Staphylococcal infections re-emerge as a concern

December 2002

---Philip A. Brunell, MD

Staphylococcal infections have again become a problem and things may get worse. In recent years, we have seen increasing methicillin resistance and the appearance of vancomycin-resistant organisms. Al-though methicillin-resistant organisms first were recognized in hospitalized patients, they are found with increasing frequency in the community. They also have been reported in neonatal intensive care units (NICU).

In the 1960s, there appeared to be a pandemic of staphylococcal disease. Newborn nurseries played a major role in dissemination of staphylococci at that time. The “confinement period” for mothers and their babies was usually about a week. This provided ample time for babies in the nursery to exchange their staphylococci and to colonize their mothers. When they returned home, they shared these organisms with household members. It was not uncommon to find “ping-pong” infections in families with abscesses, mastitis, styes and other superficial infections persisting for months. This taught us a great deal about the ability of staphylococcal infections to persist. Outbreaks in nurseries also taught us a great deal about infection control and the role of nasal colonization in transmission of staphylococci. The current practice of early discharge after delivery has had some virtue in that it likely has decreased the transmission of infection.

The rise of methicillin

The increase in staphylococcal disease in the ’60s coincided with the appearance of penicillinase-producing staphylococci. Prior to this time, penicillin was optimal treatment for staphylococcal infections. Initially, kanamycin, an aminoglycoside, replaced penicillin as the treatment of choice for ß-lactamase-producing staphylococci. Ultimately, methicillin became optimal therapy for newborn staphylococcal infections and persists as our choice to this day. In older children, “penicillinase-resistant semisynthetic penicillins,” e.g. oxacillin, methicillin and nafcillin, are used for treatment of staphylococcal infections.

These antistaphylococcal drugs appeared to be quite effective until the appearance of staphylococci in hospitalized patients that were methicillin-resistant (MRSA). Many of these could be traced to elderly patients who were transferred from nursing homes where there was excessive use of antibiotics. The original reports of community-acquired MRSA were in adult intravenous drug users in the ’80s. These organisms now are commonly found in the community where there is person-to-person transmission. This also is found in out-of-home day care settings. Now MRSA has been found in increasing frequencies in children from a variety of locations, and the frequency appears to be rising (JAMA. 1998;279[8]:593-598). At the Infectious Diseases Society Meeting in October, alarming increases in MRSA infections in Providence, R.I., Louisville, Ky., and Corpus Christi, Texas, and an epidemic in a NICU in Chicago were reported.

Most of the infections caused by community-acquired MRSA appear to involve the skin (JAMA. 1998;279[8]:593-598) although invasive infections have certainly been well documented. Indeed, four deaths have been reported in children with community-acquired MRSA (MMWR. 1999;48[32]:707-710). The description of these cases is reminiscent of the severe staphylococcal pneumonia of the ’60s. Severe community-acquired staphylococcal pneumonia, frequently in normal children and young adults, has been associated with organisms carrying Panton-Valentine leukocidin, a toxin causing leukocyte and tissue destruction. These patients were critically ill on presentation, having leukopenia, positive blood cultures and often with pneumatoceles. This toxin also has been identified commonly in staphylococci recovered from furuncles (Clin Infect Dis. 1999;29[5]:1128-1132).

How does one treat MRSA? For inpatients, vancomycin would be the choice. However, indiscriminate use of this drug is discouraged as there now have been staphylococci that are resistant (MMWR. 2002;51[26]:565-567). These isolates are sensitive in vitro to linezolid (Zyvox, Pharmacia) and quinupristin/dalfopristin (Synercid, Aventis Pasteur). Most of the MRSA that we will be seeing in practice will be treated as outpatients, and vancomycin, which is given intravenously, is not an option. Unfortunately, many MRSA also are resistant to multiple other antibiotics. Resistance to methicillin is most commonly conferred by acquisition of the mecA gene. This often is acquired with the “mec region” which contains multiple insertion sites for transposons which confer resistance to other antibiotics (JAMA. 1998;279[8]:593-598). Most experts would advise clindamycin for the therapy of MRSA infections. These experts also suggest that in vitro testing of the isolate against both erythromycin and vancomycin is performed. The appearance of a “D” zone of inhibition, with blunting on the erythromycin side, suggests the presence of a gene that will result in the rapid induction of clindamycin resistance. In this case trimethoprim-sulfa or possibly rifampin might be a reasonable alternative. Fortunately, most of the MRSA infections seen in practice will be superficial and will respond to drainage or local application of mupirocin (Bactroban, GlaxoSmithKline).

Our choice of antibiotic therapy must reflect the increase in MRSA in our communities. Although most of the infections will be superficial, invasive disease has been devastating. Finally, we must use the antimicrobial agents that are still effective prudently so as not to compromise existing options.

For more information:

• CDC. Staphylococcus aureus resistant to vancomycin – United States, 2002. MMWR. 2002;51(26):565-567.
• Lina G, Piémont Y, Godail-Gamot F, et al. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus in primary skin infections and pneumonia. Clin Infect Dis. 1999;29(5):1128-1132.
• CDC. Four pediatric deaths from community-acquired methicillin-resistant Staphylococcus aureus – Minnesota and North Dakota, 1997-1999. MMWR. 1999;48(32):707-710.
• Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998;279(8):593-598.