ABSTRACT
BACKGROUND: Clostridium difficile infection (CDI) is a significant nosocomial infection worldwide, that recurs in as many as 35% of infections. Risk of CDI recurrence varies by ribotype, which also vary in sporulation and germination rates. Whether sporulation/germination mediate risk of recurrence and effectiveness of treatment of recurring CDI remains unclear. We aim to assess the role of sporulation/germination patterns on risk of recurrence, and the relative effectiveness of the recommended tapered/pulsing regimens using an in silico model. METHODS: We created a compartmental in-host mathematical model of CDI, composed of vegetative cells, toxins, and spores, to explore whether sporulation and germination have an impact on recurrence rates. We also simulated the effectiveness of three tapered/pulsed vancomycin regimens by ribotype. RESULTS: Simulations underscored the importance of sporulation/germination patterns in determining pathogenicity and transmission. All recommended regimens for recurring CDI tested were effective in reducing risk of an additional recurrence. Most modified regimens were still effective even after reducing the duration or dosage of vancomycin. However, the effectiveness of treatment varied by ribotype. CONCLUSION: Current CDI vancomycin regimen for treating recurrent cases should be studied further to better balance associated risks and benefits.
Subject(s)
Anti-Bacterial Agents/pharmacology , Clostridioides difficile/drug effects , Clostridium Infections/drug therapy , Models, Statistical , Spores, Bacterial/drug effects , Vancomycin/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Bacterial Toxins/antagonists & inhibitors , Bacterial Toxins/biosynthesis , Clostridioides difficile/classification , Clostridioides difficile/genetics , Clostridioides difficile/growth & development , Clostridium Infections/microbiology , Clostridium Infections/pathology , Computer Simulation , Drug Administration Schedule , Drug Dosage Calculations , Humans , Microbial Sensitivity Tests , Recurrence , Ribotyping , Spores, Bacterial/growth & development , Spores, Bacterial/pathogenicity , Vancomycin/pharmacokineticsABSTRACT
OBJECTIVE: the purpose of this study was to explore healthcare providers' perceptions and reactions to the Ebola Virus Disease (EVD) epidemic. DESIGN: a descriptive, qualitative study design was employed. Focus groups were conducted with Liberian healthcare providers who participated in care of patients with EVD. SETTING: the study was conducted in Bong County, Liberia (population: 333,000), which was severely affected, with over 650 reported cases and close to 200 deaths by the end of 2015. PARTICIPANTS: the total sample of 58 participants, included 11 nurses, ten traditional birth attendants (TBAs), four midwives, 28 general community health volunteers, three physician assistants, one community member and one pharmacy dispenser. MEASUREMENTS AND FINDINGS: five core themes related to changes in healthcare practices and interactions since the EVD outbreak were identified based on the results of the focus groups; fear, stigma, resource constraints, lack of knowledge and training, and shifting cultural practices. KEY CONCLUSIONS: this work represents a preliminary understanding of Liberian healthcare workers reactions to the EVD epidemic, and highlights the significant issues they faced as they attempted to care for patients and protect themselves. IMPLICATIONS FOR PRACTICE: while the EVD epidemic has been declared over, preparedness activities for future disease outbreaks must continue. This study can inform future healthcare policy initiatives as well as preparedness activities targeted towards healthcare workers in low resource settings.