Search Results (403)

Ceftazidime–avibactam (CAZ-AVI) is a second-generation intravenous β-lactam/β-lactamase inhibitor combination. In recent years, substantial evidence has emerged regarding the efficacy and safety of CAZ-AVI. However, data on its use in critically ill patients remain limited. Background/Objectives: This multicenter, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure—defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy—in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Results: Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapse or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. Furthermore, treatment failure was more frequent among immunosuppressed individuals, particularly liver transplant recipients. Conclusions: This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies. Full article

Chronic coronary syndrome (CCS) and atrial fibrillation (AF) are prevalent cardiovascular conditions that share numerous risk factors and pathophysiological mechanisms. While clinical scores commonly used in AF—such as CHA₂DS₂VA (which includes congestive heart failure, hypertension, age ≥ 75, diabetes, stroke/TIA, vascular disease, and age 65–74), HAS-BLED (which incorporates hypertension, abnormal renal/liver function, stroke, bleeding history, labile INR, elderly age, and drug/alcohol use), and C₂HEST (incorporating coronary artery disease, COPD, hypertension, elderly age ≥ 75, systolic heart failure, and thyroid disease)—are traditionally applied to rhythm or bleeding risk prediction, their value in estimating the angiographic severity of coronary artery disease (CAD) remains underexplored. We conducted a prospective, single-center study including 131 patients with suspected stable CAD referred for coronary angiography, stratified according to coronary angiographic findings into two groups: significant coronary stenosis (S-CCS) and non-significant coronary stenosis (N-CCS). At admission, AF-related scores (CHA₂DS₂, CHA₂DS₂VA, CHA₂DS₂VA-HSF, CHA₂DS₂VA-RAF, CHA₂DS₂VA-LAF, HAS-BLED, C₂HEST, and HATCH) were calculated. CAD severity was subsequently assessed using the SYNTAX and Gensini scores. Statistical comparisons and Pearson correlation analyses were performed to evaluate the association between clinical risk scores and angiographic findings. Patients in the S-CCS group had significantly higher scores in CHA₂DS₂VA (4.09 ± 1.656 vs. 3.20 ± 1.338, p = 0.002), HAS-BLED (1.98 ± 0.760 vs. 1.36 ± 0.835, p < 0.001), CHA₂DS₂VA-HSF (6.00 ± 1.854 vs. 5.26 ± 1.712, p = 0.021), and C₂HEST (3.49 ± 1.501 vs. 2.55 ± 1.279, p < 0.001). Multivariate logistic regression identified HAS-BLED and C₂HEST as independent predictors of significant coronary lesions. A threshold value of HAS-BLED ≥ 1.5 and C₂HEST ≥ 3.5 demonstrated moderate discriminative ability (AUC = 0.694 and 0.682, respectively), with acceptable sensitivity and specificity. These scores also demonstrated moderate to strong correlations with both Gensini and SYNTAX scores. AF-related clinical scores, especially HAS-BLED and C₂HEST, may serve as practical and accessible tools for early CAD risk stratification in patients with suspected CCS. Their application in clinical practice may serve as supplementary triage tools to help prioritize patients for further diagnostic evaluation, but they are not intended to replace standard imaging or testing. Full article

Background: Selective serotonin reuptake inhibitors (SSRIs) are among the most commonly prescribed antidepressants and are generally considered safe. However, emerging data suggest a potential association with intracranial hemorrhage (ICH), especially among elderly patients and those on anticoagulation. Methods: We conducted a retrospective pharmacovigilance analysis using data from the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS). Reports up to May 2025 listing an SSRI (sertraline, fluoxetine, paroxetine, escitalopram, citalopram, or fluvoxamine) as a suspect or interacting drug and involving an ICH event were included. Disproportionality was assessed using reporting odds ratios (RORs) with 95% confidence intervals. Results: Among 226 eligible ICH cases, sertraline (30.5%), paroxetine (28.8%), and fluoxetine (27.9%) were most frequently implicated. Sertraline showed a strong signal for cerebral hemorrhage (ROR = 4.97), while fluoxetine was associated with subarachnoid hemorrhage (ROR = 4.51). Sertraline had a pronounced signal among patients aged >60 years (ROR = 7.92) and in combination with anticoagulants (ROR = 9.56). Fluoxetine was underrepresented in elderly cases. Given the very small number of fluvoxamine-related cases (n = 2), interpretation should be cautious due to limited statistical power. Gender-stratified analyses showed female predominance in sertraline-related ICH and male predominance for paroxetine. Citalopram demonstrated a potentially protective profile with inverse association with cerebral hemorrhage. Conclusions: This study highlights significant differences in ICH reporting patterns across SSRIs, modified by patient age, gender, and co-medication. These findings underscore the need for individualized SSRI prescribing, particularly in patients receiving anticoagulant therapy particularly in elderly patients and those receiving anticoagulant therapy, where sertraline and fluoxetine may pose increased risk. Full article

Canada’s national surveillance shows an 11% year-over-year decline in deaths from opioid and other unregulated drug poisonings, and a 10% drop in related hospitalisations in 2024. In stark contrast, Québec, home to more than nine million residents, and Montréal, the country’s second-largest city, experienced a continued rise in suspected drug-poisoning mortality through 2024, with fentanyl or analogues detected in almost two-thirds of opioid deaths. We conducted a narrative synthesis of provincial coroner and public-health surveillance tables, Health Canada dashboards, and the 2022–2025 Québec Strategy on Psychoactive-Substance Overdose Prevention. Results indicate a 40% increase in opioid-related mortality since 2018, a parallel uptick in stimulant toxicity, and a five-fold rise in overdose reversals at Montréal supervised-consumption services during the COVID-19 pandemic recovery. We aim to summarise the key problems underlying this epidemic and offer province-specific public-health strategies while also sending a call to action for first-line clinicians and psychiatrists to integrate overdose-risk screening, take-home naloxone, and stimulant-use-disorder treatments into routine care. We further urge Québec healthcare professionals to deepen their knowledge of provincial services such as supervised-injection sites and stay up to date with the rapidly evolving substance-use-prevention literature. Québec’s divergent trajectory underscores the need for region-tailored harm-reduction investments and stronger policy-to-clinic feedback loops to reduce preventable deaths. Full article

Background/Objectives: The combination drug sulfamethoxazole/trimethoprim (ST) is a broad-spectrum antibiotic used against various infections; however, it is associated with several serious adverse events. The ST package inserts contain warnings about these adverse events. However, warnings vary internationally, and specific measures to address ST-related adverse events are unclear. Therefore, we aimed to comprehensively evaluate ST-related adverse events using the Japanese Adverse Drug Event Report (JADER) database and analyze the onset time for each event. Methods: Adverse events due to ST were analyzed using the JADER database between April 2004 and June 2023. The reported odds ratio and 95% confidence interval (95% confidence interval [CI]) were calculated, with a signal detected if the 95% CI lower limit exceeded 1. The Weibull distribution was used to characterize the onset time of adverse events with detected signals. Results: The total number of cases in the JADER database during the study period was 862,952, and the number of adverse events involving ST as a suspected drug was 4203. Adverse events associated with ST include hyperkalemia, syndrome of inappropriate antidiuretic hormone secretion, hematopoietic cytopenia, acute renal failure, hypoglycemia, disseminated intravascular coagulation syndrome, hepatic disorder, and the Stevens–Johnson syndrome/toxic epidermal necrolysis. Conclusions: Weibull analysis indicated an early failure-type onset time for all adverse events, suggesting the need for intensive adverse event monitoring of ST, especially in the first month of use. These findings may support revising drug package inserts in Japan to better reflect the identified risks. Full article

Background: Sarcoidosis is a multisystem inflammatory disease characterized by the immune-mediated formation of non-necrotizing epithelioid granulomas. Several commonly used medications can induce similar granulomatous reactions, known as drug-induced sarcoid-like reactions (DISRs), which closely mimic sarcoidosis. Despite their specificity in targeting molecular pathways, certain therapies—particularly targeted treatments—have increasingly been linked to DISRs. Methods: This narrative review was based on a PubMed search using the terms “SARCOID LIKE REACTION” and “DRUG”. A cross-check was performed with “SARCOID” combined with each identified drug to identify misclassified cases. Drugs with limited evidence or weak pathogenetic plausibility were excluded, leaving only molecularly targeted therapies for consideration. Sources included case reports, case series, and reviews selected based on their clinical and scientific relevance, without any restrictions on time or language. Results: In light of the available data, five main pharmacological groups were found to be associated to DISR: immune checkpoint inhibitors, TNF-α antagonists, BRAF inhibitors, monoclonal antibodies, and miscellaneous agents. Each group has distinct mechanisms of action and clinical indications, which likely affect the frequency, presentation, and timing of DISRs. Conclusions: Diagnosing DISRs is challenging, and a structured approach is crucial for differentiating them from other conditions. To support clinicians, we propose a diagnostic algorithm to guide decision-making in suspected cases. Management should be individualized, as most DISRs either resolve spontaneously or improve after the discontinuation of the causative drug. Important factors influencing therapeutic decisions include the severity of the underlying disease, the availability of alternative treatments, and the extent of DISR manifestations. Full article

Background and objectives: As part of Vision 2030, Saudi Arabia aims to strengthen its healthcare system by enhancing efficiency, reducing medical errors, and ensuring drug safety. Evidence on pharmacists’ experiences with adverse drug reactions (ADRs) in daily practice remains limited. Gaining insight into their perspectives is essential for improving patient safety and optimizing pharmaceutical care. Therefore, we aimed to assess pharmacists’ ability to identify ADRs in daily practice and the subsequent actions taken upon identification. Methods: Between July and August 2024, an email-based invitation was sent to randomly selected registered community and hospital pharmacists in Saudi Arabia to participate in the study, which employed a piloted questionnaire. Results: The study involved 305 pharmacists, including 169 hospital/clinical pharmacists (HCPs, 55.4%) and 136 community pharmacists (CPs, 44.6%). A majority (n = 251, 82.3%) indicated direct patient encounters, while 67.2% (n = 205) reported observing suspected ADRs in the preceding 12 months. Most respondents filed ADR reports to the Saudi Food and Drug Administration/National Pharmacovigilance Centre (HCP = 103, CP = 60) and hospital drug information centers (HCP = 89, CP = 64), with online forms being the favored mode (HCP = 122, CP = 96). Awareness of ADR reporting procedures was reported by 128 HCPs and 80 CPs. Conclusions: More than two-thirds of participants reported having participated in ADR reporting, with greater adherence observed in hospital settings. Pharmacists predominantly depend on the Saudi Food and Drug Administration/National Pharmacovigilance Centre and hospital drug information centers for reporting, with a preference for online submission methods. Targeted educational interventions addressing gaps in knowledge, reporting procedures, and form complexity could improve ADR reporting practices. These findings support the need for structured training and policy measures to strengthen pharmacovigilance system. Full article

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis complex (MTBC), remains a global health challenge and can lead to severe pulmonary and extrapulmonary complications. Multidrug-resistant TB (MDR-TB) poses additional challenges, requiring advanced diagnostic and treatment strategies. This study evaluates the BD MAX MDR-TB molecular test for a rapid diagnosis of MDR-TB, detecting resistance to rifampicin (RIF) and isoniazid (INH). The BD MAX MDR-TB test, utilizing real-time PCR, was used to analyze specimens collected from TB-suspected patients, identifying MTB DNA and mutations associated with rifampicin and isoniazid resistance. Results were compared with traditional drug susceptibility testing, and 79 out of 638 samples tested were positive for MTB DNA, with 65 showing a sufficient amount of genetic material for resistance gene identification. The BD MAX test showed a 100% correlation with phenotypic rifampicin resistance, though discrepancies were noted for isoniazid resistance, with a 93% concordance. The BD MAX MDR-TB test is an effective tool for a rapid diagnosis of MDR-TB, especially for rifampicin resistance. However, it may not detect certain mutations related to isoniazid resistance. Complementary tests like Xpert MTB/XDR or whole-genome sequencing could improve diagnostic accuracy and support more effective TB control strategies. Full article

Background/Objectives: Patients’ perspectives on adverse drug reactions (ADRs) may be used to update the safety profile of a drug. We aimed to prospectively follow-up on type 2 diabetes (T2D) patients who were new users of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and to characterize the patient-reported ADRs within routine practice in Romania. Methods: T2D patients from ambulatory settings were interviewed over the phone based on standardized forms, at four time-points across 12 months. We captured the patients’ history and auto-medication, as well as any ADR that implied causality to SGLT2i, based on the patient’s perspective. Results: In total, 64 patients, with genders being equally represented and with a median age of 59 years (Q1, Q3: 51, 64) were followed-up with. We identified 73 ADRs to SGLT2i that were suspected to be associated with the drug, with an average of 2.35 ADRs per patient (range 0–7 ADRs/patient). The most reported ADR was pollakiuria (7; 9.58%), followed by vulvovaginal candidiasis (6; 8.21%), dysuria (4; 5.47%), and hypoglycemia (4; 5.47%). SGLT2i treatment was interrupted for eight patients. Three (4.10%) ADRs were considered serious as important medical events (hypertensive crisis, angina pectoris, and dyspnea). A positive dechallenge was recorded for 14 ADRs, of which 9 ADRs had a positive rechallenge as well. A probable causality was assessed for 13 of the 73 patient-reported ADRs. Conclusions: Most of the identified ADRs were in line with the known safety profile of SGLT2i. Only three ADRs were serious and unexpected relative to the safety profile, but these had confounding factors that could explain the reactions. Therefore, no new safety concerns related to SGLT2i were determined in this observational study. Full article

Background: Cephalosporins are considered safe antibiotics. However, serious hematological abnormalities may occur, although rarely, after their therapeutic use. Case Presentation: We present a case of pancytopenia in a 72-year-old female patient treated with ceftriaxone for a urinary tract infection. After five days of therapy, pancytopenia was observed. Other causes were excluded through extensive diagnostic evaluation, including immunological tests, viral serologies, bone marrow aspiration, and peripheral blood smear. The patient’s clinical condition significantly improved following the discontinuation of ceftriaxone and the administration of granulocyte colony-stimulating factor (G-CSF). Bone marrow findings revealed hypocellularity without malignant infiltration, and peripheral smear showed no dysplasia, blasts, or hemolysis. Conclusions: This case demonstrates that ceftriaxone, although widely regarded as a safe antibiotic, can induce rare but serious hematologic complications such as pancytopenia. A high index of suspicion is required when patients on antibiotic therapy develop unexplained cytopenias. Detailed medication history, exclusion of other causes, and prompt discontinuation of the suspected drug are essential. The patient’s favorable outcome supports the likelihood of an idiosyncratic, immune-mediated mechanism. Future research should explore pharmacogenomic screening in patients at increased risk, particularly involving HLA variants. Full article

Background: Respiratory syncytial virus (RSV) poses a significant health burden in children, being the major cause of lower respiratory tract infection (LRTI), including bronchiolitis. During the 2023–2024 RSV season, Spain introduced nirsevimab, a monoclonal antibody for universal RSV prophylaxis in infants. This study reviews the safety of nirsevimab through post-marketing surveillance. Material and Methods: A descriptive pharmacovigilance study was made based on spontaneous reporting data of suspected adverse events (SAEs) from the Spanish Pharmacovigilance System for Medicinal Products for Human Use (SEFV-H) and industry reports. SAEs reported between September 2023 and May 2024 were extracted from the Spanish Pharmacovigilance Adverse Reactions Data (FEDRA) database. Cases were analysed by sex, age, severity, and SAEs classification using the Preferred Terms (PT) level of the Medical Dictionary for Regulatory Activities (MedDRA). Reporting rates were estimated based on immunization coverage and birth data. Results: Sixty-seven cases reported 141 SAEs, yielding an overall rate of 23.1 cases per 100,000 doses. Common events included rash (8.51%), drug ineffectiveness (7.09%), and pyrexia (7.09%). Serious events constituted 53.70% of reports, including two fatalities (3.00%). No new safety signals or unexpected risks, such as antibody-dependent enhancement (ADE), were identified. Discussion: SAEs reported peaked early in the campaign, reflecting heightened reporting in new immunization programs. The safety profile aligns with clinical trial findings and regulatory expectations, confirming nirsevimab’s benefit–risk balance. Continued pharmacovigilance is critical for maintaining public trust in RSV prophylaxis. Nirsevimab demonstrated a favorable safety profile during Spain’s initial universal RSV immunization campaign in infants, supporting its continued use in reducing RSV-related morbidity. Full article

Background/Objectives: Cushing’s syndrome (CS), including Cushing’s disease (CD)—the most common type—has a substantial negative impact on morbidity, mortality, and patients’ quality of life. Medical management of CS is essential for controlling hypercortisolism as part of preoperative preparation for definitive surgical treatment and for managing residual or relapsed hypercortisolism post-surgery. Osilodrostat, a dual inhibitor of glucocorticoid and mineralocorticoid biosynthetic pathways, has been approved for the medical treatment of CS since early 2020. However, real-world data on its adverse effects remain limited. We mined the FAERS database and analyzed the reports associated with osilodrostat up to 1 October 2024. Methods: Descriptive and disproportionality methods based on Relative Odds Ratio (ROR), Chi-square (χ²), and Proportional Reporting Ratio (PRR), were used to discern potential safety signals and assess the significance of osilodrostat-associated adverse events. Results: This study identified 782 reports in which osilodrostat was the primary suspected drug, containing 593 preferred terms (PTs) and 2481 occurrences. The most frequently registered events belonged to the following SOCs: “General disorders and administration site conditions” (n = 457, 18.4%), “Injury, poisoning and procedural complications” (n = 311, 12.5%), “Gastrointestinal disorders” (n = 278, 11.2%), “Investigations” (n = 260, 10.5%), and “Nervous system disorders” (n = 184, 7.4%). Among PTs, off-label use was the most commonly reported, aligning with the fact that the vast majority of cases originated from the U.S. (84%), where osilodrostat is officially approved only for the treatment of CD. Disproportionality analysis confirmed previously known and new potential adverse drug reactions associated with osilodrostat treatment, including reports of cardiac flutter (n: 4; PRR: 19.42; χ²: 49.57), ventricular extrasystoles (n: 4; PRR: 11.85; χ²: 29.62), muscular weakness (n: 8; PRR: 2.25; χ²: 4.38), rib fracture (n: 4; PRR: 6.66; χ²: 13.99), spinal fracture (n: 3; PRR: 4.66; χ²: 5.35), sepsis (n: 9; PRR: 2.63; χ²: 7.56), fungal infections (n: 4; PRR: 3.67; χ²: 5.33), and COVID-19 (n: 32; PRR: 5.07; χ²: 101.16). Conclusions: This study highlights new risks and offers valuable insights into osilodrostat use; however, further research and validation are necessary, particularly for adverse reactions not yet explicitly documented in the summary of product characteristics. Full article

The ubiquity of diclofenac (DCF) in the environment has raised significant concerns. Diclofenac is a non-steroidal anti-inflammatory drug that has been found in various environmental matrices at minimum concentrations that are harmful to aquatic and terrestrial organisms. Traditional wastewater treatment plants (WWTPs) are not fully equipped to remove a range of pharmaceuticals, and that explains the continued ubiquity of DCF in surface waters. In this study, an Fe₃O₄/SiO₂ nanocomposite prepared from acid mine drainage and coal fly ash was applied for the removal of DCF from wastewater. Major functional groups (Si–O–Si and Fe–O) were discovered from FTIR. TEM revealed uniform SiO₂ nanoparticle rod-like structures with embedded dark spherical nanoparticles. SEM-EDS analysis discovered a sponge-like structure fused with Fe₃O₄ nanoparticles that had significant Si, O, and Fe content. XRD demonstrated the crystalline nature of the nanocomposite. The surface properties of the nanocomposite were evaluated using BET and were 67.8 m²/g, 0.39 cm³/g, and 23.2 nm for surface area, pore volume, and pore size, respectively. Parameters that were suspected to be affecting the removal process were evaluated, including pH, nanocomposite dosage, and sample volume. The detection of DCF was conducted on high-performance liquid chromatography with diode-array detection (HPLC-DAD). Under optimum conditions, the adsorption process was monolayer, and physisorption was described using the Langmuir and Dubinin-Radushkevich (D-R) isotherm models. The kinetic data best fitted the pseudo-first order kinetic model, indicating a physisorption adsorption process. The thermodynamic experimental data confirmed that the adsorption process was spontaneous. The results obtained from real water samples showed 95.28% and 97.44% removal efficiencies from influent and effluent: 94.83% and 88.61% from raw sewage and final sewage, respectively. Overall, this work demonstrated that an Fe₃O₄/SiO₂ nanocomposite could be successfully prepared from coal fly ash and acid mine drainage and could be used to remove DCF in wastewater. Full article

Background: Proton pump inhibitors (PPIs) are widely used for gastric acid suppression, yet their efficacy and safety in neonates and infants remain unclear. While esomeprazole is the only Food and Drug Administration (FDA)-approved PPI for neonates and infants under 1 year of age, other PPIs are also frequently prescribed. Objectives: This study utilizes FDA Adverse Event Reporting System (FAERS) data to evaluate potential adverse drug events (ADEs) of PPIs, providing crucial real-world insights into their safety in this vulnerable population. Methods: This observational cross-sectional study was conducted using an individual case safety report (ICSR) database. Only reports in neonates or infants receiving omeprazole, pantoprazole, lansoprazole, rabeprazole, or esomeprazole monotherapy were evaluated. The most frequently prescribed PPI, the most common indication, the most reported ADE, the seriousness of AEs, and the countries reporting the highest ADE number were analyzed using 2D disproportionality analyses (e.g., reporting odds ratio (RORs)). Results: A total of 464 patients were included; 323 (69.6%) of them were stated as serious and 15 (3.2%) of them were stated as time-related to mortality. Most of the ADEs were reported for lansoprazole (45.9%). The most reported PPI-associated ADE was vomiting (8.8%). According to the RORs analysis, vomiting associated with PPI monotherapy was more likely to occur (RORs: 2.88, 95% CI: 2.09–3.96), which is followed by diarrhea, hypertrichosis, choking, and erythema. Additionally, medication errors were reported in 50 (10.8%) patients. Conclusions: ICSR databases are valuable pharmacovigilance tools. The absence of access to a causality assessment is a limitation since it limits its ability to confirm whether the ADEs are truly caused by the suspected drug, mitigated using RORs analysis. Integrating neonatal-specific algorithms could enhance drug safety evaluations, strengthen evidence-based decision-making, and improve risk–benefit assessments in neonates and infants. Full article

Spondylodiscitis is a devastating invasive infection that can lead to debilitating pain, motor weakness, or paralysis, even with appropriate medical and surgical treatment. Over the past two decades, there has been a worldwide increase in the incidence of spondylodiscitis, which can be attributed to a higher prevalence of various risk factors including intravenous drug use, hemodialysis, and spinal surgeries. The lumbar spine is the most likely region to be affected, with Staphylococcus aureus being the predominant pathogen. Management of spondylodiscitis requires a multi-disciplinary approach, with close coordination between the spinal surgeon and the infectious diseases specialist. Clinicians should become familiar with the epidemiology and presentation of patients with suspected spondylodiscitis because timely diagnosis and treatment may lead to improved outcomes. This unique review incorporates the perspectives from infectious disease and spine surgery specialists. Full article