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Once Daily Levofloxacin for 5 Days in the Treatment of Acute Pyelonephritis and Associated Bacteraemia: Presented at ECCMID-ICC

By Chris Berrie

MUNICH, GERMANY -- April 2, 2007 -- Five doses of levofloxacin are non-inferior to 20 doses of ciprofloxacin for the eradication of blood pathogens in patients with acute pyelonephritis (AP), according to data from a double-blind, randomised study presented here at the joint 17^th European Congress of Clinical Microbiology and Infectious Diseases and 25^th International Congress of Chemotherapy (ECCMID-ICC).

"Acute pyelonephritis is a systemic urinary tract infection that involves the kidney, with approximately a quarter of a million cases per year in the USA," said James B. Kahn, MD, study designer and sponsor and head of infectious diseases research, Ortho-McNiel, Johnson & Johnson, Raritan, New Jersey, United States. Interestingly, while more common in females, it shows higher mortality in males.

Escherichia coli is the most common pathogen in AP. Bacteraemia is seen in 5% to 20% of uncomplicated cases, and in 20% to 45% complicated cases.

Dr. Kahn and colleagues defined complicated AP (cAP) as AP in the presence of any of the following features: male sex, nosocomial acquisition, obstruction, post-void residual > 100 mL, stones, diabetes, immunocompromised status, pregnancy, neurogenic bladder, indwelling or intermittent catheter, recent invasive procedure, ileal loop, or sickle cell disease.

The researchers enrolled patients who were hospitalised, in a nursing home or ambulatory and were aged 18 years or older. The primary endpoint was microbiological eradication. Infection was defined as 10⁵ or more colony forming units (CFU) with no more than 1 or 2 uropathogens, while eradication was defined as fewer than 10⁴ CFU post-therapy.

Of 1,109 patients enrolled, the intention-to-treat (ITT) population for randomisation comprised 782 with complicated urinary tract infection (cUTI) and 311 with AP. Of these, 619 satisfied the clinical diagnosis and the required infection definition (n = 427, n = 192, respectively), representing the modified ITT (mITT) population, of which 42 had cAP.

The mITT AP group consisted of 94 patients who received their randomisation-designated treatment of levofloxacin 750 mg IV/oral per day for 5 days, and 98 mITT AP patients received ciprofloxacin 400/500 mg IV/oral twice a day for 10 days. Of these patients, 80 and 76, respectively, represented the microbiologically evaluated (ME) patients, of which 33 had cAP.

At end of therapy, microbiological and clinical responses in the mITT population were not significantly different, 80.3% and 85.1% for levofloxacin, respectively, and 78.6% and 88.2%, respectively, for ciprofloxacin. Post-therapy, these were 83.0% and 79.6% for levofloxacin, and 86.2% and 80.6% for ciprofloxacin.

The incidence of bacteraemia in the analysis populations after adjustment for those who provided for baseline blood cultures were: ITT (n = 280), 8.6%; mITT (n = 176), 13.6%; and ME (n = 144), 11.8%.

In his presentation on April 1^st, Dr. Kahn noted that cAP showed higher incidence of bacteraemia (mITT, 14.3% vs 12.0%; ME, 12.1% vs 10.6%), and lower clinical response (ME, 85% vs 93%) and microbiological eradication (ME, 85% vs 95%) compared with uncomplicated AP.

The final breakdown of the mITT patients in the AP group showed 24 with bacteraemia, who were divided equally between the levofloxacin and ciprofloxacin treatments; within these, 6 had cAP (3 each with levofloxacin, ciprofloxacin). For all of these bacteraemia AP patients at post-therapy, there were no differences between levofloxacin and ciprofloxacin treatments, whereby pathogen eradication in the repeat blood culture bacteraemia AP patients (mITT, n = 21) was 100% with both agents post-therapy.

All blood and urine pathogens were Escherichia coli. Among urine pathogens in the ciprofloxacin group there was a ciprofloxacin-resistant pathogen isolated from 1 patient (minimum inhibitory concentration >32 mcg/mL).

Therefore, Dr. Kahn stressed, in this large population of patients with AP, this 5-dose regimen with levofloxacin was non-inferior to the 20 doses of ciprofloxacin. He noted that patients with uncomplicated AP had higher eradication and clinical success rates than those with cAP, while both of these treatment regimens were seen to eradicate the blood pathogens in all of the patients who supplied a post-treatment blood sample.

This study was supported by Johnson & Johnson.


[Presentation title: Once Daily Levofloxacin 750 mg for 5 Days in the Treatment of Acute Pyelonephritis and Associated Bacteraemia. Abstract O142]

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