Systemic infections can decrease the threshold of statin-induced muscle injury.

To the Editor: We read with interest the report of Finsterer and Zuntner (1) describing the possible relationship between rhabdomyolysis, statin therapy and systemic infection. We report a similar occurrence in a patient with septicemia. There are various risk factors described which increase the likelihood of statin-induced muscle injury, but little is known about the significance of systemic infections in this state. We report a case of atorvastatin-induced severe acute muscle injury leading to acute renal failure in a patient who had enterococcal bacteremia.

An 80-year-old male patient presented with complaints of acute onset generalized muscle weakness. He denied fever, palpitations, chest pain, vomiting, diarrhea, or other symptoms. He had a previous history of hypertension, coronary artery bypass surgery and bioprosthetic aortic valve replacement in 1999. He was being treated with metoprolol, atorvastatin and hydrochlorothiazide. On examination he was normotensive, but had a fever of 101.5[degrees] F. The rest of the examination was unremarkable. His initial laboratory workup showed a WBC of 17,200 with 86% neutrophils and 7% bands, a creatinine of 1.9 mEq/L, myoglobin >2,000 ng/mL, creatine phosphokinase (CPK) of 1918 IU/L, creatinine kinase myocardial band (CKMB) of 10.5 ng/mL, and a CKMB index of 0.5. His urine examination was significant for more than 50 white blood cells per high powered field. An initial diagnosis of urinary tract infection versus acute muscle injury causing acute renal failure was made. IV fluids and ceftriaxone were started and atorvastatin was stopped. The following day, the patient's creatinine increased to 7.0 mEq/L with a blood urea nitrogen (BUN) of 87 mg/dL, CPK of 42,976 IU/L, and a myoglobin > 2,000 ng/mL.

His culture results showed significant growth of Enterococcus faecalis species in the blood, and > 100,000 colonies/mL of Escherichia coli in the urine. His antibiotics were changed in light of sensitivity results. Daily follow-up of renal functions and CPK was carried out. His muscle strength gradually improved and he was able to sit in a chair. After 10 days of treatment, the CPK started trending downward. He was discharged after 12 days with improving creatinine and improved muscle strength.

Statin-related muscle injuries range from myalgias to frank rhabdomyolysis and occur in 1 to 7% of treated patients. (2) Statins inhibit HMG-CoA reductase which is a rate-limiting enzyme in cholesterol synthesis. As a result, there is depletion of certain substances, eg, ubiquinone and mevalonate. Deficiency of these substances may play a role in myotoxicity. The reduction in ubiquinone leads to mitochondrial abnormalities which may increase the risk of muscle injury. (3) Infections with certain microorganisms, especially Gram positive bacteria, are known to cause muscle injury. Enterococci are also reported as a cause of muscle injury. (4)

This report raises the question whether the patient's systemic infection induced acute muscle injury or if his symptoms were the result of the combined effect of infection and statin-induced predisposition to myolysis. The well known risk factors for muscle injury with statin therapy includes old age, female sex, low body mass index, hypothyroidism, diabetes, impaired renal hepatic functions and combined statins-fibrate therapy.

Interestingly, statins also exert anti-inflammatory and immunomodulatory functions which are considered beneficial in reducing the risk of bacteremia. A recently published study revealed that there was a significant reduction in mortality among patients taking statin medications compared with patients not taking statin. (5) The observations in this case and that of Finsterer and Zuntner (1) highlight the potential role of systemic bacterial infections in statin-induced muscle injury. Clinical investigations to further describe the frequency of these interactions are needed.

Sohail K. Mahboobi, MD

Ephron Z. Shohat, MD

Samantha P. Jellinek, PHARMD, BCPS

Malcolm Rose, MD

Maimonides Medical Center

Brooklyn, NY

References

1. Finsterer J, Zuntner G. Rhabdomyolysis from simvastatin triggered by infection and muscle exertion. South Med J 2005;98:827-829.

2. Ucar M, Mjorndal T, Dahlqvist R. HMG-CoA reductase inhibitors and myotoxicity. Drug Saf 2000;22:441-457.

3. Flint OP, Masters BA, Gregg RE, Durham SK. HMG-CoA inhibitor-induced myotoxicity: pravastatin and lovastatin inhibit the geranylgeranyolation of low-molecular-weight proteins in neonatal rat muscle cell culture. Toxicol Appl Pharmacol 1997;145:99-110.

4. Betrosian A, Thireos E, Kofinas G, et al. Bacterial sepsis-induced rhabdomyolysis. Intensive Care Med 1999;25:469-474.

5. Liappis AP, Kan VL, Rochester CG, Simon GL. The effect of statins on mortality in patients with bacteremia. Clin Infect Dis 2001;33:1352-1357.