An essential component of antimicrobial stewardship during the COVID-19 pandemic in the intensive care unit: de-escalation.

BACKGROUND: The antimicrobial de-escalation strategy (ADE) plays a crucial role in antimicrobial stewardship, reducing the likelihood of bacterial resistance. This study aims to evaluate how often the intensive care unit (ICU) used ADE for empirical treatment during COVID-19. MATERIALS: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infections were retrospectively studied from September 2020 to December 2021. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of the antimicrobial to narrow the antimicrobial spectrum within the first 3 days of therapy, according to the test results and clinical picture. RESULTS: A total of 99 patients were included in the study. The number of patients who received empirical combined therapy (38.4%) was lower than those who received monotherapy (61.6%). The most preferred monotherapy (45.9%) was piperacillin-tazobactam, while the most preferred in combination treatment (22.7%) was meropenem. Within the first 3 days of admittance to the ICU, 3% of patients underwent ADE for their empirical antimicrobial therapy, 61.6% underwent no change, and 35.4% underwent change other than ADE. Procalcitonin levels were below 2 µg/L on the third day of treatment in 69.7% of the patients. Culture or culture-antibiogram results of 50.5% of the patients were obtained within the first 3 days of empirical therapy. There was no growth in the culture results of 21 patients (21.2%) during their ICU stay. CONCLUSION: In this study, ADE practice was much lower than expected. In order to reduce the significant differences between theory and reality, clinical, laboratory, and organisational conditions must be objectively assessed along with patient characteristics.

Potentially Inappropriate Medication Use in Older Adults with Chronic Kidney Disease.

Objectives: This study aimed to identify the prevalence of potentially inappropriate medication use (PIMU) in adults above the age of 65 with chronic kidney disease (CKD) according to the American Geriatric Society Beers Criteria (Beers), Screening Tool of Older People's Potentially Inappropriate Prescriptions Criteria (STOPP) and medication appropriateness index (MAI) 30 criteria and to compare them to justify their use in this specific patient group. Materials and Methods: This was a retrospective and descriptive study conducted between October 1st, 2019 and March 18th, 2020 at Ibni Sina Hospital, Nephrology Department, Faculty of Medicine, Ankara University. Results: Among 269 patients discharged from the hospital during the study period, 100 of them were eligible for the study. The mean age was 73.3 ± 6.9 years and 51.9% of them were male. The prevalence of 35 PIMU was 91%, 42%, and 70% according to the Beers, STOPP, and MAI criteria, respectively. There was a statistically significant difference in terms of prevalence among 3 criteria (p<0.001). Beer detected more PIMU (11.3% vs. 6.4%) and had higher sensitivity among older adults with CKD (0.97 vs. 0.56) compared to the STOPP criteria. Most patients had at least one drug-drug interaction (DDIs) in their discharge prescription (93%) and DDI was one of the main contributors of PIMU. Proton pump inhibitors were the most common medication associated with PIMU in all 3 criteria. Conclusion: The prevalence of PIMU was high among older adults with CKD at discharge according to these criteria. To improve the prescriptions after hospital discharge, it is considered appropriate to use Beers criteria under guidance of a clinical pharmacist.

Potential drug-drug interactions of immunosuppressants in kidney transplant recipients: comparison of drug interaction resources.

Background Drug-drug interactions are frequently observed in kidney transplant recipients due to polypharmacy and use of immunosuppressants. However, there is only one study evaluating clinically relevant potential drug-drug interactions of immunosuppressants specially in kidney transplant recipients by means of online databases and Stockleys Drug Interactions, as a gold standard. Aim This study aimed to compare four online databases used frequently to determined clinically relevant potential drug-drug interactions of immunosuppressants in kidney transplant recipients according to the Renal Drug Handbook. Method This was a descriptive cross-sectional study conducted between October 1, 2019, and March 18, 2020, in the nephrology ward of Ankara University School of the Medicine, Ibn-i Sina Hospital. In total, 52 adult patients' discharge prescriptions were retrieved from their medical records and analyzed retrospectively. Micromedex®, Lexicomp®, Medscape, and Drugs.com databases were used to evaluate drug interactions. The Renal Drug Handbook was used as a gold standard to do specificity and sensitivity analysis. Results A total of 127 potential drug-drug interactions between the immunosuppressants and co-medications were detected by at least one online database. 32 (25.2%) of these were approved as clinically relevant potential drug-drug interactions by the Renal Drug Handbook. Lexicomp® and Drugs.com have exhibited the highest sensitivity (0.72 and 0.75) while Micromedex® has shown the highest specifity (0.83). Furthermore, the highest positive predictive value has been observed in Micromedex® (0.53). Micromedex® and Medscape had the highest negative predictive value (0.83 and 0.82). However, the kappa value of all was low. The values of inter-rater agreement (Kappa index) between online databases and the Renal Drug Handbook were weak (range 0.05-0.36). In addition, only 11 (8.7%) of potential drug-drug interactions were identified by all online databases. Conclusion This study showed that there was a weak compatibility between each database examined and the Renal Drug Handbook to detect clinically relevant potential drug-drug interactions for immunosuppressants in kidney transplant recipients. Therefore, we suggest that although databases might be practical to take a quick glance in detection of potential drug-drug interactions between immunosuppressants and co-medications, the data should be evaluated in detail and interpreted with caution in combination with a reference book like Renal Drug Handbook.

A study to enhance the oral bioavailability of s-adenosyl-l-methionine (SAMe): SLN and SLN nanocomposite particles.

The endogenous molecule, S-adenosyl-l-methionine (SAMe) is a key factor due to its role in the methylation cycle and modulation of monoaminergic neurotransmission. Since many mental disorders have linked to the monoaminergic system, the level of SAMe in blood and cerebrospinal fluid is important in the treatment of major depression. In this study, solid lipid nanoparticles (SLN) were prepared in order to increase the limited oral bioavailability of SAMe, and SLN based nanocomposite particles (SAMe-SLN-NC) were further developed using an enteric polymer for passive targeting of intestinal lymphatic system. In this manner, it was also aimed to protect SAMe loaded SLN from harsh gastric environment as well as hepatic first-pass metabolism. Dynamic light scattering (DLS) analysis of SLN was performed, drug content was measured, SAMe release patterns were examined and the permeation ability of SAMe was investigated by the Parallel Artificial Membrane Permeability Assay (PAMPA) to characterize SAMe loaded SLN formulation. According to the PAMPA results, SAMe-SLN with the average particle size of 242 nm showed enhanced SAMe permeability in comparison to pure drug. Delayed drug release obtained by SLN nanocomposite particles indicated the protection of drug-loaded SLN in the acidic gastric medium and their intact presence in the intestine. SAMe solution or particle suspensions were prepared using 0.45 (w/v) hydroxypropyl methylcellulose aqueous solution to be applied to groups of animals for pharmacokinetic studies. In vivo pharmacokinetic parameters revealed enhancement in relative bioavailability of SAMe upon oral administration of SLN based formulations. This was attributed to intact absorption of lipid matrix through lymphatic path. A statistically significant increase in SAMe plasma levels was obtained at 15th and 30th minutes with SAMe-SLN and at 2nd and 4th hours with SAMe-SLN-NC. Overall results suggest that SLN is a promising carrier to passive lymphatic targeting of SAMe and novel SLN nanocomposite particles which presented efficient oral bioavailability is a potential way for oral delivery of SAMe and treatment of major depression.