80 year old patient with a recent history of c. diff presents with symptoms of dysuria and urinary frequency for 12 hours. The patients calculated creatinine clearance is consistent with a UTI. Do I reach for my script pad and send her home on Macrobid or not?
Acute uncomplicated cystitis is becoming more difficult to treat in the setting of increasing antimicrobial resistance. In the 2010 IDSA Guideline, nitrofurantoin is listed as the first-line choice, surpassing ciprofloxacin and sulfamethoxazole/trimethoprim from the previous iteration.
Why not just prescribe 5 days nitrofurantoin for all patients with acute uncomplicated cystitis?
1. Up through 2012, the American Geriatrics Society’s Beers Criteria for Potentially Inappropriate Use in Older Adults recommended against using nitrofurantoin in this age group. The 2015 Beers Criteria iteration now suggests it is safe in older adults with a creatinine clearance > 30 mL/min, but should still be avoided in long-term use for suppression.
2. Nitrofurantoin is contraindicated in patients with creatinine clearance < 60 mL/min.
- A retrospective chart review of 356 patients (mostly older adults) was conducted in 2009 that assessed the efficacy and safety of nitrofurantoin in patients with renal impairment. The study concluded that nitrofurantoin cure rates for UTI and adverse events were similar between those with and those without renal impairment.
- In a cohort of 21,317 women, nitrofurantoin treatment was not associated with a higher risk of ineffectiveness in women with UTI and moderate renal impairment (30-50 ml/min/1.73 m2). However, the authors did find a significant association between renal impairment (1.73 m2) and pulmonary adverse events leading to hospitalization (HR 4.1, 95% CI 1.31-13.09).
- Concern exists for an associated increased risk for serious adverse reactions in patients with renal impairment.
- Pulmonary toxicity, hepatotoxicity, and hemolytic anemia are rather rare occurrences, and are often linked to prolonged treatments (6 months or longer).
While both recent studies had some limitations, they still suggest that patients with an estimated creatinine clearance >40 mL/min are probably safe to receive a 5-day course of nitrofurantoin. Although it may be safe, the clinician must keep in mind that there is a significant association between renal impairment and pulmonary adverse events leading to hospitalization and should communicate this to the patient. For this patient, this might be the time I reach for the single dose Fosfomycin!
Mercy Medical Center Antibiogram Data – January through December 2015
The most recent guidelines for uncomplicated cystitis which were published in 2010 recommend nitrofurantoin, Bactrim, or fosfomycin first line and reserve quinolones and beta-lactams for second line due to resistance to most commonly associated pathogens. The most common pathogens implicated in the urinary infections we treat here remain e.coli number one followed by Klebsiella pneumonia and proteus and to a much lesser extent enterobacter and enterococcus.
If you look at the antibiogram, nitrofurantoin is our best bet to cover e.coli, but has very low susceptibility for most of the other common pathogens (Kleb pneumo only 46%, proteus 1%, enterobacter 24%). Bactrim provides pretty reliable coverage for Kleb pneumo (94%) and then is about on par with the other common pathogens. Fosfomycin has presumed susceptibility for the pathogens it is known to cover (MSSA, MRSA, S. epidermidis, Strep pneumonia, enterococcus faecalis, VRE, e.coli, proteus, kleb pneumo, enterobacter, serratia, salmonella, ESBL) but is still more expensive if the patient requires more than the single dose in the ED.
Quinolones offer reasonable coverage, but the most recent FDA warnings encourage physicians reserve this medication as a second line agent. http://www.fda.gov/Drugs/DrugSafety/ucm500143.htm
For pyelonephritis, quinolones or Bactrim x 14 days are still recommend first line. If a beta-lactam is used it should be x14 days as well. Nitrofurantoin should not be used in these cases as it only concentrates in the bladder and there isn’t much evidence to support or recommend fosfomycin for these either.
Hijinio Carreon DO & Jessica Nesheim PharmD
1. Bains A, Buna D, Hoag NA. A retrospective review assessing the efficacy and safety of nitrofurantoin in renal impairment. Can Pharm J. 2009;142(5):248–52.
2. Geerts, A.F., Eppenga, W.L. 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, vol. 69, iss. 9, (2013), pp. 1701-1707