1. Update in Infectious Diseases 2012
Keith B. Armitage, MD
Professor of Medicine
Case Western Reserve University

2. Disclosures
No conflicts

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”
NEJM 12/05; NAP1 strain
Increase in frequency and severity
10x increase in reports of CDI as primary cause of death
Change in antimicrobial risk
Quinolones >> cephalosporins > clindamycin

5. Clostridium difficile
New testing method
PCR 85 % to 95 % sensitive; quick turnaround time
Prior toxin assays- 28 % sensitive!
Relapses- 20 %- predicted by age, severity of presentation, hospital exposure, prior CDI relapse
New therapies
Fidaxomicin
Stool transplants

6. Audience Response Question
For hospitalized patients with suspected or proven mild to moderate CD- I most often start with :
1. oral metronidazole
2. oral vancomycin
3. IV metronidazole
4. oral vanco + IV metronidazole
5. fidaxomicin

7. 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

8. 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

9. 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

10. 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?

11. 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

12. 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

13. 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

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

15. Update on antimicrobial agents
New antimicrobial agents for gram negative infections in the past decade, or in the pipeline………. Tigecycline ? otherwise

16. Audience Response Question
For outpatients with suspected Staphylococcus aureus skin and soft tissue infections, I most prescribe:
1. Augmentin
2. Bactrim
3. Clindamycin
4. Doxycycline
5. Linezolid
6. One of the above plus Keflex

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

18. 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

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

20. 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

21. 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

22. 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

23. 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

24. 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
Larger trials needed for confirmation

25. 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 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

26. 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

27. 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

28. Chronic Fatigue Syndrome- 2012
Retraction of two studies that initially associated CFS with retrovirus infection

29. 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

30. 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