The impact of improper empirical usage of antipseudomonals on admission to an acute care hospital.

BACKGROUND: Many septic patients are receiving empirical antipseudomonal (or Gram-negative non-glucose fermenting [GNNGF]) coverage on admission to acute care hospitals, despite the fact that the indications are not scientifically established. Overuse of antipseudomonals might contribute to the burden of resistance. MATERIALS AND METHODS: Retrospective observational analyses of the characteristics of septic adult patients who received empirical antipseudomonals, along with its impact on outcomes, were executed at Shamir Medical Center, Zerifin, Israel (08-12/2016). Proper empirical antipseudomonal usage was defined by the following: (1) if the patient received the agents as per Infectious Disease Society of America (IDSA) guidelines; (2) if the patient had a positive multidrug-resistant organism (MDRO) test on his or her admission score (https://assafharofe.azurewebsites.net); or (3) if a GNNGF was the eventual causative pathogen. Risk factors and outcomes were queried by logistic and Cox regression. RESULTS: GNNGF was the causative pathogen in only 57 (3.7%) of 1536 patients with acute sepsis. There were 192 (13%) who received empirical antipseudomonals, of whom 161 (84%) were defined as proper. Patients who received empirical antipseudomonals were significantly older (P < 0.001), with higher indices of chronic and acute conditions, and higher rates of past MDRO carriage; 24 patients received empirical antipseudomonals only because of IDSA guidelines (15%), and that was an independent predictor for later acquisition (up to 90 days) of carbapenem-resistant A. baumannii (CRAB; odds ratio [aOR] = 7.1; P = 0.03). CONCLUSIONS: Improper empirical usage of antipseudomonals in acute care hospitals is common. Instituting empirical antipseudomonals solely due to IDSA guidelines was independently associated with later acquisition of CRAB. Empirical antipseudomonal usage should be based on scientifically established prediction tools and not on IDSA guidelines.

The Role of an Interventional Program for Improving Pharmacovigilance at a Pediatric Facility.

Background: The reporting rate of adverse drug reactions (ADRs) by healthcare professionals is low. ADR interventional programs may improve the reporting rate by the medical team. Our literature search revealed that only a few interventional studies among the pediatric population have been published. Objective: We aimed to create an interventional program in order to improve the reporting rate of ADRs during the interventional period compared to the control period, detect which drugs frequently lead to ADRs and determine the most serious ADRs. Design: A 3-month prospective intervention study compared with one year prior to the intervention (control period). ADR data was also collected for the year following the study period. Healthcare professionals were encouraged to report ADRs and an ADR reporting system was created for them. Setting: Pediatric Division at Shamir Medical Center (Assaf Harofeh), a tertiary care medical center. Results: The study population included 3,753 admitted patients with 1,323 prescriptions during the study period. During the period before the intervention was started, the ADR reporting rate was null. During the study period, 46 reports were collected: 46% from the general pediatric department, 26% from the pediatric neurology department, and 22% and 6% from the pediatric and neonatal intensive care units, respectively. Antiepileptic medications, IVIG, steroids and antibiotics were frequently reported to induce ADRs. Serious ADRs were also reported in 5 cases. One year of follow up after the intervention revealed a significant decline in the reporting rate. Conclusion: It is important to periodically encourage healthcare professionals to report any ADRs in order to increase knowledge about medication safety and prevent fatal harm.

Correction: Chronic use of psychotropic medications in breastfeeding women: Is it safe?

[This corrects the article DOI: 10.1371/journal.pone.0197196.].

Chronic use of psychotropic medications in breastfeeding women: Is it safe?

BACKGROUND: Current knowledge regarding chronic use of psychotropic medications during breastfeeding is limited. The objective of this study was to evaluate the long-term effects of psychotropic monotherapy use during lactation on the breastfed infant. MATERIALS AND METHODS: In this prospective study, we followed 280 infants whose mothers contacted the Drug Consultation Center (DCC) at Assaf Harofeh Medical Center between January 2011 and December 2015, seeking information regarding the chronic use of psychotropic medications during lactation. This group was compared with a group of 152 callers, who inquired evidence regarding the use of antibiotics compatible with breastfeeding. Information on adverse effects, physical measures and gross motor developmental milestone achievements of the breastfed infants was obtained during a follow-up telephone interview. At follow up, the median age of the infants in the Psychotropic-drug group was 20 (11-33) months versus 36 (20-48) months in the Antibiotic group (p < 0.001). The outcomes were compared between the groups followed by a propensity score matching to control for difference in baseline characteristics. RESULTS: At follow-up, no significant differences between infants in the two groups were observed with regard to height, weight, head circumference and weight-length ratio percentile (p = 0.339, p = 0.223, p = 0.738, p = 0.926, respectively). Children in both groups were, according to their parents, within the normal developmental range for all milestones, according to the Denver Developmental Scale. Use of psychotropic medications during breastfeeding was not significantly associated with adverse reactions. After propensity score matching (n = 120 pairs) to control for differences in baseline characteristics and the length of lactation, only one significant difference was reported, sleepiness in infants in the study group (7/120) and none in the comparison group (p = 0.008). CONCLUSIONS: Chronic use of psychotropic monotherapy during lactation is associated with normal growth and gross motor developmental as by milestone achievements reported by parents. Sleepiness was reported, it seemed self-limited with no developmental effect.

Use of Psychotropic Medications in Breastfeeding Women.

BACKGROUND: Breastfeeding women who are prescribed with psychotropic medications on a regular basis are often concerned, regarding the possible implications of such treatment on the breastfed infant. A mother's well-being has a direct influence on the well-being of the baby. However, the notorious reputation of psychotropic medications may lead to suboptimal prescribing by the physician and poor adherence by the mother. METHODS: A PubMed search (from 1976 through February 2017) was conducted for commonly used psychotropic drug classes, as well as individual medications commonly prescribed in these classes, along with the MeSH terms "breastfeeding"/"lactation". In each case, we chose studies that describe the pharmacokinetics of passage into breast milk and/or adverse effects in breastfed infants. RESULTS: No large-scale controlled studies regarding the safety of psychotropic medications in breastfeeding mothers were reported. Based on case reports and small studies, most psychotropic medications produce low milk levels and low plasma levels in the infant, while serious adverse effects in the breastfed infant are rarely reported. Safety data for some psychotropic medications are still unavailable. CONCLUSION: According to the data available in the literature to date, most psychotropic medications are expected to produce low levels in breast milk with no clinical importance. Nevertheless, an individual risk-benefit assessment of a proposed treatment should always be performed, as inter-individual differences may have a substantial effect on the breastfeeding infant's response to the treatment. Further studies and additional objective data are needed to consolidate and improve our current knowledge of psychopharmacotherapy in breastfeeding women. Birth Defects Research 109:957-997, 2017. © 2017 Wiley Periodicals, Inc.

International Normalized Ratio Is Significantly Elevated With Rivaroxaban and Apixaban Drug Therapies: A Retrospective Study.

PURPOSE: Direct factor Xa inhibitors such as rivaroxaban or apixaban may prolong prothrombin time (PT) and elevate international normalized ratio (INR). However, these tests are not reliable for assessing the anticoagulation effects of these agents. PT assay sensitivity is relatively weak at therapeutic drug concentrations and is subjected to significant variations depending on the reagent used. Conversion of PT to INR may even increase the variability. We conducted a retrospective cross-sectional study aiming to assess the prevalence and extent of INR elevation in hospitalized patients receiving rivaroxaban or apixaban as part of their home medications and to find out whether other existing factors could elevate INR apart from the drug entity itself. METHODS: The data collected from 218 hospitalized patients׳ charts included PT and INR taken on admission, patients׳ characteristics, laboratory results, other medications regularly used, and coexisting clinical conditions. FINDINGS: No statistically significant association between INR elevation and the parameters examined was found in our study. INR was significantly elevated in both drug groups (P < 0.001), with 84.2% of rivaroxaban patients and 78.3% of apixaban patients presenting with INR levels above the higher limit of the normal range. Furthermore, INR was significantly higher in the rivaroxaban group than in the apixaban group (P < 0.001). IMPLICATIONS: Both of the reviewed drugs significantly elevated INR. Moreover, rivaroxaban elevates INR significantly more than apixaban, and there are apparently no other factors affecting INR but the drugs themselves. Larger prospective studies are needed to confirm and clarify the clinical significance of these results.