-
Kidney International Reports Dec 2023Intraperitoneal (IP) vancomycin is often first-line empiric therapy and then maintenance therapy for peritoneal dialysis (PD) peritonitis. However, how vancomycin serum...
INTRODUCTION
Intraperitoneal (IP) vancomycin is often first-line empiric therapy and then maintenance therapy for peritoneal dialysis (PD) peritonitis. However, how vancomycin serum levels correlate with clinical outcomes remains unclear.
METHODS
We conducted a retrospective single-center adult cohort study of 98 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022. The association between nadir vancomycin level and cure was evaluated in a logistic regression model, first unadjusted and then adjusted for age, sex, weight, glomerular filtration rate (GFR), and total number of days on PD. Vancomycin was assessed both as a continuous exposure (per 1 mg/l increase) and as a categorical exposure (<15 mg/l vs. ≥15 mg/l). A receiver operating characteristic curve (ROC) was created to explore nadir vancomycin level thresholds in an attempt to identify an optimal target level during treatment.
RESULTS
Of the patients, 81% achieved cure, and patients with nadir vancomycin level ≥15 mg/l were 7.5 times more likely to experience cure compared to those with a nadir level <15 mg/l (odds ratio [OR] 7.58, 95% confidence interval [CI] 1.71-33.57, = 0.008). Weight, GFR, days on PD, sex, and age were not independently associated with outcome. The vancomycin level with the greatest discriminatory capacity for cure on the ROC analysis was 14.4 mg/l.
CONCLUSION
Increasing IP vancomycin serum levels are associated with increased odds of cure; and maintaining vancomycin serum levels above 14-15 mg/l throughout the course of PD peritonitis treatment is likely to improve clinical outcomes.
PubMed: 38106569
DOI: 10.1016/j.ekir.2023.09.013 -
Therapeutic Drug Monitoring Aug 2023Conventionally, vancomycin trough levels have been used for therapeutic drug monitoring (TDM). Owing to the increasing evidence of trough levels being poor surrogates of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Conventionally, vancomycin trough levels have been used for therapeutic drug monitoring (TDM). Owing to the increasing evidence of trough levels being poor surrogates of area under the curve (AUC) and the advent of advanced pharmacokinetics software, a paradigm shift has been made toward AUC-guided dosing. This study aims to evaluate the impact of AUC-guided versus trough-guided TDM on vancomycin-associated nephrotoxicity.
METHODS
A systematic review was conducted using PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Google scholar, and Cochrane library databases; articles published from January 01, 2009, to January 01, 2021, were retrieved and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies that evaluated trough-guided or AUC-guided vancomycin TDM and vancomycin-associated nephrotoxicity were included. Random-effects models were used to compare the differences in nephrotoxicity.
RESULTS
Of the 1191 retrieved studies, 57 were included. Most studies included adults and older adults (n = 47, 82.45%). The pooled prevalence of nephrotoxicity was lower in AUC-guided TDM [6.2%; 95% confidence interval (CI): 2.9%-9.5%] than in trough-guided TDM (17.0%; 95% CI: 14.7%-19.2%). Compared with the trough-guided approach, the AUC-guided approach had a lower risk of nephrotoxicity (odds ratio: 0.53; 95% CI: 0.32-0.89). The risk of nephrotoxicity was unaffected by the AUC derivation method. AUC thresholds correlated with nephrotoxicity only within the first 96 hours of therapy.
CONCLUSIONS
The AUC-guided approach had a lower risk of nephrotoxicity, supporting the updated American Society of Health-System Pharmacists guidelines. Further studies are needed to evaluate the optimal AUC-derivation methods and clinical utility of repeated measurements of the AUC and trough levels of vancomycin.
Topics: Humans; Aged; Vancomycin; Anti-Bacterial Agents; Area Under Curve; Drug Monitoring; Retrospective Studies; Microbial Sensitivity Tests
PubMed: 36728329
DOI: 10.1097/FTD.0000000000001075 -
Cureus Aug 2023Introduction Hospital-acquired or nosocomial infections caused by the rapidly emerging bacteria vancomycin-resistant enterococci can be dangerous and even fatal....
Introduction Hospital-acquired or nosocomial infections caused by the rapidly emerging bacteria vancomycin-resistant enterococci can be dangerous and even fatal. Therefore, this study aimed to investigate the presence of enterococci in various clinical specimens along with their vancomycin resistance status and biofilm-producing capabilities. Methods A total of 164 species were isolated and further included in this study. Isolation and identification were done by the standard bacteriological procedure, antibiotic susceptibility testingwas done by clinical laboratory standard guidelines, and biofilm production test was done by microtiter plate methods. Results Among the total of 164 isolates, constituted 60.97% and constituted 39.02%. Maximum isolates were from urine samples. The prevalence of vancomycin-resistant was 6.70%, and 18.29% of isolates were biofilm producers. The sensitivity among the biofilm producers was maximum for linezolid (87.33%), followed by teicoplanin (86.43%) and vancomycin (79.64%). Conclusion High prevalence of enterococci was found in urine samples andbiofilm producers isolates were more antibiotic-resistant than non-biofilm producers.
PubMed: 37701006
DOI: 10.7759/cureus.43351 -
Journal of Virology Jul 2023Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host...
Short-Chain Fatty Acids Alleviate Vancomycin-Caused Humoral Immunity Attenuation in Rabies-Vaccinated Mice by Promoting the Generation of Plasma Cells via Akt-mTOR Pathway.
Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host immunogenicity to vaccines. However, it remains unknown whether and how SCFAs improve the immunogenicity of the rabies vaccine. In this study, we investigated the effect of SCFAs on the immune response to rabies vaccine in vancomycin (Vanco)-treated mice and found that oral gavage with butyrate-producing bacteria () and butyrate supplementation elevated RABV-specific IgM, IgG, and virus-neutralizing antibodies (VNAs) in Vanco-treated mice. Supplementation with butyrate expanded antigen-specific CD4 T cells and IFN-γ-secreting cells, augmented germinal center (GC) B cell recruitment, promoted plasma cells (PCs) and RABV-specific antibody-secreting cells (ASCs) generation in Vanco-treated mice. Mechanistically, butyrate enhanced mitochondrial function and activated the Akt-mTOR pathway in primary B cells isolated from Vanco-treated mice, ultimately promoting B lymphocyte-induced maturation protein-1 (Blimp-1) expression and CD138 PCs generation. These results highlight the important role of butyrate in alleviating Vanco-caused humoral immunity attenuation in rabies-vaccinated mice and maintaining host immune homeostasis. The gut microbiome plays many crucial roles in the maintenance of immune homeostasis. Alteration of the gut microbiome and metabolites has been shown to impact vaccine efficacy. SCFAs can act as an energy source for B-cells, thereby promoting both mucosal and systemic immunity in the host by inhibiting HDACs and activation of GPR receptors. This study investigates the impact of orally administered butyrate, an SCFA, on the immunogenicity of rabies vaccines in Vanco-treated mice. The results showed that butyrate ameliorated humoral immunity by facilitating the generation of plasma cells via the Akt-mTOR in Vanco-treated mice. These findings unveil the impact of SCFAs on the immune response of the rabies vaccine and confirm the crucial role of butyrate in regulating immunogenicity to rabies vaccines in antibiotic-treated mice. This study provides a fresh insight into the relationship of microbial metabolites and rabies vaccination.
Topics: Mice; Animals; Rabies; Rabies Vaccines; Plasma Cells; Immunity, Humoral; Vancomycin; Proto-Oncogene Proteins c-akt; Antibodies, Viral; TOR Serine-Threonine Kinases; Fatty Acids, Volatile; Butyrates
PubMed: 37338411
DOI: 10.1128/jvi.00656-23 -
Antibiotics (Basel, Switzerland) May 2024This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC) and trough...
This study conducted a quantitative meta-analysis to investigate the association of vancomycin indicators, particularly area under the curve over 24 h (AUC) and trough concentrations (C), and their relationship with both nephrotoxicity and efficacy. Literature research was performed in PubMed and Web of Science on vancomycin nephrotoxicity and efficacy in adult inpatients. Vancomycin C, AUC, AUC/minimum inhibitory concentration (MIC), nephrotoxicity evaluation and treatment outcomes were extracted. Logistic regression and models were conducted, stratified by evaluation criterion for nephrotoxicity and primary outcomes for efficacy. Among 100 publications on nephrotoxicity, 29 focused on AUC and 97 on C, while of 74 publications on efficacy, 27 reported AUC/MIC and 68 reported C. The logistic regression analysis indicated a significant association between nephrotoxicity and vancomycin C (odds ratio = 2.193; 95% CI 1.582-3.442, < 0.001). The receiver operating characteristic curve had an area of 0.90, with a cut-off point of 14.55 mg/L. Additionally, 92.3% of the groups with a mean AUC within 400-600 mg·h/L showed a mean C of 10-20 mg/L. However, a subtle, non-statistically significant association was observed between the AUC and nephrotoxicity, as well as between AUC/MIC and C concerning treatment outcomes. Our findings suggest that monitoring vancomycin C remains a beneficial and valuable approach to proactively identifying patients at risk of nephrotoxicity, particularly when C exceeds 15 mg/L. C can serve as a surrogate for AUC to some extent. However, no definitive cut-off values were identified for AUC concerning nephrotoxicity or for C and AUC/MIC regarding efficacy.
PubMed: 38927164
DOI: 10.3390/antibiotics13060497 -
Antimicrobial Resistance and Infection... Aug 2023Vancomycin-resistant Staphylococcus aureus, identified as a "high priority antibiotic-resistant pathogen" by the World Health Organization, poses a significant threat to... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Vancomycin-resistant Staphylococcus aureus, identified as a "high priority antibiotic-resistant pathogen" by the World Health Organization, poses a significant threat to human health. This systematic review and meta-analysis aimed to estimate the pooled prevalence of vancomycin-resistant Staphylococcus aureus in Ethiopia.
METHODS
This systematic review and meta-analysis was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies that reported VRSA prevalence due to infection or carriage from human clinical specimens were extensively searched in bibliographic databases and grey literatures using entry terms and combination key words. Electronic databases like PubMed, Google Scholar, Wiley Online Library, African Journal Online, Scopus, Science Direct, Embase, and ResearchGate were used to find relevant articles. In addition, the Joanna Briggs Institute quality appraisal tool was used to assess the quality of the included studies. Stata version 14 software was used for statistical analysis. Forest plots using the random-effect model were used to compute the overall pooled prevalence of VRSA and for the subgroup analysis. Heterogeneity was assessed using Cochrane chi-square (I) statistics. After publication bias was assessed using a funnel plot and Egger's test, trim & fill analysis was carried out. Furthermore, sensitivity analysis was done to assess the impact of a single study on pooled effect size.
RESULTS
Of the 735 studies identified, 31 studies that fulfilled the eligibility criteria were included for meta-analysis consisted of 14,966 study participants and 2,348 S. aureus isolates. The overall pooled prevalence of VRSA was 14.52% (95% CI: 11.59, 17.44). Significantly high level of heterogeneity was observed among studies (I = 93.0%, p < 0.001). The region-based subgroup analysis depicted highest pooled prevalence of 47.74% (95% CI: 17.79, 77.69) in Sidama region, followed by 14.82% (95% CI: 8.68, 19.88) in Amhara region, while Oromia region had the least pooled prevalence 8.07% (95% CI: 4.09, 12.06). The subgroup analysis based on AST methods depicted a significant variation in pooled prevalence of VRSA (6.3% (95% CI: 3.14, 9.43) for MIC-based methods, and 18.4% (95% CI: 14.03, 22.79) for disk diffusion AST method) which clearly showed that disk diffusion AST method overestimates the pooled VRSA prevalence. The total number of S. aureus isolates was found to be the responsible variable for the existence of heterogeneity among studies (p = 0.033).
CONCLUSION
This study showed an alarmingly high pooled prevalence of VRSA necessitating routine screening, appropriate antibiotic usage, and robust infection prevention measures to manage MRSA infections and control the emergence of drug resistance. Furthermore, mainly attributable to the overestimation of VRSA burden while using disk diffusion method, there is an urgent need to improve the methods to determine vancomycin resistance in Ethiopia and incorporate MIC-based VRSA detection methods in routine clinical laboratory tests, and efforts should be directed at improving it nationally.
TRIAL REGISTRATION
PROSPERO registration identification number: CRD42023422043.
Topics: Humans; Vancomycin-Resistant Staphylococcus aureus; Ethiopia; Methicillin-Resistant Staphylococcus aureus; Staphylococcus aureus; Prevalence; Anti-Bacterial Agents
PubMed: 37649060
DOI: 10.1186/s13756-023-01291-3 -
Medicine Jul 2023This study aimed to investigate the clinical characteristics, management and prognosis of Bacillus cereus sepsis in premature neonates. The clinical information of 8...
This study aimed to investigate the clinical characteristics, management and prognosis of Bacillus cereus sepsis in premature neonates. The clinical information of 8 premature neonates with B cereus sepsis who were treated in Shanghai Children Hospital from January 2015 to December 2019 was retrospectively collected from the medical records and analyzed. The neurodevelopment related conditions were collected at follow up visits at corrected age of 6 months and 12 months. Five patients developed meningitis, and cerebral magnetic resonance image showed abnormal in 5 patients. After treatment with meropenem and vancomycin, 1 patient died, and 7 patients survived and were smoothly discharged. At follow up visits, 1 patient was diagnosed with hydrocephalus and showed severely delayed neurodevelopment, 2 patients had mild delayed neurodevelopment, and the neurodevelopment was basically normal in remaining 4 patients. B cereus infection can cause severe complications of central nervous system, and affect neurodevelopmental outcome. Antibiotic treatment with meropenem and vancomycin is proven to be effective. Refreshing the central catheters is helpful for the prevention of B cereus sepsis and cerebral magnetic resonance image may be employed for the prognosis assessment.
Topics: Infant, Newborn; Child; Humans; Infant; Vancomycin; Bacillus cereus; Meropenem; Retrospective Studies; China; Sepsis; Prognosis; Infant, Newborn, Diseases
PubMed: 37443518
DOI: 10.1097/MD.0000000000034261 -
Frontiers in Pharmacology 2023Vancomycin is a frequently used antibiotic for treating severe infections caused by multidrug-resistant, Gram-positive pathogens. To ensure its effectiveness and...
Vancomycin is a frequently used antibiotic for treating severe infections caused by multidrug-resistant, Gram-positive pathogens. To ensure its effectiveness and minimize the risk of nephrotoxicity, safe administration and dose monitoring are crucial. Understanding the impact of vancomycin serum levels on clinical outcomes is of paramount importance, necessitating improved knowledge on its use, dose monitoring, nephrotoxicity, and safe administration. This study aimed to evaluate the incidence of acute kidney injury (AKI) in patients receiving vancomycin before and after the implementation of an institutional protocol for vancomycin administration in a public tertiary hospital in southern Brazil. A cross-sectional study design was employed, analyzing data from the electronic medical records of 422 patients who received vancomycin. The patient population was divided into two independent cohorts: those treated in 2016 (pre-protocol) and those treated in 2018 (post-protocol), following the implementation of the institutional vancomycin administration protocol. The study included 211 patients in each year of assessment. Patients from both cohorts had a Charlson Comorbidity Index (CCI) score of 4. The post-protocol cohort consisted of older individuals, with a mean age of 62.8 years. In addition, patients in the post-protocol year had higher baseline creatinine levels, higher rates of intensive care unit (ICU) hospitalization, and increased use of vasopressors. In the pre-protocol year, patients received vancomycin therapy for a longer duration. When comparing the incidence of AKI between the two groups, an intervention study revealed rates of 38.4% in group 1 and 20.9% in group 2, indicating a significant reduction ( < 0.001) in the post-protocol group. A logistic regression model was developed to predict AKI, incorporating variables that demonstrated significance ( ≤ 0.250) in bivariate analysis and those recognized in the literature as important factors for AKI, such as the duration of therapy, vancomycin serum level, and ICU hospitalization. The logistic regression classification performance was assessed using a receiver operating characteristic (ROC) curve, yielding an area under the curve of 0.764, signifying acceptable discrimination of the regression model. Implementation of the institutional protocol for vancomycin administration resulted in a significant and cost-effective impact, ensuring appropriate therapeutic dosing, reducing adverse events (e.g., nephrotoxicity), and improving clinical outcomes for patients in the study population.
PubMed: 37841919
DOI: 10.3389/fphar.2023.1154573 -
Antibiotics (Basel, Switzerland) Nov 2023Antimicrobial resistance (AMR), a serious global public health challenge, may have accelerated development during the COVID-19 pandemic because antibiotics were...
Antimicrobial resistance (AMR), a serious global public health challenge, may have accelerated development during the COVID-19 pandemic because antibiotics were prescribed for COVID-19. This study aimed to assess antibiotics use before and during the pandemic and correlate the results with the rate of resistant microorganisms detected in hospitalized patients during the study period. This single-center study looked retrospectively at four years of data (2018-2021) from Royal Hospital, Muscat, which is the biggest hospital in Oman with approximately 60,000 hospital admissions yearly. The consumption rate of ceftriaxone, piperacillin tazobactam, meropenem, and vancomycin was presented as the antibiotic consumption index, the ratio of defined daily dose (DDD) per 100 bed days. Analyses were performed using the nonparametric test for trend across the study period. Correlation between antibiotic consumption indexes and the isolated microorganisms in the four-year study period was performed using Spearman's rank correlation coefficient. We compared data from the pre-COVID-19 to the COVID-19 period. Though more patients were admitted pre-COVID-19 (132,828 versus 119,191 during COVID-19), more antibiotics were consumed during the pandemic (7350 versus 7915); vancomycin and ceftriaxone had higher consumption during than before the pandemic (-values 0.001 and 0.036, respectively). Vancomycin-resistant Enterococcus (VRE) and were detected more during the COVID-19 period with -values of 0.026 and 0.004, respectively. Carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant spp., and were detected more often during the pandemic with -values of 0.011, 0.002, and 0.03, respectively. Significant positive correlations between antibiotic consumption and drug-resistant isolates were noted. This study confirms that the overuse of antibiotics triggers the development of bacterial resistance; our results emphasize the importance of antibiotic control.
PubMed: 38136699
DOI: 10.3390/antibiotics12121665 -
Heliyon Jul 2023has caused life-threatening infections and developed resistance against conventional antimicrobials, posing a significant threat to human health worldwide. Biofilms...
has caused life-threatening infections and developed resistance against conventional antimicrobials, posing a significant threat to human health worldwide. Biofilms that surround the bacteria cells act as a protective layer, allowing cells inside the biofilm to be resistant to external stresses such as antimicrobials. Therefore, biofilms further complicate treatment available for infections caused by multi-drug resistant . A previous study on alpha-amyrin (AM), derived from ursane, was reported to significantly reduce the biomass and inhibit the metabolic activity of reference strain methicillin-resistant and methicillin-sensitive (MRSA and MSSA, respectively). In this study, the antibiofilm activity of AM was extended to include clinical isolates of MSSA and MRSA, and laboratory-generated vancomycin-intermediate (VISA) collected from University Kebangsaan Malaysia Medical Center (PPUKM) and Universiti Kebangsaan Malaysia Medical Molecular Biology Institute (UMBI). Pre-formed biofilms of biofilm-forming isolates identified from the Congo Red Agar (CRA) assay were then exposed to AM, vancomycin and oxacillin, and evaluated using the crystal violet and resazurin assays. The results showed that AM reduced the biofilm biomass of three isolates of MSSA, eight isolates of MRSA and four isolates of VISA but increased the metabolic activity in certain MSSA, MRSA and VISA isolates, indicating AM may possess biofilm reduction effects but not bactericidal effects. Based on these findings, AM could be further studied and developed as a potential therapeutic agent for chronic infections.
PubMed: 37456062
DOI: 10.1016/j.heliyon.2023.e17892