Chapter 17 Microbiology and Infectious Disease Devan Jaganath, MD, MPH, and Rebecca G

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Chapter 17 Microbiology and Infectious Disease Devan Jaganath, MD, MPH, and Rebecca G. Same, MD

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I. MICROBIOLOGY A. Collection of Specimens for Blood Culture 1. Preparation: To minimize contamination, clean venipuncture site with 70% isopropyl ethyl alcohol. Apply tincture of iodine or 10% povidone–iodine and allow skin to dry for at least 1 minute, or scrub site with 2% chlorhexidine for 30 seconds and allow skin to dry for 30 seconds. Clean blood culture bottle injection site with alcohol only. 2. Collection: Two sets of cultures from two different sites of equal blood volume should be obtained for each febrile episode, based on patient weight: <8 kg, 1–3 mL each; 8–13 kg, 4–5 mL; 14–25 kg, 10–15 mL each; >25 kg, 20–30 mL each.1 Peripheral sites preferred. If concern for central line infection, collect one from central access site, second from peripheral.

B. Rapid Microbiologic Identification of Common Aerobic Bacteria (Fig. 17.1) and Anaerobic Bacteria (Fig. 17.2)

C. Choosing Appropriate Antibiotic Based on Sensitivities 1. Minimum inhibitory concentration (MIC): Lowest concentration of an antimicrobial agent that prevents visible growth; MICs are unique to each agent, and there are standards to determine if susceptible, intermediate, or resistant. Antibiotic selection should generally be based on whether an agent is “susceptible” rather than the MIC. 2. See Tables 17.1 through 17.6 for spectrum of activity of commonly used antibiotics.2,3 Note: Antibiotic sensitivities can vary greatly with local resistance patterns. Follow published institutional guidelines and culture results for individual patients and infections. When possible, always use agent with narrowest spectrum of activity, particularly when organism susceptibilities are known. Downloaded for dr.Rahmat Dani Satria, M.Sc, Sp.PK ([email protected]) at Universitas443 Gadjah Mada from ClinicalKey.com by Elsevier on July 28, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. 444 Part II Diagnostic and Therapeutic Information

II. INFECTIOUS DISEASE A. Fever without Localizing Source: Evaluation and Management Guidelines4,5 1. Age <28 days: Hospitalize for full evaluation (Fig. 17.3). Owing to the greater risk of serious bacterial infections in young infants with fever, a conservative approach is warranted. 2. Age 29–90 days: Well-appearing infants who meet low-risk criteria can potentially be managed as outpatients if reliable follow-up and monitoring is ensured. 3. Age >90 days: The marked decline in invasive infections due to Haemophilus influenzae type b and Streptococcus pneumoniae, since introduction of conjugate vaccines, has reduced the likelihood of

Gram stain

Gram-negative bacteria

Cocci BacilliCoccobacilli

Neisseria Enteric Haemophilus Moraxella Kingella Curved Lactose Bordetella* or spiral fermenter Brucella*,† Francisella*,† Vibrio Campylobacter Ϫ Nonenteric ϩ Oxidase Escherichia coli Moraxella Enterobacter Kingella Citrobacter Pasteurella Ϫ ϩ Klebsiella Legionella* Eikenella Bartonella Salmonella Pseudomonas Shigella Aeromonas Proteus Burkholderia Serratia Citrobacter * Special media needed to Acinetobacter grow these organisms. Stenotrophomonas † Potential laboratory hazard—warn laboratory if these organisms are suspected.

FIGURE 17.1 Algorithm demonstrating identification of aerobic bacteria.

Gram-positive bacteria

Bacilli Cocci

Listeria Chains Clusters Bacillus spp. or pairs Corynebacteria Streptococci Staphylococci

Coagulase test ϩ Quellung S. aureus Ϫ Ϫ ϩ S. epidermidis S. saprophyticus Hemolysis S. pneumoniae Micrococcus spp.

␤ Viridans streptococci ␣ Enterococci ␥

Group A streptococci (S. pyogenes) Group B streptococci (S. agalactiae) Group C streptococci Group G streptococci

FIGURE 17.1, cont’d

serious bacterial infection in a well-appearing child within this age group: a. If ill-appearing without source of infection identified, consider admission and empirical antimicrobial therapy. b. If source of infection identified,treat accordingly. c. If well-appearing and without foci of infection, many experts advocate

urinalysis and urine culture as the only routine diagnostic test if 17 reliable follow-up and monitoring is ensured, including all females and uncircumcised males aged <2 years, all circumcised males aged <6 months, and all children with known genitourinary tract abnormalities. 4. Fever of unknown origin6,7 a. Generally defined as fever> 38.3°C for 2 or more weeks b. Often an unusual presentation of a common disease c. Broad differential, such as infectious (including deep-seated bone infections or abscesses), neoplasms, collagen vascular disease (i.e., juvenile idiopathic arthritis), drug fever, and Kawasaki syndrome

Gram stain

Gram-negative

Bacilli Cocci

Bacteroides spp. Veillonella Fusobacterium Gram-positive

Bacilli Cocci

Clostridium spp. Peptostreptococcus Propionibacterium Actinomyces Lactobacillus spp Listeria

FIGURE 17.2 Algorithm demonstrating identification of anaerobic bacteria.

d. Confirmation of feveris essential, thorough history of fever pattern, associated signs/symptoms, family history, ethnic/genetic background, environmental and animal exposures, and complete physical exam e. Labs and imaging will be guided by history and physical, and corresponding category of differential (i.e., infectious vs. oncologic vs. autoimmune/rheumatologic vs. immunodeficiency) B. Evaluation of Lymphadenopathy8 1. Etiology a. Reactive lymph nodes (LNs): Majority of lymphadenopathy b. Direct infection of LN: Suppurative lymphadenitis (typically due to Staphylococcus aureus or Streptococcus pyogenes) or indolent lymphadenitis (e.g., Bartonella henselae, atypical Mycobacterium) c. Malignancy: Can be observed with leukemia, and lymphoma Text continued on p. 452

Continued burgdorferi, Leptospira interrogans, Treponema pallidum L. interrogans, T. pallidum Spirochetes Borrelia B. burgdorferi, anaerobes Anaerobes Oral anaerobes Oral anaerobes Oral and intestinal Escherichia Haemophilus ) ) and respiratory H. influenzae E. coli -lactamase–producing respiratory β -lactamase–producing , other Gram-negative enterics, and β coli non– Gram-negatives such as influenzae intestinal ( organisms ( -Lactamase–producing Gram-negative Gram-Negative Organisms Neisseria meningitidis Non– β

Viridans Listeria Viridans L. monocytogenes, , , , Streptococcus agalactiae, Streptococcus pneumoniae (with about 10%–20% resistance depending on local epidemiology), streptococcus monocytogenes, Corynebacterium diphtheriae resistance) S. pneumoniae streptococcus Enterococcus faecalis ampicillin plus MSSA Gram-Positive Organisms Streptococcus pyogenes, MSSA, CoNS (high levels of S. pyogenes, agalactiae, Organisms covered by amoxicillin/ 17 –resistant Staphylococcus -lactamase inhibitors without penicillins: Nafcillin, oxacillin, dicloxacillin ampicillin β pseudomonal activity: Amoxicillin/clavulanic acid, ampicillin/sulbactam PENICILLINS Natural penicillins (Pen G or Pen V) Anti- Aminopenicillins: Amoxicillin, Extended-spectrum TABLE 17.1 -LACTAMS: INHIBIT CELL WALL SYNTHESIS -LACTAMS: INHIBIT CELL β

and E. coli, , Moraxella ) , some spp., Proteus Enterobacteriaceae Enterobacter -lactamase–producing E. coli, H. influenzae ), β ) spp., Pseudomonas aeruginosa spp. and other -lactamase–producing Gram-negatives E. coli, H. influenzae, M. catarrhalis, enterics, (percent susceptibility varies based on local epidemiology) Gram-negative organisms (e.g., Klebsiella organisms ( Klebsiella catarrhalis Neisseria β ( Klebsiella, Proteus, Neisseria Gram-negative spp. P. aeruginosa -Lactamase–producing Gram-negative -Lactamase–producing Gram-negatives, Gram-Negative Organisms E. coli Very good coverage of enteric β Ceftriaxone/cefotaxime and orals: Ceftazidime: β , MRSA (except for ceftaroline), and Enterococci]

Chlamydia S. pyogenes, and (majority), cont’d , MSSA, S. pyogenes, agalactiae Mycoplasma S. agalactiae first-generation; cephamycins: little activity S. pyogenes, agalactiae Viridans streptococcus MSSA MRSA Gram-Positive Organisms E. faecalis MSSA, Cefuroxime: same as S. pneumoniae Same as third-generation plus Same as third-generation plus Atypicals such as Listeria, -lactamase inhibitors with β pseudomonal activity: Piperacillin/tazobactam cefazolin the cephamycins (cefotetan and cefoxitin) ceftazidime cefdinir Extended-spectrum CEPHALOSPORINS Do not cover LAME [ First-generation: Cephalexin, Second-generation: cefuroxime and Third-generation: IV/IM: Ceftriaxone, cefotaxime, Enteral: Cefixime, cefpodoxime, Good CNS penetration Fourth-generation: Cefepime Good CNS penetration Fifth-generation: Ceftaroline TABLE 17.1 -LACTAMS: INHIBIT CELL WALL SYNTHESIS— -LACTAMS: INHIBIT CELL β

TABLE 17.2 FLUOROQUINOLONESa: INHIBIT DNA TOPOISOMERASES Gram-Positive Gram-Negative Organisms Organisms Anaerobes Other Ciprofloxacin, Bacillus Broad coverage, Ofloxacin anthracis, including Staphylococcus Shigella spp., saprophyticus Pseudomonas aeruginosa; emerging Neisseria resistance Levofloxacin Excellent Similar coverage Great atypical Streptococcus as coverage, pneumoniae ciprofloxacin including coverage Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella spp. Moxifloxacin Same as Good enteric Best anaerobic Good for MTB levofloxacin coverage; poor coverage of and atypical Pseudomonas quinolones Mycobacteria coverage

aThe American Academy of Pediatrics does not generally recommend fluoroquinolones for patients younger than 18 years unless no alternative options or for specific situations such as multidrug resistance, Pseudomonas, and Mycobacterium (Bradley and Jackson, 2011). MSSA, Methicillin-sensitive Staphylococcus aureus; MTB, Mycobacterium tuberculosis

TABLE 17.3 MACROLIDES: INHIBIT PROTEIN SYNTHESIS, BIND 50S RIBOSOMAL SUBUNIT Gram-Positive Organisms Atypicals Others Clarithromycin Reasonably Mycoplasma Bartonella henselae, Bordetella good against pneumoniae, pertussis, Campylobacter, Streptococcus Chlamydia Borrelia burgdorferi, H. pneumoniae pneumoniae, influenza, MAI and other (50%–70%) Legionella spp. atypical Mycobacteria Erythromycin Same as Above and Haemophilus ducreyi, Moraxella clarithromycin Chlamydia catarrhalis trachomatis Azithromycin Same as Same as above B. henselae, H. ducreyi, Neisseria clarithromycin gonorrhoeae

MAI, Mycobacterium avium subsp. intracellulare

TABLE 17.4 TETRACYCLINES: INHIBIT PROTEIN SYNTHESIS, BIND 30S RIBOSOMAL SUBUNIT Gram-Positive Organisms Atypicals Others Doxycycline and Streptococcus Mycoplasma, Haemophilus influenzae, tetracycline pneumoniae, Chlamydia, Helicobacter pylori, Vibrio spp., MSSA, MRSA, Legionella some anaerobic activity, Propionibacterium Borrelia burgdorferi, Coxiella acnes burnetii, Francisella tularensis, Rickettsia, Treponema pallidum, Yersinia pestis

MRSA, Methicillin-resistant Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus

TABLE 17.5 AMINOGLYCOSIDES: INHIBIT PROTEIN SYNTHESIS, BIND 30S RIBOSOMAL SUBUNIT Gram-Negative Organisms Gentamicin and streptomycin Almost all Gram-negative organisms; synergy with ampicillin for Enterococcus endocarditis Tobramycin and amikacin Almost all Gram-negative organisms 17

TABLE 17.6 SINGLE DRUG CLASS Gram-Positive Gram-Negative Organisms Organisms Other Clindamycin (Binds Broad Gram-positive Oral anaerobes 50S ribosomal coverage: MRSA, subunit) MSSA, Streptococcus spp. Linezolid (Binds MRSA, MSSA, Mycobacterium 50S ribosomal Enterococcus spp., Nocardia subunit) (including VRE), CoNS, Streptococcus spp., Viridans streptococci Metronidazole Anaerobic Broad anaerobic Entamoeba (Inhibits nucleic Gram-positive coverage histolytica, acid synthesis) organisms: Giardia lamblia, Clostridium spp., Trichomonas Peptostreptococcus vaginalis, and spp. Gardnerella vaginalis Nitrofurantoin Enterococcus faecalis, Citrobacter spp., (Damages Staphylococcus Escherichia coli, intracellular saprophyticus some Klebsiella macromolecules) spp., some Enterobacter spp. Trimethoprim + MRSA, MSSA, Listeria Many Gram-negative Pneumocystis Sulfamethoxazole (second choice if bacilli, including jirovecii, (Inhibits folate PCN allergy) Stenotrophomonas, Toxoplasma synthesis) Maltophilia, gondii, Nocardia Burkholderia cepacia Vancomycin MRSA, MSSA, (Inhibits Enterococcus (except peptidoglycan VRE), CoNS, synthesis) Streptococcus spp., Viridans streptococci, C. difficile (orally)

CoNS, Coagulase-negative staphylococci; MRSA, methicillin-resistant Staphylococcus aureus; MSSA, methicillin- sensitive Staphylococcus aureus; PCN, penicillin; VRE, vancomycin-resistant Enterococcus

d. Other causes: Autoimmune disorders, drug reactions, serum sickness, acute human immunodeficiency virus (HIV) 2. Physical findings a. Size: Cervical and axillary LN are typically <1 cm in size. Inguinal LN are typically <1.5 cm in size. Cervical LN >2 cm or palpable supraclavicular LN are associated with higher risk for malignancy.

b. Palpation: Tenderness is more common with reactive or infected LN but does not exclude malignancy. Fluctuance, warmth, and/or overlying erythema are more common in lymphadenitis. Hard, rubbery, fixed, or matted LN are suspicious for malignancy and require further investigation (see Section 22.III for features of malignant LN). c. If reactive lymphadenopathy is suspected, consider observation, with expected decrease in size over 4–6 weeks and resolution in 8–12 weeks. d. If lymphadenitis is suspected, consider a 5–7-day trial of antibiotics with streptococcal and staphylococcal coverage. e. Laboratory studies: Complete blood cell count (CBC) with differential, erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), specific serologies based on exposures and symptoms B.[ henselae, Epstein–Barr virus (EBV), HIV], tuberculin skin testing (TST). f. Imaging: Chest x-ray, consider ultrasound if etiology unclear. CT may be needed to evaluate anatomy for excision or evaluation of retropharyngeal abscess.8 g. Excision/fineneedle aspiration: See Section 22.III for criteria. 3. Cervical Lymphadenopathy in Children8,9 a. Differential diagnosis of enlarged cervical LN (Fig. 17.4)

Cervical lymphadenopathy (≥1 cm)

Acute Chronic (≥4 weeks) (<4 weeks)

HIV Unilateral Bilateral Malignancy Bartonella (cat−scratch disease) Atypical Mycobacteria Reactive lymph node Reactive Toxoplasmosis Lymphadenitis Lymph node Histoplasmosis (Staph/GAS, Lymphadenitis Legionella anaerobic from (Staph/GAS, Brucellosis dental abscess) EBV, CMV) Unicentric Castleman Late−onset GBS Sinus histiocytosis Kawasaki disease Sarcoidosis Cutaneous anthrax Yersinia pestis (Plague)

FIGURE 17.4 Differential diagnosis of cervical lymphadenopathy.

b. Correlate location of nodes and drainage patterns of head and neck (Fig. EC 17.A). c. Rule out other causes of cervical masses including branchial cleft cysts, epidermoid cysts, thyroglossal duct cysts, thyroid nodule, cystic hygroma, fibroma, cervical rib, and lymphatic malformation. C. Intrauterine and Perinatal Infections 1. Intrauterine (congenital) infections: The acronym TORCH [toxoplasmosis, other, rubella, cytomegalovirus (CMV), herpes simplex virus (HSV)] is used to describe a group of infections (including a large number that fall under “other”) outlined individually in Table 17.7. These infections often present in the neonate with overlapping findings: intrauterine growth retardation (IUGR), hematologic insult, ocular abnormalities, central nervous system (CNS) signs, and other organ system involvement (e.g., pneumonitis, myocarditis, nephritis, and hepatitis).10-12 Workup and management of these infections are detailed in Table 17.7. 2. Perinatal viral infections: Perinatal varicella-zoster virus (VZV), HSV, lymphocytic choriomeningitis virus and CMV infections can be severe, with profound morbidity and mortality. It can be difficult to clinically distinguish neonatal VZV and HSV lesions.14 Workup and management of these infections are also detailed in Table 17.7. 3. Group B streptococcal (GBS) infection: a. Adequate maternal intrapartum prophylaxis is intravenous (IV) penicillin, ampicillin, or cefazolin ≥4 hours before delivery.13 Fig. 17.5 shows an algorithm for secondary prevention of early-onset GBS disease in newborns. b. Late-onset GBS: See Table 17.8. D. Common Neonatal and Pediatric Bacterial Infections: Guidelines for Initial Management (See Table 17.8) 1. Deep neck infections19,20 a. Submandibular. Ludwig angina, causes rapidly progressive indurated cellulitis and swelling of the floor of mouth, significant risk of airway compromise; often caused by dental infection. Treat with antibiotics targeting oral flora, such as ampicillin–sulbactam or clindamycin AND

ceftriaxone, surgical decompression, and drainage. 17 b. Parapharyngeal. Posterior compartment infection by Fusobacterium tonsillitis can lead to suppurative jugular thrombophlebitis or Lemierre syndrome. This can cause bloodstream infection, septic emboli, and intracranial venous thrombosis. Signs include neck pain and swelling around sternocleidomastoid, torticollis, and increased intracranial pressure. Consider magnetic resonance imaging or computed tomography (CT) with contrast of the neck. Requires at least 2 weeks of IV antibiotics with anaerobic coverage. Text continued on p. 470

Preauricular

Submandibular

Mastoid

Jugulodigastric Submental Occipital Submaxillary Deep Superficial cervical chain cervical chain

FIGURE EC 17.A Drainage of cervical lymph nodes. (From Healy CM, Baker CJ. Cervical lymphadenitis. In: Cherry JD, Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ, eds. Feigin and Cherry’s Textbook of Pediatric Infectious Diseases. 7th ed. Philadelphia, PA: Elsevier Saunders; 2014). 17

TABLE EC 17.A GUIDE FOR INTERPRETATION OF THE SYPHILIS SEROLOGY OF MOTHERS AND THEIR INFANTS Treponemal Nontreponemal Test (e.g., Test (e.g., FTA-ABS, VDRL, RPR) TP-PA) Mother Infant Mother Infant Interpretation* − − − − No syphilis or incubating syphilis in mother or infant + + − − No syphilis in mother or infant (false-positive nontreponemal test with passive transfer to infant) + + or − + + Maternal syphilis with possible infant infection; mother treated for syphilis during pregnancy; or mother with latent syphilis and possible infection of infant† + + + + Recent or previous syphilis in the mother; possible infant infection. − − + + Mother successfully treated for syphilis before or early in pregnancy; or mother with Lyme disease (i.e., false-positive serologic test result); infant syphilis unlikely

*Table presents a guide and not the definitive interpretation of serologic tests for syphilis in mothers and their newborns. Other factors that should be considered include the timing of maternal infection, the nature and timing of maternal treatment, quantitative maternal and infant titers, and serial determination of nontreponemal test titers in both mother and infant. †Mothers with latent syphilis may have nonreactive nontreponemal tests. FTA-ABS, Fluorescent treponemal antibody absorption; RPR, rapid plasma reagin; TP-PA, Treponema pallidum particle agglutination; VDRL, Venereal Disease Research Laboratory. From American Academy of Pediatrics. Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book®: 2015 REPORT OF THE COMMITTEE ON INFECTIOUS DISEASES. American Academy of Pediatrics; 2015.

† + / − other urine, oral fluids, respiratory tract secretions, blood, or CSF within 2–4 weeks of birth mouth, rectum, skin vesicles surface sites CXR for pneumonitis occurred 2–4 months earlier See Table EC 17.A . 5 days or IgA after 10 persistence of IgG beyond 12 months is diagnostic. Positive PCR in CSF, blood, or urine is also diagnostic using nontreponemal test such as VDRL or RPR such as FTA-ABS or MHA-TP. Isolation of virus in culture or by PCR from Diagnostic Testing Surface culture: conjunctiva, nasopharynx, PCR: blood, CSF, skin vesicles Ancillary: CMP for elevated transaminases; Positive serum IgM suggests infection Test for IgM, IgA, IgG. Presence of IgM after Eye examination Cerebral calcifications best seen on CT IgM–positive at birth–3 months Eye examination Echocardiogram All women should be screened prenatally If maternal serology positive, screen infant Confirmatory test using treponemal ial calcifications, pneumonitis and hepatitis as well CNS involvement in 60%–75% Disease localized to SEM (45%) Localized CNS infection (30%) Disseminated disease (25%) with severe dysfunction, or consumptive coagulopathy. thrombocytopenia, intracran hearing loss (may develop later in life), retinitis. pleural and pericardial effusions pregnancy is 2%–6%, greatest risk in first half of pregnancy calcifications, hydrocephalus. lymphadenopathy, hepatosplenomegaly, jaundice, pneumonitis, petechiae, thrombocytopenia, microcephaly, seizures, and hearing loss weeks of life as: ”blueberry muffin rash” nasal secretions), lymphadenopathy, mucocutaneous lesions, pneumonia, osteochondritis, hemolytic anemia, or thrombocytopenia. Skin lesions and secretions are highly infectious. affecting CNS, bones and joints, teeth, eyes, or skin Consider HSV in neonates with sepsis, liver 90% asymptomatic at birth IUGR, jaundice, hepatosplenomegaly, microcephaly, Developmental delay is common. Fetal hydrops, IUGR, intellectual disability, isolated Risk of fetal death when infection occurs during Clinical Findings May be asymptomatic at birth Major clinical signs: chorioretinitis, cerebral Additional signs: maculopapular rash, generalized 1. 2. 3. HSV can present any time within the first 1–4 IUGR, cataracts, cardiac anomalies, deafness, Early signs: hepatosplenomegaly, snuffles (copious If untreated, may develop late manifestations (CMV) (HSV) Parvovirus B19 Toxoplasmosis Infective Agent Cytomegalovirus Herpes simplex virus Rubella * Syphilis * TABLE 17.7 CONGENITAL AND PERINATAL INFECTIONS CONGENITAL AND PERINATAL

for with days days CNS involvement or disseminated disease at least 12 months examination: penicillin G G (see Formulary for dosing) neurodevelopmental outcomes at 2 years of age in infants with symptomatic disease Therapy Pyrimethamine For abnormal neonatal testing/physical For negative neonatal testing: benzathine penicillin Supportive care for newborn Ensure mother is immunized Treatment not indicated for asymptomatic CMV 6 months of valganciclovir improves audiologic and May use ganciclovir if unable to absorb enterally Supportive care Acyclovir • 14 • 21 other −

† + 5 days or IgA after 10 persistence of IgG beyond 12 months is diagnostic. Positive PCR in CSF, blood, or urine is also diagnostic using nontreponemal test such as VDRL or RPR such as FTA-ABS or MHA-TP. See Table EC 17.A. urine, oral fluids, respiratory tract secretions, blood, or CSF within 2–4 weeks of birth occurred 2–4 months earlier mouth, rectum, skin vesicles surface sites CXR for pneumonitis Diagnostic Testing Test for IgM, IgA, IgG. Presence of IgM after Eye examination Cerebral calcifications best seen on CT All women should be screened prenatally If maternal serology positive, screen infant Confirmatory test using treponemal IgM–positive at birth–3 months Eye examination Echocardiogram Isolation of virus in culture or by PCR from Positive serum IgM suggests infection Surface culture: conjunctiva, nasopharynx, PCR: blood, CSF, skin vesicles Ancillary: CMP for elevated transaminases; ial calcifications, 17 pneumonitis and hepatitis as well CNS involvement in 60%–75% Disease localized to SEM (45%) Localized CNS infection (30%) Disseminated disease (25%) with severe calcifications, hydrocephalus. lymphadenopathy, hepatosplenomegaly, jaundice, pneumonitis, petechiae, thrombocytopenia, microcephaly, seizures, and hearing loss nasal secretions), lymphadenopathy, mucocutaneous lesions, pneumonia, osteochondritis, hemolytic anemia, or thrombocytopenia. Skin lesions and secretions are highly infectious. affecting CNS, bones and joints, teeth, eyes, or skin ”blueberry muffin rash” thrombocytopenia, intracran hearing loss (may develop later in life), retinitis. pleural and pericardial effusions pregnancy is 2%–6%, greatest risk in first half of pregnancy weeks of life as: dysfunction, or consumptive coagulopathy. Clinical Findings May be asymptomatic at birth Major clinical signs: chorioretinitis, cerebral Additional signs: maculopapular rash, generalized Early signs: hepatosplenomegaly, snuffles (copious If untreated, may develop late manifestations IUGR, cataracts, cardiac anomalies, deafness, 90% asymptomatic at birth IUGR, jaundice, hepatosplenomegaly, microcephaly, Developmental delay is common. Fetal hydrops, IUGR, intellectual disability, isolated Risk of fetal death when infection occurs during HSV can present any time within the first 1–4 1. 2. 3. Consider HSV in neonates with sepsis, liver (CMV) (HSV) Infective Agent Toxoplasmosis Syphilis* Rubella* Cytomegalovirus Parvovirus B19 Herpes simplex virus TABLE 17.7 CONGENITAL AND PERINATAL INFECTIONS CONGENITAL AND PERINATAL

mother primary

infants

developed

1000 < preterm mother

< 28 weeks or > 28 weeks if mother lacks historical or serologic evidence of immunity neonates hospitalized

varicella (not zoster) between 5 days before and 2 days after delivery has active lesions at delivery (regardless of duration): • •

• All • To administered to: if giving VZIG aged 3–17 years, but no data for neonates. Refer to pediatric hepatitis specialist feeding alternatives are available, including in the United States VZIG (or IVIG if unavailable) should be Therapy Acyclovir: If lesions develop, some consider treating No therapy until HCV status ascertained Peginterferon plus ribavirin approved in children Breastfeeding not contraindicated See Table 17.12 . Breastfeeding contraindicated where safe infant For HBIG and HBV vaccine guidelines, see Fig. 16.4. Breastfeeding not contraindicated. IVIG plasma within 1–2 weeks after exposure. up to 18 months. done at 9 and 18 months in infants with HBsAg-positive mothers urine, blood, or CSF DFA of vesicle scraping PCR from vesicle or CSF Diagnostic Testing HCV RNA can be detected in serum or Maternal anti-HCV antibodies can persist See Table 17.12 . ALT is usually normal at birth. Testing for HBsAg and anti-HBs should be RNA PCR from throat, stool, rectal swab, 12 < 2% of vertical cont’d > 5 days before delivery and GA in utero and postnatally through Red Book for isolation recommendations Treponema pallidum antibodies; PCR, polymerase chain reaction; sAg, surface antigen; RPR, rapid plasma reagin; > 28 weeks causes milder disease only from women who are HCV RNA–positive at time of delivery. Maternal co-infection with HIV is associated with increased risk of perinatal transmission. breastfeeding. increases risk, as does longer duration of ruptured membranes, more months of breastfeeding, vaginal delivery, or laboring before cesarean section. trimester may result in fetal death or varicella embryopathy: limb hypoplasia, cutaneous scarring, eye anomalies, and CNS damage (congenital varicella syndrome) delivery can result in severe neonatal infection first 2 weeks. Can include pneumonitis, encephalitis, purpura fulminans, bleeding, death. transmission. Perinatal transmission is much more efficient, and 90% develop chronic hepatitis B. transmission. perinatally, with lower rates of transmission occurring pneumonitis, coagulopathy Risk of perinatal transmission is 5% and occurs Greater viral exposure, especially maternal VL, Clinical Findings Maternal infection during first or early second Maternal infection from 5 days prior or 2 after Maternal infection In utero transmission accounts for Appropriate prophylaxis can prevent 95% of vertical Most mother-to-child transmission occurs Hepatitis, myocarditis, meningitis, encephalitis, § 14 15 (HCV) immunodeficiency virus (HIV) (HBV) Varicella Infective Agent Hepatitis C virus Enterovirus Human Hepatitis B virus TABLE 17.7 See 2015 American Academy of Pediatrics Link to diagnostic algorithm for syphilis: http://redbook.solutions.aap.org/data/Books/1484/fig3-12.jpeg From Panel on Treatment of HIV-Infected Pregnant Women and Prevention Perinatal Transmission. Recommendations for use ant iretroviral drugs in pregnant HIV-1-infected women maternal health CONGENITAL AND PERINATAL INFECTIONS— CONGENITAL AND PERINATAL SEM, skin, eyes, mouth; VDRL, Venereal Disease Research Laboratory test; VL, viral load; VZIG, varicella-zoster immune globulin ‡ *All mothers should be screened prenatally for rubella immune status and syphilis. † § interventions to reduce perinatal HIV transmission in the United States. Available at https://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf . Accessed Sep 22, 2015 ALT, Alanine aminotransferase; CMP, comprehensive metabolic panel; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest x-ray; DFA, direct fluorescent antibody; FTA-ABS, fluorescent treponemal antibody absorption test; GA, gestational age; HBIG, hepatitis B immune globulin; IM, intramuscular; IUGR, intrauterine growth retardation; IV, intravenous; IVIG, intravenous immunoglobulin; MHA-TP, microhemagglutination assay for

Downloaded for dr.Rahmat Dani Satria, M.Sc, Sp.PK ([email protected]) at Universitas Gadjah Mada from ClinicalKey.com by Elsevier on July 28, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. Chapter 17 Microbiology and Infectious Disease 459 mother primary if infants developed 1000 g < preterm mother if 28 weeks or 28 weeks if mother lacks historical or < > serologic evidence of immunity neonates hospitalized varicella (not zoster) between 5 days before and 2 days after delivery has active lesions at delivery (regardless of duration): • • administered to: • All • To if giving VZIG aged 3–17 years, but no data for neonates. Refer to pediatric hepatitis specialist feeding alternatives are available, including in the United States Therapy VZIG (or IVIG if unavailable) should be Acyclovir: If lesions develop, some consider treating IVIG For HBIG and HBV vaccine guidelines, see Fig. 16.4. Breastfeeding not contraindicated. No therapy until HCV status ascertained Peginterferon plus ribavirin approved in children Breastfeeding not contraindicated See Table 17.12. Breastfeeding contraindicated where safe infant urine, blood, or CSF done at 9 and 18 months in infants with HBsAg-positive mothers plasma within 1–2 weeks after exposure. up to 18 months. Diagnostic Testing DFA of vesicle scraping PCR from vesicle or CSF RNA PCR from throat, stool, rectal swab, ALT is usually normal at birth. Testing for HBsAg and anti-HBs should be HCV RNA can be detected in serum or Maternal anti-HCV antibodies can persist See Table 17.12. 12 2% of vertical < antibodies; PCR, polymerase chain reaction; sAg, surface antigen; RPR, rapid plasma reagin; 5 days before delivery and GA and postnatally through > for isolation recommendations in utero Red Book 17 Treponema pallidum transmission accounts for 28 weeks causes milder disease trimester may result in fetal death or varicella embryopathy: limb hypoplasia, cutaneous scarring, eye anomalies, and CNS damage (congenital varicella syndrome) delivery can result in severe neonatal infection first 2 weeks. Can include pneumonitis, encephalitis, purpura fulminans, bleeding, death. > pneumonitis, coagulopathy transmission. Perinatal transmission is much more efficient, and 90% develop chronic hepatitis B. transmission. only from women who are HCV RNA–positive at time of delivery. Maternal co-infection with HIV is associated with increased risk of perinatal transmission. perinatally, with lower rates of transmission occurring breastfeeding. increases risk, as does longer duration of ruptured membranes, more months of breastfeeding, vaginal delivery, or laboring before cesarean section. Clinical Findings Maternal infection during first or early second Maternal infection from 5 days prior or 2 after Maternal infection Hepatitis, myocarditis, meningitis, encephalitis, In utero Appropriate prophylaxis can prevent 95% of vertical Risk of perinatal transmission is 5% and occurs Most mother-to-child transmission occurs Greater viral exposure, especially maternal VL, § 14 15 (HBV) (HCV) immunodeficiency virus (HIV) Infective Agent Varicella Enterovirus Hepatitis B virus Hepatitis C virus Human See 2015 American Academy of Pediatrics Link to diagnostic algorithm for syphilis: http://redbook.solutions.aap.org/data/Books/1484/fig3-12.jpeg From Panel on Treatment of HIV-Infected Pregnant Women and Prevention Perinatal Transmission. Recommendations for use ant iretroviral drugs in pregnant HIV-1-infected women maternal health ‡ *All mothers should be screened prenatally for rubella immune status and syphilis. † § interventions to reduce perinatal HIV transmission in the United States. Available at https://aidsinfo.nih.gov/contentfiles/ lvguidelines/perinatalgl.pdf. Accessed Sep 22, 2015 ALT, Alanine aminotransferase; CMP, comprehensive metabolic panel; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest x-ray; DFA, direct fluorescent antibody; FTA-ABS, fluorescent treponemal antibody absorption test; GA, gestational age; HBIG, hepatitis B immune globulin; IM, intramuscular; IUGR, intrauterine growth retardation; IV, intravenous; IVIG, intravenous immunoglobulin; MHA-TP, microhemagglutination assay for SEM, skin, eyes, mouth; VDRL, Venereal Disease Research Laboratory test; VL, viral load; VZIG, varicella-zoster immune globulin

Maternal chorioamnionitis?§ Yes Limited evaluation¶ Antibiotic therapy† No

GBS prophylaxis indicated No Routine clinical for mother? care††

Yes

Mother received intravenous penicillin, ampicillin, Observation for Yes or cefazolin for Ն4 hours Ն48 hours††§§ before delivery?

Ն37 weeks and duration Observation for of membrane rupture Yes Ն48 hours††¶¶ Ͻ18 hours?

Either Ͻ37 weeks or Limited evaluation¶ duration of membrane Yes Observation for rupture Ն18 hours? Ն48 hours††

* Full diagnostic evaluation includes a blood culture, a complete blood count (CBC), including white blood cell differential and platelet counts, chest radiograph (if respiratory abnormalities are present), and lumbar puncture (if patient is stable enough to tolerate procedure and sepsis is suspected). † Antibiotic therapy should be directed toward the most common causes of neonatal sepsis, including intravenous ampicillin for GBS and coverage for other organisms (including Escherichia coli and other gram-negative pathogens) and should take into account local antibiotic resistance patterns. § Consultation with obstetric providers is important to determine the level of clinical suspicion for chorioamnionitis. Chorioamnionitis is diagnosed clinically and some of the signs are nonspecific. ¶ Limited evaluation includes blood culture (at birth) and CBC with differential and platelets (at birth and/or at 6–12 hours of life). †† If signs of sepsis develop, a full diagnostic evaluation should be conducted and antibiotic therapy initiated. §§ If ≤ 37 weeks’gestation, observation mayoccur at home after24hours if other discharge criteria have been met, access to medical care is readily available, and a person who is able to comply fully with instructions for home observation will be present. If any of these conditions is not met, the infant should be observed in the hospital for at least 48 hours and until discharge criteria are achieved. ¶¶ Some experts recommend a CBC with differential and platelets at age 6–12 hours.

FIGURE 17.5 Algorithm for secondary prevention of early-onset group B streptococcal (GBS) disease among newborns. (From Verani JR, McGee L, Schrag SJ. Division of Bacterial Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention (CDC). Prevention of perinatal group B streptococcal disease: Revised Downloadedguidelines forfrom dr.Rahmat CDC, 2010. Dani MMWRSatria, M.Sc, Recomm Sp.PK Rep. ([email protected]) 2010;59:1-36.) at Universitas Gadjah Mada from ClinicalKey.com by Elsevier on July 28, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. Chapter 17 Microbiology and Infectious Disease 461 Continued abscess and should be performed when indicated; obtain cultures for susceptibility. threatening infections, immunocompromised status debridement are critical. (tetanus, hepatitis B) and HIV risk. rabies Remove catheter 5 days Incision and drainage alone may be adequate for Hospitalize for severe infections, limb- Suggested Length of Therapy/Comments For all bites, cleaning, irrigation, and Human: 5–7 days. Assess immunization status Animal: 7–10 days Assess tetanus immunization status, risk of

+ aminoglycoside (third-generation − / + clindamycin + + (third-generation cephalosporin OR − / cephalosporin or TMP/SMX) + aminoglycoside) OR OR cefepime (piperacillin/tazobactam ceftazidime) PO: nonsuppurative: cephalexin Suppurative or PCN allergy: clindamycin TMP/SMX has poor activity against GAS Suggested Empirical Therapy PO: amoxicillin/clavulanate Alt: clindamycin IV: ampicillin/sulbactam Alt: TMP/SMX Same Immunocompetent: vancomycin Immunocompromised: vancomycin

Eikenella spp. , oral anaerobes Staphylococcus Pseudomonas, spp., spp. , CoNS, enteric Gram-negative , oral anaerobes, Capnocytophaga Pasteurella multocida, Streptococcus aureus corrodens, Haemophilus spp., bacilli including Candida 17 Nonsuppurative: GAS, MSSA Suppurative: GAS, MSSA, and MRSA Usual Etiology Streptococcus Add S. aureus CELLULITIS Infectious Syndrome BITES Human Dog/cat CATHETER-RELATED BLOODSTREAM INFECTIONS TABLE 17.8 COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL MANAGEMENT COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL

viral spp ., , other Streptococcus pyogenes, Clostridium spp ., Peptostreptococcus, P. aeruginosa, S. aureus Gram-negative bacilli CoNS, Pseudomonas aeruginosa influenzae, Moraxella, S. aureus, Yersinia spp. Campylobacter spp. Clostridium difficile Salmonella spp. Shigella spp. E. coli, Enterococcus, Bacteroides Escherichia coli Oral flora, including anaerobes Streptococcus pneumoniae, Haemophilus N. gonorrhoeae, C. trachomatis S. pneumoniae, H. influenzae, aureus, Neisseria gonorrhoeae Usual Etiology Chlamydia trachomatis INTRA-ABDOMINAL INFECTIONS GASTROENTERITIS (BACTERIAL) DENTAL ABSCESSES Suppurative, non-neonatal DACRYOCYSTITIS Infectious Syndrome CONJUNCTIVITIS Neonatal Exudative conjunctivitis TABLE 17.8 COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL MANAGEMENT— COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL

., viral spp , other ., Peptostreptococcus, spp. spp spp. Streptococcus pyogenes, spp. spp. CoNS, Pseudomonas aeruginosa Clostridium P. aeruginosa, S. aureus Gram-negative bacilli influenzae, Moraxella, S. aureus, 17 S. pneumoniae, H. influenzae, aureus, Oral flora, including anaerobes Escherichia coli Salmonella Shigella Yersinia Campylobacter Clostridium difficile E. coli, Enterococcus, Bacteroides Usual Etiology Chlamydia trachomatis Neisseria gonorrhoeae Streptococcus pneumoniae, Haemophilus N. gonorrhoeae, C. trachomatis DACRYOCYSTITIS DENTAL ABSCESSES GASTROENTERITIS (BACTERIAL) INTRA-ABDOMINAL INFECTIONS Infectious Syndrome CONJUNCTIVITIS Neonatal Exudative conjunctivitis Suppurative, non-neonatal

Actinomyces, M. catarrhalis Streptococcus spp. S. aureus , anaerobes, Candida in patients with Mycobacterium tuberculosis Kingella ( ≤ 4 years) S. aureus , resistant enteric E. coli, Listeria monocytogenes P. aeruginosa coverage Salmonella spp. coverage influenzae GNRs, and prolonged hospitalization atypical mycobacteria, Bartonella henselae (cat–scratch disease), influenzae (including GBS in neonates), GNRs such as (nontypeable), catarrhalis, S. aureus , GAS S. pneumoniae, Neisseria meningitidis GBS, Consider S. pneumoniae, pyogenes, aureus, H. Pseudomonas Add S. aureus , GAS, Add S. pneumoniae, H. influenzae Usual Etiology Viruses, GAS, S. pneumoniae, H. influenzae, Moraxella With trauma: anaerobes, GNRs 17 > 1 month) MENINGITIS Neonatal Non-neonatal (age MASTOIDITIS (ACUTE) OTITIS EXTERNA (UNCOMPLICATED) Foot puncture OTITIS MEDIA (ACUTE) OSTEOMYELITIS Uncomplicated Sickle cell disease Infectious Syndrome LYMPHADENITIS ORBITAL CELLULITIS TABLE 17.8 COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL MANAGEMENT— COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL

+ vancomycin + third-generation + vancomycin cefotaxime + + 3 days) × chloramphenicol vancomycin aminoglycoside past 30 days or has concurrent purulent conjunctivitis, amoxicillin/clavulanate is recommended ceftriaxone amoxicillin (persistent symptoms 48–72 hours after initial treatment): amoxicillin/clavulanate or ceftriaxone (IM daily cephalosporin neomycin MRSA prevalent MRSA prevalent For severe PCN allergy, consider Ampicillin/sulbactam OR ceftriaxone Oxacillin, nafcillin, or clindamycin Alt: vancomycin Ceftazidime OR antipseudomonal PCN Add ceftriaxone High-dose amoxicillin 80–90 mg/kg/day If child has received amoxicillin within the Alt/PCN Allergy: cefdinir, cefpodoxime, For treatment failure with high-dose Alt: clindamycin Eardrops: ciprofloxacin or polymyxin– Suggested Empirical Therapy PO: amoxicillin/clavulanate; clindamycin if Alt: cephalexin or dicloxacillin IV: oxacillin or cefazolin; clindamycin if Vancomycin OR clindamycin Ampicillin Ceftriaxone H. , spp.

Actinomyces, , GAS , anaerobes, (cat–scratch 4 years) in patients with ≤ ( , resistant enteric coverage M. catarrhalis Streptococcus spp. coverage S. aureus Candida Mycobacterium tuberculosis Kingella S. aureus , GAS, E. coli, Listeria monocytogenes P. aeruginosa Salmonella catarrhalis, S. aureus (including GBS in neonates), GNRs such as (nontypeable), atypical mycobacteria, Bartonella henselae disease), influenzae GNRs, and prolonged hospitalization influenzae 17 S. pneumoniae, H. influenzae, Moraxella With trauma: anaerobes, GNRs S. aureus Add Add S. pneumoniae, H. influenzae Pseudomonas Usual Etiology Viruses, GAS, S. pneumoniae, pyogenes, aureus, H. GBS, Consider S. pneumoniae, Neisseria meningitidis 17 1 > month) ORBITAL CELLULITIS OSTEOMYELITIS Uncomplicated Foot puncture Sickle cell disease OTITIS MEDIA (ACUTE) OTITIS EXTERNA (UNCOMPLICATED) Infectious Syndrome LYMPHADENITIS MASTOIDITIS (ACUTE) MENINGITIS Neonatal Non-neonatal (age

(nafcillin or + cefotaxime azithromycin (aminoglycoside + ± + cont’d 1 month 1 azithromycin < × ± azithromycin clindamycin + + piperacillin/tazobactam + gentamicin + or ceftriaxone) clavulanate or third-generation cephalosporin clindamycin if concern for MRSA benzathine PCN G cephalosporin oxacillin) doxycycline in areas with endemic Borrelia azithromycin (atypical coverage) influenza season cefotaxime) Suggested Empirical Therapy PO: clindamycin Alt: nafcillin/oxacillin In neonates: vancomycin Ampicillin/sulbactam or amoxicillin/ Consider adding vancomycin, TMP/SMX, or Azithromycin, erythromycin Azithromycin for age Alt: TMP-SMX, limited evidence For GAS: PCN V or amoxicillin Alt: clindamycin, macrolide, or Erythromycin Alt: azithromycin for 5 days Outpatient: amoxicillin (high dose) (Cefotaxime or gentamicin) (Clindamycin or oxacillin) For all ages, consider amoxicillin or Ampicillin Alt: clindamycin Inpatient: ampicillin Alt: ceftriaxone Consider influenza antiviral therapy during Ceftriaxone or cefotaxime Ampicillin/sulbactam OR (ceftriaxone or Vancomycin oral spp., , viruses , viruses spp.; S. aureus, H. M. catarrhalis S. aureus, spp., Haemophilus S. aureus S. pneumoniae, Kingella , GAS, (nontypeable), 4 years), ≤ most common; also oral flora, , GBS, Gram-negative bacilli , GAS, Streptococcus ( E. coli Gram-negative rods, viruses (including mumps, HIV, EBV), or noninfectious causes influenzae Arcanobacterium haemolyticum (including Coxsackie virus, other enteroviruses, EBV) pneumoniae are most common, including influenza kingae Borrelia burgdorferi anaerobes enteric or genitourinary Gram-negative organisms Usual Etiology S. aureus GAS and Bordetella pertussis GAS, group C and G streptococci, C. trachomatis S. pneumoniae, Mycoplasma, Chlamydia S. aureus S. aureus GBS, See above GAS, other streptococci, Staphylococcus, Streptococcus H. ) 3 months 5 years > < influenzae, S. pneumoniae Infectious Syndrome PAROTITIS PERIORBITAL CELLULITIS (PRESEPTAL) PERTUSSIS PHARYNGITIS Age SEPTIC ARTHRITIS Neonatal Age PNEUMONIA Neonatal Nonimmunized child (for RETROPHARYNGEAL OR PERITONSILLAR ABSCESS SPINAL FUSION INFECTIONS TABLE 17.8 COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL MANAGEMENT— COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL

(nafcillin or + cefotaxime azithromycin (aminoglycoside + ± + 1 month 1 azithromycin < × ± azithromycin clindamycin + + piperacillin/tazobactam + gentamicin + or ceftriaxone) clavulanate or third-generation cephalosporin clindamycin if concern for MRSA benzathine PCN G cephalosporin oxacillin) doxycycline in areas with endemic Borrelia azithromycin (atypical coverage) influenza season cefotaxime) Suggested Empirical Therapy PO: clindamycin Alt: nafcillin/oxacillin In neonates: vancomycin Ampicillin/sulbactam or amoxicillin/ Consider adding vancomycin, TMP/SMX, or Azithromycin, erythromycin Azithromycin for age Alt: TMP-SMX, limited evidence For GAS: PCN V or amoxicillin Alt: clindamycin, macrolide, or Erythromycin Alt: azithromycin for 5 days Outpatient: amoxicillin (high dose) (Cefotaxime or gentamicin) (Clindamycin or oxacillin) For all ages, consider amoxicillin or Ampicillin Alt: clindamycin Inpatient: ampicillin Alt: ceftriaxone Consider influenza antiviral therapy during Ceftriaxone or cefotaxime Ampicillin/sulbactam OR (ceftriaxone or Vancomycin oral spp., , viruses , viruses spp.; S. aureus, H. M. catarrhalis S. aureus, spp., Haemophilus S. aureus S. pneumoniae, Kingella , GAS, (nontypeable), 4 years), ≤ most common; also oral flora, , GBS, Gram-negative bacilli , GAS, Streptococcus ( E. coli Gram-negative rods, viruses (including mumps, HIV, EBV), or noninfectious causes influenzae Arcanobacterium haemolyticum (including Coxsackie virus, other enteroviruses, EBV) pneumoniae are most common, including influenza kingae Borrelia burgdorferi anaerobes enteric or genitourinary Gram-negative organisms 17 Usual Etiology S. aureus GAS and Bordetella pertussis GAS, group C and G streptococci, C. trachomatis S. pneumoniae, Mycoplasma, Chlamydia S. aureus S. aureus GBS, See above GAS, other streptococci, Staphylococcus, Streptococcus H. ) 3 months 5 years > < influenzae, S. pneumoniae Infectious Syndrome PAROTITIS PERIORBITAL CELLULITIS (PRESEPTAL) PERTUSSIS PHARYNGITIS Age SEPTIC ARTHRITIS Neonatal Age PNEUMONIA Neonatal Nonimmunized child (for RETROPHARYNGEAL OR PERITONSILLAR ABSCESS SPINAL FUSION INFECTIONS

M. The Harriet Lane Handbook of Pediatric Antimicrobial Therapy Borrelia Borrelia Haemophilus influenzae type b; HIV, human immunodeficiency virus; IM, intramuscular; IV, intravenous; MRSA, methicillin-resistant Enterococcus Proteus spp. GAS, Staphylococcus N. gonorrhoeae Streptococcus spp., Streptococcus spp., Alternative treatment regimens are listed in italics Staphylococcus aureus ; PCN, penicillin; PO, by mouth; QID, four times daily; STI, sexually transmitted infection; TMP/SMX, trimethoprim/sulfamethoxazole; UTI, Proteus spp., S. aureus , anaerobes Pseudomonas , Gram-negative bacilli, Pseudomonas , resistant burgdorferi , burgdorferi catarrhalis, H. influenzae, Pseudomonas Mucor, Rhizopus, Aspergillus Gram-negative organisms catarrhalis spp., saprophyticus Gram-negative organisms (including Pseudomonas) S. aureus , Add Add Add S. aureus , Usual Etiology S. pneumoniae, H. influenzae, M. S. aureus, pneumoniae, E. coli , Enterobacteriaceae, E. coli , Enterobacteriaceae, Staphylococcus epidermidis, S. aureus, 18 ≥ 5 years immunocompromised SINUSITIS Adolescent Chronic Seriously ill or Abnormal host/urinary tract Infectious Syndrome Age Acute TRACHEITIS UTI Cystitis Pyelonephritis VENTRICULOPERITONEAL SHUNT, INFECTED TABLE 17.8 COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL MANAGEMENT— COMMON PEDIATRIC AND NEONATAL INFECTIONS: GUIDELINES FOR INITIAL First antibiotics listed indicate treatment of choice. organism and susceptibility information is available. Alt . , Alternative; BID, twice daily; CoNS, coagulase-negative staphylococci; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest x-ray; EBV, Epstein–Barr virus; FQ, fluoroquinolone; GAS, group A streptococcus; GBS, group B GNR, Gram-negative rods; Hib, Staphylococcus aureus ; MSSA, methicillin-sensitive urinary tract infection Recommendations modified from American Academy of Pediatrics. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book®: 2015 REPORT OF THE COMMITTEE ON INFECTIOUS DISEASES. Academy of Pediatrics; 2015 and McMillan JA, Lee CKK, Siberry GK, Carroll KC.

± response successful treatment. observed chlamydia and test for other STIs worsening course drainage eliminate the organism if endotracheal tube is present susceptibility results) as soon able to tolerate enteral antibiotics 14–21 days, depending on organism and Shunt removal or revision is required for Suggested Length of Therapy/Comments Switch to oral antibiotics after improvement If gonorrhea suspected, always treat for 7 days Antibiotics indicated for severe onset or If severe/fails to respond, consider imaging 10–14 days Consider culture to guide therapy. Surgical intervention needed 5 days Antibiotics will treat the acute illness but not 5 days 7 days Consider oral cephalexin (or therapy as guided by 7 days

+ . Philadelphia, PA: Saunders Elsevier; 2014. present

± clindamycin ± N. gonorrhoeae cefepime clavulanate + ± . Cultures should be obtained when clinically appropriate; antibiotic coverage narrowed once coverage clindamycin OR vancomycin amphotericin B dependent therapy or for patients with PCN allergy) type b; HIV, human immunodeficiency virus; IM, intramuscular; IV, intravenous; MRSA, methicillin-resistant Suggested Empirical Therapy Nafcillin, oxacillin, or clindamycin Alt: vancomycin Add ceftriaxone if Amoxicillin Alt: cefpodoxime or cefixime PCN allergy: levofloxacin If no improvement in 3–5 days, broaden Amoxicillin/clavulanate Alt: ceftriaxone OR cefotaxime Cefepime OR piperacillin/tazobactam Ceftriaxone if community-acquired Cefepime if ventilator or tracheostomy– PO: cephalexin, TMP/SMX Alt: nitrofurantoin or ciprofloxacin Ceftriaxone Cefepime (ciprofloxacin as oral step-down Vancomycin

spp. M. The Harriet Lane Handbook of Pediatric Antimicrobial Therapy Borrelia Borrelia Haemophilus influenzae Enterococcus Proteus ; PCN, penicillin; PO, by mouth; QID, four times daily; STI, sexually transmitted infection; TMP/SMX, trimethoprim/sulfamethoxazole; UTI, GAS, spp., spp., Staphylococcus , Gram-negative bacilli, , resistant spp., N. gonorrhoeae , anaerobes , Streptococcus Streptococcus , , Alternative treatment regimens are listed in italics Staphylococcus aureus Proteus , Enterobacteriaceae, , Enterobacteriaceae, S. aureus Pseudomonas Pseudomonas burgdorferi burgdorferi catarrhalis Mucor, Rhizopus, Aspergillus catarrhalis, H. influenzae, Pseudomonas spp., saprophyticus Gram-negative organisms Gram-negative organisms (including Pseudomonas) 17 Usual Etiology S. aureus S. aureus S. pneumoniae, H. influenzae, M. Add Add S. aureus, pneumoniae, E. coli E. coli Add Staphylococcus epidermidis, S. aureus, ; MSSA, methicillin-sensitive 18 5 years ≥ immunocompromised , Alternative; BID, twice daily; CoNS, coagulase-negative staphylococci; CSF, cerebrospinal fluid; CT, computed tomography; CXR, chest x-ray; EBV, Epstein–Barr virus; FQ, fluoroquinolone; GAS, group A Infectious Syndrome Age Adolescent SINUSITIS Acute Chronic Seriously ill or TRACHEITIS UTI Cystitis Pyelonephritis Abnormal host/urinary tract VENTRICULOPERITONEAL SHUNT, INFECTED . First antibiotics listed indicate treatment of choice. organism and susceptibility information is available. Alt streptococcus; GBS, group B GNR, Gram-negative rods; Hib, Staphylococcus aureus urinary tract infection Recommendations modified from American Academy of Pediatrics. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book®: 2015 REPORT OF THE COMMITTEE ON INFECTIOUS DISEASES. Academy of Pediatrics; 2015 and McMillan JA, Lee CKK, Siberry GK, Carroll KC.

c. Peritonsillar abscess. Involves space surrounding palatine tonsil and is most common deep neck infection. Presents with sore throat, muffled voice, odynophagia, dysphagia, trismus, drooling, cervical lymphadenopathy, and uvular deviation. More likely unilateral, but can be bilateral. Most common in adolescents and young adults. Requires drainage and antibiotic coverage against β-lactamase–producing bacteria and anaerobes. Treat for about 5–7 days after drainage. d. Retropharyngeal abscess. Most common in ages 2–4 years, when space has small LNs that atrophy in adolescents. Etiology often polymicrobial, including S. aureus, S. pyogenes, viridans streptococci, Haemophilus, and anaerobes. Symptoms include sore throat, odynophagia, dysphagia, neck pain, swelling, reduced range of motion, and deviation of lateral wall of the oropharynx to midline. Lateral neck x-ray can show widening of retropharyngeal space, although CT is most sensitive. Depending on clinical situation, IV antibiotics alone may be tried (polymicrobial coverage including for S. aureus, such as ampicillin–sulbactam or clindamycin AND ceftriaxone) and if not better within 24–48 hours, consider intraoral surgical or CT-guided drainage. E. Selected Viral Infections: Table 17.9 and Fig. 17.6 Treatment for most viral illnesses is supportive care unless otherwise specified. F. Selected Tickborne Infections12: Table 17.10 For all tickborne illnesses, infection typically occurs between spring and fall seasons. G. Fungal and Yeast Infections 1. Diagnosis a. Place specimen (nail or skin scrapings, biopsy specimens, fluids from tissues or lesions) in 10% potassium hydroxide (KOH) on glass slide to look for hyphae, pseudohyphae. b. Germ tube screen of yeast (3 hours) for Candida albicans: All germ tube–positive yeast are C. albicans, but not all C. albicans are germ tube–positive. 2. Common community-acquired fungal infections, etiology, and treatment (Table 17.11) H. Sexually Transmitted and Genitourinary Infections For information about the diagnosis and treatment of common sexually transmitted infections as well as the evaluation and management of pelvic inflammatory disease, please see Chapter 5, Tables 5.3 and 5.4. I. Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS) Recommendations provided are current at the time of publication. Please see the Centers for Disease Control and Prevention (CDC) guidelines on Text continued on p. 477

4 antibodies over time in acute mononucleosis appropriate if infectious mononucleosis suspected with negative heterophile throughout life, diagnosis in immunocompetent individuals depends on signs of acute infection, usually combined with CMV-specific IgG seroconversion or CMV-specific IgM. IgM may persist for months depending on assay. urine, saliva, blood, and tissue can also be helpful and allow for monitoring of treatment in immunocompromised hosts. the first week for 75%, second week for 90%–95%, only present in 50% of children < PCR amplification from vesicular fluid or scabs Diagnosis EBV-specific Ab testing See Fig. 17.6 for changes in EBV Because virus can be shed PCR-based detection of virus in Congenital: see Table 17.7 Heterophile antibody positive in Primarily clinical diagnosis Also via direct fluorescence or Virus intermittently shed throughout life after infection. Through saliva and urine. Breastmilk is most common source in early childhood most common source in adolescence and early adulthood organ transplantation transmission contact with fluid of skin lesions. period. Infection is ubiquitous. Community exposure: Sexual transmission is Nosocomial: Via blood or Congenital: Intrauterine Transmission Airborne spread or direct 10–21-day incubation Oral secretions Sexual transmission β -lactam cont’d thrombocytopenia, mild hepatocellular dysfunction. liver, lung, GI tract, and rarely CNS or mononucleosis-like syndrome with fatigue and cervical lymphadenopathy, can have mildly elevated transaminases and thrombocytopenia degree of compromise Less severe: Fever, leukopenia, Disseminated infection can involve Fever, malaise, headache followed by pruritic macules that evolve into vesicles Predisposes to severe GAS and S. aureus infections, encephalitis, pneumonia Vesicles clustered in 1–2 adjacent dermatomes. Can be complicated by postherpetic neuralgia. 20–30% lifetime risk in those with history of varicella fever, fatigue, exudative pharyngitis, headache, myalgia. Cervical and submandibular lymphadenopathy, splenomegaly; hepatomegaly if given Immunocompetent: Usually asymptomatic, Immunocompromised: Proportionate to Congenital/neonatal: See Table 17.7 Syndrome Primary infection: Varicella (chickenpox): Herpes zoster: reactivation of latent VZV. Congenital infection: see Table 17.7 Infectious mononucleosis: prodrome of Can have maculopapular rash, especially Also associated with oncogenesis (CMV) virus (VZV) Virus Varicella-zoster Cytomegalovirus Epstein–Barr virus TABLE 17.9 SELECTED VIRAL INFECTIONS—

Downloaded for dr.Rahmat Dani Satria, M.Sc, Sp.PK ([email protected]) at Universitas Gadjah Mada from ClinicalKey.com by Elsevier on July 28, 2018. For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. Chapter 17 Microbiology and Infectious Disease 475 Continued intravenous acyclovir in individuals at risk of moderate-to-severe infection. as routine treatment for uncomplicated varicella because of usual benign self-limited course. famciclovir, and valacyclovir reduce duration of illness and risk of postherpetic neuralgia. herpes zoster in immunocompromised children. athletic activities during splenomegaly and/or first 2–3 weeks of infection foscarnet, also used for prophylaxis in allograft transplant recipients valganciclovir or ganciclovir may limit hearing loss and improve neurologic development. Treatment/Comments For varicella: oral valacyclovir or Antiviral therapy not recommended For herpes zoster: acyclovir, IV acyclovir for varicella and Supportive care Avoid contact sports or strenuous Immunocompromised: Ganciclovir, Infants: Treatment with 4 yr. PCR amplification from vesicular fluid or scabs the first week for 75%, second week for 90%–95%, only present in 50% of children < appropriate if infectious mononucleosis suspected with negative heterophile antibodies over time in acute mononucleosis throughout life, diagnosis in immunocompetent individuals depends on signs of acute infection, usually combined with CMV-specific IgG seroconversion or CMV-specific IgM. IgM may persist for months depending on assay. urine, saliva, blood, and tissue can also be helpful and allow for monitoring of treatment in immunocompromised hosts. Diagnosis Primarily clinical diagnosis Also via direct fluorescence or Heterophile antibody positive in EBV-specific Ab testing See Fig. 17.6 for changes in EBV Because virus can be shed PCR-based detection of virus in Congenital: see Table 17.7 contact with fluid of skin lesions. period. Virus intermittently shed throughout life after infection. Through saliva and urine. Breastmilk is most common source in early childhood most common source in adolescence and early adulthood organ transplantation transmission Transmission Airborne spread or direct 10–21-day incubation Oral secretions Sexual transmission Infection is ubiquitous. Community exposure: Sexual transmission is Nosocomial: Via blood or Congenital: Intrauterine -lactam infections, encephalitis, β 17 thrombocytopenia, mild hepatocellular dysfunction. liver, lung, GI tract, and rarely CNS Fever, malaise, headache followed by pruritic macules that evolve into vesicles Predisposes to severe GAS and S. aureus pneumonia Vesicles clustered in 1–2 adjacent dermatomes. Can be complicated by postherpetic neuralgia. 20–30% lifetime risk in those with history of varicella fever, fatigue, exudative pharyngitis, headache, myalgia. Cervical and submandibular lymphadenopathy, splenomegaly; hepatomegaly if given or mononucleosis-like syndrome with fatigue and cervical lymphadenopathy, can have mildly elevated transaminases and thrombocytopenia degree of compromise Less severe: Fever, leukopenia, Disseminated infection can involve Syndrome Primary infection: Varicella (chickenpox): Herpes zoster: reactivation of latent VZV. Congenital infection: see Table 17.7 Infectious mononucleosis: prodrome of Can have maculopapular rash, especially Also associated with oncogenesis Immunocompetent: Usually asymptomatic, Immunocompromised: Proportionate to Congenital/neonatal: See Table 17.7 virus (VZV) (CMV) Virus Varicella-zoster Epstein–Barr virus Cytomegalovirus

1:320

1:160 IgG – VCA 1:80 Early antigen

1:40 Nuclear antigen Antibody IgM – VCA 1:20 (≥4 yr)

IgM – VCA

1:10 Infectious mononucleosis (<4 yr)

0 02424613 Weeks Months Years Time after clinical onset

FIGURE 17.6 Graphic representation of the development of antibodies to Epstein–Barr virus antigens as a function of time from infection. Antibody titers are calculated as geometric mean values expressed as reciprocals of the serum dilution. The immunoglobulin M (IgM) response to viral capsid antigen (VCA) varies according to age of the patient. IgG, Immunoglobulin G. (From Jenson HB. Epstein-Barr Virus. In: Kliegman RE, Stanton B, St Geme J, et al. Nelson Textbook of Pediatrics. 20th ed. Philadelphia, PA: Elsevier; 2016.)

the diagnosis and management of children with HIV infection at www.aidsinfo.nih.gov/ for the most up-to-date recommendations. 1. Clinical presentation12,21 a. Acute infection with nonspecific findings, including intermittent fever, diarrhea, failure to thrive, parotitis, malaise, myalgia,

hepatosplenomegaly, lymphadenopathy, rash, oral ulcers, 17 leukopenia, thrombocytopenia, elevated transaminases b. May present with opportunistic infections, including Pneumocystis jirovecii pneumonia, candidiasis, herpes zoster, varicella, toxoplasmosis, cryptosporidiosis c. Thorough history essential, including in utero exposure, injection drug use, unprotected sexual intercourse, and international adoption d. If abnormal findingsor confirmed diagnosis, consult pediatric HIV specialist

TABLE 17.10 SELECTED TICKBORNE ILLNESSES Disease Geographic Distribution Presentation Transmission Diagnosis Treatment Lyme disease New England Early localized: Up to 1 month after Spirochete Borrelia Early: Clinical diagnosis. Tests No antibiotics recommended Middle Atlantic tick bite. Erythema migrans, fever, burgdorferi carried by deer are insensitive and not for ticks attached Upper Midwest headache, myalgia, malaise tick, Ixodes scapularis or recommended in first 4 <24–48 hr Pacific Northwest Early disseminated: 3–10 weeks after Ixodes pacificus; requires weeks of infection Early localized: Doxycycline for bite. Secondary erythema migrans 24–48 hr of tick Early disseminated and late 14 days for children ≥8 with multiple smaller target attachment. Disseminates disease: EIA or IFA for years. Amoxicillin or lesions, cranioneuropathy systemically through blood antibodies. IgM detectable cefuroxime for 14 days for (especially facial nerve palsy), and lymphatics for first 30 days, IgG younger children systemic symptoms, detectable by week 6. False Early disseminated or late lymphadenopathy, 1% develop positives occur with viral onset: same medications for carditis with heart block or aseptic infections, other spirochetes, 14–21 days meningitis and autoimmune disease. See AAP Redbook for more Late disease: 2–12 months from If antibody negative, no further details on treatment course initial bite. Pauciarticular arthritis testing required. If positive, for complications of large joints in 7% of untreated, confirm with western blot. peripheral neuropathy, Perform LP as clinically encephalopathy indicated for CNS involvement.

Rocky Mountain Widespread; most Incubation period is ~1 week (range Rickettsia rickettsii, an Identification of R. rickettsii Doxycycline is recommended spotted fever common in South 2–14 days) obligate intracellular DNA by PCR in blood and for children of any age and Atlantic, Southeastern, Fever, headache, myalgia, nausea, Gram-negative bacillus serum specimens, preferably should be started as soon and South Central anorexia, abdominal pain, diarrhea transmitted to humans by within the first week of as the diagnosis is United States Rash: Usually appears by day 6; a tick bite symptoms and within 24 suspected. Duration: 7 days initially erythematous and macular; hours of starting antibiotics and continue until patient is progresses to maculopapular and Gold standard is indirect afebrile for ≥3 days and has petechial due to vasculitis. Usually fluorescent antibody; IgG demonstrated clinical appears on wrists and ankles and and IgM increase around improvement spreads proximally. Palms and 7–10 days. soles are often involved. Negative result (PCR or Laboratory manifestations: antibody testing) does not Thrombocytopenia, hyponatremia, rule out the diagnosis and anemia. White blood cell count usually normal Severe disease may manifest in CNS, cardiac, pulmonary, gastrointestinal tract, renal involvement, disseminated intravascular coagulation (DIC), and shock leading to death. 20%–80% case fatality if untreated TABLE 17.10 SELECTED TICKBORNE ILLNESSES Disease Geographic Distribution Presentation Transmission Diagnosis Treatment Lyme disease New England Early localized: Up to 1 month after Spirochete Borrelia Early: Clinical diagnosis. Tests No antibiotics recommended Middle Atlantic tick bite. Erythema migrans, fever, burgdorferi carried by deer are insensitive and not for ticks attached Upper Midwest headache, myalgia, malaise tick, Ixodes scapularis or recommended in first 4 <24–48 hr Pacific Northwest Early disseminated: 3–10 weeks after Ixodes pacificus; requires weeks of infection Early localized: Doxycycline for bite. Secondary erythema migrans 24–48 hr of tick Early disseminated and late 14 days for children ≥8 with multiple smaller target attachment. Disseminates disease: EIA or IFA for years. Amoxicillin or lesions, cranioneuropathy systemically through blood antibodies. IgM detectable cefuroxime for 14 days for (especially facial nerve palsy), and lymphatics for first 30 days, IgG younger children systemic symptoms, detectable by week 6. False Early disseminated or late lymphadenopathy, 1% develop positives occur with viral onset: same medications for carditis with heart block or aseptic infections, other spirochetes, 14–21 days meningitis and autoimmune disease. See AAP Redbook for more Late disease: 2–12 months from If antibody negative, no further details on treatment course initial bite. Pauciarticular arthritis testing required. If positive, for complications of large joints in 7% of untreated, confirm with western blot. peripheral neuropathy, Perform LP as clinically encephalopathy indicated for CNS involvement. Gadjah Madafrom ClinicalKey.com byElsevier onJuly 28,2018.For personal useonly. Noother Downloaded fordr.RahmatDani Satria,M.Sc,Sp.PK ([email protected]) atUniversitas

uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved. TABLE 17.10 SELECTED TICKBORNE ILLNESSES—cont’d Disease Geographic Distribution Presentation Transmission Diagnosis Treatment Ehrlichiosis Southeastern, South Systemic febrile illness with Ehrlichia chaffeensis Identification of DNA by PCR Doxycycline for at least 3 days Central, East Coast, headache, chills, rigors, malaise, (human monocytic from whole blood is highly after defervescence, for a and Midwestern myalgia, nausea. Rash is variable ehrlichiosis) and Ehrlichia sensitive and specific. minimum total course of 7 United States in location and appearance ewingii associated with Isolation in culture must be days Laboratory manifestations: the bite of a Lone Star done at CDC specialty labs Leukopenia, anemia, and tick (Amblyomma from samples prior to transaminitis. CSF with lymphocytic americanum), although initiation of antibiotics. pleocytosis or elevated protein other tick species may be More severe disease: Pulmonary vectors. Mammalian infiltrates, bone marrow hypoplasia, reservoirs include respiratory failure, encephalopathy, white-tailed deer and meningitis, DIC, spontaneous white-footed mice. hemorrhage, and renal failure Anaplasmosis North Central, and Same as Ehrlichia Anaplasma Same as Ehrlichia Same as Ehrlichia Northeastern United phagocytophilum, States, Northern transmitted by the deer California tick (Ixodes scapularis) or western black-legged tick (Ixodes pacificus)

CDC, Centers for Disease Control and Prevention; CNS, central nervous system; CSF, cerebrospinal fluid; EIA, enzyme immunoassay; Hr, Hour; IFA, immunofluorescent assay; IgG, immunoglobulin G; IgM, immunoglobulin M; PCN, penicillin; PCR, polymerase chain reaction Data from American Academy of Pediatrics. In: Kimberlin DW, Brady MT, Jackson MA, Long SS, eds. Red Book®: 2015 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; 2015. Chapter 17 Microbiology and Infectious Disease 481

TABLE 17.11 COMMON COMMUNITY-ACQUIRED FUNGAL INFECTIONS Suggested Length of Disease Usual Etiology Suggested Therapy Therapy Tinea capitis Trichophyton tonsurans, Oral griseofulvin 4–8 weeks or 2 (ringworm of Microsporum canis, (ultramicro) or weeks after scalp) Microsporum terbinafine clinical audouinii, Alt: 2–4 weeks of resolution Microsporum itraconazole or Addition of gypseum, fluconazole (once corticosteroid Trichophyton weekly) may augment mentagrophytes, Fungal shedding treatment of Trichophyton decreased with kerion violacea, selenium sulfide or Trichophyton ketoconazole shampoo, soudanense but shampoo alone is not sufficient treatment Tinea corporis/pedis/ Epidermophyton Topical antifungal 4 weeks for tinea cruris (ringworm of floccosum, (miconazole, corporis body/feet/genital Trichophyton rubrum, clotrimazole, 1–4 weeks for region) T. mentagrophytes, ketoconazole) once daily tinea pedis M. canis or BID; terbinafine BID 4–6 weeks for Alt: griseofulvin, tinea cruris itraconazole, fluconazole Oral candidiasis Candida albicans, Nystatin suspension or 7–10 days, then (thrush) in Candida tropicalis clotrimazole troche (only continue immunocompetent nystatin for infants) 3 days after patients clinical resolution Candidal skin C. albicans Topical nystatin, 7 days infections miconazole, clotrimazole (intertriginous) Tinea unguium T. mentagrophytes, T. Itraconazole or terbinafine 6–12 weeks (ringworm of nails) rubrum, E. floccosum

BID, Twice daily Modified from McMillan JA, Lee CKK, Siberry GK, Carroll KC. The Harriet Lane Handbook of Pediatric Antimicrobial Therapy. Philadelphia, PA: Elsevier; 2014. See Table 1.4 in The Harriet Lane Handbook of Pediatric Antimicrobial Therapy for further details regarding treatment of fungal infections. 17

2. Diagnosis a. Counseling: Legal requirements for consent vary by state. Counseling includes informed consent for testing, implications of positive test results, and prevention of transmission. b. Testing (1) Perinatal: See Table 17.12 for diagnosis in perinatal period.22

TABLE 17.12 DIAGNOSIS AND MANAGEMENT FOR INFANTS WITH IN UTERO HIV EXPOSURE Age Laboratory Tests* Next Steps Prenatal/Labor Opt-out testing of all pregnant Start ART in mother women If viral load RNA >1000 copies/mL or HIV antibody testing in third unknown at labor, start IV zidovudine trimester, before 36 weeks’ and consider cesarean section if gestation preferred greater than 38 weeks’ gestation Rapid HIV testing with confirmation if unknown HIV status during labor Newborn HIV DNA PCR if maternal status Start ZDV within 6–12 hours of delivery unknown, or high risk of Nevirapine if no maternal ART; three infection doses: first dose within 48 hours of Baseline CBC with differential birth, second dose 48 hours after first dose, third dose 96 hours after second dose 2–3 weeks HIV DNA PCR (or RNA assay) Check ZDV dosing and administration CBC with differential Assess psychosocial needs, consider case management referral 4–6 weeks HIV DNA PCR (or RNA assay) Discontinue ZDV regardless of PCR CBC with differential result (ZDV monotherapy is used during first 6 weeks for prophylaxis only) Presumptively exclude HIV infection if results of ≥2 weeks PCR and ≥4 weeks PCR both negative. No TMP-SMX needed If PCR results not yet known, begin Pneumocystis jirovecii pneumonia prophylaxis, such as TMP-SMX 2 months Discontinue TMP-SMX if DNA or RNA testing negative 4–6 months HIV DNA PCR (or RNA assay) Definitively exclude HIV infection: Two negative PCRs at ≥1 month and ≥4 months, as long as no signs/ symptoms of HIV infection 18–24 months Antibody testing may be performed to confirm clearance of maternal HIV antibodies. If present, need to use nucleic acid testing

*Any abnormal result requires prompt pediatric HIV specialist consultation. ART, Antiretroviral therapy; CBC, complete blood cell count; HIV, human immunodeficiency virus; IV, intravenous; PCR, polymerase chain reaction; TMP-SMX, trimethoprim–sulfamethoxazole; ZDV, zidovudine Modified from Department of Health and Human Services guidelines for pediatric and perinatal HIV infection (see www.aidsinfo.nih.gov for more detailed information).

(2) Children >24 months23: HIV antibody testing possible as maternal antibodies likely cleared. If concern for breastmilk exposure, test immediately, then 4–6 weeks, 3 months, and 6 months after stopping breastfeeding. (3) Adolescents24: HIV screening with antigen/antibody assay with opt-out consent as part of routine clinical care. If positive, confirm with HIV-1/HIV-2 immunoassay; if indeterminate, HIV-1 nucleic acid testing. 3. Management21-24 a. Perinatal exposure (1) See Table 17.12 for management during perinatal period. b. Criteria for starting antiretroviral therapy (ART) in HIV-positive patients: U.S. Department of Health and Human Services Guidelines22-24 (1) <12 months: All HIV-infected infants, regardless of immunologic, virologic, or clinical status (2) 12 months to 18 years: Urgently start if CDC Stage 3 defining opportunistic infections or Stage 3 immunodeficiency <( 500 cells/ mm3 if age 1 to <6 years, <200 cells/mm3 if ≤6 years). Recommended if moderate symptoms (CDC stage 2), viral load >100,000 copies/mL, and Stage 2 CD4 counts (500–999 cells/ mm3 for 1 to <6 years, 200–499 cells/mm3 if ≤6 years). Milder symptoms and greater CD4 counts can be considered on a case-by-case basis. (3) Adolescents 18 years and older: Initiate ART regardless of CD4 count at diagnosis. (4) Note: World Health Organization guidelines recommend treatment for all individuals diagnosed with HIV.25 c. Therapy: Mainstay is combination ART of at least three drugs from at least two different classes. Go to http://www.aidsinfo.nih.gov/ for most current therapy recommendations. 4. Lab monitoring a. Absolute CD4 count is now preferred over percentage. b. At diagnosis: CD4 count, plasma HIV RNA viral load, genotype resistance. If starting therapy, HLA-B*5701 (for abacavir) and hepatitis B. c. Not on ART: Every 3–4 months, CD4 count, plasma HIV RNA viral

load, CBC with differential, complete metabolic panel with glucose, 17 renal function, albumin, transaminases, lipid panel. Every 6–12 months, obtain urinalysis to evaluate for nephropathy. Other testing should be performed based on concern for opportunistic infections. d. On ART: At 2–4 weeks after initiation or switching therapy, CD4, viral load, and labs according to possible toxicities of ART. Then similar testing as above every 3–4 months. e. Once viral suppression achieved, CD4 improved, good adherence, and otherwise stable for 2–3 years, can space to every 6–12 months.

f. Latent tuberculosis skin testing starting at age 3 to 12 months, and then annually.

J. Tuberculosis (TB) 1. Clinical presentation12 a. Infection often asymptomatic (latent TB). b. Can progress to TB disease 1–6 months after infection with nonspecific findings including fever, cough, lymphadenopathy, weight loss, failure to thrive, night sweats, and chills. Cavitation and necrosis is uncommon in children. Infants and postpubescent adolescents are at greater risk of progression. c. Extrapulmonary involvement can include any organ. 2. Diagnosis a. Screening guidelines12,26: The American Academy of Pediatrics recommends risk assessment questionnaire, testing for infection in at-risk individuals at first well-child visit and then every 6 months in first year of life, and then routine care (at least annually). Screening questions include: (1) Born outside the United States in countries with endemic infection (2) Traveled outside United States in countries with endemic infection for ≥1 week (3) Family member with positive TST (4) Exposed to someone who had TB disease (5) Special populations including children with HIV, organ transplant, and those on immunosuppressive therapies including tumor necrosis factor blockers/antagonists b. Latent TB infection (LTBI) (1) IGRA (interferon gamma release assay): Similar sensitivity to TST but higher specificity [because antigens used are not found in bacillus Calmette–Guérin (BCG) or most pathogenic nontuberculous Mycobacteria]. Preferred for children 5 years or older, BCG-positive individuals, those unlikely to return for TST read, and if TST negative and still at high risk. (2) TST i. Inject five tuberculinunits of purified protein derivative (0.1 mL) intradermally with a 27-gauge needle on the volar aspect of the forearm to form a 6- to 10-mm wheal. Results of skin testing should be read 48–72 hours later. ii. Definition of positiveMantoux test (regardless of whether BCG has been previously administered): Box 17.1 iii. The incubation period from TB infection to a positive TST or IGRA is approximately 2–10 weeks. iv. Measles vaccine can suppress tuberculin for 4–6 weeks. c. Active TB disease (1) If positive for LTBI, obtain chest x-ray (2) If symptoms indicate TB disease, determine source

BOX 17.1 DEFINITIONS OF POSITIVE TUBERCULIN SKIN TESTING12

Induration ≥5 mm

• Children in close contact with known or suspected contagious cases of tuberculosis • Children suspected to have tuberculosis based on clinical or radiographic findings • Children on immunosuppressive therapy or with immunosuppressive conditions (including HIV infection) Induration ≥10 mm

• Children at increased risk for dissemination based on young age (<4 yr) or with other medical conditions (cancer, diabetes mellitus, chronic renal failure, or malnutrition) • Children with increased exposure: Those born in or whose parents were born in endemic countries; those with travel to endemic countries; those exposed to HIV-infected adults, homeless persons, illicit drug users, nursing home residents, or incarcerated or institutionalized persons Induration ≥15 mm

• Children ≥4 yr without any risk factors

(3) Specimen sources include sputum, bronchial washings, gastric aspirates (three mornings before feeding/ambulation), pleural fluid, cerebrospinal fluid, urine, tissue biopsy. i. Solid media culture can take as long as 10 weeks, liquid media 1–6 weeks. Nucleic acid amplification testing can provide more rapid diagnosis. (4) Lumbar puncture to assess TB meningitis depending on signs and symptoms. Strongly consider in children aged <24 months with confirmed TB as it is difficult to assess for TB meningitis. 3. Treatment a. Latent TB infection (1) Indications:

i. Children with positive tuberculin tests but no evidence of 17 clinical disease ii. Recent contacts, especially with HIV-infected children, of people with TB disease, even if tuberculin test and clinical evidence are not indicative of disease (2) Isoniazid susceptible: 9 months of isoniazid daily [if daily therapy not possible, alternative is DOT (directly observed therapy) twice weekly for 9 months] or 12 weeks of weekly isoniazid and rifapentine by DOT for those aged 12 years and older (3) Isoniazid resistant: Rifampin daily for 4 months

b. Active TB disease: Consult infectious disease specialist. Includes 6-month regimen, including 2 months RIPE (rifampin, isoniazid, pyrazinamide, ethambutol) followed by 4 months of rifampin/isoniazid. See Red Book 2015 for more details on different regimens, including for meningitis. c. Multidrug resistance (MDR): Consult infectious disease specialist. At least isoniazid and rifampin resistant. Will require four or five anti-TB drugs for 12–24 months, including an injectable for 4–6 months. Extensively drug resistant (XDR) if also resistant to at least a fluoroquinolone and at least one of the parenteral drugs.

K. Exposures to Bloodborne Pathogens and Prophylaxis 1. General practice27 a. Always practice universal precautions, use personal protective equipment, and safely dispose of sharps to reduce chance of transmission. b. Regardless of status of patient, if you experience a needlestick or splash exposure, immediately wash with soap/water, irrigate, report to supervisor, and seek medical assistance. c. There is an increased risk of transmission if large volume of blood, prolonged exposure, high viral titer, deep injury, or advanced disease. d. Initial testing: Source should be tested for HIV antibody, hepatitis C antibody, and hepatitis B surface antigen. Exposed person should be tested for HIV antibody, hepatitis C antibody, hepatitis B surface antibody (to look for immune status), and hepatitis B surface antigen. e. For assistance, contact Clinicians’ Postexposure Prophylaxis (PEP) Line at 1-888-448-4911. 2. HIV: Updated guidelines may be found at aidsinfo.nih.gov: a. Pre-exposure prophylaxis (PrEP)28: Studies have all been conducted in individuals 18 years and older. Current CDC guidelines recommend PrEP (tenofovir, disoproxil, fumarate, and emtricitabine) as an option for HIV prevention for individuals 18 years and older who are at high risk for HIV acquisition. For adolescent minors, they recommend considering risks, benefits, and that local laws and rules about autonomy vary by state. b. Postexposure prophylaxis (PEP)29,30 (1) Indications for occupational PEP: Consider with percutaneous, mucosal, or skin exposure to blood or bodily fluids from a patient with known HIV or if unknown, at high suspicion of infection. (2) Indications for nonoccupational (nPEP): Consider with unprotected vaginal/anal intercourse, oral sex with ejaculation or blood exposure, needle sharing, or injuries with blood exposure from an individual with known HIV or unknown status. (3) Regimen: Initiate as soon as possible (lower likelihood of efficacy at greater than 72 hours), three-drug (or more) ART regimen for 28 days. Preferred tenofovir and entricitabine with raltegravir or

dolutegravir. Consult infectious disease expert for alternative regimens. (4) Follow-up testing can occur at 6 weeks, 12 weeks, and 6 months; if fourth–generation testing available, can be done at 6 weeks and 4 months. 3. Hepatitis B31: Risk of transmission 37%–62% if surface antigen and e-antigen positive, 23%–37% if surface antigen positive, e-antigen negative. Postexposure management includes hepatitis B immune globulin and initiation of hepatitis B vaccine series depending on immune status. For details, see Chapter 16. 4. Hepatitis C31: Risk of transmission about 1.8%. No preventive therapy available. Serologic testing and follow-up are important to document if infection occurs.

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