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Issue: August 2010
August 01, 2010
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USA300 S. aureus pulsotype emerging as an important health care-associated pathogen

Issue: August 2010
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Staphylococcus aureus is one of the most important organisms causing health care-associated infections with onset either in the hospital or in the community.

Sheldon Kaplan, MD
Sheldon Kaplan

Surgical site (including device-related) infections, hospital-acquired pneumonia (including ventilator-associated pneumonia) and catheter-related bloodstream infections are perhaps the most common S. aureus infections.

Methicillin-resistant S. aureus is an especially important nosocomial pathogen that has been associated with increased medical costs and length of stays, and in some studies, increased mortality when compared with nosocomial infections due to methicillin-susceptible S. aureus isolates.

MRSA in pediatrics

S. aureus infections in children are common.

In a study of 35 pediatric ICUs, S. aureus was the third most common organism behind coagulase-negative staphylococcus and enterococcus that caused nosocomial infections. Srinivasan and colleagues prospectively studied 60 infants and children who underwent intubation and mechanical ventilation for at least 24 hours; 19 developed ventilator-associated pneumonia. S. aureus was the most common organism (n=9) and accounted for 23% of all isolates.

Investigators associated with the Surveillance and Control of Pathogens of Epidemiologic Importance (SCOPE) project looked at bloodstream infections in children between 1995 and 2001.

More than 3,400 bloodstream infections in children younger than 16 years were reported, and 75% occurred in the pediatric ICU or neonatal ICU. Underlying conditions included pulmonary disorders (24%), malignancies (8%) and gastrointestinal conditions (7%). Central venous catheters were in place in 75% of the patients. S. aureus accounted for 9% of the bloodstream infection isolates, of which 16% were MRSA.

Lessa and colleagues — using data from the National Nosocomial Infections Surveillance System — found that the incidence of late-onset MRSA infections among neonates of all birth weights increased more than 300% from 1995 through 2004. In contrast, MSSA incidence decreased 20% during the same time period. The overall incidence of S. aureus infections increased 13%. Bloodstream infections and pneumonia accounted for 49% of the late onset MRSA infections.

MRSA in the community

During the 1990s, MRSA became increasingly recognized as a pathogen causing community-associated MRSA infections in the United States and throughout the world.

By using molecular techniques, including pulsed-field gel electrophoresis, the CA-MRSA isolates were shown to be different than the MRSA isolates that caused infections in the health care setting.

The CA-MRSA isolates typically were classified as USA300 or USA400 by pulsed-field gel electrophoresis and most commonly carried the staphylococcal chromosomal cassette mec (SCCmec) type IV, as well as the genes encoding for Panton-Valentine leukocidin (PVL). In contrast, the health care-associated MRSA isolates were non-USA300 or non-USA400 pulsotypes, typically carried a SCCmec type that was not type IV and rarely carried the genes encoding PVL.

Not long after CA-MRSA isolates emerged, investigators recognized that the MRSA isolates with the molecular characteristics typically associated with the CA-MRSA isolates were also causing health care-associated infections.

Early reports from New York, Atlanta, Detroit, Denver and Houston documented USA300 MRSA isolates as important causes of nosocomial infection, especially bloodstream infections, and focused primarily on adult patients. Data from the Active Bacterial Core surveillance from July 2004 to December 2005 indicated that 16% of the tested HA-MRSA invasive isolates and 22% of the community onset health care-associated isolates were USA300. Similar reports from around the world documented the emergence of MRSA USA300 or other local CA-MRSA pulsotypes as an increasingly important nosocomial pathogen.

S. aureus USA300 is as common a nosocomial pathogen in children as it is in adult patients.

In a case series from a children’s hospital in Memphis, Tenn., four of nine tested MRSA health care-associated isolates from 1999 to 2002 were USA300. Investigators from Minnesota reported that among 83 HA-MRSA isolates recovered from children in the Children’s Hospital and Clinics in Minneapolis from 1991 through 2003, 26 were USA400 and nine were USA300 pulsotypes.

Healy and colleagues found six of eight HA-MRSA isolates from neonates to be USA300 in a neonatal ICU in Houston during 2003. The infections occurred at a median of 26 days of age. Among S. aureus isolates from patients with risk factors for health care-associated infections at The Children’s Hospital of Philadelphia from 2001 to 2003, most had molecular characteristics consistent with USA300.

Four of 676 neonates in a San Antonio neonatal ICU during an 18-month period during 2004-2005 had MRSA infection or colonization. Three health care workers helping to care for these infants, as well as two children of one of these workers, developed MRSA skin and soft tissue infections over this same period. All isolates tested were USA300.

By 2003, USA300 MRSA was increasingly isolated from children with cystic fibrosis followed at St. Louis Children’s Hospital. Children with PVL-positive MRSA isolates had greater reductions in FEV1 at the time of MRSA detection than children with PVL-negative isolates. Researchers reviewed 88 HA-MRSA infections in children with cancer at St. Jude Children’s Research Hospital from 2000 to 2007. Skin and soft tissue infections and bloodstream infections accounted for 68% and 10% of episodes, respectively. Thirty-two isolates were USA300. Thus, USA300 has been an important health care-associated infection pathogen in children with a wide variety of underlying conditions in the United States for almost a decade.

Nosocomial S. aureus infections

Colonization by USA300 MRSA in children with underlying conditions or in the hospital has been reported. Fritz and colleagues assessed nasal colonization by S. aureus in children at community pediatric practices in St. Louis in 2005-2006; 60% of children from whom a MRSA isolate with the SCCmec IVb element was recovered (n=21) had a chronic health problem.

Milstone and colleagues determined the incidence of nosocomial acquisition of MRSA nasal colonization among children admitted to the pediatric ICU of Johns Hopkins Hospital in Baltimore in 2007 and 2008. Among the 1,674 children in the pediatric ICU during the course of the study, eight cases were detected, resulting in an incidence density of 1.01 cases per 1,000 patient days of risk. Four of seven isolates available for testing were identical or related to USA300.

Hulten and colleagues reported the nosocomial S. aureus infections at Texas Children’s Hospital in Houston in a prospective study from 2003 to 2007. Of the 242 isolates available for testing, 95 were MRSA, and 69 of these isolates were USA300. Of the 147 MSSA isolates, 14 were classified as USA300. Of the 95 MRSA isolates, 51 were recovered from children with nosocomial skin and soft tissue infections, and USA300 accounted for 43 of these isolates. MRSA bloodstream infections occurred in 29 children; 13 isolates were USA300. Children with USA300 isolates were less likely to be admitted to the ICU than children with non-USA300 isolates during their hospital admission.

Children with underlying neuromuscular disorders or without an underlying condition were more likely than children with other underlying conditions to be infected with USA300 isolates. USA300 MRSA isolates were more likely to be susceptible to other non-beta-lactam antibiotics and to cause infections in the first 10 days after admission than non-USA300 MRSA isolates. In addition, more than 90% of MRSA isolates associated with community onset health care-associated infections at Texas Children’s Hospital during 2001 to 2004 were USA300.

A subset of health care-associated S. aureus isolates from children with catheter-related bloodstream infections at Texas Children’s Hospital from 2001 to 2007 were studied by Carillo-Marquez and colleagues. MRSA caused 26% of the initial catheter-related bloodstream infection among 112 children. Overall, 19% of the isolates were USA300; 12 of 29 of the MRSA isolates and nine of 83 MSSA isolates.

Thus, the USA300 S. aureus pulsotype is now established as a frequent health care-associated pathogen, as well as the dominant pulsotype causing community infections in healthy children in the United States. Consequently, molecular characteristics of S. aureus isolates recovered from patients with health care-associated infections are not helpful in determining the source of hospital transmission or for distinguishing isolates causing community-associated vs. health care-associated infections. This is true for both MRSA and MSSA isolates. Applying several strategies, including bundles, have been successful in reducing some HA-MRSA infections, and vaccines for prevention of surgical sites infections are under investigation.

Future studies may reveal clues as to why the USA300 pulsotype is so successful in causing infections, as well as lead to innovative approaches to prevent infections caused by USA300 S. aureus either in or out of the hospital.

Sheldon Kaplan, MD, is Chief of Infectious Disease Service at Texas Childrens’ Hospital in Houston and is an Infectious Diseases in Children Editorial Board member.

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