pneumonia: overprescribed antibiotics

A hospital-based study found that 2/3 of patients with pneumonia received longer courses of antibiotics than necessary, with more reported adverse outcomes (see pneumonia excess abx AIM2019 in dropbox, or doi:10.7326/M18-3640)

Details:

--6481 medical patients from 43 hospitals in the Michigan Hospital Medicine Safety Consortium, a collaborative sponsored by Blue Cross/Blue Shield, from 2017-18

--mean age 70, 80% white, 51% female, median Charlson Comorbidity Index score 3 (an array of comorbidities which predict mortality within 1 year of hospitalization, with a score of 3 suggesting moderate severity of comorbidities) and, specifically, CKD 29%/CHF 27%/COPD 46%/home oxygen 16%/current or former smoker 67%/diabetes 31%/cancer 22%

--pneumonia severity score: >75% had class III to class V (ie more severe disease, as determined by age, comorbidities, vitals, lab abnormalities, pleural effusion)

--26% had concurrent COPD exacerbation]

--54% with sepsis; median symptoms 2 days

--median time to clinical stability (afebrile 48 hours and no more than 1 vital sign abnormality): 3 days (87% were stable by day 5); median length of stay 5 days

--antibiotics: azithromycin 47%, ceftriaxone 19%, levofloxacin 18%

--community-acquired pneumonia (CAP) 73% (though 19% were complicated CAP with moderate immune compromise, structural lung disease or moderate-to-severe COPD); health care-associated pneumonia (HCAP) 27% (eg, from nursing home, etc)

--they excluded patients with <5 days of antibiotics or duration at least 2 days shorter than expected for pneumonia (to exclude patients who may have been empirically treated for infection but ultimately had other diagnosis), and patients had to have begun antibiotics in the first 2 days of admission (to exclude the potential of hospital-acquired pneumonia)

--they used established guidelines for their expected antibiotic duration, including: whether the pneumonia was CAP vs HCAP, the organism, time to clinical stability

    --eg, patients with CAP were expected to have treatment at least 5 days, longer if it took longer for clinical stability

    --patients with HCAP, staph aureus or nonfermenting Gram-neg bacillus (eg pseudomonas) expected to have at least 7 days of antibiotics

--primary outcome: rate of excess antibiotic treatment duration; excess days = actual duration of antibiotics minus the shortest effective treatment duration based on time to clinical stability, pathogen, and whether CAP vs HCAP. And, patient outcomes, were assessed at 30 days through medical records, and telephone calls to patients 30 days after discharge with scripted question about side effects

Results:

--excess antibiotic therapy:

    --67.8% of patients

        --CAP, median duration of antibiotics 8 days, 72% exceeded expectation; median excess 2 days

        --HCAP, median duration of antibiotics 9 days, 57% exceeded expectation; median excess 1 day

    --overall 2526 excess days of treatment per 1000 patients hospitalized with pneumonia

--excess treatment higher if:

    --respiratory culture or nonculture diagnostic testing done, had high-risk antibiotic given within prior 90 days, had CAP, or did not have total antibiotic treatment duration documented at time of discharge [ie, they might have been sicker patients, in ways not controlled for]

    --7% higher in those with sputum production, and also was higher in the non-academic hospitals

--antibiotics prescribed at discharge were:

    --fluoroquinolones (esp levoflox) 31%, 39% of the excess days

    --azithromycin and amoxacillin-clavulanate were next most common, though % not mentioned

--prescribing at discharge:

    --50% of total antibiotics were prescribed at discharge

    -- 93.2% of excess antibiotics were prescribed at discharge

    -- and, 45% actually received full antibiotic course (5,7, or 10 days) after discharge [ie, as if they got no antibiotics in the hospital]

--adverse outcomes:

    --excess antibiotics not associated with lower outcomes of death, readmission, ED visit, or C diff infection

    --BUT: patient reported adverse outcomes (about 60% of patients were able to be reached): each excess day of treatment was associated with 5% increase in odds of antibiotic-associated adverse events. mostly diarreha, gatrointestinal distress and mucosal candidiasis

Commentary:

--pneumonia is the most common reason for inpatient antibiotic use

--studies over the last 25 years or so have shown that shorter courses of antibiotics are safe and equally effective (eg, 5 days of treatment being sufficient for most patients with CAP) [see guidelines below]

   --and, longer courses put patients at risk for antibiotic-associated adverse outcomes, incl C diff infections/resistant organisms

--in this study, the majority of patient with CAP (87%) stabilized quickly, were therefore candidates for 5 day courses of therapy, yet less than 25% received just a 5-day course

    --there are even studies suggesting that 1-3 day courses of therapy might be appropriate (eg, see antibiotics short vs long course hosp pts JHospMed2018 in dropbox, or  Royer S. J Hosp Med 2018; 13: 336-42)

--guidelines from the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America as well as the CDC promote antibiotic stewardship programs to reduce antibiotic use to the shortest possible duration (eg see antibiotic stewardship program ClinInfDis2016 in dropbox, or DOI: 10.1093/cid/ciw118)

--treatment guidelines from the Infectious Diseases Society of America for CAP (see pneumonia CAP Rx guidelines ClinInfDis2007 in dropbox, or DOI: 10.1086/511159):

    --recommended outpatient treatments (for previously healthy patient with no risk factors for drug-resistant S. pneumonia): strong recommentation for macrolide: azithro, clarithro, erythro, with weak recommendation for doxycycline

    --for those with comorbiditiies (heart, lung, diabetes, kidney, alcohol, immunosuppressed, use of antibiotics in prior 3 months): strong recommendation for fluoroquinolone (eg levoflox 750mg), or b-lactam (high-dose amoxacillin, 1-3g daily, or amox-clavulanate, 2g bid) plus macrolide (see the article for inpatient regimens, though these are the same for patients not in the ICU as for those with comorbidities)

    --duration of therapy: "patients with CAP should be treated for a minimum of 5 days (level 1 evidence), should be afebrile for 48-72 hours, and should have no more than 1 CAP-associated sign of clinical instabilty before discontinuation of therapy (level II evidence), moderate recommendation" [ie pretty much the same as in the above study, though this statement could have been worded more forcefully]

--the setting for this study, with reference to some prior blogs:

    -- http://gmodestmedblogs.blogspot.com/2019/04/surgical-antibiotic-prophylaxis-and.html reviews a VA study on surgical antibiotic prophylaxis, finding significant antibiotic overprescribing without benefit but with more C diff infections and acute kidney injury

    -- http://gmodestmedblogs.blogspot.com/2019/01/antibiotic-overprescribing-2-more.html reviews 2 articles on antibiotic overprescribing with reference to several prior blogs on antibiotic resistance, microbiome changes (one finding long-term effects even after a single exposure to antibiotics), several on inappropriate antibiotic prescribing (eg, for viral upper respiratory infections), some hopeful signs in decreasing antibiotic prescribing more recently and one on the benefits of antibiotic stewardship programs, and a couple on the negative role that drug companies have been playing...

so, this study confirms that longer courses of antibiotics do not provide better infection outcomes, but do lead to more patient-reported adverse outcomes. And, the main culprit to excessive antibiotics is prescriptions written at discharge. Clearly, this could be fixed pretty easily with a simple discharge algorithm, best monitored under the umbrella of an antibiotic stweardship program. As per the many prior blogs on antibiotic overprescribing and the diverse effects of antibiotics on the body (eg, on the microbiome), we in clinical medicine should reduce the use of antibiotics to those conditions where the benefit is clear (and, with either very close followup on those where the decision is not so clear, or possibly giving a script but advising the patient strongly not to take the meds unless they do not improve, get worse, or develop some trigger symptoms/signs, as per last blog on UTIs: http://gmodestmedblogs.blogspot.com/2019/07/utis-increasing-drug-resistant-bugs.html). And when antibiotics are prescribed, giving the narrowest spectrum ones that are appropriate and for the shortest appropriate duration

and, my guess, we are very likely overprescribing antibiotics for patients in the outpatient setting, where it is particularly likely that a 5-day course is more than adequate for CAP....

geoff​

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