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Pharmacological Treatment of UTIs

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UTIs in persons with SCI with neurogenic bladder are termed “complicated UTIs” which refers to the presence of a UTI in a functionally, metabolically, or anatomically abnormal urinary tract or that are caused by pathogens that are resistant to antibiotics (Stamm & Hooton 1993). Complicated UTIs may be caused by a much wider variety of pathogens in persons with SCI and are often polymicrobial. It is generally recommended that persons with SCI be treated for bacteriuria only if they have symptoms, as many individuals especially with indwelling or SPC typically have asymptomatic bacteriuria (Biering-Sorensen et al. 2001). Once symptomatic UTI is confirmed, the first line of empirical treatment is via antibiotics and the most common antibiotics chosen for UTI treatment include fluorquinolones (e.g., ciprofloxacin), TMP-SMX, amoxicillin, nitrofurantoin and ampicillin. Fluorquinolones are often chosen because of their effectiveness over a wide spectrum of bacterial strains (Waites et al. 1991; Garcia Leoni & Esclarin De Ruz 2003). Although much experience with treating UTIs in SCI has been gleaned from other indications, there are several studies that are reviewed below which have investigated a variety of antibiotic agents in this population.

Table: Antibiotics in Treatment of UTIs

Discussion

The range of effective antibiotic treatment duration can vary widely depending on the specific microorganism causing the infection, the antibiotic used and the patients’ UTI history. Dow et al. (2004) conducted a RCT (n=60) to compare a 14 day versus 3 day course of ciprofloxin treatment in SCI patients with UTI symptoms or microbially documented bacteriuria and concluded that a 14 day Ciprofloxin treatment results in improved clinical and microbiological outcomes. Microbiological relapse rates were significantly lower for those patients treated for 14 versus 3 days. Although, this high study advocates for the use of a 14 versus 3 day course of ciprofloxacin in SCI UTI, as the author notes, it does not address the optimal treatment period which may be 5, 7 or 10 days, nor does it examine the question of whether a higher dose might have been more effective with the shorter therapy.

Ofloxacin is a fluoroquinolone antibiotic shown to be promising in its ability to penetrate and eradicate bacterial biofilms in the bladder in vitro and in SCIpatients (Reid et al. 1994a; Reid et al. 1994b). Bacterial biofilms are colonies of microorganisms along with their extracellular products that may form on surfaces as a structured community that enables the pathogens to resist antibiotics and persist in the urinary tract thereby potentially causing recurrent UTI. Reid et al. (2000) employed a randomized, double blind design (n=42) to assess the relative effectiveness of a 7 day course of ofloxacin as compared to TMP-SMX or other more appropriate antibiotics as detected by culture sensitivity. Study participants had symptomatic UTI and clinical cure rates, defined as patients becoming asymptomatic with sterile urine, were assessed at day 4 and day 7. Clinical cure rate was significantly greater for Ofloxacin as compared to TMP-SMX or other antibiotic at day 4 (90% versus 48%; p=0.003) and day 7 (90% versus 57%; p=0.015). In addition, both treatments were effective at reducing bacterial biofilms at day 4 and 7 (p<0.001), although the biofilm eradication rate was significantly higher with Ofloxacin versus TMP-SMX or other antibiotic at day 4 (62% versus 24%; p=0.005); and day 7 (67% versus 35%; p=0.014). This finding was supported by an earlier study (Reid et al. 1994a) noting that fluoroquinolone therapy was more effective at reducing bladder cell adhesion counts in 63% of asymptomatic SCI UTIs versus 44% of SCI subjects treated with TMP-SMX.

Reid et al. (2000) suggested that a 3-day regimen in the treatment of SCI UTI could be sufficient based on significant biofilm eradication detected in bladder epithelial cells in patients treated with Ofloxacin compared to TMP-SMX. Shorter courses of antibiotic treatment are currently considered by clinicians and patients who are concerned with side effects, cost and antimicrobial resistance due to longer term use. Treatment course durations as short 3 days are not uncommon while the more common treatment duration is 14 days. The difference in effective treatment duration, compared to the findings of Dow et al. (2004), is due, in part, to the difference in anti-microbial used. However, further study comparing the two antimicrobials (and others) and differing treatment durations are required to clarify the question of optimum treatment duration for the antimicrobial being considered for use.

Gram-negative bacteria such as Pseudomonas, Acinetobacter, Enterobacter and mycobacteria are susceptible to aminoglycosides such as tobramycin and amikacin which may be chosen for complicated UTI treatment. Due to their toxicity and inconvenient route of administration (i.e. intramuscular injection), their use is limited. To investigate the effectiveness of a lower dose of these aminoglycosides, Sapico et al. (1980) compared infection, persistence and reinfection rates of SCI UTI against a standard dose. It was found that there was an overall low rate of success and no difference between the dose strengths or between tobramycin and amikacin even though high antibiotic concentrations were found in the urine of all subjects; this suggests that alternative antimicrobial agents may be better to consider for use in this population.

Although Waites et al. (1991) showed norfloxacin, another fluoroquinolone, to be 73% effective in eradicating UTIs by mid-treatment, the rate of reinfection was 84% after 8 to 12 weeks post initial eradication. Furthermore, 16% of strains isolated after eradication became resistant to norfloxacin. This trial, employing a pre-post study design (n=78) with a 14 day course of treatment, enrolled participants with symptomatic UTI and the equivocal results point to the utility of controlled study designs when assessing antibiotic effectiveness. The authors concluded that norfloxacin is a reasonable treatment choice for SCI UTI but the subsequent and problematic emergence of resistance must be monitored (as with other antimicrobials).

In addition to decisions on selecting the most appropriate antibiotic, the clinician is sometimes faced with additional treatment option challenges when multi-drug resistant bacteria or the patient’s allergy to the appropriate antibiotic are encountered. Although conflicting results have been obtained with the use of antiseptic agents as part of a prophylactic strategy to lower urine pH and thereby assist in the prevention of UTIs, Linsenmeyer et al. (1999) used a case series review (n=10) to investigate the use of medicated bladder irrigation as a method to alter the existing antimicrobial resistance. They found that intermittent neomycin/polymyxin bladder irrigation was effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment, therefore proving preliminary evidence advocating for a short course treatment of neomycin/polymyxin irrigant to alter existing antimicrobial resistance.

Conclusion

There is level 1b evidence (from one RCT; Dow et al. 2004) that supports the use of 14 versus 3 days of Ciprofloxcin for improved clinical and microbiological outcomes in the treatment of UTI in persons with SCI.

There is level 1b evidence (from one RCT; Reid et al. 2000) that 3 or 7 day Ofloxacin treatment is more effective than trimethoprim-sulfamethoxazole in treating UTI and results in significant bladder bacterial biofilm eradication in persons with SCI patients.

There is level 1b evidence (from one RCT; Sapico et al. 1980) that there is a low success with aminoglycosides for the treatment of UTI post SCI.

There is level 4 evidence (from one pre-post study; Waites et al. 1991) that norfloxacin may be a reasonable treatment for UTI post SCI but subsequent resistance must be monitored.

There is level 4 evidence (from one case series study; Linsenmeyer et al. 1999) that intermittent neomycin/polymyxin bladder irrigation is effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment.

Optimum antimicrobial treatment duration and dosage is uncertain due to the lack of comparative trials in persons with SCI.

  • Ciprofloxin administered over 14 (vs 3) days may result in improved clinical and microbiological SCI UTI treatment outcome.

    Ofloxacin administered over either a 3 or 7 day treatment regimen may result in significant SCI UTI cure and bladder bacterial biofilm eradication rate, moreso than trimethoprim-sulfamethoxazole.

    Norfloxacin may be a reasonable treatment choice for UTI in SCI but
    subsequent resistance must be monitored.

    Aminoglycosides have a low success rate in the treatment of SCI UTI.

    Intermittent neomycin/polymyxin bladder irrigation may be effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment.