Topical Antibiotic use and Circumcision-Associated Neonatal Tetanus: Protective Factor or Indicator of Good Wound Care?

Sérgio De A Nishioka

Centro de Ciências Biomédicas, Universidade Federal de Uberlândia, Av. Pará 1720, 38400–902 Uberlândia, MG, Brazil. E-mail: snishioka{at}hc.ufu.br

Sir—In their interesting study Bennett et al. demonstrated that circumcision is a risk factor for neonatal tetanus (NNT) in Punjab Province, Pakistan.1 They also showed that the use of topical antibiotics on the circumcision wound decreased the risk of NNT to the same level observed in babies who were not circumcised. Based on these findings Bennett et al. suggest that topical antibiotics should be routinely applied to every circumcision wound, and add that topical application of other substances commonly used in the region should be avoided. I would like to comment on these recommendations.

One of Bradford-Hill's well-known criteria used for assessing a hypothesized causal relationship is biological plausibility.2 When an association is plausible the hypothesis is usually more acceptable. In the assessment of the protective effect against NNT of topical antibiotics used in the circumcision wound it is important to know whether topical antibiotics inactivate Clostridium tetani spores or, more likely, vegetative forms, or if there are alternative mechanisms that explain why the use of such ointments would prevent this disease. Among the several topical antibiotics at least bacitracin is active against clostridia, and has also been shown to enhance epidermal healing of wounds.3 This makes the observed protective effect of topical antibiotics on circumcision-associated NNT plausible, when the ointments used contained this antibiotic. However it is also possible that the use of topical antibiotics is just an indicator of good wound care. In such cases caregivers who used topical antibiotics in the circumcision wounds of their babies did it instead of using dung, ghee, urine etc, which explains why the babies did not get NNT.

Adjustment for use on the circumcision wound of the above-mentioned substances was apparently not done in the multivariate analysis. It would be interesting to know whether the use on the circumcision wound of dung and other substances likely to be contaminated with tetanus spores could have confounded the observed protective effect of local antibiotics in preventing NNT. I would not be surprised if these variables were highly negatively correlated to each other, i.e. those individuals who used topical antibiotics did not use dung in the circumcision wound, and vice-versa. Even if the correlation is not as high as I expect, analysis of a possible interaction between these variables would also be of interest. In which case my bet would be that those who used dung plus topical antibiotics had a higher risk of NNT than those who used only antibiotics.

If the use of topical antibiotics is only an indicator that wounds are kept clean and free of tetanus spores, what would be the best advice for health care workers involved in neonatal care in Punjab Province? Education of the population to not use substances that could contaminate the wound is an obvious solution that might not be easy to execute, at least in the short term. Dr Bennett et al. are familiar with the region and the local culture, so their recommendation to promote the topical use of antibiotics deserves respect. It may be the best short-term solution as it might decrease the use of dung and other substances rich in tetanus spores. On the other hand it would increase cost, create false expectations as to the effectiveness of antibiotic ointments, and increase the risk of side effects associated with the use of topical antibiotics.3 Promoting the use of ointments containing only antiseptics is an alternative that deserves consideration.

References

1 Bennett J, Breen C, Traverso H, Agha SB, Macia J, Boring J. Circumcision and neonatal tetanus: disclosure of risk and its reduction by topical antibiotics. Int J Epidemiol 1999; 28:263–66.[Abstract]

2 Hill AB. The environment and disease: association or causation? Proc R Soc Med 1965; 58:295–300.[ISI][Medline]

3 Tunkel SR. Topical antibacterials. In: Mandell GL, Bennett JE, Dolin R (eds.) Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases, 4th edn. New York: Churchill Livingstone, 1995, pp.381–89.


 

Authors' Response

John Bennett, Catherine Breen, Jennifer Macia and John Boring

Department of Epidemiology, Rollins School of Public Health of Emory University, 1518 Clifton Rd, N.E. Atlanta, Georgia 30322, USA.

Sir—Dr Nishioka correctly surmises that there is a strong negative correlation between applying topical antibiotics and dirty substances to circumcision wounds. In fact, there were no reports of the combined use of both antibiotics and dirty substances in our study.1 While it is possible that topical antibiotics are thus only markers signifying the absence of exposure to hazardous substances, other data suggest that this is not likely to provide a full explanation for the observed effects.

In a companion paper,2 we demonstrated that applying nothing to umbilical wounds was significantly risky compared with topical antimicrobials. Small numbers prevent a confident evaluation of the magnitude of risk of dry care with circumcision wounds; only two cases and one control had dry care reported before the day of onset of NNT or onset date in a matched case, respectively. However, applying nothing is clearly not without risk.

We believe that failure to proactively protect both umbilical and circumcision wounds with antimicrobials will lead to increased risks of NNT in environments similar to our study areas, where animals and animal dung exist in close proximity to living areas, and frequent exposure of wounds to tetanus spores is likely. In addition, antimicrobials should also reduce risks of sepsis deriving from either of these frequently contaminated wounds.

Antiseptics were used too infrequently in our present study to assess their independent effects, although they have been shown to be protective against NNT from umbilical wounds in other studies.2,3 We thus agree that topical antiseptics deserve careful consideration as alternatives to topical antibiotics.

References

1 Bennett J, Breen C, Traverso H, Bano Agha S, Macia J, Boring J. Circumcision and neonatal tetanus: disclosure of risk and its reduction by topical antibiotics. Int J Epidemiol 1999;28:263–66.[Abstract]

2 Bennett J, Macia J, Traverso H, Bano Agha S, Malooly C, Boring J. Protective effects of topical antimicrobials against neonatal tetanus. Int J Epidemiol 1997;26:897–903.[Abstract]

3 Parashar U, Bennett J, Boring J, Hlady WG. Topical antimicrobials applied to the umbilical stump: a new intervention against neonatal tetanus. Int J Epidemiol 1998;27:904–908.[Abstract]





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