Hubris –the extreme arrogance that was so offensive to the old Greek gods that they reacted with punishment and an exile from grace- is that what this is? I’m not sure anymore… It’s not, perhaps, so obvious as the vaulting ambitions of a Macbeth or the arrogance of a Caesar, nor even the overweening pride of an Oedipus in the Sophoclean plays, and yet… And yet, viewed from a distance, it’s hard not to notice the similarities that inhere in the attitude that End justifies Means, that intentions trump consequences, that methodology is the servant of results –however narrowly beneficent we define them. And it’s important that we not be so blinded by those touted benefits that we ignore other, perhaps less harmful routes, to achieve them.
And what, you may reasonably ask, prompted this jeremiad? It was a study reported in the New England Journal of Medicine (NEJM) on the addition of a second and possibly more powerful prophylactic antibiotic during non-elective Caesarian Sections to reduce post-operative infection rates: http://www.nejm.org/doi/full/10.1056/NEJMe1610010?query=gynecology-obstetrics -certainly a worthy aim, to be sure. Who could possibly take issue with that? Well, in this era of increasing antibiotic resistance, and the unfortunate dearth of replacement antibiotics in the wings, I think not only the study, but also the idea demands more than a cursory analysis. This is not to criticize the intent, so much as to explore alternative roads to the same destination.
Few would argue that antibiotics, when they are deemed necessary, should be used according to the infecting bacterial sensitivities if they are available –or considered expectations as to sensitivities if they are not. It’s why we can no longer use penicillin for everything –not all infections would respond. Surgical prophylaxis (where there is not yet an infection) is one of the few exceptions, and even there, the antibiotics are chosen in anticipation of the type of bacteria that might reasonably be expected in the surgical field (although there are some who believe that their effect is merely that of decreasing the total bacterial load in the area whether or not the expected ones have been targeted). But, nevertheless, we toy with resistance at our peril.
I’ve chosen to link the editorial rather than the study itself because of the insights it offers. The full-length study to which it refers can be accessed via a link in that editorial, however.
As I mentioned, the study by Tita and colleagues, in a randomized trial, attempted to reduce post-operative infections by adding another broad-spectrum antibiotic (Azithromycin) to the usual antibiotic (cefazolin) in non-elective Caesarian sections (i.e. there was some condition in mother or baby that required urgent delivery) where the current infection rate was 12% -and it worked! Compared to the usual group that just received the cefazolin alone, they dropped the infection rate to 6.1% -not zero, but at least an improvement. And, ‘Neonatal outcomes, which were tracked up to 3 months, were similar in the two trial groups.’
But on closer analysis, 73% of the population in the study was obese -and that, plus the fact that the Caesarians were unplanned, certainly added to their risk of infections. So far, so good.
But, as the editorialist wonders, could the fact that these women were obese have meant that the usual dose of cefazolin was inadequate: ‘[…] should the potential pharmacologic benefit of higher doses of cefazolin alone be evaluated further before the addition of a second agent?’
Another consideration leading to the study of adding azithromycin to the regimen, was that it may be useful for eliminating a potentially infective organism in the vagina –ureaplasma– that cefazolin doesn’t touch. Unfortunately, there are no prospectively adequate data for the contention that the organism was even present in the studied women.
And finally, the azithromycin was more beneficial in those women whose incisions were closed with staples, and there seems to be evidence that staples, themselves, may increase the post-operative infection rate.
So why, you may ask, have I chosen to comment on this rather obscure study –especially since it seems to have demonstrated the benefits it expected? First of all, I think we have to be careful that we don’t lose sight of the forest as we wend our way through the undergrowth. There do seem to be other options that could be explored before the addition of yet another antibiotic –and indeed should be anyway, given the non-zero infection rate even with the addition of azithromycin. Such things as more ‘stringent adherence to infection-control protocols’, avoiding the use of staples in this high-risk population, or even re-calculating the dose of the standard prophylaxis (cefazolin) to account for differing patient weights before deciding to add the new antibiotic.
I don’t mean to be the new Cassandra, issuing thundering prophesies of doom that will not be heeded anyway, or aspersing well-intentioned attempts to improve our lot… And yet we must not forget that consequences follow actions, not precede them. To be fair, we do try our best to anticipate and thereby avoid, or at least minimize them, but history is riddled with examples of unintended outcomes. The road to disaster is paved with should’ves –only seen with clarity, after arrival.
It seems to me that, wherever possible, we should be exploring options that reduce the likelihood of incurring bacterial resistance. And the answer may not lie in the reliance on new antibiotics -new guns for our on-going war with the microscopic world. It’s a battle in which we cannot hope for more than a temporary truce while we search for peace. Without that, as the map makers of old were said to write on unexplored regions, Here be dragons.