Hot Topics in Pediatric Infectious Diseases - Duke Pediatrics Intranet

Time for“change you can believe in”….

Live attenuated Flu vaccine• FluMist (MedImmune)• Attenuated influenza strains that have been adapted togrow well at lower temperatures in the nose• Intranasal delivery induces local immunity to preventsevere lower respiratory disease• Approved for ages 2-49 years old– 2-8 years need 2 doses if never vaccinated or only 1 if vaccinatedagainst flu before, >9 years need 1 dose• Still only indicated for healthy patients– High risk patients excluded

New data on FluMist• Study comparing CAIV vs. TIV in children6-71 months in 2002-3 season– Over 1000 kids in each group– 2 doses of either for everyone– Followed kids for ILI, confirmed flu cases andadverse events including wheezeAshkenazi et al, Pediatr Infect Dis J 2006;25: 870–879

New data on FluMistAshkenazi et al, Pediatr Infect Dis J 2006;25: 870–879

More data on FluMist• Study comparing CAIV vs. TIV in children6-17 years old with asthma in 2002-3season– Over 1000 kids in each group– 1 dose of either for everyone– Followed kids for ILI, confirmed flu cases andpulmonary function including wheezingFleming et al, Pediatr Infect Dis J 2006;25: 860–869

More data on FluMistFleming et al, Pediatr Infect Dis J 2006;25: 860–869

More data on FluMist• No significant differences in asthmaexacerbations, hospitalizations, antibioticuse, etc.Fleming et al, Pediatr Infect Dis J 2006;25: 860–869

Other considerations…• 2002-03 was a year when the vaccine was apretty good match for the circulating strains, andCAIV was still twice as good as TIV• I expect when data is available for the yearswhen the vaccine was not matched as well,CAIV will be even better• Recent study shows CAIV safe in infants asyoung as 6 weeks (Vesikari et al, Pediatrics 2008; 121:e568-e573)

What to do for now?• Issue right now is cost and coverage– Fully approved down to 2 years old– Fridge stored version approved (CAIV vs. LAIV)• Depending on your population,– Consider keeping some doses on hand for yourrecurrent infection kids (AOM, sinusitis, pneumonias)– For anyone that is willing to pay for it• No thimerosal in this product

Flu Vaccine coverage in kids 2006-7• Rate for 24-59 montholds nationally–

Current Influenza Activityhttp://www.cdc.gov/flu/weekly/http://www.epi.state.nc.us/epi/gcdc/flu.html

Ripped from the headlines….

An Epidemic that progresses…• 16 y.o previously healthy female presents to PMDwith fever, fatigue. PE at the time is unremarkable.• Over the course of 24 hours, the patient developsrespiratory failure, hemodynamic instability andmultisystem organ failure.• She is transferred to Duke PICU where she is foundto have an overwhelming pneumonia. Maximalsupportive and antimicrobial therapy are institutedbut the efforts are futile.Life support is withdrawn.

An Epidemic that progresses…• Outside blood culture grows CA-MRSA…

CA-MRSA• Community Acquired (or Associated)Methicillin Resistant Staphylococcus aureus• First noticed in the early 2000s as causingfrequent skin-soft tissue infections as well asfatal necrotizing pneumonias• Contains a shorter cassette for antibioticresistance than Hospital MRSA so it morefreely transmits to other bacteria

CA-MRSA• MRSA is in the news on a weekly, maybe evennightly basis• Confusion and widespread panic is being exploitedby news and advertisers• We as physicians need to emphasize facts:• CA-MRSA is in the community being spread• All the hand sanitizer in the world is not going to stop it!• While I agree with measures to help with hospital hygiene, thehorse is out of the barn– We need better science, better drugs and best, a vaccine

CA-MRSA: better science• A recent study in the Proceedings of theNational Academy of Science attempts tobetter understand the genetic evolutionand diversity of CA-MRSA to help answersome key questions– When and how did these isolates evolve?– How can we better understand thephenotypic/virulence differences that we see?– WARNING: These next slides will involve basic science..I will go slow and hold your hand through this….

CA-MRSA: better scienceKennedy et al, PNAS Jan 2008

CA-MRSA: better scienceKennedy et al, PNAS Jan 2008

CA-MRSA: better scienceKennedy et al,PNAS Jan 2008

CA-MRSA: better science• What are the lessons from this study:– These clones evolved fairly recently– Subtle differences can result in a significantvirulence change– It is not necessarily PVL that is doingeverything– We still know very little about host susceptibility

Scare tactics

Expanding clone• Article in “Infectious Diseases in Children”Dec 2006 discusses a S. pneumoniaeclone 19A that is highly resistant to mostcommonly used antibiotics• Quote rates of 20% resistance• Only susceptible to Fluoroquinolones andTelithromycin

Serotype 19A clone has increased since theintroduction of vaccineOverall, researchers found that frequency ofserotype 19A among multiple antibioticresistantstrains had risen from around one in100 in 2000, to more than one in five by 2005…Farrell and colleagues speculate this may bedue to the overuse of antibiotics and theintroduction of the PCV7 vaccine….An analysis of resistance showed 100%resistance rates to penicillin, cefuroxime(Zinacef, GlaxoSmithKline), the macrolides(erythromycin, azithromycin, clarithromycin)cotrimoxazole and tetracycline.Farrell said amoxicillin-clavulanate (Augmentin,GlaxoSmithKline) would commonly be given tochildren suspected of having antibiotic resistantpneumococcal infection. However, for this clonein 2000, it was effective just less than half thetime. By 2005, 83.1% of the 19A clone wereresistant to amoxicillin-clavulanate.No strains were resistant to levofloxacin(Levaquin, Ortho-McNeil) and only 0.7% ofstrains were resistant to telithromycin (Ketek,Sanofi-Aventis). However, the FDA indicatesneither of these drugs for pediatric use.Here’s what they don’ttell you…

The real truth…• They never give you a denominator to theirpercentages– They sampled macrolide resistant clones (20% of total)and 20% of those were MDR• 20% of 20% is 4% of the total! Worrisome yes, but does notmean we should panic!• The study was funded by Sanofi-Aventis, makersof Ketek (telithromycin)– At the time, the company wanted to continue with pediatric developmenteven though their drug was investigated because of severe liver toxicity(deaths and FHF requiring transplant in 5 patients!)– The FDA, after much embarrassment, withdrew approval inFeb07

The real truth…• Serotype 19A is showing up as a frequentcause of invasive S. pneumo disease• However, overall rates of invasive diseaseare stable nationally and significantlybetter than pre-PCV7• SO, even though the “pie” of invasivepneumococcal disease is “changingflavor”, it is still much smaller than before• 19A may cause a future increase, but itmay not….• Best for you to keep vaccinating and keepusing antibiotics prudently

Take 2 aspirin and call me in themorning…

Febrile Child• The work up of the febrile child has always beenbased on the premise that a proportion of febrilechildren with a non-focal physical exam havebacteremia that would progress to more severefocal infections:– Meningitis– Osteomyelitis– Other disseminated infections

Febrile Child• ALL of this data is from the H. flu type b days• Our guidelines in place for the FWLS patientsare from 1993 and have never been updated toreflect H. flu immunization and the fact that S.pneumo did not cause disseminated infection atnearly the rates as did H. flu• Now that we are post-PCV7, what about now?Should we still do blood cultures?

Febrile Child• I have personally believed for several years, ashave others, that we need to abandon thispractice of doing blood cultures on children withFWLS• I hired an undergraduate and examined the datafrom Duke in the years pre- 1997-9) and post-PCV7 (2001-mid 2004) for all children 3-36months with FWLS that had a blood culturedrawn

• From 1997-9What we found…– There were 148 children with FWLS– 17 had positive cultures, but 7 were false+– 10 pathogens: 6 S. pneumo• From 2001-mid 2004– There were 275 children with FWLS– 14 had positive cultures, but 11 were false+– 1 pathogen: NOT S. pneumo

What we found…• Rates of UTI were essentially unchanged, about7% in both periods• UTI now is the most commonly identifiedbacterial infection in this group of patients• Not everyone was tested for UTI– How many were potentially missed?

What we found…• Occult bacteremia rate from S. pneumo dropped100% from 2.8% to 0% between the pre- andpost-PCV7 period• False positive cultures still make up 4-5% of allculture results– All these patients get phone calls, some come to EDfor follow up• Half of all FWLS kids received antibiotics!

If you follow my math…• Let’s say the current rate of OB is 0.5%• That means that to prevent one case of possiblemeningitis– You would see 20,000 children, of which 100 would havebacteremia, of which one has meningitis– You would have given up to 10,000 of those kids empiricantibiotics– 1,000 of those kids would have had a false positive bloodculture– AND, there is no reliable data that the one case ofmeningitis would have done better than if you had justwaited until he had the first signs of meningitis

Time for a change…• The data shows that occult bacteremia is a termthat we need to put in the history books becauseit does not occur at rates we have to worry about• Stop drawing blood cultures on these febrilechildren if they have been vaccinated and stopgiving antibiotics!• Test the urine on all of these FWLS kids

Just in case you were wondering• Opponents of getting rid of blood cultures point tothe emergence of 19A as an example of thedanger of doing that• We decided to do a follow up study from 2004-2006 to see if things had changed• Results: There were still NO cases ofpneumococcal OB• Bottom line: What I said before about 19A andflavors of a smaller pie

Boldly go where no man(one) hasgone before

Viruses and Asthma• Study looking at adults withasthma trying to identifyviruses associated with onsetof symptoms• Used “ViroChip”, aspecialized gene chip toidentify all of the commonrespiratory virus families• Novel HCoV and HRVisolates may be newlyidentified triggersJournal of Infectious Diseases 2007; 196:817–25

The future in viral diagnosis.• Your patients have an NP aspirate for viraldiagnosis• The aspirate has nucleic acids extracted andsimultaneous detection of all the majorrespiratory viruses using real-time PCR orMicroarray is performed• You have a specific answer is a few hours• New therapies to offer? We’ll see…

In related news…• The previous study identified new speciesof Rhinovirus that were distinct from the Aand B groups well known to cause thecommon cold• They called these isolates group X• A subsequent study from Germanyshowed this group of Rhinoviruses isresponsible for many severe respiratoryillnesses in childrenRenwick et al, JID 2007; 196:1754–60

In related news…Renwick et al,JID 2007;196:1754–60

A cool way to prove what weprobably knew already…

Exhaled aerosols• Huynh et al used a mask to collect exhaledaerosols from 20 adult volunteers with URI• They asked them to do the following:– Quietly breathe for 20 minutes– Read aloud for 20 minutes– 20 loud coughs over 3-5 min– They changed masks after each activity and usedPCR to document whether virus RNA was present onthe maskHuynh et al, Clin Inf Dis 2008; 46:93–5

Exhaled aerosolsHuynh et al, Clin Inf Dis 2008; 46:93–5

Microbiology Folklore:The dangers of the “Double Dip”and the “5 second rule”

Food Folklore• Dr. Paul Dawson studies foodmicrobiology at Clemson• He has conducted studies that addresssome of the common folklore in Foodsafety• I’ll discuss 2 projects: the “5 second rule”and the “Double Dip”

The “Double Dip”• For those of you that maynot remember, a 1993episode of Seinfeldfeatured George at awake where he dips hischip, takes a bite, anddips again• He is immediatelychastised by “Timmy” atthe party but dismisseshis concerns of “puttinghis whole mouth in thedip”www.nytimes.com,1/30/08,accessed 3/21/08,©NBC

The “Double Dip”• Dr. Dawson and his students set up anexperiment where they tested dips forbacteria after a double dip– They used sterile water as a control, a thinsalsa and a thicker cheese dip and achocolate sauce– Students took bites of wheat crackers andeither single or double dipped–The dip was then cultured for bacteriawww.nytimes.com, 1/30/08

The “Double Dip”• The study found that potentially 10 5bacteria could be isolated from dip after adouble dip– The more acidic the dip, the less bacteria– The thicker the dip, the less bacteria• My advice: put a spoon in your party dip toencourage people to take a little on theirown plate!www.nytimes.com, 1/30/08

5 second rule• They also used various surfaces coveredwith Salmonella to see how many bacteriawere transferred after 5 seconds ofcontact• They used bologna and bread• They tested carpet, tile and wood• They also tested how long the bacteriasurvived in a high enough # to transferDawson et al, J Applied Micro 2007Apr;102(4):945-53

5 second rule• They found that Salmonella lived on the surfacesfor 4 weeks in high #’s• 99% of bacteria on a surface could transfer after5 seconds of contact with food• Efficiency decreased over time but was stillsignificant• My read: Wipe surfaces down frequently,separate potentially contaminated foods andwhen in doubt, throw it out!Dawson et al, J Applied Micro 2007Apr;102(4):945-53

Questions?