2/16/2016

Learning Objectives
• Discussion general principles regarding
Antibiotic Prescribing in 2016: antibiotic resistance
Pediatric Infectious Diseases Update • Understand how to determine local
antimicrobial resistance patterns when
making prescribing decisions.
Teri Moser Woo PhD, CPNP-PC, ARNP, FAANP • Review of commonly used antibiotics in and
Pacific Lutheran University their resistance patterns
• Recommendations for practice

Antibiotic Resistance Antibiotic Resistance

• 2 million antibiotic resistant infections annually
in US
• 23,000 deaths from resistant infections
• Resistance to invasive pneumococcal strains has
decreased since vaccinating with PCV (Tomczyk, S. et al. (2014)
• Uropathogens resistant to TMP/SMX (range 23% to 31%)
(Edlin & Copp, 2014)

• CDC has prioritized bacteria into three categories

– Urgent, serious, and concerning • Enterobacteriaceae (Klebsiella pneumoniae,
Escherichiacoli,and Proteus mirabilis) resistance to
– Urgent third-generation cephalosporins (G3CR) and extended-
• Clostridium difficile spectrum β-lactams is increasing (Logan et al, 2014)
• Carbapenem-resistant Enterobacteriaceae (CRE)
• Drug-resistant Neisseria gonorrhoea • Predicted 10 million deaths per year worldwide due to
antimicrobial resistant by 2050 (O’Neil, 2014)
CDC, 2013

How Antibiotic Resistance Develops and Spreads Urgent Threat: C. difficile

CDC, 2013

http://www.cdc.gov/drugresistance/about.html

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Urgent Threat: Carbapenem-resistant

Enterobacteriaceae (CRE) Urgent Threat: Gonorrhea

CDC, 2013 CDC, 2013

Serious Threat Level MRSA

• Multidrug-resistant Acinetobacter
• Drug-resistant Campylobacter
• Fluconazole-resistant Candida
• Extended spectrum β-lactamase producing
Enterobacteriaceae
• Vancomycin-resistant Enterococcus
• Multidrug-resistant Pseudomonas aeruginosa
• Drug-resistant non-typhoidal Salmonella
• Drug-resistant Salmonella Typhi
• Drug-resistant Shigella
• Methicillin-resistant Staphylococcus aureus (MRSA)
• Drug-resistant Streptococcus pneumoniae
• Drug-resistant tuberculosis

Local Resistance – Antibiogram Antibiogram: Seattle Children’s 2014

Seattle Children’s Hospital

http://www.seattlechildrens.org/healthcare-professionals/resources/ Seattle Children’s Hospital
http://www.seattlechildrens.org/healthcare-professionals/resources/

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Regional Trends in Resistance

CDC, 2013

Logan et al, 2014

Upper Respiratory Pathogens

Acute Otitis Media: Guidelines
(AOM/Sinusitis)
• S. pneumoniae
Lieberthal, AS et al. (2013). Diagnosis and Management of Acute
Otitis Media, Pediatrics, 131, e964-e999.
• Nontypeable H. influenzae
• M. catarrhalis Diagnosis of AOM
• moderate to severe bulging of the tympanic membrane
(TM) or new onset of otorrhea not due to acute otitis externa
• mild bulging of the TM and recent (less than 48 hours) onset
of ear pain (holding, tugging, rubbing of the ear in a
***Viruses*** nonverbal child) or intense erythema of the TM
• Clinicians should not diagnose AOM in children who do not
have middle ear effusion

Duration of Therapy
AOM Treatment
• High-dose amoxicillin is still first line • < 2 yrs: 10 days
– Efficacy against common pathogen, safety, low cost, acceptable
taste, and narrow microbiologic spectrum • 2 yr to 5 yr olds with mild to moderate
symptoms: 7 days
• If amoxicillin in past 30 days or β-lactamase–positive H
influenzae and M catarrhalis suspected • > 6 yrs with mild to moderate symptoms: 5 to
– High-dose amoxicillin-clavulanate (90 mg/kg/day amoxicillin)
– cefdinir (14 mg/kg per day in 1 or 2 doses)
7 days
– cefuroxime (30 mg/kg per day in 2 divided doses)
– cefpodoxime (10 mg/kg per day in 2 divided doses) Lieberthal, AS et al. (2013). Diagnosis and Management
of Acute Otitis Media, Pediatrics, 131, e964-e999.
– ceftriaxone (50 mg/kg, administered intramuscularly)

Lieberthal, AS et al. (2013). Diagnosis and Management of Acute Otitis Media, Pediatrics, 131, e964-e999.

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Recommended Antibiotics for (Initial or Delayed) Treatment and

for Patients Who Have Failed Initial Antibiotic Treatment Penicillin allergy and Cephalosporins
Initial Immediate or Delayed Antibiotic Treatment Antibiotic Treatment After 48–72 h of Failure
of Initial Antibiotic Treatment

Recommended First-line Alternative Treatment Recommended First- Alternative Treatment

Treatment
Amoxicillin (80–90 mg/ kg per
day in 2 divided doses)
or
• Beltran et al (2015) National Children’s Hospital
(if Penicillin Allergy) line Treatment
– One case of non-anaphylactic reaction (N = 153)
Cefdinir (14 mg/kg per Amoxicillin- Ceftriaxone, 3 d
• Terico & Gallagher (2014)
a
day in 1 or 2 doses) clavulanate (90 mg/kg Clindamycin (30–40
per day of amoxicillin, mg/kg per day in 3
with 6.4 mg/kg per day divided doses), with or
of clavulanate in 2
divided doses)
without third-generation
cephalosporin
– Review of 1950 to 2013 literature
– Cross-reactivity of < 5%
Cefuroxime (30 mg/kg or Failure of second
per day in 2 divided antibiotic

a
Amoxicillin-clavulanate (90
mg/kg per day of amoxicillin,
with 6.4 mg/kg per day of
clavulanate [amoxicillin to
clavulanate ratio, 14:1] in 2
divided doses)
doses) • Campagna et al (2012)
Cefpodoxime (10 mg/kg Ceftriaxone (50 mg IM or Clindamycin (30–40
per day in 2 divided
doses)
IV for 3 d) mg/kg per day in 3
divided doses) plus third-
– Review
generation cephalosporin
– Overall cross reactivity rate ~ 1%
b
Tympanocentesis
b
Ceftriaxone (50 mg IM or Consult specialist
IV per day for 1 or 3 d)

Use of Macrolides to treat AOM

• Meta-analysis of 10 trials indicated greater
likelihood of clinical failure if macrolides were
prescribed (azithromycin or clarithromycin)

• BUG-DRUG MISMATCH!

• Recommendation: Only use macrolides in

Type I allergic patients
Courter, J., Baker, W., Nowak, K., Smogowicz, L., Desjardins, L., Coleman, C., &
Campagna et al 2012 Girotto, J. (2010). Increased clinical failures when treating acute otitis media with
macrolides: a meta-analysis. The Annals Of Pharmacotherapy, 44(3), 471-478.

Uncomplicated viral URI.

Sinusitis
• 2012 Guidelines from Infectious Disease Society
– Chow et al (2012). IDSA Clinical Practice Guideline for
Acute Bacterial Rhinosinusitis in Children and Adults.
http://www.idsociety.org/Guidelines_Patient_Care/
• 2013 Guidelines from American Academy of
Pediatrics
– Wald et al. (2013). Clinical Practice Guideline for the
Diagnosis and Management of Acute Bacterial Sinusitis
in Children Aged 1 to 18 Years. Pediatrics, 132;e262-
e280.
• New 2015 adult guidelines by American Academy of
Otolaryngology—Head and Neck Surgery Wald E R et al. Pediatrics 2013;132:e262-e280

©2013 by American Academy of Pediatrics

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Sinusitis Treatment
AAP Guidelines Wald et al (2013)

• Amoxicillin is first line (Wald et al, 2013)

Clinical Presentation Severe Acute
Bacterial
Worsening
Acute Bacterial
Persistent Acute
Bacterial
– In children > age 2 yrs, no daycare and no antibiotics for 4
Sinusitisa Sinusitisb Sinusitisc weeks use 45 mg/kg/day divided BID
Uncomplicated acute Antibiotic Antibiotic therapy Antibiotic therapy or – High risk of resistance: amox 80-90 mg/kg/day
bacterial sinusitis without therapy additional
coexisting illness observation for 3
d
• Children < 2 yrs, daycare or recent antibiotics
days
– Amoxicillin-clavulnate 80-90 mg/kg/day of amox (max 2
Acute bacterial sinusitis Antibiotic
with orbital or intracranial therapy
Antibiotic therapy Antibiotic therapy gm/day)
complications
• PCN allergic
Acute bacterial sinusitis Antibiotic Antibiotic therapy Antibiotic therapy • Cefdinir, cefuroxime or cefpodoxime
with coexisting acute otitis therapy
media, pneumonia, • Moderate to severe sinusitis in children < 2 yrs with Type I allergy:
adenitis, or streptococcal – Clindamycin and cefixime
pharyngitis

Second-line antibiotics for Sinusitis Sinusitis: Duration of Therapy

• Start amoxicillin or amox-clav for 3 days • Wald (2013) “optimal duration has not
– If symptoms improving, continue for 7 more days
received systematic study”
(total of 10 to 14 days)
• If worsening or no improvement after 3 days: • AAP (2013) 10 days or 7 days after
– High dose amoxicillin/clavulanate
improvement
– Children – majority have improvement in 3 days
• cefuroxime (Ceftin) • ISDA (2012) 5 to 7 days
• cefdinir (Omnicef)
• cefpodoxime (Vantin)
• AAO (2015) 5 to 10 days

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Sinusitis Community Acquired Pneumonia

Don’t Forget • S. pneumoniae is the most common cause of
• Saline nasal spray or drops bacterial pneumonia in patients of all ages
– Liquefies secretions • Infants 4 to 16 weeks:
– Decreases crusting near the sinus ostia
– Consider chlamydia
• Topical decongestants • Respiratory viruses most common in first 2 to 3 years
– Decrease tissue edema and nasal resistance, probably of life (80% of CAP)
enhances drainage of secretion from sinus ostia
• Corticosteroids • Over 5 yrs through adolescence:
– Consider mycoplasma
– Helpful in chronic sinusitis or if allergic rhinitis
concurrently • CA-MRSA
– No evidence for use in acute sinusitis • Virus

Pneumonia antibiotic choices in

Children 5 yrs or older
Children
Fully immunized children < age 5 years: • Guidelines say amoxicillin 90 mg/kg to max 4
• Bacterial pneumonia (S. pneumoniae) gm per day
– Amoxicillin 80-90 mg/kg/day • Treat for 10 days
– PCN allergy: Clindamycin or a macrolide
• Mycoplasma or other atypical most likely
• Unimmunized for Hib or PCV
– Ceftriaxone 50 mg/kg – Azithromycin
• Infant with suspected chlamydial pneumonia – Erythromycin
– Azithromycin (American Academy of Pediatrics Red Book, 2012) – Doxycyline if > 7 yrs

Strep pharyngitis Strep Pharyngitis

• Pathogen: Streptococcus Treatment (Red Book, 2015; ISDA, 2012):
pyogenes – Penicillin
• PO 250 mg BID if < 27 kg or 500 mg BID if > 27 Kg
• Strep 20-30% of • IM penicillin G benzathine single dose of 600 000 U (<27kg), > 27 kg and
pharyngitis adults 1.2 million U

• Most rapid strep tests – Amoxicillin 50 mg/kg in a single daily dose (max 1gm)
– 1st generation cephalosporin
are 90 to 95% accurate
• Cephalexin (Keflex) 40-50 mg/kg/day dosed BID (max 500 mg
BID)
Committee on Infectious Diseases et al. Red Book Online
668-680
• Cefadroxil (Duricef) 30 mg/kg/day (max 1 gm)
– Clindamycin 7 mg/kg/dose tid (max 500 mg tid)

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PCN allergic GAS Carriers

1st generation cephalosporin (cephalexin)
• 20-25% of children may be asymptomatic
carriers during the winter months
– May be colonized by GAS pharyngitis for ≥6 months

If immediate Type 1 hypersensitivity:
• Eradication therapy

clindamycin 20 mg/kg/day divided TID (max 1.8
gm/day) – Clindamycin 30 mg/kg/day in 3 doses (max 300
mg/dose) x 10 days

Or macrolide
– Augmentin 40 mg amoxicillin/kg/d in 3 doses (max =

Azithromycin (12 mg/kg/day [maximum, 500 mg]) for 2000mg amoxicillin/d)
5 days – Penicillin V: 50 mg/kg/d in 4 doses × 10 d (max = 2000
mg/d) PLUS rifampin: 20 mg/kg/d in 1 dose × last 4 d
• Macrolides have resistance (5% to 10%, up to 20%) of treatment (max = 600 mg/d)
(AAP Red Book, 2015)

(Red Book, 2015; ISDA, 2012):

Skin and Soft Tissue Infections

S. Aureus Skin and Soft Tissue Infections
Guidelines
• Impetigo
• I & D is primary treatment
– Bullous or nonbullous impetigo:
• Moist heat for small
mupirocin or retapamulin BID x
furuncles
5 days (Stevens et al, 2014;
• Antibiotics if cellulitis is
RedBook 2015)
present
– Oral therapy for 7 days • Culture
(dicloxacillin or cephalexin)
Liu, C. et al (2011; Stevens et al, 2014 .
Red Book® 2015, 2015

Purulent skin and soft tissue infections (SSTIs).

Dennis L. Stevens et al. Clin Infect Dis. 2014;cid.ciu296

Red Book® 2015, 2015

© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases
Society of America. All rights reserved. For Permissions, please e-mail:
journals.permissions@oup.com.

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Antibiotic choices for MRSA –

Antibiogram
outpatient
• Purulent cellulitis
– TMP-SMX
– Clindamycin
– If > 8 yrs: Doxycycline
• Non-purulent cellulitis
– Cover for both CA-MRSA and β strep
– cephalexin and dicloxacillin
– amoxicillin and/or TMP-SMX or a tetracycline
• Duration of therapy: 5 to 7 days
Liu, C. et al. (2011); Stevens et al. (2014)
http://www.tpchd.org/files/library/3dcf2f5336023ce6.pdf

C. difficile C. Difficile Treatment

• Stop antibiotics
• The diagnosis of C. difficile disease is based on • Moderate or severe disease: empirical antibiotic
C. difficile toxins in stool OR enzyme treatment
immunoassay (EIA) OR nucleic acid – Metronidazole
• (30 mg/kg per day, orally, in 4 divided doses, maximum 2 g/day)
amplification tests/PCR – Oral vancomycin or vancomycin administered by enema
• Routine testing not recommended • (40 mg/kg per day, orally, in 4 divided doses, to a maximum daily dose not to exceed 2 g)

– Duration of therapy: 10 days

• Pathogen shedding for weeks • Up to 30% of patients experience a recurrence after
– 13% to 24% at 2 weeks and 6% at 4 weeks after discontinuing therapy
therapy AAP Committee on Infectious Disease (2013). • Good hand washing to prevent spread
Clostridium difficile Infection in Infants and Children. AAP Committee on Infectious Disease (2013). Clostridium difficile Infection in Infants and Children. Pediatrics, 131(1), 196-200
Pediatrics, 131(1), 196-200; AAP RedBook 2015 ISDA C.difficile guidelines http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf
AAP RedBook, 2015

National Focus on Antimicrobial

Antibiotic Stewardship
Resistance
• Prescribing for acute respiratory infections has
not changed from 1999-2010 (Nett et al., 2013)

• President Obama’s FY2016 budget included

$1.2 billion for National Strategy on
Combating Antibiotic-Resistant Bacteria

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What YOU Can Do References

• AAP Committee on Infectious Disease (2013). Clostridium difficile Infection in Infants and Children.
Pediatrics, 131(1), 196-200
• Know what pathogen you are treating and • AAP Committee on Infectious Disease (2015). RedBook® Online.
• Beltran, R. J., Kako, H., Chovanec, T., Ramesh, A., Bissonnette, B., & Tobias, J. D. (2015). Penicillin allergy and
prescribe appropriately surgical prophylaxis: Cephalosporin cross-reactivity risk in a pediatric tertiary care center. Journal Of Pediatric
Surgery, 50(5), 856-859. doi:10.1016/j.jpedsurg.2014.10.048

• Do not prescribe antibiotics for viral infection • Bradley, et al (2011) The Management of Community-Acquired Pneumonia in Infants and Children Older
Than 3 Months of Age: Clinical Practice Guidelines by the Pediatric Infectious Diseases Society and the
Infectious Diseases Society of America. Clinical Infectious Disease, 53.
• Know your local resistance pattern • Campagna, J. D., Bond, M. C., Schabelman, E., & Hayes, B. D. (2012). The use of cephalosporins in penicillin-
allergic patients: a literature review. The Journal Of Emergency Medicine, 42(5), 612-620
• Center for Disease Control (2013). Antibiotic resistance treats in the United States 2013. Retrieved from
http://www.cdc.gov/drugresistance/threat-report-2013/
• Courter, J., Baker, W., Nowak, K., Smogowicz, L., Desjardins, L., Coleman, C., & Girotto, J. (2010). Increased
clinical failures when treating acute otitis media with macrolides: a meta-analysis. The Annals Of
Pharmacotherapy, 44(3), 471-478.
• Edlin, RS & Copp, HL (2014). Antibiotic resistance in pediatric urology. Therapeutic Advances in Urology,
6(2), 54-61
• Lieberthal, AS et al. (2013). Diagnosis and Management of Acute Otitis Media, Pediatrics, 131, e964-e999.

• Liu, C. et al (2011). Clinical Practice Guidelines by the Infectious Diseases Society of

America for the Treatment of Methicillin-Resistant Staphylococcus AureusInfections
in Adults and Children . Clinical Inf Disease, 52.
• Logan, LK, Meltzer, LA, McAuley, JB, Hayden, MK, Beck, T., Braykov, NP,
Lexminarayan, R & Weinstein, RA (2014). Extended-spectrum Β lactamase-
producing Enterobacteriaceae Infections in Children: A two-center Case-case-
controlled study of risk factors and outcomes in Chicago, Illinois. Journal of the
Pediatric infectious Diseases Society, 3(4), 312-319.
• Shulman et al. (2012) Clinical Practice Guideline for the Diagnosis and Management
of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases
Society of America. Clinical Infectious Disease, 55(10), e86-e102
• Stevens, et al. (2014). Practice Guidelines for the diagnosis and management of
skin and soft tissue infections: 2014 update by the Infectious Diseases Society of
America. Clinical Infecious Diseases First published online: June 18, 2014
• Terico, A. T., & Gallagher, J. C. (2014). Beta-lactam hypersensitivity and cross-
reactivity. Journal Of Pharmacy Practice, 27(6), 530-544.
doi:10.1177/0897190014546109
• Tomczyk, S. et al. (2014). Prevention of antimicrobial resistant infection among
children ages < 5 years with the 13-valent pneumococcal conjugate vaccine –
selected U.S. areas, 2005-2013. Oral presentation at Infectious Disease Society ID
Week Philadelphia, PA October 9, 2014
– Wald et al. (2013). Clinical Practice Guideline for the Diagnosis and Management of Acute
Bacterial Sinusitis in Children Aged 1 to 18 Years. Pediatrics, 132;e262-e280.