Spectrum of Action--Clinical Uses: Choramphenicol, Tetracyclines, Macrolides, Clindamycin
Chloramphenicol is seldom systemically used because of availability of other, better medications and because of its toxicity.
Clinical uses: serious rickettsial infections (typhus or Rocky Mountain spottend fever) in children under 8 (when tetracyclines are contraindicated)
Alternative treatment for bacterial meningitis due to a very penicillin-resistant pneumococcal isolate
Meningococcal infections in patients with significant penicillin hypersensitivity.
Chloramphenicol may be used for eye infections because of its broad antibacterial spectrum and because of its effective penetration of ocular tissue.
GI: nausea vomiting diarrhea (adults);Oral or vaginal candidiasis due to alteration in normal flora
Bone marrow suppression: Chloramphenical--dose-related
Gray baby syndrome in newborns is due to chloramphenicol accumulation due to ineffective gluruonidation of the drug.
Syndrome includes: gray color, shock, hypothermia, flaccidity and vomiting.
Chambers, H.F., Chloramphenicol, Tetracyclines, Macrolides, Clindamycin and Streptogramins, in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 744-745.
Tetracyclines: broad spectrum antibiotics: protein synthesis inhibitors
Tetracycline bacteriostatic: many gram-positive and gram-negative bacteria including:
some protozoa (amebas).
Antibacterial spectrum is similar between tetracyclines although bacteria resistant to tetracyclines may remain sensitive to minocycline
Resistance: Tetracyclines (Archer,G.L. and Polk, R.E. Treatment and Prophylaxis of Bacterial Infections, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, p. 859.;Chambers, H.F., Chloramphenicol, Tetracyclines, Macrolides, Clindamycin and Streptogramins, in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 745.)
Most common mechanism for gram-negative bacterial resistance: insertion of a plasmid-encoded active-efflux pump that translocates tetracycline out of the cell.
Mechanisms for gram-positive bacterial resistance may be either through this active efflux mechanism or through changes in its ribosomal target.
Three mechanisms for resistance:
decreased intracellular concentration by decreased influx or increased efflux
decreased tetracycline ribosomal binding
enzymic inactivation of tetracycline
Classification: short-acting (tetracycline (Achromycin), oxytetracycline, chlortetracycline: 1/2 life: 6-12 h) intermediate-acting (demeclocycline (Declomycin), methacycline: 1/2 life 12 h) long-acting (doxycycline (Vibramycin, Doryx), minocycline (Minocin), 1/2 life: 16-18h).
Clinical Use A tetracycline is the drug of choice for treating these infections:Mycoplasma pneumoniae, chlamydiae, rickettsia, some spirochetes.
Used in combination with other drugs to treat gastric and duodenal ulcer casue by Helicobacter pylori.
May be used in a variety of gram-positive and gram-negative bacterial infections in the absence of resistance.
No longer recommended for treatment of gonococcal disease due to the emergence of resistant strains.
Tetracyclines + aminoglycoside for: plague tularemia and brucellosis. May be used in treatment of protozoal infections: Entamoeba histolytica or Plasmodium falciparum
Other uses: acne, bronchitis, Lyme disease leptospirosis some mycobacterial infections (nontuberculous)
GI: Nausea, vomiting--most common
Bone-Teeth: Tetracyclines bind to calcium incorporated into newly formed bone (young children) leading to discoloration; in the case of incorporation into bone, deformity or growth inhibition may occur.
Chambers, H.F., Chloramphenicol, Tetracyclines, Macrolides, Clindamycin and Streptogramins, in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 746-747.
Erythromycin, Clarithromycin (Biaxin) and Azithromycin (Zythromax)
Macrolides include erythromycin and semisynthetic derivatives clarithromycin and azithromycin
Mechanisms of Resistance
reduced cellular permeability or enhancement of efflux
production by Enterobacteriaceae of enzymes that hydrolyze macrolides
following chromosomal mutation or by macrolide-inducible or normally present change in ribosomal binding site properties.
Methylase production is responsible for most of gram-positive microbe resistance Cross-resistance is complete between erythromycin and clarithromycin and azithromycin.
Clinical Use (note: clarithromycin is similar to erythromycin with respect to spectrum of action but has a lower frequency of GI upset)
Erythromycin is the drug of choice in treatment corynebacterial infections (diphtheria, corynebacterial sepsis, erythrasma)
in respiratory, neonatal ocular or genital chlamydia infections community-acquired pneumonia because its broad spectrum of treatment of action allows effective treatment of pneumoncoccus, Mycoplasma and Legionella
Erythromycin: penicillin-substitute for patients allergic to penicillin
Liver toxicity: may produce cholestatic hepatitis (fever, impaired hepatic function, jaundice)
Chambers, H.F., Chloramphenicol, Tetracyclines, Macrolides, Clindamycin and Streptogramins, in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 747-749
Clindamycin Spectrum of Action
Streptococci, staphylococci and pneumococci are inhibited by clindamycin; however, in contrast to their susceptability to erythromycin, enterococci and gram-negative aerobic microbes are resistant (due to poor permeability of outer membrane)
Bacterioides (and other anaerobes), both gram-positive and gram-negative are mostly susceptable.
Clindamycin Mechanism of Resistance
mutation of the ribosomal binding site
Inactivation of clindamycin by methylase
Modification of the receptor site by methylase production
Primary, important indication for clindamycin: severe anaerobic infections due to Bacterioides and other anaerobes in mixed infections.
prophylaxis: Clindamycin (Cleocin) instead of erythromycin for endocarditis prior to dental procedures on patients who have valvular diseas
Clindamycin (Cleocin)+ primaquine: effective alternative to trimethoprim-sulfamethoxazole (Bactrim) in treating moderate to moderately-severe Pneumocystis carinii pneumonia in AIDS patients.
Clindamycin (Cleocin): useful in treating AIDS-related CNS toxoplasmosis.combination with pyrimethamine (Daraprim).
Hepatic dysfunction and neutropenia (occasional)
Colitis due to antibiotic selection and growth of toxigenic C. difficile
Chambers, H.F., Chloramphenicol, Tetracyclines, Macrolides, Clindamycin and Streptogramins, in Basic and Clinical Pharmacology,(Katzung, B. G., ed) Appleton-Lange, 1998, p. 749-750.