Reports

Early diagnosis is important to understand the extent of the Staphylococcus aureus infection, initiate the most appropriate therapy, and take all necessary infection-control measures. The first step is to confirm colonization by S. aureus and reliably define methicillin resistance. Routine culture assays for detecting methicillin-resistant S. aureus (MRSA) are labour-intensive and time-consuming (two to three days per procedure) and do not provide results in a clinically useful time frame.

Molecular Screening Tests

Due to the need for rapid identification and screening tools, molecular methods have been developed. Detection of the mecA gene has become the reference method for confirmation of MRSA strains. “However, attention should be paid to the diagnostic accuracy of these tests because results based on molecular methods for detection of MRSA directly from clinical specimens may be influenced by the coexistence of methicillin-susceptible S. aureus [MSSA] and methicillin-resistant coagulase-negative staphylococci [MR-CoNS] which also contain mecA,” alerted Dr. Georg Peters, Institute of Medical Microbiology, University of Münster, Germany.

A study has shown that a molecular MRSA screening test targeting the mecA gene and an S. aureus-specific gene in parallel and applied directly to clinical specimens had a positive predictive value of only 39.3%, a value characterized by Dr. Peters as “unacceptable.”

Treatment Guidelines for MRSA Infections

MRSA is found in 60% of surgical sites and in 20 to 40% of patients with ventilator-associated pneumonia. Several evidence-based guidelines on infection management that refer to MRSA have recently been published in the US and Europe. The US guidelines address skin and soft-tissue infections (SSTIs) and hospital-acquired pneumonia (HAP), while the UK guidelines include specific recommendations on the prophylaxis and treatment of MRSA. Although management strategies obviously vary according to local conditions, there is agreement on therapy in patients with severe infection.

Treatment should be started immediately without waiting for microbiological results. Diagnosis of the likely pathogen should be guided by a risk assessment of the patient and knowledge of the local microbiological epidemiology. “If there is a high local prevalence of community-acquired (CA) MRSA, assume S. aureus is resistant and start empirical therapy with linezolid or vancomycin,” advised Prof. Gary French, Professor of Microbiology and Infectious Disease, King’s College and St Thomas’ Hospital, London, UK. Once the test results are known, the initial therapy may need to be modified. If possible, treatment should be stepped down or de-escalated so as not to encourage further resistance problems, especially if using a glycopeptide, as these agents have been associated with potential resistance problems. Less toxic and less expensive agents may also be appropriate, depending on the choice of initial therapy. While linezolid has a high purchase cost, its early use has been associated with early discharge and a reduction in hospital costs; overall cost should be considered in the treatment decision, especially in patients with severe gram-positive S. aureus infection.

For surgical-site infection with MRSA, it is preferable to treat and perform drainage rather than drainage alone. For persistent infection, the choice of agents should be based on local microbiology because this varies between institutions. Given that delaying therapy is associated with increased mortality, the overall guiding principle is to treat early and then stop or de-escalate antibiotics if there is clinical improvement. “There is limited evidence for the effectiveness of older agents such as tetracyclines and trimethoprim in the treatment of serious MRSA and no evidence that combination therapy is more effective than single agents alone; at the time of writing the guidelines, little data were available to comment on the newer agents such as daptomycin, dalbavancin and tigecycline,” Prof. French told the audience.

Hospital-acquired Pneumonia: Early Diagnosis and Appropriate Treatment

HAP is the second most common infection acquired in hospitals and a leading cause of mortality. Crude mortality is around 70% and attributable mortality is 30%.

The incidence is 5 to 10 cases out of 1000 but is higher in mechanically-ventilated patients. Risk factors for higher mortality are severity and type of infection, time of onset, colonization with highly virulent or resistant pathogens, underlying disease, advanced age, gender and inappropriate antibiotic therapy. Delay in appropriate therapy is the major risk factor for higher mortality in patients with severe infections such as sepsis, meningitis and pneumonia. In one study of patients with sepsis or septic shock, mortality was 16% in patients receiving appropriate treatment as opposed to 28% in those who did not receive appropriate treatment (P<0.001). In patients with meningitis, a delay of more than six hours in receiving appropriate treatment increases mortality. According to Dr. Pramod Shah, Professor of Internal Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany, “The principles of therapy are not to waste time, act fast, and use appropriate treatment because this helps to reduce mortality.” He added, “In the very near future, we’re going to have to isolate the negative patients.”

Accurate diagnosis of HAP remains problematic as clinical signs can often be misleading. Collecting cultures of tracheal aspirates using invasive or non-invasive techniques is recommended. The presence of soluble triggering receptor expressed on myeloid cells (sTREM-1) in bronchoalveolar-lavage fluid from patients is an indicator of pneumonia.

Dr. Shah recommended that decisions on empirical therapy should take into account local epidemiology, risk factors, and whether the onset of pneumonia occurred early or late. For example, in non-ventilated patients with early-onset, second-generation cephalosporin, a beta-lactam or beta-lactamase inhibitor should be administered. In ventilated patients with late onset, vancomycin or linezolid should be used.

Best Practice in the Treatment of Complicated Skin and Soft-tissue Infection Due to MRSA

The management of complicated SSTIs is becoming more intricate due to the rising prevalence of hospital-acquired and CA MRSA as a pathogen in these conditions. Risk factors include local endemicity, patient characteristics, socioeconomic factors, and prior antibiotic exposure. Confirmed Dr. Robert G. Sawyer, Co-director, Surgical Trauma Intensive Care Unit, and Associate Professor of Surgery, University of Virginia, Charlottesville, “It is hard to predict MRSA in patients with or without the presence of risk factors.” Although studies in patients with SSTIs have shown that there is no significant difference between patients receiving active therapy and those receiving inactive therapy, these did not distinguish between patients with uncomplicated vs. complicated SSTIs.

He told delegates, “I ask myself five questions to establish a treatment algorithm:

• Does the patient require a drainage or debridement procedure?

• Does he need systemic antimicrobial therapy? • Does he need to be hospitalized for treatment or can he be treated with an oral-based regimen?

• What are the culture results so I can tailor antibiotic therapy? • How long does the patient need to be treated with antibiotics?

The bottom line is that when I treat MRSA SSTI, I look at all the options available and select the most appropriate one for individual patients,” concluded Dr. Sawyer.

Summary

MRSA is associated with high rates of mortality and morbidity. There was unanimous agreement here during the scientific sessions that the optimal approach to treating MRSA is to treat early with appropriate initial therapy, diagnose as early as possible, and tailor therapy based on the microbiologic test results. Once the microbiological results are known, a step-down approach may be implemented.