Association between single trough-based area under the curve estimation of vancomycin and treatment outcome among methicillin-resistant Staphylococcus aureus bacteremia patients.

BACKGROUND: Failure of antibiotic treatment increases mortality of critically ill patients. This study investigated the association between the treatment resolution of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and vancomycin pharmacokinetic variables. METHODS: A total of 28 critically ill patients were included in this study. All data were collected from medical, microbiology and pharmacokinetic records. The clinical response was evaluated on the basis of clinical and microbiological parameters. The 24-h area under the curve (AUC_0-24) was estimated from a single trough level using established equations. RESULTS: Out of the 28 patients, 46% were classified as responders to vancomycin treatment. The trough vancomycin concentration did not differ between the responders and non-responders (15.02 ± 6.16 and 14.83 ± 4.80 µg mL-1; P = 0.929). High vancomycin minimum inhibitory concentration (MIC) was observed among the non-responders (P = 0.007). The ratio between vancomycin trough concentration and vancomycin MIC was significantly lower in the non-responder group (8.76 ± 3.43 vs. 12.29 ± 4.85 µg mL-1; P = 0.034). The mean ratio of estimated AUC_0-24 and vancomycin MIC was 313.78 ± 117.17 µg h mL-1 in the non-responder group and 464.44 ± 139.06 µg h mL-1 in the responder group (P = 0.004). AUC_0-24/MIC of ≥ 400 µg h mL-1 was documented for 77% of the responders and 27% of the non-responders (c2 = 7.03; P = 0.008). CONCLUSIONS: Ratio of trough concentration/MIC and AUC_0-24/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC_0-24 alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.

Antibacterial effects of ellagitannins from Acalypha wilkesiana var. macafeana hort.: surface morphology analysis with environmental scanning electron microscopy and synergy with antibiotics.

The present study served to gain further insight into the bactericidal effects of ellagitannins from Acalypha wilkesiana var. macafeana hort. against pathogenic bacteria. Ellagitannins from the aerial parts of A. wilkesiana var. macafeana hort. (EAW) inhibited the growth of Bacillus cereus (ATCC 11778), Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 11632) and Methicillin-resistant Staphylococcus aureus (MRSA) clinical strain with inhibition zones equal to 11.01 ± 1.53 mm, 16.63 ± 0.11 mm, 11.40 ± 1.10 mm and 8.22 ± 0.19 mm, respectively. The minimal inhibition concentration and the minimal bactericidal concentration of ellagitannins from A. wilkesiana var. macafeana hort. (EAW) against MRSA were 750 µg/mL and 3000 µg/mL, respectively. We then examined the synergistic effect of EAW with three antibiotics, i.e. ampicillin, streptomycin and tetracycline, via the checkerboard assay and time-kill assay and observed that EAW is synergistic with ampicillin against S. aureus (ATCC 11632). Environmental electron scanning microscopy analysis showed cell lysis against S. aureus (ATCC 11632) upon treatment with the ellagitannin fraction. The ellagitannin fraction from A. wilkesiana var. macafeana hort. is bactericidal against gram-positive bacteria tested and works synergistically with ampicillin against S. aureus. Morphology analysis of the cell suggests that the bactericidal property of the ellagitannin fraction mechanism involves lysis of the cell wall. In summary, our studies demonstrate that A. wilkesiana var. macafeana hort. produces bactericidal ellagitannins of clinical and/or cosmetological value.