Nancy A. Melville

June 20, 2011

June 20, 2011 (Milan, Italy) — Overall hospitalization rates for Staphylococcus aureus increased only moderately in the United States between 2004 and 2008; however, the rate of hospitalizations related to the USA300 strain of isolates expanded dramatically, more than tripling during the same period, according to a study presented here at the 21st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID).

In combining data from the Surveillance Network (Eurofins Medinet) and the Nationwide Inpatient Sample (Healthcare Cost and Utilization Project), researchers identified 3 major groups of clonal complexes to corresponded with 89% of all isolates during the 4-year study period. Two of these groups are methicillin-resistant, and 1 is methcillin-sensitive.

The USA300 strain represented just 7.3% of all S aureus hospitalizations in 2004, with a hospitalization rate of 1.03 ± 0.08 per 1000 discharges. However, the rate had increased as much as 3.5 times by 2008 to represent 23.9% of all S aureus hospitalizations, with a rate of 3.62 ± 0.24 per 1000 discharges (P < .001).

Increases in the USA300 strain have been previously documented outside the hospital and among skin and soft tissue infections, but the study documents the rise among invasive disease at the hospital level, said lead author Robertino Mera MD, PhD, director of the Research Statistics Unit with GlaxoSmithKline in Collegeville, Pennsylvania.

"The strength of our study is to show [increases in] incidence rates at the national level and among invasive diseases such as pneumonia and bacteremia," Dr. Mera said.

The increase has been greater among children than adults, he noted. "The rate of USA300 increased 2.8 times among children compared with 1.95 times among adults during the study period."

The study showed that overall, S aureus hospitalization rates per 1000 discharges significantly increased, from 14.1 ± 0.25 in 2004 to 15.1 ± 0.24 in 2008 (P < .05).

Rates of clonal complex 5 PVL-MRSA, the most common hospital genotype in 2004 (41.3% of all S aureus hospitalizations, with a hospitalization rate of 5.83 ± 0.14), declined significantly by 2008, dropping down to become the second most common group (28.3% of all S aureus hospitalizations, with a rate of 4.28 ± 0.11 per 1000 discharges; P < .01).

No significant change was seen in the polyclonal methcillin-sensitive clonal complex over time, which accounted for 39.7% of all hospitalizations in 2004 (rate, 5.59 ± 0.19) and 38.5% of all S aureus hospitalizations in 2008 (rate, 5.83 ± 0.19 per 1000 discharges).

"Although the overall S. aureus hospitalization rate increased moderately during the period of observation, the share of USA300 isolates dramatically increased from 1 out of 13 S. aureus hospitalizations in 2004 to one out of four in 2008," the authors concluded.

USA300 has likely been able to spread because of its resistance to antibiotics and its robust ability for transmission, Dr. Mera said.

"The key factor that explains the expansion of the clonal group USA300 is its capacity to transmit and invade, coupled with innate resistance to most penicillins and macrolide [azithromycin, clarithromycin] antibiotics," he said.

Loren G. Miller, MD, MPH, associate professor of medicine and director of the Infection Care Program at Harbor-UCLA Medical Center in Torrance, California, agreed that the USA300 strain appears to have a stronger endurance than other methicillin-resistant S aureus (MRSA) strains.

"The USA300 strain is known to live on inanimate objects longer than other MRSA strains and be a relatively fit S aureus strain compared with other MRSA strains in in vitro and in vivo studies, in terms of growth rates and ability to cause disease. These features may give USA300 advantages to spread to other persons and cause disease more easily than other MRSA strains," Dr. Miller said.

"This study presents further support that the USA300 strain is very successful at causing disease and may be more pathogenic and transmissible than other MRSA strains," he added.

Dr. Mera indicated that more recent data from the Centers for Disease Control and Prevention will likely show a plateau in the USA300 strain, and Dr. Miller said that has also been his observation.

"Data I have seen and my clinical experience all suggest that the rapid increase in incidence of USA300 MRSA seen in the early-mid 2000s has leveled off, and infection rates haven't significantly changed over the past few years."

Nevertheless, the strain may remain a powerful force in boosting S aureus infection rates indefinitely, Dr. Miller noted.

"The success of USA300 causing disease may mean that S aureus infection rates may be above historical averages for many years to come," he said. "This rise could have a significant impact on patient morbidity and healthcare expenditures."

GlaxoSmithKline is currently working to develop an S aureus vaccine, which, if successful, could play an important role in preventing widespread infection, Dr. Miller said.

"An S aureus vaccine, if successful, could be a huge step in disease prevention and would have the potential to prevent many ambulatory infections that cause or complicate hospitalizations, and prevent deaths from serious S aureus infections," he noted.

"Even a vaccine that works against USA300...would have enormous public health implications, given [that] S aureus infections are so common."

The study received support from GlaxoSmithKline, which is developing an S aureus vaccine. Dr. Mera is an employee of GlaxoSmithKline. Dr. Miller's financial disclosures include that he served as an advisor or consultant for: Forest Laboratories, Inc, and received grants for clinical research from Pfizer Inc and Cubist Pharmaceuticals Inc.

21st European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). Presented May 9, 2011.

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