A recent BMJ analysis article argued that taking the “full course of antibiotics” is often\u00a0likely counterproductive (see\u00a0doi: 10.1136\/bmj.j3418 )\u200b.<\/p>\n
Details:<\/strong><\/p>\n –international health organizations and the WHO have pushed for completing antibiotic regimens:\u00a0a 2016 WHO advisory to patients stated\u00a0“always complete the full prescription, even if you feel better, because stopping treatment early promotes the growth of drug-resistant bacteria”. The CDC has a\u00a0similar message<\/p>\n –the authors\u00a0note that there is impressive evidence that some micro-organisms (eg TB, gonorrhea, HIV, S. typhi)\u00a0can create spontaneous resistant mutations on treatment, and these mutants\u00a0subsequently can\u00a0be transmitted as resistant strains. [and there are good data supporting longer term therapies]<\/p>\n –but many of the organisms with growing resistance worldwide\u00a0are normal commensal flora (E coli, enterococci, staph, klebsiella, acinetobacter, pseudomonas, enterobacter),\u00a0which actually\u00a0develop resistance by longer antibiotic exposure<\/strong><\/p>\n <\/p>\n Commentary:<\/strong><\/p>\n –this article does bring up several important points<\/p>\n \u200b–though some infectious agents can develop resistance with inadequate antimicrobial therapy (eg HIV etc), all 3 of the “critical” resistant\u00a0species per the WHO\u00a0and 3 of the 6 listed as\u00a0“high priority” bugs\u00a0fall into the group of commensal flora, where more antibiotics leads to more resistance (see blog <\/a>)<\/p>\n –we really do have a dearth of studies looking at what the optimal course should be, both by infection site and by antibiotic used<\/p>\n — the article mentions the lack of efficacy of shorter courses of antibiotics for otitis media.\u00a0\u00a0When this study\u00a0came out, I was surprised that the shorter course did not work, in part because otitis media is one of those bacterial infections that often\u00a0seems to resolve spontaneously\u00a0without\u00a0antibiotics, depending on the organism, and in part because there was a similar situation with a few other infections where shorter courses worked well\u00a0(see below). \u00a0In fact, this otitis\u00a0study was limited to kids <2yo and\u00a0treated only\u00a0with amoxicillin-clavulanate. Those on the longer course had a shorter duration of symptoms,\u00a0but\u00a0there was no difference\u00a0in\u00a0recurrence rates,\u00a0and no difference in\u00a0nasopharyngeal colonization with penicillin-nonsususceptible\u00a0pathogens<\/strong>\u00a0(N Engl J Med 2016; 375: 2446).<\/p>\n –In the past, uncomplicated UTIs in women were treated with 7-10 day courses of antibiotics. Then there were studies showing efficacy of single-dose therapy. Now, because of somewhat improved efficacy, the recommendations are usually for longer courses, such as TMP\/SMX DS bid for 3 days, fluoroquinolones for 3 days, nitrofurantoin for 5 days, or (as a last holdout)\u00a0fosfomycin\u00a0as a single dose. However, a study which I\u00a0think was pivotal in promoting\u00a0the longer\u00a0antibiotic course\u00a0found that although single dose\u00a0amoxacillin\u00a03 grams was only 69% effective vs multi-dose regimens being 84% effective, the data on TMP\/SMX was no different between these lengths of treatment, with a single dose of\u00a02-3 tablets of DS leading to the insignificant difference of 87% cure rate\u00a0vs\u00a090% with multi-dose regimens\u00a0(see\u00a0Philbrick\u00a0JT.\u00a0Arch Intern Med 1985;145:1672-1678).\u00a0It would be interesting to know if single-dose therapy\u00a0is still as effective, given changes in flora and antibiotic sensitivity over these decades, but the single dose is certainly easier, likely to have less effect on the microbiome or create resistance in commensals, and apparently fewer adverse reactions (though the quality of the data here is questionable). Single-dose TMP\/SMX may still be reasonable???<\/p>\n –and\u00a0there are some trials showing that shorter courses of therapy for community-acquired\u00a0 pneumonia do well, including one using fever as a guideline to stop antibiotics; some other\u00a0studies in patients with mild to moderate clinical disease have found that clinical outcomes were similar with 3-7 day treatments vs 7-10 day ones (eg, see\u00a0Dimopoulos\u00a0G. Drugs. 2008; 68:1841).<\/p>\n –one concern here is that there is not much incentive nowadays to do the necessary trials. Drug companies, the dominant funder of clinical studies, have no interest:\u00a0many of the commonly used antibiotics are generic, and even for those expensive ones that are only available as brand-names, documenting efficacy by taking fewer days of meds is not in the interest of their stockholders<\/p>\n <\/p>\n So,<\/p>\n –as a perspective here for the above study on “finish the complete course”:<\/p>\n –90%\u00a0of\u00a0antibiotics go to animals, largely to improve their growth and not to treat infections, and this practice seriously augments\u00a0the incidence of antibiotic-resistant bacteria (see\u00a0WHO\u00a0report<\/a> of the scary increase in antibiotic resistance, targeting the 12 bacterial families with the greatest\u00a0threat\u00a0to humans;\u00a0and\u00a0on the emergence of untreatable superbugs<\/a> such as\u00a0colistin-resistant E\u00a0coli<\/p>\n \u200b–studies suggest<\/a> that >70% of antibiotics prescribed in humans are for inappropriate indications (eg, acute bronchitis, non-strep pharyngitis, acute\u00a0rhinosinusitis, upper respiratory\u00a0infections), and 85% of antibiotic prescriptions\u00a0are written in\u00a0primary care.<\/p>\n –one option to consider is holding off on antibiotics for infections that seem to do reasonably\u00a0well left untreated, as long as there can be good followup.\u00a0for example, in patients with\u00a0uncomplicated\u00a0skin\u00a0abscesses, antibiotics were efficacious\u00a0only for staph infections (2\/3 of the infections), though even then the actual differences were not great (80+% do well without them):\u00a0see blog\u00a0\u00a0<\/a>. I have been trying to decrease\u00a0antibiotics in not-so-sick\u00a0kids\u00a0with otitis media, where for decades in\u00a0Europe clinicians\u00a0have been reluctant to use antibiotics, and the suggestion here was that it seemed reasonable to follow patients\u00a0closely off antibiotics. Another suggested solution, the one\u00a0I have been using, is to\u00a0offer a prescription but suggest to the parents\u00a0to hold off on giving the antibiotics unless the child does not improve in\u00a0a few days\u00a0or if the kid’s symptoms are getting worse, pointing out\u00a0that antibiotics can unusually\u00a0have very severe adverse reactions and\u00a0their use should be minimized. (though I’m\u00a0not sure exactly what parents are doing.) And, parenthetically, one of my kids had otitis at a young age,\u00a0i held off on antibiotics, then he developed a generalized rash (all fitting with a viral etiology). but if i had given him amoxacillin, he would likely have been labeled as penicillin-allergic…<\/p>\n So,\u00a0to me the overwhelming issue is the necessity to\u00a0dramatically decrease antibiotic use in livestock and in humans for inappropriate indications (and there has been some movement in both of these areas, but needs to be increased lots), but that we really do need to have\u00a0good studies looking at the shortest courses which work. And the old addendum\u00a0\u201cand make sure you complete the full course of antibiotics\u201d is likely wrong in many if not most cases. In my experience, many patients are ahead of the curve on this one: they often just stop the antibiotics when they are feeling better, and it seems that they often do well\u2026\u2026<\/p>\n other\u00a0relevant past blogs:\u200b<\/p>\n —\u00a0\u00a0current disturbing increase\u00a0in untreatable gonorrhea<\/a>;<\/p>\n