Acute Cholangitis

Acute cholangitis is a bacterial infection superimposed on an obstruction of the biliary tree most commonly from a gallstone, but it may be associated with neoplasm or stricture. The classic triad of findings is right upper quadrant (RUQ) pain, fever, and jaundice. A pentad may also be seen, in which mental status changes and sepsis are added to the triad.

A spectrum of cholangitis exists, ranging from mild symptoms to fulminant overwhelming sepsis. Thus, therapeutic options for patient management include broad-spectrum antibiotics and, potentially, emergency decompression of the biliary tree.[1]

The main factors in the pathogenesis of acute cholangitis are biliary tract obstruction, elevated intraluminal pressure, and infection of bile. A biliary system that is colonized by bacteria but is unobstructed, typically does not result in cholangitis. It is believed that biliary obstruction diminishes host antibacterial defenses, causes immune dysfunction, and subsequently increases small bowel bacterial colonization. Although the exact mechanism is unclear, it is believed that bacteria gain access to the biliary tree by retrograde ascent from the duodenum or from portal venous blood. As a result, infection ascends into the hepatic ducts, causing serious infection. Increased biliary pressure pushes the infection into the biliary canaliculi, hepatic veins, and perihepatic lymphatics, leading to bacteremia (25-40%). The infection can be suppurative in the biliary tract.

The bile is normally sterile. In the presence of gallbladder or common duct stones (CBD), however, the incidence of bactibilia increases. The most common organisms isolated in bile are Escherichia coli (27%), Klebsiella species (16%), Enterococcus species (15%), Streptococcus species (8%), Enterobacter species (7%), and Pseudomonas aeruginosa (7%). Organisms isolated from blood cultures are similar to those found in the bile. The most common pathogens isolated in blood cultures are E coli (59%), Klebsiella species (16%), Pseudomonas aeruginosa (5%), and Enterococcus species (4%). In addition, polymicrobial infection is commonly found in bile cultures (30-87%) and less frequent in blood cultures (6-16%). For related pathophysiology, please see the Cholelithiasis and Cholecystitis and Biliary Colic articles.

Primary sclerosing cholangitis is a chronic liver disease that is thought to be due to an autoimmune mechanism.[2] It is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. This condition ultimately leads to portal hypertension and cirrhosis of the liver with the only definitive treatment being a liver transplant.[3] For more on this condition, please refer to the Primary Sclerosing Cholangitis article.

In Western countries, choledocholithiasis is the most common cause of acute cholangitis, followed by ERCP and tumors.

Any condition that leads to stasis or obstruction of bile in the CBD, including benign or malignant stricture, parasitic infection, or extrinsic compression by the pancreas, can result in bacterial infection and cholangitis. Partial obstruction is associated with a higher rate of infection than complete obstruction.

Common bile duct stones

CBD stones predispose patients to cholangitis. Approximately 10-15% of patients with cholecystitis have CBD stones.

Approximately 1% of patients post cholecystectomy have retained CBD stones. Most CBD stones are immediately symptomatic, while some remain asymptomatic for years.

Some CBD stones are formed primarily rather than secondarily to gallstones.

Obstructive tumors

Obstructive tumors cause cholangitis. Partial obstruction is associated with an increased rate of infection compared with that of complete neoplastic obstruction. Obstructive tumors include the following:

• Pancreatic cancer

• Cholangiocarcinoma[4]

• Ampullary cancer

• Porta hepatis tumors or metastasis

Other causes

Additional causes of cholangitis include the following:

• Strictures or stenosis

• Endoscopic manipulation of the CBD

• Choledochocele

• Sclerosing cholangitis (from biliary sclerosis)

• AIDS cholangiopathy

• Ascaris lumbricoides infections

United States data

Cholangitis is relatively uncommon. It occurs in association with other diseases that cause biliary obstruction and bactibilia (eg, after endoscopic retrograde cholangiopancreatography [ERCP], 1-3% of patients develop cholangitis). Risk is increased if dye is injected retrograde.

International data

Recurrent pyogenic cholangitis, sometimes referred to as Oriental cholangiohepatitis, is endemic to Southeast Asia. It is characterized by multiple occurrences of biliary tract infection, intrahepatic and extrahepatic biliary stone formation, hepatic abscesses, and dilatation and stricturing of the intrahepatic and extrahepatic bile duct.[5] For more on this condition, please refer to the Recurrent Pyogenic Cholangitis article.

Race-related demographics

Cholangitis frequently occurs secondary to a gallstone obstructing the common bile duct. Therefore, it carries the same risk factors as that of cholelithiasis.

Prevalence of gallstones is highest in fair-skinned people of Northern European descent as well as in Hispanic populations, Native Americans, and Pima Indians.

In addition, certain Asian populations and inhabitants of countries where intestinal parasites are common are also at increased risk. Asians are more likely to have primary stones due to chronic biliary infections, parasites, bile stasis, and biliary strictures. Recurrent pyogenic cholangitis (Oriental cholangiohepatitis) rarely is observed in the United States.

Black individuals with sickle cell disease are at increased risk.

Sex- and age-related demographics

Although gallstones are more common in women than in men, the male-to-female ratio is equal in cholangitis.

Elderly patients are more likely to progress from asymptomatic gallstones to serious complications of gallstones and cholangitis.

Suspect cholangitis in older patients presenting with sepsis and mental status changes. Elderly patients are more prone to gallstones and CBD stones and, therefore, cholangitis.

The median age at presentation is between 50 and 60 years.

The prognosis depends on several factors, including the following[6] :

• Early recognition and treatment of cholangitis

• Response to therapy

• Underlying medical conditions of the patient

Mortality rate ranges from 5-10%, with a higher mortality rate in patients who require emergency decompression or surgery. Early endoscopic retrograde cholangiopancreatography (ERCP) for acute cholangitis within 24 hours appears to be associated with a lower 30-day mortality.[7]

In patients responding to antibiotic therapy, the prognosis is good.

Schneider et al proposed a risk prediction model for in-hospital mortality in patients with acute cholangitis using 22 predictors and the Tokyo criteria to stratify them into high- and low-risk mortality groups and then into different management groups.[8] In univariate analysis, organ failure had the strongest association with mortality—with mental confusion, hypotension requiring catecholamines, Quick value below 50%, serum creatinine level above 2 mg/dL, and a platelet count below 100,000/mm3 as prognostic factors contributing to organ failure. Patients classified as low risk for mortality would be considered for elective biliary drainage, whereas those considered to be at high risk for mortality would undergo urgent biliary drainage.[8]

Schwed et al indicate that leukocytosis greater than 20,000 cells/μL and total bilirubin level above 10 mg/dL, but not timing of ERCP, are independent prognostic factors for adverse outcomes.[9] In a separate study, Tabibian et al did not find adverse outcomes from weekend admission and weekend endoscopic retrograde cholangiography (ERC) on patients with acute cholangitis admitted to a tertiary care center.[10]

Morbidity/mortality

Mortality from cholangitis is high due to the predisposition in people with underlying disease. Historically, the mortality rate was 100%. With the advent of endoscopic retrograde cholangiography, therapeutic endoscopic sphincterotomy, stone extraction, and biliary stenting, the mortality rate has significantly declined to approximately 5-10%.

The following patient characteristics are associated with higher morbidity and mortality rates:

• Hypotension

• Acute renal failure

• Liver abscess

• Cirrhosis

• Inflammatory bowel disease

• High malignant strictures

• Radiologic cholangitis: Post percutaneous transhepatic cholangiography

• Female gender

• Age older than 50 years

• Failure to respond to antibiotics and conservative therapy

Advanced age, concurrent medical problems, and delay in decompression increase the emergent operative mortality rate (17-40%).

The mortality rate of elective surgery after medical stabilization is significantly less (approximately 3%).

In the past, suppurative cholangitis was thought to have increased morbidity; however, prospective studies have not found this to be true.

Complications

Patients are increasingly likely to have complications with greater degrees of illness, as follows:

• Liver failure, hepatic abscesses, and microabscesses

• Bacteremia (25-40%); gram-negative sepsis

• Acute renal failure

Catheter-related problems in patients treated with percutaneous or endoscopic drainage include the following:

• Bleeding (intra-abdominally or percutaneously)

• Catheter-related sepsis

• Fistulae

• Bile leak (intraperitoneally or percutaneously)

In 1877, Charcot described cholangitis as a triad of findings of right upper quadrant (RUQ) pain, fever, and jaundice. The Reynolds pentad adds mental status changes and sepsis to the triad. A spectrum of cholangitis exists, ranging from mild symptoms to fulminant overwhelming sepsis. With septic shock, the diagnosis can be missed in up to 25% of patients.

Consider cholangitis in any patient who appears septic, especially in patients who are elderly, jaundiced, or who have abdominal pain. A history of abdominal pain or symptoms of gallbladder colic may be a clue to the diagnosis.

Symptoms include the following:

• Charcot's triad consists of fever, RUQ pain, and jaundice. It is reported in up to 50-70% of patients with cholangitis. However, recent studies believe it is more likely to be present in 15-20% of patients.

• Fever is present in approximately 90% of cases.

• Abdominal pain and jaundice is thought to occur in 70% and 60% of patients, respectively.

• Patients present with altered mental status 10-20% of the time and hypotension approximately 30% of the time. These signs, combined with Charcot's triad, constitute Reynolds pentad.

• Consequently, many patients with ascending cholangitis do not present with the classic signs and symptoms.[11]

• Most patients complain of RUQ pain; however, some patients (ie, elderly persons) are too ill to localize the source of infection.

Other symptoms include the following:

• Jaundice

• Fever, chills, and rigors

• Abdominal pain

• Pruritus

• Acholic or hypocholic stools

• Malaise

The patient's medical history may be helpful. For example, a history of the following increases the risk of cholangitis:

• Gallstones, CBD stones

• Recent cholecystectomy

• Endoscopic manipulation or ERCP, cholangiogram

• History of cholangitis

• History of HIV or AIDS: AIDS-related cholangitis is characterized by extrahepatic biliary edema, ulceration, and obstruction. The etiology is uncertain, but it may be related to cytomegalovirus or Cryptosporidium infections. The management of this condition is described below, although decompression is usually not necessary.

In general, patients with cholangitis are quite ill and frequently present in septic shock without an apparent source of the infection.

Physical examination may reveal the following:

• Fever (90%), although elderly patients may have no fever

• RUQ tenderness (65%)

• Mild hepatomegaly

• Jaundice (60%)

• Mental status changes (10-20%)

• Sepsis

• Hypotension (30%)

• Tachycardia

• Peritonitis (uncommon, and should lead to a search for an alternative diagnosis)

Procalcitonin may have potential as a useful biomarker for determining the need for emergency biliary drainage and intensive care  in patients with acute cholangitis.[12] Shinya et al noted that significantly elevated procalcitonin levels were found in their cohort of patients with grade III inflammation based on the 2013 Tokyo guidelines versus those with grade I inflammation, as well as those with positive hemocultures compared to those with negative hemocultures. Moreover, procalcitonin levels were significantly increased in severe cases that were underestimated as grade I or II.[12]

Imaging studies are important to confirm the presence and cause of biliary obstruction and to rule out other conditions.[1] Ultrasonography and computed tomography (CT) scanning are the most commonly used first-line imaging modalities. Endoscopic retrograde cholangiography, magnetic resonance cholangiopancreatography, and endoscopic ultrasonography are commonly used for both diagnostic and therapeutic purposes.[1]

Laboratory studies include the following:

• CBC: Leukocytosis: In patients with cholangitis, 79% had a WBC greater than 10,000/mL, with a mean of 13.6. Septic patients may be leukopenic.

• Electrolyte panel with renal function may be performed.

• Calcium level is necessary to check if pancreatitis, which can lead to hypocalcemia, is a concern.

• Expect liver function test results to be consistent with cholestasis, hyperbilirubinemia (88-100%), and increased alkaline phosphatase level (78%).

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are usually mildly elevated.

• Prothrombin time and activated partial thromboplastin time: Do not expect either to be elevated unless sepsis is associated with disseminated intravascular coagulation or underlying cirrhosis exists. A coagulation profile may be required if the patient needs operative intervention.

• C-reactive protein level and erythrocyte sedimentation rate are typically elevated.[5]

• Blood cultures (2 sets): Between 20% and 30% of blood cultures are positive. Many exhibit polymicrobial infections.

• Urinalysis result is usually normal.

• Blood type, screen, and crossmatch: With urgent operating room dispatch, patients need to have blood available.

• Lipase: Involvement of the lower CBD may cause pancreatitis and an elevated lipase level. One third of patients have a mildly elevated lipase level.

• Pancreatic enzyme elevations suggest that bile duct stones caused the cholangitis, with or without gallstone pancreatitis.[13]

• Biliary cultures (not performed in the ED): Send biliary cultures if the patient has biliary drainage by interventional radiology or endoscopy.

Ultrasonography is excellent for gallstones and cholecystitis.[14] It is highly sensitive and specific for examining the gallbladder and assessing bile duct dilatation (see the following image). However, it often misses stones in the distal bile duct.[15]

Sonogram of dilated intrahepatic ducts.

Consider the following:

• Transabdominal ultrasonography is the initial imaging study of choice.

• Ultrasonography can differentiate intrahepatic obstruction from extrahepatic obstruction and image dilated ducts.

• In one study of cholangitis, only 13% of CBD stones were observed on ultrasonography, but dilated CBD was found in 64%.

• Advantages to sonography include the ability to be performed rapidly at the bedside by the ED physician, capacity to image other structures (eg, aorta, pancreas, liver), identification of complications (eg, perforation, empyema, abscess), and lack of radiation.

• Disadvantages to sonography include operator and patient dependence, cannot image the cystic duct, and decreased sensitivity for distal CBD stones.

• A normal sonogram does not rule out acute cholangitis.

Endoscopic retrograde cholangiopancreatography (ERCP) is both diagnostic and therapeutic and is considered the criterion standard for imaging the biliary system.

ERCP should be reserved for patients who may require therapeutic intervention. Patients with a high clinical suspicion for cholangitis should proceed directly to ERCP.

ERCP has a high success rate (98%) and is considered safer than surgical and percutaneous intervention.

Diagnostic use of ERCP carries a complication rate of approximately 1.38% and a mortality rate of 0.21%. The major complication rate of therapeutic ERCP is 5.4%, and it has a mortality rate of 0.49%. Complications include pancreatitis, bleeding, and perforation.[16]

Computed tomography (CT) scanning is adjunctive to and may replace ultrasonography. Spiral or helical CT improves imaging of the biliary tree. CT cholangiography uses a contrast agent that is taken up by the hepatocytes and secreted into the biliary system. This enhances the ability to visualize radiolucent stones and increases detection of other biliary pathology.

Dilated intrahepatic (see the image below)and extrahepatic ducts and inflammation of the biliary tree are imaged. Gallstones are poorly visualized with traditional CT scan.

CT scan of dilated intrahepatic bile ducts. Image courtesy of David Schwartz, MD, New York University Hospital.

Advantages of CT include the following:

• Other pathologies that are causes or complications of cholangitis (eg, ampullary tumors, pericholecystic fluid, liver abscesses) can be imaged.

• Pathology that must be distinguished from cholangitis also can be observed (eg, right-sided diverticulitis, papillary necrosis, some evidence of pyelonephritis, mesenteric ischemia, ruptured appendix).

• Detection of biliary pathology with CT cholangiography approaches that of ERCP.

Disadvantages of CT include poor imaging of gallstones, allergic reaction to contrast, exposure to ionizing radiation, and diminished ability to visualize the biliary tree with elevated serum bilirubin level.

Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive imaging modality that is increasingly being used in the diagnosis of biliary stones and other biliary pathology.

MRCP is accurate for detecting choledocholithiasis, neoplasms, strictures, and dilations within the biliary system.

Limitations of MRCP include the inability for invasive diagnostic tests such as bile sampling, cytologic testing, stone removal, or stenting. It has limited sensitivity for small stones (< 6 mm in diameter).

Absolute contraindications are the same as for a traditional MRI, which include the presence of a cardiac pacemaker, cerebral aneurysm clips, ocular or cochlear implants, and ocular foreign bodies. Relative contraindications include the presence of cardiac prosthetic valves, neurostimulators, metal prostheses, and penile implants.

The risk of MRCP during pregnancy is not known.

In general, abdominal films aid little in the diagnosis of acute cholangitis. Findings may include the following:

• An ileus may be observed.

• Between 10% and 30% of gallstones have a ring of calcium and, as a result, are radiopaque.

• Films may show air in the biliary tree after endoscopic manipulation or if the patient has emphysematous cholecystitis, cholangitis, or a cholecystic-enteric fistula.

• Air in the gallbladder wall indicates emphysematous cholecystitis.

Biliary scintigraphy (hepatic 2,6-dimethyliminodiacetic acid [HIDA] and diisopropyl iminodiacetic acid [DISIDA]) scans are functional studies of the gallbladder.

Obstruction of the CBD causes nonvisualization of the small intestine. A HIDA scan with complete biliary obstruction does not visualize the biliary tree.

Advantages include their ability to assess function and positive results may appear before the ducts are enlarged sonographically.

One disadvantage is that high bilirubin levels (>4.4) may decrease the sensitivity of the study. Recent eating or no food in 24 hours also may affect the study. In addition, anatomic imaging for other structures is lacking. The study takes several hours, so it is not recommended in critically ill or unstable patients.

ED physicians generally do not perform procedures for cholangitis (eg, ERCP and transhepatic decompression).

If an obstruction is observed, ERCP provides direct visualization and potential treatment. It is best performed after 72 hours of antibiotics or after resolution of fever.

In unstable patients, a reasonable option for decompression of the biliary tract is percutaneous transhepatic cholangiogram and biliary drain. The biliary ducts are observed, even when no ductal dilatation is present.

Diagnosis of cholangitis is not a prehospital diagnosis. Mild cholangitis may present with abdominal pain, jaundice, and fever. When transporting these patients to the hospital, place the patient on a monitor and insert an intravenous (IV) line.

In unstable patients with cholangitis, prehospital care should include the following:

• Immediate assessment of ABCs (airway, breathing, circulation)

• Monitoring (eg, pulse oximetry, cardiac monitor, frequent blood pressure measurements, blood glucose measurement)

• Stabilization (eg, oxygen, placement of 2 large-bore IVs, administration of IV fluids to unstable patients)

• Rapid transport

Suspect mild cholangitis in patients with jaundice and a fever; consider cholangitis in all patients with sepsis.

The degree of urgency of treatment depends on severity of illness. Important points are resuscitation, diagnosis, and treatment.

Management of acute cholangitis in the emergency department includes the following:

• After assessment of the ABCs (airway, breathing, circulation), place the patient on a monitor with pulse oximetry, provide oxygen via nasal canula, and obtain an electrocardiogram (ECG). Draw and send laboratory studies (including blood cultures) when the intravenous line is placed.

• Provide fluid resuscitation with intravenous (IV) crystalloid solution (eg, 0.9% normal saline).

• Administer parenteral antibiotics empirically after blood cultures are drawn. Do not delay administration of antibiotics if blood cultures cannot be drawn.

• Correct any electrolyte abnormalities or coagulopathies.

• For management of patients in septic shock, see Shock, Septic.

• Standard therapy for cholangitis consists of broad-spectrum antibiotics with close observation to determine the need for emergency decompression of the biliary tree.[17]

• A nasogastric tube may be helpful for patients who are vomiting.

• Patients should be nothing by mouth (NPO). Place a Foley catheter in ill patients to monitor urine output.

The surgical literature states that, in patients with mild cholangitis, 80-90% respond to medical therapy.[5] Approximately 15% do not respond and subsequently require immediate surgical or endoscopic decompression. Mortality rates approach 100% for patients who fail medical therapy and do not have surgical decompression.

In severely ill patients, treatment is immediate biliary decompression. The method depends on the degree of illness. In the past, drainage was performed surgically. Today, options of percutaneous or endoscopic drainage exist in addition to medical management with antibiotics. Endoscopic drainage has been shown to decrease mortality rates from 30% to 10%.

Zhang et al indicate that endoscopic sphincterotomy is safe and effective for temporary biliary decompression in patients with acute obstructive cholangitis, and endoscopic nasobiliary drainage without sphincterotomy may be considered as a first-line therapy in this setting.[18]  The investigators also suggested that endoscopic sphincterotomy may improve the effectiveness of endoscopic nasobiliary drainage in those with papillary inflammation stricture and thick bile.

Medical therapy can be complementary to surgical or endoscopic treatments. In less ill patients, medical treatment may be all that is necessary. Perform the following:

• Maintain medical therapy and consider elective surgery with patients who show improvement. Patients who are being medically managed and do not improve or who deteriorate should rapidly be referred to undergo either endoscopic retrograde cholangiopancreatography (ERCP), sphincterotomy, or percutaneous drainage.[14] See the management algorithm below.

  Algorithm for management of patients with acute cholangitis.

• The mainstay of therapy is drainage. ERCP is the best method to accomplish biliary drainage. A study by Sharma showed equal safety and effectiveness when using a 7 Fr stent or 10 Fr stent for biliary drainage in patients with severe cholangitis.[19]

Endoscopic nasobiliary drainage (ENBD) is a technique that is being used in Asia in the surgical management of acute cholangitis.[20]  Data from a meta-analysis indicate that ENBD may cause fewer perioperative complications (eg, preoperative cholangitis rate, postoperative pancreatic fistula rate) than endoscopic biliary stenting (EBS) in patients with malignant biliary obstruction.[21] However, a limitation of the meta-analysis was that there were no data from randomized controlled trials.

Admission to the intensive care unit (ICU) for ill patients is appropriate. Continue intravenous antibiotics; monitor the blood cultures so that the antibiotics can be narrowed to the appropriate pathogen, and provide supportive measures including administration of intravenous fluids.[17] Administer intravenous antibiotics 12-24 hours prior to nonemergent endoscopic retrograde cholangiopancreatography (ERCP). Refer worsening patients to emergent ERCP for sphincterotomy or percutaneous drainage.

Traditionally, antibiotics were administered for 7-10 days to treat cholangitis. However, it now appears that a 3-day course may be sufficient in patients who undergo adequate biliary drainage.

In addition, a study by Park et al indicated that in patients with acute cholangitis with bacteremia who have achieved successful biliary drainage, treatment with an early switch from intravenous to oral antibiotics is just as effective as conventional 10-day intravenous antibiotic therapy. The study involved 59 patients, including 30 who underwent conventional intravenous antibiotic treatment and 29 who were switched early in treatment to oral antibiotics. At follow-up, 30 days after diagnosis, the investigators determined that the bacterial eradication rate was not significantly different between the two groups, being 93.3% for the conventional treatment patients and 93.1% for the early switch group. Moreover, the groups showed no statistically significant differences in the recurrence rate for acute cholangitis and the 30-day mortality rate.[22]

Transfer

Transfer is appropriate in hospitals unable to manage significantly ill patients with intensive medical care, surgery, and endoscopic consultation.

Optimize patient stabilization prior to transfer.

Minimum initial stabilization includes the following:

• Appropriate diagnostics
• ABCs (including volume resuscitation)
• Administration of broad-spectrum antibiotics
• Critical care transport

Immediately consult a surgeon and a gastroenterologist.

Although most patients respond to antibiotics and conservative care, a subset requires emergent procedures (eg, ERCP, percutaneous drainage). In deciding to drain, consult with a gastroenterologist and a surgeon.

Increased mortality is observed in patients with hypotension, acute renal failure, liver abscess, cirrhosis, high malignant strictures, female gender, and advanced age. Therefore, consider decompression earlier for these patients. Patients with malignant obstruction usually do not respond to antibiotics (59% compared to 85%).

Unstable septic patients require clinical judgment to determine if they will survive until medical therapy has a chance to work or if they require emergency decompression with its associated high mortality rate.

Prophylactic antibiotics prior to endoscopic retrograde cholangiopancreatography (ERCP) may decrease risk of cholangitis.

Prompt recognition and treatment of symptomatic cholelithiasis in patients at higher risk for complications (eg, those with diabetes) decrease risk of cholangitis.

Aggressive search for commond bile duct stones during diagnosis and treatment of cholecystitis may be necessary to prevent cholangitis.

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.