General Principles of Antibiotic Prophylaxis

Effective antibiotics for use in neurosurgical procedures provide adequate coverage of the organisms commonly associated with neurosurgical infections, such as staphylococci. An ideal antibiotic will have minimal adverse effects and be low in cost.1 In addition, it should reach adequate concentrations in the tissues of the operative site, have the least potential for adverse side effects, have a half-life that permits single-dose injections, and not interact with other drugs given perioperatively.2

The Centers for Disease Control and Prevention (CDC) has provided recommendations in regard to the administration of prophylactic antibiotics. The CDC recommendations are based on a thorough review of the literature and are categorized based on the level of evidence to support them. These recommendations are outlined in Tables 14.1 and 14.2 .3 The CDC recommends that a prophylactic antibiotic be administered intravenously at the appropriate time before an incision is made such that the bactericidal concentration of the drug has been established when the incision is made.3 Prophylactic antibiotics should not be extended significantly into the postoperative period.

The administration of prophylactic antibiotics is not without risks. Before administration, the clinical history should be examined to prevent the administration of antibiotics to which the patient may have an allergic reaction. Other risks associated with antibiotic use include thrombophlebitis and the suppression of natural flora, which can lead to urinary or gastrointestinal infections.4 Allergic reactions to penicillin derivatives are quite common. Cephalosporins cause fewer allergic reactions; however, they demonstrate cross reactivity in roughly 10% of patients with penicillin allergy.2 In addition, prophylactic antibiotics have been found to be associated with the risk for developing Clostridium difficile colitis, although C. difficile colonization is more commonly associated with prolonged antibiotic treatment.5,6

Antibiotics for surgical prophylaxis should be chosen to have as narrow a spectrum as possible while still covering relevant pathogens. The widespread use of broad-spectrum antibiotics leads to the development of resistant organisms.2 For example, the increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) is concerning.4 Antibiotics that are typically used to treat resistant organisms should not routinely be used for prophylaxis unless no alternative is available.2

Even with the use of prophylactic antibiotics, infections are not completely preventable. Inherent factors may exist that increase the risk for developing a postoperative infection, such as malnutrition, immunosuppression, diabetes mellitus, and steroid use. Intraoperative conditions that increase the risk for infection include longer duration of the operation, placement of drains in the wound, blood transfusions, cerebrospinal fluid (CSF) fistulas, and tissue injury.2

Clinical Data Regarding Systemic Antimicrobial Prophylaxis in Neurosurgical Procedures Neurosurgical Issues

The incidence of infection after clean neurosurgical procedures ranges from 1 to 3%.1 Although the incidence of infection is low, such infections carry the risk for potentially devastating complications in neurosurgical procedures. Currently, prophylactic antibiotics in clean neurosurgical procedures are used routinely and have become the standard of care.7 Randomized controlled trials have demonstrated that the use of prophylactic antibiotics reduces the incidence of surgical site infections. Randomized studies from the 1970s, 1980s, and early 1990s have concluded that systemic antibiotic prophylaxis is effective at reducing the infection rate in clean neurosurgical procedures.8–16

In 1994, Barker conducted a meta-analysis of randomized studies published prior to 1992, comparing antibiotics with placebo in clean neurosurgical procedures.17 Pooled data from eight eligible randomized studies showed 19 infections in 1,014 craniotomies with prophylactic antibiotics and 93 infections in 1,061 craniotomies without prophylactic antibiotics. The difference was statistically significant, and the author estimated that the odds of infection without the use of antibiotics are 4.2 times higher than the odds of infection with the use of antibiotic prophylaxis. Over all, the estimated incidence of infection was 2% with antibiotics and 8% without antibiotics (p < 0.001).17 These results confirmed that systemic antibiotic prophylaxis is effective in reducing the infection rate after clean neurosurgical procedures. After the establishment that systemic antibiotic prophylaxis is superior to placebo, subsequent trials have focused on comparing different antibiotic regimens.

When the blood–CSF barrier is intact, the cephalosporins commonly used for prophylaxis in neurosurgical procedures do not penetrate the CSF.18–20 In 1979, Friedrich et al demonstrated that cephacetril, a first-generation cephalosporin, is not detectable in the CSF when the blood–CSF barrier is intact.19 Similarly, Knoop et al demonstrated that cefotiam, a second-generation cephalosporin, does not penetrate the CSF during surgery.20 On the other hand, cephalosporins do demonstrate good penetration of the CSF when the blood–brain barrier is disrupted, as in the case of meningeal inflammation. For example, Cherubin et al in 1989 and Cadoz et al in 1981 described the excellent penetration of ceftriaxone into the CSF and the quick clearance of bacteria in children with meningitis.21,22 Case series and randomized controlled trials have shown that ceftriaxone used as prophylaxis in neurosurgical procedures is effective at reducing surgical site infections.14,23,24

Even though cephalosporins do not effectively penetrate the CSF in the absence of meningeal inflammation, they are able to reach effective concentrations in the tissue to prevent surgical site infections.25 However, after a neurosurgical procedure, damage may occur to the blood–brain barrier that enables the CSF penetration of antibiotics.26,27 Other prophylactic systemic antibiotic regimens that have been used in neurosurgical procedures include piperacillin, vancomycin, vancomycin with gentamicin, cloxacillin, and oxacillin.9–12,14–16,28

At present, no regimen has been shown to be superior to others in terms of reducing the infection rate. The attempt to demonstrate different degrees of effectiveness for different antibiotics is constrained by the sample sizes required for definitive studies. When the clean neurosurgical procedure infection rate with the use of antibiotic prophylaxis approximates 1%, trials with an 80% chance of demonstrating an infection rate decrease to 0.5% need to have approximately 2,000 patients. Decisions regarding the appropriate prophylactic antibiotic to administer will depend on local microorganism sensitivity profiles and external factors, such as cost.

In 2001, Zhu et al conducted a prospective randomized trial comparing the use of prophylactic ceftriaxone and ampicillinsulbactam in clean neurosurgical operations. Surgical site infections occurred in 3.3% of patients in the ceftriaxone group and 2.3% of patients in the ampicillinsulbactam group. There was no statistically significant difference in the infection rates.1 However, because the trial was not designed as an equivalence trial, the absence of a significant difference must be interpreted with caution. We cannot reliably conclude whether differences actually exist in various antibiotic regimens unless such trials are designed as equivalence trials or unless they are adequately powered to detect differences in infection rates.

Similarly, Whitby et al29 compared infection rates in neurosurgical procedures that used either cefotaxime or trimethoprimsulfamethoxazole as systemic antibiotic prophylaxis. The infection rate in the cefotaxime group was 2.5%, and the infection rate was 2.3% in the trimethoprim-sulfamethoxazole group. The authors concluded that both regimens are equally effective at controlling neurosurgical infection rates.29 The sample size was calculated to achieve a power of 0.8 or greater, assuming an infection rate of 4% in the absence of prophylaxis and a reduction in the rate to 2% with prophylaxis.

The neurosurgical literature discussing the use of prophylactic antibiotics in clean–contaminated procedures is limited. Clean–contaminated procedures are defined by entry into the respiratory, gastrointestinal, or genitourinary tract under controlled conditions. This circumstance is encountered during transnasal trans-sphenoidal approaches, transoral approaches, or other complex cranial base approaches. The general surgery literature has demonstrated the beneficial role of prophylactic antibiotics in this group, such as in cases in which the bowel or biliary tract is entered.30,31

Dirty and contaminated wounds are frequently encountered in the trauma setting. The use of antibiotics in this situation is of therapeutic value and no longer prophylactic. Factors such as the level of contamination, the patient′s immune status, violation of the dura mater, and the extent of débridement required will play a role in determining the administration of antibiotics.

Timing and Duration of Prophylaxis

Early animal model experiments by Burke and by Miles et al established the importance of the timing of antibiotic administration in preventing incision infections.32,33 Burke established that systemic antibiotics have no effect on primary staphylococcal infections if the bacteria have been present in the tissue longer than 3 hours before the administration of antibiotics. In order for the antibiotic to suppress an infection, the antibiotic has to be present before the bacteria have time to gain access to the tissue.

With regard to the timing of the administration of prophylactic antibiotics, the antibiotic should be given at the appropriate time before the operation begins such that the bactericidal concentration of the drug has been established when the incision is made.3 The exact timing will depend on the pharmacokinetics of the drug. In general, prophylactic antibiotics are suggested to be given within 1 hour before the incision is made.2 A study by Galandiuk et al showed that the infection rate is higher in general surgery patients who receive prophylactic antibiotics more than 1 hour before the incision is made.34

Similarly, Classen et al35 showed that the timing of prophylactic antibiotic administration has an impact on the rate of developing an infection. They prospectively monitored the infection rate in 2,847 patients undergoing elective clean or clean–contaminated surgical procedures. The patients were divided into four groups according to the time of prophylactic antibiotic administration. The groups included patients who received antibiotics between 24 and 2 hours before incision time (early), within 2 hours before incision (preoperative), within 3 hours after incision (perioperative), and between 3 and 24 hours after incision (postoperative). The patients who received the antibiotic within 2 hours before incision had the lowest infection rate (0.6%), which suggested that appropriate timing of administration should fall within this window.

In terms of the duration of prophylactic antibiotic, there is no evidence to support multiple-dose versus single-dose administration. No neurosurgical trials exist on this topic, although it has been examined in the surgery literature. DiPiro et al have reported on eight studies that compared a single-dose prophylactic regimen versus multiple-dose regimens of the same drug. In all of these studies, no difference in the infection rates was witnessed.36 Such results fit with pioneering experimental animal data, which showed that antimicrobials administered as soon as within 3 hours after bacterial contamination of the wound do not influence the size of the skin lesion measured at 24 hours.32,33,36

Similarly, in a prospective randomized trial by Nooyen et al, no statistically significant difference in infection rates was seen in patients undergoing coronary artery bypass grafting who were randomized to receive either a single dose of cefuroxime at the induction of anesthesia or the same dose for an additional 3 days consecutively.37 A total of 844 patients were randomized, and the sternal site infection rate was 14% in the single-dose group compared with 13% in the 3-day-course group.

These trials demonstrate that there is no significant benefit to extending the administration of prophylactic antibiotics. Given the risks and complications that can occur with antibiotic administration, without any definitive evidence for extended use, such a practice is not recommended. However, antibiotics may need to be redosed in lengthy operations and in cases in which there is significant blood loss.2

Antimicrobial Prophylaxis in Special Circumstances

Related posts:

Postoperative Intracranial Infections Implanted Devices and Central Nervous System Infection Postoperative Intracranial Infections Implanted Devices and Central Nervous System Infection Radiology of Central Nervous System Infections Parasitic Infections of the Central Nervous System

Stay updated, free articles. Join our Telegram channel

Join