Clinical Efficacy Of Vancomycin Research Articles

Monitoring of Blood Concentration and Clinical Efficacy of Vancomycin in the Treatment of Patients with Critically Ill Infections

We attempt to discuss the clinical efficacy and safety of vancomycin in different blood concentrations in patients with critically ill infections. We collected 50 patients who received vancomycin treatment from infectious diseases department in our hospital from June 2017 to June 2021. Monitored the trough concentration of vancomycin and selected the trough concentration after reaching the steady state. We divided patients into three groups according to the minimum blood concentration value i.e. minimum blood concentration <10 mg/l (n=16), minimum blood concentration 10 mg/l~15 mg/l (n=18) and minimum blood concentration >15 mg/l (n=16), compare the clinical effective rate and adverse reactions rate among the three groups of patients. 16 cases, 18 cases and 16 cases were enrolled into the three groups of minimum blood concentration <10, 10-15, >15 mg/l and the clinical cure rates were 68.8 %, 66.7 % and 66.7 % respectively. The differences in effective rates among the groups had no statistical significance (p=0.983); the overall adverse reactions rate in 50 patients was 18 % (9/50) and adverse reactions rate in minimum blood concentration >15 mg/l group was (43.8 %, 7/16), especially it is acute renal dysfunction, which is statistically different from the other two groups (p=0.025). The high blood concentration of vancomycin in patients with critically ill infection does not increase its clinical efficacy, but will increase adverse reactions rate in patients and provide a basis for providing the best vancomycin dose in clinical practice.

Determination of vancomycin exposure target and individualised dosing recommendations for neonates: model-informed precision dosing

IntroductionFew studies incorporating population pharmacokinetic/pharmacodynamic (Pop-PK/PD) modelling have been conducted to quantify the exposure target of vancomycin in neonates. A retrospective observational cohort study was undertaken in neonates to determine this target and dosing recommendations (chictr.org.cn, ChiCTR1900027919). MethodsA Pop-PK model was developed to estimate PK parameters. Causalities between acute kidney injury (AKI) occurrence and vancomycin use were verified using Naranjo criteria. Thresholds of vancomycin exposure in predicting AKI or efficacy were identified via classification and regression tree analysis. Associations between exposure thresholds and clinical outcomes, including AKI and efficacy, were analysed by logistic regression. Dosing recommendations were designed using Monte Carlo simulations based on the optimised exposure target. ResultsPop-PK modelling included 182 neonates with 411 observations. On covariate analysis, neonatal physiological maturation, renal function and concomitant use of vasoactive agents (VAS) significantly affected vancomycin PK. Seven cases of vancomycin-induced AKI were detected. Area under the concentration-time curve from 0–24 hours (AUC0–24) ≥ 485 mg•h/L was an independent risk factor for AKI after adjusting for VAS co-administration. The clinical efficacy of vancomycin was analysed in 42 patients with blood culture-proven staphylococcal sepsis. AUC0–24 to minimum inhibitory concentration (AUC0–24/MIC) ≥ 234 was the only significant predictor of clinical effectiveness. Monte Carlo simulations indicated that regimens in Neonatal Formulary 7 and Red Book (2018) were unsuitable for all neonates. ConclusionAn AUC0–24 of 240–480 (assuming MIC = 1 mg/L) is a recommended exposure target of vancomycin in neonates. Model-informed dosing regimens are valuable in clinical practice.

Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Children: a Reappraisal of Vancomycin.

In the last 50years, vancomycin has been the agent of choice to treat infections due to methicillin-resistant Staphylococcus aureus (MRSA). However, vancomycin treatment failure is not uncommon, even when MRSA strains are fully susceptible to vancomycin. Treatment with vancomycin requires careful monitoring of drug levels as there is a potential for nephrotoxicity. Resistance to clindamycin is not infrequent, which also limits therapeutic options for treating infections due to MRSA in children. This paper reviews the current data on pharmacokinetics and pharmacodynamics and clinical efficacy of vancomycin in children. Resistance to vancomycin in MRSA (MIC >2mg/L) is infrequent; there is increasing evidence in the literature that vancomycin maybe ineffective against increasing proportion of isolates with MICs between 1 and 2mg/L. Recent studies and meta-analyses have demonstrated that strains with high vancomycin MICs are associated with poor outcomes especially in patients with bacteremia and deep tissue infections due to MRSA. This gradual increase in vancomycin MIC has been reported as MIC creep or vancomycin heteroresistance. Patients infected with MRSA isolates that exhibit MIC creep experience poorer clinical outcomes, including delayed treatment response, increased mortality, increase rate of relapse, and extended hospitalization. There are limited data to guide vancomycin dosing in children with MRSA. Although the vancomycin area under the curve AUC24/MIC ratio > 400 has been shown to predict clinical efficacy in adults, this relationship has not been documented very well for treatment outcomes in MRSA infections in children. Use of higher vancomycin dosages in attempts to achieve higher trough concentrations has been associated with increased nephrotoxicity. New recently approved antibiotics including ceftaroline, dalbavancin, and tedizolid offer a number of advantages over vancomycin to treat staphylococcal infections: improved antimicrobial activity, superior pharmacokinetics, pharmacodynamics, tolerability, and dosing, including once-daily and weekly regimens, and less need for monitoring drug levels.

Accessory gene regulator group II polymorphism in methicillin-resistant Staphylococcus aureus is predictive of failure of vancomycin therapy.

We studied methicillin-resistant Staphylococcus aureus (MRSA) isolates to determine if the group II polymorphism at the accessory gene regulator (agr) locus demonstrated any relationship with the clinical efficacy of vancomycin. One hundred twenty-two MRSA isolates from 87 patients treated with vancomycin were evaluated. Forty-five of 87 patients had no clinical or bacteriological response to vancomycin. Among the 36 clinically evaluable patients with the agr group II polymorphism, 31 had an infection that failed to respond to vancomycin, whereas only 5 had an infection that responded successfully to vancomycin. This finding is of interest in light of our previous findings that glycopeptide-intermediately resistant S. aureus (GISA) and hetero-GISA clinical isolates in the United States and Japan are enriched for the agr group II polymorphism, and it suggests a possible intrinsic survival advantage of some S. aureus clones with this genetic marker under vancomycin selective pressure.

Vancomycin: pharmacokinetics and administration regimens in neonates.

This review describes the use of vancomycin in neonates over the last three decades. Given the relation of late-onset neonatal septicaemia to outcome and the increase in coagulase-negative staphylococcal infection as causative organism, vancomycin remains an important antibacterial in the neonatal intensive care unit. The pharmacokinetic behaviour of vancomycin in neonates can be adequately described by a one- or two-compartment model and is mainly determined by postconceptional age and renal function. In neonates, a patent ductus arteriosus as well as treatment with indomethacin or extracorporeal membrane oxygenation (ECMO) leads to an increase in volume of distribution and a decrease in clearance. Microbiological studies in vitro have shown that an increase in vancomycin concentrations above the minimum inhibitory concentration does not result in more effective killing. The microbiological and clinical efficacy of vancomycin in neonates has only been studied explicitly in a restricted number of patients. There are no definitive data relating serum concentrations to effect in this patient group. Vancomycin-related nephrotoxicity and ototoxicity in neonates is rare, and no clear relation to serum concentrations has been demonstrated. Based on the pharmacokinetic profile of vancomycin in neonates, several administration regimens have been constructed. Recent guidelines have suggested that dosage can be independent of gestational age or postconceptional age in neonates without renal failure. In patients with renal failure, therapy can be adequately tailored by using a regimen based on serum creatinine. The usefulness of routine monitoring of peak serum concentrations is doubtful based on the current literature. Recent research demonstrates a shift towards taking only routine trough serum concentrations in order to optimise efficacy. Patients with renal failure and other special subpopulations, such as patients exposed to ECMO or indomethacin, need to be monitored more closely.