what is the chemistry of lincosamides?
amino acids linked to amino sugars; clindamycin is a chloro analogue of lincomycin
what is the MOA or lincosamides?
bind to the same 50S ribosomal binding sites as the macrolides and chloramphenicol; protein synthesis is inhibited in early chain elongation by interference with transpeptidation
do lincosamides have cross-resistance with macrolides?
what are the in vitro susceptibilities to clindamycin?
gram positive, anaerobes, and some protozoal pathogens
what is the absorption of lincosamides?
absorption of clindamycin is about 90% and is slightly delayed, but no decreased by food, whereas that of lincomycin is markedly reduced
what is the distribution of lincosamides?
insignificant entry into CSF, but effective concentrations in bone
how are lincosamides metabolized?
extensively metabolized; half-life is about 2.4 hours; half-life extended in severe renal failure
what are adverse reactions of lincosamides?
- allergic reactions - rashes
- hepatoxicity (minor reversible elevation of transaminase)
what are drug interactions with lincosamides?
- clindamycin may block neuromuscular transmission and may enhance the action of other neuromuscular blocking agents
- clindamycin phosphate is chemically incompatible with solutions of drugs that require a basic pH to maintain solution
- may antagonize the action of macrolides
what are the uses of clindamycin?
- antimicrobial agent of choice for the treatment of infections by GI strains of anaerobes and infections caused by oropharyngeal strains of Bacteroides spp. - alternate agent for the treatment of gram + cocci infections; acne vulgaris, topical use
what is a linezolid?
linezolid was the first commercially available oxazolidinone antibiotic
what is the MOA of linezolid?
works on the initiation of protein synthesis; does this by stopping the 30S and 50S subunits of the ribosome from binding together by binding to the 23S portion of the 50S subunit (which stops its interaction with the 30S subunit)
what is the spectrum of action of linezolid?
includes activity against gram + bacteria and some gram - anaerobic species but not gram - aerobes; multi-drug resistant organisms such as, MRSA, staphyl with reduced susceptibility to vancomycin, penicillin- and macrolide- resistant pneumococci and vancomycin-resistant enterococci are fully susceptible
is the activity of linezolid bacteriostatic or bactericidal?
both; bacteriostatic against some species (e.g. enterococci) and bactericidal against others (e.g. pneumococci)
what are the clinical uses of linezolid?
- usually reserved for the treatment of serious bacterial infections where older antibiotics have failed to antibiotic resistance
- conditions such as skin infections or nosocomial pneumonia where methicillin or penicillin resistance is found are indicators for linezolid use
what are the side effects of linezolid?
- generally well tolerated
- bone marrow suppression, most commonly thrombocytopenia in patients who receive longer courses (more than 2 weeks), or who have renal failure
- may cause serotonin syndrome
- toxic to mitochondria
what can linezolid not be used with?
tyramine containing foods or pseudoephedrine (will cause serotonin syndrome)
what are streptogramins?
a group of natural cyclic peptides produced by bacteria, consists of two structurally unrelated molecules: group A streptogramins (macrolactones) and group B streptogramins (cyclic hexadepsipeptides)
what is the MOA of streptogramins?
the two components (group A and group B) bind to distinct sites on the 50S ribosomal subunit - cooperate to inhibit protein synthesis
are streptogramins bacteriostatic or bactericidal?
each component is bacteriostatic but the combination of the two components is bactericidal
what is the spectrum of action of streptogramins?
most gram + bacteria and most respiratory pathogens; 90% of Staph. Aureus and coagulase negative staph including methicillin resistant strains; penicillin resistant pneumococci; Enterococcus faecium including strains which are resistant to ampicillin, gentamicin and vancomycin; not active against E. faecalis
what is an example of a streptogramin?
how is quinupristin/dalfopristin metabolized and excreted?
in the liver and excreted mainly in bile
what are adverse reactions of quinupristin/dalfopristin?
- related to the infusion site, including pain, edema, inflammation and thrombophlebitis
- also arthralgias, myalgias, and increase in conjugated bilirubin
what drug interactions does quinupristin/dalfopristin have?
potent inhibitor of CYP34A and should be used with caution in patients taking drugs that are substrates of 3A4
what is quinupristin/dalfopristin used for?
- life-threatening infections caused by vancomycin-resistant Enterococcus faecium (VREF)
- complicated skin structure infection caused by Staphylococcus aureus and Streptococcus pyogens
what is the MOA of chloramphenicol?
inhibits protein synthesis after entering the cell by an active transport mechanism; reversibly binds to the larger 50S subunit of the 70S ribosome
what is the spectrum of action of chloramphenicol?
variety of organisms: bacteria, spirochetes, rickettsia, chlamydiae, mycoplasmas
what is chloramphenicol used for?
- generally not considered first line therapy in U.S., toxicities limit use
- good CNS penetration so used for childhood meningitis, brain abscess, richettsial infections, typhoid fever and invasive salmonellosis
what are adverse reactions of chloramphenicol?
- gray baby syndrome (in neonates, abdominal distension, vomiting, flaccidity, cyanosis, circulatory collapse, and death)
- bone marrow disturbance decrease RBC, increase Fe
- aplastic anemia (rare, non-dose related)
- GI disturbances; optic neuritis (rare), decreased visual acuity, usually reversible
- hypersensitivity and anaphylaxis are rare
what are drug interactions with chloramphenicol?
- inhibits hepatic microsomal enzymes
- increased half-life of Tolbutamide, chlorpropamide, phenytoin, cyclophosphamide, and warfarin