bacteriostatic

DEFINITION: A bacteriostatic drug prevents bacterial multiplication (reversible growth arrest). If the drug is removed, bacteria can resume growth. Contrast with bactericidal drugs, which kill bacteria (typically defined as MBC/MIC ratio ≤ 4; bacteriostatic if MBC/MIC > 4).

MNEMONIC for bacteriostatic drugs: "Buy AT 30, CCEL at 50" - 30S inhibitors: Aminoglycosides (these are actually bactericidal, the exception) and Tetracyclines (bacteriostatic) - 50S inhibitors: Chloramphenicol, Clindamycin, Erythromycin (macrolides: azithromycin, clarithromycin), Linezolid Other bacteriostatic agents: Sulfonamides, Trimethoprim (TMP-SMX can be bactericidal in combination), Tigecycline, Streptogramins (quinupristin/dalfopristin, variable), Nitrofurantoin (concentration dependent), Ethambutol, Dapsone, Fusidic acid.

MECHANISMS: - Tetracyclines (doxycycline, minocycline): bind 30S, block aminoacyl-tRNA attachment to the A site. - Macrolides: bind 23S rRNA of 50S, block translocation. - Clindamycin: binds 50S, blocks translocation. - Chloramphenicol: inhibits 50S peptidyl transferase. - Linezolid: binds 50S, prevents formation of the 70S initiation complex. - Sulfonamides/trimethoprim: sequentially block folate synthesis (inhibit dihydropteroate synthase and dihydrofolate reductase, respectively).

CLINICAL SIGNIFICANCE: - Effective when the host immune system is intact. Bactericidal agents are preferred in immunocompromised patients (e.g., neutropenia), endocarditis, meningitis, and osteomyelitis, where host defenses are limited or the infection site is poorly accessible. - Bacteriostatic vs. bactericidal is not absolute: it depends on drug concentration, bacterial species, inoculum size, and growth phase. For example, linezolid is bacteriostatic against staphylococci and enterococci but bactericidal against most streptococci. Chloramphenicol is bactericidal against H. influenzae, N. meningitidis, and S. pneumoniae. - Antagonism: combining a bacteriostatic drug with a bactericidal drug that requires actively dividing bacteria (e.g., beta-lactams) can theoretically reduce efficacy. This is clinically significant mainly in settings such as meningitis. - Bactericidal drugs (beta-lactams, vancomycin, aminoglycosides, fluoroquinolones, metronidazole, daptomycin, rifampin, isoniazid) are often grouped by mechanism: cell wall synthesis inhibition, DNA damage/inhibition, or membrane disruption.

PHARMACODYNAMIC TERMS: - MIC: lowest concentration that inhibits visible growth. - MBC: lowest concentration that kills ≥99.9% of the initial inoculum. - Bacteriostatic: MBC much higher than MIC (ratio > 4).

HIGH-YIELD ADVERSE EFFECTS: - Tetracyclines: tooth discoloration, bone growth inhibition (avoid in pregnancy and children <8), photosensitivity, Fanconi syndrome (expired). - Macrolides: QT prolongation, GI motility effects, cholestatic hepatitis, CYP450 inhibition (except azithromycin). - Clindamycin: C. difficile colitis. - Chloramphenicol: dose-dependent anemia, aplastic anemia (idiosyncratic), gray baby syndrome. - Linezolid: myelosuppression, serotonin syndrome, optic neuropathy. - Sulfonamides/TMP: hyperkalemia (TMP), kernicterus in neonates, hemolysis in G6PD deficiency, Stevens-Johnson syndrome, megaloblastic anemia.