Most patients with sepsis don't need anti-anaerobic antibiotics. But most get them anyway. Why not, what's the harm?

I worry the harm is considerable.

Our new study in @JAMAInternalMed: using a 15-month pip-tazo shortage to answer this question.

1/n

jamanetwork.com/journals/jamai…


Background: we know that gut anaerobes matter in sepsis. In multiple animal models, depleting the gut of commensal anaerobes consistently makes animals more vulnerable to infectious and non-infectious models of critical illness.

2/n

The gut microbiome is an "organ" that participates in metabolism, immunity, and infection prevention.

Anti-anaerobic antibiotics thus cause a kind of "organ failure."

I worry this is hurting our patients.

New from our lab in @ERSpublications

1/9

tinyurl.com/cmv63rnn




In multiple animal models, if you kill gut anaerobes, it worsens pneumonia, organ failure, and mortality. Yet we give anti-anaerobic antibiotics to patients all the time (most often pip-tazo, metronidazole, and amp-sulbactam).

What are the clinical consequences of this?

2/9

I'm thrilled to share our lab's latest publication, now online at @ScienceTM. Here comes a Twitter walkthrough. 1/

stm.sciencemag.org/content/12/556… First: acknowledgements. This was ~ 5 years of work, major team effort. Shanna Ashley was its brains & motor; this was her post-doc project, and she's now a Senior Scientist @ AbbVie. Contributions from colleagues in Pulm, Micro, Peds, Path, etc. Will thank along the way.

2/

[thread] The paradox of treating ARDS is this: because we don't have a drug to reverse lung injury, we provide supportive care with two therapies - oxygen and mechanical ventilation - that can both cause ARDS.

Like treating cancer w/ carcinogens. Or infections w/ pathogens.

1/n We've known that oxygen causes lung injury for 250 years. Lavoisier stuck guinea pigs in "l'air vital" and watched them die from "une fièvre ardente" and a "maladie inflammatoire." Their lungs were flacid, red, and engorged with blood. Their right ventricles were dilated.

2/n

The *alveolar poncho* (copyright @jopo899) theory of hyaline membrane deposition reminds me of a broader idea: maybe the more "pathognomonic" a finding is in a disease, the more likely it is to be protective, and the less beneficial it would be to reverse it.

1/n

https://twitter.com/jopo899/status/1262125268388532225

Hyaline membranes are a hallmark of diffuse alveolar damage (DAD), which is the pathological hallmark of ARDS, which has been called "hyaline membrane disease" in the past. If you had to pick one specific biologic finding that implies ARDS: hyaline membranes.

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[thread] You know what's frustrating? There ARE phenotypes of ARDS. They've been rigorously derived, independently validated, and interrogated for biological and clinical significance. Yet they've been abandoned in COVID, replaced with unsupported "L vs H" speculation.

1/n Carolyn Calfee and her team have done extensive, meticulous work identifying subphenotypes of ARDS. They didn't base it on hunches. They systematically studied tons of patients, predictors, and outcomes, using unsupervised clustering.

2/n

ncbi.nlm.nih.gov/pubmed/?term=C…

@PatSchloss @vnsriniv @watermicrobe @gregcaporaso @DNAkendra 1/n Thanks Pat. Happy to discuss, Varun. In the meantime, here's a quick (incomplete) recommended reading list on handling the "noise" in low biomass microbiome studies: @PatSchloss @vnsriniv @watermicrobe @gregcaporaso @DNAkendra 2/n "Reagent and laboratory contamination can critically impact sequence-based microbiome analyses" (The seminal "Salter paper.") @Zannah_Du bmcbiol.biomedcentral.com/articles/10.11…