Medication Summary
The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.
Antibiotics
Class Summary
Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.
Ampicillin (Polycillin, Omnipen)
DOC if no penicillin allergy. Must be administered in combination with an aminoglycoside if bactericidal activity is required (eg, endocarditis).
Amoxicillin (Trimox, Amoxil)
Oral equivalent of ampicillin. PO therapy is appropriate for mild-to-moderate enterococcal infections and for continuing therapy after stabilization of patients with severe infections. PO therapy should not be used for treatment of endocarditis. Interferes with synthesis of cell wall mucopeptides during active multiplication.
Ceftriaxone (Rocephin)
Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin binding proteins. Exerts antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural component of bacterial cell wall. Bacteria eventually lyse due to the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.
Highly stable in presence of beta-lactamases, both penicillinase and cephalosporinase, of gram-negative and gram-positive bacteria. Approximately 33-67% of dose excreted unchanged in urine, and remainder secreted in bile and ultimately in feces as microbiologically inactive compounds. Reversibly binds to human plasma proteins, and binding have been reported to decrease from 95% bound at plasma concentrations < 25 mcg/mL to 85% bound at 300 mcg/mL.
Vancomycin (Vancocin, Lyphocin, Vancoled)
Used to treat enterococcal infections when ampicillin is contraindicated due to significant penicillin allergy and when strains are resistant to ampicillin but susceptible to vancomycin. Target levels of 30-50 mcg/mL (peak) and 10-15 mcg/mL (trough) for endocarditis and other serious infections.
Dalbavancin (Dalvance)
Dalbavancin is lipoglycopeptide antibiotic that prevents cross-linking by interfering with cell wall synthesis. It is bactericidal in vitro against Staphylococcus aureus and Streptococcus pyogenes at concentrations observed in humans at recommended doses. It is indicated for treatment of acute bacterial skin and skin structure infections caused by Gram-positive bacteria including Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant S aureus [MRSA]), S pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S anginosus, S intermedius, S constellatus).
Oritavancin (Orbactiv)
Oritavancin is lipoglycopeptide antibiotic that inhibits cell wall biosynthesis and disrupts bacterial membrane integrity that leads to cell death. It is indicated for treatment of acute bacterial skin and skin structure infections caused by gram-positive bacteria including S aureus (including methicillin-susceptible S aureus and MRSA), S pyogenes, S agalactiae, S dysgalactiae, S anginosus group (S anginosus, S intermedius, S constellatus) and E faecalis (vancomycin-susceptible isolates only).
Telavancin (Vibativ)
Lipoglycopeptide antibiotic that is a synthetic derivative of vancomycin. Inhibits bacterial cell wall synthesis by interfering with polymerization and cross-linking of peptidoglycan. Unlike vancomycin, telavancin also depolarizes the bacterial cell membrane and disrupts its functional integrity. Indicated for complicated skin and skin structure infections caused by susceptible gram-positive bacteria, including Staphylococcus aureus (both methicillin-resistant and methicillin-susceptible strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus anginosus group, and Enterococcus faecalis (vancomycin-susceptible isolates only).
Gentamicin (Garamycin, Gentacidin)
Aminoglycoside antibiotic administered in combination with ampicillin or vancomycin to provide bactericidal activity for treatment of enterococcal endocarditis and other serious enterococcal infections. Target levels of 3 mcg/mL (peak) and < 1 mcg/mL (trough). Drug levels should be drawn with third dose and then prn until target drug levels achieved. Thereafter, levels should be rechecked weekly during therapy or with any significant change in serum creatinine level.
Daptomycin (Cubicin)
Cyclic lipopeptide antibiotic that binds to components of the cell membrane and inhibits DNA, RNA, and protein synthesis; bactericidal in a concentration-dependent manner. Approved for vancomycin-sensitive E faecalis infections.
Linezolid (Zyvox)
Oxazolidinone antibiotic effective for treatment of both E faecalis and E faecium vancomycin-resistant enterococci (VRE) strains. Inhibits protein synthesis and is bacteriostatic. Has been effective in treating a variety of infections caused by VRE species, including a few cases of enterococcal endocarditis.
The FDA warns against the concurrent use of linezolid with serotonergic psychiatric drugs, unless indicated for life-threatening or urgent conditions. Linezolid may increase serotonin CNS levels as a result of MAO-A inhibition, increasing the risk of serotonin syndrome.
Tedizolid (Sivextro)
Tedizolid is an oxazolidinone antibiotic indicated for skin and skin structure infections caused by susceptible isolates of Gram-positive bacteria including Staphylococcus aureus (including methicillin-resistant [MRSA] and methicillin-susceptible [MSSA] isolates), Streptococcus pyogenes, S agalactiae, S anginosus Group (including S anginosus, S intermedius, and S constellatus), and Enterococcus faecalis. Its action is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis.
Nitrofurantoin (Macrodantin)
Effective for treatment of VRE urinary tract infections. Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations.
Quinupristin/dalfopristin (Synercid)
Belongs to the group that includes macrolide, lincosamide, and streptogramin. Inhibits protein synthesis and is usually bacteriostatic. Effective against E faecium but not E faecalis strains. Option for treatment of vancomycin-resistant E faecium infections.
Tigecycline (Tygacil)
Used to treat complicated skin infections to include methicillin-resistant S aureus and vancomycin-sensitive E faecalis. Inhibits protein synthesis.
Tetracyclines
Omadacycline (Nuzyra)
Omadacycline is indicated for the treatment of adult patients with acute bacterial skin and skin structure infections caused by several different susceptible organisms including Enterococcus faecalis. Although it has in vitro activity against Enterococcus faecium, including vancomycin resistant strains, it has not been approved to treat infections due to this species. It is available in both intravenous and oral formulations.
Eravacycline (Xerava)
Eravacycline is a fluorocycline indicated for the treatment of complicated intra-abdominal infections caused by many susceptible microorganisms including both Enterococcus faecalis and Enterococcus faecium (including VRE if in vitro susceptibility testing is available). It is not indicated for the treatment of complicated urinary tract infections or for endocarditis. It is available only for injection.
Antibiotics, Other
Fosfomycin (Monurol)
Fosfomycin tromethamine is a synthetic broad spectrum antibiotic that has activity against many gram negative and gram positive organisms, as well as E. faecalis and E. faecium including many VRE. It is available in the U.S. only as a sachet containing 3gm of active antibiotic for oral administration in a single dose, mixed with 4oz of water, taken with or without food. It is indicated for the treatment of uncomplicated urinary tract infections (i.e. cystitis) due to either E. coli or E. faecalis in women.
Tables
Critical Illness/Sepsis |
Endovascular Infection (eg, Infectious Endocarditis) |
Central Nervous System Infection |
Bone/Joint Infection |
Serious Organ Infection (eg, Intra-abdominal or Kidney) |
Uncomplicated Skin Infections |
Bladder Infections |
|
Penicillin-Susceptible Enterococci |
Ampicillin 2 g IV q4h plus gentamicin 1 mg/kg IBW q8h Penicillin 18-30 MU daily via continuous infusion or in divided doses plus gentamicin 1 mg/kg IBW q8h Ampicillin 2 g IV q4h plus ceftriaxone 2 g IV q12h [Ampicillin plus imipenem-cilastatin] |
Ampicillin 2 g IV q4h for 4-6 weeks plus gentamicin 1 mg/kg IBW q8h for 2-6 weeks (or streptomycin 7.5 mg/kg IBW IV or IM] Penicillin 18-30 MU daily via continuous infusion or in divided doses for 4-6 weeks plus gentamicin 1 mg/kg IBW q8h for 2-6 weeks [or streptomycin 7.5 mg/kg IBW IV or IM] Ampicillin 2 gm IV q4h plus ceftriaxone 2 g IV q12h for 6 weeks [Ampicillin plus imipenem-cilastatin for 6 weeks] |
Ampicillin 2 g IV q4h plus gentamicin 1 mg/kg IBW q8h for 2-3 weeks Penicillin 18-30 MU daily via continuous infusion or in divided doses for 4-6 weeks plus gentamicin 1 mg/kg IBW q8h for 2-3 weeks Ampicillin 2 g IV q4h plus ceftriaxone 2 g IV q12h for 2-3 weeks [Ampicillin plus imipenem-cilastatin for 2-3 weeks] |
Penicillin G 20-24 MU IV q24h in continuous dosing or divided q4h for 4-6 weeks Ampicillin 12 g IV q24h continuously or in 6 divided doses for 4-6 weeks (For both regimens above, synergistic aminoglycoside is optional) |
Penicillin G 20-24 MU IV q24h in continuous dosing or divided q4h Ampicillin 12 g IV q24h continuously or in 6 divided doses (For both regimens above, synergistic aminoglycoside is optional) |
Ampicillin 8 g IV daily in divided doses Penicillin G 12 MU IV divided q4-6h |
Amoxicillin (or IV ampicillin) (Other options may include oral doxycycline, linezolid, fosfomycin or chloramphenicol) |
Penicillin-Resistant Enterococci or Patient Unable to Tolerate Beta-lactams |
Vancomycin 15 mg/kg q12h plus either gentamicin 1 mg/kg/8h IV or IM or streptomycin 7.5 mg/kg IV or IM every 12 hours |
Vancomycin 15 mg/kg q12h plus either gentamicin 1 mg/kg IV or IM q8h or streptomycin 7.5 mg/kg IV or IM q12h for 6 weeks |
Vancomycin 15 mg/kg q12h plus either gentamicin 1 mg/kg IV or IM q8h or streptomycin 7.5 mg/kg IV or IM q12h for 6 weeks |
Vancomycin 15 mg/kg IV q12h for 4-6 weeks (Addition of aminoglycoside is optional) |
Vancomycin 15 mg/kg IV q12h (Addition of aminoglycoside is optional) |
Vancomycin 15 mg/kg IV q12h (Addition of aminoglycoside is optional) |
Nitrofurantoin Doxycycline Linezolid Chloramphenicol |
VRE |
Linezolid 600 mg IV or PO q12h Daptomycin 10-12 mg/kg once daily |
Linezolid 600 mg IV or PO q12h for a minimum of 6 weeks Daptomycin 10-12 mg/kg once daily for minimum of 6 weeks |
Linezolid 600 mg IV or PO q12h for 2-3 weeks |
Linezolid 600 mg IV or PO q12h for 4-6 weeks Daptomycin 6 mg/kg once daily for 4-6 weeks |
Linezolid 600 mg IV or PO q12h Daptomycin 6 mg/kg once daily |
Linezolid 600 mg IV or PO q12h Daptomycin 4-6 mg/kg once daily |
Nitrofurantoin Doxycycline Linezolid Daptomycin Chloramphenicol |
