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Antimicrobial Chemoprophylaxis
Chemoprophylaxis is prevention of disease by administration of an anti-infective drug product. An antimicrobial product is given to an individual who is at risk of developing an infection following exposure to bacteria, viruses, fungi, mycobacteria, or parasites. The term “prophylaxis” as used in this chapter does not apply to those situations in which infection is already established; however, for some children who already are infected but asymptomatic, the term has been used in situations to denote the prevention of “disease” rather than infection. Other chapters discuss immunoprophylaxis (see Chapter 5, Chapter 6 ) and barrier prophylaxis (e.g., use of condoms; see Chapter 51, Chapter 52 ). Specific discussions of the prevention of travelers diarrhea (see Chapter 8 ), neonatal conjunctivitis (see Chapter 80 ), malaria (see Chapter 271 ), and human immunodeficiency virus (HIV) infection (see Chapter 109 ) can also be found elsewhere. Similarly, immunoprophylaxis and chemoprophylaxis for immunocompromised hosts, such as solid-organ or bone marrow transplant recipients, or patients being treated for cancer, are not discussed specifically in this chapter.
Ideally, recommendations for antimicrobial prophylaxis should be based on data documenting efficacy in prospective, randomized controlled studies, but most prophylactic regimens are presumed to be efficacious on the basis of data collected in adults, or small clinical trials in children supported by pharmacology and biologic plausibility. In addition, the use of unproven prophylaxis can be justified solely by the severe consequences of possible infection (e.g., infection of implanted neurosurgical or cardiac foreign material).
Chemoprophylaxis of infection in children can be classified as general or specific. Chemoprophylaxis is general when all children, regardless of underlying disease or other factors, are at substantial risk of infection following exposure to a pathogen (e.g., Neisseria meningitidis in a crowded classroom). Chemoprophylaxis is specific when it is administered to certain children who are deemed at special risk for infection because of the presence of an immunodeficient state or anatomic structural anomalies or because these children have undergone procedures or operations that can be associated with an increased risk of subsequent infection. Chemoprophylaxis should be administered during the entire interval of documented increased risk of infection; the duration of general or specific chemoprophylaxis varies with each situation, but follows general principles regarding balancing benefits of prophylaxis with risks of antibiotic use. Prophylaxis can be short term, following a specific exposure (e.g., N. meningitidis ), more prolonged with ongoing exposure (e.g., malaria), or administered over several years (e.g., rheumatic fever).
The benefits of chemoprophylactic strategies to decrease morbidity and mortality and their attendant costs to the healthcare system should be weighed against potential risks, including drug toxicities, costs, alteration of the host microbiome, and the development and spread of antimicrobial resistance. Every effort should be made to limit the duration of prophylaxis or to find alternative methods to prevent infection (e.g., clean intermittent catheterization of the urinary bladder to prevent urinary tract infections). Recommendations change periodically on the basis of evolving knowledge, changing pathogens, and susceptibility to antimicrobial agents. Updated guidelines for prevention of specific infections are published periodically by the Centers for Disease Control and Prevention, by the American Academy of Pediatrics, in the Medical Letter on Drugs and Therapeutics, by the American Heart Association, , and in peer-reviewed journals.
For chemoprophylaxis to be effective, three criteria should be met:
- 1.
The antimicrobial drug or drugs used must have activity against the likely infectious agent and attain appropriate tissue-specific drug concentrations.
- 2.
The host should have a well-defined increased risk of development of disease that justifies prophylaxis. Other important factors include the severity of infection with associated risk of morbidity or mortality, and communicability to others.
- 3.
The safety of a chemoprophylactic agent must be such that complications of its administration do not outweigh the risks of infection (i.e., an acceptable benefit-to-risk ratio).
Chemoprophylaxis in Healthy Children
Chemoprophylaxis is recommended to prevent surgical and trauma-related infections ( Table 7.1 ), as well as to prevent disease associated with significant morbidity and mortality caused by bacterial, viral, fungal, mycobacterial, and parasitic agents. Pathogen-specific chemoprophylactic agents, doses, and durations as well as alternative regimens are shown in Table 7.2 .
TABLE 7.1
Classification of Operative Wounds and Risk of Infection
| Classification | Criteria | Risk (%) |
|---|---|---|
| Clean | Elective, not emergency, nontraumatic; primarily closed; no acute inflammation; no break in technique; respiratory, GI, biliary, and GU tracts not entered | <2 |
| Clean-contaminated | Urgent or emergency, otherwise clean; elective opening of respiratory, GI, biliary, or GU tract with minimal spill and not infected urine or bile; minor technique break | <10 |
| Contaminated | Nonpurulent inflammation; gross spill from GI tract; entry into biliary or GU tract in the presence of infection; major break in technique; penetrating trauma lasting <4 hr; chronic open wounds to be grafted or covered | ∼20 |
| Dirty | Purulent inflammation (e.g., abscess); preoperative perforation of respiratory GI or GU tract; penetrating trauma lasting >4 hr | ∼40 |
GI, gastrointestinal; GU, genitourinary.
TABLE 7.2
Chemoprophylaxis for Healthy Children Exposed to Specific Pathogens a
| Pathogen or Disease | Prophylactic Agent | Dose/Day | Maximum Daily Dose | Divided Doses | Duration |
|---|---|---|---|---|---|
| Bordetella pertussis b | Erythromycin | 40 mg/kg•<1 mo: 10 mg/kg/day single dose daily for 5 days•1–5 mo: 10 mg/kg/day single dose daily for 5 days•≥6 mo and children: 10 mg/kg single dose on day 1 (max 500 mg), then 5 mg/kg/day single dose on days 2–5 (max 250 mg/day) •Adolescents: 500 mg single dose on day 1, then 250 mg as a single dose on days 2–5 | 2 g | 4 | 14 days |
| Azithromycin | <6 mo: 10 mg/kg/day as single dose daily for 5 days6 mo–adolescence: 10 mg/kg as single dose on day 1 (max 500 mg), then 5 mg/kg/day as single dose on days 2–5 (max 250 mg/day) | 500 mg | 1 | 5 days | |
| or | |||||
| Clarithromycin | 15 mg/kg | 1 g | 2 | 7 days | |
| Haemophilus influenzae type b | Rifampin | 20 mg/kg | 600 mg | 1 | 4 days |
| Corynebacterium diphtheriae | Erythromycin | 40 mg/kg | 2 g | 4 | 7 days |
| or | |||||
| Benzathine penicillin | 600,000 units (IM) if <30 kg 1.2 million units (IM) if ≥30 kg |
Once | |||
| Neisseria meningitidis | Rifampin | 20 mg/kg if ≥1 mo 10 mg/kg if <1 mo |
1.2 g | 2 | 2 days |
| or | |||||
| Ceftriaxone | 125 mg (IM) if <12 yr 250 mg (IM) if ≥12 yr |
2 g | Once | ||
| or | |||||
| Ciprofloxacin | 20 mg/kg if ≥1 mo | 500 mg | Once | ||
| Yersinia pestis (pneumonic) | Sulfonamide | 40 mg/kg if <8 yr | 2 | 7 days | |
| or | |||||
| TMP-SMX | 8 mg/kg TMP if <8 yr | 2 | 7 days | ||
| Tetracycline | 50 mg/kg if ≥8 yr | 1 g | 4 | 7 days | |
| Vibrio cholerae c | |||||
| <8 yr | TMP-SMX | 8 mg/kg TMP | 2 | 3 days | |
| 8–17 yr | Tetracycline | 50 mg/kg | 2 g | 4 | 3 days |
| ≥18 yr | Ciprofloxacin | 15 mg/kg | 1 g | 2 | 3 days |
| Streptococcus agalactiae | Penicillin G (maternal intrapartum); for those with penicillin allergy at high risk for anaphylaxis, clindamycin or vancomycin should be used; test maternal isolate for susceptibility if possible | 5 million units; then 2.5–3 million q 4 hr | Until delivery | ||
| or | |||||
| Ampicillin (maternal intrapartum) | 2 g; then 1 g (IV) q 4 hr | Until delivery | |||
| or (For history of penicillin allergy, but at low-risk of significant reaction) Cefazolin |
2 g; then 1 g (IV) q 8 hr | Until delivery | |||
| Mycobacterium leprae (borderline or lepromatous) | Dapsone | 1 mg/kg | 100 mg | 1 | 3 yr |
| Herpes simplex virus d | Acyclovir (preemptive following perinatal exposure for the neonate; see text) | 60 mg/kg (IV) | 3 | 10 days for preemptive | |
| Acyclovir (suppression of active infection in neonates with CNS infection; see text) | 300 mg/m 2 /dose | 3 times/day | 6 mo | ||
| Acyclovir (suppression of oral, genital or ocular infection) | 10–20 mg/kg | 800 | 2–4 | Up to 12 mo or longer | |
| Influenza A e | Oseltamivir | By body weight, children ≥12 mo: >40 kg: 75 mg; >23–40 kg: 60 mg; >15–23 kg: 45 mg Infants 9–11 mo: 3.5 mg/kg Term infants 0–8 mo: 3 mg/kg Preterm infants f |
75 mg | 1 | See text |
| Zanamivir inhaled (for prophylaxis for children ≥5 yr) | 2 inhalations (5 mg per inhalation, 10 mg total per dose) | 2 inhalations total | 1 | See text | |
| Scabies | 5% permethrin | Topically | Once | ||
| Neisseria gonorrhoeae | |||||
| Ophthalmia neonatorum | 0.5% erythromycin | Topically | Once | ||
| Sexual exposure | Once | ||||
| <45 kg | Ceftriaxone | 25–50 mg/kg (IM) | 125 mg | ||
| 45 kg and ≥8 yr | Ceftriaxone plus | 500 mg (IM) | 250 mg | Once | |
| Doxcycline (for chlamydia) | 200 mg in 2 divided doses for 7 days | ||||
| or | |||||
| Cefixime plus | 800 mg | Once | |||
| Doxycycline, as above | |||||
| Chlamydia trachomatis | |||||
| <8 yr | Erythromycin | 40 mg/kg | 2 g | 4 | 7 days |
| ≥8 yr | Doxycycline | 4 mg/kg | 200 mg | 2 | 7 days |
| or | |||||
| Azithromycin | 1 g | Once | |||
| Treponema pallidum | Benzathine penicillin G | 50,000 units/kg (IM) | 2.4 million units (IM) | 2 | Once |
| Alternative a | |||||
| Doxycycline | 4 mg/kg | 200 mg | 14 days | ||
| Alternative | |||||
| Azithromycin | 2 g | Once | |||
| Klebsiella granulomatis | Doxycycline | 4 mg/kg | 200 mg | 2 | 3 wk |
| or | |||||
| TMP-SMX | 8 mg/kg TMP | 320 mg TMP | 2 | 3 wk |
CNS, central nervous system; IM, intramuscularly; IV, intravenously; SMX, sulfamethoxazole; TMP, trimethoprim.
a Alternative drugs used only if other cannot be used; listings are not exhaustive. Some regimens are not of proven benefit. Administration is oral except as noted.
b See Chapter 162 for doses by age. Azithromycin dose for immunized at age ≥6 months is 10 mg/kg once followed by 5 mg/kg on subsequent 4 days (or maximum 500 mg, followed by 250-mg doses).
c Resistance of isolate requires revision of chemoprophylactic regimen.
d Based on current American Academy of Pediatrics recommendations for neonates and young infants.
e Oseltamivir not recommended for routine prophylaxis for infants <3 months of age because of the lack of safety data in that age group. Prophylaxis is indicated in very young infants when benefits outweigh possible risks.
f Oseltamivir dosing for preterm infants. The weight-based dosing recommendation for preterm infants is lower than for term infants. Preterm infants can have lower clearance of oseltamivir because of immature renal function, and doses recommended for full-term infants can lead to very high drug concentrations in this age group. Limited pharmacokinetic data provide the basis for once-daily dosing for prophylaxis of preterm infants using postmenstrual age (gestational age + chronologic age): 1.0 mg/kg per dose, orally, for those <38 weeks of postmenstrual age; 1.5 mg/kg per dose, orally, for those 38 through 40 weeks of postmenstrual age; 3.0 mg/kg per dose, orally, for those >40 weeks of postmenstrual age. For extremely premature infants (<28 weeks), please consult a pediatric infectious diseases physician.
Specific Pathogens With a Defined Point of Exposure
Neisseria meningitidis
The reported secondary attack rates for meningococcal disease among household contacts of index cases range from 0.25% in adults to 10% for infants <1 year of age, reviewed in Chapter 125 . Regimens using rifampin, ciprofloxacin, and ceftriaxone are effective in eliminating nasopharyngeal carriage of N. meningitidis . The largest experience in children is with the use of rifampin. Prophylaxis should be instituted as soon as possible (preferably within 24 hours) for contacts in households and childcare centers, for close school contacts, as well as for persons who have had contact with infected oral secretions. Rifampin alters the metabolism of some drugs, including oral contraceptives, phenytoin, phenobarbital, carbamazepine, warfarin compounds, and other agents using the hepatic cytochrome P450 enzyme system. Safety of rifampin in pregnancy has not been established. Alternative agents include ceftriaxone and ciprofloxacin. Ceftriaxone requires injections, but compliance and antimicrobial exposure are ensured. Ciprofloxacin has been evaluated in adults and documented to eradicate carriage; fluoroquinolone agents have a relative contraindication in pregnant women, and prepubertal children out of concern for possible arthropathy. However, additional safety data on fluoroquinolones in children suggest that a single 10-day treatment course is unlikely to lead to long-term injury ; arthropathy is highly unlikely to occur with a single dose used for prophylaxis. Resistance of N. meningitidis to antibiotics is followed closely by the CDC, with an alert issued in 2020 regarding the emergence of ciprofloxacin-resistant, beta-lactamase–producing strains. Prophylaxis with usual antibiotics should be carried out as quickly as possible, while assessment of local antibiotic resistance is undertaken with local public health officials in case additional prophylaxis for a resistant strain is deemed appropriate.
Haemophilus influenzae Type B
Prophylaxis against Haemophilus influenzae infections is discussed in Chapter 172 . Infection caused by H. influenzae type b (Hib) is exceedingly rare in adequately immunized children. Rifampin is approximately 95% effective in the eradication of nasopharyngeal carriage of Hib in children.
Group B Streptococcus
Early-onset disease caused by group B Streptococcus (Streptococcus agalactiae) can be greatly reduced by intrapartum administration of penicillin or ampicillin (see Chapter 119 ). Intrapartum administration of antibiotics does not prevent disease in infants who were infected before intrapartum therapy was started, nor does it prevent late-onset group B Streptococcus infections. For women who have beta-lactam allergy, susceptibility testing of their isolate during pregnancy to macrolide or clindamycin should be performed as resistance exists.
Human Immunodeficiency Virus
Perinatal or intrauterine transmission of HIV is diminished by the administration of zidovudine and other anti-HIV retroviral therapy to the mother during pregnancy, with continued treatment of the infant for various periods of time after delivery, depending on the regimen used. The most current information on treatment and prophylaxis is posted on the AIDSinfo website of the National Institutes of Health ( http://aidsinfo.nih.gov/ ). Specific, current recommendations on regimens to prevent neonatal HIV infection can be found at http://aidsinfo.nih.gov/ContentFiles/PerinatalGL.pdf Current HIV maternal and neonatal prophylactic regimens with zidovudine and other agents or cesarean deliveries have reduced the rate of transmission in worldwide studies to <2% (see Chapter 109 ). For recommendations for healthcare worker exposure or sexual or injection-drug nonoccupational HIV exposure, detailed antiviral drug recommendations based on risks of transmission balanced by risks of antiviral drug toxicity with chemoprophylaxis also are provided on the AIDSinfo website. The risk of HIV infection can be decreased after exposure, particularly if antiviral prophylaxis is provided within 12–24 hours of exposure (see Chapter 109 ).
Herpes Simplex Virus
Maternal Infection During Pregnancy
Neonatal herpes simplex virus (HSV) infection usually results from exposure and transmission at the time of labor and delivery (see Chapter 204 ). With vaginal delivery during maternal primary genital infection, the rate of transmission of HSV to the infant can exceed 50%, whereas delivery during maternal reactivation disease carries a risk of <3%–5%. Guidelines for testing and treating pregnant women with genital HSV infection are published by the American College of Obstetrics and Gynecology. It can be difficult to determine whether an active HSV infection is primary or recurrent because primary genital infection often is asymptomatic. Diagnostic tests for maternal HSV infection, including specific culture, antigen, histopathology and serologic tests for HSV-1 and HSV-2, as well as nucleic acid amplification tests (NAATs) for HSV DNA from mucosal surfaces, aid in defining the neonate’s risk of infection, although many of these tests are not widely or rapidly available in hospitals to help with management decisions. For pregnant women, benefit of antiviral prophylaxis with acyclovir or valacyclovir in patients with a history of genital HSV on reducing cesarean deliveries has prompted the use of antiviral agents during the last month of pregnancy. Prophylaxis can prevent recurrent maternal infection at the time of delivery, although the impact of prophylaxis on preventing neonatal infection has not yet been demonstrated.
Perinatal Infection
For the neonate potentially exposed to a mother with recurrent genital HSV infection at the time of delivery, current guidance recommends cultures (e.g., cultures of the conjunctiva, mouth, nasopharynx, and rectum) and NAAT tests such as polymerase chain reaction (PCR), on blood at 12–24 hours of age in all infants who are asymptomatic, without starting antiviral therapy, whereas other experts consider that documented exposure to virus at the time of vaginal delivery constitutes sufficient risk to the infant to begin intravenous acyclovir therapy to prevent symptomatic infection. Positive results from culture specimens taken 24 hours or more after delivery are more likely to indicate infection, with a higher risk of developing symptomatic disease, thus leading the American Academy of Pediatrics to recommend intravenous acyclovir therapy when such cultures are positive, to prevent symptomatic infection. For mothers with a history of genital HSV who have no lesions at delivery no cultures are recommended for the neonate, but close clinical follow-up is important.
Prophylaxis/Suppression Following Perinatal Infection
For neonates with surviving perinatal HSV infection, administration of oral acyclovir to suppress HSV and prevent symptomatic infection for the first 6 months of life has been associated with fewer clinical recurrences and a modest benefit in improved cognitive development.
Prophylaxis/Suppression Following Infection in Children and Adolescents
Acyclovir and valacyclovir prophylaxis have been used to reduce the number of symptomatic recurrent genital and oral-cutaneous HSV infections in otherwise healthy adolescents and adults who experience frequent recurrences. In addition, acyclovir has been used prophylactically in children <3 years of age who were exposed to HSV infections in daycare nursery outbreaks (30–60 mg/kg/day in 3–5 divided doses). Some experts also recommend acyclovir prophylaxis following ocular HSV infections (recurrent HSV keratitis or recurrent infection of skin adjacent to the eye) to prevent corneal ulcerations and scarring. No prospective, controlled data exist on the safety and efficacy of prophylaxis for children, but epidemiologic data document the increase in acyclovir resistance with long-term prophylaxis for keratitis (see Chapter 295 ). In contrast to otherwise healthy children, antiviral prophylaxis for HSV is recommended for immune-compromised children, depending on the underlying condition, state of immunodeficiency (congenital or acquired), receipt of chemotherapy or biologic response modulating therapies, and consequences of reactivation and likelihood of dissemination.
Respiratory Tract Bacterial and Viral Pathogens
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