Infectious Disease Update

Christopher Belcher MD FAAPDirector, Pediatric Infectious DiseasesPeyton Manning Children’s Hospital

Indianapolis, IN

Case #1

• 2 yo girl previously healthy• Presented to ER with fever• Found leukopenia / neutropenia and

thrombocytopenia• Moderately ill, no rash, no HSM• A piece of historical information led to the

diagnostic test.

Case #1

Case #1 – P. falciparum Malaria

• Family had spent a month in Nigeria• Claim to have taken antimalarials• Parasite burden initially above 3%• Was treated with atovaquone / proguanil• Received treatment in hospital – defervesced,

showed count recovery, and clearance of parasitemia

CLOSTRIDIUM DIFFICILE COLITIS

Clostridium difficile

• Presentation:– Often fever, abd pain, diarrhea - bloody, mucousy– Associated with antibiotic use, abd surgery

• Has been held children under 2 do not have the receptor for the toxin– Issue being re-examined

• Outcomes– Morbidity - diarrhea, fever, prolonged hospital stay– Toxic megacolon / colectomy

Background: Impact

• Hospital-acquired, hospital-onset: 165,000 cases, $1.3 billion in excess costs, and 9,000 deaths annually

• Hospital-acquired, post-discharge (up to 4 weeks): 50,000 cases, $0.3 billion in excess costs, and 3,000 deaths annually

• Nursing home-onset: 263,000 cases, $2.2 billion in excess costs, and 16,500 deaths annually

Campbell et al. Infect Control Hosp Epidemiol. 2009:30:523-33. Dubberke et al. Emerg Infect Dis. 2008;14:1031-8.

Dubberke et al. Clin Infect Dis. 2008;46:497-504. Elixhauser et al. HCUP Statistical Brief #50. 2008.

Date of download: 9/4/2012Copyright © 2012 American Medical Association.

All rights reserved.

From: Clostridium difficile Infection in Hospitalized Children in the United States

Arch Pediatr Adolesc Med. 2011;165(5):451-457. doi:10.1001/archpediatrics.2010.282

Trend in Clostridium difficile infection (CDI) in hospitalized children.

Figure Legend:

Clostridium difficile

• Since 2005 an increase in resistant, aggressive C. difficile colitis (NAP-1)

• Associated with fluoroquinolone resistance and increased toxin production

• Incidence 22.5 vs 6 per 1000 admissions in 2004 vs 1997

• 30-day attributable mortality rate was 6.9% vs. 1.5% in 1997

N Engl J Med 2005;353:2433-2449,2503-2505.

Risks Factors for Disease

• Antibiotics put patients at risk– Adults : fluoroquinolones– Children : penicillins and cephalosporins

• Clindamycin resistant strain “J” was more prevalent in 1990s

• Risks in children include: cancer and IBD

Findings of Children Discharged with C. difficile from pediatric hospitals

• Increasing trend from 1997 - 2006• 20% higher mortality rate• 36% more likely to have had a colectomy• Increased LOS 4x, charges 2x• 11 times more likely to have IBD• More likely to be on immunosuppression or

antibiotics• UNLIKE adults, no increase in severity

Arch Ped Adolesc Med 2011; 165: 451-7

What to do with Infants

• C. difficile can be a part of the normal flora in newborns and young infants

• 70% can be colonized and asymptomatic• The environment, not maternal transmission

seems to be the major factor• After 2 years of age, the gut flora should

mimic an adult and it is not normal

J. Clin. Microbiol. January 1984 vol. 19 no. 1 77-78

David A. Enoch , Matthew J. Butler , Sumita Pai , Sani H. Aliyu , J. Andreas Karas Clostridium difficile in children: Colonisation and disease Journal of Infection Volume 63, Issue 2 2011 105 - 113

C. difficile Colonization by Age Up to 13 Years of Age

Testing for C. difficile

• C difficile culture• C difficile toxin detection: EIA, mouse IP• C difficile molecular methods (PCR)

– 027/Nap1/BI• In a study of 5 testing methods – molecular

methods detected 35-54% more positive specimens

• Only need to order PCR once - ONCE

Chapin KC. J Mol Diagn. 2011; 13:395-400

Clostridium difficile Prevention and Treatment

• Prevention– Good hygiene– C. difficile spores NOT killed by alcohol– Limit antibiotic use

• Treatment– STOP the antibiotics– Metronidazole– Oral vancomycin– Fidaxomicin– Nitazoxanide (Alinia)– Under study: ramoplanin, CB-183315– Others: po bacitracin, tinidazole, IVIG, cholestyramine,

probiotics, fecal enemas

Metronidazole Therapy

• Can be given iv or po• 30 mg/kg/day divided q 6 hours x 10 days

– Maximum 2gm/day• 20% or more may relapse after therapy

Vancomycin Therapy

• Only given po for C. difficile– Can use capsules (125mg, 250 mg)– or IV solution orally

• IV vancomycin does not enter gut• 40 mg/kg/day po divided into 4 doses

– Maximum 500mg/dose• The best way to create VRE

– Vancomycin resistant enterococci

Fidaxomicin

• Narrow spectrum macrocyclic antibiotic• ONLY approved in adults• 200mg twice a day for 10 days• No more effective than vancomycin• Lower relapse rate• Orphan drug status for children under 16

Probiotic Therapy

• 138 hospitalized adults received probiotics or placebo (Plummer S, et al. Clostridium difficile pilot… Int Microbiol . 2004;7:59-62)

– Of those with diarrhea:• 2.9% of probiotic group were C. diff positive• 7.2% of placebo group were C. diff positive

• The relapse rate of adults with recurrent C. diff was lower when given probiotics (McFarland LV, et al. A randomized placebo-controlled… JAMA . 1994;271:1913-1918)

• Metaanalysis shows benefit for AAD and C. diff with S. boulardii and L. rhamnosus (Am J Gastroenterol 2006;101:812-822)

• But data are still mixed and no clear recommendation can be made

The Potential for Vaccines

• Approaches to Vaccines:– Toxoid Vaccine to toxin A and B

• Similar to other toxoid vaccines – tetanus, diphtheria• Delivered IM• Do produce antibody responses• Further in development cycle

– Recombinant subunit vaccines• Truncated toxin A and B• Newer in development cycle

http://www.discoverymedicine.com/Dale-N-Gerding/2012/01/25/clostridium-difficile-infection-prevention-biotherapeutics-immunologics-and-vaccines/

(Aboudola et al., 2003; Kotloff et al., 2001; Intercell , 2011).

Case #2

• 15 year old boy, previously well• Developed red scaly lesions L clavicle and arm• No relief with hydrocortisone• Sent to dermatology for psoriasis

Case #2

Case #2

• Biopsy of the lesion revealed:– Blastomyces

• We live in the land of Histoplasma• Treated with Itraconazole

VACCINE SAFETY

Vaccine Safety

• CDC email study of 476 families• Concerns included:

– 38% - too many shots in one visit– 34% - too many vaccines in 2 years– 32% - vaccines may cause fever– 30% - vaccines may cause autism / neurol– 26% - vaccine ingredients are unsafe– 23% - no safety concerns

Health Aff. 2011; 30:61151-9

Vaccine Safety - Who Do Parents Trust

• 1500 parents online national survey– 76% said they trust their doctor "a lot”– 26% said they trust other HCP "a lot"– 23% said they trust government experts "a lot"

Pediatrics 2011; 127:S107-12

Vaccine Safety - Who Do Parents Trust

• Family and friends 67% reported as "somewhat trustworthy"

• Parents of children harmed by vaccines 65% reported as "somewhat trustworthy"

• Celebrities "somewhat trustworthy" by 24%• Mothers more likely than fathers to report

influence by parents of children harmed by vaccines, media, celebrities

Vaccine Safety

• Institute of Medicine - literature review• Vaccines: MMR, VAR, HepA, HepB, HPV, MCV,

DTaP– NO association of MMR vaccine with autism based

on scientific literature– NO association of Type I diabetes with MMR or

DTaP– NO association of asthma, RAD, Bell's palsy with

TIVInstitute of Medicine http://www.iom.edu/Reports/2011/

Adverse-Effects-of-Vaccines-Evidence-and-Causality/Report-Brief.aspx

Vaccine Safety

• The report did find convincing evidence for:– Var association with disseminated varicella and

with zoster– MMR vaccine and febrile seizures as well as

measles inclusion body encephalitis– Hypersensitivity with: MMR, Var, TIV, HepB, MCV,

TT

Vaccine Safety

• The report did find evidence that favored acceptance for:– HPV and anaphylaxis– MMR and transient arthralgia in females and

children• Most other associations - the evidence was

inadequate to accept or reject

Vaccine Safety - What to Do

• US Dept of Health and Human Services Study• 272 new mothers

– Given written vaccine safety info and VIS– One of 3 groups: prenatal, 1 wk, 2mo

• All groups improved attitude• Preferred info before 2 month visit

Pediatrics 2011; 127:S120-6

Vaccine Safety - What to Do

• Know what parents are reading and talking about

• Listen to parental concerns• Dispel myths and misunderstandings with

information• Top down your office MUST believe in

vaccination and BE vaccinated

Case #3

• 10 day old infant• Delivered by NSVD• Clinically well• Developed a rash

Case #3

Case #3

• At this point the correct thing to do is:– Obtain HSV swabs and start acyclovir– Obtain a culture and apply mupirocin– Obtain a dermatology consult

• The diagnosis was confirmed as:– Incontinentia pigmenti

MISCELLANEOUS INFLUENZA UPDATES

2012-13 Influenza Vaccine Composition

• A/California/7/2009 (H1N1)• A/Victoria/361/2011 (H3N2)• B/Wisconsin/1/2010

How to Deal with Egg Allergy

MMWR Weekly August 17, 2012 / 61(32);613-618

2012-13 Vaccine for Children <9

MMWR Weekly August 17, 2012 / 61(32);613-618

Quadrivalent Influenza Vaccine

• Traditional influenza vaccine is trivalent – containing 2 A strains and one B strain

• B strains are usually one of two lineages – Victoria and Yamagata

• In the first 10 flu seasons this millennium the lineage in the vaccine did not match what circulated HALF the time!

• Thus, putting in two B strains is an attractive strategy for future seasons 2013-14

www.cdc.gov/flu/weekly/

H3N2v Influenza

• Most symptomatic cases are typical of seasonal influenza

• No evidence of sustained human to human transmission

• All isolates contain M gene of 2009 H1N1 strain that increases human transmission

• Concern when exposed to pigs (not eating pork)• Our PCR detects as unclassified Influenza

Case Count: Detected U.S. Human Infections with H3N2v by State since August 2011

States Reporting H3N2v Cases in 2011 Cases in 2012Hawaii 1Illinois 4Indiana 2 138Iowa 3 Maine 2 Maryland 12Michigan 6Minnesota 4Ohio 107Pennsylvania 3 11Utah 1*West Virginia 2 3Wisconsin 20Total 12 307

http://www.cdc.gov/flu/swineflu/h3n2v-case-count.htm#table1

Case Count: Detected U.S. Human Infections with H3N2v by State since August 2011

States Reporting H3N2v Cases in 2011 Cases in 2012Hawaii 1Illinois 4Indiana 2 138Iowa 3 Maine 2 Maryland 12Michigan 6Minnesota 4Ohio 107Pennsylvania 3 11Utah 1*West Virginia 2 3Wisconsin 20Total 12 307

http://www.cdc.gov/flu/swineflu/h3n2v-case-count.htm#table1

Case #4

• A thirteen year old girl previously well• Developed moderately painful nodules on her

palms• No systemic symptoms

Case #4

Case #4

• Diagnostic considerations include:– Syphilis– Papular purpuric gloves and socks syndrome– Non tuberculous mycobacterium– Enterovirus 71

Case #4

• Diagnostic considerations include:– Syphilis– Papular purpuric gloves and socks syndrome– Non tuberculous mycobacterium– Enterovirus 71

Case #4

ID MISCELLANY

PMCH ER E. coli Urine SensitivitiesAntibiotic Susceptible Intermediate ResistantAMPICILLIN 80 49% 0 0% 82 51%AMPICILLIN/SULBACTAM

112 69% 19 12% 31 19%

CEFAZOLIN154 95% 3 2% 5 3%

CEFTRIAXONE NON CSF162 100% 0 0% 0 0%

CIPROFLOXACIN155 96% 0 0% 7 4%

GENTAMICIN153 94% 0 0% 9 6%

NITROFURANTOIN158 98% 3 2% 1 1%

TRIMETH-SULFAMETHOXAZOLE 119 73% 0 0% 43 27%

Tuberculosis Testing in Children

• Mantoux skin test is the gold standard– 15mm is positive for most over 4 years old– 10mm if they have risk factors (<4 yo, overseas, contact with

high risk, medical conditions)– 5mm if they are very high risk (household contact, dz,

suppressed)• Interferon gamma release assays

– Quantiferon TB or T-SPOT– Only require single visit for blood draw– No false positives with BCG– Unreliable under 5 years old

DTaP Vaccine Administration Site• Study of over 230,000 patients• 5th dose DTaP (age 4-6)• 75% given in the arm• 0.4% of children had medically attended local

reaction• 47.4 vs 32.1 (arm to leg) reactions / 10,000• Thus, the leg may be an attractive site.

Jackson LA et al. Pediatrics. 2011;127:e581-5876

Rabies Prevention

• Virus transmitted in saliva of infected animal– Bats are most common source in IN– Tiny teeth and claws– Exposure considered if bat contact cannot be ruled out in room of

sleeping or your individual– ***DON’T let them kill the animal***

• PEP involves:– wound cleaning– rabies immune globulin 20 IU/kg around wound / IM– vaccine - 1ml IM on days 0, 3, 7, 14

• 2009 changed recommendation for PEP vaccine from 5 doses to 4 (got rid of day 28)

Pneumococcal Disease in 2011

• Had been seeing 140-180 cases of vaccine preventable invasive pneumococcal disease / year

• In 2011 was down to 40• Likely due to introduction and boosters with

PCV13• Drug resistant S. pneumoniae was not seen at

PMCH in 2011

Pneumococcal Meningitis

Meant to Gross You Out

• Hospital Curtains (Schweizer, ICAAC 2011)– 42% of curtains had VRE– 21% had MRSA– 92% were colonized with a pathogen in 1 week

• Ties and lab coats are nasty too!

Case #5

• 6 year old boy• Had 1 week of fever, cough• Presented with Hb 2.6 Hct 7.8 WBC 1.8• Required transfusion in PICU• Found to have a warm reactive antibody

Case #5

• Testing was postive for:– Influenza– Adenovirus– Mycoplasma pneumoniae– Parvovirus B19

Case #5

• Testing was postive for:– Influenza– Adenovirus– Mycoplasma pneumoniae– Parvovirus B19

Case #5

Infectious Disease Update

Christopher Belcher MD FAAPDirector, Pediatric Infectious DiseasesPeyton Manning Children’s Hospital

Indianapolis, IN