Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy

Roberts, Darren M.; Roberts, Jason A.; Roberts, Michael S.; Liu, Xin; Nair, P. V.; Cole, Louise; Lipman, Jeffrey; Bellomo, Rinaldo

doi:10.1097/ccm.0b013e318241e553

Cited by 187 publications

(150 citation statements)

References 28 publications

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“…Continuous venovenous hemofiltration is known to impact the clearance of vancomycin, an antimicrobial often recommended for empirical coverage in sepsis (5,10,12,14,23). Published literature on vancomycin clearance during CVVH is limited to small sample sizes, limited patient populations, and lower hemofiltration rates than those currently used (5,9,12,21). With the change in CVVH practices, the adequacy of existing vancomycin dosing strategies has not been investigated.…”

mentioning

confidence: 99%

Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations

Frazee

Kuper

Schramm

et al. 2012

Antimicrob Agents Chemother

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The vancomycin dose necessary for the achievement of target serum trough concentrations during continuous venovenous hemofiltration (CVVH) remains to be elucidated. This was a retrospective cohort study of critically ill adults at a tertiary medical center on concurrent CVVH and vancomycin between 2006 and 2010 with a steady-state vancomycin trough concentration. The 87 included patients were grouped according to low (<30 ml/kg/h; n ‫؍‬ 10) or high (>30 ml/kg/h; n ‫؍‬ 77) CVVH hemofiltration rate (HFR) for analysis. Vancomycin goal trough achievement occurred in only 32 (37%) patients. The primary endpoint of trough attainment significantly differed between HFR subgroups: 90% versus 30% in low-and high-HFR individuals, respectively (P < 0.001). Patients with subtherapeutic trough concentrations had a median (interquartile range) HFR of 40 ml/kg/h (range, 37 to 47 ml/kg/h) compared to 36 ml/kg/h (range, 30 to 39 ml/kg/h) in those who achieved the trough goal. Irrespective of goal trough, an inverse correlation existed between HFR and serum vancomycin concentration (r ‫؍‬ ؊0.423; P < 0.001). In the subgroup of 14 methicillin-resistant Staphylococcus aureus (MRSA) patients, trough achievement was similar to the aggregate cohort (36%). Mortality at 28 days was unrelated to trough achievement in both the overall sample (P ‫؍‬ 0.516) and in culturepositive MRSA patients (P ‫؍‬ 0.396). Critically ill patients undergoing CVVH therapy may experience clinically significant reductions in goal vancomycin troughs. The results of the present study justify prospective evaluations in this population to determine the optimal vancomycin dosing strategy for attainment of goal trough concentrations.

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mentioning

confidence: 99%

Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations

Frazee

Kuper

Schramm

et al. 2012

Antimicrob Agents Chemother

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“…In particular, patients with augmented renal clearance (ARC) have been demonstrated to exhibit substantially increased meropenem clearances and thereby decreased meropenem exposures (17,(19)(20)(21). This results in a significant risk of subtherapeutic antibiotic concentrations.…”

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confidence: 99%

Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model

Bergen

Bulitta

Kirkpatrick

et al. 2017

Antimicrob Agents Chemother

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Critically ill patients frequently have substantially altered pharmacokinetics compared to non-critically ill patients. We investigated the impact of pharmacokinetic alterations on bacterial killing and resistance for commonly used meropenem dosing regimens. A Pseudomonas aeruginosa isolate (MIC meropenem 0.25 mg/ liter) was studied in the hollow-fiber infection model (inoculum ϳ10 7.5 CFU/ml; 10 days). Pharmacokinetic profiles representing critically ill patients with augmented renal clearance (ARC), normal, or impaired renal function (creatinine clearances of 285, 120, or ϳ10 ml/min, respectively) were generated for three meropenem regimens (2, 1, and 0.5 g administered as 8-hourly 30-min infusions), plus 1 g given 12 hourly with impaired renal function. The time course of total and less-susceptible populations and MICs were determined. Mechanism-based modeling (MBM) was performed using S-ADAPT. All dosing regimens across all renal functions produced similar initial bacterial killing (Յϳ2.5 log 10 ). For all regimens subjected to ARC, regrowth occurred after 7 h. For normal and impaired renal function, bacterial killing continued until 23 to 47 h; regrowth then occurred with 0.5-and 1-g regimens with normal renal function (fT Ͼ5ϫMIC ϭ 56 and 69%, fC min /MIC Ͻ 2); the emergence of less-susceptible populations (Ն32-fold increases in MIC) accompanied all regrowth. Bacterial counts remained suppressed across 10 days with normal (2-g 8-hourly regimen) and impaired (all regimens) renal function (fT Ͼ5ϫMIC Ն 82%, fC min /MIC Ն 2). The MBM successfully described bacterial killing and regrowth for all renal functions and regimens simultaneously. Optimized dosing regimens, including extended infusions and/or combinations, supported by MBM and Monte Carlo simulations, should be evaluated in the context of ARC to maximize bacterial killing and suppress resistance emergence.

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“…Drugs such as aminoglycosides may accumulate in patients with severe sepsis, but there may also be augmented excretion of antibiotics such as beta-lactams with resultant poor therapeutic levels [64]. In patients on continuous renal replacement therapy there also may be very significant differences in antibiotic levels achieved [65]. Although there is no definitive evidence that monitoring of antibiotic drug levels will improve outcomes, there is an urgent need for investigation of this particular question [66].…”

Section: Antibioticsmentioning

confidence: 99%

What’s New in the Recognition and Management of Septic Shock in Children: Dos and Don'ts

Argent

2013

Curr Pediatr Rep

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While there has been a reduction in the number of children dying of septic shock in the richer countries of the world, septic shock remains an important cause of both mortality and morbidity for children across the world. Major reduction in the incidence of septic shock will depend on the implementation of public health measures, including immunization. Improvements in outcome of pediatric septic shock have been closely linked to early recognition (although this may be challenging in many situations); early antibiotic administration; early and appropriate fluid administration and subsequent escalation of critical care. A particular challenge has been the development and implementation of systems to ensure that these elements of management are reliably and efficiently implemented in children (even in well-resourced countries). Recent studies have highlighted the complexity of caring for patients with acute severe sepsis and septic shock in countries with fewer resources, and there is an urgent need for further studies to elucidate the implications of these studies for the management of children with septic shock, particularly in settings where additional critical care support such as inotropic or ventilator support may not be readily available.

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Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy

Cited by 187 publications

References 28 publications

Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations

Effect of Continuous Venovenous Hemofiltration Dose on Achievement of Adequate Vancomycin Trough Concentrations

Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model

What’s New in the Recognition and Management of Septic Shock in Children: Dos and Don'ts

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