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Diagnostic Considerations:  C.. difficile toxin can be detected with commercially available immunoassays.. Endoscopic finding of pseudomembranous colitis is the definitive method of diagnosis although rarely indicated..

Pitfalls:  C.. difficile may be normal flora in infants < 1 year of age and probably does not cause illness in this age group.. The finding of C.. difficile toxin in an infant should not be equated with cause and additional evaluations should be perused.. Antimotility drugs may worsen symptoms and should be avoided..

Therapeutic Considerations:  Cessation of antibiotics is recommended if possible in the presence of significant C.. difficile colitis.. Patients with severe symptoms or persistent diarrhea × 2–3 days after discontinuing antibiotics should then be treated with oral metronidazole or oral vancomycin.. Up to 25% relapse after a single course; re-treatment using the same initial antibiotic is recommended.. For persistent infection alternate therapies such as nitazoxanide, rifaximin, tinidazole, oral immune globulin therapy, toxin binders or repopulating intestinal flora may be considered..

Prognosis:  Good..

Empiric Therapy of Bone and Joint Infections

Septic Arthritis

		Preferred IV	Alternate IV
Subset	Usual Pathogens	Therapy†*	Therapy†*	IV-to-PO Switch†
Newborns	S.. aureus‡	Combination	Combination	Not applicable
(≤ 3 months)	Group B	therapy with	therapy with
	streptococci	Nafcillin or	Vancomycin or
	Enterobacteriaceae	Vancomycin	Clindamycin
	N.. gonorrhoeae	plus either	plus either
		Ceftriaxone or	ceftriaxone or
		Cefotaxime*	cefotaxime or
			gentamicin or
			tobramycin*
Child	S.. aureus‡	Combination	Combination	Dicloxacillin or
(> 3 months to	Group A	therapy with	therapy with	Cephalexin or
14 years)	streptococci	Nafcillin or	Vancomycin or	Clindamycin (PO)
	S.. pneumoniae	Vancomycin	Clindamycin	after 1 week of IV
	Gram-negative	plus either	plus either	therapy*
	bacilli	Ceftriaxone or	Ceftriaxone or
	N.. meningitidis	Cefotaxime*	Cefotaxime*
	(H.. influenzae
	type b if
	unvaccinated)
	Kingella

†See pp. 414–422 for drug dosages.

*Total duration of therapy for non-gonococcal septic arthritis ≥3 weeks based on clinical response..

‡If CA-MRSA is suspected based on clinical presentation/local epidemiology, consider empiric coverage for CA-MRSA with clindamycin, TMP–SMX, doxycycline, or vancomycin pending culture results..

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Septic Arthritis (cont’d)

		Preferred IV	Alternate IV
Subset	Usual Pathogens	Therapy†*	Therapy†*	IV-to-PO Switch†
Adolescents	As above plus	Combination	If GC isolated and	GC arthritis with
(sexually	N.. gonorrhoeae	therapy with	penicillin allergy:	prompt response
active)	(typically 2 or 3	Nafcillin or	Azithromycin	to IV therapy
	joints involved)	Vancomycin		may switch to
		plus either		Cefixime to
		Ceftriaxone or		complete 7 days
		Cefotaxime*		of total therapy

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.. Taper to individual drug therapy once organism isolated and sensitivities are available..

†See pp. 414–422 for drug dosages..

*Total duration of therapy for non-gonococcal septic arthritis ≥3 weeks based on clinical response..

‡If CA-MRSA is suspected based on clinical presentation/local epidemiology, consider empiric coverage for CA-MRSA with clindamycin, TMP–SMX, doxycycline, or vancomycin pending culture results..

Clinical Presentation:  Varies with age of the child.. Presentation is often nonspecific in infants (i..e.., fever, poor feeding, tachycardia).. Physical exam findings can be subtle: asymmetrical tissue folds, unilateral swelling of an extremity, subtle changes in limb/joint position.. In older children, signs and symptoms are more localized to the involved joint.. Commonly affected joints: hips, elbows, knees..

Diagnostic Considerations:  Joint aspiration (large-bore needle) shows 50,000–250,000 WBCs/ mm3 with a marked predominance of PMNs. . Gram stain/culture of joint fluid confirm the diagnosis. . Toxic synovitis, Lyme arthritis, rheumatoid arthritis, traumatic arthritis, and sympathetic effusion from adjacent­ osteomyelitis can mimic septic arthritis on presentation, but joint fluid has fewer WBCs and cultures are negative.. Multiple joint involvement is more typical of rheumatic/Lyme disease.. In young infants, persistence of the nutrient artery can lead to osteomyelitis and septic arthritis..

Pitfalls:  Septic arthritis of the hip is an emergency concomitant condition requiring prompt joint aspiration and irrigation to minimize the risk of femoral head necrosis, which may occur within 24 hours. . Toxic synovitis of the hip, which is treated with anti-inflammatory agents and observation, typically causes less fever, pain, and leukocytosis than septic arthritis; however, at times the two can not be differentiated and aspiration of the joint is indicated. . In sexually active adolescents, consider N.. gonorrhoeae and culture aspirate appropriately..

Therapeutic Considerations:  Therapy is recommended for at least 3–4 weeks (IV followed by oral therapy), for a total antibiotic course of 4–6 weeks based on clinical response and laboratory parameters (WBC, ESR, CRP).. Intra-articular therapy is not helpful.. Empiric coverage is broader than for osteomyelitis in children..

Prognosis:  Good with prompt joint aspiration and at least 3 weeks of antibiotics..

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Acute Osteomyelitis, Osteochondritis, Diskitis

			Preferred	Alternate	IV-to-PO Switch
	Subset	Usual Pathogens	IV Therapy†	IV Therapy†	or PO Therapy†
Acute		S.. aureus§	Combination	Vancomycin	Not applicable
osteomyelitis		Gram-negative bacilli	therapy with Nafcillin	plus either
	Newborn	Group B streptococci	or Oxacillin plus	Cefotaxime or
	(0–3 months)		either Cefotaxime	Ceftriaxone ×
			or Ceftriaxone × 4–6	4–6 weeks
			weeks
> 3 months*		S.. aureus§	Nafcillin or Oxacillin or	Clindamycin	Cephalexin or
		Group A streptococci	Cefazolin ×	or Ampicillin-	Clindamycin or
		Gram-negative	4–6 weeks	sulbactam or	Cefadroxil ×
		bacteria (rare)		Vancomycin ×	4–6 weeks
		Salmonella (sickle cell		4–6 weeks
		disease)
Osteochondritis		P.. aeruginosa	Ticarcillin clavulanate ×	Piperacillin/	Ciprofloxacin** ×
		S.. aureus§	7–10 days after surgery	tazobactam or	7–10 days
			or combination	Ciprofloxacin ×	after surgery
			therapy with Nafcillin	7–10 days after
			plus Ceftazidime ×	surgery
			7–10 days after surgery
Diskitis		S.. aureus, K.. kingae	PO Therapy: Cephalexin or Cefadroxil or Clindamycin × 3–4
		Enterobacteriaceae	weeks or ESR returns to normal††
		S.. pneumoniae
		S.. epidermidis

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

†See pp. 414–422 for drug dosages.

**Not approved for children but might consider in adolescent..

*Treat only IV or IV-to-PO switch..

†† Add gram-negative coverage only if culture proven..

§If CA-MRSA is suspected based on clinical presentation/local epidemiology, consider empiric coverage for CA-MRSA with clindamycin, TMP–SMX, doxycycline, or vancomycin pending culture results..

Acute Osteomyelitis

Clinical Presentation:  Acute onset of fever and pain/decreased movement around the infected area.. Can be difficult to localize, especially in younger children.. Occurs primarily via hematogenous spread (vs.. direct inoculation) to metaphysis of long bones..

Diagnostic Considerations:  Acute phase reactants are elevated (ESR, CRP, WBC).. X-rays may not reveal osteolytic lesions for > 7 days, but soft tissue swelling and periosteal reaction may be seen as early as

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3 days.. Bone scan/MRI reveal changes in the first 24 hours, but bone scans are insensitive in neonates.. Blood cultures may be positive, especially in younger children.. Definitive diagnosis by bone aspirate for gram stain and culture, but empiric therapy is often initiated based on clinical history and the presence of an acute lytic lesion on MRI, bone scan, or x-ray..

Pitfalls:  Bony changes on x-ray may not be present initially.. It may be difficult to differentiate cellulitis from osteomyelitis, even on bone scan..

Therapeutic Considerations:  Initiate empiric therapy by IV route.. Treatment is required ≥ 4 weeks, but children with a prompt clinical response can complete therapy with high-dose oral antibiotics.. With adequate treatment, CPR and ESR normalize over 2 weeks and 4 weeks, respectively..

Prognosis:  Good with 4–6 weeks of total therapy.. Long-term growth of affected bone may be impaired..

Osteochondritis of the Foot (“Puncture Wound Osteomyelitis”)

Clinical Presentation:  Tenderness, erythema, and swelling several days to weeks after a nail puncture wound through a sneaker/tennis shoe (Pseudomonas found in foam layer between sole and lining of shoe).. Fever and other systemic complaints are rare.. Develops in 1–2% of puncture wounds of foot..

Diagnostic Considerations:  P. . aeruginosa is the primary pathogen, although infection with S.. aureus is also a concern..

Pitfalls:  Antibiotics with surgical debridement of necrotic cartilage..

Therapeutic Considerations:  With prompt debridement, 7–10 days of antibiotic therapy is usually sufficient..

Prognosis:  Good with debridement and antibiotics..

Diskitis

Clinical Presentation:  Typically involves the lumbar region and occurs in children < 6 years old.. Presents with gradual onset (over weeks) of irritability and refusal to walk. . Fever is low-grade or absent.. Older children may be able to localize pain to back, hip, or abdomen.. Pain is exacerbated by motion of the spine and can be localized by percussion of the vertebral bodies..

Diagnostic Considerations:  ESR is elevated, but WBC count is normal.. X-rays are usually ­normal initially, but later reveal disk space narrowing and sclerosis of the vertebrae.. Increased disk space uptake can be seen on bone scan.. MRI is very sensitive for assessing disk space involvement..

Therapeutic Considerations:  Diskitis is probably a low-grade bacterial infection, but the role of antibiotic therapy is unclear.. Bed rest and anti-inflammatory medications are the mainstays of treatment.. Immobilization may be required for severe cases.. Oral antibiotics are given for 3–4 weeks or until the ESR returns to normal..

Pitfalls:  Difficult to isolate an organism, even with needle aspiration of disk space. . S. . aureus is the most common pathogen, but diskitis can also be caused by coagulase-negative staphylococcus, K.. kingae, coliforms, S.. pneumoniae..

Prognosis:  Fusion of involved vertebrae may occur as the infection resolves.. Otherwise, outcome is generally good..