Page 20 - Recurrent uncomplicated urinary tract infections in women: AUA/CUA/SUFU guideline

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American Urological Association (AUA)/Canadian Urological Association (CUA)/ Recurrent Uncomplicated
Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction (SUFU) Urinary Tract Infection

TMP-SMX, norfloxacin, and cefaclor (p for interaction While nitrofurantoin remains a first-line choice for
91
0.79). However, nitrofurantoin was associated with a treatment of acute UTI as recommended by IDSA,
decreased risk of rUTI compared to TMP in one trial (RR and has been shown to be effective as a prophylactic
0.58, 95% CI 0.36 to 0.94; ARD -28%, 95% CI -50% antibiotic for UTI prevention, all antibiotics including
to -5%). 129 One trial of nitrofurantoin versus fosfomycin nitrofurantoin have potential risks. These risks should
was published in 2007 (RR for ≥1 UTI 0.87, 95% CI be discussed with patients prior to prescribing for short-
0.44 to 1.71); 137 all of the other trials were published in , medium-, or long-term prophylaxis. Nitrofurantoin is
or before 1995. commonly prescribed in women of all ages and has rare
but potentially serious risks of pulmonary and hepatic
While quinolones have been studied as prophylaxis, the toxicity. 151-154 The rate of possible serious pulmonary or
use of fluoroquinolones, such as ciprofloxacin, for hepatic adverse events has been reported to be
prophylactic antibiotic use is not recommended in 0.001% and 0.0003%, respectively. 155 One 2015
current clinical practice. In 2008 the U.S. FDA issued a systematic review 156 observed no pulmonary or
black box warning on the increased risk of tendinitis hepatotoxic events related to nitrofurantoin among
and tendon rupture associated with ciprofloxacin. 148 4,807 patients from 27 controlled trials. A 2018
These serious side effects associated with retrospective chart audit 157 of an urban academic
fluoroquinolone use, which also include QT interval medical center found 0.7% of patients experienced
prolongation, seizures, and C. difficile infection, possible serious pulmonary or hepatic adverse effects,
generally outweigh the benefits of its use for and 0.15% (5 of 3,400 patients) were highly suspicious
uncomplicated UTI.
for having a serious lung or liver reaction. These
There is little evidence on the benefits of rotating patients were more likely to have long-term exposure
antibiotics used for prophylaxis. In a different to nitrofurantoin, highlighting the need for caution
population of inpatient hospital treatment of infection, when prescribing long-term and avoiding nitrofurantoin
informed switching strategies, 149,150 have been used in patients with chronic lung disease.
that take the frequency of antibiotic resistance Nitrofurantoin use in older adults has been
mutations into account. They used local antibiogram- controversial. Nitrofurantoin is listed as a potentially
guided therapy, which can potentially serve as a inappropriate medication for older adults by the AGS
valuable strategy to curb resistance. However, there is 158
not enough evidence in the existing published literature Beers Criteria, with the strength of recommendation
as strong and a listed quality of evidence of low. The
to reach reliable conclusions regarding the efficacy of 2015 Beers update has been modified to recommend
cycling antibiotics as a means of controlling antibiotic avoidance of nitrofurantoin when creatinine clearance is
resistance rates.
below 30mL/min. The rationale for avoiding
Adverse Events Associated with Prophylactic Antibiotics nitrofurantoin included pulmonary toxicity,
hepatotoxicity, and peripheral neuropathy, with concern
There was no difference in risk of any adverse event (4 about long-term use if other alternatives are available
2
studies, RR 1.59, 95% CI 0.58 to 4.42, I =89%), but for use. Nitrofurantoin-induced lung injury 159-164 can
estimates were inconsistent, 128,129,139,146 and occur in the acute, subacute or chronic setting, most
nitrofurantoin was associated with increased risk of commonly presenting with a dry cough and dyspnea. 165
study withdrawal compared to other antibiotics The mechanism underlying pulmonary toxicity is related
(norfloxacin, TMP, and TMP-SMX) (4 studies, RR 2.42, to the direct effects of nitrofurantoin metabolites on
2
95% CI 1.14 to 5.13, I =5%; ARD 7%, 95% CI 1% to lung tissue. 166 Acute pulmonary reactions appear after
13%). 126,128,129,139 All trials except for one 139 found a mean of nine days from starting nitrofurantoin
nitrofurantoin associated with increased risk of any therapy, while symptoms of subacute and chronic
adverse event (RR estimates ranged from 2.00 to pulmonary reactions develop between one and six
2.40). There were no differences between months of treatment, respectively. 162 In a 1980
nitrofurantoin and other antibiotics in risk of analysis of 921 reported cases by Holmberg et al., 151
gastrointestinal adverse events (3 studies, RR 1.78, 47% of cases of chronic respiratory disease occurred
2
95% CI 0.57 to 5.50, I =0%), 128,137,146 or vaginitis (2 after more than 12 months of nitrofurantoin therapy.
2
studies, RR 0.45, 95% CI 0.13 to 1.54, I =0%), 128,146 Risk assessment, shared decision-making, and clinical
but estimates were imprecise. Other side effects monitoring is important to avoid the potential adverse
included vaginal and oral candidiasis, skin rash, and events associated with nitrofurantoin.
nausea.
Potential adverse effects of gastrointestinal

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