Cholangitis in Emergency Medicine Medication

The goal of antimicrobial therapy is to resolve the infection. Debate exists as to whether the most effective antibiotics must have high biliary concentrations. When high intrabiliary pressures exist due to biliary obstruction, whether any antibiotic is excreted effectively into the bile is doubtful, thus making biliary levels irrelevant. The choice of antibiotics should be guided by local sensitivity patterns.

It is critical that antibiotics are administered early in the management of cholangitis. In the ED, empiric antibiotic therapy should cover against gram-negative aerobic enteric organisms (eg, E coli, Klebsiella species, Enterobacter species), gram-positive organisms (eg, Enterococcus and Streptococcus species), and anaerobes (eg, Bacteroides fragilis, Clostridium perfringens). There is an increase of up to 85% in infectious complications when biliary cultures are not susceptible to the empiric antibiotics. Therefore, traditional therapy with ampicillin and an aminoglycoside is now a less ideal regimen secondary to weakened activity of ampicillin against both aerobic and anaerobic gram-negative bacilli, and is concern for nephrotoxicity of aminoglycosides.

Many newer combinations have been shown to be effective as either a single agent or combination therapy. Combinations include extended-spectrum cephalosporin, metronidazole, and ampicillin. Single-agent regimens include piperacillin and tazobactam; mezlocillin; imipenem; meropenem; ticarcillin and clavulanate; or ampicillin and sulbactam, which can also be combined with metronidazole.

In patients with few comorbidities and who are well-appearing, using a single agent such as cefoxitin (second-generation cephalosporin) may be appropriate. However, cefoxitin’s anaerobic coverage is poor. Newer-generation fluoroquinolones (eg, moxifloxacin) also have broad gram-positive and gram-negative coverage and better anaerobic activity, but they are poorly effective against Pseudomonas species. In patients with multiple comorbidities or who are ill-appearing, broad-spectrum antimicrobials with pseudomonal and enterococcal coverage are recommended. Once blood cultures results are available, the antibiotic regimen can be narrowed based on the culture results.

The following dosages are general recommendations. Please check current sources prior to administration.

Ampicillin (Omnipen, Marcillin)

Interferes with bacterial cell wall synthesis during active multiplication, causing bactericidal activity against susceptible organisms. Must be used in combination.

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Usually used in combination with other antimicrobial agents.

Gentamicin (Gentacidin, Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.

Not DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM.

Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion.

Cefoxitin (Mefoxin)

A second-generation cephalosporin that has broad gram-negative coverage, while retaining efficacy against gram-positive organisms. It also has activity against anaerobes.

However, it lacks pseudomonal and enterococcal coverage.

Piperacillin/tazobactam (Zosyn)

Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication. Used in combination therapy.

Cefotaxime (Claforan)

Third-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms.

Arrests bacterial cell wall synthesis and inhibits bacterial growth by binding to one or more of the penicillin-binding proteins.

Can be used in combination with metronidazole or clindamycin.

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Mezlocillin (Mezlin)

During growth phase, interferes with bacterial cell wall synthesis, causing death in susceptible microorganisms. Has antipseudomonal activity. Use in combination therapies.

Imipenem and cilastatin (Primaxin)

A carbapenem; may be used alone or in combination. Used for treatment of multiple-organism infections for which other agents do not have wide-spectrum coverage or are contraindicated due to potential for toxicity.

Meropenem (Merrem)

A carbapenem; may be used alone or in combination. Broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis and has bactericidal activity. Effective against most gram-positive and gram-negative bacteria.

Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem.

Ticarcillin and clavulanate potassium (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth.

Antipseudomonal penicillin plus a beta-lactamase inhibitor that provides coverage against most gram-positive and gram-negative organisms and most anaerobes.

Ampicillin and sulbactam sodium (Unasyn)

Combination antimicrobial agent that uses a beta-lactamase inhibitor with ampicillin. Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens.