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

Therapeutic Considerations:  Choice of initial therapy depends on stage of disease and likelihood of resistant organisms (based on index case, geographical region of acquisition).. For HIV-infected patients, duration of therapy is prolonged to ≥ 12 months.. For tuberculosis meningitis and miliary disease, the addition of corticosteroids to anti-TB therapy is beneficial..

Prognosis:  Varies with extent of disease, drug resistance and underlying immune status, but is generally good for pulmonary disease in children.. Bone infection may result in orthopedic sequelae (e..g.., Pott’s disease of the spine with vertebral collapse).. The prognosis for meningitis is guarded once focal neurological deficits and persistent depression of mental status occur..

Empiric Therapy of Vascular Infections

Central Venous Catheter (CVC) Infections (Broviac, Hickman,

Mediport)

Subset	Usual Pathogens	Preferred IV Therapy†	Alternate IV Therapy†
Empiric; immuno-	S.. aureus¶	Meropenem or	Piperacillin/tazobactam
compromised	Enterobacteriaceae	Piperacillin/tazobactam	plus an aminoglycoside ×
host	Pseudomonas	or cefepime × 7–14 days	7–14 days
	Viridans
	Streptococci
	Enterococcus
Isolate-based	S.. aureus	Nafcillin or Oxacillin for ≥	Cefazolin or Vancomycin
	MSSA	2 weeks	(preferred if severe beta-
			lactam allergy) for ≥ 2 weeks
	MRSA	Vancomycin with or	Linezolid or Quinupristin/
		without Gentamicin for	dalfopristin for ≥ 2 weeks
		≥ 2 weeks	(addition of Rifampin may be
			of benefit, for MRSA)
	Enterobacteriaceae	Piperacillin/tazobactam	Meropenem or Imipenem
	Pseudomonas	or Ticarcillin/clavulanate	with or without an
		with or without an	aminoglycoside* for ≥ 2
		aminoglycoside*	weeks
		for ≥ 2 weeks
	ESBL-producing	Meropenem or
	gram-negative	Ertapenem with
	bacilli	or without an	—
		aminoglycoside* for
		≥ 2 weeks

Chapter 7.  Pediatric Infectious Diseases and Pediatric Drug Summaries

403

Central Venous Catheter Infections (Broviac, Hickman, Mediport)

(cont’d)

Subset	Usual Pathogens	Preferred IV Therapy†	Alternate IV Therapy†
	Candida	Amphotericin B × 2–6	Fluconazole or Caspofungin
		weeks‡	or liposomal amphotericin
			B (if renal dysfunction) × 2–6
			weeks‡

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

† See pp. 414–422 for drug dosages.

*Gentamicin, tobramycin, or amikacin..

‡Based on promptness of line removal, clearance of blood cultures, evidence of metastatic foci..

¶If severely ill or suspicion of MRSA based on local epidemiology, include vancomycin in initial regimen pending culture results..

Clinical Presentation:  Fever ± site tenderness, erythema..

Diagnostic considerations:  Quantitative blood cultures from the peripheral blood/vascular catheter are best used to make the diagnosis.. However in clinical practice these are not often obtained, and the diagnosis is based on culture results in conjunction with one or more of the following features: local phlebitis or inflammation at the catheter insertion site; embolic disease distal to the catheter; sepsis refractory to appropriate therapy; resolution of fever after device removal; or clustered infections caused by infusion-associated organisms..

Pitfalls:  It may be difficult to differentiate infection from contamination in blood cultures, especially with coagulase-negative staphylococci.. Multiple positive cultures with the same organism and/or clinical features noted above suggest infection, not colonization.. Semiquantitative culture of the catheter tip yielding ≥ 15 colonies may also be useful in confirming the diagnosis but requires removal of the device..

Therapeutic Considerations:  Indications for catheter removal include septic shock, tunnel infection, failure to respond to treatment within 48–72 hours, or infection with Candida, atypical mycobacteria, or possibly S.. aureus.. Otherwise attempt to retain the catheter while treating with antibiotics.. Localized exit site infections (erythema, induration, tenderness, purulence) within 2 cm of the exit site should be treated topically (e..g.., Neosporin, Bacitracin, Bactroban) in conjunction with systemic therapy..

Prognosis:  Major complications (septic emboli, endocarditis, vasculitis) are rare with aggressive therapy. . Recrudescent infection can occur after therapy/apparent clearance and can often be successfully­ treated with additional courses of antibiotics; persistence ultimately requires line removal..

Empiric Therapy of Gastrointestinal Infections

Acute Diarrheal Syndromes (Gastroenteritis)

Subset	Usual Pathogens	Preferred Therapy†	Alternate Therapy†
Community-acquired	Viruses (Rotavirus,	No specific therapy	No specific therapy
	Norwalk agent,	indicated	indicated
	enteric adenovirus,
	enteroviruses)

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Acute Diarrheal Syndromes (Gastroenteritis) (cont’d)

Subset	Usual Pathogens	Preferred Therapy†	Alternate Therapy†
	Salmonella non-	Ceftriaxone (IV) or	TMP–SMX (IV or PO) or
	typhi	Cefotaxime (IV) ×	Amoxicillin (PO) or cefixime
		10–14 days*	(PO) ×10–14 days
	Shigella	Ceftriaxone (IV) or	TMP–SMX (PO) or
		Azithromycin (PO) ×	Cefixime (PO) or
		5 days	Ampicillin (PO) × 5 days
	Campylobacter	Erythromycin (PO) ×	Doxycycline (PO) (> 8 year
		7 days or Azithromycin	old) × 7 days
		(PO) × 5 days
	Yersinia	TMP–SMX (PO) ×	Cefotaxime (IV) or
	enterocolitica	5–7 days	Doxycycline (PO) ×
			5–7 days
Traveler’s diarrhea	E.. coli	TMP–SMX (PO) ×	Azithromycin (PO) ×
		3 days	3 days
Typhoid (enteric)	Salmonella typhi	Ceftriaxone (IV) or	TMP–SMX (IV or PO)
fever		Cefotaxime (IV) ×	or Amoxicillin (PO) or
		10–14 days	Cefixime (PO) ×
			10–14 days
Antibiotic-associated	Clostridium difficile	Metronidazole	Vancomycin (PO) ×
colitis		(PO) × 7–10 days or	7–10 days
		Nitazoxanide (PO) ×
		3 days
Chronic watery	Giardia lamblia‡	Metronidazole	Tinidazole (PO) × 1
diarrhea		(PO) × 5–7 days or	dose or Furazolidone
		Nitazoxanide (PO) ×	(PO) × 7–10 days or
		3 days	Albendazole × 5–7 days
	Cryptosporidia‡	Nitazoxanide (PO) ×	Human immunoglobulin
		3 days	(PO) or bovine
			colostrum (PO) for
			immunocompromised
			hosts
Acute dysentery	E.. histolytica	Metronidazole (PO) ×	Tinidazole (PO) × 3–5
		10 days followed by	days followed by either
		either Iodoquinol	Iodoquinol (PO) × 20 days
		(PO) × 20 days or	or Paromomycin (PO) ×
		Paromomycin (PO) ×	7 days
		7 days

Chapter 7.  Pediatric Infectious Diseases and Pediatric Drug Summaries

405

Acute Diarrheal Syndromes (Gastroenteritis) (cont’d)

Subset	Usual Pathogens	Preferred Therapy†	Alternate Therapy†
	Shigella**	Ceftriaxone (IV) or	TMP–SMX (PO) or
		Azithromycin (PO) ×	Cefixime (PO) or
		5 days	Ampicillin (PO) × 5 days

†See pp. 414–422 for drug dosages.

*Therapy only indicated in child < 3 to 6 months of age, immunocompromised host, or toxic appearing child.

**Mild cases acquire no antibiotic therapy.. However, antibiotic therapy shortens durations of symptoms and by decreasing the duration of diarrhea limits potential syneral..

‡May also present as acute watery diarrhea..

Acute Gastroenteritis (Community-Acquired)

Clinical Presentation:  Typically presents with the acute onset of diarrhea with fever. . This is not an indication for antibiotic therapy unless illness is severe (≥ 6 unformed stools/day, fever ≥ 102o F, bloody stools).. Travel history regarding risk for potential E.. coli and parasitic exposures is ­important..

Diagnostic Considerations:  In the absence of blood in the stools viruses are the most common cause of acute community-acquired gastroenteritis.. Rotaviruses are the most common cause of acute gastroenteritis in 4–24 month old children.. Enteric adenoviruses, Norwalk-like virus, enteroviruses and astroviruses are common causes of gastroenteritis in older children.. Commercially available antigen tests using ELISA or latex agglutination techniques are readily available to detect rotavirus. . Testing for the other viral agents may not be as readily available.. Inflammatory changes (presence of white blood cells and/or blood) in the stool are more consistent with bacterial infection.. When requesting stool cultures, it may be necessary to order special conditions/media for the detection of yersinia or E.. coli O157..

Pitfalls:  Antimotility drugs may worsen the course of illness in children with colitis.. Empiric therapy with antibiotics may prolong the carriage of Salmonella or increase the risk for developing hemolytic uremic syndrome (HUS) with E.. coli O157 infection.. The benefit of antibiotics in treating diarrhea caused by yersinia is also unproven.. Thus, antibiotic therapy is not routinely indicated prior to culture results in most instances of mild diarrheal disease, especially as most such infections are self-limited..

Therapeutic Considerations:  As above, pending cultures in the absence of severe symptoms or dysentery antibiotics may not be indicated.. Overall, the fluoroquinolones have the most complete spectrum for pathogens causing bacterial diarrhea but are not presently approved for use in children < 18 years of age..

Prognosis:  Good.. Up to 5–10% of children with E.. coli O157 are at risk for hemolytic-uremic ­syndrome..

Giardiasis (Giardia lamblia)

Clinical Presentation:  Giardia lamblia is the most common parasite causing diarrheal illness in children.. Giardiasis may present as acute watery diarrhea with abdominal pain and bloating or as a chronic, intermittent illness with foul smelling stools, abdominal distension, and anorexia..

Diagnostic Considerations:  Trophozoites or cysts of Giardia lamblia can be identified in direct examination of infected stools with 75%–95% sensitivity on a single specimen.. Testing 3 or more stools further

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

increases sensitivity of detection.. If giardiasis is suspected with negative stool tests, examination of duodenal contents (Enteroor string test) may be helpful..

Pitfalls:  Asymptomatic infection is commonly seen in children in day care; therefore, indications to treat must take into account stool testing results and clinical findings..

Therapeutic Considerations:  Treatment failures occur commonly, and retreatment with the same initial drug is recommended.. Furazolidone is the only pediatric liquid available for treating giardiasis < 3 years of age..

Prognosis:  Good..

Cryptosporidiosis

Clinical Presentation:  Usually presents as fever, vomiting, and non-bloody, watery diarrhea.. Infection may also be asymptomatic.. More severe and chronic infection is seen in immunocompromised patients (e..g.., HIV infection).. Cryptosporidia parasite is resistant to chlorine and maybe transmitted in swimming pools.. Transmission can also occur from livestock, and a major outbreak through contamination­ of a public water supply has been reported..

Diagnostic Considerations:  Cryptosporidium cysts are detected by microscopic examination of Kinyoun-stained stool specimens using a sucrose floatation method or formalin-ethyl acetate method to concentrate oocysts. . This test is not part of routine stool ova and parasite examination and must be specifically requested.. Shedding is intermittent; therefore, 3 stool samples should be submitted for optimal detection..

Pitfalls:  The oocysts of cryptosporidium are small and may be missed by an inexperienced exam-iner.. A commercially available ELISA test is available but may have false-positive and false-negative results.. Therapeutic Considerations:  Treatment failures are frequent. . In immunocompromised hosts oral human immune globulin and bovine colostrum are beneficial.. Improvement in CD4 counts with antiretroviral­ therapy in HIV-infected patients shortens the clinical illness..

Prognosis:  Good.. Recovery may take months..

Amebiasis (Entamoeba histolytica)

Clinical Presentation:  E. . histolytica can lead to a spectrum of clinical illnesses from asymptomatic infection to acute dysentery to fulminant colitis. . Disseminated disease, primarily manifest as hepatic abscesses, can also occur.. E.. histolytica is most prevalent in developing countries and is transmitted by the fecal-oral route..

Diagnostic Considerations:  Trophozoites or cysts of E.. histolytica can be identified in stool specimens.. In more severe disease (amebic colitis, hepatic abscesses), serum antibodies can be detected..

Pitfalls:  Treatment with steroids or antimotility drugs can worsen symptoms and should not be used.. Therapeutic Considerations:  Treatment is two-staged to eliminate tissue-invading trophozoites and organisms in the intestinal lumen.. Surgical drainage of large hepatic abscesses may be beneficial..

Prognosis:  Good..

Clostridirim difficile Colitis

Clinical Presentation:  Classically occurs in a child receiving antibiotic therapy and presents as diarrhea, cramping, bloody/mucousy stools, abdominal tenderness, fever, and toxicity.. It may also present weeks after a course of antibiotics..