Update in infectious diseases 1

1. Update in Infectious
Diseases
SAMIR EL ANSARY

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Wellcome in our new group ..... Dr.SAMIR EL ANSARY

3. Topics
• Clostridium difficile infection (CDI)
• Update on antimicrobial agents
• Miscellaneous updates

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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?

10. 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

11. 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

12. 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

13. Update on antimicrobial agents
• New antimicrobial agents for gram positive
infections in the past fifteen years
– Daptomycin
– Linezolid
– Synercid
– Ceftaroline
– Telavancin
– Tigecycline

14. Update on antimicrobial agents
• New antimicrobial agents for gram negative
infections in the past decade Tigecycline
?

15. New antimicrobial agents for gram
positive infections
• Linezolid
– Not new, but……
– Best oral bioavailability
– SSRIs
– Cytopenias
– Cost

16. 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

17. Vancomycin dosing/levels
• New dosing recommendations
• Vancomycin levels
– Serious infections; increased MICs- trough 15-20
– ‘minor infections’- 5-10
– Dosing apps

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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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Wellcome in our new group ..... Dr.SAMIR EL ANSARY

29. GOOD LUCK
SAMIR EL ANSARY
ICU PROFESSOR
AIN SHAMS
CAIRO
elansarysamir@yahoo.com