Empagliflozin-Associated EDKA and Staphylococcus aureus Bacteremia: A Complex Case of Severe Illness

Sodium-glucose cotransporter-2 inhibitors⁤ (SGLT2is) like empagliflozin have revolutionized the management of type 2 diabetes and heart failure,⁤ demonstrating cardiovascular and ‌renal benefits. However,their use is increasingly linked to⁢ a rare but⁤ life-threatening ⁣complication: euglycemic‍ diabetic ketoacidosis (EDKA).This case report details a complex presentation of EDKA secondary to empagliflozin, elaborate‌ by Staphylococcus aureus bacteremia and mitral valve endocarditis, highlighting the diagnostic challenges and management strategies required for optimal patient outcomes.

Clinical Presentation and Initial Course

A 78-year-old ‌female with a history of type 2 diabetes, hypertension, and hyperlipidemia presented to⁤ the emergency department following⁤ a ground-level fall resulting in an occipital scalp ‌wound. Initial assessment revealed no neurological deficits, and the wound ⁣was debrided and sutured. Her ⁣long-term medications ‌included esomeprazole and oral antidiabetic ⁣agents. Notably, her oral antidiabetic medications were temporarily withheld upon admission.

The patient’s initial ‍medical course was stable, and on hospital Day​ 4, oral antidiabetic medications, including‌ empagliflozin, were cautiously reintroduced. Though, from Day 5, she developed an unexplained fever, though her overall ⁣clinical condition‌ remained seemingly stable. This subtle ⁤symptom foreshadowed a rapid deterioration.

Rapid Deterioration and Septic Shock

By Day 7,while ⁢awaiting discharge from the intensive care unit (ICU),the patient experienced acute clinical deterioration. She presented⁢ with a substantially decreased level of consciousness (Glasgow Coma Scale 7/15), atrial fibrillation with a​ heart rate​ of 150-160 bpm, hemodynamic instability (blood⁢ pressure 90/54 mmHg), tachypnea (25-30 breaths per minute), and hyperthermia (40°C). ⁤ Facial and left arm edema ⁤were also observed.

Arterial ​blood gas analysis revealed severe metabolic acidosis (pH 6.99,bicarbonate 6 mmol/L,pCO2 15 mmHg,pO2 105 mmHg,base excess −23.4 mmol/L), with a lactate concentration of 1.8 mmol/L and a glucose concentration of ‍13.7 mmol/L. These findings prompted immediate initiation of management for septic shock, including⁣ aggressive fluid resuscitation, vasopressor support, and broad-spectrum antibiotic therapy.

Diagnostic Challenges and⁢ EDKA Confirmation

Initial investigations included ‍cranial and thoraco-abdomino-pelvic computed tomography (CT) scans, which revealed dermo-hypodermitis of the face secondary to an infection originating from the occipital scalp ⁤wound. ⁢ Though, a serum creatinine level of 55 µmol/L was discordant with‍ the severity of the metabolic acidosis, raising concerns about choice etiologies beyond acute kidney injury.

This biochemical dissociation prompted evaluation for diabetic ketoacidosis (DKA) or ⁢toxic-mediated acidosis. Crucially,⁢ a plasma ketone measurement ⁢revealed a level exceeding 6 mmol/L, strongly supporting a diagnosis of‌ EDKA associated with SGLT2i use. The relatively normal glucose level (13.7 mmol/L)⁢ is ⁣characteristic of EDKA, differentiating it from conventional DKA, where glucose levels​ are typically much higher.

Management of EDKA, Bacteremia, and Endocarditis

Recognizing the link to ⁣empagliflozin, all‌ oral antidiabetic drugs were immediately discontinued. Following hemodynamic stabilization with crystalloid fluid ⁤resuscitation and correction of ‍hypokalemia, a continuous intravenous insulin infusion was initiated, concurrently with a 10% dextrose infusion to prevent iatrogenic hypoglycemia.

Microbiological analysis confirmed methicillin-susceptible Staphylococcus aureus ‍bacteremia,⁣ with​ positive blood cultures persisting for nearly six days.‌ Antibiotic therapy was adjusted based on the antibiogram, and cloxacillin was introduced. A devastating secondary complication emerged: mitral valve endocarditis,characterized by a 12 mm mobile vegetation with renal and splenic emboli. due to the patient’s recent head trauma, which‌ contraindicated‌ extracorporeal circulation, surgical ​intervention was deemed​ unsuitable.

Resolution and ​Rehabilitation

The septic shock‍ resolved after four days, allowing for the discontinuation of norepinephrine. After five days of insulin therapy,the ​patient’s acidosis resolved,and serum ⁣ketone bodies became undetectable. The continuous intravenous insulin⁤ infusion was⁣ transitioned to a ⁤basal-bolus insulin regimen.

The infectious episode ultimately had a favorable outcome with six weeks of well-managed antibiotic therapy. Following a