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not by PO therapy alone.. “PO Therapy or IV-to-PO Switch” indicates the clinical syndrome­ can be treated by IV therapy alone, PO therapy alone, or IV followed by PO therapy (unless otherwise indicated in the footnotes under each treatment grid).. Most patients on IV therapy able to take oral medications should be switched to PO equivalent therapy after clinical improvement..

Empiric Therapy of CNS Infections

Acute Bacterial Meningitis

		Preferred IV
Subset (age)	Usual Pathogens	Therapy†	Alternate IV Therapy†
Neonate (0–30 days)	Group B streptococci	Ampicillin plus	Ampicillin plus
	E.. coli	Gentamicin*	Cefotaxime*
	Listeria
	monocytogenes
	Other gram-negatives
	(e..g.., Citrobacter,
	Serratia) and gram-
	positives (e..g..,
	Enterococci)
1–3 months	Overlap neonate and	Vancomycin plus	Ampicillin plus
	> 3 months	either Cefotaxime or	either Cefotaxime or
		Ceftriaxone*	Ceftriaxone*
> 3 months	S.. pneumoniae	Before culture results:	Meropenem*
	N.. meningitidis	Vancomycin plus	Severe penicillin allergy
	H.. influenzae B	either Ceftriaxone or
			Vancomycin plus
	(very rare)	Cefotaxime*
			either Rifampin or
	Non-typable
		After culture results	Chloramphenicol*
	H.. influenzae
		Discontinue
	(rare)
		vancomycin if
		penicillin-susceptible
		S.. pneumoniae,
		N.. meningitidis,
		or H.. influenzae is
		isolated

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Acute Bacterial Meningitis (cont’d)

		Preferred IV
Subset (age)	Usual Pathogens	Therapy†	Alternate IV Therapy†
CNS shunt infection	S.. epidermidis	Vancomycin with or	Linezolid × 7–10 days
(Treat initially for	S.. aureus (MRSA)	without Rifampin	after shunt removal
		10 mg/kg (IV or PO)
S.. epidermidis; if later			If MSSA isolated
		q12h × 7–10 days after
identified as MSSA,			Nafcillin with or without
		shunt removal
treat accordingly)			Rifampin 10 mg/kg (PO)
			q12h ×7–10 days after
			shunt removal
	S.. aureus (MSSA)	Nafcillin × 7–10 days	Vancomycin × 7–10 days
		after shunt removal	after shunt removal
	Enterobacteriaceae	Cefotaxime or	Meropenem × 7–10 days
		Ceftriaxone × 7–10	after shunt removal
		days after shunt
		removal

MRSA/MSSA = methicillin-resistant/sensitive S. aureus. Duration of therapy represents total time IV 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.

*Duration of therapy: Group B strep ≥ 14 days (with ventriculitis 4 weeks); E.. coli, Citrobacter, Serratia­ ≥ 21 days; Listeria 10–14 days; Enterococcus ≥ 14 days; S.. pneumoniae 10–14 days; H.. influenzae ≥ 10 days; N.. meningitidis 4–7 days..

Acute Bacterial Meningitis (Normal Hosts)

Clinical Presentation:  Fever, headache, stiff neck (or bulging anterior fontanelle in infants), irritability, vomiting, lethargy, evolving over hours to 1–2 days.. The younger the child, the more nonspecific the presentation (e..g.., irritability, lethargy, fever, poor feeding)..

Diagnostic Considerations:  Diagnosis by CSF chemistries, gram stain, culture. . CSF findings are similar to those in adults: pleocytosis (100–5000 WBCs/mm3; predominately PMNs), ↑ protein, ↓↓ glucose.. Normal CSF values differ by age:

	WBC/mm3 (range);		Protein, mg/dL	Glucose, mg/dL
	%PMNs		(range)	(range)
Preterm	9 (0–25);	57% PMNs	115 (65–150)	50 (24–63)
Term newborn	8 (0–22);	61% PMNs	90 (20–170)	52 (34–119)
Child	0 (0–7);	0% PMNs	(5–40)	(40–80)

Modified from The Harriet Lane Handbook, 20th edition..

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Pitfalls:  The younger the child, the more nonspecific the presentation.. With prior antibiotic use (e..g.., oral therapy for otitis media), partially-treated meningitis (CSF lactic acid levels 4-6 nm/L) is a concern.. Especially in the summer season, rapid viral diagnosis (especially enteroviral PCR) can exclude ABM and prevent unnecessary hospitalization and antibiotic use.. HSV PCR can also be helpful in excluding ABM..

Therapeutic Considerations:  Meningitic doses of antibiotics are required for the entire course of treatment.. Repeat lumbar puncture (LP) is indicated at 24–48 hours if not responding clinically or in situations where a resistant organism is a concern (e..g.., penicillin-resistant S.. pneumonia, or neonate with gram-negative bacillary meningitis). . Dexamethasone (0. .3 mg/kg IV q12h× 2 days) may reduce neurologic sequelae (e..g.., hearing loss) in children ≥ 6 weeks of age when given before/with the first dose of antibiotics..

Prognosis:  Varies with causative agent and age at presentation.. Overall mortality < 5% in US (higher in developing countries).. Morbidity 30–35% with hearing loss the most common neurologic sequella.. Incidence of neurologic sequelae: S.. pneumoniae > H.. influenzae > N.. meningitidis.. Use of H.. influenzae (type B) and pneumococcal conjugate vaccines in routine childhood immunizations have greatly reduced the incidence of meningitis caused by these pathogens.. Neonates are at increased risk of mortality and major neurologic sequelae, and there is a significant incidence of brain abscesses in neonates with gram-negative meningitis (especially Citrobacter and Serratia infections)..

Acute Bacterial Meningitis (CNS Shunt Infections)

Clinical Presentation:  Indolent (lethargy, irritability, vomiting) or acute (high fever, depressed mental­ status)..

Diagnostic Considerations:  Diagnosis by CSF gram stain/culture, often obtained by shunt tap.. Pitfalls:  Blood cultures are usually negative for shunt pathogens and CSF WBCs may be low.. Therapeutic Considerations:  High risk of nafcillin resistance with coagulase-negative ­staphylococcal infection.. The addition of rifampin to vancomycin may improve clearance of bacteria.. Removal of prosthetic material is usually necessary to achieve a cure..

Prognosis:  Good with removal of prosthetic material..

Encephalitis

Subset	Usual Pathogens	IV Therapy†	IV-to-PO Switch†
Herpes	HSV-1	Acyclovir × 14–21 days	Treat IV only
Arbovirus	WNV, SLE, Powassan	No specific therapy
	encephalitis, EEE, WEE,
	VEE, JE, CE
Mycoplasma	M.. pneumoniae	Doxycycline or	Doxycycline or minocycline ×
		Minocycline ×	2–4 weeks
		2–4 weeks

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Encephalitis (cont’d)

Subset	Usual Pathogens	IV Therapy†	IV-to-PO Switch†
Respiratory	Influenza,	No specific therapy
viruses	Enteroviruses, Measles

WNV = West Nile Virus, SLE = St. Louis encephalitis, EEE = Eastern equine encephalitis, WEE = Western equine encephalitis, VEE = Venezuelan equine encephalitis, JE = Japanese encephalitis, CE = California encephalitis.

†See pp. 414–422 for drug dosages.

Herpes Encephalitis (HSV-1)

Clinical Presentation:  Acute onset of fever and mental status/behavioral changes.. High fever with intractable seizures and profoundly depressed sensorium may dominate the clinical picture.. Diagnostic Considerations:  Diagnosis by CSF PCR for HSV-1. . CSF findings include ↑ RBC/WBC, ↓ glucose, and ↑↑ protein.. Classic EEG changes with temporal lobe spikes may be present early.. Brain biopsy is rarely, if ever, indicated..

Pitfalls:  MRI/CT scan can be normal initially.. Delays in diagnosis and therapy adversely affect ­outcome.. Therapeutic Considerations:  HSV is the only treatable viral encephalitis in normal hosts..

Prognosis:  Antiviral therapy improves survival based on level of consciousness at presentation. . Mortality is 10–20%, and major neurologic sequellae are frequent in survivors..

Arboviral Encephalitis

Clinical Presentation:  Acute onset of fever, headache, altered mental status.. Usually seasonal (more common in summer/fall), based on vector/travel history.. Can be very severe with high mortality.. Symptomatic West Nile encephalitis is rare in children..

Diagnostic Considerations:  Serological studies are the primary means of diagnosis.. PCR “encephalitis­ panels” are being developed for clinical use..

Therapeutic Considerations:  No specific antiviral therapy.. Supportive therapy is crucial..

Pitfalls:  Be sure to elicit potential exposures/travel history in children with fever/altered mental status.. Prognosis:  Varies with agent.. Severe residual deficits and high mortality rates can occur, especially with Eastern Equine encephalitis..

Mycoplasma Encephalitis

Clinical Presentation:  Acute onset of fever and mental status changes.. Prodromal cough, sore throat, respiratory symptoms may occur..

Diagnostic Considerations:  CSF shows mild pleocytosis with a predominance of mononuclear cells, normal or mildly ↓ glucose, and mildly ↑ protein.. Mycoplasma IgG/IgM titers are elevated..

Pitfalls:  CSF findings can be confused with viral encephalitis..

Therapeutic Considerations:  Often self-limited illness even without antibiotic therapy.. Doxycycline or minocycline penetrate CNS and can be used in children > 8 years of age.. Macrolides may treat pulmonary infection but do not penetrate CNS..

Prognosis:  Good.. Neurologic sequelae are rare..