396 A n t i b i o t i c E s s e n t i a l s

Diagnostic Considerations:  Laboratory testing for GAS is recommended, since clinical differentiation of viral pharyngitis from GAS is not possible. . Rapid tests for GAS antigens are reliable with excellent specificities, but due to variable sensitivities of the assays, a negative rapid test should be confirmed by a throat culture.. The accuracy of antigen and culture tests is dependent on obtaining a good throat swab containing pharyngeal/tonsillar secretions..

Pitfalls:  Be sure to obtain a good throat swab.. Post-treatment testing is generally not recommended­

unless the patient is at high risk for rheumatic fever (e. .g. ., family history, ongoing outbreak) or is still symptomatic after 10 days of therapy.. Asymptomatic GAS carriers do not require antibiotic therapy, but identifying a “true carrier” may be difficult.. Eradication of GAS carriage should be considered in the following situations: an outbreak of acute rheumatic fever or post-streptococcal glomerulonephritis; an outbreak of GAS in a closed community; a family history of rheumatic fever; multiple episodes of GAS infection within the family for many weeks despite therapy; family anxiety about the presence of GAS; or tonsillectomy is being considered based on persistent carriage.. Eradication is achieved using the same antimicrobial regimen as for “persistent/recurrent disease” (see treatment grid p.. 395)..

Therapeutic Considerations:  Penicillin V (or amoxicillin) is the drug of choice for GAS pharyngitis.. Erythromycin is still considered the drug of choice for penicillin-allergic individuals, although macrolide-resistant GAS strains are being reported.. First-generation cephalosporins are also useful alternatives.. Broader spectrum agents, although likely effective, should not be used routinely.. Macrolides or sulfonamides may not eradicate GAS pharyngitis. . When eradication of carriage is indicated amoxicillin, amoxicillin/clavulanate or clindamycin alone or penicillin plus rifampin may be useful..

Prognosis:  Excellent.. Rheumatic fever is rare in the US..

Empiric Therapy of Lower Respiratory Tract Infections

Community-Acquired Pneumonia

				PO Therapy or
Subset (age)	Usual Pathogens	IV Therapy†		IV-to-PO Switch†
Community-	Group B streptococci,	Ampicillin Plus		Not applicable
acquired	Gram-negative	either Gentamicin
pneumonia	enteric bacteria	or Cefotaxime	×
Birth to 20 days		10–21 days

Duration of therapy represents total time IV or IV, PO, or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy after clinical improvement..

†See pp. 414–422 for drug dosages.

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Community-Acquired Pneumonia (cont’d)

			PO Therapy or
Subset (age)	Usual Pathogens	IV Therapy†	IV-to-PO Switch†
3 weeks to	RSV	None (supportive	None
3 months	Parainfluenza	care)
	Human
	metapneumovirus
	(hmpv)
	C.. trachomatis	Cefotaxime or	Afebrile: Erythromycin × 14 days
	S.. pneumoniae	Ceftriaxone ×	or Azithromycin × 5–7 days..
	B.. pertussis	10–14 days*..	Lobar, febrile: Amoxicillin or
	S.. aureus	Alternative:	amoxicillin/clavulanic acid
		Ampicillin or	or Cefdinir or Cefuroxime or
		Clindamycin*	Cefpodoxime × 10–14 days
> 3 months to	Viruses (RSV,	RSV: consider ribavirin..§ For infants at highest risk for severe
< 5 years	parainfluenza,	RSV infection, consider palivizumab 15 mg/kg/month ×
	influenza, adenovirus,	1–2 seasons for prevention.. Influenza: Oseltamivir (influenza
	rhinoviruses)	A, B)..¶ Routine immunization for all children > 6 months
	S.. pneumoniae	Ampicillin** or	Amoxicillin or Amoxicillin/
	H.. influenzae	Ceftriaxone or	clavulanate or Clarithromycin or
	M.. pneumoniae	Cefotaxime ×	Azithromycin × 10–14 days
		10–14 days*
5–15 years	M.. pneumoniae	Ceftriaxone plus	Amoxicillin plus a macrolide or
	C.. pneumoniae	a macrolide ×	Doxycycline (age > 8 years) ×
	S.. pneumoniae	10–14 days*	10–14 days
Pertussis	Bordetella spp..‡	Azithromycin ×	Erythromycin estolate × 14 days
	certain	5 days or	or Clarithromycin × 7 days
	Adenoviruses	Erythromycin ×	or Azithromycin × 5 days.. If
	M.. pneumoniae	14 days	macrolide-intolerant:
	C.. trachomatis		TMP–SMX × 14 days
	C.. pneumoniae
Tuberculosis	M.. tuberculosis	See pp.. 400–401	See pp.. 400–401

Duration of therapy represents total time IV or IV, PO, or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy after clinical improvement..

†See pp. 414–422 for drug dosages.

*If chronic cough of more insidious onset, consider adding IV or PO macrolide (azithromycin, clarithromycin, erythromycin) to cover Pertussis/C.. trachomatis (3 weeks–3 months of age), Mycoplasma (> 5 years of age), or Mycoplasma/C.. pneumoniae (5–15 years of age)..

**If fully immunized against H.. influenzae and S.. pneumoniae..

‡B.. pertussis, B.. parapertussis, B.. bronchiseptica..

§ Use should be limited to the most severely ill with RSV, i..e.., transplant patients..

¶Influenza A strains now circulating are amantadine resistant..

398 A n t i b i o t i c E s s e n t i a l s

Community-Acquired Pneumonia

Clinical Presentation:  Fever ± dyspnea, cough, tachypnea with infiltrates on chest x-ray..

Diagnostic Considerations:  Usual pathogens differ by age.. In neonates, pneumonia is typically diffuse and part of early-onset sepsis.. In young infants, there is significant overlap between signs and symptoms of bronchiolitis (primarily due to RSVU) and pneumonia. . Severe pneumonia is usually due to bacterial infection, although the organism is frequently not isolated (e..g.., blood cultures are positive in only 10–20% of children < 2 years of age with bacterial pneumonia).. In young infants, Chlamydia trachomatis can be detected by or culture of nasopharyngeal (NP) secretions.. Mycoplasma pneumonia, suggested by high titer cold agglutinins > 1:64.. Diagnosis by nucleic acid amplification testing or ↑ IgM titers.. Although cases in children < 5 years have been reported.. Respiratory viruses (RSV, influenza, adenoviruses, parainfluenza viruses, hMPV) can also be detected by PCR of throat/nasal secretions.. If child lives in area with high prevalence of tuberculosis, consider tuberculosis in the differential diagnosis of primary pneumonia..

Pitfalls:  Reliance on upper airway specimen for gram stain/culture leads to misdiagnosis and mistreatment, as true deep sputum specimen is rarely obtainable in children..

Therapeutic Considerations:  Therapy is primarily empiric based on child’s age, clinical/epidemiologic features and chest x-ray findings.. Mycoplasma requires 2–3 weeks of treatment; C.. pneumoniae may require up to 4 weeks of treatment.. Routine use of pneumococcal vaccines has decreased the incidence of pneumococcal pneumonia..

Prognosis:  Varies with pathogen, clinical condition at presentation, and underlying health status.. Prognosis is worse in children with chronic lung disease, congenital heart disease, immunodeficiency, neuromuscular disease, hemoglobinopathy..

Lower Respiratory Tract Infections due to Respiratory Viruses

Clinical Presentation:  Viruses cause the majority of lower respiratory tract infections (LRTIs) in children.. Respiratory syncytial virus (RSV) is the leading cause of LRTI in young infants, manifesting as bronchiolitis/viral pneumonia and causing annual mid-winter epidemics.. The risk of secondary bacterial infection (other than possibly otitis media) is very low.. Fever is typically low grade and usually improves over 3–5 days, even if hospitalized.. Influenza viruses are another major cause of winter epidemic LRTIs in children of all ages.. Hospitalization rates in infants under one year of age rival those in the > 65 year old population.. Characteristic findings include high fever and diffuse inflammation of the airways.. Young infants may have prominent GI symptoms as well.. Secondary bacterial infection (otitis media, pneumonia, sepsis) are frequent complications of influenza.. Primary influenza pneumonia,­ encephalopathy, and myocarditis are rare, severe complications.. Other respiratory viruses associated with LRTIs in children include parainfluenza type 3 (viral pneumonia), parainfluenza types 1 and 2 (croup), adenoviruses, and human metapneumovirus (hMPV).. Influenza in children resembles that in adults, but in children, lymphocytosis is usual.. Atypical lymphocytes are common in children, but not in adults.. Thrombocytopenia­ is common in both children and adults..

Diagnostic Considerations:  Viral syndromes are often diagnosed based on clinical assessment alone.. For confirmation or in more severe cases, rapid diagnosis by PCR..

Pitfalls:  Routine use of corticosteroids or bronchodilators in RSV bronchiolitis are not supported by clinical evidence. . Overuse of the diagnosis of “flu” (e. .g. ., stomach flu, summer flu) has led to diluted appreciation for true influenza and its severity. . Influenza vaccine (RIDT) has been traditionally ­underutilized in children. . As in adults, a negative rapid influenza diagnostic test does not rule out ­influenza.. ILI with negative RIDTs should be retested by PCR for respiratory viruses..

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Therapeutic Considerations:  For most viral LRTIs treatment is primarily supportive (e..g.., adequate hydration, fever control, supplemental oxygen for severe illness).. Ribavirin is approved for RSV infection­ but is very rarely used due to uncertain clinical benefit, high cost, and cumbersome method of administration (prolonged aerosol). . For infants at greatest risk of severe RSV disease (e. .g. ., premature­ infants, infants with underlying chronic lung disease or congenital heart disease), monthly prophylaxis with palivizumab (synagis) 15 mg/kg/ month (IM) decreases RSV hospitalization rates.. Per American Academy of Pediatrics guidelines, palivizumab is indicated for infants with chronic lung disease and ≤ 32 weeks gestational age (GA) or congenital heart disease who are 12months of age at start of RSV season.. For premature infants, palivizumab is consi­dered for premature infants < 29 weeks GA for a maximum of 5 doses through the winter season are recommended..

Annual influenza vaccination is indicated for all individuals > 6 months of age.. All circulating influenza A strains are resistant to amantadine.. The neuraminidase inhibitors oseltamivir and zanamivir have pediatric indications for treatment and prophylaxis of influenza (Table 7..1)..

Table 7.1. Influenza Antiviral Medication Dosing Recommendations

Antiviral			Treatment	Chemoprophylaxis
Oseltamivir*
Adults			75-mg capsule twice per	75-mg capsule once per
			day 3 5 days	day 3 10 days
Children		15 kg or less	60 mg per day divided into 2 doses	30 mg once per day
(age,
		15–23 kg	90 mg per day divided into 2 doses	45 mg once per day
12 months
		24–40 kg	120 mg per day divided into 2 doses	60 mg once per day
or older),
weight:		> 40 kg	150 mg per day divided into 2 doses	75 mg once per day
Zanamivir
Adults			Two 5-mg inhalations (10 mg total)	Two 5-mg inhalations (10 mg
			twice per day	total) once per day
Children			Two 5-mg inhalations (10 mg total)	Two 5-mg inhalations (10 mg
			twice per day (age, 7 years or older)	total) once per day (age,
				5 years or older)

* CDC recommends oseltamivir 3 mg/kg (PO) q12h × 5 days for full term infants <12 months of age.. Lower doses recommended for pre-term infants..

Prognosis:  Most children with viral LRTIs do well and recover without sequelae.. Infants hospitalized with RSV infection have higher rates of wheezing episodes over the next 10 years.. The highest rates of hospitalization from influenza occur in children < 2 years of age and in the elderly..

Pertussis

Clinical Presentation:  Upper respiratory tract symptoms (congestion, rhinorrhea) over 1–2 weeks (catarrhal stage) progressing to paroxysms of cough (paroxysmal stage) lasting 2–4 weeks, often with a characteristic inspiratory whoop, followed by a convalescent stage lasting 1–2 weeks during which

400	A n t i b i o t i c E s s e n t i a l s

cough paroxysms decrease in frequency and severity. . Fever is low grade or absent. . In children < 6 months, whoop is frequently absent and apnea may occur.. Duration of classic pertussis is 6–10 weeks.. Older children and adults may present with persistent cough (without whoop) lasting 2–6 weeks.. Complications include seizures, secondary bacterial pneumonia, encephalopathy, death; risk of complications is greatest in children < 1 year..

Diagnostic Considerations:  Diagnosis is usually based on nature of cough and duration of symptoms.. Laboratory diagnosis may be difficult.. A positive culture for Bordetella pertussis from a nasopharyngeal swab inoculated on fresh selective media is diagnostic, but the organism is difficult to recover after 3–4 weeks of illness.. PCR of nasal secretions is the best rapid diagnostic test for pertussis..

Pitfalls:  Be sure to consider pertussis in older children and adults with prolonged coughing illness.. Family contacts of index case should receive post-exposure antimicrobial prophylaxis.. Virtually all children should be vaccinated against pertussis.. A single booster dose of acellular pertussis is recommended at 11–12 years of age (additional guidelines for catch-up for older adolescents and adults up to 64 years of age).. Pregnant women should be vaccinated during the 2nd – 3rd trimester of each pregnancy to protect themselves and provide passive immunity to their infants. Relative precautions to further pertussis immunization include: seizure within 3 days of a dose; persistent, severe, inconsolable crying for ≥ 3 hours within 48 hours of a dose; collapse or shock-like state within 48 hours of a dose; or temperature of ≥ 40.5°C without other cause within 48 hours of a dose..

Therapeutic Considerations:  Infants < 6 months frequently require hospitalization.. By the ­paroxysmal stage, antibiotics have minimal effect on the course of the illness but are still indicated to decrease transmission.. An association has been made between oral erythromycin and infantile hypertrophic pyloric stenosis in infants < 6 weeks of age; consider an alternative macrolide (azithromycin or clarithromycin) in these cases..

Prognosis:  Good. . Despite the prolonged course, long-term pulmonary sequelae have not been described after pertussis.. Children < 1 year are at greatest risk of morbidity and mortality, although mortality rates remain very low..

Tuberculosis

		PO or IM Therapy
Subset	Pathogen	(see footnote for drug dosages)
Latent infection (positive PPD,	M.. tuberculosis	INH × 9 months or Rifampin × 6 months
clinically well, negative chest		(if INH-resistant) or INH unavailable and
x-ray)		child at risk
Pulmonary and extrapulmonary	M.. tuberculosis	INH plus Rifampin plus PZA × 2 months
TB (except meningitis)		followed by INH plus Rifampin × 4 months†

Duration of therapy represents total time IV or IV, PO, or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy after clinical improvement..

†If drug resistance is a concern, EMB or streptomycin (IM) is added (4-drug regimen in areas where MDR TB is prevalent) to the initial regimen until drug susceptibilities are determined..

Chapter 7.  Pediatric Infectious Diseases and Pediatric Drug Summaries			401
Tuberculosis (cont’d)
		PO or IM Therapy
Subset	Pathogen	(see footnote for drug dosages)
Meningitis	M.. tuberculosis	INH plus Rifampin plus PZA plus either
		Streptomycin (IM) or Ethionamide ×2 months,
		followed by INH plus Rifampin ×7–10 months
		(i..e.., 9–12 months total therapy)‡
Congenital	M.. tuberculosis	INH plus rifampin plus PZA plus
		streptomycin (IM)

Duration of therapy represents total time IV or IV, PO, or IV + PO.. Most patients on IV therapy able to take PO meds should be switched to PO therapy after clinical improvement..

‡ Plus steroids..

		Twice weekly dosage
TB Drug	Daily dosage (mg/kg)	(mg/kg)
Isoniazid (INH)	10–15	20–30
Rifampin (RIF)	10–20	10–20
Ethambutol (EMB)	15–25	50
Pyrazinamide (PZA)	20–40	50
Streptomycin	20–40 (IM)	–
Ethionamide	15–20 (in 2–3 divided doses/day)	–

Alternative drugs (capreomycin, ciprofloxacin, levofloxacin, cycloserine, kanamycin, para-aminosalicylic acid) are used less commonly and should be administered in consultation with an expert in the treatment of tuberculosis..

Tuberculosis

Clinical Presentation:  Most children diagnosed with tuberculosis have asymptomatic infection detected by tuberculin skin testing.. Symptomatic disease typically presents 1–6 months after infection with fever, growth delay, weight loss, night sweats, and cough.. Extrapulmonary involvement may present with meningitis, lymphadenopathy, bone, joint, or skin involvement..

Diagnostic Considerations: A positive tuberculin skin test indicates likely infection with M. . tuber­­­ culosis.. Tuberculin reactivity develops 2–12 weeks after infection.. Children < 8 years old cannot produce sputum for AFB smear and culture.. Interferon gamma release assays (IGRAs) may be used to diagnose TB in children > 5 years.. Testing recommended only for children or increased risk, e..g.., HIV, immigrants from TB endemic areas clinical and those with clinical findings suggestive of TB..

Pitfalls:  Tuberculosis may be missed if not considering the diagnosis in children at increased epidemiological risk for exposure.. Tuberculous meningitis often presents insidiously with nonspecific irritability and lethargy weeks prior to the development of frank neurological defects..