Discrepancies between prescribed daily doses and WHO defined daily doses of antibacterials at a university hospital

AIMS: The defined daily doses (DDD) defined by the WHO are widely used as an indicator to measure antibiotic use in the hospital setting. However, discrepancies exist between countries in terms of antibiotic dosage. The aim of the present study was to compare, for each antibacterial agent available at our university hospital, the prescribed daily doses (PDD) with the DDD. METHODS: Data were extracted from the pharmacy computer system. Antibiotic use was expressed in DDD per 1000 patient days. We also calculated the ratio of number of DDD:number of treatment-days and estimated the average PDD for each antibiotic and route of administration. RESULTS: The average PDD did not correspond to the DDD for many classes of antibiotics. If fluoroquinolones and cephalosporins were prescribed at a dosage close to the DDD, other antimicrobial classes such as penicillins, aminoglycosides or macrolides were not. Overall, the number of DDD overestimated the number of treatment days by 40%. For the most consumed antibiotic at our hospital, i.e. oral amoxicillin-clavulanic acid, the PDD was three times the DDD. CONCLUSIONS: Our study shows that, except for the fluoroquinolones and the cephalosporins, the number of DDD did not correctly reflect the number of antibiotic treatment days at our hospital. This does not invalidate the systematic approach of the WHO and hospitals should use the DDDs to make national and international comparisons of their antibiotic use. However, each hospital should define and validate its own indicators to describe the local exposures to antibiotics and to study the relationship with resistance.     

Correlation between prescribed daily dose,seizure freedom and defined daily dose in antiepileptic drug treatment

Background Although defined daily doses (DDD) for antiepileptic drugs (AED) have been assigned only in combination therapy, based on the literature, most patients take them in monotherapy. Furthermore, discrepancies between DDD and prescribed daily dose (PDD) were observed. Objective First, to determine PDDs of AEDs and to reveal PDD/DDD ratio among seizure free versus not seizure free patients in everyday clinical practice. Second, to test the applicability of 75% cut-off of DDD to achieve seizure freedom. Furthermore, to find out what factors might influence PDD. Setting Outpatient data files at a Hungarian university hospital were studied. Methods A retrospective, 20-year cross-sectional database was compiled from 1282 epileptic outpatients’ files. Main outcome measure Seizure freedom and PDD were used as outcome measures. Results The mean DDD% of all prescribed AEDs increased steadily from monotherapy, through bitherapy towards polytherapy (p < 0.0001). Most seizure free patients took AEDs in doses in the range of ≤75% of DDDs in monotherapy and bitherapy. Older AEDs (carbamazepine and valproate) were given in a significantly higher mean dose in bitherapy in the seizure free group. Among the newer types, only levetiracetam and lamotrigine had a significantly higher DDD% in mono-, bi-, and polytherapy. Confirmed by logistic regression analysis, gender, age, type of epilepsy, and number of AEDs had a significant impact on the value of 75% DDD. Conclusion No significant unfavourable impact of the lower ratio of PDD/DDD on the outcome of achieving seizure freedom has been confirmed. As a measure of seizure freedom, 75% of DDD may be used, although individual therapy must be emphasised. Precisely quantified DDD would provide a more accurate calculation of other derived values.     

Comparison of prescribed and defined daily doses (DDD) of selected antihypertensives--problems and conclusions

The comparison of prescribed and defined daily doses of 21 antihypertensive drugs showed minor to major differences, which have an impact on how to assess future drug demand and how to evaluate the therapeutic equivalence of various drugs. Relating problems concerning prescribing habits of drugs and research in drug demand are being discussed.     

The use of TDM data to assess the validity of defined daily doses of antiepileptics: a comparison between a Czech and Swedish University Hospital

Prescribed daily doses (PDDs) of antiepileptic drugs (AED) (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Plasma concentrations were used as an indicator of the quality of treatment. PDDs were compared with the defined daily doses (DDDs) suggested by WHO in the ATC/DDD index 2005. Request and reply forms for therapeutic drug monitoring (TDM) were used as a source of mean PDDs. The study included 2,824 adult out- and in-patients in Huddinge treated from 1995 to 1999 and 1,268 out-patients treated in Ostrava from 1993 to 2004. The differences in PDD were tested by Student's t-test. Mean values of PDD were used when patients were examined more than once. Doses given in mono- and polytherapy were compared. Mean PDDs (in mg) in mono-/polytherapy in Huddinge and Ostrava were as follows (DDDs in parenthesis): carbamazepine 588/842 and 618/770 (1,000), clonazepam 3.0/2.5 and 3.4/2.4 (8), phenytoin 278/314 and 291/288 (300), gabapentin -/1,533 and -/921 (1,800), lamotrigine 228/228 and 216/195 (300), phenobarbital 90/75 and 183/117 (100), vigabatrin -/1,794 and -/1,259 (2,000), valproic acid 1,139/1,476 and 814/950 (1,500). The PDDs of most of the AEDs were lower than the DDDs with the exceptions for valproic acid (Huddinge, in polytherapy only), phenytoin, for which PDDs and DDDs were very close, and phenobarbital for which they were similar in Huddinge but higher in Ostrava. PDDs in monotherapy were only slightly lower than in combination therapy. Patients with plasma concentrations within the therapeutic range were usually treated with slightly higher doses than the remainder. In general, plasma concentrations tended to be in the low therapeutic range. The differences in PDDs between hospitals were significant in the case of valproic acid (P < 0.001), phenobarbital (except monotherapy within), vigabatrin, and gabapentin (P < 0.01), and carbamazepine (in monotherapy P < 0.05, polytherapy P < 0.01). Our data suggest that the DDDs of AEDs should be reconsidered as, in the majority of cases, they appear to be too high.     

Actual versus prescribed timing of lovastatin doses assessed by electronic compliance monitoring

Summary The objective of the study was to compare compliance with and the hypocholesterolaemic effect of lovastatin given once daily as a morning or an evening dose. Twenty-four out-patients with familial hypercholesterolaemia were randomly assigned to receive placebo first, then lovastatin 20 mg, to be taken once daily for 4 weeks, either with the breakfast or evening meal, in a single-blind fashion.Drug compliance was assessed by pill counts and continuous electronic monitoring. Two compliance parameters were evaluated, consumption, defined as percentage of prescribed doses taken, and time compliance, the percentage of total dosing events recorded within defined intervals (6.00–10.00 h, and 17.00–21.00 h), for the morning and evening regimes.Both regimes satisfactorily reduced the total and LDL-cholesterol concentrations, and there was no significant difference in the extent of the reductions.Pill counts overestimated compliance, as revealed by the monitoring method. The times of actual consumption of doses by the patients often differed from that prescribed, predominantly in patients who were told to take the evening dose. Partial time compliance may have confounded the efficacy of the drugs. Electronic compliance monitoring appears to be particularly useful in chronopharmacological studies.Professor Ellen Weber died on 7th December 1992     

Risk of medication safety incidents with antibiotic use measured by defined daily doses

Background Medication incidents (MIs) account for 11.3 % of all reported patient-safety incidents in England and Wales. Approximately one-third of inpatients are prescribed an antibiotic at some point during their hospital stay. The WHO has identified incident reporting as one solution to reduce the recurrence of adverse incidents. Objectives The aim of this study was to determine the number and nature of reported antibiotic-associated MIs occurring in inpatients and to use defined daily doses (DDDs) to calculate the incident rate for the antibiotics most commonly associated with MIs at each hospital. Setting Two UK acute NHS teaching hospitals. Methods Retrospective quantitative analysis was performed on antibiotic-associated MIs reported to the risk management system over a 2-year period. Quality-assurance measures were undertaken before analysis. The study was approved by the clinical audit departments at both hospitals. Drug consumption data from each hospital were used to calculate the DDD for each antibiotic. Main outcome measures The number of antibiotic-related MIs reported and the incident rate for the 10 antibiotics most commonly associated with MIs at each hospital. Results Healthcare staff submitted 6,756 reports, of which 885 (13.1 %) included antibiotics. This resulted in a total of 959 MIs. Most MIs occurred during prescribing (42.4 %, n = 407) and administration (40.0 %, n = 384) stages. Most common types of MIs were omission/delay (26.3 %, n = 252), and dose/frequency (17.9 %, n = 172). Penicillins (34.5 %, n = 331) and aminoglycosides (16.6 %, n = 159) were the most frequently reported groups with co-amoxiclav (16.8 %, n = 161) and gentamicin (14.1 %, n = 135) the most frequently reported drugs. Using DDDs to assess the incident rate showed that cefotaxime (105.4/10,000 DDDs), gentamicin (25.7/10,000 DDDs) and vancomycin (23.7/10,000 DDDs) had the highest rates. Conclusions This study highlights that detailed analysis of data from reports is essential in understanding MIs and developing strategies to prevent their recurrence. Using DDDs in the analysis of MIs allowed determination of an incident rate providing more useful information than the absolute numbers alone. It also highlighted the disproportionate risk associated with less commonly prescribed antibiotics not identified using MI reporting rates alone.     

我院2014-2019年铜绿假单胞菌耐药率与抗菌药物用药频度的相关性分析

摘要：目的 分析铜绿假单胞菌(PA)耐药率与抗菌药物用药频度(DDDs)的相关性。方法 分析我院2014-2019年间PA耐 药率与抗菌药物用药频度变化情况,运用SPSS 20.0软件分析两者的相关性。以DDDs为自变量,耐药率为因变量,耐药率与 多个品种DDDs具有相关性时,进行多重线性回归分析并以方差膨胀因子(VIF)考察自变量间的共线性。当自变量间存在共线 性时,采用岭回归法分析。结果 我院PA对庆大霉素、阿米卡星、氨曲南和左氧氟沙星的耐药率均与多个品种抗菌药物DDDs 具有显著相关性(P<0.05)。多重线性回归分析发现,某些品种的用药频度间存在共线性。其中庆大霉素与氨基糖苷类存在共 线性,莫西沙星、美罗培南和碳青霉烯类三者间存在共线性,头孢他啶、莫西沙星和喹诺酮类三者间DDDs均存在共线性。 岭回归分析表明,PA对庆大霉素耐药率与庆大霉素DDDs(β=0.532,P=0.004)、酶抑制剂合剂类累计DDDs呈正相关(β=0.330, P=0.035),与头孢他啶DDDs呈负相关(β=-0.430,P=0.024),回归模型通过F检验(R2=0.652,F=8.914,P=0.0003)。对氨曲南耐药 率与喹诺酮类累计DDDs呈正相关(β=0.283,P=0.046),回归模型通过F检验(R2=0.350,F=3.588,P=0.0319)。结论 我院PA耐 药率的变迁与多种抗菌药物用药频度存在相关性。     

Platelet serotonin uptake inhibition as a basis for monitoring antidepressant drug treatment

A quantitative method for measuring serotonin uptake inhibition in fresh platelets incubated in diluted plasma (stored frozen until analyzed) from patients treated with tricyclic and related antidepressants is described. The method was used in a clinical trial comparing the specific serotonin uptake inhibitor zimelidine with the mixed serotonin-norepinephrine uptake inhibitor desipramine in patients with endogenous depression, and correlating this with plasma drug concentration assessment. The bioassay, based on the use of one single, low concentration of serotonin, was found to be very sensitive and to have a high reliability (coefficient of variation about 2% as calculated from duplicate samples), and to correlate highly with log plasma concentration of zimelidine, norzimelidine, and of desipramine. This bioassay may have some advantages in relation to plasma drug concentration assessment, but only future studies can show whether it provides a better basis for antidepressant drug monitoring.     

Differences in cognitive factors between "true drug" versus "placebo pattern" response to fluoxetine as defined by pattern analysis

OBJECTIVE: Pattern analysis has identified two types of response patterns to antidepressants: "true drug" response (TDR) and "placebo pattern" response (PPR). This study examines the relationship between cognitive factors and TDR and PPR to fluoxetine. METHODS: We assessed 310 outpatients meeting DSM-III-R criteria for major depressive disorder (MDD) who were enrolled in an 8-week open trial of fluoxetine 20 mg/day. Response patterns were determined using the clinical global impressions-improvement (CGI-I). We administered the following self-rated scales to all patients at the baseline visit and at endpoint: perceived stress scale (PSS), cognitions questionnaire (CQ), Beck hopelessness scale (BHS) and dysfunctional attitudes scale (DAS). RESULTS: One hundred and thirty-four patients had TDR, 66 patients had PPR, and 110 patients were non-responders (NR). Demographic variables and severity of depression at baseline (HAMD-17) were not significantly different between the two response pattern groups. We compared cognitive factors before and after treatment across patients with TDR and PPR, and there were no significant differences at baseline in CQ, PSS, BHS, and DAS scores. At endpoint, outpatients with PPR had significantly lower scores on the PSS (p < 0.001) compared to the patients with TDR, even after adjusting for multiple comparisons and severity of depression at endpoint. CONCLUSIONS: Significant differences in cognitive/psychological factors, specifically lower post-treatment perceived stress, accompany "placebo" pattern of response to antidepressant treatment and differentiate it from "true drug" response pattern, as defined by pattern analysis.     

治疗冠心病、心绞痛的4种中成药限定日剂量数分析

目的：通过比较长江流域6城市近3a治疗冠心病、心绞痛的中成药用药特点及趋势,为医院合理用药及医保用药提供参考。方法：依据上海、南京、杭州、武汉、成都、重庆6城市样本医院用药数据库中4种药物的用药数量、金额,根据各自的限定日剂量(DDD)值分别计算出各药的DDDs及每DDD价格,同种药物不同规格的DDDs分别计算,然后合并成该药的总的DDDs。结果：地奥心血康的每DDD价格最具优势,而复方丹参滴丸的用药成本最高；上海、杭州、南京的用药成本低于武汉、成都及重庆；大剂量包装的药物的每DDD价格相对更低。结论：DDDs可为中成药合理用药及医保用药提供参考。     

Reliable HPLC method for therapeutic drug monitoring of frequently prescribed tricyclic and nontricyclic antidepressants

A new high-performance liquid chromatography method is presented for the determination of 10 frequently prescribed tricyclic and nontricyclic antidepressants: imipramine, amitriptyline, clomipramine, fluoxetine, sertraline, paroxetine, citalopram, mirtazapine, moclobemide and duloxetine. The simple and accurate sample preparation step, consisted of liquid:liquid extraction with recoveries ranging between 72% and 86%, except for moclobemide (59%). Separation was obtained using a reverse phase Select B column under isocratic conditions with UV detection (230 nm). The mobile phase consisted of 35% of a mixture of acetonitrile/methanol (92:8, v/v) and 65% of 0.25 mol L(-1) sodium acetate buffer, pH 4.5. The standard curves were linear over a working range of 2.5-1000 ng mL(-1) for moclobemide, 5-2000 ng mL(-1) for citalopram, duloxetine, fluoxetine, 10-2000 ng mL(-1) for sertraline, imipramine, paroxetine, mirtazapine and clomipramine. The intra-assay and inter-assay precision and accuracy were studied at three concentrations (50, 200, and 500 ng mL(-1)). The intra-assay coefficients of variation (CVs) for all compounds were less than 8.8%, and all inter-CVs were less than 10%. Limits of quantification were 2.5 ng mL(-1) for moclobemide, 5 ng mL(-1) for citalopram, duloxetine and amitriptyline, and 10 ng mL(-1) for mirtazapine, paroxetine, imipramine, fluoxetine, sertraline, and clomipramine. No interference of the drugs normally associated with antidepressants was observed. The method has been successfully applied to the analysis of real samples, for the drug monitoring of ten frequently prescribed tricyclic and non-tricyclic antidepressant drugs.