By Valentin Sosa MD

DRUG CLASS AND NAME

MECHANISM OF ACTION COMMENT HALF-LIFE TOXICITY

ANTIBACTERIAL SPECTRUM

Penicillins

Penicillin G β-Lactam mechanism: inhibits bacterial cell wall by binding to penicillin-binding proteins (PBPs). It inhibits the final transpeptidation step of peptidoglycan synthesis in the bacterial cell wall

Prototype. Hydrolyzed by all β-lactamases

Short Low, but rarely an allergic reaction may be life threatening

Streptococcal species except enterococci and penicillin-resistant pneumococci, Neisseria species except lactamase-producing gonococci

Antistaphylococcal

 Methicillin β-Lactam mechanism. Also penicillinase resistant and acid stable

First antistaphylococcal drug

Short Interstitial nephritis Staphylococcal species (methicillin sensitive) and streptococcal species except enterococcus

 Oxacillin     Short Interstitial nephritis Narrow spectrum; generally used for staphylococcal infections only

 Nafcillin     Short Interstitial nephritis  

“Easy” gram-negative

 Ampicillin β-Lactam mechanism Hydrolyzed by all β-lactamases

Short Low; diarrhea and rash

Streptococcal species, including many enterococci, Neisseria species (non– lactamase producing), Haemophilus influenzae (non– lactamase producing), some Escherichia coli and Proteus mirabilis

 Amoxicillin Medium

Expanded spectrum

 Carbenicillin β-Lactam mechanism Hydrolyzed by all β-lactamases

Short High sodium load. Inhibition of platelet aggregation

Greatly expanded gram-negative spectrum while still active against streptococcal species, including enterococci. Moderate antianaerobe activity. May not be reliable as the sole agent for established gram-negative rod infections

 Ticarcillin β-Lactam mechanism Same Short   Same, but less activity against enterococci

Very advanced spectrum

 Mezlocillin β-Lactam mechanism Hydrolyzed by all β-lactamases Same

Short Low Same as expanded-spectrum penicillins but with more activity against Pseudomonas, Acinetobacter, and Serratia species

 Piperacillin Short Low

β-Lactamase inhibitor combination

β-Lactam mechanism, plus

    Low; same as constituent β-lactam

 

Clavulanic acid plus Clavulanic acid mechanism: β-lactamase inhibitor that increases the antibacterial activity of β-lactam antibiotics

       

 Ticarcillin     Short   Same as ticarcillin or amoxicillin plus staphylococci (methicillin sensitive), lactamase-positive H. influenzae and some lactamase-producing gram-negative rods, and anaerobes

Cephalosporins

“First” generation β-Lactam mechanism       Streptococcal species except enterococci, staphylococcal species (methicillin sensitive), and “easy” gram-negative rods

 Short half-life        

  Cephalothin   Prototype of class Short Low

  Cephapirin     Short Low

 Longer half-life        

  Cefazolin     Medium Low  

“Second” generation β-Lactam mechanism       Same as first-generation cephalosporins with expanded gram-negative activity not including Pseudomonas, Acinetobacter, or Serratia

 Poor anaerobic activity        

  Shorter half-life        

   Cefamandole     Short Low  

   Cefuroxime     Medium Low  

  Longer half-life          

   Ceforanide   Reduced antistaphylococcal activity

Long    

   Cefonicid   Long    

 Good anaerobic activity

        Same as above, plus many anaerobes

  Short half-life        

   Cefoxitin     Short Low  

  Longer half-life

   Cefmetazole     Medium Low  

   Cefotetan     Long Prolonged prothrombin times

 

“Third” generation β-Lactam mechanism

      Very active against most gram-negative rods except Pseudomonas, Acinetobacter, and Serratia. Poor against anaerobes. Less activity against streptococcal and staphylococcal species than first-and second-generation cephalosporins.

 Poor Pseudomonas activity

       

  Short half-life        

   Cefotaxime     Short Low

   Ceftizoxime     Medium Low

  Long half-life        

   Ceftriaxone     Long Low

Good Pseudomonas activity

         

  Cefoperazone     Medium Low Same as above plus activity against many Pseudomonas, Acinetobacter, and Serratia species

  Ceftazidime     Medium Low

  Cefepime     Medium Low Same as above with increased activity against gram-positive cocci

Monobactams

Aztreonam β-Lactam mechanism: preference to PBP-3 of gram-negative bacteria. Very stable against β-lactamases

Safe for most patients with penicillin allergy

Short Low Excellent activity against most gram-negatives, including Pseudomonas and Serratia. Inactive against gram-positive cocci, anaerobes, and most Acinetobacter strains

Carbapenems β-Lactam mechanism, plus

       

Imipenem/cilastatin Cilastatin mechanism: inactivates dehydropeptidases, which would normally break the β-lactam ring of imipenem in the proximal tubule

Provided in combination with cilastatin to prevent renal breakdown and renal toxicity

Short Low. Seizures in certain high-risk patients

Extremely broad gram-positive and gram-negative aerobic and anaerobic. Modest activity against enterococci. Inactive against Stenotrophomonas (formerly Xanthomonas) maltophilia

Meropenem   Provided alone without cilastatin

Short Reduced potential for seizures

Same activity as imipenem

Quinolones

Poor anaerobic activity

Inhibit bacterial enzyme DNA-gyrase, thus inhibiting DNA replication

       

 Norfloxacin   Oral only; urine levels only

Long Low Very broad Gram-negative activity. Gram-positive and very broad gram-negative activity, including Pseudomonas, Acinetobacter, and Serratia. Poor activity against anaerobes

Interaction leads to accumulation of theophylline

 Ciprofloxacin   Oral and intravenous (applies to all below)

Long  

 Ofloxacin   Racemic mixture of levofloxacin (active) and dextrofloxacin (inactive)

Long    

 Levofloxacin     Long    

Aminoglycosides Bind to a specific protein in the 30S subunit of the bacterial ribosome, which leads to faulty alignment or recognition by RNA during initiation of microbial peptide chain formation

All have a low ratio of therapeutic-to-toxic levels. All are frequently underdosed. All exhibit a significant postantibiotic effect[*]

Medium Nephrotoxicity and nerve VIII toxicity, both auditory and vestibular

Extremely broad coverage of gram-negative rods. Poor activity against streptococci. Some synergism with penicillin or vancomycin against enterococci. No activity against anaerobes

Gentamicin   See above Medium See above Most active against enterococci and Serratia spp.

Tobramycin   See above Medium Statistically but questionably clinically significant decrease in nephrotoxicity

More active against Pseudomonas spp.

Amikacin   See above Medium See above (aminoglycosides)

Active against a significant number of gentamicin- and tobramycin-resistant organisms

Netilmicin   See above Medium See above (aminoglycosides)

See above (aminoglycosides)

Vancomycin Inhibits cell wall synthesis by binding to carboxyl subunits on peptide subunits containing free D-alanyl-D-alanine (different site from β-lactams—no cross resistance), plus may affect permeability of membrane, plus may inhibit RNA synthesis

Only IV. No oral absorption

Very long Hypotension and histamine release phenomena (redman syndrome) during infusion.

Streptococcal species, including many enterococci, staphylococci (including methicillin-resistant strains), Clostridium species. No activity against gram-negative rods

Streptogramins

Quinupristin/dalfopristin

Binds to different sites on the 50S subunit of bacterial ribosomes A 5- to 10-fold decrease in the dissociation constant of quinupristin is seen in the presence of dalfopristin

Significant postantibiotic effect[*]

Medium Reversible transaminase elevations

Most gram-positive pathogens, including vancomycin-resistant Enterococcus faecium, methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis, and penicillin-resistant Streptococcus pneumoniae but not Enterococcus faecalis

Oxazolidinones

Linezolid Attaches to the 50S subunit of the bacterial ribosome and inhibits protein synthesis

Oral or IV Long Reversible monoamine oxidase inhibition with the potential to interact with adrenergic or serotoninergic drugs and cause hypertension

Most gram-positive bacteria, including methicillin-resistant S. aureus and vancomycin-resistant enterococci

Macrolides

Erythromycin Attaches to the 50S subunit of the bacterial ribosome and may interfere with translocation reactions of the peptide chains

Oral or IV Medium Cholestasis with estolate (IV) form

Most gram-positive, Neisseria, Campylobacter, Mycoplasma, Chlamydia, Rickettsia, Legionella

Tetracyclines

Tetracycline Inhibit protein synthesis by attaching to the 30S subunit of the bacterial ribosome

Oral or IV Long Stain teeth of children

Many gram-positive, easy gram-negative rods, some anaerobes, Rickettsia, Chlamydia, Mycoplasma

Doxycycline Oral or IV Very long Same

Antifungal Triazoles

Fluconazole Inhibition of cytochrome P-450–dependent ergosterol synthesis

Oral or IV Very long Elevation of liver function test result

Most fungi except Candida krusei, Candida glabrata

Voriconazole Long Visual disturbances, fever

Most fungi