Our data support formulary guidelines recommending maintenance metronidazole for recurrent malodour. Dimethyl trisulfide, a product of anaerobic necrosis causes malodour and can attract maggot-producing flies to decaying tissues. Therefore, to reduce anaerobic malodour in vulnerable settings, we propose a ladder for metronidazole titration. High-risk patients should start with 400 mg thrice daily ×7 days and continue 200 mg once daily. The SNIFFF severity (Smell-Nil, Faint, Foul or Forbidding) can guide follow-up dosage: 200 mg once daily to continue for nil or faint smell; breakthrough courses of 400 mg thrice daily ×1 week for foul smell and 2 weeks for forbidding smell, followed by 200 mg once daily.The effectiveness and limitations of maintenance metronidazole and the SNIFFF ladder should be prospectively evaluated.
PURPOSE Anaerobic necrosis in cervical cancer can lead to malodor, fistulae, and treatment abandonment. In this retrospective cohort study, we examined the association between maintenance metronidazole and the incidence of malignant fistulae in recurrent cervical cancer. METHODS We screened all cervical cancer records registered between 2007 and 2016 in the local palliative care database at Christian Medical College, Vellore, India. There were 208 eligible patients with post-treatment residual/recurrent pelvic disease. Among them, 76 had received oral maintenance metronidazole 200 mg once per day for 2 to 86 weeks (interquartile range, 4-16 weeks). RESULTS Seventy-two patients developed at least one fistula. Forty-nine had vesicovaginal fistulae, 10 had rectovaginal fistuale, and 13 developed both types of fistulae. Patients on maintenance metronidazole had fewer fistulae (22.4% v 41.7%; P = .005), a longer median fistula-free survival (42.9 months v 14.1 months; P < .001), and a postrecurrence survival of 11.5 months versus 8.7 months ( P = .112). We performed Cox multivariable proportional hazards regression analysis on the data from the subset of 146 patients observed until death. Bladder/rectal infiltration had a higher risk of fistula (HR, 5.24; P = .011), whereas distant metastases (HR, 2.46; P = .012) and Eastern Cooperative Oncology Group performance status greater than 1 (HR, 1.64; P = .008) were associated with a higher risk of death. Maintenance metronidazole was associated with a lower risk of fistula (hazard ratio [HR], 0.33; 95% CI, 0.16 to 0.67; P = .002) and a lower risk of death (HR, 0.56; 95% CI, 0.39 to 0.81; P = .002). CONCLUSION Our data indicate that there is a significant inverse association between oral maintenance metronidazole and malignant fistulae in locally recurrent cervical cancer. The impact of this simple intervention on pelvic symptoms, fistulae, and survival should be evaluated in prospective studies.
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