A Retrospective, post hoc, Subgroup Analysis of the Phase 3 ATTAIN Studies

BMC Infectious Diseases 2014, 14:183

簡百秀

2015.1.21

Existing data are not consistently supportive of improved clinical outcome when vancomycin dosing regimens aimed at achieving target trough levels are used.

Two phase III ATTAIN studies: the efficacy and safety of telavancin vs. vancomycin for treatment of G(+) nosocomial pneumonia in adults patients

Gave vancomycin 1 g Q12H and adjusted for weight and/or renal function.

274 studies sites across 38 countries, total 98 patients with Staphylococcus aureus nosocomial pneumonia and available vancomycin trough levels

Then grouped by vancomycin trough level: < 10 mcg/mL, 10~15 mcg/mL, ≧ 15 mcg/mL.

No significant differences in clinical cure

High vancomycin trough more renal adverse events

1. ARF may have influenced vancomycin distribution and associated with poor clinical outcome

Excluding pt with previous preexisting ARF the same trend

2. Concomitant nephrotoxic medication

3. Limitations: 1) ATTAIN studies were not designed to evaluate the

impact of vancomycin trough levels.

2) Patients were not randomized to achieve a specific trough target.

3) Sample size is too small to draw a definitive conclusion.

95 received

vancomycin

11 nephrotoxicity

1 without other

nephrotoxic

drugs

10 with other

nephrotoxic

drugs

84 no

nephrotoxicity

17 with other

nephrotoxic

drugs

67 without other

nephrotoxic

drugs

11 of 63 high vancomycin

trough group

Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A: High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med 2006, 166(19):2138–2144.

1. Higher vancomycin trough levels Not result in improved clinical response

Increase the incidence of nephrotoxicity.

2. Prospective controlled studies are required to further assess the validity of the current vancomycin dosing recommendations.

Barriere et al. BMC Infectious Diseases 2014, 14:183

Hidayat LK, Hsu DI, Quist R, Shriner KA, Wong-Beringer A: High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med 2006, 166(19):2138–2144.

Association Between Vancomycin Minimum Inhibitory Concentration MIC & Mortality among Patients with Staphylococcus aureus BSIs: a Systematic Review & Meta-analysis. JAMA. 2014;312(15):1552-1564.