“Crystals in the Mud”: Cefepime-Induced Crystalluria
A 68-year-old man presented to the emergency department (ED) with a 2-day history of nausea, watery diarrhea, loss of appetite, weakness, and dizziness. He had been diagnosed with prostate cancer 12 years ago and had undergone prostatectomy. Gradually, he had developed symptoms of intermittent bladder outlet obstruction and had had a recurrent urinary tract infection (UTI).
He had presented a year ago to the ED for urinary retention; at that time, a dense bulbar stricture prevented placement of a Foley catheter, so a suprapubic catheter was placed.
One month ago, he presented to the ED again, this time with a UTI, and underwent direct-vision internal urethrotomy and transurethral incision of the bladder neck contracture. He was treated with cefepime for ciprofloxacin-resistant Pseudomonas aeruginosa.
At this admission, his blood pressure was 100/60 mm Hg. Physical examination revealed poor skin turgor, sunken eyes, and listlessness. Electrolyte levels were within the normal range, as was the serum creatinine level (1.13 mg/dL; reference range, 0.6-1.4 mg/dL). Urinalysis demonstrated a pH of 7.0, with normal specific gravity (1.019; reference range, 1.005-1.030), and 11 to 20 white blood cells (WBCs) per high-power field (reference range, 0-5 per high-power field). The urine was negative for nitrite and positive for leukocyte esterase.
Based on previous cultures, he was started on cefepime for ciprofloxacin-resistant P aeruginosa and received intravenous fluids.
The next morning, his urine had become muddy brown. Urinalysis showed a reduction in pH to 6.5, and the WBCs now were too numerous to count. Under the microscope, Wright-Giemsa staining of the urinary sediment helped to identify numerous WBCs along with innumerable intracellular and extracellular needle-shaped crystals (Figure). Under polarized light, the crystals were found to be nonbirefringent.
Based on the distinct morphology of the urinary crystals and their temporal relationship with cefepime administration, the diagnosis of cefepime-induced crystalluria was established.
Magnetic resonance imaging (MRI) of the abdomen without contrast showed no signs of hydronephrosis. Circumferential bladder wall thickening was seen, which could have been associated with chronic outlet obstruction. Results of a basic metabolic panel revealed the following values: normal blood urea nitrogen (14 mg/dL; reference range, 8-23 mg/dL); normal creatinine (0.9 mg/dL; reference range, 0.6-1.4 mg/dL); normal sodium (143 mEq/L; reference range, 133-145 mEq/L); borderline low potassium (3.2 mEq/L; reference range, 3.3-5.1 mEq/L); borderline high chloride (110 mEq/L; reference range, 96-108 mEq/L); and normal bicarbonate (22.4 mEq/L; reference range, 22-30 mEq/L).
When unidentifiable urinary crystals are encountered, a thorough search into the etiology is warranted (Table). Uric acid, calcium monohydrate, calcium phosphate, and triple phosphate normally are present in urine.1 Certain foods, dehydration, changes in urine pH, and/or changes in temperature can cause supersaturation of these compounds in urine, leading to physiologic crystalluria.2,3 Although the asymptomatic cefepime crystalluria in our patient proved to be benign, other medications are known to cause acute renal failure, interstitial nephritis, and obstructive uropathy as a result of the precipitation of crystals in the kidney or the ureters. If the crystals are suspected to be medication-related, a reduction in the drug dosage, or its withdrawal, should be considered to prevent subsequent renal damage. Adequate hydration must be maintained, and renal function should be monitored.
More than 80% of cefepime is excreted unmetabolized in the urine, irrespective of the dose taken.1 Urinary excretion of unmetabolized cefepime can lead to its precipitation when coupled with other factors, such as acidic urine pH, dehydration, hypoalbuminemia, or medication overdose.
In our patient’s case, dehydration due to watery diarrhea increased the likelihood of precipitation of cefepime crystals. Because the crystals were promptly recognized, the patient’s fluid status was corrected, and the cefepime was stopped. No untoward effects of crystalluria were seen.
Urine microscopic examination is a noninvasive test that is readily available even at primary care clinics and in rural areas but that is underutilized at this time.
Further studies are warranted to understand the consequences of cefepime-induced crystalluria and to establish clinical guidelines for management.
Poorva Bindal, MBBS, is a first-year resident physician in the Department of Internal Medicine at the University of Connecticut in Farmington, Connecticut.
Padmashri Rastogi, MD, is an associate professor in the Department of Internal Medicine at the University of Texas Southwestern Medical School and at the Veterans Affairs Medical Center in Dallas, Texas.
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