In the first section of this chapter we summarised the main findings.81 Some evidence from our trial for possible modest bacteriologicaleffectiveness of the nitrofurazone catheter is provided by the results using differing definitions of CAUTI reported as secondary outcomes, which show
68 Discussion
removal, an outcome particularly relevant to the control of health-care-related infection in hospitals, showed a modest trend from 5.9% to 4.9% (p = 0.14). The rate of the more stringent CDC criterion outcome of microbiologically proven symptomatic UTI at 3 days was reduced from 1.3% to 0.7% (p = 0.05) and at 6 weeks from 4.6% to 3.2% (p = 0.02), the latter representing a 30% relative risk reduction. None of these results was changed by adjustment for pre-set confounding factors. The suggestion that, in this trial, the findings related to nitrofurazone- impregnated catheters for secondary bacteriological outcomes have borderline statistical
significance would be in line with those reported from the most recent meta-analysis of previous RCTs.42 The study given most weight in this meta-analysis was that by Stensballe et al.,82 which is also methodologically closest to the present trial. They used treatment for CAUTI with antibiotics as a secondary outcome, finding a RR of 0.27 (a reduction in incidence from 17.5% to 4.8%) in favour of nitrofurazone catheters among 200 patients admitted with trauma. The difference in our results is likely to reflect a lower risk profile in our sample together with a shorter catheter duration and lower intensity of care.
Our trial was not designed to explain any superiority in clinical effectiveness found for the technology under study and, given the lack of evidence for overall effectiveness of the nitrofurazone catheters, the results of any subgroup analysis should be interpreted with great caution. None of the tests for interaction was significant. It is plausible that participants randomised to use of nitrofurazone-impregnated catheters who had used antibiotics in the 7 days prior to catheterisation would be less likely to benefit in terms of reduction in CAUTI rate compared with those with no previous antibiotic use, and there is some suggestion of this. This might reflect alteration of urogenital flora that protect against UTI.83 There is also some in vitro data to suggest that nitrofurazone-impregnated catheters inhibit the growth of a wider range of uropathogens and for a longer period compared with silver alloy-coated catheters.79 This in vitro superiority may not be relevant to day-to-day use for short-term catheterisation and also may be affected by differing release mechanisms for the antimicrobial agents in the two catheter designs. The nitrofurazone catheters were made from silicone impregnated with the active agent, unlike the latex-based coated construction of the silver alloy and standard catheters. They might therefore be expected to have different physical characteristics that may impact on their use. We did find evidence that participants allocated to nitrofurazone catheters found the presence and removal of the catheter more uncomfortable than the standard group. The cause of these differences are not known but, given that the Cochrane review found that silicone catheters tended to result in fewer urethral side effects than latex catheters, then the material of manufacture is unlikely to be the problem.42 It is possible that surface changes resulting from the impregnation technique may be at fault or that the catheter was more rigid or had subtle differences in retention balloon or drainage eyelet configuration. We understand that the manufacturer has recently changed the manufacturing process with the aim of greater comfort of use (Rochester Medical, personal communication, 2010).
Evidence from previous studies comparing nitrofurazone catheters with standard silicone controls suggest that it is unlikely that the possible lower rate of CAUTI seen in the nitrofurazone group was due to its latex-free construction rather than the antibiotic content.42,82 In addition, we found no evidence of unsuspected latex allergy among randomised participants, although we did not collect data concerning the number of participants deemed ineligible because of known or suspected latex allergy.
Previous studies have suggested that the antimicrobial activity of the nitrofurazone coating has reduced effectiveness beyond 7 days of catheterisation.42 In the present trial, the effect size in terms of reduction in rate of symptomatic UTI in comparison with the control group did reduce by a further statistically non-significant degree among participants catheterised for 4 days or
longer, although the study lacked power to specifically address this question with any certainty. Overall we did not find any evidence of interaction between duration of catheterisation and relative clinical effectiveness in terms of reduction in UTI risk.
Although our model-based health economic analysis suggested that nitrofurazone-impregnated catheters may be cost-effective, the principal driver of these results was that, based on the balance of data, the cost savings from avoiding an infection would compensate for the increased unit cost of the nitrofurazone catheter compared with PTFE. The 97.5% CI for cost savings per patient includes £0 but even at the upper end are relatively modest (mean difference –£7.07; 97.5% CI –£36.19 to £11.45). Nevertheless, given the volume of catheterisation within the NHS, even this small difference may lead to substantial savings overall. This finding should be treated cautiously given the limitations of the analysis and the considerable uncertainty particularly regarding estimates of key parameters, such as length of stay.