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Update in Infectious Diseases
SAMIR EL ANSARY
Global Critical Carehttps://www.facebook.com/groups/1451610115129555/#!/groups/145161011512
9555/ Wellcome in our new group ..... Dr.SAMIR EL ANSARY
Topics
• Clostridium difficile infection (CDI)
• Update on antimicrobial agents
• Miscellaneous updates
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
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
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
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
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
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?
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
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
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
Update on antimicrobial agents
• New antimicrobial agents for gram positive infections in the past fifteen years
– Daptomycin
– Linezolid
– Synercid
– Ceftaroline
– Telavancin
– Tigecycline
Update on antimicrobial agents
• New antimicrobial agents for gram negative
infections in the past decade Tigecycline ?
New antimicrobial agents for gram positive infections
• Linezolid– Not new, but……
– Best oral bioavailability
– SSRIs
– Cytopenias
– Cost
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
Vancomycin dosing/levels
• New dosing recommendations
• Vancomycin levels
– Serious infections; increased MICs- trough 15-20
– ‘minor infections’- 5-10
– Dosing apps
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
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
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
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
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
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
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
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
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
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
Global Critical Carehttps://www.facebook.com/groups/1451610115129555/#!/groups/145161011512
9555/ Wellcome in our new group ..... Dr.SAMIR EL ANSARY
