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How To Treat Infections How To Treat Infections Without Using AntibioticsWithout Using Antibiotics
DisclosuresDisclosuresNo drug company interactionsSlides are my own Reflect my perspective on
“best/useful” evidenceI am an antibiotic minimalist Don’t fully understand the ins &
outs of family practice
My ObjectivesMy ObjectivesReview rationale for less Abx useIntroduction to Abx stewardshipExemplify areas in outpatient ID
where◦Less antibiotics can be used◦No antibiotics are required◦Provide some 1st principles
Not to steal too much from Dr. Low’s talk
Your ObjectivesYour ObjectivesReflect on the myths
◦Abx are risk free ◦Abx efficacy is untouchable◦Practices patterns in ID stable
Examine your Abx prescribing as it relates to the evidence
Find ways to reduce unnecessary Abx use (“practical stewardship”)
Bottom of the R&D BarrelBottom of the R&D Barrel
No novel Abx classes◦ Cross resistance
Big pharma disinterestedNothing anticipated for
10 yearsAbx efficacy under siege
Multi-drug R gram negative era emerges
Nosocomial MenaceNosocomial Menace“ESKAPE” (IDSA)
◦VRE◦MRSA◦ESBL producing E. coli & Klebsiella◦Carbapenemase producing Klebsiella◦Acinetobacter baumannii◦Pseudomonas aeruginosa◦Enterobacter sp.
Community MenaceCommunity MenaceCA-MRSAPenicillin/MDR S. pneumoniaeEBSL E. coli (CTX type)C. difficileSpread of classic hospital
acquired antibiotic resistant bacteria◦Quicker discharges◦More “advanced” community care◦IV antibiotic therapy
Darwin and the MicrobesDarwin and the MicrobesEvolutionary forces favour microbes
◦Generation time permits rapid adaptation◦Abx pressure = ongoing mutant selection
Precedent for quick adaptation◦E. coli R to penicillin◦S. aureus R to penicillin/methicillin
Resistance costs organism◦Cellular energy to run machinery◦Decreased fitness to replicate
Playing for StalematePlaying for Stalemate
Ecological Burden of Ecological Burden of ResistanceResistanceGenes are the “currency”
◦Inter- & intra species trade◦Survival advantage
The “markets”◦Individual - colon◦Community – water, soil, biofilms◦Hospitals – synergistic mix of both
Less Abx use less evolution◦Favour wild-type strains◦Decrease resistance gene acquisition
“TreatmentStenosis”
“TreatmentStenosis”
New Infection
Abx TherapyClinical Cure
Abx Stopped
More use of fewer effective Abx
Self amplifying cycle
Basic Tenants of Basic Tenants of StewardshipStewardshipPatient safety initiative
◦Too much Abx use with no clear benefit◦Too much harm with no clear reason◦Abx benefit plateaus at some point
Risks exceed benefitPrevent/control antibiotic resistance
◦Patient or population focusMoving target for application
◦Severity of illness◦Clinical uncertainty
Antibiotic Balance - Antibiotic Balance - PatientPatientProper empiric
Abx◦ Common bacteria for
syndrome◦ Patient co-morbidities◦ Previous culture
results◦ Unique exposures
Occupation/hobbies Animal Travel Previous Abx
Avoid Abx harm◦ Protect health flora◦ Eliminate
unnecessary combinations
◦ Evidence based durations
◦ Narrow spectrum◦ Avoid/reduce IV
catheter days
Antibiotic “Co-lateral Antibiotic “Co-lateral Damage”Damage”The 7 C’s
◦Colonization with AROs◦C. difficile◦Candidemia◦Continuing need for IVs◦Cytochrome 450 drug-drug
interactions ◦Catastrophic adverse reactions◦Cost
Antibiotic Balance - Antibiotic Balance - PopulationPopulationIncreasing Abx needs
◦Advances in transplant/oncology◦More chronic illness◦Longevity
Quality assurance around use has not advanced◦When/if to treat◦Helpful diagnostics◦Overtreatment is ubiquitous
Antibiotic “Co-lateral Antibiotic “Co-lateral Damage”Damage”
Antibiotic StewardshipAntibiotic StewardshipHospitals based
◦ Multidisciplinary team
◦ Controlled prescribing
◦ Quality assurance cycle
Non acute care◦ Hard to replicate◦ Education (non
bias)◦ Taper therapy
Summary 1Summary 1Antibiotic resistant organism on
the rise are uncheckedNew Abx not the answer (per se)Abx use fuels selection pressureStewardship a logical start
◦Patient safety◦Protect Abx efficacy (population
level)Community stewardship model
needs different emphasis
Strategies for OutpatientsStrategies for OutpatientsAvoid prescribingFix the underlying problemDo not over value non sterile site
culturesMake the diagnosisTaper to or use narrow spectrum
AbxShorter durationNon bias education/CME
Infectious Syndromes to Infectious Syndromes to TargetTargetAcute pharyngitisAcute otitis mediaAcute sinusitisAcute bronchitis AECOPD (mild)CellulitisOutpatient pneumoniaAsymptomatic bacteriuriaUTIs (cystitis)
Viral or self limited bacteria
Excessive Abx use
AVOID ANTIBIOTIC AVOID ANTIBIOTIC PRESCRIBINGPRESCRIBING
Avoid Prescribing When Avoid Prescribing When SafeSafeAbx have no/little effect on
natural history◦Mild illness◦Minimal risk of complications if
untreated◦Common etiological agents are viral
“False disease” from micro tests◦Colonization
SinusitisSinusitisUnited Kingdom
◦90% get Abx◦£10 million pounds/year
USA◦85-98% get Abx◦$2.4 billion/year
Placebo effect 60-85%◦Benefit for Abx from non 1˚ care
settings
Sinusitis – Primary Care Sinusitis – Primary Care RCTRCT
Amox 500 mg3 x 7 daysBlock randomized (ITT)Healthy >15 yrMedian 7 days symptomsNo difference at day ≥10
◦ Symptom duration◦ Symptom severity
No severe complications at 6 wks
No interactions◦ Factorial trial with nasal
steroids
Sinusitis – Meta-analysisSinusitis – Meta-analysis15 pts treated before 1 addition pt
benefitsCommon clinical features can not
◦ Differentiate viral from bacterial◦ Determine “Abx beneficial” subgroup(s)
65% pts cured at 2 wks on placebo◦ 1/1381 placebo pt serious complication
Antibiotics not useful despite◦ Symptoms >7-10 days◦ Severe symptoms in absence of complications
Symptomatic relief and time for healthy adults
Asymptomatic BacteriuriaAsymptomatic BacteriuriaLack cystitis/pyelonephritis S&S
◦Pyuria is not a “symptom”◦Cloudy or smelly urine not diagnostic
>105 cfu/mL single species◦Female – 2 consecutive samples ◦Male – 1 sample
>102 cfu/mL single species◦Single catheterized sample
Exclude◦Pregnant women◦Pre TURP/other urological procedures
Asymptomatic BacteriuriaAsymptomatic Bacteriuria No treatment benefit
◦ Premenopausal non pregnant women
◦ Diabetic women◦ Male/female elderly
Community or LTCF
◦ Spinal cord injuries◦ Short/long term Foley
May benefit - bacteriuria >48 hr post short term Foley removal
No long term risk of not treating◦ Short term sterilization◦ Drug side effects◦ Resistance with subsequent
infections
Otitis MediaOtitis Media15 million Rx per year in USASpontaneous resolution commonComplication rate similar treated
& untreatedUK guidelines for Tx
◦Age <2 yr with bilateral acute otitis media
◦Otorrhea on presentation◦No/delay Tx for all else
Otitis MediaOtitis MediaRCT – Standard vs. Wait & See
◦Well 6-12 mos old seen in ER◦Co intervention with analgesia
Wait & see (statistical significance): ◦49% less Abx use◦Fever & otalagia triggers to fill Rx◦0.5 day more fever/otalagia
(relevant?)◦15% less diarrhea
Otitis MediaOtitis MediaMeta analysis favour Abx
◦Clinical cure (RR = 1.13)◦Symptoms at day 2 to 4 of Tx (RR =
0.68)◦More diarrhea (RR = 1.5)◦No difference in severe complications
Margin of benefit very narrow◦Parental relief & less absenteeism◦Side effects & resistant bacteria
RCT F/U Amox vs. placebo◦20% more recurrences in Abx group
FIX THE UNDERLYING FIX THE UNDERLYING PROBLEMPROBLEM
Infection as a “Symptom”Infection as a “Symptom”Predisposition from other disease
◦Unknown or known◦1 condition repeatedly◦Multiple infectious syndromes
Fix underlying cause◦Global health improvement◦Reduced infections & repeat visits◦Reduced Abx need (therefore risks)◦Prevent resistant flora development◦Avoid lure of chronic prophylaxis
Case Example - CellulitisCase Example - Cellulitis38 yr M outdoor construction worker
◦HealthyClassic GAS
◦Lymphadenitis/fever cellulitis3 standard 14 day 1st gen
cephalosporin courses◦Fully resolution each time
Relapses within 30 day each timeInpatient admission 2 to 3
day/episodeCause?
Case Example - CellulitisCase Example - Cellulitis
Courtesy of Center for Disease Control and Prevention Image Library
Case Controlled StudiesCase Controlled Studies
Bjornsdottir et al. Clin Infect Dis 2005; 41:1416-22Dupuy et al. BMJ 1999; 318:1591-4
Risk factors at least partially reversible
Not prospectively tested
More frequent cellulitis likely will benefit more
Prevent multiple Tx courses or prophylaxis
Big 2Tinea pedisChronic venous
insufficiency
Prophylaxis PitfallsProphylaxis PitfallsRecurrent UTI risk
Severe vesicoureteral reflux
Abx prophylaxis no effect
Controversial – no Abx prophylaxis for at least mild disease
Abx resistant infections Prophylaxis exposure
Fix the problemRepeated Abx creates
new problems
DO NOT OVER VALUE DO NOT OVER VALUE NON STERILE SITE NON STERILE SITE CULTURESCULTURES
Non Sterile Site CulturesNon Sterile Site CulturesClinical impression your guide
◦ When to test and its interpretation◦ Not vice versa
Avoid unnecessary testing◦ During or post Abx with clinical improvement◦ Asymptomatic state◦ Low probably of helping (e.g. cellulitis)
Leads to “bug – drug – kill” mentality◦ Colonization not a disease ◦ Can not sterilize these sites
Polymicrobial results ≠ multiple pathogens
ColonizationContamination
DiseaseInvasion
Non Sterile Site Sample Sterile Site Sample
Skin Flora – Low Virulence(e.g. CoNS, Corynebacterium sp., Viridans Group Strep)
Skin Flora – Moderate Virulence(e.g. Staphylococcus aureus, E. coli, Pseudomonas)
Professional Pathogen - High Virulence(e.g.M.tuberculosis, Brucella, Franciella)
More LessClinical Correlation to Culture Results
A Typical CaseA Typical CaseLongstanding DM2Acute foot ulcer – S. aureus
◦Better with cefazolinNon infected non healing ulcer
◦Re swabbed – cefazolin R E.coli Ciprofloxacin added
◦Re swabbed – cipro R P. aeruginosa Piperacillin-tazobactam subbed in
◦Re swabbed – multiple R GNBs, E. faecium
“Survivor phenomena” of non sterile sites
DM Foot DiscordanceDM Foot DiscordanceAbx not recommended for non
infected/non healing ulcersChronic osteomyelitis
◦Bone biopsy gold standard◦Non bone specimen poor correlation
52% false negative 36% false positive 28% concordance with bone biopsy
MAKE THE MAKE THE DIAGNOSISDIAGNOSIS
Death to Empiric TherapyDeath to Empiric TherapyClinical exam has limitations
◦Bacterial vs. viral◦ Infectious vs. non infectious
Diagnostic test can confirm/refute clinical impression◦Abx needed?◦Understand why if empiric Tx fails◦Risk benefit alignment
Avoid repeated rounds of AbxNot always convenient for Family
MDs
Community Acquired Community Acquired PneumoniaPneumoniaNo symptom can rule in/rule outSigns with modest likelihood ratios
◦ Temp >37.8˚C LHR+ 2.4-4.4◦ Dullness to percussion LHR+ 2.2-4.3◦ Decreased breath sound LHR+ 2.2-2.5◦ Crackles LHR+ 2.6-2.7◦ Bronchial breath sounds LHR+ 3.5◦ Egophony LHR+ 5.3-8.6
No sign can rule out◦ Lack of any vital abnormalities reduces
probability LHR- 0.16CXR infiltrate recommended for
diagnosis
Acute BronchitisAcute Bronchitis9th most common outpatient issue
◦5% of adults annuallyViral etiology predominatesAntibiotics not recommended
◦Reduce cough by 0.6 of a day◦Trend towards Abx adverse events◦B. pertussis an exception
Reduce transmission Decrease cough duration (given) in 1st
week
TAPER TO (OR USE) TAPER TO (OR USE) NARROW SPECTRUM NARROW SPECTRUM THERAPYTHERAPY
Less is MoreLess is MoreBroad spectrum therapy
◦Risk and/or uncertainty◦Culture & wait
Narrow spectrum therapy generally equivalent
With results (based on CLSI) Safer for patient
Best hints for empiric therapy◦Know the common pathogens by
syndrome◦Previous culture results◦Previous Abx use
Community Acquired Community Acquired PneumoniaPneumonia
Outpatient ◦ PSI I to III◦ Benign disease
Broader therapy (quinolones) no effect◦ Mortality◦ Treatment success◦ Microbiological eradication
for S. pneumoniaeEquivalent to -lactams or
macrolidesWhy the over coverage?
COPD ExacerbationsCOPD Exacerbations 50/50 viral & bacterial Problems studying Abx
benefit◦ Study design flaws◦ Bacterial colonization in
stable disease◦ Small benefit overall
Atypical bacteria no clear role
P. aeruginosa advanced disease
Avoid overly broad coverage◦ Mild exacerbations◦ Uncomplicated COPD
SHORTER DURATIONSSHORTER DURATIONS
Longer Is Not BetterLonger Is Not BetterLength of therapy generally too long
◦Poorly studied◦Shorter therapy equivalent when studied
Especially for outpatients Risk of progressing to severe disease less VAP – CAP example
Longer therapy ◦Does not prevent resistance◦Harms healthy flora◦Raises risk of adverse events
Shorter Duration - Shorter Duration - CellulitisCellulitisDouble blinded RCT
◦All patients - 5 days of levofloxacin◦Randomized - 5 days placebo or
levofloxacinNo difference
◦Day 14 for clinical endpoints◦Day 28 for recurrence
Levofloxacin likely overkill ◦S. aureus, -hemolytic Streptococcus◦Cephalexin could of been used but no
evidence exists Rapid improvement duration should be <10 days
Shorter Duration - CystitisShorter Duration - CystitisWell studied in women3 = 5-10 days for
symptomatic improvement◦ Most relevant outcome
5-10 > 3 days for microbiological eradication
Balance◦ 5-10 day group
More side effects More drug resistance (possible)
◦ Risk of recurrence with 3 day group Pyelonephritis extremely rare
Shorter Duration - CAPShorter Duration - CAP Recommended 7-14 days ?
evidence RCTs with various Abxs Peds (2-5 yr) non severe
◦ 3 = 5 days of therapy Clinical cure Tx failure or relapse
Adults (admitted) mild-mod severe◦ 3 = 8 days Amoxicillin
Treatment success, symptoms, radiographic, adverse effects
◦ Improved at day 3 needed Adults outpatient
◦ 3 = 5 days respiratory quinolone◦ Clinical, microbiological,
radiographic
Summary 2Summary 2Multiple “mild” conditions over
treatedPractical tips
◦Treat bacterial infections Not colonization or viruses
◦Understand value of culture results◦Use less Abx when possible◦Establish Dx & fix reversible risk factors
Ongoing ID education provides the evidence