MÜNSTER, GERMANY--A substantial proportion of cases of Staphylococcus aureus bacteremia are endogenous, originating from organisms carried in the patient's own nasal mucosa, a recent German investigation suggests.[1] "S aureus isolates from the anterior nares were clonally identical to those from the blood in more than 80% of our bacteremic patients," lead investigator Christof von Eiff, MD, told PULMONARY REVIEWS.

The anterior nares act as a reservoir for S aureus, pointed out Dr. von Eiff, an Assistant Professor in the Institute of Medical Microbiology at the University of Münster in Germany. About 20% of healthy individuals almost always harbor the organism in their noses, and another 60% harbor the organism intermittently. Moreover, some studies have already demonstrated that eliminating nasal carriage of S aureus with topical antibiotics may make bacteremia less likely to develop.

Dr. von Eiff's investigation is the first to compare S aureus isolates from patients' nasal mucosa and blood using modern molecular-typing techniques. This study also provides additional evidence to support bacteremia prevention strategies that eradicate S aureus from the nasal mucosa.

The investigation consisted of a multicenter and a single-center study. In the multicenter study, which was conducted at 32 German hospitals, swabs of the anterior nares of 219 patients with S aureus bacteremia were obtained and cultured. The nasal cultures were taken immediately after S aureus was isolated from the patients' blood. More specimens were obtained and cultured if patients had a focal point of infection. All isolates were genotyped.

In the second study, S aureus specimens were obtained prospectively from the anterior nares of 1,278 patients treated on general wards or in the intensive care unit (ICU) of one hospital. The cultures were frozen so that they would be available for comparison with blood isolates if the patients later developed S aureus bacteremia during their current hospital stay or a later one.

In both studies, S aureus isolates obtained from blood were tested for methicillin resistance. Only one isolate from each patient was examined unless the patient had clonally different strains. In such cases, all strains were tested.

A total of 723 S aureus isolates were collected and genotyped in the multicenter study. The majority of the patients from whom the isolates were obtained were being treated on general wards. Slightly more than one-quarter were in ICUs. About 9% of the patients harbored methicillin-resistant strains of S aureus.

Clinical findings suggested that catheter-related infection was the most frequent cause of S aureus bacteremia in these patients. Osteomyelitis, skin and soft-tissue infections, and lower respiratory tract infections were other common causes.

In more than 80% of the patients, however, isolates from the anterior nares were clonally identical to those from the blood, suggesting that the bacteremia originated from colonization in the nasal mucosa. The blood isolates matched those from other body sites in 94% of the patients, the investigators also reported.

The study at the single center produced similar results. Of the 14 patients in this study who subsequently developed S aureus bacteremia, isolates from the anterior nares were clonally identical to those from the blood in 12, or 86%. These patients ranged in age from 4 to 79 years old.

Considering the two studies' similar findings, Dr. von Eiff and his colleagues concluded that nasal colonization with S aureus preceded the bloodstream infection in at least half of all of the bacteremic patients in their investigation. "Our results provide evidence that strategies to interrupt transmission of S aureus by the elimination of nasal carriage may prevent systemic S aureus infections," they also noted. In the past, the most successful eradication trials were performed with mupirocin, according to Dr. von Eiff.

In an editorial accompanying the von Eiff study, Gordon L. Archer, MD, and Michael W. Climo, MD, noted that its results may be even more important in the United States than in Germany.[2] According to the Centers for Disease Control and Prevention, an estimated 34% of S aureus isolates obtained from patients with nosocomial bacteremia in US hospitals in 1995 were resistant to methicillin; this rate is far higher than the 6% to 9% reported by Dr. von Eiff and colleagues. Also, comparatively few of the patients in the German study were being treated in the ICU. "Therefore, if anything, the low number of methicillin-resistant isolates and number of patients in the intensive care unit…in the German study may underrepresent the risk of bacteremia after nasal colonization with S aureus," they said.

Eliminating nasal colonization should be a priority in efforts to prevent S aureus bacteremia, agreed the two physicians, who are at the Medical College of Virginia in Richmond. However, the available tools for this are inadequate, they said. For example, topical mupirocin is reasonably successful in eliminating nasal carriage, but recolonization can occur if patients harbor S aureus (particularly methicillin-resistant strains) in sites other than the nares, such as chronic wounds and dermatitides. According to Drs. Archer and Climo, it is difficult to eradicate S aureus from these sites. Moreover, they pointed out, S aureus is likely to become resistant to mupirocin in areas where the drug is heavily used.

Drs. Archer and Climo therefore recommend the development of better agents. "These may include novel topical agents (such as lytic enzymes, peptides, and antibodies) and strategies that prevent colonization by interfering with bacterial and host factors that promote attachment," they suggested. "A realistic goal of immunization with S aureus antigens may be to prevent nasal colonization."

They also call for the development of a rapid diagnostic test, which would be used to screen all patients for nasal colonization with S aureus at hospital admission. And, because more than three quarters of nosocomial S aureus infections are from methicillin-susceptible strains, Drs. Archer and Climo suggest that eradication programs should target all strains, not just those that are methicillin-resistant.

--Timothy Begany

References
1. von Eiff C, Becker K, Machka K, et al. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med. 2001;344:11-16.

2. Archer GL, Climo MW. Staphylococcus aureus bacteremia--consider the source. N Engl J Med. 2001;344:55-56.

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