Letters to the Editor

Ceftriaxone-associated urolithiasis treated with ureteral stenting and extracorporeal shock wave lithotripsy A 79-year-old man who had no previous or family history of urolithiasis or renal disorder presented with a fever and precordial pain. The laboratory findings revealed elevated white blood cell counts and C-reactive protein level. Hepatic enzymes, renal function, electrolytes and urine analysis were normal. Contrast-enhanced computed tomography (CT) and pericardiocentesis confirmed infectious pericarditis. Antibiotic therapy was initiated. He had relapsing febrile episodes when the antibiotics were stopped. We started intravenous ceftriaxone 2 g/day divided into two equal doses on day 44. A repeat contrast-enhanced CT was performed on day 47. It suggested the antibiotic therapy was effective. There were no noteworthy biliary or urinary findings. Hence, we doubled the dose of ceftriaxone to 4 g/day and added amikacin. His serum creatinine rose on day 58, and a subsequent urinalysis showed 3 + haematuria. He underwent contrast-enhanced CT with hydration. Biliary precipitation was detected along with multiple high-density deposits in the urinary tract, accompanied by pyelectasis (Fig. 1). Ceftriaxone and amikacin were



immediately discontinued and hydration was continued, but his renal function deteriorated. He became anuric on day 61. He underwent cystoscopy with insertion of a double-J stent, and his renal function gradually recovered. He was discharged on day 70. He reported passing gravel on micturition, and we collected samples for mass spectrometry. The amount of gravel was so small that only a qualitative analysis was done; the recorded spectrum analysis suggested the material was composed of ceftriaxone. Urinary calculi persisted, and he underwent extracorporeal shock wave lithotripsy (ESWL) 4 months after discharge. The double-J stent was removed. Ceftriaxone-associated urolithiasis is rare, and only a few cases have been reported in the literature, mostly in paediatric patients and rarely in adults.1,2 Risk factors for drug-induced urolithiasis depend on both the patient and drug.2 Ceftriaxone is primarily eliminated through the kidneys, with the remainder eliminated through the biliary system. Anionic ceftriaxone binds to cationic calcium ions to form insoluble precipitates that can cause biliary and renal calculi.3 In the present case, we diagnosed ceftriaxoneassociated urolithiasis with mass spectrometry. The




Figure 1 Computed tomography, day 58. (a) Biliary precipitation and high-density deposits are visible (b) in the renal calyx, (c, arrow) at the ureteropelvic junction, (d, arrow) in the lower ureter (e, arrow) and at the ureterovesical junction.


© 2013 The Authors Internal Medicine Journal © 2013 Royal Australasian College of Physicians


Letters to the Editor

urinary calculi were not seen on the CT performed on day 47 but were visible on day 58. The long treatment period, high dose and concomitant administration of amikacin, a potentially nephrotoxic drug, may have all been involved. The largest urinary stone detected on CT was about 8 mm. It is reported that the size and number of crystals formed in vitro by ceftriaxone sodium and calcium chloride will grow in proportion with incubation time and ceftriaxone concentration.3 We believe that the long treatment period and high dose of ceftriaxone together promoted formation of multiple large urinary stones, which resulted in ureteral obstruction and required stenting with persistent residual stones that required ESWL.

References 1 Li Z-L, Li H-L, Chen H-W, Li H-C, Zhang P, Wang Z-M et al. Anuria and abdominal pain induced by ceftriaxone-associated ureterolithiasis in adults. Int Urol Nephrol 2013; 45: 73–6.

This is the first report of ceftriaxone-associated urolithiasis requiring ureteral stenting and ESWL. This case emphasises the need for clinicians to keep in mind the possibility of urolithiasis, especially in cases of prolonged and high-dose ceftriaxone therapy, even in adult patients who have no apparent predisposition to renal stones. Received 2 April 2013; accepted 5 May 2013. doi:10.1111/imj.12267

T. Nakabori, M. Fukunaga, S. Hayashi, K. Yamamoto, M. Ichiba and M. Inada Department of Internal Medicine, Toyonaka Municipal Hospital, Toyonaka, Japan

2 Daydon M, Jungers P. Drug-induced renal calculi: epidemiology, prevention and management. Drugs 2004; 64: 245–75. 3 Chutipongtanate S, Thongboonkerd V. Ceftriaxone crystallization and its

potential role in kidney stone formation. Biochem Biophys Res Commun 2011; 406: 396–402.

General correspondence

Venous thromboprophylaxis audit in two Queensland hospitals As a quality assurance exercise by a perioperative medical service, two (unpublished) audits on venous thromboembolism prophylaxis were recently conducted among medical, surgical and orthopaedic patients in a local hospital. The audit results were mostly consistent with those of the larger study by Phillips and Heazlewood,1 but additionally, our studies highlighted some issues of interest especially in the medical care of orthopaedic patients. Our first study comprised a snapshot survey of all medical, surgical and orthopaedic inpatients (n = 73) on a particular day with respect to appropriate use of prophylactic venous thromboembolism plans, as per the same guidelines as those used in the article by Phillips and Heazlewood (R. A. Wallace and C. Marathe, unpubl. data, 2009). Of the 18 orthopaedic patients requiring prophylaxis, all had appropriate inpatient use of venous thromboembolism chemoprophylaxis, but only four (22%) had mechanical devices. On follow up of this © 2013 The Authors Internal Medicine Journal © 2013 Royal Australasian College of Physicians

group, no patients were discharged on chemoprophylaxis as per the guidelines (up to 14 days for total knee replacement and up to 35 days for hip replacements). Of the 29 (9 high risk) medical patients requiring prophylaxis by the guidelines, 20 (69%) (8 high risk) had neither chemoprophylaxis nor mechanical prophylaxis. Of the 20 surgical (neurosurgical, general, colorectal, urological) patients, 3 of 12 (25%) high risk and 4 of 8 (50%) moderate risk patients had neither chemoprophylaxis nor mechanical prophylaxis. Our second audit was based around the perioperative medical profile of patients undergoing traditional versus anterior hip replacements over a 6-month period and included venous thromboembolism prophylaxis assessment (R. A. Wallace, G. Girao and R. G. Edillon, unpubl. data, 2010). In this study, 139 patients underwent elective hip replacement over a 6-month period, 48 (35%) anterior and 91 (64%) traditional group. During inpatient care, 36 (75%) of the anterior approach patients had chemoprophylaxis (with aspirin), and 76 (83%) of the traditional group had usual chemoprophylaxis with low 1167

Ceftriaxone-associated urolithiasis treated with ureteral stenting and extracorporeal shock wave lithotripsy.

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