Evaluation of traditional initial vancomycin dosing versus utilizing an electronic AUC/MIC dosing program

BACKGROUND: Area under the curve to minimum inhibitory concentration (AUC/MIC) has been recommended by the 2020 updated vancomycin guidelines for dosing vancomycin for both efficacy and safety. Previously, AUC/MIC has been cumbersome to calculate so surrogate trough concentrations of 15-20 mg/dL were utilized. However, trough-based dosing is not a sufficient surrogate as AUC/MIC targets of 400-600 can usually be reached without achieving troughs of 15-20 mg/dL. Targeting higher trough levels may also lead to adverse events including acute kidney injury (AKI) and nephrotoxicity. OBJECTIVE: To compare the mean total first day vancomycin dose in traditional trough-based dosing versus dosing recommended by an AUC/MIC dosing program. METHODS: Adult inpatients who received at least 24 hours of IV vancomycin treatment were included in this single-center, retrospective cohort study. The primary endpoint was difference in mean total first day vancomycin dose in milligrams (mg) received between patients' traditional trough-based dosing and recommended dose via AUC/MIC electronic dosing calculator. Patients served as their own control by analyzing both actual dose received and dose recommended by the electronic AUC/MIC program. Rates of vancomycin induced adverse events, including acute kidney injury, elevated steady-state trough concentrations, and Red Man's syndrome were also compared between patients who received doses consistent with the AUC/MIC dosing recommendation versus those who did not. RESULTS: 264 patients were included in this study. Initial 24-hour vancomycin exposure was significantly lower with the recommended AUC/MIC dose versus the dose received (2380.7; SD 966.6 mg vs 2649.6; SD 831.8 mg, [95% CI 114.7:423.1] p = 0.0007). CONCLUSIONS: Utilizing an electronic AUC/MIC vancomycin dosing calculator would result in lower total first day vancomycin doses

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Resumenes de articulos de la literatura pediatrica: vancomicina en combinación con otros antimicrobianos en el tratamiento de infecciones graves por staphylococcus aureus meticilino-resistente / Abstracts of articles in the pediatric literature: vancomycin in combination with other antimicrobials in the treatment of serious infections due to methicillin-resistant staphylococcus aureus

La vancomicina frecuentemente es combinada con otros antimicrobianos debido a su deficiencia en el tratamiento de infecciones graves por Staphylococus aureus meticilino resistente (MRSA).

VanE, a new type of acquired glycopeptide resistance in Enterococcus faecalis BM4405.

Enterococcus faecalis BM4405 was resistant to low levels of vancomycin (MIC, 16 microg/ml) and was susceptible to teicoplanin (MIC, 0.5 microg/ml). No PCR product was obtained when the total DNA of this clinical isolate was used as a template with primers specific for glycopeptide resistance genes vanA, vanB, vanC, and vanD. However, a 604-bp PCR fragment was obtained when V1 and V2 degenerate primers were used and total DNA was digested with HindIII as a template. The product was cloned and sequenced. The deduced amino acid sequence had greater identity (55%) with VanC than with VanA (45%), VanB (43%), or VanD (44%). This was consistent with the fact that BM4405 synthesized peptidoglycan precursors that terminated in D-serine residues. After induction with vancomycin, weak D,D-dipeptidase and penicillin-insensitive D,D-carboxypeptidase activities were detected in cytoplasmic extracts of BM4405, whereas a serine racemase activity was found in the membrane preparation. This new type of acquired glycopeptide resistance was named VanE.

Structural features of vancomycin.

Recent analytical methods have advanced knowledge of the structure of vancomycin from a description of only several molecular fragments to a complete understanding of the intact molecule. The molecular weight is 1,448. The molecule consists of a seven-membered peptide chain that is formed by parts of three phenylglycine systems, two chlorinated tyrosine units, aspartic acid, and N-methylleucine. Two ether bonds and a carbon-carbon bond join the various substituents on the peptide chain into three large rings. A disaccharide, composed of glucose and vancosamine, is also present but is not part of the cyclic structure. Details of the vancomycin structure have been related to hydrogen bonding between the antibiotic and bacterial cell-wall precursors that have a D-alanyl-D-alanine carboxyl terminus; such bonding would provide a molecular basis for the cell-wall mode of action for vancomycin. With one carboxyl, two amino, and three phenolic groups, vancomycin undergoes a variety of ionic interactions in solutions of different pH and composition.