A Monocentric Retrospective Study of AUC/MIC Ratio of Vancomycin Associated with Clinical Outcomes and Nephrotoxicity in Patients with Enterococcal Infections

Vancomycin is an antibiotic commonly used for the treatment of enterococcal infections. However, there is no clear correlation regarding of vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) ratio and clinical outcomes for the treatment of enterococcal infections. The aims of this study were to evaluate the relationship of vancomycin AUC/MIC ratio in patients with clinical outcomes and nephrotoxicity for patients with documented enterococcal infections. A Bayesian technique was used to calculate the average vancomycin AUC0–24. The MIC was determined using the VITEK 2 automated microbiology system, and the average AUC0–24/MIC value was calculated for the first 72 h of therapy. All medical records of patients prescribed vancomycin with therapeutic drug monitoring were collected during January 2010–October 2020 at Chiang Mai University Hospital (CMUH). A retrospective single-center cohort of 312 participants were met the inclusion criteria. The results of this study showed that, a vancomycin AUC/MIC of ≥400 mg•·hr/L was associated with significant differences in clinical response compared to a vancomycin AUC/MIC of <400 mg•hr/L (aHR: 0.50, 95% CI: 0.26–0.97; p = 0.042). Likewise, a vancomycin AUC/MIC of ≥400 mg*hr/L was associated with significant differences in the microbiological response (aHR: 0.37, 95% CI: 0.14–0.94; p = 0.036), compared to a vancomycin AUC/MIC of <400 mg•hr/L. However, nephrotoxicity in patients with a vancomycin AUC/MIC of ≥400 mg•hr/L was higher than those with a vancomycin AUC/MIC of <400 mg•hr/L (aHR: 3.96, 95% CI: 1.09–14.47; p = 0.037). Declining renal function may be a result of high vancomycin concentrations. In addition, declining renal function (e.g., failure to resolve the focus of infection, co-administration of other antibiotics) might result in higher AUC/MIC. We found a target vancomycin AUC/MIC of ≥400 mg•hr/L and this AUC/MIC target value could be optimal for the use for monitoring treatment of enterococcal infections. Thus, vancomycin dosage must be adjusted to achieve the AUC/MIC target and closely monitored for renal function. These findings are not transferable to critically ill patients.

Enterococcal Infections the First Year after Liver—A Prospective Cohort Study

This study aimed to investigate the incidence of enterococcal infections and determine risk factors associated with enterococcal bloodstream infection (BSI) within the first year post-liver transplantation (LTx). We included 321 adult liver transplant recipients transplanted from 2011 to 2019 in a prospective cohort study. Cumulative incidence of enterococcal infections and risk factors associated with BSI were investigated in a competing risk model and time-updated Cox models, respectively. A total of 223 enterococcal infections were identified in 89 recipients. The cumulative incidences of first enterococcal infection and first enterococcal BSI were 28% (95% CI (23–33)) and 11% (CI (7–14)), respectively. Risk factors associated with enterococcal BSI were previous infections in the biliary tract (HR, 33; CI (15–74); p < 0.001), peritoneum (HR, 8.1; CI (3–23); p < 0.001) or surgical site (HR, 5.5; CI (1.4–22); p = 0.02), recipient age (HR per 10 years increase, 1.2; CI (1.03–1.6); p = 0.03), and cold ischemia time (HR per one hour increase, 1.2; CI (1.1–1.3); p < 0.01). Enterococcal infections are highly prevalent the first year post-LTx, and recipients with enterococcal infections in the biliary tract, peritoneum, or surgical site are at increased risk of BSI. These findings may have implications for the choice of empiric antibiotics early post-LTx.

Exploring the Therapeutic Potenital of the Leaderless Enterocins K1 and EJ97 in the Treatment of Vancomycin-Resistant Enterococcal Infection

The membrane-bound protease Eep is an important virulence factor in pathogenic enterococci. The protein is involved in stress response via the RIP pathway which is crucial for pathogenic enterococci to evade host immune attacks during infection. Eep serves also as a receptor for the bacteriocins enterocin K1 and enterocin EJ97. The bacteriocins kill Enterococcus faecium and E. faecalis, respectively, and their antibiotic resistant derivatives including vancomycin resistant enterococci (VRE). This functional duality of Eep makes these two enterocins very promising as options in the prospective treatment of enterococcal infections because wildtype enterococcal cells (with an intact Eep) are sensitive to the bacteriocins while bacteriocin-resistant-mutants (without a functional Eep) become less virulent. As a first step to explore their therapeutic potential in the treatment of systemic enterococcal infections, we investigated the compatibility of the bacteriocins with human blood, and the phenotypic changes of eep-mutants toward different stress conditions. We found that the bacteriocins were compatible with blood, as they did not cause haemolysis and that the bacteriocins retained most of their antibacterial effect when incubated in blood. The bacteriocins were autoclavable which is a crucial criterium for the development of parenteral administration. Eep-mutants, which became resistant to the bacteriocin were, as expected, less capable to withstand stress conditions such as exposure to lysozyme and desiccation. Further, their ability to chain, a trait implicated in niche adaptation as well as being necessary for genetic transfer via conjugation, was also severely affected. Together, these results indicate that the bacteriocins are promising for treatment of VRE infection.

RISK FACTORS AND OUTCOMES OF ENTEROCOCCUS SPECIES ISOLATED FROM CLINICAL SPECIMENS

Introduction: Enterococci are the most common aerobic and facultative anaerobic gram-positive cocci. They show intrinsic resistance to many antibiotics, acquire resistance genes and are capable of transferring resistance genes. Immunosuppression, abdominal surgery, structural abnormalities of urinary tract, long hospital/ICU stay, previous antibiotic use, mechanical ventilation, etc. are all risk factors for enterococcal infections. Objectives: A study was undertaken to nd out the risk factors and outcomes of Enterococcus species isolated from clinical specimens. Material and Methods: Single enterococcal isolates recovered from clinical specimens received for bacterial culture in this hospital during a period of one and half years were included in the study. Clinical details of the patient and risk factors were noted down in a structured proforma. Enterococci were identied and speciated by standard biochemical tests. Patient was followed up to see the outcome. Total 96 enterococci Results: were isolated during this period from hospitalized patients, out of which 86 were Enterococcus faecalis, 8 E. faecium and 2 E. solitarius. Out of these, 4.2% isolates were vancomycin resistant enterococci. Out of 96, 52.1% had a hospital stay >7 days, 28.1% were on mechanical ventilation and 19.8% had central line insertion. In this study, 26% patients with enterococcal infection expired. Mortality among patients with E. faecium infection was more (62.5%) than among patients with E. faecalis infection (23.3%). Mortality in patients whose hospital stay was >7 days was 42%, whereas those on mechanical ventilation was 48.1% and those with central line insertion was 52.6%. This study revealed that in Conclusion: enterococcal infections, hospital stay of >7 days, mechanical ventilation and central line insertion are signicantly associated with mortality.