Single Dose Aminoglycosides for Acute Uncomplicated Cystitis in the Emergency Department Setting

Urinary tract infections (UTIs) account for more than 8 million office visits and 1 million emergency department visits each year in the United States, making them one of the most often encountered indications for antibiotic use in ambulatory care. Escherichia Coli has been shown to be the main cause of uncomplicated cystitis, occurring in 75-95% of cases, with other Enterobacteriaceae like Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus saprophyticus comprising the majority of the other potential causes of cystitis. E. coli is also the most frequently encountered nitrite positive Enterobacteriaceae locally as well, representing nearly 3 out of every 4 culture specimens in the Boardman-specific gram-negative urine antibiogram (74%), 209 out of 284 to be exact. Some of the typical antibiotics used to treat these organisms had seen rising resistance rates from 2003-2012, with substantial increases in the resistance to both ciprofloxacin (3.6% to 11.8%) and trimethoprim-sulfamethoxazole (17.2% to 22.2%) in the United States. Gentamicin offers 93% sensitivity towards E. coli in the local antibiogram, whereas sulfamethoxazole-trimethoprim and fluoroquinolones offer 75% and 69%, respectively. More importantly, the current standard of care, cefdinir, only offers around 80% sensitivities locally. While nitrofurantoin has retained high levels of antibiotic activity against E. coli, it is contraindicated in the elderly and patients with poor renal function. This growing rate of resistance has placed a larger emphasis on finding alternative treatment options.

As stated above, Goodlet et al. reviewed 13 studies totaling 13,804 patients, and data from 11 out of the 13 revealed a microbiological cure rate of 94.5% +/- 4.3% using single dose aminoglycosides to treat urinary tract infections. Seven of these studies had comparator groups that included medications such as oral cephalosporins, Fosfomycin, trimethoprim-sulfamethoxazole and amoxicillin. No difference in initial or sustained microbiological cure rate in those that received aminoglycosides versus other medications was demonstrated. Only two of the thirteen studies evaluated clinical cure rates which were shown to be 82.8% and 94.7%, respectively. In the studies with 30 day follow up, an overall recurrence rate at 30 days was found to be 19% (84/443 patients). The recurrence rate seen using aminoglycosides is improved when compared to the general population, as 27% of women have been found to experience recurrence of their symptoms within 6 months of having urinary tract infections. Aminoglycosides were at one time a standard first-line therapeutic option to treat UTIs but fell out of favor due to their side effect profile.

The most concerning adverse effects of aminoglycosides were mainly seen in association with multi-day regimens of the drugs. Their nephrotoxic and ototoxic effect are seen in less than 1% of patients evaluated, but saw their use decrease roughly 41% between 2002-2009. In the Goodlet et al. study only 63 of the 13,804 patients (0.5%) reported adverse effects associated with the single dose aminoglycoside treatment. Only 7 total cases (0.05%) reported nephrotoxicity and 53 total cases (0.38%) reported signs of vestibular toxicity such as tinnitus and equilibrium disorders. Additionally, in a study of over 10,000 patients receiving single dose amikacin for UTI, nephrotoxicity was only reported in 0.04% of cases. Another review looking at 24,107 patients that had received a single dose of gentamicin reported no cases of ototoxicity as well. Comparably, sulfamethoxazole-trimethoprim carries common and rare risks of hyperkalemia, blood dyscrasias, hypersensitivity reactions, and other adverse events affecting nearly every organ system of the body. Fluoroquinolones carry common and rare risks of QT segment prolongation, peripheral neuropathy, dysglycemia, adverse events affecting the whole body and even a long-term syndrome effecting tens of thousands of people called fluoroquinolone-associated disability (FQAD). Beta-lactams such as cefdinir commonly cause gastrointestinal symptoms but more rarely effect other organ systems such as the skin, metabolic and hematologic abnormalities, and other adverse events as well. While adverse effects may occur with aminoglycosides, the studied risk of single dose use is not extreme and comparable with adverse effects seen with current standards of care.

While there is a proven cure rate utilizing single dose aminoglycosides to treat acute uncomplicated cystitis, they will also provide several other benefits when used in the emergency department setting. The single dosing of antibiotic in the emergency department removes the need for patient adherence to outpatient antibiotic therapy, thus reducing possible bounce back visits. Gentamicin can also be administered intramuscularly, as it was in all the above studies, both removing the need for IV access and expediting possible disposition in the emergency department. Lastly, greater than 75% of outpatient UTI prescriptions are written for durations that are not recommended, which is an issue that can be removed from the equation entirely utilizing single dose treatment. Treating patients with single dose aminoglycosides for acute uncomplicated cystitis in the emergency department may provide better compliance with the same efficacy, resulting in a new standard of care for treatment in the emergency department.