Several investigations have been conducted which explore the effectiveness of a prophylactic antibiotic approach although cost and conflicting results, along with issues of adverse events and increasing likelihood of enhancing resistant organisms, have led reviewers to not recommend this approach for routine use (Garcia Leoni & Esclarin De Ruz 2003; Morton et al. 2002). Although researchers and clinicians have reservations about this approach, an obvious and important variable is the specific antibiotic that is used for prophylaxis. For the most part, investigations in SCI patients have involved different dosages and regimens of orally administered ciprofloxacin or co-trimoxazole (trimethoprim-sulfamethoxazole; TMX-SMX) as prophylactic measures.
An RCT comparing low-dose, long-term treatment with ciprofloxacin (100 mg nightly) versus placebo concluded that ciprofloxacin prophylaxis for up to 39 months resulted in a marked reduction from the pre-study infection rate (p<0.00005, corrected) with no severe side effects and only 1 instance of ciprofloxacin resistant E. coli found in the feces of 1 patient (Biering-Sorensen et al. 1994). Another RCT involved a 3 day course of ciprofloxacin (500 mg twice daily) or suitable placebo as a pre-cursor to urodynamic investigation (Darouiche et al. 1994), which has been associated with subsequent development of UTI (Pannek & Nehiba 2007). Of those receiving ciprofloxacin, none had a symptomatic UTI at the study follow-up visit (3-5 days post urodynamic testing), whereas 3 of 22 study participants (14%) in the placebo group developed a symptomatic UTI. This finding was statistically non-significant (p=0.24), but the trend for reduced UTI incidence and the fact that no subjects in the treatment group actually developed a UTI suggests that a study with greater power may demonstrate the benefit of pre-urodynamic testing prophylaxis more conclusively.
Conflicting results have been obtained across separate controlled trials conducted in individuals undergoing acute SCI inpatient rehabilitation of sustained (i.e., >3 months) prophylaxis with TMP-SMX. Gribble and Puterman (1993) reported that oral administration of a TMP-SMX (40 mg and 200 mg, respectively) formulation once daily was found to significantly reduce frequency and relapse rates of bacteriuria (p=0.0001) and symptomatic UTI (p=0.0003) in persons with recent SCI using intermittent catheterization for bladder management (n=129). Conversely, Sandock et al. (1995) reported on an investigation of patients at least 6 months post-injury within an inpatient SCI rehabilitation program in which the standard of care was to prescribe TMP-SMX liberally as a prophylaxis. This practice was stopped for the purpose of conducting a prospective controlled trial in 1 of 2 units and it was noted that there was no significant difference in the number of symptomatic UTIs between those stopping versus those continuing suppressive therapy (0.043 versus 0.035 UTIs/week; p>0.5). In addition, there was a significant decrease in the emergence of TMP-SMX resistant asymptomatic bacteriuria in the patients stopping suppressing therapy (78.8% versus 94.1%; p<0.05). This latter finding was also consistent with that noted by Gribble and Puterman (1993) who noted this, along with TMP-SMX related adverse events as serious limitations of TMP-SMX prophylaxis therapy. Reid et al. (1994b) also showed an inability of a higher dose of TMP-SMX (160 mg and 800 mg, respectively) to reduce rates of symptomatic UTI among inpatients using intermittent catheterization for bladder management.
Given the conflicting findings noted above and in other patient groups, a novel approach to UTI prevention in SCI patients was undertaken by Salomon et al. (2006). After a prospective, pre-post study with 2-year follow-up, they concluded that a weekly oral cyclic antibiotic (WOCA) program was beneficial in preventing UTI in SCI patients, decreasing antibiotic consumption and decreasing the number and length of hospitalizations, without severe adverse events or the emergence of multi-drug resistant bacteria. The WOCA regimen involved alternating between two antibiotics, administered once per week over at least 2 years. The specific antibiotics selected as prophylaxis were customized to the patient, chosen based on allergy and antimicrobial susceptibility. The most frequent combination of antibiotics utilized were TMP-SMX and cefixime (30%) followed by cefixime and nitrofurantoin (25%). The combination of antibiotics was modified in 40% of the patients once, 20% twice and 10% on three occasions during the follow-up. Salomon et al. (2009) expanded on earlier work specifically to employ a WOCA program in pregnant women with SCI. In this study, UTI rate during pregnancy (which is commonly elevated) was significantly reduced, no complications were observed during delivery, and all newborns were a healthy weight (Salomon et al. 2009). This level 4 evidence for the effectiveness of WOCA in SCI UTI prevention, treatment and cost, and would serve well as guidance in design of a randomized, double-blind, placebo-controlled study to confirm these results.
There is level 1b evidence (from one RCT; Biering Sorensen et al. 1994) that low-dose, long-term ciprofloxacin may prevent symptomatic UTI.
There is level 1b evidence (from one RCT; Gribble & Puterman 1993) that TMP-SMX as prophylaxis may reduce symptomatic UTI rates although conflicting findings were obtained from two prospective controlled trials (Sandock et al. 1995; Reid et al. 1994b). The potential for emergence of drug resistant bacteria and TMP-SMX related adverse events further limit the potential use of TMP-SMX for prophylaxis.
There is level 4 evidence (from one pre-post study; Salomon et al. 2006) that suggests weekly oral cyclic antibiotic use, customized as to individual allergy and antimicrobial susceptibility, may be effective for UTI prevention in SCI patients, and UTI reduction in pregnant patients.