BackgroundCandida albicans is a commensal fungus that resides on mucosal surfaces and in the gastrointestinal and genitourinary tracts in humans. However, it can cause an infection when the immune system of the host is impaired or if a niche becomes available. Many C. albicans infections are due to the organism’s ability to form a biofilm on implanted medical devices. A biofilm represents an optimal medium for the growth of C. albicans as it allows cells to be enclosed by a self-produced extracellular matrix (ECM).ObjectivesThe present work investigated certain aspects of the resistance of C. albicans biofilms to drugs and the host immune system.ResultsAn ECM was found to provide the infrastructure for biofilm formation, prevent disaggregation, and shield encapsulated C. albicans cells from antifungal drugs and the host’s immune system. By influencing FKS1 and upregulating multiple glucan modification genes, β-1, 3-glucan, an important component of ECM, was shown to be responsible for many of the biofilm’s drug-resistant properties. On being engulfed by ECM, the fungal cell was found to switch from glycolysis to gluconeogenesis. Resembling the cellular response to starvation, this was followed by the activation of the glyoxylate cycle that allowed the use of simple molecules as energy sources.ConclusionMature biofilms were found to be much more resistant to antifungal agents and the host immune system than free cells. The factors responsible for high resistance included the complex architecture of biofilms, ECM, increased expression of drug efflux pumps, and metabolic plasticity.

Purpose The pharmacology, pharmacokinetics, pharmacodynamics, antimicrobial activity, efficacy, safety, and current regulatory status of a recently approved triple-drug therapy for complicated infections are reviewed. Summary Imipenem/cilastatin/relebactam is a newly approved anti-infective combination of a well-established β-lactam and a new β-lactamase inhibitor for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and complicated intra-abdominal infections (cIAIs) caused by susceptible gram-negative bacteria in patients 18 years of age or older with limited or no alternative treatment options; the medication is also indicated for use in treating hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The medication is active in vitro against a wide range of pathogens, including multidrug-resistant (MDR) Pseudomonas aeruginosa and carbapenemase-resistant Enterobacterales such as Klebsiella pneumoniae carbapenemase. The addition of relebactam does not restore the activity of imipenem against metallo-β-lactamase (MBL)–producing Enterobacterales and carbapenem-resistant Acinetobacter baumannii. Two phase 3 clinical trials of imipenem/cilastatin/relebactam were conducted. In the RESTORE-IMI 1 trial, the efficacy and safety of the triple-drug combination was found to be comparable to that of colistin/imipenem for treatment of infections caused by imipenem-nonsusceptible gram-negative bacteria in patients with HABP or VABP, cUTIs, and cIAIs, with a significantly lower incidence of nephrotoxicity reported with triple-drug therapy. The RESTORE-IMI 2 trial demonstrated the noninferiority of the triple-drug combination to piperacillin/tazobactam for the treatment of HABP and VABP. Commonly reported adverse events in clinical trials included anemia, elevated liver enzymes, electrolyte imbalances, nausea, vomiting, diarrhea, headache, fever, phlebitis and/or infusion-site reactions, and hypertension. Conclusion Imipenem/cilastatin/relebactam is a new β-lactam/β-lactamase inhibitor combination with activity against MDR gram-negative bacteria, including many CRE but not including MBL-producing Enterobacterales and carbapenem-resistant Acinetobacter isolates. It is approved for the treatment of cUTIs, cIAIs, HABP, and VABP.

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Background In Lebanon, the role of the pharmacist remains underestimated in the medication reconciliation process, especially in surgical departments. This study aims to assess the impact of pharmacist-conducted medication reconciliation performed within 48 h of hospital admission to the orthopedic surgical department. Methods This was a prospective single-arm study conducted in a tertiary-care teaching hospital in Lebanon between October 2019 and April 2020. Participants were adult inpatients hospitalized for orthopedic surgeries with ≥ 1 outpatient medications. Properly trained pharmacy resident obtained the Best Possible Medication History (BPMH) and led the reconciliation process. The primary endpoint was the number of reconciliation errors (REs) identified. Descriptive statistics were used to report participants’ responses and relevant findings. Linear regression was performed with the number of REs as a continuous dependent variable using backward method. Results were assumed to be significant when p was < 0.05. Results The study included 100 patients with a mean age of 73.8 years, admitted for elective (54%) or emergency (46%) surgeries. Half of the study population had ≥ 5 home medications. The mean time for taking BPMH was around 8 min. A total of 110 REs were identified in 74 patient cases. The most common discrepancies consisted of medication omission (89.1%) and the most common medications involved were antihyperlipidemic agents. Twenty-four REs were judged as clinically significant, and four as serious. The most common interventions included the addition of a medication (71.9%). Most of the relayed interventions (84.5%) were accepted. The number of home medications was the only variable significantly associated with the number of REs (β 0.492; p < 0.001). Conclusion Pharmacy-led medication reconciliation upon admission to orthopedic surgery department can reduce reconciliation errors and improve medication safety. Trial registration Retrospectively registered in the Lebanon Clinical Trials Registry (LBCTR2020124680).