On 28 December 2001, she enrolled in the Program and was prescribed ciprofloxacin for an additional 40 days. She elected not to receive AVA. At the time of enrollment, she did not indicate to the clinician the severity of her ongoing nausea. She stopped taking ciprofloxacin 3 days after enrollment because of continued severe nausea. Ten days later, she sought medical attention for the first time for severe nausea that continued after she was no longer adhering to the ciprofloxacin regimen. She was admitted to the hospital on the day of her initial examination, 10 January 2002, with a diagnosis of acute renal failure and started hemodialysis. While hospitalized, she received one 500-mg tablet of ciprofloxacin per day. After her discharge from the hospital, ciprofloxacin therapy was stopped. She continued to undergo hemodialysis, and her nephrologist performed a renal biopsy on 30 January 2002. The results of the biopsy showed acute inflammatory changes diagnostic of allergic interstitial nephritis (AIN) that were consistent with ciprofloxacin use. She also exhibited chronic vascular changes consistent with hypertensive nephrosclerosis. Telephone consultation with her nephrologist confirmed her diagnosis as AIN. A course of corticosteroid treatment did not improve her renal function, and the participant was still undergoing hemodialysis at the time of this writing. The medical monitor determined that the AIN was probably associated with the use of ciprofloxacin therapy provided by the Program. Follow-up of this participant by her nephrologist and the CDC was ongoing at the time of this writing.

This participant received a diagnosis, after undergoing a renal biopsy, of acute renal failure secondary to AIN and underlying chronic hypertensive nephropathy. The results of the biopsy revealed both acute and chronic tubulointerstitial nephritis, with a diffuse lymphocytic infiltrate and occasional eosinophils, edema, basement membrane thickening, and fibrosis. The presence of acute inflammatory changes, including eosinophils and edema, established the diagnosis of AIN. The chronic appearance may reflect the 3-month delay between the participant's initial exposure to ciprofloxacin and performance of the biopsy. In addition, chronic vascular changes, tubular atrophy, and glomerulosclerosis are indicative of long-standing hypertensive nephrosclerosis.

The literature contains reports of AIN as a recognized but unusual complication of treatment in patients receiving ciprofloxacin therapy. A review of 43 cases of fluoroquinolone-associated nephrotoxicity reported in the medical literature between 1985-1999 included 21 suspected cases of AIN [15]. Of these 43 cases only 12 of the 21 suspected AIN cases were confirmed to be AIN by renal biopsy. Renal biopsy is usually required to make a definitive diagnosis of AIN. In a review of the literature to date, we found only 1 additional case of ciprofloxacin-induced nephrotoxicity, which was reported by Bald et al. [22] in 2001. The results of the renal biopsy performed on this patient revealed only discrete interstitial infiltration without interstitial nephritis. AIN is typically not dose related and symptoms usually develop within 3-10 days of initiating therapy. Treatment of AIN typically involves discontinuation of therapy, transient dialysis, and consideration of short-course corticosteroid treatment. The gradual onset of nonspecific symptoms makes diagnosis of renal failure difficult in these patients and dependent on detection of an elevated serum creatinine level.

This participant's concern about developing anthrax if medication was discontinued caused her to be reluctant to report her increasing symptoms of nausea. Thus, prolonged use of ciprofloxacin, in combination with her long-standing, but unrecognized, hypertensive nephropathy, resulted in the development of acute renal failure that did not resolve when ciprofloxacin therapy was discontinued. Although the diagnosis of AIN was made after the participant entered the program, her history and the known clinical course of AIN suggest the possibility that renal failure developed secondary to ciprofloxacin therapy received before enrollment and may not have been directly associated with prophylaxis she received in the Program.