Antimicrobial agents play a critical role in the prevention, control, and treatment of surgical infections. Currently, hundreds of antimicrobial drugs are in clinical use, and misuse remains common. Inappropriate use may result in toxic side effects, allergic reactions, increased resistance of pathogens, and secondary infections. Therefore, rational use of antimicrobials is essential.
Basic Principles of Rational Antimicrobial Use
Early Identification of Pathogens
In cases of confirmed or suspected surgical infections, efforts should be made to promptly identify the causative organisms and conduct susceptibility testing to guide targeted antimicrobial therapy. For critically ill patients, empirical treatment should be initiated based on clinical diagnosis, taking into account the most likely pathogens and local antimicrobial resistance patterns. Once culture and sensitivity results become available, the treatment regimen should be adjusted accordingly based on the response to prior therapy.
Selection of the Most Appropriate Antimicrobial Agents
Each antimicrobial drug has a specific spectrum of activity and indications. Pathogens vary in their sensitivity to different agents. Drug selection should be based on clinical diagnosis, microbiological findings, pharmacokinetic and pharmacodynamic (PK/PD) properties, aiming for agents that offer high efficacy, low toxicity, and ease of administration.
Development of a Rational Dosing Regimen
The following factors should be considered:
Route of Administration
For mild infections, oral agents with good absorption may be used. In severe infections, intravenous administration is preferred to ensure adequate drug levels.
Dosage
The dosing should fall within the therapeutic range. For concentration-dependent agents (e.g., aminoglycosides, fluoroquinolones), efficacy is linked to drug concentration, and higher-end dosing is usually required. For time-dependent agents (e.g., β-lactams, macrolides), maintaining plasma concentrations above the minimum inhibitory concentration (MIC) is sufficient, so lower-end dosing is often adequate.
Dosing Frequency
This is determined by PK/PD principles. Agents with short half-lives (e.g., penicillins, cephalosporins) typically require multiple daily doses. Agents such as fluoroquinolones and aminoglycosides may be given once daily.
Duration of Therapy
Antimicrobial therapy may be discontinued once the patient's temperature, white blood cell count, and clinical condition have returned to normal, and local infections are controlled. Most surgical infections can be controlled with 5–7 days of effective treatment. However, conditions such as osteomyelitis, infective endocarditis, or prosthetic infections often require 6–12 weeks of therapy. Premature discontinuation may result in persistent or recurrent infection.
Combination Therapy
Indications include:
- Severe infections of unknown origin, particularly in immunocompromised patients;
- Mixed or severe infections unresponsive to single-agent therapy, such as sepsis;
- Infections requiring prolonged therapy with high risk of resistance, such as tuberculosis;
- Reduction of individual drug dosages to minimize toxicity, such as combining amphotericin B with flucytosine.
Principles of Antimicrobial Prophylaxis in the Perioperative Period
The goal of prophylactic antimicrobial use is to prevent or reduce surgery-related infections, including postoperative wound infections, deep or cavity infections, and possible systemic infections. Indications for prophylaxis primarily include clean-contaminated and contaminated procedures, as well as selected clean surgeries under specific conditions, as outlined below:
Clean Surgery
When the surgical field is free of contamination, prophylaxis is generally unnecessary. However, antimicrobial prophylaxis may be considered under the following circumstances:
- Large or prolonged procedures with increased risk of contamination;
- Operations involving critical areas or organs, such as the brain, heart, or eyes, where infection would have serious consequences;
- Procedures involving implantation of foreign bodies;
- High-risk populations, including the elderly and immunocompromised individuals.
Clean-Contaminated Surgery
This category includes procedures involving the respiratory, gastrointestinal, urinary, or female reproductive tracts, or surgeries that traverse these organs. Due to the presence of normal flora, intraoperative contamination of the surgical field may occur, making prophylaxis necessary.
Contaminated Surgery
This includes procedures where the surgical field has already been heavily contaminated, such as cases involving spillage of gastrointestinal, urinary, or biliary contents or open traumatic wounds. Prophylactic antimicrobials are required in these situations.
Use of Antimicrobial Agents in Special Populations
The pharmacological effects of drugs can be influenced by a patient’s pathophysiological and immune status. Even the same drug may exhibit differences in absorption, distribution, metabolism, and excretion among individuals. In special populations, antimicrobial therapy should follow individualized principles.
Patients with Renal Impairment
Drug selection should be based on the severity of infection, the type of pathogen, and susceptibility test results, with preference for agents that have low or no nephrotoxicity. If nephrotoxic drugs must be used, renal function should be closely monitored, and both dosage and administration methods should be adjusted accordingly.
Patients with Hepatic Impairment
For drugs primarily eliminated by the liver, hepatic impairment significantly reduces drug clearance. If no significant toxicity occurs, the drug may still be used at the usual dose, with close monitoring of liver function and dosage adjustment if necessary. If toxic reactions develop, such drugs should be avoided.
For drugs eliminated through both hepatic and renal pathways, dose reduction is required in severe liver disease.
For drugs primarily excreted via the kidneys, no dosage adjustment is usually necessary.
Elderly Patients
Due to physiological decline in renal function, dosage should generally be reduced to 1/2 to 2/3 of the standard therapeutic dose, similar to the adjustment for mild renal impairment. Drugs with low toxicity and strong bactericidal activity are preferable. If potentially toxic agents must be used, therapeutic drug monitoring should be conducted to guide dosage adjustment.
Neonates
Drugs with high toxicity should be avoided. If their use is necessary, therapeutic drug levels should be monitored, and dosages adjusted accordingly. Agents associated with severe adverse reactions should be avoided. For drugs primarily metabolized by the kidneys, dose reduction is necessary. Dosing regimens should be tailored according to postnatal age.
Pediatric Patients
Drugs with known ototoxicity or nephrotoxicity, such as aminoglycosides, should be avoided when possible. If their use is required, adverse effects must be closely monitored. Tetracyclines, which may cause tooth discoloration and enamel hypoplasia, are contraindicated in children under 8 years of age. Fluoroquinolones, due to potential negative effects on skeletal development, should be avoided in individuals under 18 years of age.
Pregnant Patients
Drugs with teratogenic or significant toxic effects on the fetus, such as tetracyclines and fluoroquinolones, should be avoided. Agents harmful to both the mother and fetus, such as aminoglycosides and vancomycin, should also be avoided; if necessary, therapeutic drug monitoring should be performed. Drugs that pose minimal risk to both the mother and fetus, and are not teratogenic—such as β-lactams—are suitable for use.
Lactating Patients
Antimicrobial agents can be secreted into breast milk and may potentially affect the infant, regardless of the drug concentration in the milk. Therefore, breastfeeding should be suspended during antimicrobial treatment.
In conclusion, rational antimicrobial selection should be guided not only by the type of pathogen and drug susceptibility results, but also by the specific physiological and pathological condition of the patient.