This educational activity is targeted at infectious disease physicians, nurses, hospital epidemiologists, clinical microbiloogists, pharmacists, public health authorities, practicing physicians, and other health care professionals interested in the treatment of serious infections due to methicillin-resistant Staphylococcus aureus.
The learner will be able to describe the epidemiology, the pathogenesis, and the clinical characteristics of methicillin-resistant Staphylococcus aureus infections in the pediatric population.
PARTICIPATION IN THE LEARNING PROCESS
Credit is based upon the approximate time it should take to read this publication and complete the assessment and evaluation. A minimum assessment score of 80% is required. Publication date is July 1, 2010. Requests for credit or contact hours must be postmarked no later than January 1, 2011, after which this material is no longer certified for credit.
Continuing Medical Education
The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for Continuing Education to provide continuing medical education for physicians. The NFID designates this educational activity for a maximum of 0.25 AMA PRA Category 1 credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.
The NFID must ensure balance, independence, objectivity, and scientific rigor in its educational activities. All individuals with control over the content are required to disclose any relevant financial interest or other relationship with manufacturer(s) of any product or service discussed in an educational presentation and/or with the commercial supporters of this activity. Disclosure information is reviewed in advance to manage and resolve any conflict of interest, real or apparent, that may affect the balance and scientific integrity of an educational activity.
Carol J. Baker, MD (faculty), reports no relevant financial relationships.
Lauren Ero, MS (managing editor), reports no relevant financial relationships.
Thomas M. File, Jr, MD (reviewer), served as an advisor or consultant for Advanced Life Sciences, Astellas/Theravance, Cerexa/Forest, Ortho-McNeil, Protez, Merck, Nabriva, Pfizer, Schering Plough, Targanta, and Wyeth and received grants for clinical research from Cerexa, Ortho-McNeil, Protez, Pfizer, Beohringer Ingelheim, Gilead, and Tibotic.
Marguerite Jackson, PhD, RN (reviewer), owns stock, stock options, or bonds from Cellestis, Inc.
Susan J. Rehm, MD (senior editor) served as an advisor or consultant for Cubist Pharmaceuticals, Inc. and Pfizer Inc, served as a speaker for Cubist Pharmaceuticals, Inc. and Roche, and received grants for clinical research from Cubist Pharmaceuticals, Inc.
CONTINUING MEDICAL EDUCATION INSTRUCTIONS
To receive credits after reading the publication, complete the self-assessment examination, the evaluation, and your contact information. Return the completed form via fax to 301-907-0878 or by mail to the following address: The NFID Office of Continuing Medical Education, 4733 Bethesda Ave, Suite 750, Bethesda, MD 20814.
No fee is required. Please allow 4 to 6 weeks for processing. Inquiries may be directed by phone to 301-656-0003 extension 19 or by e-mail to email@example.com.
Methicillin-resistant Staphylococcus aureus (MRSA) infection traditionally has been associated with health care settings, colonizing patients with underlying health conditions until its emergence in the community among healthy adults and children in the late 1990s. Since then, physicians and the public have become increasingly aware of issues related to MRSA infections in the pediatric population. Community-acquired MRSA (CA-MRSA) has become a successful pathogen. The emergence of new clones of CA-MRSA-USA-300 and, to a lesser extent, USA-400-is evident in adults and children. USA-300 is the predominant CA-MRSA clone. These MRSA clones are now appearing in new hosts, previously healthy children. The emergence of clinical syndromes with MRSA infections (eg, skin and soft tissue infections and hematogenous osteomyelitis with multiple bone involvement) requires a more vigilant approach to diagnosis and treatment, including routine cultures, emergent surgical drainage, and new empirical antimicrobial therapies.
Most children do not have risk factors for acquiring CA-MRSA infection. The most common risk factors are listed in Table 1. Children with chronic skin conditions, particularly eczema, are most vulnerable. Children of Native American, Pacific Islander, or African American heritage are more likely to have CA-MRSA infections. Children in day care centers and their childcare providers are also at a higher risk for CA-MRSA infections. Also, children with obesity are at an increased risk for CA-MRSA skin and soft tissue infections.
Children participating in contact sports such as wrestling and football are at risk for acquiring CA-MRSA infection because abrasion of the skin or penetration of the skin barrier is usually the access point for CA-MRSA. A history of previous infections in family members is a risk factor that is often overlooked by pediatricians. Most (80%-85%) CA-MRSA infections originate in skin and soft tissue. In the current CA-MRSA landscape, patients may have had multiple episodes of skin and soft tissue infections.
REPORTS OF CA-MRSA OUTBREAKS IN THE PEDIATRIC (AND RELATED) POPULATION
In 2003, Saiman et al1 reported on an outbreak of CA-MRSA infections that occurred in 8 postpartum women in a New York hospital. Mastitis occurred in 4 patients; 3 cases progressed to breast abscess. Other infections attributed to CA-MRSA included a postoperative cesarean delivery wound infection (1 patient), cellulitis (1 patient), pustulosis (1 patient), and a urinary tract infection (1 patient). The median onset occurred at 23 days after delivery (range, 4-73 days). Five patients were readmitted for infection. Surveillance cultures of hospital employees and newborns were negative for CA-MRSA, and the route of transmission was never discovered. The CA-MRSA strain was identified as a USA-300 clone that contained the staphylococcal chromosomal cassette mec type 4 gene and expressed the Panton-Valentine leukocidin and staphylococcal enterotoxins C and H.
The first report of CA-MRSA in a neonatal intensive care unit came from the Texas Children's Hospital neonatal intensive care unit in 2003 in infants who had not been outside the hospital.2 Five infants had a median birth weight less than 1500 g. The median age at onset was 24 days (range, 11-394 days). Of 8 infants with MRSA bacteremia, 6 carried the staphylococcal chromosomal cassette mec gene characteristic of CA-MRSA (all USA-300 clones). Other manifestations included pneumonia, soft tissue infection, and endocarditis with vegetations. Three infants died and 3 required prolonged antimicrobial therapy. There was no evidence of an outbreak or a point source, as the deaths were spread out by date, caregivers, and nursery. Transmission likely occurred through horizontal contact with an adult or through vertical transmission from the mother at the time of delivery.
An outbreak of CA-MRSA infection was reported in 22 full-term and otherwise healthy infants in a Chicago hospital and in a Los Angeles hospital in 2004.3 The median age of the infants was 7 days (range, 4-23 days). Ninety-one percent (n = 20) of infants were male. A higher incidence of MRSA infections in males has also been noted in older children, although the reason for the sex differences in MRSA infections is unknown. Most infants were delivered by cesarean section, suggesting the possibility of vertical transmission. The mean age at the onset of infection after discharge was 21 days (range, 1-18 days) for 95% of the infants. All infants had superficial skin lesions, and 43% of the infants were admitted presumably because of physicians' concern of immunologic immaturity. Eight infants (73%) received intravenous therapy; 13 (59%), topical treatment; and 3 (14%), oral treatment. No community sources were identified. All isolates were identified as the USA-300 clone.
In a retrospective study conducted at Texas Children's Hospital between August 2001 and March 2005, 61 previously healthy neonates aged 30 days and younger acquired CA-MRSA infection after nursery discharge.4 The infants had no hospitalizations other than that at birth and no surgery other than circumcision. The peak age at the onset of infection was 7 to 12 days. One infant died. The number of CA-MRSA infections increased each year. A maternal skin infection history was present in 20% of the infants. The predominant community clone was USA-300 with the Panton-Valentine leukocidin toxin gene.
In a follow-up study between August 2001 and July 2006 at Texas Children's Hospital, 126 community-acquired S. aureus infections of previously healthy neonates aged 30 days and younger (>36 weeks' gestation at birth) were evaluated.5 Eighty-four isolates (67%) were MRSA isolates. The peak age at the onset of infection was 11 to 17 days. Staphylococcus aureus infections included pustulosis (n = 43), cellulitis/abscess (n = 68), and invasive (n = 15) infections. One patient died with systemic S. aureus and herpes simplex virus infection. The predominant clone was USA-300. Diagnostic procedures and treatment strategies varied; therefore, optimal management strategies were not identified by the authors.
Children with serious CA-MRSA septic infections and complications may need to be admitted to the pediatric intensive care unit (Table 2).6 These complications can include multiple large abscesses requiring surgery; extensive cellulitis involving multiple areas; suspected septic arthritis, pyomyositis, and/or multifocal osteomyelitis; necrotizing pneumonia; and septicemic syndromes such as DVT, septic pulmonary emboli, and purpura fulminans.
In a prospective surveillance study of 3578 S. aureus isolates at Texas Children's Hospital between August 2001 and July 2004, the percentage of CA-MRSA isolates increased from 71.5% in year 1 to 76.4% in year 3. Sixty-two percent of children with MRSA isolates were admitted to the hospital. Among CA-MRSA isolates, 4.4% were obtained from children with invasive infections. The most common invasive infections caused by CA-MRSA isolates were musculoskeletal and pulmonary infections. Clinical syndromes of CA-MRSA infections included osteomyelitis (54 cases), pulmonary involvement (23 cases; either necrotizing pneumonia or septic pulmonary emboli), and septic arthritis (9 cases).
DIAGNOSIS, TREATMENT, AND FOLLOW-UP
An important message to pediatricians is that diagnosis requires culture and susceptibility testing. First, patients with soft tissue infection, bone, or joint foci optimally should have more than 1 blood culture before therapy. Pediatricians should not depend on a single (and sometimes poor quality) blood culture to determine whether a patient has bacteremia. Second, physicians need to identify the foci of infection, usually by magnetic resonance imaging, to assess the need for drainage by a surgeon or by interventional radiology. Third, if there are septic pulmonary emboli, Doppler and echocardiography should be used to identify DVT, and if detected, anticoagulation should be considered. Finally, daily reassessment by blood culture until sterility is documented, and careful physical examination is essential to detect new foci of infection.
Empirical antibiotic therapy of hospitalized pediatric patients begins with vancomycin (a loading dose of 20 mg/kg followed by 15 mg/kg every 8 hours), plus nafcillin or oxacillin, because of the difficulty in differentiating methicillin-susceptible S. aureus from MRSA clinically and the superiority of a semisynthetic penicillin if methicillin-susceptible S. aureus is the pathogen (Table 3). Trough levels of vancomycin should be determined after the third dose to achieve concentrations from 15 to 20 μg/mL. Gentamicin can be added for synergy, but clinical data documenting enhanced efficacy is absent. Fluoroquinolones, TMP/SXT, or linezolid should not be used for invasive disease in children because of the lack of efficacy and safety data (drug metabolism PK studies) in children. Similarly, the lack of efficacy and safety in children for the new antimicrobial agents, such as daptomycin or tigecycline, precludes their use in the pediatric population.
Community-acquired MRSA has become a successful pathogen in the pediatric population. The increasing incidence of CA-MRSA infection over recent years suggests that pediatricians take a more vigilant approach to the diagnosis and treatment of CA-MRSA infection to prevent serious complications and recurrence of infections. This approach may include routine cultures, emergent surgical drainage, new empirical antimicrobial therapies, and careful follow-up physical examination.7