METHODS: MEDLINE and Embase databases were searched from inception up to September 2019 to identify all studies that compared the predictive performance of cystatin C- and/or creatinine-based eGFR in predicting the clearance of vancomycin. The prediction errors (PEs) (the value of eGFR equations minus vancomycin clearance) were quantified for each equation and were pooled using a random-effects model. The root mean squared errors were also quantified to provide a metric for imprecision.
RESULTS: This meta-analysis included evaluations of seven different cystatin C- and creatinine-based eGFR equations in total from 26 studies and 1,234 patients. The mean PE (MPE) for cystatin C-based eGFR was 4.378 mL min-1 (95% confidence interval [CI], -29.425, 38.181), while the creatinine-based eGFR provided an MPE of 27.617 mL min-1 (95% CI, 8.675, 46.560) in predicting clearance of vancomycin. This indicates the presence of unbiased results in vancomycin clearance prediction by the cystatin C-based eGFR equations. Meanwhile, creatinine-based eGFR equations demonstrated a statistically significant positive bias in vancomycin clearance prediction.
CONCLUSION: Cystatin C-based eGFR equations are better than creatinine-based eGFR equations in predicting the clearance of vancomycin. This suggests that utilising cystatin C-based eGFR equations could result in better accuracy and precision to predict vancomycin pharmacokinetic parameters.
RESULTS: Unique and specific primer pairs were designed to amplify the 8 genes. The specificity of the primers was confirmed by DNA sequencing of the nanoplex PCR products and BLAST analysis. The sensitivity and specificity of V-BiA-RE nanoplex PCR assay was evaluated against the conventional culture method. The analytical sensitivity of the assay was found to be 1 ng at the DNA level while the analytical specificity was evaluated with 43 reference enterococci and non-enterococcal strains and was found to be 100%. The diagnostic accuracy was determined using 159 clinical specimens, which showed that 97% of the clinical isolates belonged to E. faecalis, of which 26% showed the HLGR genotype, but none were vancomycin resistant. The presence of an internal control in the V-BiA-RE nanoplex PCR assay helped us to rule out false negative cases.
CONCLUSION: The nanoplex PCR assay is robust and can give results within 4 hours about the 8 genes that are essential for the identification of the most common Enterococcus spp. and their antibiotic sensitivity pattern. The PCR assay developed in this study can be used as an effective surveillance tool to study the prevalence of enterococci and their antibiotic resistance pattern in hospitals and farm animals.
METHODS: PMMA pellets were prepared with three separate concentrations of each of the two antibiotics tested. They were tested to determine the effect of increasing concentration of antibiotics on the biomechanical properties of PMMA and antibiotic activity by measuring the zone of inhibition and broth elution assay.
RESULTS: Ceftaroline PMMA at 3 wt%, three-point bending was 37.17 ± 0.51 N ( p < 0.001) and axial loading was 41.95 N ± 0.51 ( p < 0.001). At 5-wt% vancomycin-PMMA, three-point bending was 41.65 ± 0.79 N ( p = 0.02) and axial loading was 49.49 ± 2.21 N ( p = 0.01). Stiffness of ceftroline-loaded PMMA in low and medium concentration was significantly higher than the vancomycin. The zone of inhibition for ceftaroline was higher than vancomycin. Ceftaroline at 3 wt% eluted up to 6 weeks (0.3 ± 0.1 μg/ml) above the minimum inhibitory concentration (MIC) and vancomycin at 2.5 wt% eluted up to 3 weeks, same as MIC, that is, 0.5 ± 0.0 μg/ml.
CONCLUSIONS: Ceftaroline, loaded at similar concentrations as vancomycin into PMMA, is a more potent alternative based on its more favourable bioactivity and elution properties, while having a lesser effect on the mechanical properties of the cement. The use of 3-wt% ceftaroline as antibiotic laden PMMA against MRSA is recommended. It should be noted that this was an in vitro study and to determine the clinical efficacy would need prospective, controlled and randomized studies.
OBJECTIVE: The present study examines the antibacterial properties of 18 medicinal plants used by the Khyang tribe in day-to-day practice against human pathogenic bacteria.
MATERIALS AND METHODS: Leaves, bark, fruits, seeds, roots and rhizomes from collected plants were successively extracted with hexane, ethyl acetate and ethanol. The corresponding 54 extracts were tested against six human pathogenic bacteria by broth microdilution assay. The antibacterial mode of actions of phytoconstituents and their synergistic effect with vancomycin and cefotaxime towards MRSA was determined by time-killing assay and synergistic interaction assay, respectively.
RESULTS AND DISCUSSION: Hexane extract of bark of Cinnamomum cassia (L.) J. Presl. (Lauraceae) inhibited the growth of MRSA, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii with MIC values below 100 µg/mL. From this plant, cinnamaldehyde evoked at 4 × MIC in 1 h an irreversible decrease of MRSA count Log10 (CFU/mL) from 6 to 0, and was synergistic with vancomycin for MRSA with fractional inhibitory concentration index of 0.3.
CONCLUSIONS: Our study provides evidence that the medicinal plants in Bangladesh have high potential to improve the current treatment strategies for bacterial infection.
METHODS: The antimicrobial activity was tested against the planktonic S. aureus cells using the microdilution broth assay, while the antibiofilm activity were evaluated using the crystal violet and resazurin assays. The cytotoxicity of the SBDs was assessed on MRC5 (normal lung tissue), using the MTT assay.
RESULTS: The individual SBDs showed significant reduction of biomass and metabolic activity in both S. aureus strains. Combinations of the SBDs with OXA and VAN were mainly additive against the planktonic cells and cells in the biofilm. Both the compounds showed moderate toxicity against the MRC5 cell line. The selectivity index suggested that the compounds were more cytotoxic to S. aureus than the normal cells.
CONCLUSION: Both the SBD compounds demonstrated promising antimicrobial and antibiofilm activities and have the potential to be further developed as an antimicrobial agent against infections caused by MRSA.
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 (AUC0-24) 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 AUC0-24 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). AUC0-24/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 AUC0-24/MIC of vancomycin are better predictors for MRSA treatment outcomes than trough vancomycin concentration or AUC0-24 alone. The single trough-based estimated AUC may be sufficient for the monitoring of treatment response with vancomycin.