Acute uncomplicated cystitis is becoming more difficult to treat in the setting of increasing antimicrobial resistance. In the 2010 IDSA Guideline, nitrofurantoin (Macrobid) is now listed as the first-line choice, surpassing ciprofloxacin and sulfamethoxazole/trimethoprim from the previous iteration.
For tested E. Coli strains at my institution in 2012, the susceptibility to common agents is as follows:
- Ciprofloxacin 61%
- Levofloxacin 72%
- Sulfamethoxazole/trimethoprim 69%
- Nitrofurantoin 97%
- The American Geriatrics Society's Beers Criteria for Potentially Inappropriate Use in Older Adults recommends against using nitrofurantoin in this age group.
- Nitrofurantoin is contraindicated in patients with creatinine clearance < 60 mL/min.
- Concern exists for an associated increased risk for serious adverse reactions in patients with renal impairment (possible older adults).
- Pulmonary toxicity, hepatotoxicity, and hemolytic anemia are rather rare occurrences, and are often linked to prolonged treatments (6 months or longer). 
- Published cases of peripheral neuropathy associated with nitrofurantoin in patients with renal insufficiency have occurred most often with treatments lasting beyond the 5-day period recommended by the IDSA. 
Use with Reduced Renal Function
Is it really true that nitrofurantoin is not effective when CrCl drops below 60 mL/min?
Two more recent studies evaluated clinical efficacy.
- 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). The authors did, however, find a significant association between renal impairment (<50 ml/min/1.73 m2) and pulmonary adverse events leading to hospitalization (HR 4.1, 95% CI 1.31-13.09). AIn absolute terms, only 4 out of 187 (2.1%) patients had adverse effects in the group with poor renal function and it is unclear if patients with with the lowest CrCl had more adverse events. 
Bryan Hayes, PharmD
Clinical Assistant Professor, University of Maryland (UM) Clinical Pharmacy Specialist, EM and Toxicology
- Guay DR. An update on the role of nitrofurans in the management of urinary tract infections. Drugs 2001;61:353-64. [PMID 11293646]
- Oplinger M, et al. Nitrofurantoin contraindication in patients with a creatinine clearance below 60 mL/min: looking for the evidence. Ann Pharmacother 2013;47(1):106-11. [PMID 23341159]
- Bains A, Buna D, Hoag NA. A retrospective review assessing the efficacy and safety of nitrofurantoin in renal impairment. Can Pharm J 2009;142:248-52.
- Geerts AF, et al. Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care. Eur J Clin Pharmacol 2013 May 10. [Epub ahead of print] [PMID 23660771]