CA-MRSA in neonates a sign of the times

December 2006

NEW YORK – Community-associated methicillin-resistant Staphylococcus aureus is fast becoming everyone’s problem, according to a speaker at the 19th Annual Infectious Diseases in Children Symposium, held here.

Sarah S. Long, MD, a professor of pediatrics at Drexel University College of Medicine, and chief of the section of infectious diseases at St. Christopher’s Hospital for Children, both in Philadelphia, said that methicillin-susceptible Staphylococcus aureus almost seems “quaint,” in the era of the multi-drug resistant strains of hospital-associated MRSA and the ever-expanding problem of community-associated MRSA.

The community-associated MRSA problem is becoming more and more pronounced with a predominance of the major clone, USA300, circulating in the community.

This strain of 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 predominant hospital strains, USA100 and USA200. 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, it is more commonly associated with skin and soft tissue abscesses and severe necrotizing pneumonia.

This community-acquired type of MRSA makes up a substantial and increasing proportion of Staphylococcus aureus infections in previously healthy neonates, Long said. She cited data from the Morbidity and Mortality Weekly Report and other sources that noted CA-MRSA in infants in Chicago, Los Angeles and Texas.

The Chicago outbreak

A Chicago nursery reported that a number of newborns were returning to the hospital within a few days after birth with MRSA skin lesions.

These reports included newborns who were younger than 30 days old and who were delivered at the hospital between May and December 2004. When they returned to the hospital, these patients had recognizable skin lesions but not colonization.

Eleven babies (nine boys and two girls) delivered between May and December were identified as having MRSA. The mean age of the babies was 7 days, with a range of 4 to 23 days. Their mean hospital stay was four days, with a range of three to 11 days. Nine of the babies were delivered by cesarean section, and one baby had onset of MRSA before discharge.

The skin lesions were documented by health care providers as looking like blisters, vesicles or pustules, and were found all over the body. Two babies had single lesions, and nine had multiple lesions affecting multiple body parts. Ten infants received topical treatment, and three of these also received oral antibiotics. None of the lesions required draining.

None of the mothers or other family members had a history of skin lesions, and there were no links to other risk factors for MRSA, such as history of hospitalization, dialysis, surgery, prison stays for family members or living in military barracks.

As part of the investigation, 135 health care workers were cultured. One physician and one nursery nurse had nasal colonization of MRSA. The nurse was present in the nursery during the stays of all 11 babies, while the physician was present with just a few of them.

After reinforcement of infection control measures, hand hygiene, direct observation and training and enhanced environmental cleaning, the two health care workers were successfully decolonized, and no further cases were identified.

Fortunav et al reported 61 cases of CA-MRSA that may have been acquired from a Texas hospital. They prospectively identified patients with community-acquired S. aureus infections and collected their S. aureus isolates from the clinical microbiology laboratory.

The Baylor Infectious Disease Laboratory coded and froze the specimens in horse blood at 80°C, and tested for susceptibility and resistance.

During the study period, 89 neonates were identified. The researchers selected patients who were younger than 30 days old when they were seen between Aug. 1, 2001, and March 30, 2005. Participants were further identified by medical chart review to determine which were born past 36 weeks gestation and were determined to be previously healthy.

The researchers analyzed antibiotic susceptibility and found that 28 isolates were susceptible to oxacillin by disk diffusion and 61 were resistant. The number of S. aureus isolates recovered from previously healthy infants increased each year, the researchers noted.

Mechanism of resistance

The mechanism of resistance in MRSA is related to the mecA gene that alters penicillin-binding. These proteins reduce binding to all beta-lactams, including penicillins, cephalosporins, cephamycins and carbapenems. The mec 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, Long said, and has forced physicians to look at alternatives like vancomycin and linezolid.

Fortunately right now, the community-associated type of MRSA has little resistance to other non-beta lactams, and clindamycin, doxycycline and TMP-SMX still work very well in these organisms. Unfortunately, the prevalence of CA-MRSA is higher in pediatric populations than the hospital-associated form, which could mean as these agents are prescribed with more frequency, resistance could become a problem. In fact, an increasing amount of clindamycin resistance is already being witnessed. Long urged the use of 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 15 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.

Treatment options

Discussing treatment options for MRSA, Long said in many cases, that draining is curative and sometimes, oral antibiotic therapy is not needed. For uncomplicated skin and soft tissue infections, clindamycin, TMP-SMX, doxycycline, minocycline or linezolid may be used. For severe infections and osteomyelitis, vancomycin with or without rifampin can be started empirically.

To prevent MRSA, Long recommended routine hygiene and hand washing, mupirocin to anterior nares two to three times a day for seven to 10 days, and chlorhexidine baths.

For more information:

• Long S. MRSA in pediatrics: Challenges in management and control. Presented at: The 19th Annual Infectious Diseases in Children Symposium. Nov. 18-19, 2006. New York.