disease were incorporated into a one-compartment pharmacokinetic model. Virtual vancomycin and daptomycin doses were administered post-HHD and drug exposures were determined in 5,000 virtual patients receiving ten different HHD regimens. Serum concentration monitoring with subsequent dose changes was incorporated into the vancomycin models. Pharmacodynamic target attainment rates were determined for each studied dose. The lowest possible doses that met predefined targets in virtual patients were chosen as optimal doses. RESULTS HHD frequency, total dialysate volumes and HHD durations influenced drug exposure and led to different dosing regimens to meet targets. Antibiotic dosing regimens were identified that could meet targets for 3- and 7-h HHD regimens occurring every other day or 4-5 days/week. HHD regimens with 3-day interdialytic periods required higher doses prior to the 3-day period. The addition of vancomycin serum concentration monitoring allowed for calculation of necessary dosing changes which increased the number of virtual subjects meeting pharmacodynamic targets. CONCLUSIONS Doses of vancomycin and daptomycin that will meet desired pharmacodynamic targets in HHD are dependent on patient and HHD-specific factors. Doses used in conventional thrice weekly hemodialysis are unlikely to meet treatment goals. The antibiotic regimens paired with the HHD parameters studied in this analysis are likely to meet goals but require clinical validation.
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Affiliation(s)
- Susan J. Lewis
- University of Findlay College of Pharmacy, 1000 N. Main Street, Findlay, OH 45840 USA
- Mercy Health - St. Anne Hospital, Toledo, OH 43623 USA
| | - Soo Min Jang
- Proacture Consulting Group, 6905 Telegraph Rd, Bloomfield Hills, MI 48304 USA
| | - Bruce A. Mueller
- University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109-1065 USA
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Matusik E, Boidin C, Friggeri A, Richard JC, Bitker L, Roberts JA, Goutelle S. Therapeutic Drug Monitoring of Antibiotic Drugs in Patients Receiving Continuous Renal Replacement Therapy or Intermittent Hemodialysis: A Critical Review. Ther Drug Monit 2022; 44:86-102. [PMID: 34772891 DOI: 10.1097/ftd.0000000000000941] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2021] [Accepted: 09/16/2021] [Indexed: 11/26/2022]
Abstract
PURPOSE Antibiotics are frequently used in patients receiving intermittent or continuous renal replacement therapy (RRT). Continuous renal replacement may alter the pharmacokinetics (PK) and the ability to achieve PK/pharmacodynamic (PD) targets. Therapeutic drug monitoring (TDM) could help evaluate drug exposure and guide antibiotic dosage adjustment. The present review describes recent TDM data on antibiotic exposure and PK/PD target attainment (TA) in patients receiving intermittent or continuous RRT, proposing practical guidelines for performing TDM. METHODS Studies on antibiotic TDM performed in patients receiving intermittent or continuous RRT published between 2000 and 2020 were searched and assessed. The authors focused on studies that reported data on PK/PD TA. TDM recommendations were based on clinically relevant PK/PD relationships and previously published guidelines. RESULTS In total, 2383 reports were retrieved. After excluding nonrelevant publications, 139 articles were selected. Overall, 107 studies reported PK/PD TA for 24 agents. Data were available for various intermittent and continuous RRT techniques. The study design, TDM practice, and definition of PK/PD targets were inconsistent across studies. Drug exposure and TA rates were highly variable. TDM seems to be necessary to control drug exposure in patients receiving intermittent and continuous RRT techniques, especially for antibiotics with narrow therapeutic margins and in critically ill patients. Practical recommendations can provide insights on relevant PK/PD targets, sampling, and timing of TDM for various antibiotic classes. CONCLUSIONS Highly variable antibiotic exposure and TA have been reported in patients receiving intermittent or continuous RRT. TDM for aminoglycosides, beta-lactams, glycopeptides, linezolid, and colistin is recommended in patients receiving RRT and suggested for daptomycin, fluoroquinolones, and tigecycline in critically ill patients on RRT.
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Affiliation(s)
- Elodie Matusik
- Pôle Pharmacie & Pôle Urgences-Réanimation-Anesthésie, Centre Hospitalier de Valenciennes, Valenciennes, France
| | - Clément Boidin
- Hospices Civils de Lyon, Groupement Hospitalier Sud, Service de Pharmacie, Pierre-Bénite
- Univ Lyon, Université Claude Bernard Lyon 1, EA 3738 CICLY - Centre pour l'Innovation en Cancérologie de Lyon, Oullins
| | - Arnaud Friggeri
- Hospices Civils de Lyon, Groupement Hospitalier Sud, Service d'Anesthésie, Médecine Intensive et Réanimation, Pierre-Bénite
- Univ Lyon, Université Claude Bernard Lyon, Faculté de Médecine Lyon Sud-Charles Mérieux, Oullins
- UMR CNRS 5308, Inserm U1111, Centre International de Recherche en Infectiologie, Laboratoire des Pathogènes Émergents
| | - Jean-Christophe Richard
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Médecine Intensive Réanimation, Lyon
- Université de Lyon, Université Claude Bernard Lyon 1, INSA-Lyon, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR CNRS 5220, Inserm U1206, Villeurbanne, France
| | - Laurent Bitker
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Médecine Intensive Réanimation, Lyon
- Université de Lyon, Université Claude Bernard Lyon 1, INSA-Lyon, UJM-Saint Etienne, CNRS, Inserm, CREATIS UMR CNRS 5220, Inserm U1206, Villeurbanne, France
| | - Jason A Roberts
- Faculty of Medicine the University of Queensland, University of Queensland Centre for Clinical Research
- Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia
- Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes
| | - Sylvain Goutelle
- Hospices Civils de Lyon, Groupement Hospitalier Nord, Service de Pharmacie
- Univ Lyon, Université Claude Bernard Lyon 1, ISPB-Faculté de Pharmacie de Lyon ; and
- Univ Lyon, Université Claude Bernard Lyon 1, UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive Villeurbanne, France
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Gharibian KN, Lewis SJ, Heung M, Segal JH, Salama NN, Mueller BA. Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis. J Antimicrob Chemother 2021; 77:174-180. [PMID: 34613416 DOI: 10.1093/jac/dkab370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 09/12/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Telavancin is a lipoglycopeptide antibiotic with limited pharmacokinetic data to guide drug dosing in patients receiving haemodialysis. OBJECTIVES This study characterized telavancin pharmacokinetics in patients receiving haemodialysis. PATIENTS AND METHODS This was a Phase IV, prospective, open-label, single-centre, crossover pharmacokinetic study (ClinicalTrials.gov: NCT02392208). Eight subjects with end-stage kidney disease requiring maintenance haemodialysis (mean ± SD: 47 ± 20 years, 69.5 ± 17.1 kg) received 5 mg/kg telavancin IV 3 h before starting a 3.5 hour haemodialysis treatment with a high-permeability haemodialyser (haemodialysis period). After a 14 day washout period, a second 5 mg/kg dose was administered post-haemodialysis (control period). Telavancin plasma concentrations were measured over a 2 day period after each dose and non-compartmental pharmacokinetic analyses were performed. RESULTS The geometric mean (GM) of telavancin overall clearance was 11.2 mL/h/kg (intrinsic clearance and dialytic clearance) in the haemodialysis period and 5.9 mL/h/kg (off-haemodialysis clearance) in the control period [GM ratio (GMR) = 1.89; 90% CI: 1.70-2.10; P < 0.01]. The GM t½ was 13.1 h when haemodialysis occurred 3 h post-dosing in the haemodialysis period but extended to 20.9 h with post-haemodialysis dosing in the control period (GMR = 0.63; 90% CI: 0.54-0.73; P < 0.01). The GM of telavancin plasma concentrations removed by haemodialysis was 27.7%. The GMR of peak plasma concentration and volume of distribution of the haemodialysis period and the control period were 0.88 (90% CI: 0.79-0.98; P = 0.08) and 1.17 (90% CI: 1.05-1.30; P = 0.048), respectively. CONCLUSIONS Haemodialysis with high-permeability haemodialysers removes telavancin considerably (∼⅓ of body load). Telavancin 5 mg/kg every 48 h post-haemodialysis dosing is recommended, but dose adjustments may be warranted if haemodialysis starts within 3 h of telavancin administration.
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Affiliation(s)
| | - Susan J Lewis
- Department of Pharmacy Practice, University of Findlay College of Pharmacy, Findlay, OH, USA.,Department of Pharmacy, Mercy Health St. Anne Hospital, Toledo, OH, USA
| | - Michael Heung
- Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA
| | - Jonathan H Segal
- Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA
| | - Noha N Salama
- Department of Pharmaceutics and Industrial Pharmacy, Cairo University Faculty of Pharmacy, Cairo, Egypt.,Department of Pharmaceutical and Administrative Sciences, St. Louis College of Pharmacy at the University of Health Sciences and Pharmacy, St. Louis, MO, USA
| | - Bruce A Mueller
- Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI, USA
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Cimino C, Burnett Y, Vyas N, Norris AH. Post-Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High-Flux Hemodialysis. Drugs 2021; 81:555-574. [PMID: 33591549 PMCID: PMC7884963 DOI: 10.1007/s40265-021-01469-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2021] [Indexed: 11/24/2022]
Abstract
Patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (IHD) are at increased risk of infection, which represents a leading cause of mortality in this population. The use of additional vascular access devices such as peripherally inserted central catheters to treat such infections should be minimized in patients with ESRD requiring IHD in order to mitigate complications such as infection and thrombosis and to maintain venous patency for hemodialysis access. Intravenous antimicrobial dosing following IHD has the advantages of avoiding additional access devices and providing convenience for patients and providers. Vancomycin, cefazolin, and aminoglycosides have historically been regarded as the primary intravenous antimicrobials administered with IHD given their relatively low cost, convenient dosing, and longevity of clinical use. Despite this, a growing body of literature is evaluating the use of an expanded list of antimicrobials that may be employed using post-dialysis dosing for patients requiring IHD; however, the available data are largely limited to pharmacokinetic studies and small cohorts of infected patients or uninfected subjects. Post-dialytic dosing of intravenous antimicrobials may be considered on a patient-by-patient basis after careful consideration of clinical, microbiological, and logistical factors that may influence the probability of treatment success. This document reviews and evaluates currently available information on the post-dialytic administration of an expanded list of intravenous antimicrobials in the setting of thrice-weekly, high-flux IHD.
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Affiliation(s)
- Christo Cimino
- Department of Pharmaceutical Services, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA.
| | - Yvonne Burnett
- St. Louis College of Pharmacy at University of Health Sciences and Pharmacy in St. Louis, 1 Pharmacy Place, St. Louis, MO, 63110, USA.,Department of Pharmacy, Missouri Baptist Medical Center, 3015 N Ballas Road, St. Louis, MO, 63131, USA
| | - Nikunj Vyas
- Department of Pharmacy, Jefferson Health-New Jersey, Stratford, NJ, 08084, USA
| | - Anne H Norris
- Perelman School of Medicine, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA, 19104, USA
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Jones TW, Jun AH, Michal JL, Olney WJ. High-Dose Daptomycin and Clinical Applications. Ann Pharmacother 2021; 55:1363-1378. [PMID: 33535792 DOI: 10.1177/1060028021991943] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE To evaluate evidence for high-dose daptomycin (doses ≥ 8 mg/kg/d). DATA SOURCES A PubMed/MEDLINE literature search was performed (January 2000 to December 2020) using the search terms daptomycin, high dose, and dosing. Review article references and society guidelines were reviewed. STUDY SELECTION AND DATA EXTRACTION Clinical trials, observational studies, retrospective studies, meta-analyses, and systematic reviews reporting on high-dose daptomycin were included. DATA SYNTHESIS Experimentally, daptomycin outperforms other antimicrobials for high inoculum and biofilm-associated infections. Clinically, high-dose daptomycin is supported as salvage and first-line therapy for endocarditis and bacteremia, primarily when caused by methicillin-resistant Staphylococcus aureus (when vancomycin minimum inhibitory concentration is >1 mg/L) and Enterococcus. High-dose daptomycin appears effective for osteomyelitis and central nervous system infections, although comparative studies are lacking. High dosing in renal replacement therapy requires considering clearance modality to achieve exposures like normal renal function. Weight-based dosing in obesity draws concern for elevated exposures, although high doses have not been evaluated kinetically in obesity. Some data show benefits of high doses in overweight populations. Burn patients clear daptomycin more rapidly, and high doses may only achieve drug exposures similar to standard doses (6 mg/kg). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE This review analyzes the efficacy and safety of high-dose daptomycin in serious gram-positive infections. Discussion of specific infectious etiologies and patient populations should encourage clinicians to evaluate their daptomycin dosing standards. CONCLUSIONS The efficacy of high-dose daptomycin and limited safety concerns encourage clinicians to consider high-dose daptomycin more liberally in severe gram-positive infections.
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Meaney CJ, Manley HJ, Pai AB, Battistella M, Hudson JQ, Peter WL. Nephrology practice and research network opinion paper: Pharmacists' perspectives on the Advancing American Kidney Health initiative. JOURNAL OF THE AMERICAN COLLEGE OF CLINICAL PHARMACY 2020. [DOI: 10.1002/jac5.1309] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Calvin J. Meaney
- University at Buffalo School of Pharmacy and Pharmaceutical Sciences Buffalo New York USA
| | | | | | - Marisa Battistella
- University of Toronto, Leslie Dan Faculty of Pharmacy, University Health Network‐ Nephrology Toronto Ontario Canada
| | - Joanna Q. Hudson
- The University of Tennessee College of Pharmacy Memphis Tennessee USA
| | - Wendy L. Peter
- University of Minnesota College of Pharmacy Minneapolis Minnesota USA
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Vilay AM. Antibiotic Dosing in Chronic Kidney Disease and End-Stage Renal Disease: A Focus on Contemporary Challenges. Adv Chronic Kidney Dis 2019; 26:61-71. [PMID: 30876619 DOI: 10.1053/j.ackd.2018.10.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 10/10/2018] [Indexed: 02/08/2023]
Abstract
Infections are an important cause of morbidity and mortality among patients with chronic kidney disease. Therefore, appropriate antibiotic dosing is imperative to achieve positive patient outcomes while minimizing antibiotic dose-related toxicity. Accurately assessing renal function and determining the influence of renal replacement therapy on antibiotic clearance makes drug dosing in this patient population challenging. Furthermore, as technological advances in hemodialysis and peritoneal dialysis occur, research incorporating newer dialysis parameters to guide drug dosing may not be readily available. Currently, there are limited data to guide drug dosing in the setting of automated peritoneal dialysis, short daily hemodialysis, and nocturnal hemodialysis. Antibiotic-dosing recommendations should be carefully evaluated considering the accuracy of the renal function assessment, the similarity of the operating characteristics of the renal replacement therapy studied compared with those being used, and whether the dosing strategy takes advantage of the pharmacodynamic profile of the antibiotic under consideration. After implementing the antibiotic-dosing regimen, therapeutic drug monitoring should occur when possible along with careful monitoring for antibiotic efficacy and safety.
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Spanish Clinical Guidelines on Vascular Access for Haemodialysis. Nefrologia 2018; 37 Suppl 1:1-191. [PMID: 29248052 DOI: 10.1016/j.nefro.2017.11.004] [Citation(s) in RCA: 100] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 06/21/2017] [Indexed: 12/26/2022] Open
Abstract
Vascular access for haemodialysis is key in renal patients both due to its associated morbidity and mortality and due to its impact on quality of life. The process, from the creation and maintenance of vascular access to the treatment of its complications, represents a challenge when it comes to decision-making, due to the complexity of the existing disease and the diversity of the specialities involved. With a view to finding a common approach, the Spanish Multidisciplinary Group on Vascular Access (GEMAV), which includes experts from the five scientific societies involved (nephrology [S.E.N.], vascular surgery [SEACV], vascular and interventional radiology [SERAM-SERVEI], infectious diseases [SEIMC] and nephrology nursing [SEDEN]), along with the methodological support of the Cochrane Center, has updated the Guidelines on Vascular Access for Haemodialysis, published in 2005. These guidelines maintain a similar structure, in that they review the evidence without compromising the educational aspects. However, on one hand, they provide an update to methodology development following the guidelines of the GRADE system in order to translate this systematic review of evidence into recommendations that facilitate decision-making in routine clinical practice, and, on the other hand, the guidelines establish quality indicators which make it possible to monitor the quality of healthcare.
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Diolez J, Venisse N, Belmouaz S, Bauwens MA, Bridoux F, Beraud G. Pilot Pharmacokinetic Study of High-Dose Daptomycin in Hemodialysis Patients With Infected Medical Devices. Am J Kidney Dis 2017. [DOI: 10.1053/j.ajkd.2017.05.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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O'Connor C, Casserly LF, Qazi J, Power L, Finnegan C, O'Connell NH, Dunne CP. A case of fatal daptomycin-resistant, vancomycin-resistant enterococcal infective endocarditis in end-stage kidney disease. JMM Case Rep 2015. [DOI: 10.1099/jmmcr.0.000089] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Affiliation(s)
- Ciara O'Connor
- Department of Clinical Microbiology, University Hospital Limerick, Limerick, Ireland
- Centre for Interventions in Infection, Inflammation & Immunity (4i), Graduate Entry Medical School, University of Limerick, Limerick, Ireland
| | - Liam F. Casserly
- Department of Renal Medicine, University Hospital Limerick, Limerick, Ireland
| | - Junaid Qazi
- Department of Renal Medicine, University Hospital Limerick, Limerick, Ireland
| | - Lorraine Power
- Department of Clinical Microbiology, University Hospital Limerick, Limerick, Ireland
| | - Cathriona Finnegan
- Department of Clinical Microbiology, University Hospital Limerick, Limerick, Ireland
| | - Nuala H. O'Connell
- Department of Clinical Microbiology, University Hospital Limerick, Limerick, Ireland
- Centre for Interventions in Infection, Inflammation & Immunity (4i), Graduate Entry Medical School, University of Limerick, Limerick, Ireland
| | - Colum P. Dunne
- Centre for Interventions in Infection, Inflammation & Immunity (4i), Graduate Entry Medical School, University of Limerick, Limerick, Ireland
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Kelesidis T. Origin of de novo daptomycin non susceptible enterococci. World J Clin Infect Dis 2015; 5:30-36. [DOI: 10.5495/wjcid.v5.i2.30] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2015] [Revised: 04/01/2015] [Accepted: 04/20/2015] [Indexed: 02/06/2023] Open
Abstract
The emergence of daptomycin non-susceptible enterococci (DNSE) poses both treatment and infection control challenges. Clinicians should be vigilant that DNSE may be isolated from patients with or without (de novo DNSE) prior use of daptomycin. Recent epidemiological data suggest the presence of a community reservoir for DNSE which may be associated with environmental, foodborne and agricultural exposures. The mechanisms of nonsusceptibility to daptomycin have not been well characterized and may not parallel those for Staphylococcus aureus. The identification of daptomycin resistance genes in anaerobes, in farm animals and in an ecosystem that has been isolated for million years, suggest that the environmental reservoir for de novo DNSE may be larger than previously thought. Herein, the limited available scientific evidence regarding the possible origin of de novo DNSE is discussed. The current existing evidence is not sufficient to draw firm conclusions on the origin of DNSE. Further studies to determine the mechanisms of de novo daptomycin nonsusceptibility among enterococci are needed.
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Kumar A, Singh NP. Antimicrobial dosing in critically ill patients with sepsis-induced acute kidney injury. Indian J Crit Care Med 2015; 19:99-108. [PMID: 25722552 PMCID: PMC4339912 DOI: 10.4103/0972-5229.151018] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
UNLABELLED Severe sepsis often leads to multiple organ dysfunction syndromes (MODS) with acute kidney injury (AKI). AKI affects approximately, 35% of Intensive Care Unit patients, and most of these are due to sepsis. Mortality rate of sepsis-induced AKI is high. Inappropriate use of antimicrobials may be responsible for higher therapeutic failure, mortality rates, costs and toxicity as well as the emergence of resistance. Antimicrobial treatment is particularly difficult due to altered pharmacokinetic profile, dynamic changes in patient's clinical status and, in many cases, need for renal replacement therapy. This article aims to describe the appropriate antimicrobial dosing and reviews the factors contributing to the difficulties in establishing precise guidelines for antimicrobial dosing in sepsis-induced AKI patients. SEARCH STRATEGY Text material was collected by systematic search in PubMed, Google (1978-2013) for original articles.
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Affiliation(s)
- Anish Kumar
- From: Department of Nephrology, Pushpanjali Crosslay Hospital, Ghaziabad, Uttar Pradesh, India
| | - Narinder Pal Singh
- From: Department of Nephrology, Pushpanjali Crosslay Hospital, Ghaziabad, Uttar Pradesh, India
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Haselden M, Leach M, Bohm N. Daptomycin dosing strategies in patients receiving thrice-weekly intermittent hemodialysis. Ann Pharmacother 2014; 47:1342-7. [PMID: 24259698 DOI: 10.1177/1060028013503110] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
OBJECTIVE To determine the optimal dosing regimen of daptomycin in patients receiving thrice-weekly hemodialysis. DATA SOURCES Literature was accessed via PubMed using the terms daptomycin and hemodialysis through July 2013. Reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION English language articles meeting the search criteria were evaluated. Studies were included if they addressed either thrice-weekly or intradialytic daptomycin administration. DATA SYNTHESIS Daptomycin is approved for the treatment of bloodstream infections due to methicillin-resistant Staphylococcus aureus and other Gram-positive organisms. Rapid bactericidal activity and limited potential for drug interactions make daptomycin an attractive agent. However, the daptomycin prescribing information recommends dosing every 48 hours in patients receiving hemodialysis, which results in dyssynchrony of dosing and dialysis sessions every other week. Studies evaluating a dosing regimen of daptomycin thrice weekly, coinciding with dialysis, indicate that pharmacokinetic and pharmacodynamic parameters are appropriate for therapeutic success. However, to maintain adequate serum drug concentrations throughout the 72-hour interdialytic period, an additional 50% of the dose should be provided to account for the longer interval. Intradialytic dosing, with the administration of daptomycin infusion beginning during the final 30 minutes of dialysis, may also require a dose increase. Limited clinical outcomes data have been reported, but no significant safety concerns have been identified. CONCLUSIONS Administration of daptomycin doses thrice weekly on hemodialysis days appears to be both safe and reasonable. Doses should be increased preceding the 72-hour interdialytic period or if daptomycin is infused during dialysis.
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Affiliation(s)
- Molly Haselden
- South Carolina College of Pharmacy/Medical University of South Carolina, Charleston, SC, USA
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Chaves RL, Chakraborty A, Benziger D, Tannenbaum S. Clinical and pharmacokinetic considerations for the use of daptomycin in patients with Staphylococcus aureus bacteraemia and severe renal impairment. J Antimicrob Chemother 2013; 69:200-10. [DOI: 10.1093/jac/dkt342] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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Kelesidis T, Tewhey R, Humphries RM. Evolution of high-level daptomycin resistance in Enterococcus faecium during daptomycin therapy is associated with limited mutations in the bacterial genome. J Antimicrob Chemother 2013; 68:1926-8. [PMID: 23580562 DOI: 10.1093/jac/dkt117] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
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16
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Scoville BA, Mueller BA. Medication Dosing in Critically Ill Patients With Acute Kidney Injury Treated With Renal Replacement Therapy. Am J Kidney Dis 2013; 61:490-500. [DOI: 10.1053/j.ajkd.2012.08.042] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2012] [Accepted: 08/28/2012] [Indexed: 12/20/2022]
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17
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Daptomycin pharmacokinetics and pharmacodynamics in a pooled sample of patients receiving thrice-weekly hemodialysis. Antimicrob Agents Chemother 2012. [PMID: 23208714 DOI: 10.1128/aac.02000-12] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
While the pharmacokinetic (PK) properties of daptomycin in hemodialysis (HD) patients have been evaluated previously by three groups, resultant dosing recommendations have varied. To address this clinical conundrum, this study combined concentration-time data from these PK evaluations and derived uniform dosing recommendations among patients on HD receiving daptomycin. A two-compartment model with separate HD and non-HD clearance terms was fit to the PK data from these studies by using BigNPAG. Embedded with PK parameters from the population PK analysis, 5,000-subject Monte Carlo simulations (MCS) were performed to identify HD dosing schemes that provided efficacy (cumulative and daily area under the concentration-time curve [AUC] values) and toxicity (trough concentrations of ≥ 24.3 mg/liter) profiles comparable to those from simulations employing the daptomycin PK model derived from the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. Separate HD dosing schemes were sought for the two weekly interdialytic periods (48 and 72 h). For the 48-h interdialytic period, intra- and post-HD dosing provided the most isometric cumulative and daily AUCs. For the 72-h interdialytic period, all HD dosing schemes provided noncumulative AUC values from 48 to 72 h (AUC(48-72)) that were <50% of the SAB-IE AUC(48-72) values. Increasing the parent dose by 50% intra- or post-HD provided comparable AUC(48-72) values, while maintaining acceptable trough concentration (C(min)) values. When efficacy and toxicity profiles were evaluated for each individual study, higher probabilities for C(min) reaching ≥ 24.3 mg/liter were observed in one of the three studies. Given the high probability of C(min) being ≥ 24.3 mg/liter in one of the three studies, more intensive creatine phosphokinase (CPK) monitoring may be warranted in HD patients receiving daptomycin.
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Cepeda CS. Daptomicina en el tratamiento de las infecciones por grampositivos en pacientes con insuficiencia renal crónica. Enferm Infecc Microbiol Clin 2012; 30 Suppl 1:38-42. [DOI: 10.1016/s0213-005x(12)70070-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
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Wenisch JM, Meyer B, Fuhrmann V, Saria K, Zuba C, Dittrich P, Thalhammer F. Multiple-dose pharmacokinetics of daptomycin during continuous venovenous haemodiafiltration. J Antimicrob Chemother 2011; 67:977-83. [PMID: 22210754 DOI: 10.1093/jac/dkr551] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
OBJECTIVES Daptomycin is bactericidal against Gram-positive bacteria, with peak-dependent effect but trough-dependent toxicity. This study was performed to develop dosing recommendations in continuous venovenous haemodiafiltration (CVVHDF). PATIENTS AND METHODS Nine critically ill patients in intensive care units of the Medical University Hospital of Vienna, requiring CVVHDF due to acute renal failure and antimicrobial treatment, were included. Blood and effluent samples were collected over 72 h to determine daptomycin concentrations by HPLC. Pharmacokinetic parameters were based on 10 sampling timepoints during the first 24 h, and peak and trough samples thereafter. An open two-compartment model was fitted to each subject's plasma concentration-time data. Simulations of serum concentration-time profiles after different doses and intervals were performed using ADAPT 5. RESULTS Peak plasma concentrations with 6 mg/kg daptomycin were 62.2 ± 16.2, 66.1 ± 17.3 and 78.5 ± 22.1 mg/L on days 1, 2 and 3, respectively. The total clearance was 6.1 ± 4.9 mL/min, and the elimination half-life was 17.8 ± 9.7 h. Daptomycin was filtrated and could therefore be measured in the effluent. Protein binding was lower than that seen in healthy volunteers. The unbound fraction was 16 ± 4.5%. All subjects maintained trough serum concentrations above 4 mg/L, at which relevant pathogens are considered daptomycin-susceptible. Accumulation resulted when daptomycin was given every 24 h. Simulation of 8 mg/kg daptomycin given every 48 h resulted in adequate levels without accumulation. CONCLUSIONS We recommend 8 mg/kg daptomycin every 48 h in patients on CVVHDF and therapeutic drug monitoring, if possible.
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Affiliation(s)
- Judith M Wenisch
- Department of Internal Medicine I, Division of Infectious Diseases and Tropical Medicine, Center of Excellence of Medical Intensive Care (CEMIC), Medical University of Vienna, Vienna, Austria.
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Mueller BA, Crompton JA, Donovan BJ, Yankalev S, Lamp KC. Safety of Daptomycin in Patients Receiving Hemodialysis. Pharmacotherapy 2011; 31:665-72. [DOI: 10.1592/phco.31.7.665] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Cardone KE, Lodise TP, Patel N, Hoy CD, Meola S, Manley HJ, Drusano GL, Grabe DW. Pharmacokinetics and pharmacodynamics of intravenous daptomycin during continuous ambulatory peritoneal dialysis. Clin J Am Soc Nephrol 2011; 6:1081-8. [PMID: 21393490 DOI: 10.2215/cjn.08510910] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES This study sought to (1) characterize the pharmacokinetic (PK) profile of intravenous (i.v.) daptomycin among patients receiving continuous ambulatory peritoneal dialysis (CAPD); (2) identify optimal i.v. CAPD dosing schemes; and (3) determine extent of daptomycin penetration into the peritoneal space after i.v. administration. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS A PK study was conducted among eight CAPD patients. Population PK modeling and Monte Carlo simulation (MCS) were used to identify CAPD dosing schemes providing efficacy and toxicity plasma profiles comparable with those obtained from MCS using the daptomycin population PK model derived from patients in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. The primary efficacy exposure target was the area under the curve (AUC). For toxicity, the goal was to identify CAPD dosing schemes that minimized plasma trough concentrations in excess of 24.3 mg/L. Finally, peritoneal cavity penetration was determined. RESULTS Administration of i.v. daptomycin 4 or 6 mg/kg, depending on indication, every 48 h was identified as the optimal CAPD dosing scheme. This regimen provided cumulative (AUC(0-48)) and daily partitioned (AUC(0-24 h) and AUC(24-48 h)) plasma AUC values similar to the SAB-IE or "typical patient" simulations. In addition, the proportion of patients likely to experience an elevated trough concentration in excess of 24.3 mg/L was similar between every 48 h CAPD dosing and the referent group. Penetration into the peritoneal cavity was 6% of plasma. CONCLUSIONS Daptomycin 4 or 6 mg/kg, on the basis of indication, i.v. every 48 h was found to be the optimal i.v. CAPD dosing scheme.
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Affiliation(s)
- Katie E Cardone
- Albany College of Pharmacy and Health Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA
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Daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis. Crit Care Med 2011; 39:19-25. [PMID: 20890189 DOI: 10.1097/ccm.0b013e3181fa36fb] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To investigate daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis to develop dosing recommendations. DESIGN Prospective, open-label pharmacokinetic study. SETTING : Intensive care units located within a teaching medical center. PATIENTS Eight adults with known/suspected Gram-positive infections receiving continuous venovenous hemodialysis and daptomycin. INTERVENTIONS Daptomycin at 8 mg/kg intravenously over 30 mins. Serial blood and effluent samples were collected over the next 48 hrs. Daptomycin protein binding was determined by equilibrium dialysis. Daptomycin continuous venovenous hemodialysis transmembrane clearance was determined by dividing daptomycin effluent by serum concentrations and multiplying by mean effluent production rate for each subject. Equations describing a two-compartment, open-pharmacokinetic model were fitted to each subject's daptomycin concentration-time data and pharmacokinetic parameters were determined by standard methods. Serum concentration-time profiles were simulated for two daptomycin regimens (8 mg/kg every 48 hrs and 4 mg/kg every 24 hrs). MEASUREMENTS AND MAIN RESULTS A total of 7.7 ± 0.6 mg/kg (mean ± sd) of daptomycin was administered, resulting in an observed peak concentration of 81.2 ± 19.0 μg/mL. Daptomycin steady-state volume of distribution (0.23 ± 0.14 L/kg) and free fraction (17.5% ± 5.0%) were increased in critically ill subjects receiving continuous venovenous hemodialysis compared with previous values reported in healthy volunteers. Daptomycin transmembrane clearance (6.3 ± 2.9 mL/min) accounted for more than half of total clearance (11.3 ± 4.7 mL/min). Simulations demonstrated 8 mg/kg daptomycin every 48 hrs would result in higher peak (88.8 ± 20.0 μg/mL vs. 53.0 ± 12.3 μg/mL) and lower trough concentrations (7.2 ± 5.2 μg/mL vs. 12.3 ± 5.1 μg/mL) than 4 mg/kg every 24 hrs. CONCLUSIONS Daptomycin at 8 mg/kg every 48 hrs in critically ill patients receiving continuous venovenous hemodialysis resulted in good drug exposure, achieved high peak concentrations to maximize daptomycin's concentration-dependent activity, and resulted in trough concentration that would minimize the risk of myopathy. CLINICALTRIALS.GOV IDENTIFIER: NCT00663403.
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Use of pharmacokinetic and pharmacodynamic principles to determine optimal administration of daptomycin in patients receiving standardized thrice-weekly hemodialysis. Antimicrob Agents Chemother 2011; 55:1677-83. [PMID: 21282429 DOI: 10.1128/aac.01224-10] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
This study identified optimal daptomycin dosing for patients receiving thrice-weekly hemodialysis (HD). Twelve adult patients on HD received daptomycin at 6 mg/kg of body weight intravenously (i.v.) one time; plasma and dialysate samples were collected over 3 days. A 2-compartment model with separate HD and non-HD clearance terms was fit to the data. A series of 9,999-subject Monte Carlo simulations (MCS) was performed to identify HD dosing schemes providing efficacy and toxicity profiles comparable to those obtained for MCS employing the daptomycin population pharmacokinetic (PK) model derived from patients in the Staphylococcus aureus bacteremia-infective endocarditis (SAB-IE) study. For efficacy, we selected the HD dosing scheme which generated an area-under-the-curve (AUC) exposure profile comparable to that for the SAB-IE population model. For toxicity, we selected HD dosing schemes that minimized trough concentrations of ≥ 24.3 mg/liter. Separate HD dosing schemes were developed for each FDA-approved regimen and for two weekly interdialytic periods (48 and 72 h). Administration of the same parent daptomycin dose intra-HD and post-HD resulted in AUC, maximum concentration of drug in serum (C(max)), and C(min) values most comparable to those for SAB-IE simulations for the 48-hour interdialytic period. In contrast, all candidate HD dosing schemes provided AUC(48-72) values that were at least 50% lower than the SAB-IE AUC(48-72) values. Increasing the parent dose by 50% provided more comparable AUC(48-72) values while maintaining acceptable C(min) values. Administration of the daptomycin parent dose intra-HD or post-HD was optimal for the 48-h interdialytic period. For the 72-h interdialytic period, clinicians should consider increasing the dose by 50% to achieve more comparable AUC(48-72) values.
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Azanza JR, Quetglas EG. Seguridad de daptomicina en pacientes con insuficiencia renal. Med Clin (Barc) 2010; 135 Suppl 3:55-9. [DOI: 10.1016/s0025-7753(10)70041-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
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Eyler RF, Mueller BA. Antibiotic pharmacokinetic and pharmacodynamic considerations in patients with kidney disease. Adv Chronic Kidney Dis 2010; 17:392-403. [PMID: 20727509 DOI: 10.1053/j.ackd.2010.05.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2010] [Revised: 05/12/2010] [Accepted: 05/17/2010] [Indexed: 12/31/2022]
Abstract
Although pharmacokinetic changes occurring in kidney disease are well described, pharmacodynamics in kidney disease is rarely considered. Knowledge of pharmacodynamic principles can allow a clinician to maximize an antibiotic's effectiveness while minimizing adverse effects and antibacterial resistance. An antibiotic's pharmacokinetic and pharmacodynamic profiles should drive dose adjustment decisions in patients with kidney disease. For example, although the half-lives of beta-lactams and aminoglycosides are both prolonged in these patients, beta-lactams exhibit time-dependent antibacterial activity; consequently, maintenance doses should be smaller but given at the same interval. In contrast, aminoglycosides are concentration-dependent antibiotics; hence prolongation of the dosing interval while using larger doses may be advantageous. The timing of drug administration in relation to hemodialysis may be used to achieve specific pharmacodynamic goals. Aminoglycosides given before hemodialysis generate high peaks, whereas subsequent dialytic drug removal minimizes the area under the serum concentration-time curve, potentially decreasing the risk of developing toxicity. Furthermore, new dialysis prescribing patterns (eg, automated peritoneal dialysis, nocturnal dialysis) affect pharmacokinetic and pharmacodynamic parameters in ways not appreciated by clinicians. Studies quantifying the often considerable drug removal with these therapies, as well as efforts to identify pharmacodynamic targets in patients with kidney disease are essential. This paper reviews pharmacodynamic as well as pharmacokinetic issues that should be considered when prescribing antibiotics to treat infections in this population.
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Burkhardt O, Kielstein JT. A simplified three-times weekly daptomycin dosing regimen for chronic hemodialysis patients. Expert Rev Anti Infect Ther 2010; 8:11-4. [PMID: 20014897 DOI: 10.1586/eri.09.121] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Approximately 2.3 million patients worldwide are undergoing chronic renal replacement therapy. In that population, acute infections substantially contribute to the excessive morbidity and mortality. The risk for invasive methicillin-resistant Staphylococcus aureus infections in this population is approximately 100-fold higher than in the general population, therefore dialysis patients currently account for up to approximately 15% of all invasive methicillin-resistant Staphylococcus aureus infections. A simplified three-times weekly dosing regimen for hemodialysis patients now allows for practical, hassle-free and effective treatment with daptomycin, which is licensed for the treatment of complicated skin and soft tissue infections, including resistant strains of Staphylococcus aureus and life-threatening Gram-positive infections, vancomycin-resistant enterococcal infections and right-sided endocarditis.
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Affiliation(s)
- Olaf Burkhardt
- Department of Pulmonary Medicine, Medical School Hannover, Germany.
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Bahte SK, Bertram A, Burkhardt O, Martens-Lobenhoffer J, Goedecke V, Bode-Böger SM, Hiss M, Kielstein JT. Therapeutic serum concentrations of daptomycin after intraperitoneal administration in a patient with peritoneal dialysis-associated peritonitis. J Antimicrob Chemother 2010; 65:1312-4. [PMID: 20382726 DOI: 10.1093/jac/dkq118] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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A Rapid High-Performance Liquid Chromatography Method to Measure Linezolid and Daptomycin Concentrations in Human Plasma. Ther Drug Monit 2010; 32:200-5. [DOI: 10.1097/ftd.0b013e3181d3f5cb] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Sherman RA. Briefly noted: Renal transplantation. Semin Dial 2009; 22:707-8. [PMID: 20017845 DOI: 10.1111/j.1525-139x.2009.00653.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Salama NN, Segal JH, Churchwell MD, Patel JH, Gao L, Heung M, Mueller BA. Single-dose daptomycin pharmacokinetics in chronic haemodialysis patients. Nephrol Dial Transplant 2009; 25:1279-84. [PMID: 20007981 DOI: 10.1093/ndt/gfp655] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
BACKGROUND Daptomycin has concentration-dependent antibacterial activity against Gram-positive bacteria. Its use is increasing in haemodialysis units. The manufacturer recommends a 4-6-mg/kg dose administered every 48 hrs for patients receiving haemodialysis. However, there are no published data about daptomycin pharmacokinetics and clearance during haemodialysis. The recommended dosing regimen would conflict with asymmetric thrice-weekly haemodialysis, which yields two ~44-hr and one ~68-hr interdialytic periods. This is the first study to evaluate daptomycin pharmacokinetics in haemodialysis patients, assess the extent of daptomycin dialytic removal and model serum concentrations at 44 and 68 hrs. METHODS Six otherwise healthy subjects on chronic haemodialysis (55.3 +/- 16.1 years old, three females, 66.2 +/- 14.2 kg) received a single 6-mg/kg dose of daptomycin post-haemodialysis infused over 30 minutes. Serial blood samples were collected for ~44 hrs (pre-next haemodialysis) and throughout the subsequent haemodialysis session with a high permeability haemodialyser. Individual pharmacokinetic parameters determined by compartmental analysis were used to model trough serum concentrations at 44 and 68 hrs with 6-, 8- and 10-mg/kg post-haemodialysis doses. RESULTS The haemodialysis session in this trial yielded mean urea and daptomycin reduction ratios of 79.6 +/- 5.8% and 57.6 +/- 9.2%, respectively. Daptomycin half-life was 19.4 +/- 6.5 and 3.8 +/- 1.1 hrs 'off' and 'on haemodialysis', respectively, with minimal rebound 1 hr post-haemodialysis. All modelled trough concentrations at 44 and 68 hrs at all doses exceed typical minimum inhibitory concentration (MIC(90)) values for Staphylococcus aureus and Enterococcus faecalis. CONCLUSIONS Daptomycin serum concentrations declined by ~50% after a 4-hr haemodialysis session with a high permeability haemodialyser. A 6-mg/kg i.v. post-haemodialysis thrice-weekly dose should result in sufficient pre-haemodialysis daptomycin serum concentrations even after a 68-hr interdialytic period.
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Affiliation(s)
- Noha N Salama
- University of Michigan College of Pharmacy, Department of Clinical, Social & Administrative Sciences, Ann Arbor, MI, USA
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