Streptogramins are a class of antibiotics derived from bacteria of the genus Streptomyces. These naturally produced compounds are composed of two distinct molecules that work together. Their combined action makes them an important therapeutic option, particularly as bacterial resistance to other antibiotics increases.
Mechanism of Action
Streptogramin antibiotics function by halting the process of protein synthesis in bacteria. Bacterial cells rely on structures called ribosomes to build the proteins they need to survive and multiply. Streptogramins target the bacterial ribosome, specifically a component known as the 50S ribosomal subunit. This action is similar to that of other antibiotic classes, such as macrolides, but with a unique cooperative method.
The antibiotic itself consists of two structurally different components: Group A streptogramins (like dalfopristin) and Group B streptogramins (like quinupristin). These two components bind to different locations within the peptidyl-transferase domain of the bacterial ribosome. The Group A molecule attaches first, inhibiting the early phase of protein elongation by preventing new amino acids from being added to the growing protein chain. This initial binding causes a change in the three-dimensional shape of the ribosome.
The altered ribosome shape increases its affinity for the Group B molecule by as much as 100-fold. The subsequent binding of the Group B molecule interferes with the late phase of protein synthesis and promotes the release of incomplete peptide chains. While each component on its own is typically bacteriostatic, meaning it only inhibits bacterial growth, their combined, synergistic action is bactericidal, meaning it actively kills the bacteria.
Clinical Applications
The primary streptogramin combination used in clinical practice is a mixture of quinupristin and dalfopristin, marketed under the brand name Synercid. This antibiotic is not a first-line treatment; its use is reserved for severe infections caused by multi-drug resistant bacteria. It is specifically indicated for complicated skin and skin structure infections and bacteremia, which is the presence of bacteria in the bloodstream.
The main targets for quinupristin/dalfopristin are gram-positive bacteria that have become resistant to other powerful antibiotics. One of the most significant uses is in treating infections caused by vancomycin-resistant Enterococcus faecium (VRE), a common source of hospital-acquired infections. Another major application is in combating methicillin-resistant Staphylococcus aureus (MRSA), which can cause serious skin infections, bloodstream infections, and pneumonia.
Administration and Side Effects
Due to the severity of the infections it treats, quinupristin/dalfopristin is administered intravenously (IV). This method of delivery ensures the drug enters the bloodstream directly and reaches effective concentrations quickly. Treatment typically occurs in a hospital setting where patients can be monitored, with a common dosage regimen being 7.5 mg/kg administered every 8 to 12 hours. The infusion must be managed carefully to minimize local reactions.
The most frequently reported side effects are associated with the infusion process itself. Patients often experience pain, inflammation, swelling, or edema at the IV injection site. To manage these reactions, the drug may be diluted, or the vein can be flushed after the infusion is complete. Another common set of side effects involves the musculoskeletal system, with patients reporting arthralgia (joint pain) and myalgia (muscle pain), which can sometimes be severe enough to require discontinuation of the treatment.
Streptogramins can interact with other medications. This occurs because they inhibit a liver enzyme known as CYP3A4, which is responsible for metabolizing a wide range of drugs. By slowing this enzyme’s activity, streptogramins can cause the levels of other drugs to increase in the body, raising the risk of toxicity. Less frequent side effects can include nausea, diarrhea, and headache.