Antibiotics for Pediatric Diseases

Case #1

An 8-year-old boy is seen in February because of fever, headache, sore throat, and malaise. He’s had no rhinorrhea, cough, or hoarseness. Physical examination reveals a temperature of 103.5, exudative pharyngitis, and tender cervical adenopathy.

How will you treat him?

Is penicillin still the drug of choice for treatment of streptococcal pharygitis?• AAP recommends oral penicillin

V 2-3 times daily for 10 days, a single dose of benzathine penicillin, or amoxicillin 250 mg/kg tid for 10 days

• Larger doses of penicillin once daily result in more relapses*

*Breese, 1965, Gerber, 1989

Once daily dosing?

• Recommended by the FDA:– azithromycin (Zithromax)– cefixime (Suprax)– cefdinir (Omnicef)– cefadroxil (Ultracef, Duracef)– ceftibutin (Cedax)

• Amoxicillin (750 mg once daily)**Feder, Pediatrics, 1999

Shorter courses?

• Approved by the FDA for 5-day regimen:– cefpodoxime (Vantin)– cefdinir (Omnicef)– azithromycin (Zithromax)

What about the penicillin-allergic child?• Erythromycin estolate (20-40

mg/kg/d divided bid) or ethylsuccinate (40 mg/kg/d divided bid)

• Azithromycin (12 mg/kg/d x 5 d), clarithromycin (15 mg/kg/d div q 12 hrs), clindamycin (20 mg/kg/d div q 6-8 hrs)

Why penicillin might “fail”

• Non-adherance to prescribed therapy

• failure to recognize carriers• ? beta-lactamase production

by other pharyngeal flora• new streptococcal infection

Case #2

A 13-year-old boy has had fever and sore throat for two days. He now presents with a cough. On examination he has a temperature of 104, RR 22, O2 saturation of 98%, retractions, and crackles over the posterior left lower lung. Chest x-ray confirms a left lower lobe pneumonia.

What do you think is causing his pneumonia?How will you treat him?

Common Causes of Community-Acquired Pneumonia in Otherwise Healthy Children

• Viruses– Respiratory syncytial

virus– Influenza A and B– Parainfluenza 1, 2, and 3– Adenovirus– Rhinoviruses– Measles virus

• Mycoplasma– Mycoplasma pneumoniae

• Chlamydia– Chlamydia pneumoniae– Chlamydia trachomatis

• Bacteria– Streptococcus

pneumoniae– Mycobacterium

tuberculosis– Staphylococcus aureus– Haemophilus influenzae

type b– non-typable H.

influenzae

McIntosh,K: NEJM 2002;346:429

Likelihood that the pneumonia is bacterial is greater if:• Fever is > 39 degrees C• The patient “looks sick”• There are alveolar infiltrates on chest x-

ray• WBC is > 15,000• NB: Blood culture is positive in about

10% of infants and children with bacterial pneumonia and more likely in those > 2 yrs

Bacterial pneumonia according to age:

• < 28 days: Group B streptococcus, Gram negative enterics, CMV, listeria

• 3 wks - 3 months: C trachomatis, RSV, parainfluenza, S. pneumoniae, B. pertussis, Staph aureus

• 4 months-4 years: respiratory viruses, S. pneumoniae, M. pneumoniae, H. influenzae, TB

• 5 - 15 years: M. pneumoniae, S. pneumoniae, C. pneumoniae, TB

Antibiotics for pneumonia--according to age:• < 28 days: ampicillin and gentamicin• 1 month - 3 months: macrolide (afebrile) +

cefotaxime/ceftriaxone (fever)• 4 months - 4 years:

– NO ANTIBIOTICS FOR VIRAL INFECTION Amoxicillin (80-100 mg/kg/d divided tid) OR ampicillin 200 mg/kg/d divided q 6 hrs, OR cefuroxime or cefotaxime

• 5 - 15 years: macrolide + IV ampicillin OR cefuroxime OR cefotaxime

Beta-lactam-resistant S. pneumoniae:

• Intermediate resistance: MIC = 0.1-1 microgram/ml

• High level resistance: MIC > 2 micrograms/ml

• 100,000 units/kg of penicillin G yields a serum concentration of about 10 micrograms/ml

• 500 mg of amoxicillin yields a serum concentration of about 8 micrograms/ml

Importance of beta-lactam-resistant S. pneumoniae:• Highest risk in children

– < 3 years– day care– recent antibiotics

• Can be overcome by high doses of penicillin/ampicillin

• Impact of Prevnar for immunized children?– 11% fewer episodes of pneumonia, 33%

fewer with abnormal x-ray, 73% fewer with extensive disease

What if his RR was 35, his O2 saturation was 85% and he had an effusion on chest x-ray?

Don’t forget Staphylococcus aureus and group A streptococcus in children with large effusions who look very sick. IV clindamycin should be added for these children.

Case #3

A two-month-old girl is brought to your office because of a 5-day history of rhinorrhea and cough. She has been afebrile. On exam she has rhinorrhea and coughs frequently. There are scattered crackles and wheezes throughout her lung fields.

What is the cause of her respiratory symptoms?How will you treat her?

Antibiotics for pneumonia--according to age:• < 28 days: ampicillin and gentamicin• 1 month - 3 months: macrolide (afebrile) +

cefotaxime/ceftriaxone (fever)• 4 months - 4 years:

– NO ANTIBIOTICS FOR VIRAL INFECTION Amoxicillin (80-100 mg/kg/d divided tid) OR ampicillin 200 mg/kg/d divided q 6 hrs, OR cefuroxime or cefotaxime

• 5 - 15 years: macrolide + IV ampicillin OR cefuroxime OR cefotaxime

Think about

• Pertussis– Any contacts with cough illness?– Is the cough paroxysmal?– Chest x-ray--pertussis only rarely is

associated with pulmonary infiltrates– CBC to look for lymphocytosis

• Chlamydia– Maternal history of chlamydia?

And think about

• Viruses– Contacts?– Season? (RSV, influenza,

parainfluenza, enteroviruses)

• Antibiotic?– The only class that makes sense is

macrolides--erythromycin estolate, clarithromycin, azithromycin

Case #4

A four-year-old girl has had rhinorrhea, cough, and intermittant fever for 12 days. Her mom thinks there has been no improvement in her symptoms during that time. On exam she has a temperature of 100.5, rhinorrhea, and cough.

What is your diagnosis?

AAP Clinical Practice Guideline(September, 2001)• Diagnose acute sinusitis based

upon persistent symptoms, no need for radiologic studies

• Treat with antibiotics as per acute otitis media recommendations

• BUT. . . .

Findings from Garbutt,JM, et al: Pediatrics:

2001;107:619 in a study of 161 patients

1-18 years old (50% < 7 yrs) with symptoms

between 10-28 days

Criticism of Garbutt study:

• Children included were only mildly ill• Diagnosis wasn’t confirmed by x-ray• Inclusion of older children whose

disease was likely mild• Symptomatic therapy was permitted• Antibiotic doses prescribed may

have been inadequate

Wald (letter):Pediatr 2002;109:166

Case # 5

A 6-year old girl developed varicella 7 days ago. She had fever for the first 4 days of her illness. Fever resolved but returned 1 day ago. Now she complains of pain in her left leg. On exam she has a temp of 102.5, scabbed varicella lesions over her trunk, face, and extremities, and tenderness over her left ankle region. There is also redness and tenderness around one of the scabbed lesions on her abdomen.

What is your major concern?

MMWR;1997:46:944

Cases of varicella at a childcare center, by

date of onset--Boston, MA January-February

1997

Cases of group A streptococcus at a

childcare center by date of onset--

Boston, MA, January-February, 1997

Bacterial complications associated with varicella:

Treat for group A streptococcal infection, but keep Staphylococcus aureus in mind.

Case # 6

An 18-month-old girl presents with continuing symptoms after 4 days of treatment with amoxicillin for acute otitis media. She is still complaining of ear pain, she has a temperature of 38.8 degrees C., and she is irritable. On exam you find that her TM is white and bulging with decreased mobility.

What is/are the likely cause(s) of her persistent findings?

How will you treat her?

Appropriate questions:

• What dose of amoxicillin was prescribed?

• Did she take it?• What is the likelihood of

infection with resistant pneumococcus?

• What other bacteria do you want to treat?

• Risk that this infection is due to S. pneumoniae:– Acute otitis media due to S. pneumoniae

is least likely to resolve spontaneously

• Risk factors for infection with resistant S. pneumoniae:– < 3 years– day care attendance

Treatment options:

• Continue current therapy (there is no direct relationship between the persistence of symptoms and the viability of infecting bacteria)

• Increase amoxicillin to 80-90 mg/kg/day (increase activity against resistant S. pneumoniae)

• Increase activity against beta-lactamase-producing organisms (H. influenzae and M. catarrhalis)

Enhanced treatment against beta-lactamase-producers:• Add clavulanate (could also

enhance activity against resistant S. pneumoniae by increasing amoxicillin component)

• Alternate choices: cefdinir (Omnicef), cefuroxime axetil (Ceftin), IM ceftriaxone (Rocephin), azithromycin (Zithromax)

Other approaches:

• Enhance compliance: reduced daily dosing, better taste, parenteral (ceftriaxone) therapy

• Tympanocentesis and culture

Case # 7

A 2-month old boy (born at term) is brought to the ED because of fever, irritability, and poor feeding for the past 24 hours. On exam the infant has a temp of 101, RR 50, O2 saturation 95%. He is moderately irritable, but his exam is otherwise normal.

How will you evaluate and treat him?

After blood, urine, and CSF cultures have been obtained. . .• Treatment should be aimed at

which bacterial organisms?– S. pneumoniae– Group B streptococcus– H. influenzae– E. coli and other enterics, incl

salmonella– Listeria

What’s wrong with ampicillin and gentamicin?

Nothing, as long as the CSF doesn’t reveal pleocytosis.

If it does, use ampicillin and ceftriaxone/cefotaxime (and consider vancomycin pending cultures)

Case # 8

A 15-year-old boy was wrestling with his neighbor’s dog and was bitten on the arm. On exam he has a 2 cm jagged laceration on his right forearm.

What are the bacterial agents to consider?

What antibiotic(s) will you use?

• Bacteria:– Staphylococcus aureus (amp plus clav)– Pasturella multocida (penicillin/ampicillin)– Eikenella corrodens (ampicillin)– Streptococcus and Staphylococcus

species

• Don’t forget to wash the wound and give tetanus prophylaxis if indicated

A 14-year-old girl is brought to the pediatric ED after 18 hours of fever. She had complained of sore throat and headache, and went to bed early the night before. This morning her mother found her in the bathroom somewhat disoriented. She had vomited once and had an episode of diarrhea the night before. On exam she had a temp of 103, RR 25, O2 sat 93, BP 100/35. There were no focal findings on exam.

A 3-year-old boy has had a URI for 3-4 days. This morning his mother noted a swelling in his left neck. On exam he has a temperature of 102 and a tender, firm, slightly red mass in the left anterior cervical area.

A 2-year-old boy has a fever and a 36 hour history of increasing leg pain and refusal to walk. On exam his temp is 102, he is holding his right leg in slight flexion and abduction, there is reduced range of motion of the hip, and he refuses to bear weight.

A 12-month-old boy presents with clear nasal discharge for 2 days, difficulty sleeping, and tugging at his right ear. On exam he has a temperature of 102 degrees and a bulging, white, opaque, immobile right tympanic membrane. This is his first episode of otitis media.