Prashant Nannan Panday

Drug-drug interaction checking assisted by clinical decision support: a return on investment analysis

BACKGROUND Drug-drug interactions (DDIs) are very prevalent in hospitalized patients. OBJECTIVES To determine the number of DDI alerts, time saved, and time invested after suppressing clinically irrelevant alerts and adding clinical-decision support to relevant alerts. MATERIALS AND METHODS The most frequently occurring DDIs were evaluated for clinical relevance by a multidisciplinary expert panel. Pharmacist evaluation of relevant DDIs was facilitated using computerized decision support systems (CDSS). During Phase 1, only CDSS-assisted DDI checking was implemented. During Phase 2, CDSS-assisted DDI checking remained in place, and clinically irrelevant DDIs were suppressed. In each phase, the number of alerts and duration of pharmacist DDI checking were compared to conventional DDI checking. In addition, the time invested to implement and configure the CDSS was compared to the time saved using CDSS-assisted DDI checking. RESULTS CDSS-assisted DDI checking resulted in a daily decrease of DDI checking alerts from 65 to 47 alerts in Phase 1 (P = .03) and from 73 to 33 alerts in Phase 2 (P = .003). DDI checking duration decreased from 15 to 11 minutes (P = .044) and from 15½ to 8½ minutes (P = .001) in Phases 1 and 2, respectively. Almost 298 of the 392 hours required for implementation were invested by pharmacists. An annual timesaving of 30 hours yielded a return on investment of 9.8 years. CONCLUSION CDSS-assisted DDI checking resulted in a 55% reduction of the number of alerts and a 45% reduction in time spent on DDI checking, yielding a return on investment of almost 10 years. Our approach can be used to refine other drug safety checking modules, increasing the efficiency of checking for drug safety without the need to add more staff pharmacists.

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

Like any other drug, antimicrobial drugs are prone to pharmacokinetic drug interactions. These drug interactions are a major concern in clinical practice as they may have an effect on efficacy and toxicity. This article provides an overview of all published pharmacokinetic studies on drug interactions of the commonly prescribed antimicrobial drugs oxazolidinones, rifamycines, macrolides, fluoroquinolones, and beta-lactams, focusing on systematic research. We describe drug-food and drug-drug interaction studies in humans, affecting antimicrobial drugs as well as concomitantly administered drugs. Since knowledge about mechanisms is of paramount importance for adequate management of drug interactions, the most plausible underlying mechanism of the drug interaction is provided when available. This overview can be used in daily practice to support the management of pharmacokinetic drug interactions of antimicrobial drugs.

Cost-minimization model of a multidisciplinary antibiotic stewardship team based on a successful implementation on a urology ward of an academic hospital.

Background In order to stimulate appropriate antimicrobial use and thereby lower the chances of resistance development, an Antibiotic Stewardship Team (A-Team) has been implemented at the University Medical Center Groningen, the Netherlands. Focus of the A-Team was a pro-active day 2 case-audit, which was financially evaluated here to calculate the return on investment from a hospital perspective. Methods Effects were evaluated by comparing audited patients with a historic cohort with the same diagnosis-related groups. Based upon this evaluation a cost-minimization model was created that can be used to predict the financial effects of a day 2 case-audit. Sensitivity analyses were performed to deal with uncertainties. Finally, the model was used to financially evaluate the A-Team. Results One whole year including 114 patients was evaluated. Implementation costs were calculated to be €17,732, which represent total costs spent to implement this A-Team. For this specific patient group admitted to a urology ward and consulted on day 2 by the A-Team, the model estimated total savings of €60,306 after one year for this single department, leading to a return on investment of 5.9. Conclusions The implemented multi-disciplinary A-Team performing a day 2 case-audit in the hospital had a positive return on investment caused by a reduced length of stay due to a more appropriate antibiotic therapy. Based on the extensive data analysis, a model of this intervention could be constructed. This model could be used by other institutions, using their own data to estimate the effects of a day 2 case-audit in their hospital.

Automatic day-2 intervention by a multidisciplinary antimicrobial stewardship-team leads to multiple positive effects

Background: Antimicrobial resistance rates are increasing. This is, among others, caused by incorrect or inappropriate use of antimicrobials. To target this, a multidisciplinary antimicrobial stewardship-team (A-Team) was implemented at the University Medical Center Groningen on a urology ward. Goal of this study is to evaluate the clinical effects of the case-audits done by this team, looking at length of stay (LOS) and antimicrobial use. Methods: Automatic e-mail alerts were sent after 48 h of consecutive antimicrobial use triggering the case-audits, consisting of an A-Team member visiting the ward, discussing the patient’s therapy with the bed-side physician and together deciding on further treatment based on available diagnostics and guidelines. Clinical effects of the audits were evaluated through an Interrupted Time Series analysis and a retrospective historic cohort. Results: A significant systemic reduction of antimicrobial consumption for all patients on the ward, both with and without case-audits was observed. Furthermore, LOS for patients with case-audits who were admitted primarily due to infections decreased to 6.20 days (95% CI: 5.59–6.81) compared to the historic cohort (7.57 days; 95% CI: 6.92–8.21; p = 0.012). Antimicrobial consumption decreased for these patients from 8.17 DDD/patient (95% CI: 7.10–9.24) to 5.93 DDD/patient (95% CI: 5.02–6.83; p = 0.008). For patients with severe underlying diseases (e.g., cancer) these outcome measures remained unchanged. Conclusion: The evaluation showed a considerable positive impact. Antibiotic use of the whole ward was reduced, transcending the intervened patients. Furthermore, LOS and mean antimicrobial consumption for a subgroup was reduced, thereby improving patient care and potentially lowering resistance rates.

Target attainment with continuous dosing of piperacillin/tazobactam in critical illness: a prospective observational study

Optimal dosing of β-lactam antibiotics in critically ill patients is a challenge given the unpredictable pharmacokinetic profile of this patient population. Several studies have shown intermittent dosing to often yield inadequate drug concentrations. Continuous dosing is an attractive alternative from a pharmacodynamic point of view. This study evaluated whether, during continuous dosing, piperacillin concentrations reached and maintained a pre-defined target in critically ill patients. Adult patients treated with piperacillin by continuous dosing in the intensive care unit of a university medical centre in The Netherlands were prospectively studied. Total and unbound piperacillin concentrations drawn at fixed time points throughout the entire treatment course were determined by liquid chromatography-tandem mass spectrometry. A pharmacokinetic combined target of a piperacillin concentration ≥80 mg/L, reached within 1 h of starting study treatment and maintained throughout the treatment course, was set. Eighteen patients were analysed. The median duration of monitored piperacillin treatment was 60 h (interquartile range, 33-96 h). Of the 18 patients, 5 (27.8%) reached the combined target; 15 (83.3%) reached and maintained a less strict target of >16 mg/L. In this patient cohort, this dosing schedule was insufficient to reach the pre-defined target. Depending on which target is to be met, a larger initial cumulative dose is desirable, combined with therapeutic drug monitoring.

Moxifloxacin plus rifampin as an alternative for levofloxacin plus rifampin in the treatment of a prosthetic joint infection with staphylococcus aureus

OBJECTIVES The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin. METHODS Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005-2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up. RESULTS Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C-reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P = 0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P = 0.36), treatment was successful in 89% vs. 87.5%, respectively (P = 0.89). None of the failures in the moxifloxacin group were due to rifampin- or moxifloxacin-resistant S. aureus strains. CONCLUSION Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA.

Doing the right things and doing things right: inpatient drug surveillance assisted by clinical decision support

Increased budget constraints and a continuous focus on improved quality require an efficient inpatient drug surveillance process. We describe a hospital-wide drug surveillance strategy consisting of a multidisciplinary evaluation of drug surveillance activities and using clinical decision support to augment drug surveillance practices. Key characteristics of the decision support system are the integration of the Dutch national knowledge base (G-Standard), the ability to monitor the effects of drug therapy over time and prevent irrelevant alerting by adding essential patient data to the conventional medication safety checking algorithm. Integration of existing national medication safety knowledge bases into decision support systems assures the availability of up-to-date information, minimises maintenance and prevents irrelevant alerts. Developing decision algorithms based on the desired intervention decreases the burden of validation and maintenance, as duplication of multiple similar decision algorithms is prevented.