EVALUATION OF A VANCOMYCIN DOSING NOMOGRAM IN OSTEOARTICULAR

AND ORTHOPEDIC IMPLANT INFECTIONS

Erika Esteve (1), Monica Marin (2), Sabina Herrera (1), Luisa Sorlí (1), Lluis Puig (3), Albert Alier (3), Santiago Grau (2), Juan Pablo Horcajada (1)
(1) Infectious diseases department, Hospital del Mar, Barcelona. (2) Pharmacy department, Hospital del Mar, Barcelona. (3) Orthopaedic surgery department, Hospital del Mar, Barcelona

BACKGROUND MATERIAL AND METHODS

Vancomycin is one of the most used antibiotics in osteoarticular infections. The standard initial
dose of Vancomycin is 1000 mg or 15mg/kg every 12 hours, and therapeutic drug monitoring
(TDM) is recommended because of its narrow therapeutic range. Despite this, in the last years we
have observed that in many cases therapeutic levels were not achieved with this scheme and an
increase in initial vancomycin dose was implemented. The purpose of this study was to evaluate
the adequacy of an initial dose of 1000 mg every 8 hours the first day, followed by 1000 mg every
12 hours the second day to achieve a target Cmin of 20-25 mcg/mL for these infections.
Patients with ostheoarticular infections who underwent a surgical debridement or prosthetic replacement from December
2013 to May 2015 were included. Vancomycin dosage schedule for these patients was: first day 1g every 8 hours;
second day: 1g every 12 hours and blood samples for TDM. Data collected: demographic, weight, treatment duration,
vancomycin Cmin and AUC, recommended dose to achieve Cmin 20-25 mcg/mL, initial and final renal function and
nephrotoxicity defined by RIFLE scale renal failure. Pharmacokinetic analysis: Bayesian estimation compartmental
model (PKS® System Abbott). Data values are shown as median (Q1-Q3). Statistical analysis was performed using
non-parametric tests. ROC curves were used to determine the optimal breakpoint for the augmenting dose.

RESULTS
l Patients included: 84 (50% male), median age 69.5 (57.2-78.0), median weight 79.0 (68.5-94.0) kg. Site
of infection: hip 23 (27%), knee 23 (27%), shoulder 11 (13%), others 27 (31%).
l Treatment duration: 9 (7-13) days. Cmin: 10.8 (6.3-15.9) mcg/mL. AUC0-24: 463 (348-585) mcg.h/ml.
Increasing dose required: 71 (84.5 %) decreasing dose required: 8 (9.5 %). Recommended dose: 3 (2.4-4) g/day.
l Renal function: Scr initial: 0.70 (0.56-0.87) mg/dL, Scr final: 0.74 (0.60-0.88) mg/dL. ClCrCockroft-
Gault initial: 105 (72-147) ml/min, final: 106 (77-148) ml/min. RIFLE: 1-2-0-0-0. Nephrotoxicity: (3.6%).
l On ROC curve, patients younger than 75 years or ClCr higher of 75 ml/min had a significant impact on
increasing dose (area under the curve [AUC] 0.904, p<0.05 and 0.917 p< 0.01, respectively).

PATIENTS CHARACTERISTICS N = 84
ROC curve Age > 75 ROC curve ClCr > 75
Male, n (%) 42 (50)
Median age (years) 69.5 (57.2-78)
Median weight (kg) 79.0 (68.5-94)
Site of infection (%)
Hip 23 (27%)
Knee 23 (27%)

Sensitivity
Sensitivity
Shoulder 11 (13%)
Others 27 (31%)

RENAL FUNCTION
Initial Final
Scr (mg/dl) 0.70 (0.56-0.87) 0.74 (0.60-.088)
ClCr (Crockroft-Gault) 105 (72-147) 106 (77-148)
Nephrotoxicity n (%) 3 (3.6%)
RIFLE 1-2-0-0-0 1 - Specificity 1 - Specificity

TREATMENT AND DOSE ADJUSTMENT CONCLUSION

Duration (days) 9 (7-13) l The new dosage schedule of vancomycin for PJI shows insufficient maintenance dose at the second
Cmin (mcg/mL) 10.8 (6.3-15.9) day of treatment. With the current scheme of 1g every 8 hours the first day followed by 1g every 12
AUC0-24 (mcg.h/ml) 463 (348.585) hours the second day, most of the patients required and increased dose of vancomycin to achieve
sustained trough levels of 20-25 mcg/L.
Increasing dose required 71 (84.5%)
l We propose a new therapeutic scheme of an initial dose of 1 g / 8h during the first 2 days and TDM,
Decreasing dose required 8 (9.5%) except for patients older than 75 years and those with a CLcr lower than 75 ml/min, in which cases we
Recomended dose (g/day) 3 (2.4-4) recommend a dose of 1g / 12h the second day.