Know resistance rates in your area to treat CA-MRSA

December 2006

ATLANTA – Community-associated methicillin-resistant Staphylococcus aureus is a moving target, and knowing the resistance patterns in your community can be key to treatment, according to a speaker at the 2006 American Academy of Pediatrics National Conference and Exhibition, held here.

Tina Q. Tan, MD, an associate professor of pediatrics at Northwestern University Feinberg School of Medicine, said CA-MRSA is having a significant effect on physicians’ abilities to treat a number of other infections, as bacteria develop resistance to common treatments used to treat these infections.

Beginning her discussion, Tan quoted the former Director-General of the WHO saying, “At the dawn of a new millennium humanity is faced with another crisis … formerly curable diseases are now arrayed in the increasingly impenetrable armor of antimicrobial resistance.”

MRSA has been present as a cause of nosocomial infections for decades, and today is the most widespread infection in United States hospitals, accounting for more than 50% of all nosocomial infections.

The mechanism of resistance in MRSA is related to the mecA gene that specifies the production of a protein that inhibits penicillin-binding. These proteins reduce binding to all beta-lactams, including penicillins, cephalosporins, cephamycins, and carbapenems. The mecA gene complex also contains insertion sites for plasmids and transposons that facilitate resistance to other antibiotics, like erythromycin, clindamycin, gentamicin, trimethoprim-sulfamethoxazole and ciprofloxacin. This resistance has presented a significant treatment dilemma, Tan said, and has forced physicians to look at alternatives like vancomycin and linezolid.

In 1982, MRSA was first reported outside the hospital setting among injection drug users. This community-acquired MRSA is occurring with rapid frequency, up to 80% in some cities. This is important because MRSA can cause many types of infections beyond skin and structure infections, Tan said.

Fortunately, right now, CA-MRSA has little resistance to other nonbeta-lactams, and clindamycin, doxycycline and TMP-SMX still work very well in treating many of these infections. However, the prevalence of CA-MRSA is higher in pediatric populations than the hospital-acquired form, which could mean as these agents are used with more frequency, resistance could become a problem. In fact, an increasing amount of clindamycin resistance is already being reported.

“If you look at the antibiotic susceptibility patterns of CA-MRSA, there is a pattern that can set you up for resistance to erythromycin, but susceptible to clindamycin, but you may also have inducible clindamycin resistance,” Tan said. Because of this, many hospitals have adopted policies prohibiting use of clindamycin, however, she said, this is unfortunate because it means, “losing an option to treat this.” She urged using a D-test to determine if a patient has inducible clindamycin resistance.

The D-test is performed by placing erythromycin and clindamycin disks at a distance of 15mm to 20 mm and looking for flattening of the clindamycin zone nearest the erythromycin disk. A positive D-test suggests the presence of an erm gene that could result in constitutive clindamycin resistance and clinical failure.

The two major CA-MRSA clones in the United States are USA300 and USA400, and in U.S. hospitals, the two major clones are USA100 and USA200.

Also, the CA-MRSA is more frequently associated with the Panton-Valentine leukocidin toxin gene, which in some cases can make it more virulent compared with the hospital strain. The PVL gene is a cytotoxin that causes leukocyte destruction and tissue necrosis. The genes that encode for PVL can be transmitted via bacteriophage from one organism to another, making it more commonly associated with skin and soft tissue abscesses and severe necrotizing pneumonia.

Risk factors for MRSA include the following:

• a history of infection or colonization within the past year
• admission to a long-term care facility
• diabetes mellitus
• surgery
• permanent/indwelling catheters or medical devices that pass through the skin
• a high prevalence of MRSA in the local community or patient population
• close contact with someone known to be infected or colonized with MRSA
• recurrent skin infections
• crowded living conditions
• recent frequent antibiotic use
• incarceration
• infection among sports teams that have skin-to-skin contact
• being a member of certain ethnic populations, such as Alaska Native and Pacific Islanders

Also, physicians who are seeing MRSA among families may want to consider pets as a source of transmission, as dogs and cats have been identified as reservoirs in the veterinary literature.

Tan said that skin and soft tissue infections are the most common presentations of CA-MRSA, accounting for up to 80% of all CA-MRSA infections. Others include bacteremia, necrotizing pneumonia with empyema and osteomyelitis. She said pyomyositis is being seen more commonly and physicians should think about this condition in patients presenting with bone and joint infections.

In neonates, Tan said that CA-MRSA infections are becoming more common, often seen in males in the skin and soft tissue areas ad sacral regions.

Discussing treatment, Tan called CA-MRSA “a moving target.” She said in many cases, drainage is curative and sometimes, oral antibiotic therapy is not needed. For uncomplicated skin and soft tissue infections, she recommends clindamycin, TMP-SMX, doxycycline, minocycline or linezolid. For severe infections and osteomyelitis, she recommended vancomycin with or without rifampin, started empirically. For septic shock, meningitis or other severe infections, Tan said vancomycin, rifampin and gentamicin could be used.

For more information:

• Tan TQ. Community-acquired Staphylococcus aureus disease. Session #F224. Presented at: The 2006 American Academy of Pediatrics National Conference and Exhibition. Oct. 7-10, 2006. Atlanta.