update in infectious diseases 1
TRANSCRIPT
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Update in Infectious Diseases
SAMIR EL ANSARY
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Global Critical Carehttps://www.facebook.com/groups/1451610115129555/#!/groups/145161011512
9555/ Wellcome in our new group ..... Dr.SAMIR EL ANSARY
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Topics
• Clostridium difficile infection (CDI)
• Update on antimicrobial agents
• Miscellaneous updates
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Clostridium difficile infection
• CDI > MRSA for nosocomial infection– Long term care facilities
• “Epidemic strain”– NAP1 strain
– Increase in frequency and severity• 10x increase in reports of CDI as primary cause of death
1999-2009
• Change in antimicrobial risk– Quinolones >> cephalosporins > clindamycin
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Clostridium difficile
• New testing method– PCR 85 % to 95 % sensitive; quick
– Prior toxin assays- 28 % sensitive!
• Relapses- 20 %- predicted by age, severity of presentation, hospital exposure, prior CDI relapse
• New therapies– Fidaxomicin
– Stool transplants
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Clostridium difficile- treatment options
• Oral or IV metronidazole– Mild to moderate
– Inferior to vancomycin for severe CDI
• Oral vancomycin– 125 mg dose adequate
– Impact on the gastrointestinal microbiome
– Cost- more and more pharmacies are compounding
• vs. Fidaxomicin
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Clostridium difficile
• Fidaxomicin
– First in class macrocyclic antibiotic
– Theoretical advantages
• More active against NAP1 strain
• Inhibits spore and toxin production
• Less impact on the normal flora– Decrease VRE colonization
• High fecal concentration with minimal systemic absorption
– Cost
• $ 2800 for a 10 day course
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Fidaxomicin
• Initial two licensing studies- non inferior to vancomycin with fewer relapses in the non-NAP1 strain
• Meta-analysis – superior for recurrence and global cure, including NAP1, but no difference in an intention to treat analysis
– Subgroup analysis suggests benefit
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Fidaxomicin
• Recent multicenter trial in 1164 patients with first recurrence- vancomycin vs. fidaxomicin
– Same response to therapy
– Superior in preventing second relapse
• ? More data needed to justify cost?
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Clostridium difficile-multiple relapses
• Long tapering courses
• Fidaxomicin ?
• Probiotics
– Not helpful in patients with relapses
• Stool transplants
– Strong results in case series
• Sonication, filter, instill via nasogastric tube
– No comparator trials
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Clostridium difficile- treatment options
• Nitazoxanide
• Rifaximin
– Used as chaser in multiple recurrences- small study
• Tigecycline
– Dose not promote CD growth despite broad spectrum
– Very limited data in CDI
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Clostridium difficile
• CDI and PPIs
– 2012 FDA warning
– 1.4 to 2.75x risk in patients on PPIs
– Relationship of dose and duration unknown
– FDA recommends lowest dose for lowest duration in patients at risk for CDI
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Update on antimicrobial agents
• New antimicrobial agents for gram positive infections in the past fifteen years
– Daptomycin
– Linezolid
– Synercid
– Ceftaroline
– Telavancin
– Tigecycline
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Update on antimicrobial agents
• New antimicrobial agents for gram negative
infections in the past decade Tigecycline ?
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New antimicrobial agents for gram positive infections
• Linezolid– Not new, but……
– Best oral bioavailability
– SSRIs
– Cytopenias
– Cost
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New antimicrobial agents for gram positive infections
• Daptomycin– IV only
– Not in the lung
– Once a day
• Weekly CPK
– Tends to not be particularly helpful in the VISA strains
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Vancomycin dosing/levels
• New dosing recommendations
• Vancomycin levels
– Serious infections; increased MICs- trough 15-20
– ‘minor infections’- 5-10
– Dosing apps
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Ceftaroline
• Novel cephalosporin that has activity against MRSA
– Maintains the broad spectrum gram negative activity of advanced generation cephalosporins
• Skin and soft tissue, community acquired pneumonia
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Tigecycline
• Tetracycline antibiotic
• Broad spectrum, including MRSA– Does not cover “P P P”
• Pseudomonas, Proteus, Providencia
• Used primarily in patients intolerant to other antibiotics; multiple allergies
• 2012 meta-analysis- small increase in mortality
• Tolerance
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Telavancin
• Semi-synthetic derivative of vancomycin
• Once a day
• Meta-Analysis- Telavancin vs. vancomycin
– Non inferior vs. vancomycin
– Associated with higher eradication rates and trend towards better clinical response
– All cause mortality equivalent
– High rate of adverse events, including elevations in serum creatinine
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Brief Updates-2012 FDA advisories
• Cefepime/seizures- Too high doses in patients with renal impairment
• Azithromycin/cardiovascular risk– Class effect on QT; torsades de pointes
– Large database- increased cardiovascular death vs. amoxicillin • Similar to quinolones
• Highest in patients with cardiovascular risk factors
• Quinolones/retinal detachment– Possible increased risk
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Vaccines
• HSV vaccine trial- no efficacy
• Zoster vaccination– New age recommendation
• ACIP > 60 (FDA > 50)
– Currently contraindicated in high level immunosuppression
– Safe in low levels of Imuran, mtx, steroids
– > 20 mg prednisone for 3 weeks
– Large database analysis of patient with Crohn’s and RA showed no risk of adverse reactions
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Vaccines
• Pertussis vaccination in adults– 2012 ACIM recommends T-dap booster for all adults- regardless
of age
• Pneumococcal conjugate vaccine in healthy adults– 13-valent conjugate vaccine approved December 2011 in adults
> 50– Antibody responses =/> than pneumococcal polysaccharide
vaccine– Recommended by ACIP for routine use in adults- pending
additional data – June 2012- ACIP recommended use in immunocompromised
adults age > 19• May give in addition to polysaccharide vaccine- one or more year later• Evolving recommendations- recommend ACIP web site or app
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Vaccines
• Influenza 2012-2013– 2010: all persons > 6
– A/California/7/2009 (H1N1), A/Victoria/361/2011 (H3N2), and B/Wisconsin/1/2010
– Vaccinate as soon as vaccine available……
– Fluzone high dose- indicated for persons age > 65– 4x antigen
– Shown to invoke stronger immune response, but protective efficacy not clear; studies ongoing
– Do not use in patients with prior vaccine reaction
– Egg allergy- hives only• 30 minutes observation
• trivalent inactivated vaccine only
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Mycobacterium
• New recommendation for latent TB
– Rifapentine- longer half life and greater potency than rifampin
– Three month course of weekly directly observed therapy of rifapentine/INH non-inferior to nine months of INH
– CDC recommends rifapentine/INH as alternative to nine months of INH in patients > 12 months
• Advantage of DOT
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HIV
• Rapid in-home testing approved but not yet commercially available
• 2012 US Department of Health and Human Services recommended therapy for HIV infected patients regardless of CD4 count
• Pre-exposure prophylaxis:• July 2012 FDA approved tenofovir-emtricitabine (truvada)
among confirmed HIV negative individuals at high risk for sexually acquired HIV– Counseling about factors– Evaluation for HIV prior to initiation crucial to avoid selection of
mutations
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H3N2 Variant Influenza
• CDC reports > 150 cases of H3N2 variant influenza caused by reassortment of swine H3N2 and H1N1; most cases have occurred since July 2012
– All patients reported contact with swine (including fairs)
– Mild diseases- two hospitalizations; no deaths
– CDC recommends frequent hand washing and avoiding contact with pigs that appear ill
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Global Critical Carehttps://www.facebook.com/groups/1451610115129555/#!/groups/145161011512
9555/ Wellcome in our new group ..... Dr.SAMIR EL ANSARY