This document summarizes updates in infectious diseases from Clostridium difficile infection to new vaccines and antimicrobial agents. It discusses the increasing rates and severity of C. difficile, new diagnostic tests and treatment options including fidaxomicin and stool transplants. New antimicrobial agents for gram-positive infections like daptomycin, linezolid and ceftaroline are mentioned. Brief updates are provided on FDA advisories, vaccines for herpes, shingles, pertussis, pneumococcus and influenza. Recommendations for latent tuberculosis treatment and pre-exposure prophylaxis for HIV are also summarized.

1. Update in Infectious
Diseases
SAMIR EL ANSARY

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