Several important points here. First, historical data on abx efficacy for PNA is not relevant to Q you are asking bc when the historical data were generated, there were no vaccines for pneumococcus or H flu. So they accounted for the vast majority of PNA (particularly S. pneumo).

Turns out vaccines really work. That viruses now account for the majority of CAP is a direct result of the vanishing of bacterial pathogens after introduction of vaccines. Even when I was training in the 90s we saw lots of S. pneumo. It's a last 25 yr phenomenon.

Second, there were never placebo RCTs for pneumococcal PNA because by the time the technology of placebo RCTs became available, abx had already massively reduced death. Osler referred to S. pneumo PNA as "The Captain of the Men of Death." It was the leading killer of Americans.

The article I posted has detailed review of historical data of abx effectiveness. There were alternation studies of abx vs. no, studies of serum therapy, cohort studies of abx vs. no, etc, all of which demonstrated a MASSIVE reduction in death d/t Abx. The references are there.

Yes. It just seems like all of the evidence in inapplicable to the most common CAP prescribing context. As you noted, I can't find any actual evidence that we should be giving empiric antibiotics in the outpatient setting for microbiologically typical CAP coverage based on clinical or radiographic evidence for CAP in developed countries (those with high pneumococcal vaccination rates)? As far as I have been able to find, virtually every trial is a non-inferiority trial based on prior standard dating back to penicillin use in case series of severe pna in the inpatient setting prior to pneumoccocal vaccination and not in mild or moderate disease. Almost all non-inferiority trials show that ever increasingly short courses of antibiotics are non-inferior. It seems like we should really go back and study this in the right (modern) context.

@austingmeyer I agree with slight modification. A modern placebo controlled RCT is ethical and feasible if: 1) molecular Dx have confirmed virus present and no bacterial ag/dna present and/or procal low; 2) rescue therapy available if rapid de compensation.

I'm not sure one has to require a virus be present for non-severe, right? Just that bacteria not be present. There are so many fully negative panels and most standard sputum arrays that I've seen don't have any typical bacteria on the array. To be safe, one could define a set of trials sequentially reducing duration with a small set of antibiotic options. Then, test non-inferior reduction from 5 days to 3 days. Then, 3 days to 1 day. Then, 1 day to 0 zero days.

@austingmeyer No, that's not why a viral test should be required. It's that it is unethical to randomized a patient with bacterial pneumonia to placebo. It may be ethical to randomize a patient with a viral test+ to placebo if we've excluded bacteria. Read the article I sent in detail...

@BradSpellberg Not to mention there are so many health systems pushing to remove procal from laboratory availability, which seems crazy to me.