Bladder Management

Antiseptic and Related Approaches for Preventing UTIs

Author Year

Country
Research Design
Score
Total Sample Size

 Methods Outcome
Lee et al. 2007

Australia

RCT

PEDro=7

N=305

 Population: SCI with Neurogenic bladder and stable management: Mean age: 43.5 yr; Gender: males=253, females=52; Level of injury: paraplegia=137, tetraplegia=168; Severity of injury: complete=149, incomplete=156

Intervention: Double-blinded comparison of methenamine hippurate (MH, 2g) with cranberry (1600mg), MH (2g) with cranberry placebo, cranberry (1600mg) with MH placebo or MH placebo with cranberry placebo).

Outcome Measures: Time to symptomatic urinary tract infection (UTI) (culture), predictors of UTI, adverse events collected for up to 6 mo.

 1.     The Kaplan-Meier curves for MH and Cranberry compared to placebo showed no evidence of a treatment effect.

2.   The unadjusted analysis confirms that there was no statistically significant effect of MH tablets (HR 0.94, 95% confidence interval 0.68-1.32) or cranberry tables (HR 0.93, 95% CI 0.66-1.29).

3.   The only significant predictor of a future UTI was found to be the number of UTIs in the preceding 6 mo.

4.   Common adverse effects included diarrhea or constipation.

5.   There was no difference in adverse event rates between the groups.
Waites et al. 2006

USA

RCT

PEDro=6

Nintial=89; Nfinal=52

 Population: SCI or other neurological disease with indwelling or suprapubic catheter with bacteriuria and pyuria: Mean age: 45.8 yr; Gender: males=49, females=40; Mean time post-injury=11.2 yr.

Intervention: Comparison of twice daily bladder irrigation with normal saline versus 0.25% acetic acid versus neomycin-polymyxin (N-P) GU irrigant for treatment of bacteriuria for 8 weeks.

Outcome Measures: Numbers and types of bacteria (culture and susceptibility), urinary pH, urinary leukocytes, generation of antimicrobial-resistant organisms collected at baseline, 2, 4, and 8 wk.

 1.   No difference among 3 irrigation solutions for bacteriuria.

2.   Overall, no difference in bacteriuria for any 7 of 8 species (p>0.1) other than Enterococcus spp. which increased significantly from week 0 to 8 (p=0.0006) and between solutions was significant for N-P group only (p=0.02).

3.   Mean urinary pH for all 3 groups increased from mean of 6.6 to 7.0—7.2 range (p=0.01) at wk 8.

4.   No significant increase in urinary leukocytes in any group (p≥0.6), MRSA (p≥0.37) or gram-negative resistance to common UTI antimicrobials (p≥0.11).
Castello et al. 1996

Spain

RCT

PEDro=4

Ninitial=38; Nfinal=13

 Population: SCI: Mean age: 27.83 yr; Gender: males=9, females=4; Level of injury: paraplegia=12, tetraplegia=1.

Intervention: Ascorbic acid versus placebo (lactose) for urinary tract infection (UTI) prophylaxis for an unspecified duration.

Outcome Measures: Urine pH, culture.

 1.     No significant difference in baseline or post- treatment urine pH for ascorbic acid or placebo, or number of individuals developing UTI between groups.
Sanderson & Weissler 1990b

UK

RCT

PEDro=4

N=19

 Population: SCI rehabilitation inindividuals: Gender: males=16, females=3.

Intervention: Individuals washed daily in chlorhexide versus unmedicated soap for 8 wk with crossover. Individuals receiving antibiotics for either urinary tract infections (UTIs) or skin infections were analysed separately as 3rd and 4th groups depending on their initial treatment (chlorhexide versus soap).

Outcome Measures: Bacteriuria assessed by urine culture, perineal colonization (swab), bedsheet, pillow case and environmental swab samples collected each week day.

 1.   Bacteriuria reduced by washing with chlorhexidine versus soap. (p<0.01).

2.   Bacteriuria less for those on antibiotics and using chlorhexidine (0.05<p<0.01).

3.   Proportion of negative cultures progressively rose for those on soap alone, to those on chlorhexidene alone, to those on antibiotics with soap, to those on antibiotics with chlorhexidene.

4.   Antibiotics usage resulted in significant increase in perineal swabs negative for coliforms (p<0.01).
Pearman et al. 1988 Australia

RCT

PEDro=3

Ninitial=18; Nfinal=18

 Population: SCI inindividual: Age range 18-49 yr; Gender: males=15, females=3.

Intervention: Trisdine bladder instillation following intermittent catheterisation versus kanamycin and colistin bladder instillation.

Outcome Measures: Episodes of bacteriuria, number of catheterizations.

 1.   No significant difference (chi square, no p value given) in number of episodes of bacteriuria between Trisdine versus kanamycin-colistin bladder instillations.

2.   0.56% (9 of 1609) versus 0.53% (9 of 1704) of instillations were associated with episodes of bacteriuria for Trisdine versus kanamycin-colistin respectively.
Krebs et al. 1984

USA

RCT

PEDro=4

N=40

 Population: Inindividual SCI (≤6 mo post-injury) with intermittent catheterization; Gender: males=40, females=0; Level of injury: T6 & above=27, T7 & below=13.

Intervention: Instillation of 45 ml, 5% hemiacidrin solution at each catheterization and 2 mg methanamine mandelate orally 4 times daily versus no bacterial prophylaxis.

Outcome Measures: Urinary pH determination culture, rate of urinary tract infections (UTIs), antibiotic susceptibility collected weekly during length of hospital stay.

 1.   Urine pH lower in methenamine and hemiacidrin group (p<0.01).

2.   Control group had double the number of positive cultures (p<0.001).

3.   UTI rates were higher in controls (p<0.02).

4.   Higher rate of symptomatic UTI in controls (chi-square 3.84, p<0.05).
Wikstrom et al. 2018

Sweden

Pre-Post

N=19

 Population: Mean age=43.7yr, Gender: males=19, females=2; Etiology: SCI (n=21, 100%); Inclusion criteria: SCI; IC as primary as chief method of bladder management; history of recurrent symptomatic UTI; with asymptomatic bacteriuria

Intervention: Bladder irrigation with 120 mL of 0.2% chlorohexidine solution was performed 2x/d (morning and evening) for up to 7d. The instilled solution was drained using IC after 15min of being in the bladder.

Outcome Measures: Bacteriuria levels below cut-off value; return of bacteriuria to above cut-off levels; adverse events.

 

 1.     There was a significant reduction in bacteriuria above the set cut-off after post-treatment (p<0.005).

2.     Eight of 14 subjects had a subsequent return of bacteriuria levels above the set cut-off one day post-treatment.

3.     Seven adverse events were reported by six subjects: urine leakage; cramping sensation in bladder; increased urine leakage; diarrhea, symptomatic UTI post-treatment.
Shigemura et al 2015

Japan

Pre-Post

N=41

 Population: SCI, NBD; Type of injury: SCI=38, encephalomyelitis=1, spinal tumor=1, aneurysm=1.

Intervention: Researchers recommended preventative measures to limit the spread and development of multidrug-resistant Pseudomonas aeruginosa (MDRP) outbreaks. Outbreak trends were monitored over an 8 mo period.

Outcome Measures: Spread of MDRPs within individual population, catheterization use.

 1.     Eighteen MDRPs were detected in 8 mo of surveillance. The isolation of MDRPs significantly decreased from the 1st quarter to the last (p=0.02), even though urinary tract device use significantly increased (p<0.001).

2.     Rates of hand washing, thoroughness and checking of standard precautions, the use of common shelves for personal antiseptic solutions were the measures recommended seen to improve the rates of MDRPs in individuals.
Jia et al. 2013

China

Pre-Post

N=41

 Population: Mean age: 36 yr; Gender: males=41, females=0; Severity of injury: C2-6 =9, T1-6=8, T7-12=19, L1=5.

Intervention: Individuals were administered a 300 U injection of botulinum toxin A.

Outcome Measures: Number of UTIs.

 1.     The mean number of UTIs significantly decreased post-injection (p=0.023).

2.     The decrease of UTI was significant in the detrusor over-activity individuals (p=0.015), while the decrease was not significant in norm-active detrusor individuals (p=0.319).
Game et al. 2008

France

Pre-Post

N=30

 Population: Mean age: 39.4 yr; Gender: males=18, females=12; Etiology of neurogenic detrusor over activity: Multiple sclerosis=15, SCI=14, Myelitis=1.

Intervention: Individuals were administered an injection of 300 U OnaBTx into the detrusor muscle.

Outcome Measures: Frequency of urinary tract infections (UTI).

 1.   The mean number of UTIs was significantly different from pre-injection compared to post-injection (p=0.003); just 3 individuals still acquired UTIs post injection.
Schlager et al. 2005

USA

Pre-Post

N=7

 Population: Neurogenic bladder caused by myelomeningocele=5, and traumatic SCI=2, and using clean intermittent catheterization: Age range 18-29 yr; Gender: males=3, females=4; Level of Injury: L2 & 4, T6, 8 & 12(x2); Time post-injury>2 yr.

Intervention: Phosphorus supplement (Neutra-phos®) as urine-acidifying agent. Wk 2 and 3, individual drank a phosphorus supplement 3 times/d over 4 wk study period.

Outcome Measures: Urinalysis (Urine pH) measured 3 times/d (1st morning, afternoon, evening) for 4 wk; urine sample (cultured) 2 times/wk over 4 wk.

 1.   No significant change in urine pH during the 2-wk period when individual was on phosphorus supplement (vs when off supplement).

2.   Urine acidification not achieved with phosphate supplement.

3.   Frequency of bacteriuria in an individual individual was similar on and off supplementation.

Discussion

Good hygiene practices are imperitive to UTI prevention. Therefore, it is a natural extension to expect that antiseptic agents applied either directly to the bladder or to potential vectors of indirect transference might be effective in UTI prevention. Accordingly, Sanderson and Weissler (1990a) found that perineal colonization of SCI individuals was significantly correlated with bacteriuria and may be associated with contamination of the environment and indirectly of the hands of patients and staff. As a result of this finding, this group further examined the effect of chlorhexidine antisepsis on bacteriuria, perineal colonization and environmental contamination in spinally injured patients requiring intermittent catheterization (Sanderson & Weissler 1990b). In male patients not receiving antibiotics, daily body washing in chlorhexidine and application of chlorhexidine cream to the penis after every catheterization significantly reduced bacteriuria to 60% from 74% in patients who only washed with standard soap; however, the effect was not as strong as that delivered by treatment with appropriate antibiotics. Chlorhexidine antisepsis alone did not affect perineal coliform colonization or contamination of the environment although there was a trend for this effect (p<0.1). In essence, this antiseptic effect acted to amplify the bacteria-reducing effects of antibiotics.

Acidifying urinary pH for the prevention of UTIs is based on the established fact that pH reduction to ≤5.0 will inhibit growth of urinary E. coli (Shohl & Janney 1917), a prevalent pathogen in the urinary tract. An RCT conducted by Waites et al. (2006) on individuals with indwelling or SPC with existing bacteriuria and pyuria (n=89) the effects of sterile saline, acetic acid and neomycin-polymyxin solution bladder irrigants on the degree of bacteriuria/pyuria, or development of antimicrobial resistance; the authors found no significant difference between groups. Moreover, the twice daily bladder irrigation for 8 weeks resulted in a significant increase in urinary pH (p=0.01) for all groups to a range that was more favourable for the growth of E. coli (i.e., pH 6.0-7.0). Similarly, 2 weeks of phosphate supplementation (Schlager et al. 2005) or 2 g daily ascorbic acid (Castello et al. 1996) for unspecified duration in SCI neurogenic bladder managed with IC or indwelling catheter have proved ineffective in acidifying urine or altering UTI rates.

Feasibility of treatment is a valid issue for consideration as evidenced by the study conducted by Pearman et al. (1988). These investigators compared the use of trisdine with kanamycin-colistin, a medicated bladder instillation previously demonstrated to be effective to prevent bacteriuria and UTI in SCI (Pearman 1979). In this trial (n=18), they found no difference between incidence of bacteriuria in catheterized patients yet concluded that trisdine was preferred based on its stability at room temperature, association with a reduced likelihood for antibiotic-resistant bacteria and reduced cost compared to kanamycin-colistin. Although the latter are important factors for treatment choice, this study presents no evidence for preferential beneficial effects based on incidence of bacteriuria.

Another solution shown to have some promise in UTI prevention was studied as a combination therapy, both with antiseptic properties. Krebs et al. (1984) investigated the potential of a 5% hemiacidrin solution instilled as an intravesicular acidifying agent at each intermittent catheterization combined with oral administration of methenamine mandelate (2 mg four times daily) in persons undergoing SCI inpatient rehabilitation. As compared to individuals undergoing no bacterial prophylaxis, the pH of urine was significantly reduced (p<0.01) and there was a lower rate of symptomatic UTI (p<0.05) and less bacteriuria as indicated by a reduced number of positive cultures (p<0.001). The role of hemiacidrin solution alone in these findings remains uncertain.

In contrast to these findings, as part of a double-blind, placebo-controlled RCT (n=305) conducted by Lee et al. (2007), oral methenamine hippurate (another formulation of methenamine as an antiseptic) was generally ineffective in preventing symptomatic UTIs. In this well-conducted large sample trial, active and placebo formulations (oral tablet) of both methenamine hippurate and a cranberry preparation were compared as to the occurrence of asymptomatic UTI (up to 6 months) as a primary end-point. There were no statistically significant effects with either treatment alone or in combination as compared to placebo.

These various conflicting results suggest the specific antiseptic agent, alone or in combination with others, and its mode of administration might be important in determining clinical effectiveness and that the practice of antiseptic bladder instillation along with other methods of delivery, dismissed as ineffective by some or in general practice by others (Pearman et al. 1988; Castello et al. 1996; Schlager et al. 2005; Lee et al. 2007), requires further study.

Botulinum toxin therapy has been discussed extensively in this chapter as it relates to improving urodynamic parameters. It has also been studied for the use of reducing UTIs post SCI in two pre-post studies. Both Jia et al. (2013) and Game et al. (2008) reported that after treatment with 300 U into the detrusor, indivudals had significantly fewer UTIs at follow-up. Further, Jia et al. (2013) reported that the reduction of UTIs was significant only in patients with detrusor overactivity but not in those without norm-active detrusors.

Conclusion

There is level 2 evidence (from one RCT: Sanderson & Weissler 1990a) that daily body washing with chlorohexidine and application of chlorhexidine cream to the penis after every catheterization versus using standard soap reduces bacteriuria and perineal colonization.

There is level 1b evidence (from one RCT: Waites et al. 2006) that bladder irrigation with neomycin/polymyxin or acetic acid is not effective for UTI prevention.

There is level 2 evidence (from one RCT: Castello et al. 1996) that bladder irrigation with ascorbic acid is not effective for UTI prevention.

There is level 4 evidence (from one pre-post study: Schlager et al. 2005) that phosphate supplementation is not effective for UTI prevention.

There is level 2 evidence that bladder irrigation with trisdine (RCT: Pearman et al. 1988), kanamycin-colistin (RCT: Pearman et al. 1988) or a 5% hemiacidrin solution combined with oral methenamine mandelate (2 mg four times daily; RCT: Krebs et al. 1984) may be effective for UTI prevention.

There is level 1b evidence (from one RCT: Lee et al. 2007) that oral methenamine hippurate, either alone or in combination with cranberry, is not effective for UTI prevention.

There is level 4 evidence (from two pre-post studies: Jia et al. 2013; Game et al. 2008) that 300 U botulinum toxin type A may reduce UTIs among individuals with neurodestrusor overactivity post SCI.

Daily body washing with chlorohexidine and application of chlorhexidine cream to the penis after every catheterization instead of using standard soap may reduce bacteriuria and perineal colonization.

The antiseptic agents delivered via bladder irrigation (5% hemiacidrin solution combined with oral methenamine mandelate; trisdine; kanamycin-colistin) may be effective for UTI prevention, whereas others are not (i.e., neomycin/polymyxin, acetic acid, ascorbic acid and phosphate supplementation).

Oral methenamine hippurate, either alone or in combination with cranberry, is not effective for UTI prevention.

Botulinum toxin type A (300 U) injected into the detrusory may prevent UTIs in individuals with neurodetrusor overactivity.

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