Rhabdomyolysis Secondary to Urinary Tract Infection With E coli

For 2 days, a 73-year-old woman had had high fever, altered mental status, fatigue, diffuse myalgia, cough, dysuria, and increased urinary frequency. Her medical history included hypertension, hyperlipidemia, chronic obstructive pulmonary disease, chronic pain syndrome, and gastroesophageal reflux disease.

Clinical examination revealed the patient was in shock. Temperature was 38.5°C (101.3°F); heart rate, 117 beats per minute; and blood pressure, 91/57 mm Hg. Oxygen was administered at 3 L/min to maintain a saturation of greater than 90%. She was lethargic with alertness to person and time but not to place. No murmurs were detected; breath sounds were diminished bilaterally. Diffuse abdominal tenderness was noted, most prominently in the suprapubic region.

Laboratory studies showed a white blood cell (WBC) count of 20,700/µL, with 25% bands; an initial serum creatinine level of 2.2 mg/dL; and mildly elevated liver transaminase levels. Arterial blood gas analysis revealed a pH of 7.36 with a base deficit of 2.4. Urinalysis disclosed a protein level of 15 mg/dL; occult blood, 250 red blood cells (RBCs)/µL; positive nitrites; leukocyte esterase, 500 WBCs/µL; 15 to 19 RBCs/high-power field (HPF); 50 or more WBCs/HPF; and many bacteria. Total creatine kinase (CK) level was 10,276 U/L, and myoglobin level was higher than 5000 ng/mL.

The patient was admitted to the ICU with a diagnosis of septic shock and concomitant rhabdomyolysis. Initial treatment consisted of a 1-L bolus of intravenous normal saline with 1 ampule of sodium bicarbonate. Inotropic support with norepinephrine was required for blood pressure stabilization. Broad-spectrum antibiotics were started after blood was drawn for cultures. Intravenous fluids were titrated on an hourly basis to maintain adequate urine output (>200 mL/h). The patient’s blood pressure stabilized. WBC count decreased to 19,400/µL; serum creatinine, to 1.6 mg/dL; and serum CK, to 9893 U/L. Urine cultures were positive for Escherichia coli; 2 blood cultures were negative.

During the next few days, the patient’s mental status improved to baseline. WBC count decreased to 8400/µL; serum creatinine, to 0.4 mg/dL; and serum CK, to 1819 U/L. Potassium levels were repleted. The patient was discharged after a 3-day hospital stay with oral antibiotics; simvastatin/ezetimibe was discontinued.

Discussion
Rhabdomyolysis is characterized by the breakdown and necrosis of striated muscle leading to the leakage of intracellular muscle contents into the circulation and extracellular fluid.¹ This syndrome can present with a wide range of manifestations, from asymptomatic illness with mild elevations in CK to diffuse myalgia with extreme elevations in CK, acute renal failure (ARF), electrolyte imbalances, disseminated intravascular coagulation, and/or death.^1-4 Rhabdomyolysis has numerous causes,^1-4 including infection.^5-7

From 5% to 31% of cases of rhabdomyolysis result from infection.^3,5,8-10 The mean age of patients with infection-related rhabdomyolysis (IRR) is older than 70 years; males and females are affected equally.^5-6,9 Fever is more prevalent in patients with IRR than in those who have non–infection-related rhabdomyolysis (68.7% vs 13.9%), and patients with IRR have lower mean serum CK levels (3710.1 U/L vs 19,785.4 U/L).³ CK levels are also lower in patients with sepsis-induced rhabdomyolysis (7114 U/L).⁶

The most common viral causes of rhabdomyolysis are influenza virus, HIV, and coxsackievirus; while the most common bacterial causes are Legionella species, Francisella tularensis, and Streptococcus pneumoniae.⁷ Patients with bacterial-induced rhabdomyolysis have higher rates of ARF than those with viral-induced rhabdomyolysis (57% vs 34%). In-hospital mortality of patients with IRR is 23.5%; mortality in those with bacterial-related rhabdomyolysis is 38%.⁷

A study of ICU patients with culture-confirmed bacterial sepsis-induced rhabdomyolysis found that most cases are caused by gram-positive organisms (69% vs 31% gram-negative cultures). Most of the gram-positive causative agents were Staphylococcus and Streptococcus; the most common gram-negative isolates were Pseudomonas. The most frequent sources were upper respiratory tract infections/pneumonia and urinary tract infections.⁹

However, other studies have reported that in the 50% of IRR cases in which bacterial isolates were obtained, the majority were gram-negative (62.5%⁵ and 69.4%⁶); in another study, the percentages of gram-negative, gram-positive, and atypical organisms were 40%, 36.7%, and 23.3%, respectively.⁷ The Table compiles data from these studies to show that gram-negative organisms may be slightly more common causes of IRR.

Only 19 cases of rhabdomyolysis related to E coli infection have been reported. Three of the cases involved pediatric patients who underwent treatment for acute lymphoblastic leukemia; 1 case involved an 86-year-old man with a urinary tract infection; 1 involved an 80-year-old man with blood and urine cultures positive for E coli along with other organisms, including Klebsiella pneumoniae,Clostridium perfringens, Staphylococcus aureus, and Staphylococcus epidermidis; 2 cases did not describe mechanisms of infection; and 12 cases had various foci (3 of lung origin, 2 of meningeal origin, 3 of urinary tract origin, 2 of endocardial origin, and 2 from uncertain sources).

This patient presented with sepsis syndrome attributed to E coli as confirmed by urine culture. Her other risk factors for rhabdomyolysis included hypokalemia and several medications known to cause rhabdomyolysis: alprazolam, simvastatin/ezetimibe, hydrocodone/acetaminophen, oxycodone, pantoprazole, and salsalate. However, she had been taking these medications (except salsalate) for more than 18 months.

The literature reveals little about concomitant risk factors for rhabdomyolysis; one study found that 64% of patients with sepsis-related rhabdomyolysis had diabetes mellitus and 30% of patients were also receiving statin therapy.⁶ Future studies may reveal whether concomitant risk factors increase the likelihood of rhabdomyolysis developing.

Take-Home Points
• Be aware of the signs and symptoms of rhabdomyolysis and the condition’s numerous causes.
• Keep in mind that patients who present with fever and signs of infection, especially sepsis with multi-organ failure, may have rhabdomyolysis.
• Perform medication reconciliations regularly, especially for patients who are taking drugs with adverse effects that may potentiate each other.
 
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