Update in Infectious Diseases 2012

Keith B. Armitage, MDProfessor of Medicine

Case Western Reserve University

Disclosures

• No conflicts

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”– NEJM 12/05; 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 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

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

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, or in the pipeline………. Tigecycline ? otherwise

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

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– Larger trials needed for confirmation

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

Chronic Fatigue Syndrome- 2012

• Retraction of two studies that initially associated CFS with retrovirus infection

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