JAC Advance Access originally published online on January 12, 2006
Journal of Antimicrobial Chemotherapy 2006 57(3):578-579; doi:10.1093/jac/dki476
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Correspondence |
Rhabdomyolysis and acute renal failure in a patient treated with daptomycin
Division of Nephrology, Hypertension and Renal Transplantation, University of Florida, Gainesville, FL, USA
* Corresponding author. Tel: +1-352-392-4007; Fax: +1-352-392-5465; E-mail: amir.kazory{at}medicine.ufl.edu
Keywords: daptomycin , rhabdomyolysis , renal failure , CPK
Sir,
Echevarria et al. recently reported a case of severe myopathy and possible hepatotoxicity related to daptomycin in your journal.1 Here we describe a similar case that was complicated by renal insufficiency.
A 53-year-old African-American female with a history of diabetes mellitus, hypertension and peripheral vascular disease was admitted to the hospital for evaluation of long-standing progressive low back pain. She was afebrile and had mild tenderness over the lower lumbar spine without motor or sensory changes in the lower extremities. MRI findings were compatible with L5-S1 discitis and osteomyelitis. She received an 8 week course of empirical antibiotic therapy with vancomycin and levofloxacin.
Due to lack of improvement in symptoms, a repeat MRI was performed at the end of the treatment course, which revealed evidence of persistent active discitis and osteomyelitis. The patient then underwent an open biopsy, and specimens were sent for culture, which were positive for Torulopsis glabrata, vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus (MRSA). She was started on voriconazole 250 mg twice a day orally and daptomycin 360 mg (6 mg/kg) intravenously as a single daily dose. After 10 days the patient developed generalized muscular weakness progressing to the point where she could not walk or even get out of bed, followed by non-oliguric acute renal failure with a serum creatinine rising to 27 mg/L from a baseline level of 9 mg/L. At this time, the serum creatine phosphokinase (CPK) level was checked, which was 21 243 U/L, and was associated with elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), 375 and 219 U/L, respectively. Lactate dehydrogenase (LDH) was also elevated at 666 U/L. Urinalysis was positive for red blood cells, haemoglobin and myoglobin. A diagnosis of acute renal failure secondary to daptomycin-induced rhabdomyolysis was made.
Daptomycin was discontinued and the patient was treated with intravenous fluid administration associated with urine alkalinization. This was followed by progressive amelioration of renal function, normalization of CPK and liver function tests, as well as resolution of muscular weakness.
Daptomycin is a novel cyclic lipopeptide antibiotic with rapid bactericidal activity against most Gram-positive organisms including MRSA and vancomycin-resistant enterococci.2 It is generally well tolerated by most patients. However, as with all new drugs, uncommon adverse events may become apparent during post-marketing surveillance. Skeletal muscle toxicity was recognized in Phase I clinical studies.3 CPK elevations occurred in 2.8% of cases and 0.2% experienced myopathy.4 In animal studies, the risk of adverse skeletal muscle effects appeared to be closely related to dosing frequency and were minimized by once daily administration of the drug.5
Recently, a case of muscle pain and elevation of CPK induced by daptomycin was reported followed by another case in which myopathy was associated with elevation of CPK as well as liver enzymes.1,6 In the first case, CPK elevation was moderate and there was no mention of alteration in liver or kidney function. The second patient, who had a history of hepatitis C, presented with high levels of CPK and liver enzymes, but his kidney function remained normal. Our patient presented with high levels of CPK and transaminases as well as progressive non-oliguric acute renal failure. Discontinuation of daptomycin was followed by normalization of CPK, liver enzymes and renal function as well as disappearance of myoglobin and haemoglobin from urine.
To our knowledge, this is the first reported case of acute renal failure secondary to daptomycin-induced rhabdomyolysis. Interestingly, daptomycin was administered as a once daily dose in this case and no other medication known to induce rhabdomyolysis (e.g. statins or fibrates) was concomitantly used. This shows that once daily dosing may not be completely protective and that additive muscular adverse effects of other drugs are not necessary for daptomycin to induce myopathy.
Based on this observation, we recommend close monitoring of symptoms of myopathy in patients treated with daptomycin, along with serial follow-up of serum creatinine. If muscle weakness and/or elevations in the serum creatinine develop, rapid assessment of CPK, liver function tests and also a urinalysis may be helpful in the early diagnosis of renal impairment and its management in these patients.
Transparency declarations
No specific financial support was obtained for the preparation of this article. The authors have no potential conflicts of interest to declare with respect to this paper.
References
1.
Echevarria K, Datta P, Cadena J et al. Severe myopathy and possible hepatotoxity related to daptomycin. J Antimicrob Chemother 2005; 55: 599–600.
2. Carpenter CF, Chambers HF. Daptomycin: another novel agent for treating infections due to drug-resistant gram-positive pathogens. Clin Infect Dis 2004; 38: 994–1000.[CrossRef][Web of Science][Medline]
3. Tally F, Zeckel P, Wasilewski M et al. Daptomycin: a novel agent for Gram-positive infections. Expert Opin Investig Drugs 1999; 8: 1223–38.[CrossRef][Medline]
4. Package insert. Cubicin (Daptomycin) Injection. Lexington, MA: Cubist Pharmaceuticals, September 2003.
5.
Oleson FB Jr, Berman CL, Kirkpatrick JB et al. Once daily dosing in dogs optimizes daptomycin safety. Antimicrob Agents Chemother 2000; 44: 2948–53.
6.
Veligandla SV, Louie KR, Malesker MA et al. Muscle pain associated with daptomycin. Ann Pharmacother 2004; 38: 1860–2.
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