Trends in Antibiotic Prescribing in Adults in Dutch General Practice

Background: Antibiotic consumption is associated with adverse drug events (ADE) and increasing antibiotic resistance. Detailed information of antibiotic prescribing in different age categories is scarce, but necessary to develop strategies for prudent antibiotic use. The aim of this study was to determine the antibiotic prescriptions of different antibiotic classes in general practice in relation to age. Methodology: Retrospective study of 22 rural and urban general practices from the Dutch Registration Network Family Practices (RNH). Antibiotic prescribing data were extracted from the RNH database from 2000-2009. Trends over time in antibiotic prescriptions were assessed with multivariate logistic regression including interaction terms with age. Registered ADEs as a result of antibiotic prescriptions were also analyzed. Principal Findings: In total 658,940 patients years were analyzed. In 11.5% (n = 75,796) of the patient years at least one antibiotic was prescribed. Antibiotic prescriptions increased for all age categories during 2000-2009, but the increase in elderly patients (>80 years) was most prominent. In 2000 9% of the patients >80 years was prescribed at least one antibiotic to 22% in 2009 (P<0.001). Elderly patients had more ADEs with antibiotics and co-medication was identified as the only independent determinant for ADEs. Conclusion/Discussion: The rate of antibiotic prescribing for patients who made a visit to the GP is increasing in the Netherlands with the most evident increase in the elderly patients. This may lead to more ADEs, which might lead to higher consumption of health care and more antibiotic resistance

Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study

Background: Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.Results: Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.Conclusions: Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated

Adequate antimicrobial treatment in elderly patients

This dissertation examines the use of antibiotics in elderly patients. Elderly patients use far more antibiotics than younger patients. While the same standard dosages are prescribed for all adult patients, elderly patients tend to have a higher concentration of antibiotics in their blood than younger patients. This is caused by reduced creatinine clearance of the antibiotics as a result of renal impairment. Like children, older patients require a modified dose of antibiotics. Adjusting this dose in older patients can be difficult because it is hard to make an accurate assessment of renal function in these patients, and because of significant individual differences among these patients. This study provides a number of recommendations for adjusting the dose of various types of antibiotics

Vancomycin Dosing in Neutropenic Patients

Background: To compare vancomycin pharmacokinetic parameters in patients with and without neutropenia. Methods: Patients >= 18 years admitted on general wards were included. Routinely vancomycin trough and peak plasma concentrations were measured with a fluorescence polarization immunoassay. Pharmacokinetic parameters of individual patients were determined with maximum a posterior Bayesian estimation (MW Pharm 3.60). Neutropenia was defined as neutrophils Principal Findings: A total of 171 patients were included. Patients with neutropenia (n = 56) had higher clearance of vancomycin (CLva), 67 (+/- 26) mL/min, compared to patients without neutropenia (n = 115), CLva 50 (622) mL/min (p, 0.001). No significant difference was found in serum creatinine and vancomycin volume of distribution. Neutropenia was positively associated with CLva, independently of relevant co-variables (B: 12.122, 95% CI: 1.095 to 23.149, p = 0.031). On average patients with neutropenia needed 33% higher doses of vancomycin to attain adequate exposure, i.e. AUC(24)>= 400 mgxh/L. Furthermore, 15 initially neutropenic patients in our study group received vancomycin for a second administration period. Ten patients received the second administration period during another neutropenic period and 5 patients during a non-neutropenic phase. All 5 patients with vancomycin during both neutropenic and non-neutropenic phase had higher CLva (91 (+/- 26) mL/min) during the neutropenic period and lower CLva (45 (+/- 10) mL/min) during the non-neutropenic phase (p = 0.009). Conclusion: This study shows that most patients with neutropenia have augmented CLva. In a small group of patients that received vancomycin during two episodes, the augmented CLva seems to be reversible in the non-neutropenic period. Our data indicate that it is important to increase the daily dose with one third in patients with neutropenia (from 15 mg/kg twice daily to 13 mg/kg three times daily). Frequent performance of therapeutic drug monitoring in patients with neutropenia may prevent both therapy failure due to low AUCs and overcomes toxicity due to high vancomycin trough concentrations during recovery from neutropenia