Vancomicina
La vancomicina es un antibiótico ampliamente usado para el manejo de infecciones por Staphylococcus aureus resistente a la meticilina. La dosis recomendada ha sido usualmente 1 gr cada 12 horas EV, sin embargo, estudios farmacocineticos han demostrado que esta dosis lleva a dosis pico altas y dosis valle muy bajas (<15 mcg/dL), lo cual favorece la aparicion de resistencia. Adicionalmente la baja penetracion a los tejidos (pulmon, cerebro), la nefrotoxicidad (15-35%) y el alto riesgo de mortalidad (40%) en estos casos ha llevado a plantear otras alternativas.
Entre ellos se encuentra la inquietud de que el perfil farmacocinetico es dependiente del tiempo y que probablemente la infusion continua tenga un mejor efecto terapeutico.
Pregunta:
Hay mejores desenlaces con el uso de la vancomicina en infusion en infeccion por MRSA?
Favor citar bibiliografia o enviarmela para enriquecer la discusion. Gracias.
16 comentarios
Norton Perez Gutierrez -
1. Barriere SL, Stryjewski ME, Corey GR, Genter FC, Rubinstein E. Effect of vancomycin serum trough levels on outcomes in patients with nosocomial pneumonia due to Staphylococcus aureus: a retrospective, post hoc, subgroup analysis of the Phase 3 ATTAIN studies. BMC Infect Dis. BMC Infectious Diseases; 2014 Jan;14(1):183.
Norton Perez Gutierrez -
1. Cunha B a. Vancomycin revisited: a reappraisal of clinical use. Crit Care Clin. 2008;24(2):393420.
Norton Perez Gutierrez -
Norton Perez Gutierrez -
Norton Perez -
luis Alfredo montenegro ortiz -
la referencia es: CRITICAL CARE CLINICS 24 (2008) 393-420. VANCOMYCIN REVISITED: A REAPPRAISAL OF CLINICAL USE. Burke A. Cunha, MD, MACP. Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA. State University of New York, School of Medicine, Stony Brook, NY, USA.
Norton Perez Gutierrez -
luis alfredo montenegro ortiz -
antibiotics to critically ill patients?
Jason A. Robertsa,b, Jeffrey Lipmana,c, Stijn Blotd,e,f and Jordi Rellog
Current Opinion in Critical Care 2008, 14:390396
Increasing interest is being directed toward possible benefits associated with
continuous infusion of time-dependent antibiotics such as b-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with continuous infusions are discussed.
Esta es una excelente revisión sobre el uso de antibióticos en infusión continua. Recomienda el uso de vancomicina en infusión continua y esgrime las razones por la cual lo hace. Se los recomiendo fuertemente
luis Alfredo montenegro ortiz -
Glycopeptides
Vancomycin displays moderate protein binding, whereas teicoplanin is highly protein
bound.63 In patients with hypoalbuminemia, increased Vd and CL are possible for teicoplanin
because of an increase in the unbound fraction of the drug.22,64 A teicoplanin
loading dose of 6 mg/kg every 12 hours for at least 3 doses followed by once-daily
dosing is recommended.65
Increased capillary permeability and fluid shifts in the critically ill can lead to
increased Vd for vancomycin.6668 The optimal PK/PD target for optimal antibacterial
activity of vancomycin is not well understood. In vitro and animal studies demonstrate
that bacterial killing of vancomycin is time dependent (T>MIC).69 A neutropenic mouse
model demonstrated that area under the curve AUC/MIC ratio is the best predictor of
antibacterial activity although a non-neutropenic mouse model demonstrated that
Cmax/MIC was the PK/PD index determining efficacy.69,70
In practice, therapeutic drug monitoring of vancomycin in the form of trough
concentration monitoring is recommended aiming for Cmin of between 15 and
20 mg/L to achieve a target AUC/MIC ratio of at least 400 for eradication of Staphylococcus
aureus.71 Maintenance doses of up to 30 to 40 mg/kg/d may be required in
critically ill patients with increased Vd and/or increased CL to achieve adequate antimicrobial
concentrations. Vancomycin can be administered by continuous infusion to
improve the PD and to minimize the risk of toxicity associated with the use of large
intermittent doses.72 In patients with renal impairment, dose reduction of glycopeptides
is warranted to minimize the risk of toxicity.
Adriana Franco -
Y según las referencias ya comentadas por ustedes y en esta lo más importante es la monitoria de los niveles de vancomicina y buscando las cosas en contra como sus efectos adversos este estudio, Risk factors for nephrotoxicity in patients receiving outpatient continuous infusions of vancomycin in an Australian tertiary hospital, publicado enJ. Antimicrob. Chemother. (2013) doi: 10.1093/jac/dkt402, documenta que niveles de vancomicina mayores a 30 y el uso de IECAS aumenta en riesgo de falla renal asociada a las infusiones siendo esta su principal complicación y yo les planteo un duda cual seria la mejor dosis inicial para el uso empírico de vancomicina
luis Alfredo montenegro ortiz -
luis Alfredo montenegro ortiz -
Evaluation of a dosing regimen for continuous vancomycin infusion
in critically ill patients: An observational study in intensive care
unit patients.
Bernd Saugel a,⁎, Carolin Gramm a, Julia Y. Wagner b, Marlena Messer a, Tobias Lahmer a, Agnes S. Meidert a,
Roland M. Schmid a, Wolfgang Huber a
Purpose: We aimed to evaluate a dosing algorithm for continuous vancomycin administration in intensive
care unit patients.
Materials and Methods: This observational study was conducted in a medical intensive care unit (German
university hospital; June 2012-February 2013). Following a loading dose of 20 mg per kg actual body weight,
vancomycin was administered continuously (20 or 30 mg of vancomycin per kg actual body weight over
24 hours depending on renal function). The vancomycin infusion rate was adjusted to achieve a target serum
vancomycin concentration of 20-30 mg/L.
Results: Vancomycin was administered for a median (interquartile range) of 7 (5-9) days. The median
vancomycin dose given as an initial bolus was 1750 (1400-2000) mg. The median daily vancomycin dose
ranged from 480 (180960) mg (day 6) to 3.120 (2596-3980) mg (day 1). Altogether, the achieved median
serum vancomycin concentration was 29.0 (25.2-33.2) mg/L. On treatment days 1 to 7, we observed target
serum vancomycin levels (20-30 mg/L) in 48%, 39%, 33%, 26%, 43%, 57%, and 69% of patients. Supratherapeutic
serum vancomycin concentrations (N30 mg/L) were observed in 36%, 52%, 61%, 63%, 39%, 19%, and
15% of patients on treatment days 1 to 7.
Conclusions: The evaluated vancomycin dosing regimen for continuous infusion allowed rapid achievement of
sufficient vancomycin serum levels. However, we frequently observed supra-therapeutic serum vancomycin
concentrations in the first days of vancomycin treatment.
© 2014 Elsevier Inc. All rights reserved.
Vancomycin-Associated Nephrotoxicity in
the Critically Ill: A Retrospective Multivariate
Regression Analysis
Timothy P. Hanrahan, BSc, MBBS1,2; Georgina Harlow, MB BCh, MRCPCH3;
James Hutchinson, MB BCh, FRCA3; Joel M. Dulhunty, PhD, FRACMA2;
Jeffrey Lipman, MD, FCICM1,2; Tony Whitehouse, MD, FRCA3; Jason A. Roberts, PhD, FSHP2
Objectives: To evaluate the influence of vancomycin dose, serum
trough concentration, and dosing strategy on the evolution of
acute kidney injury in critically ill patients.
Design: Retrospective, single-center, observational study.
Setting: University Hospital ICU, Birmingham, UK.
Patients: All critically ill patients receiving vancomycin from
December 1, 2004, to August 31, 2009.
Intervention: None.
Measurements and Main Results: The prevalence of new onset
nephrotoxicity was reported using Risk, Injury, Failure, Loss,
End-stage renal disease criteria, and independent factors predictive
of nephrotoxicity were identified using logistic regression
analysis. Complete data were available for 1,430 patients. Concomitant
vasoactive therapy (odds ratio = 1.633; p < 0.001),
median serum vancomycin (odds ratio = 1.112; p < 0.001),
and duration of therapy (odds ratio = 1.041; p ≤ 0.001) were significant
positive predictors of nephrotoxicity. Intermittent infusion
was associated with a significantly greater risk of nephrotoxicity
than continuous infusion (odds ratio = 8.204; p ≤ 0.001).
Conclusions: In a large dataset, higher serum vancomycin concentrations
and greater duration of therapy are independently
associated with increased odds of nephrotoxicity. Furthermore,
continuous infusion is associated with a decreased likelihood
of nephrotoxicity compared with intermittent infusion. This large
dataset supports the use of continuous infusion of vancomycin in
critically ill patients. (Crit Care Med 2014; XX:0000)
Key Words: acute kidney injury; glycopeptide; infection; intensive
care unit; sepsis; vancomycin
362: A NEW DOSE REGIMEN FOR CONTINUOUS INFUSION OF VANCOMYCIN TO RAPIDLY ACHIEVE TARGET CONCENTRATIONS.
pág. 1-328
DOI: 10.1097/01.ccm.0000424580.92779.6d
Cristallini, Stefano; Kabtouri, Hakim; Cotton, Frederic; Wolff, Fleur; Beumier, Marjorie; Hites, Maya; Jean-Louis Vincent, Frederique Jacobs,; Taccone, Fabio Silvio
Abstract
AB Introduction: Despite the development of new molecules with anti-Gram positive bacteria activity, vancomycin is still the treatment of choice in septic critically ill patients. Because sepsis can alter drug pharmacokinetics, the development of an administration strategy able to promptly provide adequate antimicrobial concentrations is crucial. Hypothesis: The aim of this study was to prospectively validate a new regimen of vancomycin given by continuous infusion (CI)1 in septic patients. Methods: We prospectively included septic patients admitted to a mixed ICU from January 2011 to May 2012, treated with a new regimen of CI vancomycin, including a loading dose (LD) of 35 mg/kg of body weight given as a 4-hr infusion, followed by a daily CI dose adapted on creatinine clearance (CrCL), estimated by the Cockroft-Gault formula. We excluded patients treated by extracorporeal replacement therapies or less than 18 years of age. Serum vancomycin levels were measured at the end of LD, 12, 24 (n=107) and 48 hours (n=56) after the start of therapy. Dose adjustment was decided on drug concentrations at 24 and/or 48 hours. Adequate vancomycin concentrations were considered between 20 and 30 [micro]g/ml. Results: A total of 107 patients were included (77 male, age: 59 [48-71] years; weight: 75 [65-85] kgs; medical admission 69 (64%). Median APACHE II score on admission was 19 [14-23]. Mechanical ventilation was used in 58 (54%) patients and septic shock was present in 54 (53%). Overall ICU mortality was 22%. Median loading and daily doses were 2650 [2288 +/- 2295] mg and 2112 [1500-2838] mg/day, respectively. Vancomycin concentrations were 44 [37-49] [micro]g/mL at the end of LD and then 25 [21-32], 22 [19-28] and 26 [22-29] [micro]g/mL at 12, 24 and 48 hrs, respectively. Insufficient drug concentrations were found in 17 (16%), 29 (27%) and 4 (7%) patients at 12, 24 and 48 hrs, respectively and excessive levels (>30[micro]g/mL) were found in 30 (28%), 19 (17%) and 5 (9%). Conclusions: Higher than recommended regimen of vancomycin is needed to avoid insufficient drug concentrations levels in septic patients within the first 48 hours of therapy. (C) 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
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MRSA pneumonia: Better outcome through continuous infusion of vancomycin? *.
pág. 2127-2128
DOI: 10.1097/01.CCM.0000178288.70057.47
Blot, Stijn
Editorial
Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?.
pág. 390-396
DOI: 10.1097/MCC.0b013e3283021b3a
Roberts, Jason A a,b; Lipman, Jeffrey a,c; Blot, Stijn def; Rello, Jordi g
Miscellaneous
AB Purpose of review: Increasing interest is being directed toward possible benefits associated with continuous infusion of time-dependent antibiotics such as [beta]-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with continuous infusions are discussed. Recent findings: One large retrospective cohort study has found clinical outcome benefits of administering a [beta]-lactam antibiotic by extended infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing continuous infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics. Summary: Continuous infusion of vancomycin and [beta]-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for continuous infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and continuous administration of [beta]-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed. (C) 2008 Lippincott Williams & Wilkins, Inc.
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Comparison of continuous infusion versus intermittent infusion of vancomycin in patients with methicillin-resistant Staphylococcus aureus.
Jaruratanasirikul S, Julamanee J, Sudsai T, Saengsuwan P, Jullangkoon M, Ingviya N, Jarumanokul R - J Med Assoc Thai - Feb 2010; 93(2); 172-6
Abstract
To compare the pharmacokinetics of vancomycin administration by continuous infusion and intermittent infusion. A prospective, randomized, two-way crossover study of 12 patients with methicillin-resistant Staphylococcus aureus infections was conducted. All patients were randomized to receive vancomycin in both regimens consecutively: (i) infusion of 15 mg/kg of vancomycin as a loading dose for 1 h followed by 30 mg/kg of vancomycin as a continuous infusion over 24 h for 48 h; and (ii) intermittent infusion of 15 mg/kg of vancomycin for 1 h every 12 h for 48 h. Vancomycin pharmacokinetic studies were carried out during hours 24-48 after the start of both regimens. For the continuous infusion regimen, the mean highest steady-state concentration was 24.88 +/- 12.75 microg/ml and the mean lowest steady-state concentration was 19.89 +/- 10.15 microg/ml. For the intermittent infusion regimen, the mean peak and trough serum concentrations were 55.02 +/- 17.36 and 12.43 +/- 12.86 microg/ml, respectively. After 10 days of vancomycin treatment, the MRSA infections were eradicated in all patients. Moreover, during both methods of infusion, no adverse events related to the use of vancomycin were observed. Either continuous infusion or intermittent infusion can be used as an effective mode of vancomycin administration to achieve bactericidal activity.
Citation
Comparison of continuous infusion versus intermittent infusion of vancomycin in patients with methicillin-resistant Staphylococcus aureus.Jaruratanasirikul S, Julamanee J, Sudsai T, Saengsuwan P, Jullangkoon M, Ingviya N, Jarumanokul R - J Med Assoc Thai - Feb 2010; 93(2); 172-6
MEDLINE is the source for the citation and abstract for this record
Full Source Title
Journal of the Medical Association of Thailand = Chotmaihet thangphaet
NLM Citation ID
20301996.1 (PubMed ID)
Publication Type
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Language
eng
Author Affiliation
Department of Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, Thailand. jasutep@medicine.psu.ac.th
Authors
Jaruratanasirikul S; Julamanee J; Sudsai T; Saengsuwan P; Jullangkoon M; Ingviya N; Jarumanokul R
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Influence of vancomycin on renal function in critically ill patients after cardiac surgery: continuous versus intermittent infusion.
Hutschala D, Kinstner C, Skhirdladze K, Thalhammer F, Müller M, Tschernko E - Anesthesiology - Aug 2009; 111(2); 356-65
Abstract
Vancomycin is frequently used in clinical practice to treat severe wound and systemic infections caused by Gram-positive bacteria after cardiac surgery. The drug is excreted almost entirely by glomerular filtration and might exhibit nephrotoxic side effects. This study compared the nephrotoxic impact of vancomycin during continuous versus intermittent administration. The authors analyzed 149 patients admitted to the intensive care unit during a 5-yr period. All patients were treated at the intensive care unit after elective open heart surgery. Thirty patients received a dosage of 1325 +/- 603 mg/d vancomycin (range 300-3400 mg/d) by intermittent infusion, and 119 patients received a mean dosage of 1935 +/- 688 mg/d (range 352-3411 mg/d) by continuous infusion. Nephrotoxicity occurred in 11 patients (36.7%) in the intermittent treatment group and in 33 patients (27.7%) in the continuous treatment group (P = 0.3; 95% CI = 0.283). Continuous veno-venous hemofiltration after vancomycin administration was required for 9 patients (9 of 30; 30%) in the intermittent treatment group and for 28 (28 of 119; 23.5%) in the continuous treatment group (P = 0.053; 95% CI = 0.256). A change of one unit (1 mg/l) in vancomycin serum concentration (DeltaVancoC) induced an average change of 0.04 mg/dl in creatinine (DeltaCrea) in the intermittent treatment group versus 0.006 mg/dl in the continuous treatment group (P < 0.001). The data show that both the intermittent and also the continuous application modality of vancomycin are associated with deterioration of renal function in critically ill patients after cardiac surgery. However, continuous infusion showed the tendency to be less nephrotoxic than the intermittent infusion of vancomycin.
Citation
Influence of vancomycin on renal function in critically ill patients after cardiac surgery: continuous versus intermittent infusion.Hutschala D, Kinstner C, Skhirdladze K, Thalhammer F, Müller M, Tschernko E - Anesthesiology - Aug 2009; 111(2); 356-65
MEDLINE is the source for the citation and abstract for this record
Full Source Title
Anesthesiology
NLM Citation ID
19602966.1 (PubMed ID)
Publication Type
Journal Article
Language
eng
Author Affiliation
Department of Cardiothoracic and Vascular Anesthesia, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
Authors
Hutschala D; Kinstner C; Skhirdladze K; Thalhammer F; Müller M; Tschernko E
Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study.
Wysocki M, Delatour F, Faurisson F, Rauss A, Pean Y, Misset B, Thomas F, Timsit JF, Similowski T, Mentec H, Mier L, Dreyfuss D - Antimicrob. Agents Chemother. - Sep 2001; 45(9); 2460-7
Abstract
A continuous infusion of vancomycin (CIV) may provide an alternative mode of infusion in severe hospital-acquired methicillin-resistant staphylococcal (MRS) infections. A multicenter, prospective, randomized study was designed to compare CIV (targeted plateau drug serum concentrations of 20 to 25 mg/liter) and intermittent infusions of vancomycin (IIV; targeted trough drug serum concentrations of 10 to 15 mg/liter) in 119 critically ill patients with MRS infections (bacteremic infections, 35%; pneumonia, 45%). Microbiological and clinical outcomes, safety, pharmacokinetics, ease of treatment adjustment, and cost were compared. Microbiological and clinical outcomes and safety were similar. CIV patients reached the targeted concentrations faster (36 +/- 31 versus 51 +/- 39 h, P = 0.029) and fewer samples were required for treatment monitoring than with IIV patients (7.7 +/- 2.2 versus 11.8 +/- 3.9 per treatment, P < 0.0001). The variability between patients in both the area under the serum concentration-time curve (AUC(24h)) and the daily dose given over 10 days of treatment was lower with CIV than with IIV (variances, 14,621 versus 53,975 mg(2)/liter(2)/h(2) [P = 0.026] and 414 versus 818 g(2) [P = 0.057], respectively). The 10-day treatment cost per patient was $454 +/- 137 in the IIV group and was 23% lower in the CIV group ($321 +/- 81: P < 0.0001). In summary, for comparable efficacy and tolerance, CIV may be a cost-effective alternative to IIV.
Citation
Continuous versus intermittent infusion of vancomycin in severe Staphylococcal infections: prospective multicenter randomized study.Wysocki M, Delatour F, Faurisson F, Rauss A, Pean Y, Misset B, Thomas F, Timsit JF, Similowski T, Mentec H, Mier L, Dreyfuss D - Antimicrob. Agents Chemother. - Sep 2001; 45(9); 2460-7
MEDLINE is the source for the citation and abstract for this record
Full Source Title
Antimicrobial agents and chemotherapy
NLM Citation ID
11502515.1 (PubMed ID)
Publication Type
Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Language
eng
Author Affiliation
Medico-Surgical Intensive Care Unit, Institut Mutualiste Montsouris, Paris, France. marc.wysocki@imm.fr
Authors
Wysocki M; Delatour F; Faurisson F; Rauss A; Pean Y; Misset B; Thomas F; Timsit JF; Similowski T; Mentec H; Mier L; Dreyfuss D
Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis.
Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N - J. Antimicrob. Chemother. - Jan 2012; 67(1); 17-24
Abstract
To summarize available evidence on the effect of continuous infusion (CoI) of vancomycin compared with intermittent infusion (InI) in adult patients with Gram-positive infections. MEDLINE, EMBASE and Cochrane databases were searched. Randomized clinical trials (RCTs) and observational studies that comparatively assessed CoI and InI of vancomycin in terms of mortality, clinical cure, toxicity rates and serum drug exposure [trough concentration (C(min)) for InI and steady-state concentration (C(ss)) for CoI; area under the curve at 24 h (AUC(24)) for both] were included. Meta-analysis was conducted combining and analysing the relative risk (RR) and computing a summary RR of the effects with 95% confidence interval (CI). The standardized mean difference was calculated for continuous outcomes. The I(2) test was calculated to assess heterogeneity across studies. One RCT and five observational studies were included in the analysis. Compared with InI, CoI of vancomycin was associated with a significantly lower risk of nephrotoxicity (RR 0.6, 95% CI 0.4-0.9, P = 0.02; I(2)= 0). Overall mortality was not different between the two groups (RR 1.03, 95% CI 0.7-1.6, P = 0.9; I(2)= 0). Our meta-analysis suggests that administration of vancomycin for the treatment of Gram-positive infections by CoI is associated with a significantly lower risk of nephrotoxicity when compared with InI of the drug. RCTs are needed to define the impact on mortality rate and on the pharmacodynamic activity in terms of AUC/MIC ratio.
Citation
Continuous versus intermittent infusion of vancomycin for the treatment of Gram-positive infections: systematic review and meta-analysis.Cataldo MA, Tacconelli E, Grilli E, Pea F, Petrosillo N - J. Antimicrob. Chemother. - Jan 2012; 67(1); 17-24
MEDLINE is the source for the citation and abstract for this record
Full Source Title
The Journal of antimicrobial chemotherapy
NLM Citation ID
22028203.1 (PubMed ID)
Publication Type
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Review
Language
eng
Author Affiliation
2nd Infectious Diseases Division, National Institute for Infectious Diseases, Lazzaro Spallanzani, via Portunse 292, 00149 Rome, Italy. adriana.cataldo@inmi.it
Authors
Cataldo MA; Tacconelli E; Grilli E; Pea F; Petrosillo N
Vancomycin intermittent dosing versus continuous infusion for treatment of ventilator-associated pneumonia in trauma patients.
Schmelzer TM, Christmas AB, Norton HJ, Heniford BT, Sing RF - Am Surg - Nov 2013; 79(11); 1185-90
Abstract
Current guidelines for the empiric treatment of ventilator-associated pneumonia (VAP) recommend that vancomycin is dosed 15 mg/kg and administered twice daily for a target trough level of 15 to 20 μg/mL. This study compared conventional intermittent vancomycin infusion (IVI) with continuous vancomycin infusion (CVI). Our prospective, randomized study compared CVI with IVI in trauma patients with suspected VAP. The primary outcome measure was a serum vancomycin level within the target level 48 hours after initiation of therapy. Treatment groups were compared using standard statistical methods. The study included 73 patients, 36 IVI and 37 CVI. Eighteen patients were withdrawn from the study as a result of discontinuation of the drug before 48 hours or failure to draw levels at the appropriate time, resulting in 27 IVI and 28 CVI study patients. There were no differences between treatment groups in gender (P = 0.97), Injury Severity Score (P = 0.70), total body weight (P = 0.36), or age (P = 0.81). The mean serum vancomycin level for the IVI group was 8.9 ± 3.9 μg/mL, and the CVI level was 19.8 ± 6.13 μg/mL (P < 0.0001). Two patients in the IVI group (7.4%) were in the therapeutic range compared with 16 (57.1%) in the CVI group (P < 0.0001). Six patients in the CVI group (21.4%) and none of the IVI patients had supratherapeutic levels. Four patients developed renal insufficiency, three IVI (11.1%) and one CVI (3.6%) (P = 0.36). The current American Trauma Society dosing recommendations for vancomycin for presumptive VAP treatment are inadequate. Continuous vancomycin infusion should be adopted as the standard dosing strategy.
Citation
Vancomycin intermittent dosing versus continuous infusion for treatment of ventilator-associated pneumonia in trauma patients.Schmelzer TM, Christmas AB, Norton HJ, Heniford BT, Sing RF - Am Surg - Nov 2013; 79(11); 1185-90
MEDLINE is the source for the citation and abstract for this record
Full Source Title
The American surgeon
NLM Citation ID
24165255.1 (PubMed ID)
Publication Type
Comparative Study
Journal Article
Randomized Controlled Trial
Language
eng
Author Affiliation
F.H. Sammy Ross, Jr. Trauma Center, Carolinas Medical Center, Charlotte, North Carolina, USA.
Authors
Schmelzer TM; Christmas AB; Norton HJ; Heniford BT; Sing RF
Continuous intravenous administration of vancomycin in medical intensive care unit patients.
Saugel B, Nowack MC, Hapfelmeier A, Umgelter A, Schultheiss C, Thies P, Phillip V, Eyer F, Schmid RM, Huber W - J Crit Care - Feb 2013; 28(1); 9-13
Abstract
The aim of this study was to evaluate continuous vancomycin infusion (contV) in intensive care unit patients. A retrospective study in 164 patients treated with contV was conducted. They were compared with 75 patients treated with intermittent vancomycin infusion. The median duration of vancomycin therapy in the contV group was 6 (5%-95% percentile range, 2-21) days. The median daily vancomycin dose in the contV group was 960 (526-1723) mg, resulting in a median serum vancomycin plateau concentration of 19.8 (9.8-29.4) mg/L (target: 15-25 mg/L). The contV administration regime was sufficient regarding achievement of the target serum vancomycin concentration. However, in the contV group, serum vancomycin levels were frequently in a subtherapeutic range on treatment days 1 (44%), 2 (29%), and 3 (23%). In the contV group, serum vancomycin concentration determinations per treatment day were performed significantly less often compared with the intermittent vancomycin infusion group (0.38 [0.15-0.75] vs 0.43 [0.22-1.00], P = .041). In medical intensive care unit patients, contV is sufficient to achieve target serum vancomycin concentrations. Because contV frequently resulted in subtherapeutic drug levels on the first days of therapy, a higher loading or starting dose might be necessary.
Citation
Continuous intravenous administration of vancomycin in medical intensive care unit patients.Saugel B, Nowack MC, Hapfelmeier A, Umgelter A, Schultheiss C, Thies P, Phillip V, Eyer F, Schmid RM, Huber W - J Crit Care - Feb 2013; 28(1); 9-13
MEDLINE is the source for the citation and abstract for this record
Full Source Title
Journal of critical care
NLM Citation ID
22459156.1 (PubMed ID)
Publication Type
Journal Article
Language
eng
Author Affiliation
II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, D-81675 München, Germany. bcs.muc@gmx.de
Authors
Saugel B; Nowack MC; Hapfelmeier A; Umgelter A; Schultheiss C; Thies P; Phillip V; Eyer F; Schmid RM; Huber W
Evaluation of a dosing regimen for continuous vancomycin infusion in critically ill patients: an observational study in intensive care unit patients.
Saugel B, Gramm C, Wagner JY, Messer M, Lahmer T, Meidert AS, Schmid RM, Huber W - J Crit Care - Jun 2014; 29(3); 351-5
Abstract
We aimed to evaluate a dosing algorithm for continuous vancomycin administration in intensive care unit patients. This observational study was conducted in a medical intensive care unit (German university hospital; June 2012-February 2013). Following a loading dose of 20 mg per kg actual body weight, vancomycin was administered continuously (20 or 30 mg of vancomycin per kg actual body weight over 24 hours depending on renal function). The vancomycin infusion rate was adjusted to achieve a target serum vancomycin concentration of 20-30 mg/L. Vancomycin was administered for a median (interquartile range) of 7 (5-9) days. The median vancomycin dose given as an initial bolus was 1750 (1400-2000) mg. The median daily vancomycin dose ranged from 480 (180-960) mg (day 6) to 3.120 (2596-3980) mg (day 1). Altogether, the achieved median serum vancomycin concentration was 29.0 (25.2-33.2) mg/L. On treatment days 1 to 7, we observed target serum vancomycin levels (20-30 mg/L) in 48%, 39%, 33%, 26%, 43%, 57%, and 69% of patients. Supra-therapeutic serum vancomycin concentrations (>30 mg/L) were observed in 36%, 52%, 61%, 63%, 39%, 19%, and 15% of patients on treatment days 1 to 7. The evaluated vancomycin dosing regimen for continuous infusion allowed rapid achievement of sufficient vancomycin serum levels. However, we frequently observed supra-therapeutic serum vancomycin concentrations in the first days of vancomycin treatment.
Citation
Evaluation of a dosing regimen for continuous vancomycin infusion in critically ill patients: an observational study in intensive care unit patients.Saugel B, Gramm C, Wagner JY, Messer M, Lahmer T, Meidert AS, Schmid RM, Huber W - J Crit Care - Jun 2014; 29(3); 351-5
MEDLINE is the source for the citation and abstract for this record
Full Source Title
Journal of critical care
NLM Citation ID
24456810.1 (PubMed ID)
Publication Type
Journal Article
Language
eng
Author Affiliation
II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany. Electronic address: bernd.saugel@gmx.de.II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany.III. Medizinische Klinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany.II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany.II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany.II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany.II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany.II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 München, Germany.
Authors
Saugel B; Gramm C; Wagner JY; Messer M; Lahmer T; Meidert AS; Schmid RM; Huber W
Review of continuous-infusion vancomycin.
DiMondi VP, Rafferty K - Ann Pharmacother - Feb 2013; 47(2); 219-27
Abstract
To evaluate the efficacy and safety of administering vancomycin as a continuous infusion. Literature was accessed through MEDLINE (1977-September 2012), Embase (1977-September 2012), and Google Scholar, using the terms vancomycin, continuous, discontinuous, infusion, pharmacokinetics, pharmacodynamics, and nephrotoxicity. In addition, reference citations from publications identified were reviewed. All English-language articles identified from the data sources were evaluated. Studies including more than 30 adults were included in the safety and efficacy review. Infections due to methicillin-resistant Staphylococcus aureus (MRSA) carry a significant risk of morbidity and mortality. Vancomycin is commonly prescribed for invasive MRSA infections and has been traditionally administered as an intermittent infusion. Administering vancomycin as a continuous infusion is a novel approach to improving its efficacy and safety profile. Fourteen clinical trials were reviewed (2 prospective, 1 meta-analysis, 11 retrospective). The pharmacodynamic profiles between continuous-infusion vancomycin and intermittent-infusion vancomycin were comparable. Continuous-infusion therapy did not significantly improve the efficacy of vancomycin in the treatment of invasive MRSA infections. Conflicting results exist regarding the safety profile of continuous-infusion compared with intermittent-infusion vancomycin. The only published prospective randomized clinical trial comparing continuous infusion with intermittent therapy found no significant difference in the rates of nephrotoxicity. The data from retrospective studies are heterogeneous and show variable rates of nephrotoxicity. In general, compatibility information for administering vancomycin as a continuous infusion is unavailable. Overall, currently available evidence is insufficient to conclude whether an improvement in vancomycin efficacy exists when it is administered as a continuous infusion. The risk of nephrotoxicity associated with continuous-infusion vancomycin requires further investigation in prospective randomized trials. Specific patient populations that would benefit from continuous-infusion vancomycin have yet to be determined.
Citation
Review of continuous-infusion vancomycin.DiMondi VP, Rafferty K - Ann Pharmacother - Feb 2013; 47(2); 219-27
MEDLINE is the source for the citation and abstract for this record
Full Source Title
The Annals of pharmacotherapy
NLM Citation ID
23386074.1 (PubMed ID)
Publication Type
Journal Article
Review
Language
eng
Author Affiliation
Department of Pharmacy, Vidant Medical Center, Greenville, NC, USA. vpdimondi@gmail.com
Authors
DiMondi VP; Rafferty K
High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion.
Vuagnat A, Stern R, Lotthe A, Schuhmacher H, Duong M, Hoffmeyer P, Bernard L - J Clin Pharm Ther - Aug 2004; 29(4); 351-7
Abstract
To compare the efficacy, ease of use and safety of intermittent vancomycin infusion (IVI) and continuous vancomycin infusion (CVI) in high-dose therapy of osteomyelitis. Forty-four patients with an osteomyelitis requiring vancomycin for more than 4 weeks were prospectively included, 21 receiving IVI and 23, CVI. The target serum concentration of vancomycin was 20-25 mg/L. Pharmacokinetics, adverse effects, and clinical efficacy were recorded. The mean daily vancomycin dosing was the same in the two groups, but the serum vancomycin concentrations (trough or plateau) were lower in the IVI group than the CVI group (21.7 +/- 9.3 and 26.0 +/- 6.1 mg/L, respectively; P < 0.0001). The target concentrations were achieved quicker with CVI, and daily dosing was changed more frequently in the IVI group. After reaching the target, variability of vancomycin serum concentration (trough or plateau concentrations) was higher in the IVI group than in CVI group (standard deviation 7.9 mg/L vs. 5.6 mg/L, respectively; P = 0.001). CVI did not show clinical superiority, but adverse drug effects were more frequent in the IVI group as compared with the CVI group, 9 (42.9%) and 2 (8.7%), respectively (P = 0.03). Survival multiple regression using Cox's proportional hazard model showed that IVI (RR = 5.9, P = 0.03) and osteomyelitis of the foot (RR = 5.2, P = 0.01) were the only factors associated with adverse drug reactions leading to treatment termination. CVI is practical and effective, and may be a good alternative for patients requiring prolonged treatment with high vancomycin serum levels.
Citation
High dose vancomycin for osteomyelitis: continuous vs. intermittent infusion.Vuagnat A, Stern R, Lotthe A, Schuhmacher H, Duong M, Hoffmeyer P, Bernard L - J Clin Pharm Ther - Aug 2004; 29(4); 351-7
MEDLINE is the source for the citation and abstract for this record
Full Source Title
Journal of clinical pharmacy and therapeutics
NLM Citation ID
15271102.1 (PubMed ID)
Publication Type
Clinical Trial
Controlled Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Language
eng
Author Affiliation
Department of Statistics, St Michel Hospital, Angoulème, France.
Authors
Vuagnat A; Stern R; Lotthe A; Schuhmacher H; Duong M; Hoffmeyer P; Bernard L
Nephrotoxicity of continuous versus intermittent infusion of vancomycin in outpatient parenteral antimicrobial therapy
Paul R. Ingram, David C. Lye, Dale A. Fisher, Wei-Ping Goh, and Vincent H. Tam
International Journal of Antimicrobial Agents, 2009-12-01, Volume 34, Issue 6, Pages 570-574
Copyright © © 2009 Elsevier B.V. and the International Society of Chemotherapy
Abstract
Intravenous (i.v.) vancomycin is increasingly used as outpatient parenteral antimicrobial therapy (OPAT). Despite the potential advantages of administration by continuous infusion (CI) compared with intermittent infusion (II), the relative nephrotoxicity of these two modes of delivery has not been well established. We compared the rate of nephrotoxicity of vancomycin given by CI and II. A retrospective cohort study of OPAT patients receiving i.v. vancomycin between January 2004 to June 2008 was performed. All patients had a normal baseline serum creatinine concentration. Propensity scoring analysis was used to adjust for risk factors of CI. The primary outcomes examined were the prevalence and rate of onset of nephrotoxicity. A total of 167 patients receiving vancomycin were identified, 112 by CI and 55 by II. The overall cumulative prevalence of nephrotoxicity was 15.6%. There were significant differences in baseline characteristics between the two groups. Matching based on propensity scores was undertaken, leaving 80 patients available for the analysis. Both in unadjusted and adjusted analyses, vancomycin CI was associated with a slower onset of nephrotoxicity but not a lower prevalence of nephrotoxicity. Both groups received a similar cumulative vancomycin dose. In adult OPAT patients with normal renal function, vancomycin CI was associated with a slower onset of nephrotoxicity.
1
Introduction
Intravenous (i.v.) vancomycin is increasingly used as outpatient parenteral antimicrobial therapy (OPAT) [1], driven by the continued emergence of antibiotic-resistant Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Although there are alternative agents active against MRSA [2], none have been shown to be superior to vancomycin in a prospective, randomised, controlled clinical trial. Given the significant difference in cost, vancomycin is likely to remain the drug of choice for the treatment of MRSA infection. Although the association of nephrotoxicity with vancomycin is controversial [3], it remains a concern for many clinicians. Higher serum vancomycin concentrations have recently been recommended [4], yet a daily vancomycin dose >4 g [5] and serum trough vancomycin concentrations ≥15 mg/L are associated with nephrotoxicity [6]. By optimising the pharmacokinetics and pharmacodynamics of vancomycin, it may be possible to maximise therapeutic concentrations whilst minimising the risk of drug toxicity, as in the experience of aminoglycosides [7] [8] .
Compared with intermittent infusion (II), continuous infusion (CI) of vancomycin is cheaper [9] and logistically more convenient, achieves target vancomycin concentrations faster [9] [10] , results in less variability in serum vancomycin concentrations [9] [10] [11] , requires less therapeutic drug monitoring [9] and achieves higher vancomycin concentrations in pleural fluid [12]. Although clinical and microbiological outcomes for CI and II of vancomycin were equivalent [9] [10] , adverse drug effects were significantly reduced in CI of vancomycin [10]. However, the relative nephrotoxicity of CI compared with II of vancomycin is not well established. The objective of this study was to compare the nephrotoxic potential of these two modes of vancomycin delivery in adult OPAT patients.
2
Patients and methods
2.1
Study sites
This study was conducted at the OPAT units of National University Hospital and Tan Tock Seng Hospital, two large, tertiary-care and university-affiliated teaching hospitals in Singapore.
2.2
Study design
A retrospective cohort study of OPAT patients administered vancomycin between January 2004 and June 2008 was performed. In view of the retrospective nature of the study, the need to obtain informed consent from subjects was not necessary.
2.3
Patients
All adult patients (aged ≥18 years) prescribed i.v. vancomycin as outpatients during the study period were identified from the OPAT database. For each patient, the mode of vancomycin administration was established by consensus between the attending physician and the patient. CI of vancomycin was administered through a peripherally inserted central catheter using an elastomeric infusor. II was administered by an electronic infusion pump at a rate of 500 mg/h. Serum creatinine and vancomycin concentrations were measured weekly during OPAT therapy. Initial dosing and duration of therapy for each patient were at the discretion of the attending physicians. Patients who underwent dialysis, experienced a systolic blood pressure 50% increase in serum creatinine compared with baseline [13], which resulted in a dose reduction) during vancomycin therapy. Only data observed prior to nephrotoxicity were used in the analysis if nephrotoxicity developed during the course of therapy. Patients were not followed up after they developed nephrotoxicity in terms of their clinical and economic sequelae. All data retrieved were de-identified for the purpose of analysis.
2.5
Statistical analysis
Baseline demographics and clinical parameters were compared between patients treated with vancomycin by CI or II. Student's t-test was used for continuous variables and Fisher's exact was used for dichotomous variables. Time to onset of nephrotoxicity was analysed using KaplanMeier survival analysis and log-rank test (BreslowGehan), stratifying the data based on the mode of vancomycin administration (i.e. CI vs. II). Right censoring was used if nephrotoxicity was not directly observed at the end of therapy. A P-value of ≤0.05 was considered significant unless stated otherwise. In view of the differences in baseline characteristics between the two cohorts detected in the preliminary analysis, a propensity scoring analysis was used in addition to the unadjusted analysis. Logistic regression was used to explore various independent risk factors associated with receiving vancomycin by CI. Univariate analyses were performed individually for each of the risk factor variables to ascertain the odds ratio and 95% confidence interval. Variables with a P-value of
Norton Pere Gutierrez -
Camilo Vélez -
Camilo Vélez -
Cito: Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: a consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm. Jan 1 2009; 66(1):82-98
Establecen que: 1. En pacientes críticos el rango de referencia para los niveles valle de vancomicina es 15-20 mg / ml y el intervalo de referencia para niveles pico es de 25-50 mg / ml. 2. Las concentraciones mínimas de vancomicina por debajo de 10 mg / ml se asocian con una terapia inadecuada y un mayor riesgo de resistencia bacteriana. 3. Las concentraciones máximas de vancomicina por encima del rango terapéutico pueden estar asociadas con un aumento del riesgo de nefrotoxicidad, aunque las concentraciones máximas no se correlacionan bien con la toxicidad.
4. Las concentraciones séricas de vancomicina deben ser evaluadas para optimizar la terapia y se utilizan como un marcador indirecto de la eficacia, por lo anterior los niveles valle son los que deben ser monitorizados, no los pico. Recomendando que los niveles valle deben ser revisados antes de la cuarta dosis cuando es probable que los niveles de estado estable de la vancomicina se hayan logrado.
Ahora bien, aparece esta revisión de la literatura posteriormente
Cito: Review of continuous-infusion vancomycin. Ann Pharmacother. 2013; 47(2):219-27.
Establece que: Se revisaron artículos sobre el tema en idioma ingles desde 1997 hasta 2012 (MEDLINE) evaluando seguridad y eficacia de la infusión continua, en total 14 estudios (11 retrospectivos, 2 prospectivos y un meta-análisis), concluyendo que: En general, la evidencia revisada no es suficiente para determinar que existe una mejoría en la eficacia de la vancomicina cuando se administra como una infusión continua y el riesgo de nefrotoxicidad asociada con la infusión continua requiere de investigaciones adicionales con ensayos prospectivos aleatorizados.
Sin embargo, encontré los siguientes estudios publicados con fecha posterior a los de la revisión citada anteriormente para nuestra consideración y la pregunta del blog, estos estudios son:
Continuous intravenous administration of vancomycin in medical intensive care unit patients. J Crit Care. 2013; 28(1) 9-13
Factors associated with inadequate early vancomycin levels in critically ill patients treated with continuous infusion. Int J Antimicrob Agents. 2013; 41(5):434-8
Vancomycin intermittent dosing versus continuous infusion for treatment of ventilator-associated pneumonia in trauma patients. Am Surg. 2013; 79 (11): 1185-90
Que en general concluyen: 1. En los pacientes la terapia de infusión es suficiente para alcanzar las concentraciones séricas de vancomicina, pero debido a que se encontraron niveles subterapéuticos los primeros días de tratamiento se plantea la posibilidad de iniciar con una dosis de carga antes de la infusión. 2. En el segundo estudio se plantea la siguiente dosificación: Dosis de carga (
luis alfredo montenegro ortiz -