Infectious Diseases Flashcards
UTI rate in febrile uncircumcised boys?
UTI rate in uncircumcised febrile boys <3 mo was 20.7%
UTI rate in febrile circumcised boys < 3 months?
2.4% if circumcised
After what age is it unusual for boys to have their first UTI?
3 years
Most positive urine Cx in infants >2 mo with bronchiolitis are due to what?
Contamination or aSSx bacteruria
What methods can you collect a urine sample?
A midstream urine sample for urinalysis and culture in toilet-trained children
Otherwise catheter or by suprapubic aspirate, or clean catch
bagged urine sample may be used for urinalysis but should not be used for urine culture
negative bag culture rules out a UTI but a positive result is not useful
What on a urinalysis is highly sensitive for a UTI?
Urinalysis
o nitrite – measures conversion of dietary nitrate to nitrite by Gram-negative bacteria
- positive nitrite result means UTI is likely (very sensitive)
- BUT may be falsely positive in Gram positive organisms
What count of a leukocyte esterase is positive for a UTI on urinalysis?
leukocyte esterase is a measure of pyuria and may be falsely negative
- absence of pyuria does not exclude UTI
- 10 white blood cells per microliter is positive for UTI
What are the minimum colony counts for a positive UTI?
Minimum colony counts for UTI Dx:
o Clean catch (midstream) ≥ 105 CFU/ml or ≥ 108 CFU/L
o In and out catheter ≥ 5 x 104 CFU/ml or ≥ 5 x 107 CFU/L
o Suprapubic aspiration: any growth
What are the common organisms causing UTIs?
Common organisms: o Escherichia coli o Klebsiella pneumoniae o Enterobacter species o Citrobacter species o Serratia species o Staphylococcus saprophyticus (adolescent females only)
When do you need to order renal function in the setting of a UTI?
• Renal function only if it is a complicated UTI or aminoglycosides for > 48 hours
When do you order a blood culture in the setting of a UTI?
• Blood Cx is not needed unless hemodynamically unstable/sepsis, or Dx UTI unclear
How do you treat (duration and route) an uncomplicated UTI?
Management
o Antibiotic treatment for 7-10 days is recommended for febrile UTI
o PO when the child is not seriously ill and is likely to tolerate every dose
Caution if 2-3 months old as safety data for PO only (no IV) is lacking
Do you treat pyelonephritis with PO or IV antibiotics?
o No convincing evidence that IV abx are superior to PO for 10-14 d for pyelo
Management of cystitis?
Cystitis: UTI without fever is usually a lower tract infection (cystitis)
mainly in postpubertal girls and presents as dysuria and frequency
Rx 2-4 day course PO that covers E coli
What are the features of a complicated UTI?
Features concerning for complicated UTI – order RBUS to r/o obs or abscess and switch to IV
o Hemodynamically unstable
o elevated serum creatinine level at any time
o bladder or abdominal mass
o poor urine flow
o not improving clinically within 24 h
o fever is not trending downward within 48 h of starting appropriate antibiotics
When and why would you order a RBUS in the context of a UTI?
renal/bladder ultrasound (RBUS)
Children <2 yo after their first febrile UTI, within 2 weeks
Can detect hydronephrosis – usually occurs with high grade (IV or V) VUR
When and why would you order a VCUG in the setting of a UTI?
o radiographic (voiding cystourethrogram)
Not required for children with a first UTI unless the renal/bladder ultrasound shows vesicoureteral reflux, selected renal anomalies, or obstructive uropathy
VCUG is indicated for children <2 yo with a second well-documented UTI
Best test to dx VUR, assessing the degree of VUR , and anatomy of male urethra
Risks: expense, exposure to radiation, the risk of causing a UTI, discomfort
When do you order a DMSA scan?
o radioisotope (dimercaptosuccinic acid [DMSA]) techniques Indication: dx acute pyelonephritis or identify renal scars primarily useful when the diagnosis of acute UTI or of repeated UTIs is in doubt
What are some antibiotic options for UTIs?
• Antibiotic Options and Doses
o Ampicillin 200 mg/kg IV/day (divided every 6 h)
o Ceftriaxone 50–75 mg/kg IV/IM every 24 h
o Cefotaxime 150 mg/kg/day IV (divided every 6 h or 8 h)
o Gentamicin 5–7.5 mg/kg IV/IM once per day
o Tobramycin 5–7.5 mg/kg once per day
o Amoxil 50 mg/kg/day (divided in three doses)
o Amoxicillin/clavulanate (7:1 formulation) 40 mg/kg/day (divided in three doses)
o Co-trimoxazole 8 mg/kg/day of the trimethoprim component, divided in two doses (0.5 mL/kg/dose)
o Cefixime 8 mg/kg/day (given as a single dose)
o Cefprozil 30 mg/kg/day (divided in two doses)
o Cephalexin 50 mg/kg/day (divided in four doses)
o Ciprofloxacin* 30 mg/g/day (divided in two doses)
What is the incidence of UTI in children?
•UTIs are common in infants & young children: 8% of girls and 2% of boys by 7 yo
o with a recurrence rate of 10% to 30%
Who gets prophylactic antibiotics for UTIs?
Antibiotic prophylaxis is no longer routinely recommended after a UTI but may still be considered when a child has grade IV or V VUR, or a significant urological anomaly
o Abx no longer than 3-6 months, then reassess
What antibiotic is used for prophylaxis?
Trimethoprim/sulfamethoxazole or nitrofurantoin
o traditionally, ¼ to 1/3rd of the daily total treatment dose is given once per day
o no evidence for alternating abx choice monthly
Why are broad spectrum antibiotics not used for prophylaxis?
broader-spectrum agents for prophylaxis (cefixime or ciprofloxacin) often results in a UTI with an organism that is resistant to any remaining oral options for therapy
What is the life cycle of lice?
o Lice live 3-4 weeks if untreated, but the continue to reproduce/create turnover
o adult head lice can survive for only 1 to 2 days away from the human host
o eggs can survive away from the host for up to 3 days
How do you diagnose a lice infestation?
o misdiagnosis is common – need to see LIVE louse
o SSx itching, but some asymptomatic for weeks
How are lice transmitted?
• Transmission - direct head-to-head (hair-to-hair) contact
o Transmission w/ fomites is debated; pets are NOT a vector, carpet/pillow cases unlikely
How do you treat a lice infestations?
o topical insecticides
pyrethrins – apply to dry hair/scalp, rest 10 mins, wash out, repeat in 7-10 days
• may causing itching/burning to scalp, allergic reaction is rare
permethrin 1% - shampoo hair, apply cream, rest 10 mins, rinse, repeat in 7 d
• may causing itching/burning to scalp, no allergic reaction
Toxicity
• pyrethrins and permethrin have minimal percutaneous absorption and favourable safety profiles, but avoid sitting child in bath to rinse hair
• Topical steroid or antihistamine may help with side effects
• Lindane is not used because of the potential risks for neurotoxicity and bone marrow suppression following percutaneous absorption
Resistance is increasing
• If 2 permethrin doses 7 days apart do not eradicate live lice, consider resistance and use another medication class; note that the treatment can cause itching and is NOT a SSx of re-infestation (need live louse)
o Topical non-insecticidal
Isopropyl myristate + ST-cyclomethicone solution for ≥ 4 yo, treat once, then repeat in 1 week
Dimeticone solution for ≥ 2 yo, treat once, then repeat in 8-10 days
Benzyl alcohol lotion 5% for > 6 months, repeat in 9 days, expensive
o Other treatments
No evidence for septra
Ivermectin (special access) is potentially neurotoxic, do not use < 15 kg
Wet combing has little evidence as primary treatment
Thick creams/oils, tea tree oil do not have enough evidence of efficacy
When can kids return to school with lice?
o Excluding children with nits or live lice from school or child care has no rational medical basis and is not recommended (just avoid close head to head activities)
o Notify parents of children in the same classroom of head lice case, and review that it is not a sign of disease or poor hygiene
Environmental cleaning for children with lice?
• Environmental Decomtamination
o environmental cleaning is not warranted
o At most, washing items in close/prolonged contact with the head (hats, pillowcases, brushes) may be warranted
wash in hot water (≥66°C) and dry them in a hot dryer for 15 minutes
storing any item in a sealed plastic bag for 2 weeks will kill both live lice and nits
Acute Osteomyelitis occurs within what time frame?
o Acute osteomyelitis is < 2 weeks
How long before you can consider it a chronic osteomyelitis?
o Chronic osteomyelitis is > 1 month with avascular bone alone (sequestrum) or surrounded by new bone (involucrum) is present (Brodies’ abscess)
When to suspect osteomyelitis vs septic arthritis?
• Acute hematogenous osteomyelitis and septic arthritis are not uncommon infections in children and should be considered as part of the differential diagnosis of limb pain and pseudoparalysis
How do most bone infections occur?
o Most bone infections arise secondary to hematogenous seeding of bacteria into bone
What are the most common bugs in osteomyelitis and septic arthritis?
Most common pathogens are Staphylococcus aureus and Kingella kingae (resp bugs)
Others: Streptococcus pneumoniae and Streptococcus pyogenes
Sickle cell anemia are prone to Salmonella
How does Osteomyelitis and septic arthritis present?
Clinical Presentation
o PAIN can be the only symptom
o Often with pseudoparalysis or limping
o Fever may or may not be present
o Most common site is the metaphysis in long tubular bones: femur, tibia, or humerus
o Always consider osteomyelitis in S aureus bacteremia with no source
o SA alone: specific swelling of the joint, joint effusion, pain on movement of the joint
Most common sites for osteomyelitis infection?
o Most common site is the metaphysis in long tubular bones: femur, tibia, or humerus
How would transient synovitis of the hip present?
Transient synovitis of hip
Usual age is 4–10 years Hip pain and new limping, +/- fever \+/- weight-bear Hx URTI in the preceding 2 weeks Nontoxic appearance CRP is usually < 20 mg/L. Gradually improves over several days, may be hastened by NSAIDs.
How would fracture or trauma present?
Fracture or trauma (Toddler’s #)
Acute onset of pain while active or after a known trauma
Localized pain, hematoma, bruising, swelling, no fever
How would Lyme Arthritis present?
Hx Lyme area within past 12 month
Usually monoarthritis of knee (occasionally hip or other large joints) without constitutional SSx
Much less painful than SA, will weight bear.
Baker’s cyst may be present.
CRP is < 40 mg/L.
How would cellulitis present?
Rapid development of swelling, redness and pain over hours-day.
Erythema usually precedes the development of pain. Area of erythema, warmth, swelling, tenderness.
Usually more extensive (not focal).
Can have lymphangitis.
Often normal ROM.
How would CRMO present?
Chronic recurrent multifocal
osteomyelitis (CRMO) (first
presentation)
Insidious onset of bone pain. Often metaphysis and epiphysis, and unusual sites (clavicle, jaw, scapula). May have fever and malaise. Pain is often worse at night. Dx based on a relapsing course. CXR intense sclerosis with healing. \+/- tenderness, warmth, swelling \+/- fever, malaise, weight loss
May have palmoplantar pustulosis,
psoriasis or other dermatologic
conditions
How would a malignancy present (hematologic)
Constitutional SSx, arthralgia, limb or muscle pain.
Metaphyseal lucencies and periosteal reactions, as with AO.
No localized pain to palpation but may have joint swelling and evidence of mild synovitis.
How would a bone neoplasm present?
Bone neoplastic lesion (benign or
malignant, including histiocytosis)
Typically, gradual onset in the diaphysis or in flat bones.
Pain is often worse at night and
with refusal to weight-bear.
Pain
May have a palpable soft tissue or bony mass.
How would JIA present?
Typically gradual onset (weeks).
Oligoarthritic (< 4 joints) or poly.
More likely to be symmetric, often with extra-articular symptoms.
Often, symptoms are less severe compared with bacterial SA.
May have contracture if subacute.
May need synovial fluid analysis to exclude SA (if mono appearance).
Fewer white blood cells in joint fluid compared with SA.
How would SLE present?
Constitutional SSx (fever, wt loss, fatigue, anorexia, diffuse LAD).
Cutaneous symptoms (rash, ulcers) are also common.
Arthritis is usually milder than SA.
May have hematologic (anemia, leukopenia) and U/A abnormalities.
How would reactive arthritis present?
Oligoarthritis of larger joints, usually 2-3 weeks after a preceeding GI or GU infection.
May have ocular and urinary SSx.
Arthritis is more subacute and less severe compared with bacterial SA
How would post strep reactive arthritis present?
Acute onset of symmetrical or asymmetrical arthritis.
Usually polyarticular, nonmigratory and can be persistent or recurrent.
Usually 3–14 days after strep.
May have extra-articular manifestations (vasculitis, GN).
Acute rheumatic fever: joints are Tender/swollen with characteristic migratory feature and exquisite
response to NSAIDs or ASA.
How do you diagnose Osteomyelitis or septic arthritis?
o Blood Cx before abx and while febrile is important as AO and SA are hematogenous
Take larger volume to increase yield; repeat in 24-48 hrs if positive
o Pathological assessment of a bone specimen is the gold standard for the diagnosis of AO
o MRI with gadolinium enhancement – most sensitive and specific noninvasive test for AO
bone marrow edema can be seen
do not need MRI if clinical dx is supported by labs and response to treatment
o Xray – classic lytic lesions and localized periosteal lifting only seen 7-21 days after onset
Xrays may be normal in acute phase, but r/o other pathology (neoplasm, #)
o U/S – fluid in subperiosteal areas and soft tissues in OA, or fluid in the joint space in SA
o Bone scan – less specific than MRI, but may be useful if multifocal presentation
o CT – if MRI or bone scan are not available
o CRP – if normal in the first new days, unlikely to be SA or osteo (better sens than ESR)
o CBC – may have leukocytosis
o Diagnose SA with joint aspiration before abx! If not possible, consider U/S or MRI
o Blood, bone and joint fluid cultures commonly test negative
How do you manage osteomyelitis or septic arthritis?
o Children with septic arthritis should be evaluated promptly by ortho for aspiration and possible debridement of concomitant osteomyelitis
o Cefazolin 100-150 mg/kg/day divided q6-8 hours
Some widen coverage to include Hib with cefuroxime
Note that kingae is predictably resistant to clindamycin, vanco, and cloxacillin
o Step down to PO abx (cephalexin) when there is clinically improved and decreasing CRP
Cloxacillin can be used, but it has poor palatability
Use clinda, septra, or linezolid for MRSA
o Antibiotics for 3 to 4 weeks total – d/c when clinically well and CRP normalized
Follow up xray not needed unless near growth plate or not responding to Rx
What procedures require IE prophylaxis?
Prophylaxis for all dental procedures that involve the manipulation of gingival tissue, the periapical region of teeth, perforation of the oral mucosa, or incision or biopsy of the respiratory mucosa (biopsy, T+A)
o Not for routine orthodontic care or anesthetic injection in healthy tissue
o Not routine for GI or GU procedures; may add enterococci to pre-op abx coverage
What cardiac conditions is IE prophylaxis recommended for?
Prophylaxis is recommended for:
o Prosthetic cardiac valve or prosthetic material used for valve repair
o Previous IE
o Congenital heart disease
Unrepaired cyanotic CHD, including palliative shunts and conduits
Completely repaired defect with prosthetic material, in first 6 months post-op
Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibit endothelialization)
o Cardiac transplant recipients who develop cardiac valvulopathy
o Rheumatic heart disease if prosthetic valves or prosthetic material used in valve repair
Which CHD is IE prophylaxis NOT recommended for?
• No prophylaxis for:
o ASD, VSD, PDA, MVP, pulmonic stenosis, calcified AS
o Previous Kawasaki disease
o Hypertrophic cardiomyopathy
o Previous coronary artery bypass graft surgery
o Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators
o Bicuspid aortic valves
o Coarctation of the aorta
What do you give for endocarditis prophylaxis?
Prophylactic Principles
o Antibiotics given in a single dose before the procedure
If not given before, give within 2 hours post procedure
o PO: Amoxil 50 mg/kg is preferred
Second line: cephalexin or another first-generation cephalosporin, clindamycin, azithromycin, or clarithromycin
o IV: ampicillin, ceftriaxone, or cefazolin
Most common bugs causing meningitis in children > 1 month
• Most common in healthy children > 1 mo: S pneumoniae and N meningitidis
o but E coli and GBS should be considered up to 3 mo
Contraindications for LP?
Contraindications: coagulopathy, cutaneous lesions at site, signs of herniation (papilledema, focal neuro sign, dec LOC), or an unstable clinical status
Do CT or MRI to rule out herniation risk (CNS lesion)
o Do not delay antibiotics for LP or imaging, but do blood Cx first
Blood Cx volumes: 2 ml if > 4 kg, up to 20 ml if > 26 kg to improve yield
Complications of meningitis?
• Complications
o SIADH
o Raised ICP
Management of ?meningitis in >1 month
o Cephalosporin is first line (ceftriaxone or cefotaxime) due to PCN resistance
Ceftriaxone 100 mg/kg/day divided BID (max 4 g/day)
Cefotzxime 300 mg/kg/day divided QID
o Add vanco (60 mg/kg/day) for cephalosporin-resistant S pneumoniae, pending Cx result
o Add ampicillin (300 mg/kg/day) to cover Listeria if immunocompromised
o Switch to ampicillin or PenG if susceptible
o Neonates with GBS: add gentamicin x5-7 days until CSF sterility confirmed
o Meropenem if unable to use a 3rd gen cephalosporin
How long to you treat for meningitis?
o Duration depends on organisms: GBS 14-21 days Strep pneumo 10-14 days Hib 7-10 days Neisseria 5-7 days
Why do we give steroids for HiB meningitis?
Steroid Adjuvant Therapy for Hib meningitis
o There is a reduction in severe hearing loss if corticosteroids are given just before or within 2 h of antimicrobials
When do you have to repeat a CSF?
• Repeat CSF recommended by some if: GBS or gram negative pathogen
When do we do neuroimaging for meningitis?
• CNS imaging if CSF fails to clear, neuro SSx, or complications arise
What is neonatal ophthalmia?
• Neonatal ophthalmia is conjunctivitis occurring within the first 4 weeks of life
What are the most common organisms causing neonatal opthalmia?
o Chlamydia is more common than gonorrhea (< 1%)
o Other major organisms: Staph, Strep, Haemophilus, other Gram-negative bacteria
o Viruses are least common: herpes simplex, adenovirus, enteroviruses
o r/o blocked tear duct and irritant
Do we recommend neonatal ocular prophylaxis?
• Neonatal ocular prophylaxis with erythromycin is not be routinely recommended
o Growing resistance to erythromycin
o Povidone-iodine or gentamicin ointment should not be used because of high rates of adverse topical effects
o Silver nitrate is no longer used, except in high prevalence areas (outside Canada)
When do we screen pregnant women for gonorrhoea and chlamydia?
• Screening and treatment of pregnant women:
o Screen all pregnant women for N gonorrhoeae and C trachomatis at the first prenatal
o Test after treatment to ensure therapeutic success and test again in T3 or delivery
o Partners should also be treated
o If negative, but at risk for acquiring infection later in pregnancy, screen again in T3
o Pregnant women who were not screened during pregnancy should be screened for N gonorrhoeae and C trachomatis at delivery, using the most rapid tests available
How do you manage newborns exposed to N gonorrhoea?
o Infants born to untreated mothers have up to 30-50% risk of gonorrhea ophthalmia
o If the mother’s test results are not available at discharge, the mother must be advised to watch for eye discharge in the first week of life and to present to a HCP if unwell
Consider ceftriaxone IM x 1 before d/c if maternal reliability is low
o Infants born to women with untreated N gonorrhoeae at delivery (SVD or C/S), should be tested and treated immediately without waiting for test results
Infants exposed to N gonorrhoeae who appear to be healthy at birth:
• conjunctival culture for N gonorrhoeae
• give single dose of ceftriaxone (50 mg/kg to a max of 125 mg IV or IM)
If the exposed infant is unwell in any way:
• Conjunctival, blood, and CSF cultures
• Consult peds ID
What are the complications of neonatal gonorrhoea?
Complications: corneal ulceration, globe perforation, permanent visual impairment
What are the complications of ceftriaxone in newborns?
o Biliary stasis from ceftriaxone is not a risk with a single dose
How do we manage newborns exposed to C trachomatis?
• Managing newborns exposed to C trachomatis:
o Infants born to women with untreated chlamydia at delivery have a 50% risk of acquiring chlamydia, a 30-50% risk of developing neonatal conjunctivitis, and a 10-20% risk of developing chlamydia pneumonia
o Ocular prophylaxis is not effective in preventing chlamydial conjunctivitis
o Infants born to mothers with an untreated chlamydia should be closely monitored for conjunctivitis, pneumonitis) and treated if infection occurs
o Routine cultures should not be performed on asymptomatic infants
o Prophylaxis of exposed newborns is not recommended because of the association of PO macrolides with pyloric stenosis, but may be considered if f/u cannot be guaranteed
What is the main side effect of macrolides in infants?
Pyloric Stenosis
What are some common illnesses where overuse of antibiotics is commonly seen?
Common overuse: URTIs, chronic serous otitis media, ‘bronchitis’, and pharyngitis
What are some ways antimicrobial stewardship can be optimized with regards to dosing medications?
ALWAYS use the correct weight-based dose and optimize the frequency and duration of the antibiotic to achieve maximal benefit from therapy; most scrips should be 5-7 days
o Prescribers should always use the higher end of the recommended dose range for a specific infection to treat children with normal kidney and liver function
o While BID can be used for AOM, more serious infections, such as pneumonia, cellulitis, cervical adenitis, sinusitis or abscess, give TID or QID for optimal time dependent killing
What are the shortest duration of antibiotics for common infections?
o penicillin therapy for streptococcal pharyngitis is still 10 days, but generally use the shortest duration possible (PNA 7 days, AOM 5 days)
How do we treat most skin infections?
• Most skin and soft tissue infections are due to S aureus or GAS and will respond to narrow-spectrum antibiotics such as cephalexin
What do you treat staph aureus with?
• Staph aureus – cloxacillin (if the child can swallow pills) or cephalexin
Treat lesions that are MRSA?
high risk for MRSA and the lesions are typical: drainage alone may work and/or trimethoprim-sulfamethoxazole orally, or vanco IV for severe infection
o MRSA isolated from nasal or rectal swabs should not prompt routine decolonization
when is antibiotic prophylaxis indicated?
• Antibiotic prophylaxis is indicated in specific settings such as defined close contacts of:
o Invasive meningococcal
o group A streptococcal
o Haemophilus influenzae type b
how is c diff transmitted?
o Person-to-person spread by the fecal-oral route is the primary mode of transmission
what is the incubation period of cdiff?
o Incubation period is 2-3 days
o Children are more commonly asymptomatic carriers compared to adults
whats increases your risk of c diff infection???
o Almost all antibiotics (including Sx prophylaxis) have caused C diff infections
o humoral immune response is important in influencing the risk for CDI
Hypogammaglobulinemia is associated with an increased risk for CDI
o Children with heme malignancies, HSCT, neutropenia, IBD, Hirshprungs are higher risk
How does C diff present withhold, moderate, severe and complicated infections?
o Most have a history of recent antibiotics or antineoplastic agents (within 3 months)
o Asymptomatic carriers
o Watery diarrhea, low grade fever, abdo pain
Mild < 4 abnormal BM/day
Moderate > 4
Severe > 4/day and systemically unwell with fevers/rigors
• Complicated: hypotension, shock, peritonitis, ileus or megacolon
• Stools may become bloody
o Pseudomembranous colitis – can be complicated and result in perforation
How do you diagnose C Diff?
Diagnostic Tests
o Stool for C diff toxins (not culture alone!)– but only do if watery diarrhea present
o PCR
o The enzyme immunoassay (EIA) for glutamate dehydrogenase (GDH), which is present in almost all strains of C difficile, including strains that do not produce toxin
o EIA for toxins A and B
o Cell cytotoxin assay – cytotoxicity of stool for human foreskin fibroblast cells ($$$)
o Molecular assays based on nucleic acid amplification tests (NAAT)
o Do NOT retest stool when symptoms resolve!
Prevention of C diff infections
Prevention o Hand hygiene o Contact precautions until diarrhea free x 48 hours o Antibiotic stewardship o Role of probiotics is unclear
Management of C diff infections
o Mild – d/c antibiotic, follow up
o Moderate or mild not improving with d/c abx
PO metronidazole 30 mg/kg/day divided QID x 10-14 days (max 2 g/day)
o Severe
PO vancomycin 40 mg/kg/day divided QID x 10-14 days (max 500 mg/day)
If complicated: PO vancomycin 40 mg/kg/day PLUS IV metronidazole 30 mg/kg/day, both divided QID x 10-14 days
• If complete ileus, consider rectal instillation of vanco; max 2 g/day
o Recurrences occur in 15-35% of cases
First recurrence – treat same as previous episode
Second recurrence – vanco in a tapered/pulsed regimen over several weeks
• Neurotoxicity could occur with chronic flagyl
• Treatment and testing is not recommended in infants, as C diff is rare < 12 mo
Is salmonella reportable to public health?
yes
What are the two types of salmonella infection?
o two distinct types of Salmonella infection are non-typhoidal (NTS) and typhoidal
only S Typhi and S Paratyphi cause typhoid fever (also known as enteric fever)
How are non typhoidal salmonella infections transmitted?
Non-typhoidal Salmonella infections
transmitted by contaminated food or water or contact with animals (reptiles)
• poultry, eggs, dairy, ground beef, produce
incubation period is typically 12-48 h but can be up to 7 days
How are typhoidal salmonella infections transmitted
o Typhoid/paratyphoid fever
Humans are the primary hosts; usually acquired in Asia (and less commonly in Africa) from water or food contaminated with feces from a carrier or from direct person-to-person spread
incubation period is usually 7 to 14 days (range 3 to 60 days)
How does non typhoidal salmonella infections present?
Non-typhoidal
Asymptomatic infection: Common
Gastro: N/V, non-bloody diarrhea (3-7 days) +/− fever
GI bleed: rare
Bacteremia (disseminated): < 8% of cases, shock is rare
CNS Meningitis or brain abscess mainly occur in the first year of life
Osteomyelitis or Septic Arthritis: Mostly in sickle cell disease
o NTS: non-bloody diarrhea, with or without vomiting and fever
How does typhoidal salmonella infection present?
Gastro: Abdo pain, constipation with Hx recent diarrhea
GI bleed: 10%
Bacteremia: 80% of cases, can progress to shock
Meningitis or brain abscess mainly occur in the first year of life
Osteomyelitis or septic arthritis: rare
o Typhoid/paratyphoid fever is an invasive infection that manifests as bacteremia and can progress to sepsis and multi-organ failure
Can present with non specific SSx +/- macular rash (rose spots) on abdo
How do you diagnose non typhoidal salmonella?
Diagnosis
o Non-typhoidal – stool culture
Also blood Cx if < 6 mo, febrile, or, immunocompromised
How do you diagnose typhoidal salmonella?
o Typhoidal – blood culture
For all children with fever NYD with travel history
Stool Cx only positive in 30% (GI infection has resolved in most by presentation)
How do you treat non typhoidal salmonella infections?
o Antibiotics do not decrease the severity or duration of diarrhea and may increase the incidence of NTS carriage, so they should only be used with suspected or
How do you treat typhoidal salmonella infections?
o Typhoid/paratyphoid – ceftriaxone
switch to PO antibiotics (azithromycin x 7d) is possible when blood Cx clears
other PO options: cipro, cefixime, amoxil, TMP-SMX – all need up to 14 days
o Relapse happens in up to 17% of cases
o Food handlers, health care workers and diapered children must have 2-3 negative stool tests 24 h apart over a variable number of days following completion of antibiotics before returning to work or to child care
Urine cultures may be required if patients have been in an area endemic for schistosomiasis, because Salmonella-Schistosoma binding promotes long-term survival of S Tyhpi or S Paratyphi, with intermittent bacteriuria
How do you prevent salmonella infections?
• Prevention
o Patients with diarrhea should be considered infectious; do not work with food prep etc
o Safe food handling and pet/animal handling
o Do not allow reptiles in kitchen or bathtub
o Vaccinate all children ≥ 2 yo travelling to South Asia (Afghanistan, Bangladesh, Bhutan, India, Nepal, Maldives, Pakistan and Sri Lanka)
Oral live vaccine or IM inactivated vaccine – approved for 2 yo+, or 5 yo
What is acute otitis external?
AOE – diffuse inflammation of the external ear canal, commonly associated with swimming
o prolonged ear canal wetness predisposes to impaired skin integrity and infection
What are the risk factors for acute otitis externa?
• Risk Factors for AOE o swimming o trauma o foreign body in the ear o hearing aid o certain dermatological conditions o chronic otorrhea o wearing tight head scarves o immunocompromised
• Chronic suppurative otitis media or AOM with t tubes or a perf can cause acute otitis externa
What are the most common pathogens of AOE?
• Pseudomonas aeruginosa and Staphylococcus aureus are MOST COMMON
o Many are polymicrobial
o Less commonly gram negative, rarely aspergillus or candida
What are the preventative measures for AOE?
• Preventative measures are controversial (most are ways to keep ear dry)
What is the clinical presentation of AOE?
• Clinical Presentation
o otalgia, itching, or fullness
with or without hearing loss, or ear canal pain when chewing
most have otorrhea (drainage)
o tenderness of the tragus when pushed and of the pinna when pulled
o canal is edematous and erythematous; may be cellulitis or chondritis of the pinna
Diagnosis of AOE?
o Rapid onset (generally within 48 h) in the past 3 weeks
AND
o SSx ear canal inflammation: otalgia, itching, or fullness +/- hearing loss or jaw pain
AND
o Signs of ear canal inflammation, including tenderness of the tragus and/or pinna
OR diffuse ear canal edema and/or erythema; with or without otorrhea, regional lymphadenitis, TM erythema, or cellulitis of the pinna and adjacent skin
*Note that swabs should only be taken in severe or refractory cases as they will likely reflect flora or colonizing organisms
Management of AOE
o Topical antibiotic with or without topical steroids for 7-10 days
If severe, use systemic abx to cover S aureus and Pseudomonas
Improvement should be seen in 2-3 days, but up to 6 days for resolution
• Nonresponse: Rx adherence, obstruction, FB, fungal, viral, dermatitis etc
o Antibiotic Options – do not use in a non-intact TM
Polysporin or Neosporin ear drops (Polymyxin B sulphate)
Cortisporin (Neomycin sulphate – polymyxin B sulfate + hydrocortisone)
Sofracort (Framycetin sulfate – gramicidin – dexamethasone)
Ciprodex (cipro - dex) 4 drops BID x 7 days
Garasone or Garamycin (gentamicin formulas)
o Treat pain: acetaminophen, NSAIDs, PO opioids
o May use an expandable ear wick to decrease edema if view is occluded for Rx delivery
o Ototoxic topical agents such as gentamicin or neomycin should not be used in the presence of t tubes or a perforated TM because there is concern for ototoxicity
What is malignant AOE?
• Malignant Otitis Externa
o invasive infection of the cartilage and bone of the canal and external ear may present with facial nerve palsy and pain
What are risk factors for malignant AOE?
o Risk factors: immunodeficiency or insulin dependent diabetes
How do you diagnose malignant AOE?
o CT or MRI to diagnose
How do you treat malignant AOE?
o Management: aggressive debridement with systemic abx targeted at P aeruginosa
What is the pathogenesis of AOM in children?
o Mucocilliary clearance mechanisms in the eustachian tube ventilate and drain fluid away from the middle ear; ET dysfn or obstruction due to a viral infection or other causes of mucosal inflammation can impair this mechanism. The lack of middle ear drainage leads to fluid stasis and, if the fluid is colonized with bacterial/viral pathogens, causes AOM
Children have shorter and more horizontal ET than adults
What are the risk factors for AOM in children?
o young age
o frequent contact with other children
o orofacial abnormalities (such as cleft palate)
o household crowding
o exposure to cigarette smoke
o pacifier use
o shorter duration of breastfeeding
o prolonged bottle-feeding while lying down
o family history of otitis media
o First Nations or Inuit ethnicity
o lower levels of secretory immunoglobulin A or persistent biofilms in the middle ear
What bugs cause AOM most commonly
• Organisms: S pneumoniae, H influenzae, Moraxella catarrhalis and (less commonly) GAS
How do you diagnose AOM?
o Middle ear effusion is necessary minimal criteria for dx of AOM
Decreased mobility with pneumatic otoscope
loss of bony landmarks or the presence of an air-fluid level
o Acute onset of symptoms such as otalgia (nonspecific SSx in nonverbal children), signs of a middle ear effusion associated with inflammation of the middle ear (TM that is bulging and, usually, very erythematous or hemorrhagic, and yellow or cloudy in colour) or a TM that has ruptured
o Bulging tympanic membrane, especially if yellow or hemorrhagic, has a high sensitivity for AOM that is likely to be bacterial and is a major diagnostic criterion for AOM
Perforation of the tympanic membrane with purulent discharge similarly indicates a bacterial cause
o Important to differentiate from otitis media with effusion (OME)
Middle ear effusion, however, in contrast to AOM, signs of acute inflammation of the middle ear are absent
What are some complications of AOM?
• Complications
o acute mastoiditis is the most common
o acute facial (CN VII) nerve palsy – associated with temporal bone inflammation
o sixth cranial nerve palsy (failure of ipsilateral eye abduction) due to petrous bone inflammation or infection (Gradenigo’s syndrome)
o labyrinthitis – infection spreads to the cochlear space
o venous sinus thrombosis of the transverse, lateral or sigmoid venous sinuses
o meningitis
Management of AOM?
• Management
o Viral or less virulent pathogens (Moraxella and some H influ) resolve without Rx
o For healthy children ≥6 mo who have mild illness, may watch for 48 hr if f/u possible:
reassess the child within 24 h to 48 h to document the clinical course; OR
caregiver can return if the child does not improve or worsens within 48 h; OR
provide an antimicrobial prescription to be filled if the child does not improve
o Children with a bulging TM who are febrile (≥39°C) and mod-severely systemically ill, or who have severe otalgia, or who have been significantly ill for 48 h should get antibiotics
SSx should improve in 24 hours and resolve by 2-3 days
o Important to provide advice about analgesia
o Middle ear effusions may persist for months, despite clinical/bacteriological resolution
Antibiotic choice for AOM?
Amoxicillin – S pneumo is most common, rarely resistant, and it also covers GAS
o M catarrhali and some strains of H influ are often amoxil resistant but they are less common and more likely to resolve on their own
o 5 days for children ≥2 yo with uncomplicated AOM
o 10 days for children < 2 yo, or with perforated TM, or recurrent AOM
o To achieve adequate middle ear levels, chose one of:
75-90 mg/kg/day divided BID
45-60 mg/kg/day divided TID
• Indications for Other Antibiotics
o AOM with purulent conjunctivitis (otitis-conjunctivitis syndrome): H influenzae and M catarrhalis are common pathogens
beta-lactamase inhibitor-amoxicillin combination (amoxicillin-clavulanate) or a second-generation cephalosporin (cefuroxime-axetil)
• Amox-clav
o ≤35 kg: 45-60 mg/kg/day divided TID x 10 days
Specify 400 mg/5 mL suspension of 7:1 formulation
o >35 kg: 500 mg PO TID x 10 days
• Cefuroxime-axetil 30 mg/kg/day divided BID or TID
• Ceftriaxone 50 mg/kg IM daily x 3 days
o Amox clav if child has received Amoxil in previous 30 days
o Allergy – cefprozil or cefuroxime-axetil if non life threatening
macrolide/azalide (clarithromycin or azithromycin) or clindamycin if anaphylactic
Is Invasive GAS reportable to public health?
• Incidence of IGAS infections has increased in Canada over the past decade
• IGAS is reportable in all provinces/territories to the Public Health Agency of Canada
o Report if severe IGAS (presentations below)
o Non-severe IGAS includes bacteremia, cellulitis, wound infections, soft tissue abscesses, lymphadenitis, septic arthritis, osteomyelitis, without TSS or soft tissue necrosis
What are considered severe presentations of IGAS?
• Most common clinical presentations of IGAS infections:
o toxic shock syndrome (TSS)
Streptococcal TSS is clinically indistinguishable from staphylococcal TSS
o necrotizing fasciitis (NF) or myositis or gangrene
o bacteremia with no septic focus
o pneumonia
may be indistinguishable, but may be rapid/progressive with pleural effusions
What are risk factors for IGAS infection?
Risk Factors for IGAS o recent pharyngitis o varicella o soft tissue trauma o NSAID use o Adults – HIV, cancer, heart dz, diabetes, lung dz, alcoholism, IV drugs, postpartum
How do you treat IGAS infections?
Management
o Penicillin remains the treatment of choice for confirmed GAS cases (no resistance)
And clindamycin, which is a potent inhibitor of toxin production with antimicrobial activity that is unaffected by inoculum size
o Consider IVIG at onset of severe IGAS (TSS or other), especially if clinically unstable
o TSS – cover for S aureus and GAS
cloxacillin in combination with clindamycin; empiric vanco if MRSA endemic
o Nec Fasc – broad coverage for gram+, gram -, anaerobes, GAS, and clostridia
piperacillin-tazobactam or a carbapenem PLUS clindamycin, +/- vanco
How do you manage close contacts of someone with an IGAS infection?
Chemoprophylaxis should only be offered to close contacts of a confirmed case of severe IGAS who have been exposed during the period from 7 days before the onset of symptoms in the index case to 24 h after initiating antimicrobial therapy in the case
Cephalexin, or cefuroxime axetil, or cefixime
• Penicillin is less effective in eradicating GAS colonization than cephalosporins
What is the most common cause of lower respiratory tract infections in young children worldwide?
RSV
How can you prevent RSV?
Young infants (and sibs) should avoid contact with people with resp infections when practical; also hand hygiene, BF, and avoidance of smoking are protective against severe URTIs
What is the preventative medication for RSV?
• Palivizumab
o humanized murine monoclonal immunoglobulin G-1 directed against an epitope on the F glycoprotein of RSV
o Standard dosing is 15 mg/kg IM q30 days during RSV season for a maximum of 5 doses
Do not continue vaccine schedule if breakthrough RSV infection occurs
o ~ $ 5600 per infant
Should you continue Palivizumab if a child becomes infected with RSV?
no
How effective is Palivizumab?
• Efficacy of palivizumab is <50% in the highest-risk groups (CLD or CHD), and most hospitalizations occur in healthy term infants, so more education should be directed at prevention strategies
Who is a candidate for RSV vaccine?
Palivizumab is recommended for:
o Children <12 months of age at the start of RSV season with hemodynamically significant CHD or CLD (need oxygen at 36 wGA) who require ongoing diuretics, bronchodilators, steroids or supplemental oxygen
o Preterm infants without CLD born < 30+0 wGA who are <6 months of age at the start of RSV season, it is reasonable (but not essential) to offer palivizumab
o Infants in remote communities who would require air transportation for hospitalization born < 36+0 wGA and <6 months of age at the start of RSV season
This is a challenging recommendation as it could apply to Inuit, all aboriginal children, or all children in remote communities
o Children with immunodeficiencies, Down syndrome, CF, upper airway obstruction or a chronic pulmonary disease other than CLD should not routinely be offered palivizumab
However, prophylaxis may be considered for children <24 months of age who are on home oxygen, have had a prolonged hospitalization for severe pulmonary disease or are severely immunocompromised
At what age do you stop offering the RSV vaccine?
• Risk of severe RSV is low after 24 months, and so children are not vaccinated after this time
Why areCanadian families visiting friends and relatives are at higher risk for infection?
o less likely to seek pre-departure advice and more likely to travel for longer periods
o more likely to be exposed to local food, drink and infectious contacts, for longer periods
o often underappreciate the severity of certain endemic infections
o often underappreciate that immunity to malaria wanes over time
Risk factors for fever/infection when travelling abroad?
Risk Factors for Infection
o Being unvaccinated or incompletely vaccinated
o Having a history of compromised or suppressed immunity (splenic dysfunction)
o Low weight or poor nutritional status
o Very young age (less than one month)
Infectious Differential for jaundice in a returning traveller?
Hep A, B, E Viral hemorrhagic fever Typhoid fever Leptospirosis Malaria
Returning traveller with LAD differential
EBV, CMV, HIV Rickettsiae Brucellosis Mycobacterium TB Visceral leishmaniasis Trypanosomiasis
Returning traveller with diarrhea differential
Rotavirus E. coli Shigella Salmonella Campylobacter Yersinia Giardia Amebiasis
Splenomegaly in a returning traveller differential
Splenomegaly EBV Typhoid fever Malaria Visceral leishmaniasis
Hemorrhagic rash in a returning travelling differential
Dengue
Viral hemorrhagic fever
Meningococccus
Rocky Mountain spotted fever
FEVER AND RASH in a retuning traveller differentia
Dengue Chikungunya Acute HIV Measles Zika Viral exanthems (roseola) Rickettsiae Enteric fever (Salmonella) Leptospirosis
Fever onset > 2 weeks in a returning traveller?
EBV, CMV, HIV (acute) Enteric fever (Salmonella) Brucellosis Toxoplasmosis Q fever mTB Leptospirosis Malaria Visceral leishmaniasis Amoebic liver abscess
Fever onset <2 weeks in a returning traveller?
URTI/LRTI Viral gastroenteritis Arboviruses Hepatitis A Acute otitis media Pneumonia UTI Enteric fever Leptospirosis Malaria
Diagnosis of malaria?
o Diagnosis: microscopy +/- rapid diagnostic testing
Malaria smear x 3
Clinical picture of someone with malaria
o medical emergency with mortality up to 20% in Plasmodium falciparum malaria
o malaria must be excluded in any febrile child with travel in the past 6 months
risk highest in Africa
o SSx non-specific: fever +/- chills, headache, N/V, diarrhea, lethargy, myalgia, abdo pain
Management of Malaria
Management: admit to hospital and treat presumptively for chloroquine-resistant malaria until speciation becomes available
Clinical presentation of typhoid fever
o Enteric (typhoid) fever is caused by infection with Salmonella typhi or Salmonella paratyphi from water or food contaminated with feces
India, Southeast Asia, South and Central America, Africa, Eastern Europe
o Incubation 7-14 day
o Biphasic presentation possible: initially as enterocolitis with diarrhea lasting several days, resolving, then recurring with more non-specific symptoms, including fever, chills, rash, diaphoresis, headache, myalgias, confusion, psychosis or apathy
Constipation and abdo pain are also common symptoms
HSM, leukopenia, thrombocytopenia
Diagnosis of typhoid fever
Dx blood Cx; more than 1 sample may be needed for diagnostic yield
Dengue Fever clinical symptoms
• Dengue Fever – flavivirus
o Southeast Asia (esp Thailand), South Pacific, Central America, Caribbean
o Incubation period varies from 2 to 14 days
o SSx: high fever, chills, headache, myalgias, and a classic erythematous reticulate rash over the thorax, face and flexion areas
Lymphocytosis, neutropenia and elevated aminotransferases are characteristic
Repeat dengue infections can present as hemorrhagic dengue or as shock syndrome, with hyponatremia, hypoproteinemia and circulatory collapse.
Treatment for dengue fever
Management is supportive: fluids, antipyretics, analgesia, transfusions
r/o bacterial sepsis and malaria
steroids, NSAIDs, and acetylsalicylic acid should be avoided due to bleeding risk
How long can zika remain in both female and male bodily fluids?
- Zika is an RNA virus and member of the flavivirus family (includes West Nile, dengue, etc)
- ZIKV has been detected in semen for ≥181 days and in female genital secretions for up to 3 wks
- Incubation period is 3 to 12 days
- Perinatal transmission appears to be benign
What is the clinical presentation of the zika virus?
• Clinical Presentation
o 75-80% are asymptomatic
o maculopapular rash (typically pruritic, starting proximally and spreading to the limbs, with associated edema), low-grade fever, arthralgias (especially of small joints in the hands and feet), myalgias, headache and nonpurulent conjunctivitis
o Recovery is usually complete within 3 to 14 days
o Features overlap with disease caused by dengue and chikungunya viruses
What is the presentation of congenital zika virus?
o Zika is teratogenic
o Presentation
Microcephaly
Intracranial calcifications
Ventriculomegaly or major structural CNS abnormalities
• cerebral atrophy, abnormal cortical development, callosal hypoplasia and diffuse subcortical calcifications
Other: Abnormal fetal tone can result in clubfoot or fetal akinesia deformation sequence, Microphthalmia, cataracts, and retinal abnormalities, sensorineural hearing loss, IUGR
o CZS can be distinguished from other congenital infections as follows:
[1] severe microcephaly with partially collapsed skull
[2] thin cerebral cortices with subcortical calcifications
[3] macular scarring and focal pigmentary retinal mottling
[4] congenital contractures
[5] marked early hypertonia and symptoms of extrapyramidal involvement
Diagnosis of zika virus
o Diagnosis is by either:
Serology (IgM or IgG or neutralizing antibody)
• IgM becomes positive in 7 days, IgG in 10 days
ZIKV RNA PCR
• Usually only positive during the first 4 days of SSx (but can persist)
o Negative maternal ZIKV serology more than 4 weeks after exposure rules out ZIKV infection and congenital ZIKV infection. However, since one may wait weeks for results, sending specimens for PCR and testing the child simultaneously is advised
o Do NOT test asymptomatic or symptomatic children with exposure to ZIKV after birth
Management of Zika virus
o Management is evolving
All children with potential in utero exposure should be followed long term
There is no treatment available; vaccines are being developed
Prevention is key – avoid mosquitoes and do not travel if pregnant or planning
What is the highest risk of transmission of HSV during pregnancy/delivery?
Most commonly during delivery from disease that is newly acquired and aSSx
• in utero is rare! But can cause skin lesions or scars, CNS disorders, and chorioretinitis
• can also be post natal
How do you classify maternal HSV infections and who is the highest risk of transmission?
Maternal infection is classified as newly acquired first episode primary infection, newly acquired first episode non-primary infection, or recurrent
• Transmission 60% primary, 30% non primary, <2% recurrent
• Antibodies to HSV-1 or HSV-2 (type-specific HSV antibodies) take approximately three weeks to develop following infection
How can you prevent HSV transmission during pregnancy/delivery?
• Prevention o Maternal recurrent genital HSV get acyclovir/valacyclovir prophylaxis starting 36 wGA o Elective C/S o Avoid scalp clip, vacuum, forceps o Avoid PROM
How does HSV present in a newborn?
Clinical Presentation – 3 categories – SSx often present within 4 weeks of birth
o Disseminated HSV – highest mortality rate
multiple organs, notably the liver and lungs
• positive HSV NP swab with SSx pneumonia is likely disseminated HSV
can present as sepsis (even if no known maternal HSV)
• may not be any skin lesions
o Localized CNS HSV
Seizure, irritability, +/- abnormal CSF findings
CNS disease can be subtle!
o Skin, eye and mucous membrane (SEM) infection
What is the work up if the mom has her first episode, non primary of HSV at the time of vaginal/ LSCS with ROM before delivery?
Full septic work up. Need swabs of mucous membranes before acyclovir.
CSF/Blood PCR
Liver enzymes
IV acyclovir for 14 days. Unless cultures +ve then 21 days
What is the work up if the mom has her first episode, non primary of HSV at the time delivery LSCS with no ROM?
swabs at 24 hours
if swabs -ve then routine observation
If swabs +ve, then full septic work up including liver enzymes
IV acyclovir for 14 days. Unless blood/CSF cultures +ve then 21 days
What is the work up if the mom has a recurrent episode, of HSV at the time delivery?
swabs at 24 hours
if swabs -ve then routine observation
If swabs +ve, then full septic work up including liver enzymes
IV acyclovir for 14 days. Unless blood/CSF cultures +ve then 21 days
How do you manage and infant with HSV?
• Management
o IV acyclovir 60 mg/kg/day divided q8h (PO bioavailability is too low for acute treament)
SEM x 14 days
CNS or disseminated x 21 days
• Repeat LP at day 21 and if still positive, continue acyclovir
• Suppressive therapy with acyclovir PO 300 mg/m2 per dose TID) x 6 months to infants with CNS disease
o Presumed first-episode primary or first-episode nonprimary infection, when an infant is delivered vaginally or by C/S after ROM
Start empiric acyclovir and do swabs of infant membranes and NP
• Swab positive: do LP to determine duration of acyclovir
• Swab negative: finish acyclovir x 10 days
o may d/c if maternal serology HSV-1 and HSV-2 (recurrent)
o C/S, no ROM, first-episode primary/nonprimary infection OR recurrent
Swab and d/c if negative – no acyclovir
o CBC and real function monthly while on acyclovir
o Treat ocular involvement with topical agent and optho Cx
Despite lack of maternal history, who should HSV infections be considered in?
• Always consider disseminated HSV in any infant with:
o IV abx for suspected sepsis (esp with seizure or abnormal CSF) who do not improve rapidly and have negative bacterial cultures at 24 h incubation
o admitted with pneumonia of uncertain etiology who do not improve after 24 h on antibiotics, especially if CXR is consistent with viral pneumonia
o unexplained bleeding from venipunctures or an unexplained documented coagulopathy
o IV antibiotics for suspected sepsis who are found to have unexplained hepatitis
What are the contact precautions for a baby with HSV?
Contact Precautions
o Neonates with HSV infection should be managed using contact precautions when mucocutaneous lesions are present and until lesions have crusted
o Asymptomatic neonates whose mothers have active HSV lesions should be managed using contact precautions until the end of the incubation period (day 14) or until samples from the infant taken after the first 24 h of life are negative.
