Methicillin-Resistant Staphylococcus aureus (MRSA) Infection
THE ORGANISM
Staphylococci are aerobic or facultative anaerobic gram-positive cocci in clusters or, less often, chains, pairs, or tetrads. Staphylococcus aureus produces coagulase. Staphylococci that do not produce coagulase are reported as coagulase-negative staphylococci (CONS) and include S. epidermidis, S. lugdenensis, S. haemolyticus, and S. saprophyticus. Both S. aureus and certain species of CONS can cause serious infection in the newborn period. This chapter deals only with infections caused by S. aureus.
Staphylococcus aureus became resistant to penicillin shortly after penicillin was introduced in the 1940s by producing penicillinase, which inactivates the β-lactam ring in penicillin. Penicillinase-stable β-lactam antibiotics (methicillin, nafcillin, and oxacillin) were developed to overcome this resistance. However, in 1961, a strain of methicillin-resistant S. aureus (MRSA) was identified that was resistant to these newer β-lactam antibiotics.1 Methicillin resistance occurs as a result of a modified drug target, penicillin-binding protein (PBP2a), encoded by the mecA gene2 on a staphylococcal cassette chromosome (SCCmec types I–V).3 SCCmec types II–III typically carry multiple resistance determinants. SCCmec types IV–V carry fewer resistance determinants but may be associated with virulence factors such as Panton-Valentine leucocidin (PVL).
Initially, most strains of MRSA were health care or hospital associated (HA-MRSA) and were SCCmec types I–III. Now, MRSA can be acquired in the community (CA-MRSA) and colonizes or infects patients who have neither been hospitalized nor had recent access to health care. CA-MRSA is associated with SCCmec types IV and V. CA-MRSA tends to be susceptible to more antibiotics compared to HA-MRSA. However, resistance patterns are variable, depending on which strains are circulating in a community.
EPIDEMIOLOGY
Staphylococcus aureus has a propensity to colonize the anterior nares, and many studies evaluating colonization rely on nasal cultures.4 In infants, other body sites are likely to be colonized, including the throat, umbilicus, skin (groin and axillae), vagina, and rectum.5–7 Approximately 25%–50% of the population is colonized with S. aureus, either methicillin-sensitive strains (MSSA) or MRSA.8–10 Colonization with MSSA is more common than with MRSA. Children are more likely to be colonized than adults. Some patients are never colonized, some only intermittently, and some persistently. The rate of MRSA colonization in the United States is reported to be low (<2%)8 but varies depending on the population studied. For example, the following holds:
• Newborns: Fewer than 1% to 40% (colonization rates higher during neonatal intensive care unit [NICU] outbreaks)11–14
• Healthy children less than 5 years old: Fewer than 1%–6.7%15, 16
• Pregnant women: Fewer than 1%–10% (anogenital cultures)17–20
– There are conflicting reports regarding the association of MRSA genital colonization and group B streptococcus genital colonization.20
• Homeless in San Francisco: 2.8%
• Veterinarians: 6.5%21
• Pediatric patients in Texas: 22%22
It is common for infants to become colonized with S. aureus after exposure to their mothers, other family members and friends, or hospital and home environmental surfaces. In most cases, colonization occurs after discharge from the nursery.23 Transmission of MRSA is reported through the following:
• Infected breast milk and colonized caregivers to neonates24
• Health care workers to neonates25
• NICU patients to health care workers and their families26
• Interinstitutional transfer of MRSA from one nursery to another27
Neonatal colonization with S. aureus increases with age. Most infants are unlikely to be colonized in the first 3 days of life.11, 28 Transmission of MRSA from mother to infant during delivery is rare but reported (proven when isolates are matched by pulsed field gel electrophoresis).23 Most infants colonized with MSSA or MRSA do not develop infection. However, in some studies, 4%–26% of MRSA-colonized infants developed MRSA infection.11, 12, 28 Risk factors for developing infection with MRSA in the newborn period include12, 13, 29–35
• MRSA chorioamnionitis
• Prematurity or very low birth weight
• Cesarean section
• Presence of a central venous or umbilical catheter
• Previous antibiotic use
• Prolonged hospitalization
• Surgical procedures
• Male gender (independent of circumcision)
• Circumcision
Colonization with MRSA clears over time in most infants without specific topical or oral antibiotics for eradication.11
Key Point
• In some circumstances, the type of S. aureus (MSSA or MRSA) isolated from the anterior nares does not predict the type of S. aureus causing infection (eg, MSSA is isolated from the nose but MRSA is isolated from the site of infection or vice versa).36
CLINICAL FINDINGS:
MRSA Colonization: Colonized infants are asymptomatic.
MRSA Infection: Clinical features of infection are indistinguishable from those caused by MSSA. Infection with MRSA typically presents after the first week of life32 but may be present shortly after delivery or a few weeks after discharge from the nursery.
Skin and soft tissue infections (SSTIs): SSTIs comprise most neonatal MRSA infections.
• Superficial skin infection lesions are typical of those seen with S. aureus (eg, impetigo) and may be pustular or bullous in appearance.
• Lesions may be present anywhere, but in newborns are often in the diaper area.
• MRSA may cause cellulitis, mastitis, or omphalitis.
MRSA conjunctivitis: MRSA is an increasingly common cause of neonatal bacterial conjunctivitis.30
Bacteremia:
• Staphylococcus aureus rarely causes early-onset neonatal sepsis.
• Approximately 8% of cases of late-onset sepsis (after 72 hours of life) in low birth weight infants are caused by S. aureus.37, 38
• Infants with MRSA bacteremia are younger at presentation than those with MSSA bacteremia (mean age at diagnosis 23 vs 32 days).39
• Blood cultures may be persistently positive, especially if catheters are not removed immediately.
• Failure to remove a central catheter in less than 4 days has been associated with complicated MRSA disease.40
Endocarditis: MRSA endocarditis has been reported in infants and has a high mortality.40 Premature infants and those with congenital heart disease are most often affected.
Bone and Joint Infections: MRSA bone and joint infections commonly involve multiple foci and are associated with deep vein thromboses with septic embolization to the lungs.
Respiratory: Though MRSA may colonize the respiratory tract or endotracheal tube in asymptomatic infants, it can cause pneumonia, empyema, and lung abscess.41
Deep Abscess: Deep abscesses involving the liver and retropharynx have been reported in infants.42,43
Central Nervous System Infection:
• Meningitis or brain abscesses are rare but reported, including one case report of an extremely premature infant who succumbed to multiple brain abscesses caused by MRSA.44
• Some infants with MRSA bacteremia have a cerebrospinal fluid (CSF) pleocytosis with negative CSF cultures.31
• MRSA may cause ventriculoperitoneal shunt infections.
Urinary Tract Infections: These may be seen in infants with bacteremia and disseminated MRSA infection.45
Coinfections: Serious coinfections with MRSA and other pathogens have been reported. Infection with MRSA and influenza virus has resulted in serious illness and death.46,47 MRSA infection occurs in conjunction with other respiratory pathogens such as respiratory synctial virus (RSV), parainfluenza virus, adenovirus, and enteroviruses.41 Staphylococcus aureus (including MRSA) has been isolated from vesiculopustular skin lesions in addition to herpes simplex virus (HSV) in patients with neonatal HSV infection.
DIAGNOSIS
Screening the Asymptomatic Infant
• There are currently no formal consensus guidelines regarding optimal screening procedures for asymptomatic infants for MRSA colonization.48
• Many nurseries screen all infants at the time of admission to the hospital. Some screen periodically thereafter until the baby is discharged home. Samples may either be sent for culture (results available within 2–3 days) or mecA PCR (results available within 1 day).
• Caregivers of infants who screen positive for MRSA should receive education regarding MRSA.49 The Centers for Disease Control and Prevention website has educational material for parents regarding MRSA colonization and infection (http://www.cdc.gov/mrsa/index.html).
• Estimated sensitivity of screening for identifying colonized infants12,50:
– Nares: 71%
– Umbilicus: 60%
– Skin: 40%
– Rectum: 21%–60%
– Nares plus umbilicus: >90%
Evaluation of MRSA in the Symptomatic Infant
• Physical Examination: Perform a complete physical examination with particular attention to numbers of venous or arterial catheters, evidence of catheter exit site or tunnel infection, eye discharge, skin lesions, respiratory distress, areas of cellulitis, joint or limb swelling, or failure to move an extremity.
• Laboratory Testing and Imaging: Laboratories identify MRSA by determining oxacillin or methicillin resistance by disk diffusion broth microdilution techniques. Larger laboratories may have the technology to identify the mecA gene by PCR.51 Other techniques to differentiate MSSA from MRSA include minilatex agglutination, colorimetric immunoassay methodology, and fluorescence screening.52
Evaluation of Specific MRSA Conditions
• Superficial skin infection in a well-appearing healthy infant:
– Obtain a Gram stain and bacterial culture of pus from skin lesions with full susceptibility testing.
– Consider testing for HSV and varicella zoster virus (VZV) by direct fluorescent antibody testing, viral culture, or HSV/VZV PCR if lesions are suspicious for HSV or varicella.
• Any infant with signs of sepsis or systemic infection: Perform a full sepsis evaluation, including
– Lumbar puncture for glucose and protein, complete blood cell count (CBC) with differential, Gram stain, and cultures
– Blood cultures
– Urine culture (suprapubic or straight catheterization)
– C-reactive protein
– A chest radiograph may show consolidation, pleural effusion, or lung abscess.
– Echocardiogram should be obtained if blood cultures are positive for S. aureus for more than 2–3 days and in patients with congenital heart disease.
– Plain radiographs of bone can indicate suspected osteomyelitis. Magnetic resonance imaging (MRI) is helpful if feasible. Consider technetium bone scan because multifocal osteomyelitis is seen frequently in neonates.
– Computed tomography or MRI of the brain should be performed if the patient has clinical or laboratory evidence of central nervous system disease.
– Abdominal ultrasound can be used to identify liver abscesses, particularly if the patient has had an umbilical catheter in place.43
Key Point