Summary Tables on Antimicrobials

Original Version by Elizabeth Jensen, MD

Drugs "Less Safe" or Contraindicated in children & pregnancy

FDA Pregnancy Risk Categories:
Caution should be taken when considering drug therapy during pregnancy

Category A: remote risk to fetus (e.g. daily multivitamin) Category B: Slight risk to fetus Category C: Greater risk than category B. Use if the potential benefit justifies the potential risk to the fetus. Category D: Proven risk of fetal harm; use only if there isn't another alternative. Category X: Proven risk of fetal harm with. Risk outweighs any possible benefit to the mother.

For additional information see: fda_pregnancy_risk_factors

Acronym: MCAT & F

1. Metronidazole (mutagenic and carcinogenic potential - Category B) 2. Chloramphenicol is contraindicated in infants (Gray baby syndrome because infants dont produce enough glucoronyl transferase - Category C during pregnancy for teratogenicity) 3. Aminoglycosides (potential 8th nerve damage - Category C) 4. Tetracycline (retardation of bone growth; stains teeth - Category D) 5. Fluoroquinolones (cartilage toxicity; avoid in <18 yo - Category C risk in pregnancy) Also (covered in Pulmonary block):

Thalidomide (severe birth defects - Category X)

Alternative drugs in patients with a history of severe (anaphylactic) penicillin allergy

1. 2. 3. 4. Aztreonam (a monobactam; primarily indicated for Gram - organisms and is not a drug of first choice) Macrolides Vancomycin Clindamycin

Synergistic drug combinations (& their mechanisms)

1. Cell Wall Synthesis Inhibitor + Aminoglycoside (CWSI increases permeability of organism to aminoglycosides) 2. Trimethoprim + Sulfa drug (blocks two steps in the synthesis of folic acid, which bacterial cells need to survive)

Mechanisms for drug resistance

1. Intrinsic resistance (gram- bacteria have outer membrane impermeable to penicillin) 2. Escape from antibiotic effect (cell membranes become permeable to folic acid to escape the effect of sulfonamides and trimethoprim) 3. Penicillinase production (previously penicillinase- can become penicillinase+ and be resistant to some penicillins and cephalosporins) 4. Methylase gene (50S subunit receptor gets methylated so macrolides and strepogramins no longer work) 5. Plasmid mediated phosphorylation, acetylation, and adenylation (affects aminoglycosidesat the amine group on the drug, or methylation of the S12 protein to which they bind; remember, amikacin is the least likely aminoglycoside to which bacteria become resistant, so it may keep on truckin while streptomycin has fallen by the wayside) 6. Decreased drug uptake (tetracyclines & aminoglycosides)

Drugs with unusual types of toxicity

1. Aminoglycosides have vestibular & auditory toxicity, nephrotoxicity & NMJ blockade 2. Vancomycin -if not administered slowly enough by IV, hypotension and the Red Man Syndrome may result 3. Sulfonamides can cause Stevens-Johnson (erythema multiforme) 4. Metronidazole causes metallic taste and disulfiram-like reaction (antabuse) 5. Fluoroquinolones causes cartilage toxicity 6. Erythromycin & Clarithromycin - IV erythromycin or high concentrations of these two macrolides, and/or concomitant administration with other drugs that prolong the QT interval (e.g. pimozide, astemizole, terfenadine) can result in potentially fatal arrhythmias 7. Chloramphenicol causes majorly fatal aplastic anemia (rare but fatal) 8. Tetracyclines cause yellowing of the teeth and can inhibit bone growth 9. Rifampin and Clofazimine can cause reddened urine 10. Ethambutol can cause red-green colorblindness 11. Drugs which can cause Hemolytic Anemia (particularly in G-6-P Dehydrogenase deficient individuals) and incidentally are also metabolized by acetylation (so their dosing needs to be adjusted in fast acetylators): o Isoniazid (INH) o Dapsone o Sulfonamides

Drug Interactions
1. Erythromycin, clarithromycin & ketoconazole - inhibit P-450 enzymes 2. Rifampin - induces P-450 enzymes

Drugs cleared by the kidney (drugs potentially useful for kidney tract infections if the bacteria are also sensitive; drugs requiring dosage adjustment with renal dysfunction)
1. 2. 3. 4. 5. 6. 7. 8. 9. Penicillins and Cephalosporins (with a few exceptions shown in the next table) Aminoglycosides * Must figure out Creatinine clearance before maintenance dosing * Tetracyclines (except doxy & mino) Chloramphenicol Fluroquinolones (80% excreted through kidney) Sulfonamides & Trimethoprim Pyrazinamide Clindamycin (is excreted by both kidney and via bile tract) Nitrofurantoin

Cleared by the kidney, but not used for UTI:

1. Isoniazid (INH) & Pyrzinamide (primarily used for M. tuberculosis) 2. Vancomycin 3. Metronidazole

Lets say I have complete renal failure. Now what can I take for my infection? (drugs typically not requiring dosage adjustments with renal dysfunction)
Primarily biliary excretion:
1. Nafcillin 2. Ceftriaxone

Both biliary & renal clearance:

1. Oxacillin, Coxacillin & Dicloxacillin 2. Ampicillin (however, dosage adjustment required in renal failure)

Okay, I have complete renal failure and Im allergic to penicillin. Now what can I take for my infection?
1. Macrolides 2. Rifampin (antimycobacterial) 3. Clofazimine (for Mycobacterium species)

Which drugs work on anaerobes?*

1. 2. 3. 4. 5. 6. 7. 8. Clindamycin (drug of choice against B. fragilis) Metronidazole (drug of choice against B. fragilis & Clostridium species) Penicillin G (Clostridium perfringens) Ticarcillin (somewhat effective against Bacteroides fragilis) Piperacillin & Mezlocillin (more effective against B. fragilis) Imipenem (effective against anaerobes) Cefoxitin (also some other cephalosporins) Chloramphenicol

*Note: Bacteroides is the most frequent anaerobic pathogen in man (80% of anaerobic infections). Bacteroides species are common in the terminal ileum & colon and are a major component of fecal matter.