Introduction/Background: A potential effect of cefazolin causing coagulopathy resulting in elevated INR and bleeding episodes is described in 2 patients. Case Presentation: In the first case, a 77-year-old male was receiving cefazolin for Methicillin- susceptible Staphylococcus aureus (MSSA) bacteremia and developed gross hematuria on day 12 of cefazolin therapy, with a measured INR of 4.1. No other causes of coagulopathy were identified, and after IV vitamin K administration, the INR decreased to 1.3. In the second case, a 77-year-old female was being treated with cefazolin for MSSA bacteremia. On cefazolin day 7, the patient had a measured INR of 9.0, with a subsequent decrease in INR to 1.3 2 days later after administration of vitamin K. Neither patient was receiving any anticoagulation, and no other cause of INR elevation was identified. Conclusion: This case describes 2 patients who experienced elevated INR measurements during cefazolin therapy. Cefazolin may have led to elevated INR values through vitamin K depletion, especially since administration of vitamin K decreased INR values. Close monitoring of bleeding and INR may be needed in patients receiving long-term cefazolin therapy, especially in those having a bleeding episode or decreased hemoglobin.
Introduction/Objective: Deep Neck Abscess (DNA) is a rapidly progressive softtissue infection with high morbidity and mortality rates, especially in the elderly. The natural course involves the soft tissues of the neck with erosion of major blood vessels. The objective of this monocenter, retrospective case series study with observational analysis was to evaluate the safety and efficacy of low-dose Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) in combination with intravenous antibiotics to improve clinical outcomes and reduce mortality in patients with severe DNAs and sepsis. Methods: Seven immunocompetent patients with confirmed bacterial sepsis and DNAs were evaluated over an 8-year period. Diagnosis was established via Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) and positive cultures. Patients received combination therapy consisting of customized intravenous antibiotics and subcutaneous GM-CSF (10 mcg/kg daily) for 5–7 days, alongside aggressive surgical debridement and supportive care. This study adhered to the CARE guidelines for case series and STROBE guidelines for observational analysis. Results: The addition of GM-CSF to intravenous antibiotics and surgical care was safe and well tolerated. All seven patients achieved full clinical recovery with a 100% survival rate through day 29. No local or systemic complications, subsequent organ dysfunction, or thoracic extension of the infection were reported. Discussion: GM-CSF acts as a potent hematopoietic growth factor that stimulates myeloid lineage proliferation and enhances macrophage phagocytosis and neutrophil microbicidal activity. Its adjunctive use provides a synergistic survival benefit and emergency myelopoiesis to accelerate pathogen clearance in non-neutropenic severe tissue infections. Conclusion: Combining targeted antimicrobial coverage with adjunctive low-dose GM-CSF immunotherapy offers a promising, safe, and effective salvage strategy for severe deep neck abscesses, associated with low complication rates and excellent survival outcomes.
Background: Carmustine, a nitrosourea alkylating medicine, is not registered for marketing in South Africa but is made available for clinical use through Section 21 of the Medicines and Related Substances Act 101 of 1965. This regulatory mechanism permits the importation and use of unregistered medicines when no suitable registered alternatives are available. Given the limited local utilisation and reliance on special authorisation, post-marketing safety monitoring is particularly important. This study aimed to characterise the global safety profile of carmustine in order to inform and contextualise pharmacovigilance practices and regulatory oversight in South Africa. Methods: A retrospective descriptive analysis was conducted using Individual Case Safety Reports (ICSRs) submitted to VigiBase from its international birth date. Reports listing carmustine as a suspected or interacting medicine were included. Demographic characteristics, reporter type, seriousness, outcomes, and reported adverse events were summarised using descriptive statistics. Results: Forty-two global ICSRs were identified and 39 ICSRs were further analysed. Most adverse events (AEs) occurred in adults, were classified as serious and were predominantly from the Americas and Europe. No reports originated from Africa. Discussion: Carmustine remains accessible in South Africa only via Section 21, with limited public regulatory transparency. Neoplasms were the most frequently reported AEs (34.8%), many classified as serious, including secondary malignancies consistent with known myelosuppressive effects. Respiratory toxicities were also common and expected. However, most reported preferred terms were deemed unexpected when assessed against product information. Death was reported in 28.6% of cases. Conclusions: These findings highlight regional pharmacovigilance disparities, under-reporting in Africa, and gaps in safety monitoring. There is a need for strengthened monitoring, regulatory transparency, and updated safety communication for Section 21 medicines.
Background/Objectives: Pericardial syndromes cause significant morbidity, decreased quality of life, and rarely mortality. Drug-associated pericardial syndromes are underreported. This study characterized reports of pericardial disorders, described demographic and reporting features, and identified disproportionality signals across suspect drugs and therapeutic classes. Methods: This study analyzed FDA Adverse Event Reporting System reports from January 2000 to March 2025, using predefined preferred terms for pericardial syndromes. Duplicate and pediatric reports (<18 years) were excluded, resulting in 12,106 unique reports. A lower 90% confidence limit of the Empirical Bayes Geometric Mean (EB05)>2 and a lower limit of the 95% credibility interval of the Information Component (IC025)>0 were indicators of signals. Results: Raw counts of reports increased from 133 in 2000 to 939 in 2024. The cohort had a balanced sex distribution and a mean age of 55.5 years. Among females, antineoplastic (e.g., rituximab, EB05 = 13.3, IC025 = 3.7) and immunomodulating agents (e.g., adalimumab, EB05 = 3.1, IC025 = 1.6) were most frequently suspected. Among males, antithrombotic agents (e.g., aspirin, EB05 = 7.1, IC025 = 2.8) predominated. A higher age-adjusted reporting odds of death was observed in females versus males (OR=1.14, 95% CI 1.03-1.25; deaths: females n=1,030, males n=925). Discussion: Raw report counts of pericardial syndromes increased over 25 years, supporting heightened vigilance for drug-induced etiologies. Sex-stratified drug rankings were exploratory and do not demonstrate drug-by-sex interactions. The results extend the existing literature by providing a broad descriptive overview of the reporting landscape for pericardial disorders within a national spontaneous reporting system. Conclusions: Immunomodulating, antineoplastic, and antithrombotic agents generated reporting signals involving pericardial disorders, with sex-based differences and reported drug classes and outcomes. These findings do not establish causality and warrant confirmatory studies.
Introduction/ Background: Acute bilateral lower-extremity edema is uncommon and often results from medication side effects, acute heart failure, nephrotic syndrome, or bilateral deep vein thrombosis. Drugs such as dihydropyridine calcium channel blockers, corticosteroids, thiazolidinediones, and nonsteroidal anti-inflammatory agents are known to cause edema. Donepezil, a widely used acetylcholinesterase inhibitor for Alzheimer's disease, has not been previously linked to leg edema. Recognizing rare adverse reactions is essential for patient safety, as edema may indicate serious conditions. Case Presentation: A 75-year-old woman with Alzheimer's disease developed bilateral pitting lower leg edema six months after starting treatment with donepezil. She had no history of cardiac, renal, hepatic, or venous diseases. Laboratory tests, electrocardiography, chest X-ray, and computed tomography venogram were normal, except for mild anemia and a slightly reduced estimated glomerular filtration rate. The edema resolved three weeks after discontinuation and did not recur after the administration of rivastigmine. Conclusion: The temporal association and resolution upon drug cessation suggest a probable association. Possible mechanisms may include cholinergic-induced vasodilation, which increases capillary permeability.
