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Lincosamides (clindamycin), oxazolidinones (linezolid), streptogramins (dalfopristin [streptogramin A] and quinupristin [streptogramin B]) are grouped together because they have a similar mode of antibacterial action and similar antibacterial spectra. Macrolides (see Bacteria and Antibacterial Drugs: Macrolides) and the ketolide telithromycin (see Bacteria and Antibacterial Drugs: Telithromycin) may be included with this group for similar reasons. All inhibit protein synthesis by binding to the 50S ribosomal subunit. Cross-resistance occurs among the following antibiotics because they bind to the same target:
However, cross-resistance does not occur between these antibiotics and dalfopristin and linezolid, which bind to different targets on the 50S ribosomal subunit.
Lincosamides
Clindamycin is primarily bacteriostatic. It binds to the 50S subunit of the ribosome, thus inhibiting bacterial protein synthesis.
Pharmacology
Clindamycin is absorbed well orally and can be given parenterally. Clindamycin diffuses well into body fluids except CSF; it is concentrated in phagocytes. Most of the drug is metabolized; metabolites are excreted in bile and urine.
Indications
The spectrum of activity for clindamycin is similar to that of the macrolide erythromycin (see Table 13: Bacteria and Antibacterial Drugs: Some Clinical Uses of Macrolides ) except that clindamycin is
Aerobic gram-negative bacilli and enterococci are resistant.
Clindamycin is usually used for anaerobic infections; however, clindamycin resistance has emerged among these organisms in some regions. Because these infections often also involve aerobic gram-negative bacilli, additional antibiotics are also used. Clindamycin is part of combination therapy for the following:
Clindamycin can be used for infections (eg, skin and soft-tissue infections) in communities where community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is common; whether clindamycin is useful depends on local resistance patterns.
Clindamycin can be used for infections due to clindamycin- and erythromycin-susceptible strains. However, some CA-MRSA strains are clindamycin-susceptible and erythromycin-resistant; erythromycin resistance in these strains may be due to an active efflux mechanism or to erythromycin-inducible modification of the ribosomal target. If the infecting strain of clindamycin-susceptible CA-MRSA is resistant to erythromycin because of the efflux mechanism, patients can be expected to respond to clindamycin. However, if the strain is erythromycin-resistant because of erythromycin-inducible ribosomal target modification, patients may not respond clinically to clindamycin because certain mutants can emerge during clindamycin therapy; these mutants are resistant to clindamycin and erythromycin because of constitutive modification of the ribosomal target. (Constitutive means that resistance is always present regardless of whether an inducer, such as erythromycin, is present.)
Erythromycin resistance due to efflux can be differentiated from that due to inducible ribosomal target modification with a commonly used double disk diffusion assay (D test). A clindamycin disk is placed at a standard distance from an erythromycin disk on an agar plate streaked with a standard inoculum of the CA-MRSA strain in question. Zone of growth inhibition (shaped like the letter “D”) around the clindamycin disk, with a flattened zone nearest the erythromycin disk indicates inducible ribosomal resistance. Patients who have moderate to severe infection with an inducible ribosomal-resistant CA-MRSA strain and a positive D test should not be treated with clindamycin.
Clindamycin cannot be used for CNS infections (other than cerebral toxoplasmosis) because penetration into the brain and CSF is poor.
Topical clindamycin is used for acne.
Contraindications
Clindamycin is contraindicated in patients who have had an allergic reaction to it or have a history of regional enteritis, ulcerative colitis, or antibiotic-associated colitis.
Use During Pregnancy and Breastfeeding
Clindamycin is in pregnancy category B (animal studies show no risk but human evidence is inadequate, or animal studies show risk and human studies do not).
Clindamycin enters breast milk. Use during breastfeeding is not recommended.
Adverse Effects
The main adverse effect is
Clindamycin, penicillins, cephalosporins, and, most recently, fluoroquinolones have been associated with C. difficile–associated diarrhea. Clindamycin has been associated with C. difficile–associated diarrhea in up to 10% of patients regardless of route, including topical.
Hypersensitivity reactions may occur. If not swallowed with water, clindamycin may cause esophagitis.
Dosing Considerations
Dose adjustments are not required for renal failure. Clindamycin is given q 6 to 8 h.
Oxazolidinones
Linezolid has activity against the following:
Contraindications
Linezolid is contraindicated in patients with a prior allergic reaction to it.
Linezolid is a reversible, nonselective monamine oxidase inhibitor (MAOI). Thus, linezolid, when used with drugs that have serotonergic activity (eg, SSRIs, MAOIs, tricyclic antidepressants, l-tryptophan, amphetamines, lithium), has the potential for causing serotonin syndrome, a hyperserotonergic state characterized by mental status changes, neurologic abnormalities, and autonomic instability.
Linezolid is contraindicated in the following patients unless they are carefully observed for symptoms and signs of serotonin syndrome:
Linezolid should not be given to the following patients unless they are monitored for potential increases in BP:
Use During Pregnancy and Breastfeeding
Linezolid is in pregnancy category C (animal studies show some risk, evidence in human studies is inadequate, but clinical benefit sometimes exceeds risk).
Whether linezolid is excreted in breast milk or is safe to use during breastfeeding is unknown.
Adverse Effects
Adverse effects include
Adverse effects are minimal, although reversible myelosuppression, including thrombocytopenia, leukopenia, and anemia, occurs in about 3% of patients, usually when therapy is used > 2 wk. Consequently, CBC is monitored weekly, especially when therapy lasts > 2 wk. Peripheral and optic neuropathy may occur with prolonged use, and patients taking long-term linezolid therapy should be closely monitored for these disorders.
Streptogramins
Quinupristin and dalfopristin are semisynthetic derivatives of pristinamycin, a naturally occurring streptogramin. Quinupristin/dalfopristin (Q/D) is given together in a fixed 30/70 combination; this combination has synergistic bactericidal activity against the following:
Q/D inhibits E. faecium, including vancomycin-resistant strains. E. faecalis is resistant.
Q/D is given via a central IV catheter because phlebitis frequently occurs when Q/D is given via a peripheral vein. Up to 30% of patients develop significant myalgias.
Dosage reduction is required for severe hepatic insufficiency but not for renal insufficiency.
Q/D may inhibit drugs that are metabolized by the cytochrome P-450 (CYP450) 3A4 isoenzyme system.
Last full review/revision July 2009 by Matthew E. Levison, MD
Content last modified July 2009
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