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1.
Curr Ther Res Clin Exp ; 97: 100687, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439399

RESUMO

Background: Current guidelines for the therapeutic monitoring of vancomycin recommend dosing based on the area under the concentration-time curve (AUC) to achieve clinical efficacy while reducing nephrotoxicity. Although a wide range of nephrotoxicity thresholds have been reported, few studies have documented clinical outcomes based on AUC-guided vancomycin dosing in Korea. Objective: The aim of the study was to evaluate whether a relationship exists between AUC and treatment outcomes in vancomycin treated patients in methicillin-resistant Staphylococcus aureus bacteremia. Furthermore, this study tries to estimate AUC threshold for treatment failure and nephrotoxicity. Methods: The records of adult patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin for ≥72 hours without dialysis between April 2013 and April 2021, were reviewed retrospectively. Treatment success was defined as defervescence and blood culture sterilization by day 7. Nephrotoxicity was defined as an increase in serum creatinine levels ≥0.3 mg/dL or a 50% increase from baseline on 2 consecutive days. Bayesian estimation was used to predict individual vancomycin AUC. Both classification and regression tree and receiver operating characteristic curve analyses were performed to estimate the optimal AUC thresholds for vancomycin efficacy and nephrotoxicity. Results: Of 118 patients, 61 (51.7%) experienced treatment failure and 42 (35.6%) developed acute kidney injury. The vancomycin AUC threshold for predicting acute kidney injury was 615.0 mg· hr/L. In the multivariate analysis, AUC ≥615.0 mg· hr/L was a significant risk factor for nephrotoxicity (adjusted odds ratio [aOR] = 5.24; 95% CI, 1.8-14.65). The lower threshold for treatment failure was not defined because it was not statistically significant. Risk factors for treatment failure included low body mass index (aOR = 0.82; 95% CI, 0.70-0.96), severity of acute illness represented by complicated infection (aOR = 77.56; 95% CI, 16.7-359.4) and comorbidities, such as solid organ tumors (aOR = 6.61; 95% CI, 1.19-36.81) and cerebrovascular disease (aOR = 6.05; 95% CI, 1.17-31.23). Conclusions: Although AUC-guided vancomycin dosing was associated with a reduced risk of acute kidney injury, its ability to predict clinical outcomes was modest. Further studies are needed to define the AUC therapeutic range to maximize efficacy and minimize nephrotoxicity. (Curr Ther Res Clin Exp. 2023; 83:XXX-XXX).

2.
Int J Infect Dis ; 146: 107150, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38914368

RESUMO

OBJECTIVE: We evaluated the changes and molecular epidemiology of meningococcal carriage in military recruits after quadrivalent meningococcal conjugate vaccines (MenACWY) vaccination. METHODS: Oropharyngeal swabs were obtained at the beginning and end of the 5-week training. Carriage rates before and after vaccination were compared to estimate vaccine effectiveness (VE). Cultured isolates were characterized by multi-locus sequence typing (MLST). RESULTS: Of 866 vaccinated participants, the overall carriage rate was 10.6% prior to MenACWY vaccination and it tended to decrease to 9.5% after 5 weeks of vaccination (P = 0.424). Carriage rate of serogroup ACWY decreased significantly after vaccination (VEACWY = 72.6%, 95% CI: 36.3-88.2), and serogroup C was particularly reduced (VEC = 83.0%, 95% CI: 50.6-94.1), whereas non-groupable isolates increased significantly after vaccination (VENG = -76.1%, 95% CI: -176.2 to -13.1). Among 99 carriage isolates with complete MLST profiles, 45 different sequence types with nine clonal complexes (CCs) were identified, and 35.3% of the carriage isolates belonged to hypervirulent strains such as CC-32, CC-41/44, and CC-269. CONCLUSIONS: MenACWY vaccination in military recruits led to reduced carriage rates of serogroups C, W, and Y within a short 5-week period. However, serogroup B isolates belonging to the hypervirulent lineage remained after the implementation of MenACWY vaccination.


Assuntos
Portador Sadio , Genótipo , Infecções Meningocócicas , Vacinas Meningocócicas , Militares , Tipagem de Sequências Multilocus , Neisseria meningitidis , Vacinas Conjugadas , Humanos , Vacinas Meningocócicas/administração & dosagem , Vacinas Meningocócicas/imunologia , Neisseria meningitidis/genética , Neisseria meningitidis/imunologia , Neisseria meningitidis/classificação , Infecções Meningocócicas/prevenção & controle , Infecções Meningocócicas/epidemiologia , Infecções Meningocócicas/microbiologia , Portador Sadio/microbiologia , Portador Sadio/epidemiologia , Estudos Prospectivos , Masculino , Adulto Jovem , República da Coreia/epidemiologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/imunologia , Feminino , Sorogrupo , Adulto , Vacinação
3.
Sci Rep ; 13(1): 14501, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37666900

RESUMO

This study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (P = 0.018). However, it significantly declined by - 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (P < 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio [OR] = 0.98; 95% confidence interval [CI] 0.96-1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16-5.50), and pneumonia (OR = 2.59, 95% CI 1.08-6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.


Assuntos
Anti-Infecciosos , Gestão de Antimicrobianos , Humanos , Carbapenêmicos/uso terapêutico , Antibacterianos/uso terapêutico , Terapia Comportamental
4.
Front Immunol ; 13: 975363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119092

RESUMO

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1ß levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Anticorpos Neutralizantes , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Humanos , Imunoglobulina G , Interleucina-6
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