Notes for IDWeek 2016 Day 2

Starting here at 7am today… here’s my live(ish) notes for the day.

Maximizing the Electronic Health Record and Clinical Decision Support Systems for Antimicrobial Stewardship

• Stewardship teams are supposed to have IT staff on them! who kneww
• Clinical decision support = “Any electronic tool that reduces the cognitive burden of patient care in an electronic health record”
• read Bates DW et al 2003 - ten commandments for effective clinical decision support: making the practice of evidence-based medicine a reality”
  • little things can make a big difference; doesn’t have to involve complicated decisions and algorithms
  • Make it easy to do the right thing & make it harder to do the wrong thing
• So far a lot of suggestions are around CPOE based solutions, things to keep in mind for someday
  • eg remove urine culture from urinalysis “quick menu” entry
  • build sets for indication based abx
    • looks like CPOE leave lots of spots where MD can make an error when ordering a med
    • eg “cipro for simple cystitis” defaults to a preset dose and duration for the right dosage form
    • don’t overbuild
  • hyperlink to dosing guidelines for complicated drugs (vanco) while ordering
  • you could also build in mandatory ID consults for restricted drugs! CPOE looks great
  • can build in shock box sepsis set right in there with the pathways and whatnot (can do things like have it bypass certain prompts and make sure it’s all instantly set as STAT)
• most important factor found in interruptive drug-drug alerts was actually the aesthetic display of the alert
• follow up alerts: can be collected and sent straight to ASP pharmacist.
  • eg: presumptive pseudomonas found on culture, no abx ordered currently that actually cover it

Maximizing Electronic Health Record and Clinical Decision Support Systems in Community Hospitals

• some CDSS can diagnose adverse drug reactions
• high maintenance associated with building your own CDSS; if you are not keeping them up to date, they get out of usefulness very quickly (for recommendation based ones)
• add indication as as a required element for ordering abx in CPOE
• IV/PO alert: if pt has been given another non PRN PO med, and is ordered an IV abx, will show an alert (suppressed with certain examples)
  • also has pharmacist alerts for drugs that have PO stepdown medical directives for pharmacists
  • issues with suppressive criteria, can’t factor things like difficulty swallowing etc; alert fatigue
• integrate recent laxative administration as part of c-diff test alerts
• DRIP score: potential for resistant bacteria in pneumonia. can develop a tool (10 criteria) which can suggest appropriate abx based on potential bugs
  • this looks to be the original paper on DRIP scores

Antibiotic Stewardship - Oral Abstract Session

Why is the air conditioning so strong in New Orleans? I wish I brought my winter midlayer

The Role of Procalcitonin in Guiding Antimicrobial Therapy Duration in Cancer

• Procalcitonin is an inflammatory marker which is elevated in bloodstream infections and sepsis. used for guiding abx in RTI and somme other things
• recent Lancet study showed monitoring PCT reduced duration of antimocrobials based on DDD and decreased mortality BUT had possibly increased rate of reinfection
  • excluded immunocompromised patients
  • what I think is the lancet paper
• This paper looked at febrile cancer pts / feb neut without obvious source
• post-hoc analysis
• short vs long abx groups (<= 7 days), similar group characteristics but the long group had a lot more people (77 vs 44)
• conc: in feb cancer pts with lower baseline PCT or a decrease of 80% from baseline, a short IV abx duration has the same outcome as a longer course
• I should read up on procalcitonin, but I am not sure we can even order it yet in Canada?

Increased Risk of Sepsis during Hospital Readmission Following Exposure to Certain Antibiotics during Hospitalization

• looked at risk based on what abx were received during previous stay
• retrospective cohort study
• divided abx by potential risk of gut microbiota disruption
  • high = 3/4th gen ceph, FQ, lincosamide, BL/BLase, PO vanco, carbepenem
  • low = 1/2nd gen, macrolide, tetracycline
  • get the rest from the slides
• control group had no abx during previous stay
• high risk had statistically significant Odds ratio, but low risk didn’t
• significant association with abx exposure and post-discharge sepsis within 90 days
• a good selling point for aggressive antimicrobial stewardship
• many confounding factors in the study because of the huge variety of comorbidities and very sick population, can’t make the association with abx since the other factors could play more into the post-discharge sepsis

Use of an Epic-Enabled Antimicrobial Stewardship Analytics Platform to Benchmark Suboptimal Restricted Antimicrobial Use Within an Academic Hospital

• IDSA prefers DOT vs DDD but the evidence is weak
• Stanford has 15 restricted ABX including fosfomycin
• When order is placed, triggers alert in Epic for ASP review. If empiric, alert is then pushed to 72 hours later
• Epic has a stewardship module
• DOT doesn’t tier by “inappropriate DOT” so this paper looked at developing ways to do that
• to separate inappropriate DOT, it’s resource intensive -> requires access to patient-level data
• Not sure how to apply this to practice
  • I think the point is that ASP team showed an overall DOT decrease of like 20-something%, but if you just look at decrease in inappropriate DOTs, the decrease is more like 40-something %
• developed detailed questions system to determine “inappropriate”

Durability of Benefits of Behavioural Interventions on Inappropriate Antibiotic Prescribing in Primary Care: Followup from a Cluster Randomized Clinical Trial

• 10% of all abumulatory visits are for Acute Resp Infections; 44% of all abx are for these, 50% of which are inappropriate
• 3 interventions
  • suggested alternatives: CPOE popup for indication for abx, and if pick a non-bacterial indication, get a bunch of non-abx suggestions for different tx
  • accountable justification: instead of alternatives, got asked to put in a “tweet-length” text justification for why they are prescribing the abx. Also made it clear that these justifications are going to go into the actual chart
  • peer comparison: if you are in 10% least inappropriate rxs, you get a monthly email saying you are a “top perfomer”. If you were really bad, you get a monthly email saying “you are NOT a top performer”
• followed the results of intervnetions active for 18 months, then again 18 months after they were deactivated
• interventions were successful while active, got worse after stopping but not as bad as baseline

Impact of Antimicrobial Stewardship and Rapid Microarray Testing on Patients with Gram-Negative Bacteremia

• Gram positive and gram negative platform, gram negative can detect 8 species; run immediately after gram stain and get immediate info on 8 different organisms AND several resistance markers
• can’t be performed on polymicrobial gram stains -> unreliable results
• At this institution paired results initially with an ASP pharmacist page with results
• Some physician hesitation to deescalate based on rapid test alone
• Reduced overall hospital stay duration

An Evaluation of Antibiotic Prescribing Practices Upon Hospital Discharge

• up to half of abx prescribed at discharge are inappropriate
• reviewed 150 discharge abx rx for appropriateness (indication, duration, spectrum, dose & frequency)
• most common indication was “no infection” - 22%
  • prolonged surgical prophylaxis
  • previous neutropenia but no longer neutropenic on discharge
• a few had duration too short, but a lot had duration too long
• inappropraite indication + inappropriate duration = 76% of inappropriate prescriptions

The Influence of the Microbiome on Infectious Disease Pathogenesis

The Microbiome in Gastrointestinal Infections

• 160 species per individual, 7010 total human gut microbiome
• rapid development of gut bacteria in neonates; delayed substantially with admin of antibiotics; huge fluctuations of bacteria type
  • may affect early immune system development
• ecoli is prevalent but relatively minor in terms of adundance
• canonical pathogens are absent in healthy human microbiome (Except SA and ecoli)
• VRE may be enabled by antibiotic treatment to dominate intestinal micorbiota; may be lurking, then activated, and may precede bloodstream infections
• decreased divrsity of the fecal biome makes greater risk for c diff recurrence (paper from 2007)
• IBD may be an exclusion criteria for FMT (worse outcomes)

The Microbiome in Infectious Diseases of the Lung

• lung was not included in the original NIH human microbiome project because it was historically thought to be sterile (which doesn’t make much sense)
• dynamic microbial environment
• many chronic lung diseases may be “infectious” eg asthma, COPD (infectious in context of changes to microbiome)
• with COPD, smoking alters the lung host defense; and see persistence of diseaese and inflammation despite smoking cessation
• only 15% of smomkers actually develop symptomatic COPD
• COPD: increased or decreased diversity, increased firmicutes/proteobacteria, decreased bacteroidetes; h flu, pseudomonas; increases in oral flora
• COPD is increased in HIV; related to pulmonary immune deficits in HIV so may be microbiome related
• early studies show no difference in microbiome between normal, COPD, and HIV lungs -> not sure why yet
• trophyrema - bug from Whipple’s disease (a gut disease) being found in several instances of normal lung microbiota . unexpected finding and don’t know what it’s doing there
• may need to consider organisms beyond just bacteria
• started looking at mycobiome = fungal
  • post-abx you can get fungal overgrowth in lung
  • pneumocystis is important in the development of COPD
• HIV-COPD appear to lose diversity in functions and interactions in their microbial

The Microbiome as a Novel Therapeutic Target

• 10x greater # of bacterial cells in our bodies than human cells
• gut microbiome in recurrent CDI (vs initial episode) is very different (2008 paper)
  • initial episode looks very much like control group
  • recurrent shows new phylotypes developing that weren’t there in initial episode group. Also a huge loss of diversity
• current options to replenish are probiotics and/or FMT
• probotic official definition “live microorganims that when adminsiterd in adequate amounts, confer a health benefit on the host” - most current products do not actually conform to this definition
• some promising data in saccharomyces but has not been followed up since then
• characterization of a strain of probiotic is important (effects are unique to that particular strain)
• 75% of probiotic products don’t contain what they say they do
• evidence seems to favour probiotics for primary prevention of c-diff but the meta-analysis was far too heterogenous; can’t actually pick one probiotic as better than another
• BMJ: lactobacillus RCT to prevent AAD (2e outomce CDI prevention)
  • used BID probiotic yogurt drink (Actimel) during abx use and 1 week after. Control group received a sterile milkshake
  • much lower AAD in probiotic group. No CDI in probiotic group (9 in placebo group)
• PLACIDE trial: Lancet 2013
  • RCT, capsule with two strains of lactobacillus acidophalus and 2 strains of bifidobacterium
  • Large patient population, bigger study than the last one
  • No statistically significant difference in AAD OR CDI
• more recent studies have not been RCT; retrospective cohort with some benefit but not strong enough for routine recommendation
• recent trial with oral tx of spores from 50 bacterial species. Early results promising but no positive results in phase 2 trial
• ADmin of nontoxigenic c diff strain m3
  • trial giving oral susp of pts at risk for recurrent c diff infection
  • primarily a safety trial but also looked at efficacy outcomes
  • recurrent CDI was lower in the treatment group
  • allows you to select the agent that you think will give protection without adding unwanted side effects from other rando things
• bile acids can inhibit growth of c diff; certain non-toxigenic strains can stimulate bile acid production
• until we know what specific bugs are best for protection, FMT is the best option
• FMT for other bugs (VRE, MRSA etc)
  • Case reports showing no effect of FMT for VRE
  • Case reports showing effect of FMT for VRE
  • bigger study for this year’s ID week showed success with VRE; future study needed

Clinical Controversies

Oral Antibiotics Appropriate Initial Therapy for Staph Osteomyelitis?

• hetergeneous disease; often also has a bloodstream infection
• uptodate: PO abx are altnerative only when IV isn’t an option for some reason
• example antibiogram: levaquin 90% sus for MSSA? interesting
  • “increasing resistance” and requires 750mg dose
• new “risk of sudden death” with septra…?
• doxy/minocycline: potentially permanent skin discolouration
• rifampin: poor tolerability, lower dose may help

Should HIV positive males with an undetectable viral load be advised to wear a condom to prevent transmission of HIV disease?

• STDs do not affect PrEP efficacy for HIV (Truvada I’m guessing)
• Syphilis incidence is on the rise - can lead to ocular syphilis (persisent visual deficits/blindness!!)
• Gonorrhea is now rated CDC “urgent” given the new prevalence of resistance
• Hep C is shed in semen of 1/3 of HIV-infected MSM
• PARTNER study - condomless sex with suppressive ART
• viral load < 1500 = virtually no risk of transmission; no transmissions found in several major studies

Which new admissions should be screened for asymptomatic carriage of c diff?

• increasing transmission of c diff from asympotmatic carriers as we get better at preventing from symptomatic
• large community reservoir constantly presenting c difficile to healthcare
• 5-15% of asmyptomatic carriage on admission
• England data showed reduction of infection from NAP1 strain of c diff thanks to ASP
• one quasi-experimental study in JAMA did the screening and found 4.8% carriers, hypothetically prevented 63 of 101 expected cases of c diff
  • from Quebec. many limitations; other interventions occurred (coindentally) during the study that would also have affected transmission rates
  • similar to early studies for VRE and MRSA screening which later had RCTs showing no impact
• BMC infectious diseases protective effect of pip-tazo : look this up!! apparently pip-tazo protects against c-diff!!?!?