Commonly Susceptible Species
 
Staphylococcus aureus *
 
Staphylococcus haemolyticus
 
Coagulase negative staphylococci
 
Streptococcus agalactiae*
 
Streptococcus dysgalactiae subsp equisimilis*
 
Streptococcus pyogenes*
 
Group G streptococci
 
Clostridium perfringens
 
Peptostreptococcus spp
 
Inherently resistant organisms
 
Gram negative organisms

* denotes species against which it is considered that activity has been satisfactorily demonstrated in clinical studies.

Information from clinical trials

In two clinical trials in complicated skin and soft tissues infections, 36% of patients treated with Cubicin met the criteria for systemic inflammatory response syndrome (SIRS). The most common type of infection treated was wound infection (38% of patients), while 21% had major abscesses. These limitations of the patients population treated should be taken into account when deciding to use Cubicin.

In a randomised controlled open-label study in 235 patients with Staphylococcus aureus bacteraemia (i.e, at least one positive blood culture of Staphylococcus aureus prior to receiving the first dose) 19 of 120 patients treated with Cubicin met the criteria for RIE. Of these 19 patients 11 were infected with methicillin-susceptible and 8 with methicillin-resistant Staphylococcus aureus. The success rates in RIE patients are shown in the table below.
Population
 Daptomycin
 Comparator
 Differences in Success
 
  n/N (%)
 n/N (%)
 Rates (95% CI)
 
ITT (intention to treat) Population
      
RIE
 8/19 (42.1%)
 7/16 (43.8%)
 1.6% (34.6, 31.3)
 
PP (per protocol) Population
      
RIE
 6/12 (50.0%)
 4/8 (50.0%)
 0.0% (44.7, 44.7)
Failure of treatment due to persisting or relapsing Staphylococcus aureus infections was observed in 19/120 (15.8%) patients treated with Cubicin, 9/53 (16.7%) patients treated with vancomycin and 2/62 (3.2%) patients treated with an anti-staphylococcal semi-synthetic penicillin. Among these failures six patients treated with Cubicin and one patient treated with vancomycin were infected with Staphylococcus aureus that developed increasing MICs of daptomycin on or following therapy (see “Mechanisms of resistance” above). Most patients who failed due to persisting or relapsing Staphylococcus aureus infection had deep-seated infection and did not receive necessary surgical intervention.

5.2 Pharmacokinetic properties

 Daptomycin pharmacokinetics are generally linear and time-independent at doses of 4 to 12 mg/kg administered as a single daily dose by 30-minute intravenous infusion for up to 14 days in healthy volunteers. Steadystate concentrations are achieved by the third daily dose.

Daptomycin administered as a 2-minute intravenous injection also exhibited dose proportional pharmacokinetics in the approved therapeutic dose range of 4 to 6 mg/kg. Comparable exposure (AUC and Cmax) was demonstrated in healthy subjects followi