Pediatrics PDF - Sepsis and Meningitis

Pediatrics I. SEPSIS AND MENINGITIS A. Clinical Presentation 1. Signs and symptoms a. Neonates (less than 28 days old or less than 44 weeks’ corrected gestational age for premature neonates who were originally born less than 37 weeks’ gestational age) i. General: Temperature instabi...

Pediatrics I. SEPSIS AND MENINGITIS A. Clinical Presentation 1. Signs and symptoms a. Neonates (less than 28 days old or less than 44 weeks’ corrected gestational age for premature neonates who were originally born less than 37 weeks’ gestational age) i. General: Temperature instability, feeding intolerance, lethargy, grunting, nasal flaring, retractions, apnea ii. More likely to be associated with meningitis: Bulging fontanelle and seizures b. Infants (1–12 months) and children (1–18 years) i. General: Fever, loss of appetite, emesis, myalgias, arthralgias, cutaneous manifestations (e.g., petechiae, purpura, rash) ii. More likely to be associated with meningitis: Nuchal rigidity, back pain, Kernig sign (restriction in passive extension at the knee because of spasm of the hamstring muscles), Brudzinski sign (consists of reflex flexion of a lower extremity after passive flexion of the opposite extremity), headache, photophobia, altered mental status, and seizures 2. Early versus late onset neonatal sepsis a. Onset i. Early: Within 72 hours of birth ii. Late: After the first 72 hours of life b. Risk factors i. Early (a) Usually related to maternal or obstetric risk factors: very low birth weight (less than 1500 g), prolonged rupture of amniotic membranes (greater than 18 hours), maternal fever, prolonged labor, maternal genitourinary tract colonization with group B Streptococcus, maternal endometritis, or chorioamnionitis ii. Late (a) Unrelated to obstetric risk factors (b) Usually related to iatrogenic/nosocomial factors (e.g., endotracheal tubes, central venous catheters) c. Incidence i. Early (a) Incidence increases with decreasing gestational age: (1) 0.5 of 1000 live births (term neonates) (2) 1 of 1000 live births (late preterm neonates 34–36 weeks’ gestation) (3) 6 of 1000 live births (preterm neonates less than 34 weeks’ gestation) (4) 20 of 1000 live births (preterm neonates less than 29 weeks’ gestation) (5) 32 of 1000 live births (preterm neonates 22–24 weeks’ gestation) (b) Meningitis occurs in less than 10% of cases. ii. Late (a) Incidence increases with decreasing gestational age: (1) 9% greater than 34 weeks’ gestation (2) 56% 24–25 weeks’ gestation (b) Meningitis occurs in 60% of cases ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-415 Pediatrics d. Mortality i. Increases with decreasing gestational age (a) 1.6% in term neonates born 37 weeks’ gestation or greater (b) 30% in preterm neonates 25–28 weeks (c) 50% in preterm neonates 22–24 weeks 3. Definition of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic shock in children a. SIRS: Presence of at least two of the four following criteria, one of which must be abnormal temperature or leukocyte count: i. Core temperature greater than 38.5°C or less than 36°C ii. Tachycardia (value based on age) over a 1/2- to 4-hour period or for infants younger than 1 year: bradycardia (value based on age) over a 1/2-hour period iii. Tachypnea (value based on age) iv. Leukocyte count elevated or depressed for age or greater than 10% immature neutrophils b. Sepsis: SIRS in the presence of, or as a result of, suspected or proven infection c. Severe sepsis: Sepsis plus one of the following: i. Cardiovascular organ dysfunction ii. Acute respiratory distress syndrome iii. Two or more other organ dysfunctions d. Septic shock: Sepsis and cardiovascular organ dysfunction, defined as one of the following despite administration of a fluid bolus of 40 mL/kg or greater in 1 hour: i. Decrease in blood pressure to less than 5th percentile on the basis of age or systolic blood pressure less than 2 SD on the basis of age ii. Need for vasoactive medications to maintain blood pressure iii. Two of the following: (a) Unexplained metabolic acidosis (b) Increased lactate (c) Oliguria (urinary output less than 0.5 mL/kg/hour) (d) Prolonged capillary refill greater than 5 seconds (e)  Core to peripheral temperature gap greater than 3°C 4. Cerebrospinal fluid findings (Table 1) Table 1. Cerebrospinal Fluid Findings Laboratory Value WBC (cells/mL) Neutrophils (%) Glucose (mg/dL) Protein (mg/dL) RBC (cells/mL) Normal Child 0–6 0 40–80 20–30 0–2 Normal Newborn 0–30 2–3 32–121 19–149 0–2 Bacterial Meningitis >1000 >50 <30 >100 0–10 Viral Meningitis 100–500 <40 >30 50–100 0–2 RBC = red blood cell count; WBC = white blood cell count. Adapted with permission from the American Academy of Pediatrics: Wubbel L, McCracken GH. Management of bacterial meningitis: 1998. Pediatr Rev 1998;19:78-84. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-416 Pediatrics Patient Case 1. An infant born at 36 weeks’ gestation develops respiratory distress, hypotension, and mottling at 5 hours of life. The child is transported to the neonatal intensive care unit, where he has a witnessed seizure, and cultures are obtained. Maternal vaginal cultures are positive for group B Streptococcus, and three doses of penicillin were given to the mother before delivery. Which is the best empiric antibiotic regimen? A. Vancomycin plus cefotaxime. B. Ampicillin plus ceftazidime. C. Ampicillin plus ceftriaxone. D. Ceftazidime plus gentamicin. B. Common Pathogens for Sepsis and Meningitis (Table 2) Table 2. Common Pathogens Age 0–1 mo 1–3 mo a Organisma Early onset: Group B Streptococcus (Streptococcus agalactiae) – 40%–45% of cases in term and late-preterm neonates (20% of cases in preterm neonates < 34 weeks’ gestation) Escherichia coli – 10%–15% of cases in term and late-preterm neonates (50% of cases in preterm neonates < 34 weeks’ gestation) Listeria monocytogenes – < 2% of cases in term and late-preterm neonates Late onset: Viral (e.g., herpes simplex virus) Coagulase-negative Staphylococcus (nosocomial) Gram-negative bacteria (e.g., Klebsiella spp., Pseudomonas spp., Enterobacter spp.; nosocomial) Neonatal pathogens (see above), Group B Streptococcus - 39% of cases Haemophilus influenzae type Bb Neisseria meningitidis - 12% of cases Streptococcus pneumoniae - 14% of cases 3 mo – 12 yr Haemophilus influenzae type Bb Neisseria meningitidis - 34%–55% of cases Streptococcus pneumoniae - 24%–45% of cases > 12 yr Neisseria meningitidis - 55% of cases Streptococcus pneumoniae - 21% of cases For healthcare-associated meningitis and ventriculitis, organisms will vary and are likely to include more resistant organisms. H. influenzae is no longer a common pathogen where the vaccine is routinely used. b C. Potential Empiric Antibiotic Regimens for Sepsis and Meningitis (Table 3) Table 3. Potential Empiric Antibiotic Regimens Age 0–1 mo 1–3 mo >3 mo Regimen Ampicillin + gentamicina Ampicillin + ceftriaxoneb or vancomycinc + ceftriaxoneb Ceftriaxone + vancomycincd  ay consider use of broader-spectrum gram-negative agents in very critically ill neonates depending on local antibiotic M resistance data. Cefotaxime (or ceftazidime with cefotaxime drug shortage) may be considered instead of gentamicin when there is a concern for meningitis. b May consider cefotaxime (or ceftazidime with cefotaxime drug shortage) instead of ceftriaxone for infants < 2 mo because of potential contraindications with ceftriaxone. c May defer vancomycin if no concern for meningitis. d For healthcare-associated meningitis and ventriculitis, the empiric regimen should be vancomycin + an antipseudomonal beta-lactam. a ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-417 Pediatrics Patient Cases 2. Culture results for the patient in question 1 reveal gram-negative rods in the cerebrospinal fluid. Which recommendation regarding antibiotic prophylaxis is best? A. The patient’s 5-month-old stepsister is at high risk because she is not fully immunized; therefore, the patient should receive rifampin. B. The patient should receive rifampin to eliminate nasal carriage of the pathogen. C. Antibiotic prophylaxis is not indicated in this case. D. All close contacts should receive rifampin for prophylaxis. 3. A 6-year-old boy presents to the emergency department with a temperature of 104°F (40°C), altered mental status, and petechiae. There is no history of trauma. The results of a toxicology screen are negative. A complete blood cell count reveals 32 × 103 cells/mm3 with 20% bands. Culture results are pending. The patient has no known drug allergies. Which antibiotic regimen provides the best empiric coverage? A. Ampicillin plus gentamicin. B. Cefuroxime. C. Ceftriaxone plus vancomycin. D. Rifampin. D. Sequelae of Meningitis 1. Hearing loss 2. Mental retardation and learning deficits 3. Visual impairment 4. Seizures 5. Hydrocephalus 6. Mortality 5%–10% (10%–20% in neonates) E. Steroids for Meningitis 1. Use of steroids for pediatric meningitis to prevent neurologic complications (e.g., hearing loss) is controversial. 2 A large meta-analysis showed reduced hearing loss with H. influenzae type B (Hib) meningitis only in children. However, Hib is less common now with routine vaccination. 3. Recommendations from the American Academy of Pediatrics (AAP) on this topic are summarized as follows: a. Dexamethasone may be considered for suspected bacterial meningitis caused by Hib in children older than 6 weeks after considering risk-benefit. i. Example: A child with signs/symptoms of meningitis has confirmed recent exposure to someone with a Hib infection b. Data are insufficient to recommend routine adjunctive corticosteroid therapy for pediatric pneumococcal meningitis. c. If dexamethasone is used, it should be administered before or at the same time as the first dose of antibiotics. d. The usual dosage is dexamethasone 0.15 mg/kg/dose every 6 hours for 2 days. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-418 Pediatrics F. Chemoprophylaxis of Bacterial Meningitis 1. Purpose: Prevent the spread of H. influenzae and N. meningitidis to contacts of the patient at high risk 2. High-risk groups a. Household contacts b. Nursery or day care center contacts c. Direct contact (e.g., health care providers) with index patient’s secretions during the 7 days preceding or up to 24 hours after initiation of appropriate antibiotic therapy d. Individuals with prolonged contact (more than 8 hours for N. meningitidis and 4 hours or more for H. influenzae) while close (less than 3 feet) to patient in the preceding 7 days of symptom onset 3. Regimens (Table 4) Table 4. Regimens for Chemoprophylaxisa Drug Rifampin Ceftriaxone Ciprofloxacinb Neisseria meningitidis <1 mo old: 5 mg/kg/dose PO every 12 hr × 2 days ≥1 mo old: 10 mg/kg/dose (maximum 600 mg) PO every 12 hr × 2 days <15 yr old: 125 mg IM × 1 dose ≥15 yr old: 250 mg IM × 1 dose ≥1 mo old: 20 mg/kg/dose (maximum 500 mg) PO × 1 dose Haemophilus influenzae <1 mo old: 10 mg/kg/dose PO daily × 4 days ≥ 1 mo old: 20 mg/kg/dose (maximum 600 mg) PO daily × 4 days Not indicated Azithromycin is a possible alternative, but it is not routinely recommended. Ciprofloxacin should only be used if fluoroquinolone-resistant strains of N. meningitidis have not been reported in the community. IM = intramuscularly; PO = orally/enterally. a b II. RSV INFECTION A. Clinical Presentation 1. Seasonal occurrence: Depends on geographic location and usually lasts 4–5 months a. Season onset ranges from October to late January b. Season offset ranges from late January to early April c. Exception: Florida has an earlier RSV season onset and longer duration than the rest of the country d. Exception: There was an unusual spike in RSV cases in summer/fall 2021 during the coronavirus disease 2019 (COVID-19) pandemic after nearly no cases during winter 2020–2021 2. Signs and symptoms a. Neonates and infants: Lower respiratory tract symptoms (e.g., bronchiolitis and pneumonia), wheezing, lethargy, fever, irritability, poor feeding, and apnea b. Older children: Upper respiratory tract symptoms (e.g., rhinorrhea, cough) c. Most cases are mild and self-limited. 3. RSV accounts for more than 80% of lower respiratory tract infections in infants younger than 1 year. 4. RSV is the most common cause of pediatric bronchiolitis and pneumonia. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-419 Pediatrics B. Risk Factors for Severe Disease 1. Premature birth 2. Chronic lung disease or bronchopulmonary dysplasia 3. Cyanotic or complicated congenital heart disease 4. Moderate to severe pulmonary hypertension 5. Immunodeficiency 6. Airway abnormalities or neuromuscular conditions compromising the handling of respiratory secretions 7. Other a. Lower socioeconomic status b. Passive smoking c. Day care attendance d. Siblings younger than 5 years Patient Case 4. You are screening infants during the current RSV season for risk factors associated with the development of severe RSV infection. Which patient is the best candidate for the use of palivizumab for RSV prophylaxis? A. An 18-month-old child, born at 26-weeks’ gestation with a history of chronic lung disease who has not received oxygen or medications during the past 8 months. B. A 5-month-old infant, born at 28-weeks’ gestation with a history of chronic lung disease who was discharged from the hospital without oxygen or medications. C. A 41-day-old infant, born at 31 weeks’ gestation, without a history of chronic lung disease who will attend day care. D. A 10-month-old infant, born at 37 weeks’ gestation, with a surgically repaired congenital heart defect. C. Prophylaxis 1. Nonpharmacologic: Avoid crowds during RSV season and conscientiously use good handwashing practice 2. Palivizumab (Synagis®) a. Dosing: 15 mg/kg/dose intramuscularly, given monthly during RSV season for up to 5 doses i. There is a 58% decrease in palivizumab serum concentration after cardiopulmonary bypass; therefore, an additional postoperative dose of palivizumab is recommended as soon as the patient is medically stable. b. Effects on outcomes i. A 55% reduction in hospitalizations for RSV ii. No reduction in overall mortality iii. Does not interfere with the response to vaccines iv. Not recommended for the prevention of nosocomial transmission of RSV c. The AAP recommendations for use were most recently updated in 2014 and were reaffirmed in 2017 and again in 2019 (Table 5). d. Note that prophylaxis should be discontinued if an RSV hospitalization occurs. e. AAP issued updated interim guidance in 2021 and again in 2022 addressing the change in RSV circulation and interseasonal spread that occurred during the COVID-19 pandemic. AAP strongly supports consideration of palivizumab for eligible patients also during the interseasonal spread of RSV and notes that use should not be limited only to the typical fall/winter season when interseasonal RSV cases are high. 3. Other monoclonal antibodies and vaccines are in development; however, palivizumab is currently the only U.S. Food and Drug Administration (FDA)-approved product recommended for RSV prevention. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-420 Pediatrics Table 5. AAP Guidelines for Palivizumab Use Gestational Age at Start of RSV Age (wk + days) Season (mo) Other Required Criteria <29 + 0 <12 — 29 + 0 to 31+6 <12 Chronic lung disease necessitating more than 21% oxygen for at least the first 28 days of life <32 + 0 <24 Consider prophylaxis for a second RSV season if chronic lung disease has necessitated medical therapy within the 6 months preceding the start of RSV season Any <12 Patient with hemodynamically significant acyanotica congenital heart disease receiving medication for congestive heart failure and will need cardiac surgery Any <12 Moderate to severe pulmonary hypertension Any <12 Congenital abnormalities of airway or neuromuscular disease that impairs the ability to clear airway secretions Any <24 Profoundly immunocompromised (may be considered) Maximum Number of Doses 5 5 5 5 5 5 5 Infants with cyanotic heart defects can be considered for prophylaxis after consultation with a pediatric cardiologist. AAP = American Academy of Pediatrics; RSV = respiratory syncytial virus. a Patient Case 5. An 18-month-old child with a history of premature birth and chronic lung disease is admitted to the pediatric intensive care unit with fever, respiratory distress necessitating intubation, and a 3-day history of coldlike symptoms. The results of a nasal swab are positive for RSV. Which is the best intervention? A. Palivizumab. B. Dexamethasone. C. Cefuroxime. D. Supportive care. D. Treatment 1. Supportive care a. Hydration b. Supplemental oxygen c. Mechanical ventilation as needed d. Analgesics for fever 2. Ribavirin a. Active against RSV replication b. Not shown to reduce mortality in immunocompetent patients c. Not shown to reduce ventilator days, stay in the intensive care unit or hospital, or hospital cost d. The AAP states that oral ribavirin “may be considered” in a select group of high-risk patients (e.g., those with complicated congenital heart disease, chronic lung disease or bronchopulmonary dysplasia, immunocompromised) but that “routine use is not recommended.” ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-421 Pediatrics 3. 4. 5. 6. Inhaled β2-agonists, racemic epinephrine a. Not shown to improve outcome measures b. Some practitioners may give a trial of these therapies, but this is not considered the standard of care, nor is it recommended by the current AAP guideline. Corticosteroids a. Not shown to improve outcome measures b. Use is not recommended. Inhaled hypertonic saline a. Should not be administered in the emergency department b. May be considered for hospitalized patients; however, the evidence supporting use is weak. Antibiotics: Not indicated unless secondary bacterial infection develops III. OTITIS MEDIA A. Clinical Presentation 1. Definitions a. Acute otitis media: Presence of middle ear effusion and evidence of middle ear inflammation i. Middle ear effusion may be indicated by bulging tympanic membrane, decreased or no mobility of the tympanic membrane, purulent fluid in the middle ear. ii. Inflammation of the middle ear may be indicated by erythema of the tympanic membrane or otalgia. b. Otitis media with effusion (OME): Fluid in the middle ear without evidence of local or systemic illness c. Recurrent AOM: Three or more episodes of acute otitis within 6 months or four episodes within 1 year with at least 1 episode within the most recent 6 months 2. Risk factors a. Younger age (generally less than school age) b. Day care attendance c. Absence of breastfeeding d. Family history of AOM e. Positioning during feeding (e.g., supine position during bottle-feeding allows reflux into Eustachian tubes) f. Lower socioeconomic status g. Smokers in the household h. Craniofacial abnormalities or cleft palate i. Lack of pneumococcal conjugate vaccine and influenza vaccine administration j. Immune deficiencies k. Cochlear implants l. Siblings in the home m. Seasonal cooler months (winter) 3. Incidence a. AOM in first year of life: 25% b. AOM by 5 years of life: 60% c. Peak incidence at 6 to 12 months of age ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-422 Pediatrics B. Common Pathogens 1. Viral 2. Streptococcus pneumoniae 3. Nontypeable H. influenzae 4. Moraxella catarrhalis C. Signs & Symptoms: 1. Otorrhea 2. Erythema 3. Tugging or pulling of ears (otalgia) 4. Fever 5. Irritability/sleep changes D. Treatment 1. General principles a. Clinical resolution will occur in a significant number of cases without antibiotic therapy. b. Immediate antibiotic therapy is warranted for AOM with bulging tympanic membrane, perforation, or otorrhea. c. Delayed antibiotic prescribing (i.e., treatment only if symptoms are severe: otalgia persists for more than 48–72 hours or temperature greater than 102.2°F [39°C] in the past 48 hours) is an acceptable strategy in children older than 2 years with AOM without severe systemic symptoms. i. Analgesics (e.g., ibuprofen, acetaminophen) are more beneficial than antibiotics for relieving otalgia within the first 24 hours and are recommended regardless of antibiotic use. (a) Ibuprofen 5–10 mg/kg every 6–8 hours (not recommended if less than 6 months old) (b) Acetaminophen 10–15 mg/kg every 4–6 hours ii. Antibiotics also can be deferred in otherwise healthy children between 6 months and 2 years of age if their symptoms are mild and otitis media is unilateral (as opposed to bilateral). iii. Caregiver must be reliable to recognize worsening of condition and gain immediate access to medical care, if needed. iv. Not recommended for infants younger than 6 months d. Persistence of middle ear fluid is likely after treatment for AOM and does not warrant repeated treatment. i. 50% persistent OME after 1 month ii. 20% persistent OME after 2 months iii. 10% persistent OME after 3 months e. Antibiotics are not generally warranted for OME because of the high rate of spontaneous resolution. i. Antibiotics are recommended only if bilateral effusions persist for more than 3 months. ii. Corticosteroids, antihistamines, and decongestants are not recommended. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-423 Pediatrics 2. Suggested treatment algorithm (Figure 1) Confirmed AOM NO Otorrhea or severe symptoms? YES Age 6 mo – 2 yr? YES NO Delayed antibiotic prescribing • N  ot recommended if child is < 6 mo • A ntibiotics prescribed only if child worsens or does not improve within 48–72 hr Unilateral Antibiotic therapy Bilateral or unilateral AOM? Bilateral • Alternatives (if penicillin allergic) • C  efdinir • C  efuroxime • C  efpodoxime • C  eftriaxone OR Antibiotic therapy • If child is < 6 mo or if reliable follow-up cannot be ensured NO • First-line agents • A  moxicillin 80–90 mg/kg/day divided BID • A  moxicillin/clavulanate: Consider if amoxicillin taken within past 30 days Reevaluate at 48–72 hr Failure of initial treatment strategy? • Continue current treatment strategy • Antibiotic duration • Optimal duration is unknown • < 2 yr or severe symptoms: 10 days • 2–5 yr with mild-moderate symptoms: 7 days • ≥ 6 yr with mild-moderate symptoms: 5–7 days YES • Start antibiotic if prescribing was delayed • Consider changing antibiotic regimen • A moxicillin/clavulanate 90 mg/kg/day divided BID (using the 14:1 formulation) • Ceftriaxone 50 mg/kg once daily × 3 days • Clindamycin 10 mg/kg every 8 hr ± 3rd-generation cephalosporin • Consider tympanocentesis • Consider tympanostomy tubes • Most beneficial for children with persistent OME and significant hearing loss (e.g., > 25-dB hearing loss bilaterally > 12 wk) BID = twice daily; OME = Otitis media with effusion. Figure 1. Suggested treatment algorithm for acute otitis media (AOM). E. Complications of AOM: Incompletely treated or untreated: 1. Hearing loss 2. Mastoiditis 3 Tympanic membrane perforation 4. Otorrhea ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-424 Pediatrics F. Prevention Strategies 1. Antibiotic prophylaxis a. Reduces occurrence by about one episode per year b. The risk of promoting bacterial resistance may outweigh the slight benefit. c. AAP recommends against routine use for children with recurrent AOM. 2. Immunization: Pneumococcal and influenza vaccines should be administered according to the AAP and Advisory Committee on Immunization Practices (ACIP) recommendations. 3. Modification of risk factors Patient Cases 6. A 5-month-old infant who was born at term and is otherwise healthy was treated for her first case of otitis media with amoxicillin 45 mg/kg/day for 7 days. On follow-up examination, her pediatrician noticed fullness in the middle ear and a cloudy tympanic membrane with decreased mobility. She is now afebrile and eating well. Which is the best recommendation for her treatment? A. No antibiotics at this time. B. High-dose (90 mg/kg/day) amoxicillin for 7 days. C. Decongestant and antihistamine daily until resolution. D. Azithromycin. 7. A 4-year-old boy receives a diagnosis of his fourth case of otitis media within 12 months. He has not shown evidence of hearing loss or delay in language skills. Which is the best intervention at this point? A. Giving long-term antibiotic prophylaxis. B. Inserting tympanostomy tubes. C. Administering high-dose amoxicillin and ensuring that he is up to date on his pneumococcal and influenza vaccines. D. No antibiotic therapy is warranted. IV. IMMUNIZATIONS A. Recommended Schedule (Figure 2) 1. Some major changes and several clarifications have been made to the routine childhood schedule in the last 10 years. a. Replacement of 7-valent conjugated pneumococcal vaccine with 13-valent conjugated pneumococcal vaccine (PCV13, Prevnar 13) for all children younger than 6 years b. Human papillomavirus vaccine (HPV4, Gardasil) received an FDA label-approved indication in males and females aged 9–26 years for prevention of genital warts and females aged 9–26 years for the prevention of cervical, vulvar, vaginal, and anal cancer. It is now recommended for routine vaccination of adolescent males and females. c. Live attenuated influenza vaccine (LAIV) was previously not recommended during the 2016-2017 and 2017-2018 influenza seasons. It was, however, considered an option again starting with the 2018-2019 season in patients to whom influenza injection would otherwise not be given. Use of LAIV must be assessed annually. LAIV should not be used in children younger than 2 years or children 2–4 years of age with a diagnosis of asthma in the preceding year. Caution should be used in children older than 5 years with asthma. d. Hepatitis B (HepB) vaccine for the birth dose should be given within 24 hours of birth added to footnote of 2017 update. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-425 Pediatrics e. For children and adolescents who have a delayed start to immunizations, a catch-up schedule exists. f. A new figure for vaccines that might be indicated for children and adolescents aged 18 years or younger based on medical indications was added. i. Most children with medical conditions can (and should) be vaccinated according to the routine schedule. ii.  It provides details for when a medical condition is a contraindication or precaution to vaccination. iii. It indicates when additional doses of vaccination may be required because of a medical condition. g. Refer to the National Immunization Program Web site (www.cdc.gov/vaccines). h. New formulations of licensed influenza vaccines with a volume of 0.5 mL per dose were approved for children 6–36 months of age in 2019. Children 6–35 months of age may now receive either the 0.25-mL or the 0.5-mL dose, with no preference, and children 36 months and older continue to receive a 0.5-mL dose. i. The first vaccine indicated for active immunization to prevent COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was approved in August 2021 for individuals 16 years of age and older. Additional vaccine approvals have been provided by emergency use authorization for children as young as 6 months, at the time when this chapter was written. CDC has provided an interim COVID-19 immunization schedule for children separate from the general child and adolescent immunization schedule. This COVID-19 immunization schedule is updated regularly as approvals and indications change. For the most up-to-date schedule, refer to the CDC website. Patient Case 8. A 1-year-old boy with a history of Kawasaki disease treated 4 months ago with intravenous immunoglobulin (IVIG) is being seen by his pediatrician for a well-child checkup. He is due for the measles, mumps, and rubella (MMR) and varicella vaccines. He has no known drug allergies, but he has many food allergies, including peanuts and eggs. His mother has several concerns about administering these vaccines. Which concern is the best reason to defer administering vaccines in this patient? A. Association between MMR vaccine administration and the development of autism. B. Allergic reaction after MMR administration in a patient with an egg allergy. C. Many concurrent vaccines can overload the patient’s immune system. D. Decreased vaccine efficacy because of previous IVIG administration. 2. Combination vaccines a. Main advantage: Reduction in the number of injections needed to complete recommended schedule b. The FDA mandates that the safety and efficacy of combination products not be less than those of the individual components. c. The MMR and varicella combination vaccine (ProQuad) i. Research from the Centers for Disease Control and Prevention and manufacturer indicated a higher incidence of febrile seizures in children 12–23 months of age who received the combination product compared with those who received the separate MMR and varicella vaccines. ii. Since June 2009, ACIP has expressed a preference for separate MMR and varicella vaccines as the first dose given to children 12–47 months of age. The combination product can be used for the second dose at any age and for the first dose in children age 48 months or older. d. Adding HepB to combination products can result in an extra dose being provided (e.g., monovalent HepB given at birth and then combination products at 2, 4, and 6 months); however, ACIP states that this is a safe practice. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-426 Pediatrics 3. Interchangeability of products a. ACIP recommends that the same product be used throughout the primary series; however, if the previous product’s identity is not known or is no longer available, any product may be used. b. For diphtheria, tetanus, and pertussis vaccine (DTaP): The current standard of care is to use the same product for at least the first three doses of the five-dose series; however, if the product used previously is not known or is unavailable, any product can be used. c. For tetanus, diphtheria, and pertussis vaccine (Tdap): Boostrix or Adacel can be used for the booster dose, regardless of the manufacturer of the DTaP product administered during the primary immunization series. d. For HepB: It is acceptable to use Engerix-B and Recombivax HB interchangeably. Children and adolescents 11–15 years of age can receive a two-dose series with Recombivax HB only, whereas Engerix-B would still be a three-dose series. Heplisav-B should only be used in patients 18 years or older. e. For polio: Oral polio vaccine and inactivated poliovirus vaccine provide equivalent protection against paralytic poliomyelitis; however, because the only cases of polio in the United States since 1979 have been vaccine associated (i.e., from the live virus in oral polio vaccine), oral polio vaccine is no longer recommended. f. For Hib: These products can be used interchangeably; however, if the regimen is completed using PedvaxHIB exclusively, only three doses are needed for routine immunization; regimens using Hiberix, ActHIB, Pentacel, or Vaxelis should include four doses even if the regimen is completed using PedvaxHIB. Vaxelis is not recommended as a booster dose. g. For Rotavirus (RV): These products can be used interchangeably; however, if the regimen is completed using Rotarix exclusively, only two doses are needed; regimens using RotaTeq or when the product is unknown should include three doses. B. Barriers to Routine Immunization 1. Contraindications a. Anaphylactic reaction to vaccine or any of its components i. Inactivated poliovirus vaccine, MMR, and varicella contain neomycin. ii. Egg allergy is not considered a contraindication to any form of influenza vaccine. LAIV was approved for use in patients with egg allergy in 2016. Additionally, ACIP evaluated 3 studies looking at use of LAIV in egg-allergic children, and no cases of anaphylaxis occurred. iii. Severe egg allergy is not considered a contraindication to MMR, which is grown in chick embryo tissue. b. Acute moderate to severe febrile illness c. Immunodeficiency: Oral polio vaccine, MMR, varicella d. Pregnancy: MMR, varicella e. Recent administration of immune globulin: MMR, varicella i. Delay administration of vaccine product. ii. Interval between immune globulin dose and administration of vaccine depends on indication for and dose of immune globulin. f. Encephalopathy within 7 days after administration of a previous dose of DTaP g. History of intussusception: Rotavirus vaccine 2. Misconceptions about contraindications (i.e., these are not contraindications) a. Mild acute illness b. Current antimicrobial therapy c. Reaction to DTaP involving only soreness, redness, or swelling at the site d. Pregnancy of the mother of the vaccine recipient e. Breastfeeding ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-427 Pediatrics f. Allergies to antibiotics other than neomycin or streptomycin g. Family history of an adverse effect after vaccine administration 3. Other factors associated with under-immunization a. Low socioeconomic status b. Late start of vaccination series c. Missed opportunities i. Provider unaware that vaccination is due ii. Failure to provide simultaneous vaccines iii. Inappropriate contraindications (see previous discussion) d. Concern about potential adverse reactions i. Autism: The association with MMR vaccine has not been proven. ii. Guillain-Barré syndrome: The association with meningococcal conjugate vaccine has not been proven. (a) Fifteen reported cases in adolescents after receiving meningococcal vaccine (b) ACIP continues to recommend the routine use of meningococcal vaccine. iii. Intussusception: An association with RV vaccine led to the market withdrawal of one particular brand of RV vaccine (RotaShield); two products are currently available. (a) Live, oral human-bovine reassortant rotavirus vaccine (RotaTeq, licensed in 2006) (b) Live, attenuated human rotavirus vaccine (Rotarix, licensed in 2008) (c) Neither product has been associated with intussusception. iv. Safety concerns about any vaccine product should be reported through the Vaccine Adverse Events Reporting System. e. Belief that vaccine-preventable diseases no longer pose a significant health risk f. Belief that too many vaccines all at once can overwhelm the immune system and make the child sick g. Religious or philosophical beliefs that oppose vaccinations Patient Case 9. The following patients are seeing their pediatrician today and are due for immunizations according to the routine schedule. For which patient would it be best to recommend deferring immunizations until later? A. A 12-month-old boy who recently completed a cycle of chemotherapy for acute lymphocytic leukemia. B. A 6-month-old girl receiving amoxicillin for otitis media. C. A 12-month-old HIV-positive boy whose most recent CD4 count was greater than 1000. D. A 12-year-old girl completing a prednisone “burst” (1 mg/kg/day for 5 days) for asthma exacerbation. C. Considerations in Special Populations (Figure 2) 1. Preterm infants a. Immunize according to chronologic age, as opposed to corrected gestational age b. Do not lower vaccine doses c. If birth weight is less than 2 kg, delay HepB vaccine because of reduced immune response until the patient is 1 month old or at hospital discharge if it occurs before 1 month of age (unless the mother is positive for HepB surface antigen, in which case the newborn should receive HepB vaccine regardless of birth weight). Newborns to mothers with Hepatitis B should also receive Hepatitis B immune globulin. 2. Children who are immunocompromised a. Should not receive live vaccines (e.g., MMR, varicella, rotavirus, LAIV, yellow fever, and oral typhoid) b. Inactivated vaccines and immune globulins are appropriate. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-428 Pediatrics c. Household contacts should not receive oral polio vaccine; however, MMR, influenza, varicella, and rotavirus vaccines are recommended. 3. Patients receiving corticosteroids a. Live vaccines can be administered to patients receiving the following: i. Topical corticosteroids ii. Physiologic maintenance doses iii. Low or moderate doses (less than 2 mg/kg/day of prednisone equivalent) b. Live vaccines can be given immediately after discontinuation of high doses (2 mg/kg/day or more of prednisone equivalent) of systemic steroids given for less than 14 days. c. Live vaccines should be delayed at least 1 month after discontinuing high doses (2 mg/kg/day or more of prednisone equivalent) of systemic steroids given for more than 14 days. 4. Patients with HIV infection a. MMR should be administered unless the patient is severely immunocompromised. b. Varicella should be considered for asymptomatic or mildly symptomatic patients. c. Inactivated vaccines should be administered routinely. ACCP Updates in Therapeutics® 2023: Pharmacotherapy Preparatory Review and Recertification Course 2-429 AL GRAWANY