Urinary Tract Infections: A Pharmacotherapy Review

Great post.

Regarding Nitrofuratonin; I think that we can probably use it in patients with UTI with moderately impaired renal function. To my knowledge, the risk of subtherapeutic concentrations in the urine is more theoretical secondary to known poor tissue penetration by nitrofuratonin. In fact, previously, the nitrofuratonin product information said that the CrCl cut-off was 40; but somewhere along the way they changed this to 60.

A recent review by Oplinger and Andrews published in Annals of Pharmacotherapy suggests that maybe the evidence isn't that great that we should draw the line at CrCl of 60. They suggest that the limited data available would support considering using Nitrofuratonin in patients with a CrCl of 40 mL/min or higher rather than 60 mL/min.

And I think that this is a legitimate point that needs to be discussed and looked into further because a lot of our options don't work so well against common UTI bugs. But nitrofuratonin does and we maybe limiting ourselves a bit by not using it on a patients who may benefit from it.

References:
M. Oplinger, and C.O. Andrews, "Nitrofurantoin contraindication in patients with a creatinine clearance below 60 mL/min: looking for the evidence.", The Annals of pharmacotherapy, 2013. http://www.ncbi.nlm.nih.gov/pubmed/23341159

Excellent.

Thank you for raising this important issue.

While there is evidence to suggest that nitrofurantoin retains clinical efficacy for cystitis with renal function of CrCl < 60 mg/dL, the main issue in patients with renal insufficiency is pulmonary toxicity.

A recent trial published in the European Journal of Clinical Pharmacology suggests that despite maintaining clinical cure with reduced clearance, adverse events increased when nitrofurantoin was utilized in patients with a eGFR below 50 mL/min. The incidence of pulmonary adverse events leading to hospitalization increased by a hazard ratio of 4.1 (95% CI 1.31-13.09) to 0.02 per 1,000 person days. Based on these results, nitrofurantoin cannot be recommended for use when eGFR is below 50 mL/min.

In addition, it’s important to recall that the absence of evidence is not evidence of safety. The manufacturer's recommendation change for minimum creatinine clearance may reflect unpublished data held by the drug company. Without evidence of safety below recommended dosing guidelines and published evidence of increased harm, the safest approach is to NOT use nitrofurantoin below the manufacturer recommended threshold of CrCl 60 mg/dL.

References:
Geerts et al. "Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care.", European Journal of Clinical Pharmacology (2013) 69:1701-1707
http://www.ncbi.nlm.nih.gov/pubmed/?term=Ineffectiveness+and+adverse+events+of+nitrofurantoin+in+women+with+urinary+tract+infection+and+renal+impairment+in+primary+care