Cubicin, Cubicin RF
Evidence Grade A — Regulatory approved. 4362 published studies. 121 registered clinical trials.
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Daptomycin (sold as Cubicin) is an intravenous antibiotic with a unique mechanism — it punches holes in bacterial cell membranes, killing them through a completely different pathway than vancomycin or other standard antibiotics. Given once daily, it is used for serious skin infections and bloodstream infections caused by gram-positive bacteria, including MRSA. One important limitation: it cannot be used for pneumonia because a natural substance in the lungs inactivates it.
4,362 published studies: 2641 human, 257 animal, 993 in-vitro, 655 reviews
Daptomycin is marketed as Cubicin (approved September 2003). It is indicated for complicated skin and soft tissue infections and S. aureus bloodstream infections including right-sided endocarditis. Administered as a once-daily intravenous infusion.
A key limitation is that daptomycin cannot be used for pneumonia — lung surfactant inactivates the drug. In the bacteraemia trial, daptomycin was non-inferior to vancomycin with significantly lower rates of kidney problems (11% versus 26%). Creatine kinase (CK) levels must be monitored during treatment, as daptomycin can cause muscle toxicity. Generics became available after patent expiry, significantly reducing cost.
Daptomycin has a remarkable calcium-dependent mechanism. In the presence of calcium, the drug changes shape to expose a fatty acid tail, which inserts into the bacterial membrane. Multiple daptomycin molecules then cluster together to form channels that allow potassium ions to rush out of the bacterium. This ion leakage collapses the electrical charge across the membrane, which halts DNA replication, RNA synthesis, and protein production simultaneously — a multi-target kill mechanism that makes resistance development difficult.
Daptomycin's clinical evidence comes from Phase III trials in skin infections and bloodstream infections including endocarditis (heart valve infection). In the bloodstream infection trial, daptomycin matched vancomycin's effectiveness while causing significantly fewer kidney problems (11% versus 26%). Muscle toxicity is a known risk, requiring weekly blood tests to monitor a muscle enzyme called creatine kinase. The drug has become an important alternative to vancomycin, particularly when vancomycin resistance or intolerance is a concern. High-dose strategies (above the standard approved dose) and combination approaches with other antibiotics are used in clinical practice for difficult-to-treat MRSA infections, though these strategies are based more on clinical experience than large randomised trials. Generic versions have made daptomycin more affordable.
Combination Antibiotic Therapy for Staphylococcus Aureus Bacteremia
Does Staphylococcus Aureus Bacteremia Early Dual Therapy Improve Outcomes?
Impact of Three Probabilistic Antibiotic Therapy on Digestive Microbiota and Colonization With Multi-resistant Bacteria
Antibiotic Impregnated Beads in Osteomyelitis
Comparative Analysis of Nemonoxacin and Other Anti-methicillin Resistant Staphylococcus Aureus (Anti-MRSA) Antimicrobial Therapy in Patients With Complicated Skin and Soft Tissue Infections (cSSTI): a Retrospective Chart Review Study
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Corticotropin is marketed as H.P. Acthar Gel (currently ANI Pharmaceuticals). It carries approximately 19 FDA-labelled indications including infantile spasms (its strongest evidence base), nephrotic syndrome, multiple sclerosis relapses, and rheumatic disorders. Acthar Gel has been at the centre of major pricing and legal controversies. The price rose from approximately $40 per vial in 2001 to over $40,000, driven by successive acquisitions and orphan-like positioning despite broad labelling. The former manufacturer Mallinckrodt agreed to a $260 million settlement over antitrust concerns. Clinically, the strongest evidence supports its use in infantile spasms, where it is considered a first-line treatment. For most other indications, debate continues over whether it offers meaningful advantages over far less expensive oral corticosteroids.
Enfuvirtide is marketed as Fuzeon (approved March 2003). It requires twice-daily subcutaneous injections, and injection-site reactions occur in nearly all patients (98%). In clinical trials (TORO-1 and TORO-2), enfuvirtide combined with an optimised background regimen achieved significantly greater viral suppression than background regimen alone in treatment-experienced patients. Enfuvirtide represented a major advance when HIV drug resistance was a more pressing clinical challenge, but its use has declined substantially with the arrival of more convenient oral antiretrovirals. The twice-daily injection burden, injection-site reactions, high cost, and complex manufacturing (it is one of the largest synthetic peptides manufactured at scale) have limited its role to a last-resort option for patients with highly resistant HIV.
Vancomycin is marketed as Vancocin and Firvanq (approved 1958, with oral solution Firvanq approved 2018). It is the standard treatment for serious MRSA infections (bloodstream infections, endocarditis, pneumonia, bone infections) and is first-line for severe C. difficile colitis. Vancomycin requires therapeutic drug monitoring — blood levels must be checked regularly to ensure the dose is effective without causing kidney damage or hearing loss. The rise of vancomycin-resistant enterococci (VRE) and occasional vancomycin-intermediate S. aureus (VISA) strains represent ongoing challenges. Despite being nearly 70 years old, vancomycin remains irreplaceable for many serious infections, though newer alternatives like daptomycin and the lipoglycopeptides offer advantages in specific settings.
