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Acute biliary tract infection, how to choose antibacterial drugs? This article makes it clear

 Last Update: 2023-01-06
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According to statistics, 5%-15% of the global population has biliary system stones, of which 1%-3% of patients cause acute cholecystitis or acute cholangitis and other biliary system infections
every year because of biliary system stones.
If acute biliary infections are left untreated, serious complications
such as gallbladder perforation, biliary peritonitis, and perigallbladder abscess may occur.
Antimicrobial therapy is an important treatment for acute biliary tract infection, and antimicrobial therapy
should be started as soon as biliary infection is suspected.

Antimicrobial drugs commonly used in acute biliary tract infections

These include cephalosporins, carbapenems, β-lactam/β-lactamase inhibitor combinations, quinolones, glycopeptides, glycylcyclines (eg, tigecycline), oxazolidinones (e.
g.
, linezolid), and nitroimidazoles
.

According to the pharmacokinetic/pharmacodynamic characteristics, antibacterial drugs with high bile penetration rate, such as cefoperazone-sulbactam, tigecycline, etc.
, can be selected to ensure sufficient concentration
in bile.
Avoid drugs with high resistance rates such as quinolones, and if β-lactam allergy or susceptibility testing confirms it
, quinolones can be used.

1 cephalosporin representative drugs: the first generation such as cefthiamidine, cefadroxampil, etc.
; The second generation such as cefotiam, cefuroxime, cefaclor and so on; The third generation such as cefotaxime, ceftriaxone, ceftazidime, cefoperazone, cefdinib, cefixime, etc.
; the fourth generation such as cefpirome, cefepime, etc.
; The fifth generation is such as cefaprolin, cefepiprib
.

Note: Ceftriaxone sodium preparations cannot be added to Calcium-containing solutions such as Hartmann's and Ringer's, and their combination with calcium-containing agents or calcium-containing products may cause adverse events
with fatal outcomes.
Cefoperazone can cause hypoprothrombinemia or bleeding and is seen in malnutrition, malabsorption (e.
g.
, cystic fibrosis), alcoholism, and long-term intravenous infusion of hypernutrient preparations
.
Can cause the development of disulfiram-like reactions, avoid alcohol
during use.

2 carbapenems representative drugs: imipenem, meropenem, ertapenem
.

Note: It can induce epilepsy, mostly in patients with central nervous system diseases such as epilepsy and those with reduced renal function and unreduced medication
.
Patients with central nervous system infection should not use imipenem
.
Combination with valproic acid or divalproic acid may cause the blood concentration of the latter two to be lower than the therapeutic concentration, and increase the risk of seizures, so it is not recommended to use together
.

3β-lactam/β-lactamase inhibitor combination preparation representative drugs: cefoperazone-sulbactam piperacillin-tazobactam
.

Precautions: Pay attention to allergic reactions
.
Before the skin test, it is recommended to stop the drug with glucocorticoids for at least 7 days, stop the systemic first-generation antihistamines for at least 2-3 days and the second-generation antihistamines for at least 3-7 days, and stop the drug with phenothiazide antipsychotics and imipramine antidepressants for at least 7 days
.
Angiotensin-converting enzyme inhibitors (ACEs) and β receptor blockers can affect the treatment of anaphylaxis, and it is recommended to stop at least 24 hours
before skin testing for patients with risk factors for anaphylaxis.

4 quinolones representative drugs: ciprofloxacin, levofloxacin, moxifloxacin
.

Note: levofloxacin, moxifloxacin can be administered once a day, ciprofloxacin due to short half-life and adverse reactions have a certain concentration dependence, can be administered
in 2-3 times a day.
It can cause glucose abnormalities, epilepsy, convulsions, Q-T interval prolongation, ventricular arrhythmias, aortic aneurysms and aortic dissection, torsades de pointes, joint lesions, photosensitive tendon rupture, etc
.
Avoid use in patients
with a history of peripheral neuropathy and myasthenia gravis.
Gatifloxacin is contraindicated in patients with
diabetes.

5 glycopeptide drugs representative drugs: vancomycin, teicoplanin
.

Note: Can cause renal ototoxicity and hearing changes
.
Avoid combination with renal ototoxic drugs
.

6 glycylcycline class of drugs representative drugs: tigecycline
.

Precautions: Causes of acute pancreatitis, including fatal cases, have been reported
.
If pancreatitis is suspected after use, the drug
should be discontinued.
Not recommended for persons under 18 years of age
.
Patients with severe liver function impairment should be used
with caution.

7 oxazolidinone representative drug: linezolid
.

Precautions: It can cause increased blood pressure, thrombocytopenia, lactic acidosis, peripheral nerve and optic neuropathy, and reports of convulsions
.
Has interactions
with serotonins.

8 oxazolidinone representative drugs: metronidazole, tinidazole
.

Precautions: Can cause peripheral neuritis, granulocytopenia, etc
.
Because it can cause disulfiram-like reactions, alcohol and alcoholic beverages
are prohibited during medication.
Caution for patients
with underlying diseases of the nervous system and blood diseases.

Selection of antimicrobial agents for acute biliary tract infection

For acute biliary tract infection, broad-spectrum anti-gram-negative drugs can be empirically used, in combination with anti-anaerobic drugs, and anti-anaerobic therapy
is recommended if there is a history of biliary anastomosis.

Try to use antimicrobials
based on susceptibility testing.
The Guidelines for the Diagnosis and Treatment of Acute Biliary Tract Infection (2021 Edition) (2021) pointed out that mild to moderate acute biliary infection should use antibacterial drugs within 6 hours after the diagnosis is clear, and severe acute biliary infections are usually complicated by septic shock, and antibacterial drugs need to be used within 1 hour of the diagnosis to control local and systemic inflammation in time
.

The indication for discontinuation is normal body temperature of more than 72 hours; Abdominal pain, abdominal tenderness, rebound pain and other manifestations are relieved or disappeared; normal WBC count in blood count; Procalcitonin < 0.
05μg/L; Severe acute biliary tract infection, hemodynamic indexes and vital organ function returned to normal<b20>.
(1) Mild to moderate acute biliary infection
can be selected with second-generation cephalosporins (such as cefuroxime), third-generation cephalosporins (such as ceftriaxone), and combined with nitroimidazoles; Or choose a combination of β-lactam/β-lactamase inhibitors such as cefoperazone-sulbactam and piperacillin-tazobactam
.

If it is combined with advanced age, underlying diseases, previous abdominal infection or history of biliary surgery, etc.
, β-lactam/β-lactamase inhibitor combination preparations such as cefoperazone-sulbactam, piperacillin-tazobactam, or carbapenems such as imipenem and ertapenem can be used
.

Antibacterial drugs for mild to moderate acute cholecystitis are used only before or during surgery, and should be used no more than 24 hours
after surgery.

(2) Severe acute biliary infection
can be selected with third-generation cephalosporins (such as ceftazidime), fourth-generation cephalosporins (such as cefepime), and combined with nitroimidazoles; Alternatively, a combination β-lactam/β-lactamase inhibitor such as cefoperazone-sulbactam, piperacillin-tazobactam, or a carbapenem such as imipenem, meropenem, ertapenem, or the glycylcycline tigecycline
.

Antimicrobials for severe acute cholecystitis are used 4 to 7 days
after infection control (surgical resection or cholecentestomy).

(3) When obstructive jaundice obstructive jaundice
has no manifestations of biliary tract infection, it is not recommended to use antibacterial drugs
.
In obstructive jaundice, if biliary infection such as elevated body temperature, abdominal pain, and WBC count >10.
0×10⁹/L, antimicrobials
can be used in addition to bile drainage.

Empiric antibacterial drugs can be used with third-generation cephalosporins (eg, ceftriaxone, ceftazidime) combined with nitroimidazoles; or β-lactam/β-lactamase inhibitor combination preparations such as cefoperazone-sulbactam, piperacillin-tazobactam, or carbapenem such as imipenem, meropenem, ertapenem, etc
.
Vancomycin, teicoplanin, or linezolid
may be used in the presence of gram-positive infection.

(4) Recurrent biliary tract infections mostly have a history of antibacterial drug use, with gram-negative bacteria being the most common, easy to be complicated with complex infections, often accompanied by drug-resistant bacterial infections

.

Third-generation cephalosporins, fourth-generation cephalosporins, combined with antianaerobic drugs, or β-lactam/β-lactamase inhibitor combination preparations such as cefoperazone-sulbactam can be empirically
selected.

In severe biliary tract infection or with a cephalosporin that does not respond well, a carbapenem such as imipenem, meropenem, or the glycylcycline tigecycline
may be used.
If infection is still not effectively controlled, combination therapy
is recommended.
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References:

Guidelines for the diagnosis and treatment of acute biliary system infection (2021 edition)[J].
Chinese Journal of Surgery,2021,59(6):422-429.
)

[2] Expert consensus on multidisciplinary diagnosis and treatment of common abdominal infections in surgery[J].
Chinese Journal of Surgery,2021,59(3):161-178.
)

[3] Expert consensus on the standardized application of antibacterial drugs in biliary surgery (2019 edition)[J].
Chinese Journal of Surgery,2019,57(7):481-487.
)

[4] Consensus opinion on the diagnosis and treatment of integrated traditional Chinese and western medicine for acute cholecystitis[J].
Chinese Journal of Integrative Medicine and Digestion,2018,26(10):805-811

[5] Guidelines for the clinical application of antimicrobial drugs (2015 edition) [J].
2015

[6] Expert consensus on the clinical application of pharmacokinetics/pharmacodynamics theory of antibacterial drugs[J].
Chinese Journal of Tuberculosis and Respiratory,2018,41(6):409-442

[7] Notice of the General Office of the National Health Commission on Printing and Distributing the Guidelines for Skin Testing of β Lactam Antibacterial Drugs (2021 Edition)-National Health Office Medical Letter [2021] No.
188

[8] Expert consensus on the clinical application of β-lactam antibiotic/β-lactamase inhibitor combination preparation (2020 edition)[J].
Chinese Medical Journal,2020,100(10):738-747.
)

[9] Expert consensus on the clinical application of carbapenems antimicrobials[J].
2018

[10] Expert consensus on the rational application of quinolone antibacterial drugs for the treatment of lower respiratory tract infection[J].
Chinese Journal of Tuberculosis and Respiratory,2009,32(9):646-653.
)

[11] Announcement of the State Food and Drug Administration on Revising the Instructions for Systemic Fluoroquinolones (No.
79 of 2017)

[12] Announcement of the State Food and Drug Administration on Revising the Instructions for Fluoroquinolone Drugs for Systemic Use (No.
44 of 2021)

[13] Gatifloxacin-induced glucose metabolism disorder is contraindicated in diabetic patients[J].
Journal of Adverse Drug Reactions,2006,8(3):231

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