As early as the 1980s and 1990s, some scholars suggested that the preventive application of antibacterial drugs in elective surgery is not a protective factor, and the indiscriminate use will promote the emergence of multi-drug resistant bacteria . Subsequently, some randomized controlled studies were published. Based on these data, some meta-analysis demonstrated that prophylactic antibiotics can significantly reduce the incidence of postoperative ICIs in the brain, 8.80% reduced to 1.90% [7, 23]. Therefore, prophylactic antibiotics have become the strategies adopted by most doctors to prevent postoperative infections.
How to provide targeted prevention measures for ICIs after craniotomy is increasingly valued by neurosurgical staff and infection preventionists. However, types of antibacterial drugs used and the mode of administration in the published researches were numerous , and the relative effects of the multiple antibacterial drugs were not analyzed.
To our knowledge, this study is the first ITC analysis provides the most recent and comprehensive analysis of the effectiveness of different antibiotic prophylaxis for the prevention of ICIs after craniotomy. More than 3000 patients were enrolled from 11 studies. Analogous to previous meta-analyses, our findings indicate that prophylactic use of intravenous antibiotics to decrease the incidence of ICIs after craniotomy. The results showed that, except fusidic acid, preoperative intravenous injection of cephalosporin, clindamycin, vancomycin, and penicillin can significantly reduce the incidence of ICIs after craniotomy, there was no statistically significance difference between four antibiotics in the indirect comparison.
Oral fusidic acid is an antibacterial agent used for the treatment of staphylococci infections in the skin and soft tissue. In step 1, pairwise meta-analysis, findings found that intravenous fusidic acid was associated with increased odds of surgical site infections compared with other antibiotics. In addition, some studies suggest that not through intravenous injection fusidic acid, in order to avoid thrombophlebitis even subcutaneous tissue necrosis, may also lead to reversible jaundice . Based on this, we do not recommend intravenous fusidic acid for prophylactic use.
By ITC, with regard to efficacy, clindamycin ranked first. After clindamycin enters the patient through an intravenous drip, the plasma concentration is quite high, and it is prevalent among the patient. It can reach an effective antibacterial level in most tissues and body fluids in a short time . Not only can it produce relatively strong antibacterial activity against common gram-positive bacteria , but it can also be effective against anaerobic bacteria, so it effectively reduces the number of intracranial infection after craniotomy. And the drug is mainly metabolism by the liver of the human body after administration, and excreted through the bile and feces, and a part can be excreted through the urine. After the drug is utilized, it will not result in adverse effects on the liver and kidney function of the patient, so clindamycin is safe. In addition, clindamycin is cheap, cost-effective in pharmacoeconomic evaluation . Considering its safety, good pharmacokinetics and acceptable price, clindamycin has been the first choice for prophylactic antibiotics for preoperative brain surgery.
Cephalosporins include: cefazolin, cefazedone and cefotiam, both first and second generation cephalosporins, mainly used to treat skin infections caused by Gram-positive cocci and streptococci. These bacteria are considered to be the main pathogens causing SSI due to improper skin disinfection in the preoperative surgical site . Cephalosporins can be used as pre-operative preventive medications for most cleansing or cleaning-contamination procedures, but not as the first choice for intravenous prophylaxis.
With the emergence of MRSA, the use of vancomycin has increased rapidly. Although some people think that prophylactic use of vancomycin is more broad-spectrum antibiotics or combined with multiple antibiotics will reduce the production of drug-resistant bacteria, but with the widespread use of vancomycin, the infection rate of vancomycin-resistant enterococci is also increasing . Since widespread use of vancomycin increases the chance of vancomycin-resistant cocci infection, prophylactic vancomycin is now only used in patients who are allergic to penicillin or cephalosporin or have a history of MRSA infection . Therefore, this study recommends a single IVA for elective type I clean surgical incision craniotomy, in principle no more than 24 h, with risk factors can be extended to 48 h, should use broad-spectrum anti-emergence, can pass the normal blood-brain barrier, necessary When referring to the in-hospital strain spectrum, select more sensitive drugs.
The results of this ITC should be interpreted with the consideration of several limitations. First, due to the limited data, inconsistency analysis could not be conducted. Nevertheless, the heterogeneity of the included studies was determined through pairwise and sensitivity analyses to comply with the assumption of indirect comparison. In addition, we included five intravenous interventions and no prophylactic antibiotic (placebo), the number of studies included in the analysis was relatively small, we could not make head-to-head comparisons in this study based on the limited sample size. Evidence is scant, mostly indirect and do not have any direct comparisons between different antibiotics. We found that clindamycin is the most effective antibiotic against ICIs after craniotomy based on the ITC, these indirectly driven comparison on the strength of direct evidence provided by clinical trials, ranking of drug effectiveness are making inferences about a causal claim. This makes it necessary to consider the actual situation of patients when using the results of this study as an evidence. Second, our meta-analysis relied on study-level and not patient-level data. From the perspective of the quality of the included studies, although there are six studies that refer to the random allocation method using the random number table method; However, many studies do not mention the blinding of participants and personnel (performance bias) and blinding of outcome assessment (detection bias), and no intentional analysis is performed, thus affecting the results and its conclusion strength. Owing to these problems, the extrapolation of the results of this study is restricted to a certain extent.
Research on the selection of preventive antibiotics for craniotomy will continue, but it has been acknowledged that the widespread use of antibacterials can cause severe drug resistance and begin to develop strict antibiotic use strategies. This study might provide new insights of prophylaxis choices against the ICIs after craniotomy whilst awaiting the arrival of higher quality evidence. Large-scale, multi-center, high-level research evidence is urgently needed to guide the application of prophylactic antibiotics for craniotomy to ensure the clinical safety of patients and improve the severe bacterial resistance.