Primary Care Corner with Geoffrey Modest MD: Decreasing antibiotic resistance by stewardship program

by Dr Geoffrey Modest

A recent systematic review and meta-analysis found that hospital antibiotic stewardship programs significantly reduced the incidence of infections and colonization with antibiotic-resistant bacteria and C difficile infections (see S1473-3099(17)30344-4).



–32 studies in a meta-analysis with 9,056,241 in-hospital patient days and 159 estimates of incidence ratios (IRs) of target infections

–studies from 20 countries: US (5 studies), Japan (4), Germany (3), France (3). Most common design was before-after analyses

–most frequent stewardship  interventions:  audits in 59%, implementation of restrictive policies in 47%, co-implementation of stewardship programs with infection control measures (mostly hand hygiene) in 25%



–antibiotic stewardship programs reduced the incidence of and colonization with:

— multi-drug resistant gram-negative bacteria: 51% reduction; IR 0.49 (0.35-0.68), p<0.0001

–specifically, a 43% reduction in carbapenem resistance; IR 0.57 (0.40-0.81), p=0.0018; this was especially true for carbapenem-resistant Acinetobacter Baumannii, 56% reduction, and P aeruginosa, 29% reduction

— extended-spectrum b-lactamase-producing gram-negative bacteria: 48% reduction; IR 0.52 (0.27-0.98), p=0.04

— methicillin-resistant staph aureus (MRSA): 37% reduction; IR 0.63 (0.45-0.88), p=0.007

— c diff infections: 32% reduction; IR 0.68 (0.53-0.88), p=0.003

–antibiotic stewardship programs were more effective when implemented with hand-hygiene interventions: 66% reduction; IR 0.34 (0.21-0.54), p<0.001; in those without hand-hygiene interventions, there was a 17% reduction; IR 0.83 (0.71-0.98), p=0.03

–no difference in vancomycin-resistant enterococci, or quinolone-resistant and aminoglycoside-resistant gram-negative bacteria

–in terms of sites in the hospital:

–59% reductions in hematology-oncology departments

–23% reduction in ICUs

–22% reduction in medical departments

–in terms of types of stewardship interventions:

–antibiotic cycling: 51% reduction in antibiotic resistance; IR 0.49, p=0.003

–audits and feedback: 34% reduction; IR 0.66 p=0.0006

–antibiotic restriction: 23% reduction; IR 0.77, p=0.0003

–interventions generally became more effective over time: 10% reduction for 1980-2000; 21% reduction for 2001-5; 32% reduction for 2006-13



–various types of antibiotic stewardship programs have had success in other studies, including use of empirical therapy as suggested in treatment guidelines, de-escalation of therapy to more targeted/narrower spectrum antibiotics, switching from IV to po antibiotics, restriction of antibiotics, and bedside consultation

–a review of their table of the studies involved in the above meta-analysis shows that the various interventions in the studies pretty consistently decreased some infections

–it is noteworthy to reinforce the pretty striking effects of hand-hygiene in preventing bacterial resistance, including both MRSA and antibiotic-resistant gram-negatives. the hand-hygiene strategies used varied from: education, to replacement of handwashing with alcohol-based hand rubbing, to substitution of hand-directed soap dispensers with elbow-directed soap dispensers.

–other studies have shown decreases in mortality and antibiotic costs through stewardship programs.

–and, other studies have shown that using guideline-based empirical therapy was associated with a 56% reduction in mortality and using de-escalation strategies led to a 35% mortality reduction

–one key feature in the meta-analysis  probably was the high compliance/involvement of physicians, educational feedback, and close relationships between physicians and the stewardship team (the authors did not comment on non-physicians).

–this meta-analysis was limited by many issues, including study heterogeneity, difficulty in culling out single interventions in more detail, the potential for secular trends/differences over time, the inability to target the different specific hand-hygiene measures, and significant differences in individual study quality (2 studies were high quality, 26 moderate, 4 low)

so, I bring up this article for a few reasons, though it does not directly apply to outpatient practice (other than that we get the output of resistant bacterial strains as they migrate from the hospital to the community):

–there may be some lessons we could apply directly to primary care, eg:

–using more guideline-based antibiotic therapies

–being more diligent specifically in limiting antibiotic use for evidently viral illnesses (a large % of antibiotic use, as per blogs below)

–using more targeted and narrower-spectrum antibiotics (eg, avoiding cipro for UTIs)

​–spending more time discussing the potential consequences of antibiotic overuse with patient

​–making sure that patients understand the importance of taking complete courses of antibiotics when indicated

–making sure we optimize hand hygiene

​–and perhaps implementing a stewardship plan: the easiest plan, with pretty strong data above, would likely be simply audit and feedback to providers on a regular basis

–and, i think it is important for us to understand the gravity of the antibiotic-resistance issue and the likely development of increasing numbers of untreatable infections, and not just the weird ones that hang out in hospitals, but even just e. coli or n. gonorrheae (eg see blog  )

for blogs going into more detail on some of these issues:

(see here for the slew of blogs on antimicrobial resistance,  and see below for some more specific ones)

— this blog found that true penicillin allergy is really uncommon, and that we may therefore be using broad-spectrum antibiotics more often than necessary

this one reviewed ​the latest WHO categorization of resistant bacteria of international concern, and also has a general assessment of the lack of drug company investments in new antibiotics, and that the major use of antibiotics and development of resistance is actually from industrial non-therapeutic use of antibiotics in livestock. there are also links to other blogs on the effects of antibiotics on the microbiome and the significant prescribing of antibiotics for human  nonbacterial conditions (eg URIs, acute rhinosinusitis, pharyngitis, bronchitis)

and this one reviewed the WHO guidelines on treating sexually-transmitted infections in this era of antibiotic resistance