Methicillin-Resistant S Aureus (MRSA)

Yesterday I read a article about daptomycin used to treat sepsis. It’s really useful. When my patients are with Gram-positive sepsis such as MSSA, MRSA, or even VRSA. We can consider daptomycin as one of the optimal antibiotics.

Daptomycin is a new type antibiotics (Class: Antibiotics, Other) that is effect on Gram-positive bacteria. The latest study and research presented by Pascal Dohmen, MD, PhD, have found daptomycin (Cubicin, Novartis) achieves clinical cure rates of 72% in sepsis caused by Staphylococcus aureus and 85% in sepsis caused by Staphylococcus epidermidis.

For the analysis of daptomycin in sepsis, data were collected from 2006 to 2011. Demographic and clinical data were drawn from patients in Europe, Russia, Latin America, and India. For study inclusion, patients had to have sepsis as the primary infection, had to have received at least 1 dose of daptomycin, and had to have had more than 30 days of follow-up.

All 302 patients who met the inclusion criteria had significant underlying disease, most commonly cardiovascular (55%) and renal disease (23.8%).

For the initial dose of daptomycin, 53.3% of patients received 6 mg/kg, 17.2% received 4 mg/kg, and 12.9% received more than 8 mg/kg. The median duration of treatment was 10 days. Dr. Dohmen reported that 80% of patients had previously received another antibiotic.

In these patients with  sepsis (I believe it should be Gram-positive sepsis), twenty percent were older than 75 years, among whom almost 20% were on dialysis, and many had comorbidities. According to the culture the primary infections included 31% S aureus, of which 50% were MRSA, 17% Enterococci, and 20% culture negative.

Assessments were based on clinical success, defined as cure or improvement. Cure entailed a resolution of clinical signs and symptoms, no additional antibiotic, and negative culture at the end of therapy. Improvement entailed partial resolution of signs and symptoms or a de-escalation of therapy.

The overall clinical success rate with daptomycin in patients with sepsis was 71% (43% cured and 28% improved); the clinical failure rate was 12%, and 18% of cases were nonevaluable. In endocarditis, 79% of patients achieved clinical success. High-dose daptomycin (at least 8 mg/kg) has been proved to be favorable and included in recent national and international treatment guidelines in Europe and in the United States.

Moreover, Dr. Dohmen found in coagulase-negative staphylococci, 84% of patients achieved clinical cure. The median time to improvement was 4 days in patients with sepsis, and the clinical success rate was 73.7% and 70.7% when used as first-line and second-line therapy.

By dose, patients receiving 6 mg/kg had a 78% clinical success rate; with the higher dose of at 8 mg/kg, a clinical success rate of 74% was achieved.

Safety and tolerance were excellent, with 3% of patients experiencing adverse or severe adverse events.

At present, the dose of daptomycin is split into three class: 4 mg/kg (low), 6 mg/kg (medium), and 8 mg/kg (high). Daptomycin 4 mg/kg once daily is approved for adult patients in the United States and the European Union for the treatment of complex skin and soft tissue infection caused by Gram-positive bacteria. Daptomycin 6 mg/kg once daily is approved for bacteremia, including right-sided endocarditis due to  S aureus.

By primary infecting pathogen, clinical success rates with high-dose daptomycin were 92.4% for coagulase-negative staphylococci, 88.9% for S aureus (88.4% for MRSA and 88% for MSSA), and 89.3% for Enterococci-related infections.

High-dose daptomycin was found to be as safe as the conventional approved doses (4 and 6 mg/kg once a day).

For patients with Gram-positive sepsis, among whom vancomycin failed, daptomycin could be used as alternate regime. Recent evidence has suggested that alternative agents, such as daptomycin, can be used for serious infection caused by S aureus in patients with elevated vancomycin MICs. When dealing with isolates having a MIC greater than 1 µg/mL, the coverage with vancomycin is very unlikely to achieve the desired pharmacodynamic target. So daptomycin is a alternative choice.

References

  1. Becky McCall. Sepsis Cure Rate With Daptomycin Up to 85%. 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID). 2012 Apr 2. Posters 1844, 1845 and 1846.