110: Methicillin-Resistant Staphylococcus aureus Infections

Infection with methicillin-resistant Staphylococcus aureus (MRSA) (clustered gram-positive cocci) causes a variety of localized and invasive suppurative infections and toxin-mediated syndromes such as toxic shock syndrome and scalded skin syndrome. MRSA infections used to be limited to health care facilities (HC-MRSA) and were strictly nosocomial; however, a significant increase in community-acquired MRSA (CA-MRSA) has been seen in the last decade. The separation between HC-MRSA and CA-MRSA is becoming less distinct, as CA-MRSA is becoming more virulent and causing significantly more health care–associated infections.

The methicillin-sensitive Staphylococcus aureus normally colonizes the nose, umbilicus, and the groin area by 1 week of age, with a colonization rate of 20–90%. Maternal anogenital colonization with MRSA ranges from 0.5% to 10.4%, with little risk for early-onset disease in the newborn. There are several documented outbreaks of invasive CA-MRSA that developed in healthy newborn infants discharged from normal newborn nurseries as well as neonatal intensive care units (NICUs). The majority of MRSA infections in the NICU are of late onset. According to neonatal data reported from National Nosocomial Infections Surveillance System for the years 1995–2004, MRSA accounted for 23% of all hospital-associated S. aureus infections. The incidence of MRSA infections per 100,000 patient-days increased by 308% during the study period from 0.7 in 1995 to 3.1 in 2004. The NICU colonization rate is variable; one study showed a rate of 10.4%, with a mean time to acquire MRSA of 17 days.

. If the newborn infant is exposed to MRSA, whether from the community or the hospital, then he or she will be colonized with more virulent strains that are more likely to cause invasive disease. MRSA has specific virulence factors that make it more invasive than methicillin-sensitive S. aureus. These include staphylococcal chromosome cassette (SCC) mecA, Panton-Valentine leukocidin (PVL), and staphylococcal enterotoxins. The SCC mecA has the genes that encode antibiotic resistance. PVL genes lead to the production of cytotoxins that form pores in the cellular membrane and cause tissue necrosis and cell lysis.

Include overcrowding, inconsistent hand washing, invasive procedures (eg, central lines, endotracheal intubations, nasogastric tubes), low birthweight, the practice of kangaroo (skin-to-skin) mother care, a high MRSA colonization rate, and prolonged hospital stay.

Invasive MRSA disease is likely to be preceded by colonization (skin, umbilicus, and nasopharynx). The source of the bacteria could be a health care worker, another patient, equipment, or a family member.

1. Bloodstream infections. These are usually catheter related. Common clinical signs are nonspecific and include apnea or hypoxia, fever, elevated C-reactive protein, and leukocytosis. The infant needs to be examined repeatedly and meticulously for subtle clues of focal infection (eg, phlebitis, pustulosis).

2. Septic arthritis and osteomyelitis. Staphylococcus aureus is the primary cause of septic arthritis and osteomyelitis in the neonate. Symptoms are nonspecific, such as poor feeding or increased irritability. Signs include soft tissue swelling and erythema.

3. Endocarditis. Neonates with congenital heart disease and percutaneous central catheters are at a higher risk for endocarditis.

4. Skin and soft tissue infections. Staphylococcus aureus is the most common pathogen causing pustulosis and cellulitis in the neonate. MRSA has virulence factors that contribute to the pathogen's ability to damage the neonatal skin that is already compromised.

5. Conjunctivitis. See Chapter 53.

6. Pneumonia. Pneumonia can be primary or associated with ventilator therapy. The course is frequently complicated by alveolar necrosis, pneumatocele formation, and pleural empyema.

7. Surgical site infections.

The gold standard for diagnosing a bloodstream infection is a positive blood culture. Diagnosing arthritis and osteomyelitis can be challenging. In addition to a blood culture, the workup should include a joint aspirate, bone culture (if surgical debridement is done), radiography, and possibly magnetic resonance imaging. Echocardiography (to diagnose endocarditis) is strongly recommended in infants with >1 positive blood culture. For skin and soft tissue infections, incision and drainage, with subsequent Gram stain and culture of aspirated fluid, is recommended. Real-time polymerase chain reaction (PCR) has been used recently for active surveillance of MRSA in the NICU; however, studies have shown PCR to have low reproducibility, low positive predictive value, and high false-positive rate. Therefore, PCR should not be used for screening MRSA in the NICU.

1. Eradication of colonization. Adult intensive care unit studies demonstrated that eradication of MRSA colonization using a combination of 5 days of intranasal mupirocin and 3 daily chlorhexidine baths resulted in reducing MRSA infections. There are no studies in neonates showing similar efficacy; however, mupirocin has been used effectively in controlling outbreaks of MRSA in NICU populations.

2. Antibiotic therapy. The Infectious Diseases Society of America issued guidelines for the management of invasive MRSA infections in adults and children including infants ≤30 days of age. Vancomycin is the first-line therapy for MRSA, and many NICUs with endemic MRSA use vancomycin as an empirical therapy for late-onset sepsis while awaiting culture results. In cases of vancomycin intermediate S. aureus (VISA) or vancomycin allergy, linezolid and clindamycin have been used effectively. Treatment duration depends on the specific infection. For skin and soft tissue infections and bacteremia, a 7- to 10-day course is generally appropriate. In cases of endocarditis and osteomyelitis, 6–8 weeks of treatment is necessary. In patients with extensive disease with persistently positive blood cultures despite therapeutic doses of vancomycin, both rifampin and gentamicin can be used for synergy. Mupirocin may be adequate for mild cases of localized neonatal pustulosis in the well-appearing full-term infant.

1. Hand hygiene. The Centers for Disease Control and Prevention recommends using an alcohol-based hand sanitizer before touching patients, after touching patients, after removing gloves, and after touching the patient care environment and equipment due to the ability of MRSA to survive on inanimate objects. Alcohol-based hand sanitizers improve compliance with hand hygiene policies as well as improve the skin integrity of health care workers.

2. Controlling outbreaks. During an outbreak, many measures are instituted concurrently. In 2006, Gerber et al released a consensus statement from the Chicago Department of Public Health on the management of outbreaks of MRSA in a NICU. Their recommendations included an alcohol-based rub for hand hygiene, isolation and cohorting of MRSA-colonized infants, and regular neonatal surveillance cultures (Table 110–1). They also emphasized the use of molecular typing as an integral part of control because it can determine the ongoing transmission of a particular clone. They did not make a recommendation for decolonization with mupirocin; this intervention was left to the discretion of the primary clinical care team because the efficacy of this strategy is uncertain. Passive protection of neonates by using the monoclonal antibody tefibazumab, which binds to the surface-expressed adhesion protein clumping factor A, has not proven to be efficacious.