Effect of antibiotic prophylaxis in the prognosis of Post-neurosurgical meningitis patients

Post-neurosurgical meningitis (PNM) is a type of infection that commonly occurs in previously damaged or malformed areas of the brain, typically caused by bacterial contamination during or after neurosurgical procedures [1]. Treatment of PNM generally involves the use of antibiotics; however, the condition can be life-threatening and has a high mortality rate, with up to 30% of patients dying even with antibiotic treatment [2]. Therefore, effective prevention of PNM is crucial to reduce morbidity and mortality [3].

Antibiotic prophylaxis (AP) is a preventive measure used to decrease the incidence of bacterial infections after surgery, and it is an essential component of standard care in patients undergoing neurosurgical procedures [4]. AP has been shown to reduce the incidence of PNM to 10–20% [5‐7]. However, despite its widespread use, many challenges still exist in the application of AP, including the high rates of PNM, which can be as high as 3–15% even with the administration of antibiotics [8, 9]. Furthermore, it is unclear if the use of 3rd, 4th generation cephalosporins or carbapenem antibiotics can improve the survival rates of PNM patients, which highlights the need for further investigation.

In this study, we conducted a clinical cohort involving more than 1000 PNM patients, aiming to evaluate the role of AP in the prognosis of PNM patients and to identify any associated risk factors. To the best of our knowledge, this is the first global analysis specifically investigating the impact of AP on the prognosis of PNM patients.

Excessive use of antimicrobial agents has become an growing concern in public health [12]. In particular, after various surgical operations, AP plays a crucial role in infection control [13]. However, the overuse of antibiotics can lead to resistance, which hampers the effective treatment of bacterial infections. In this single-center cohort study conducted in China, we evaluated the microbiology and clinical epidemiology associated with PNM and identified risk factors for mortality in patients receiving AP.

This cohort study had a relatively large sample size, enrolling over 1000 cases. We observed that as many as 75% of patients received AP, while the proportion of PNM patients could reach 15% of all neurosurgical patients, irrespective of whether or not they were administered AP. Our study revealed that the use of AP significantly decreased the all-cause mortality of PNM patients at both the 42 days and 90 days follow-up periods. Interestingly, we did not observe improved patient outcomes when different types of antibiotics were used as prophylaxis. These results indicate that AP may not provide the intended benefits for neurosurgical patients with PNM. Additionaly, we identified independent mortality risk factors for PNM patients receiving AP, which included ICU admission and AMV. Increased attention should be paid to risk factors that may lead to mortality. To the best of our knowledge, this is the largest cohort study to explore the potential benefit of AP for PNM patients in the world. Our pragmatic and detailed clinical cohort design facilitated an investigation into the impact of prophylaxis independent of other factors that may lead to mortality. This study provides valuable insights that can inform the optimization of infection control strategies in neurosurgical practice.

PNM is a significant complication of neurosurgery that may have a detrimental effect on patient outcomes [14]. The administration of antibiotics stands as a pivotal measure in mitigating patient mortality. In clinical practice, preventive and therapeutic approaches are available to improve the outcomes of PNM patients [15]. Therapeutic options encompass the utilization of antibiotics, anti-inflammatory steroids, and open wound management, among others [16, 17]. Nonetheless, patients afflicted with PNM may experience significantly longer hospitalization periods and heightened expenses compared to neurosurgery patients without meningitis, and their survival rates may be significantly lower. Therefore, prevention, besides AP, plays a crucial role in the clinical management of PNM.

The selection of antibiotics is primarily contingent upon the type of microorganism responsible for PNM. Our study findings demonstrate that the responsible microorganisms for PNM are common nosocomial pathogens [18]. Nevertheless, the role of CoNS in PNM remains enigmatic. Throughout the study's duration, CoNS constituted over half of the positive pathogen cultures. While prior research has suggested that CoNS can indeed induce PNM [19], particularly in cases involving meningitis related to ventricular peritoneal shunts [20], our own prior investigation revealed that 79% of CoNS isolates were classified as contaminants [21]. Hence, in this present study, CoNS was deliberately excluded from the cohort analysis. In the rest of cases, no significant disparities exist between the top two pathogens among patients who received or did not receive AP. However, there were significant differences in the isolation rates of the top three Gram-positive bacteria, mainly Staphylococcus aureus, which had a significantly lower proportion in the AP group than in the non-AP group. Probably reason target to this issue may be the choice of AP. Cephalosporins, such as cefuroxime and ceftriaxone, accounted for 87.1% of the whole antibiotic usage. Both of these antibiotics possess notable efficacy against Staphylococcus aureus,except the Methicillin-resistant Staphylococcus aureus [22]. However, neither had a high sensitivity rate to Enterococcus faecalis, and as we all know, antibiotics combination is the most preferred choice in Enterococcus infections [23]. Our findings suggest that AP has a greater impact on patients infected with Staphylococcus aureus, and the antibiotics used in AP are more effective against this Staphylococcus aureus than against Enterococcus spp.

Previous studies have predominantly concentrated on the reduction of infection incidence with AP. Despite guidelines advocating for the administration of antibiotics prior to neurosurgery, their impact on patient prognosis has not been reported [24, 25]. Our study reveals that AP patients exhibit significantly lower all-cause mortality rates at 42 and 90 days compared to Non-AP patients, indicating a positive effect on patient outcomes. While the optimal antimicrobial regimen for preventing PNM during the perioperative period remains uncertain, guidelines propose using a single β-lactam antibiotic for most surgical procedures [4]. Our findings align with this recommendation; however, the guidelines do not stipulate the specific antibiotic type to employ. Antibiotic management proposes utilizing different levels of antibiotics with varying application strategies in clinical practice.

With the escalation of antibiotic categorization, the emergence of antibiotic-resistant bacteria becomes increasingly evident in clinical settings.. We classified patients based on their use of high-level or low-level antibiotics and found no differences in survival indicators such as survival time, treatment costs, and the length of hospital stay. This investigation underscores that the utilization of high-grade antibiotics failed to yield enhanced patient outcomes and, conversely, could heighten the susceptibility to unfavorable reactions due to their robust bactericidal impacts. Literature reports suggest that the use of high-level antibiotics can easily lead to the emergence of drug-resistant bacteria, and vancomycin, in particular, is known to have significant adverse effects [26‐28]. Additionally, the two primary antibiotics used in our study, ceftriaxone (a high grade antibiotic) and cefuroxime (a low grade antibiotic), have differing effects on Gram-negative bacteria. Third generation cephalosposin is always effective against Gram-negative bacteria but may induce bacterial resistance (e.g., by producing AmpC) [29], while cefuroxime does not have this effect or possess slighter side effects, and even much cheaper. Therefore, we recommend that cefuroxime should be the preferred antibiotic for prophylaxis as it may offer equal or better benefits to patients.

Mitigating patient mortality and enhancing prognosis in the context of PNM represents a pivotal research objective. In addition to AP, other factors that impact patient outcomes should not be overlooked, such as AMV and EVD. Thorough scrutiny of risk factors across all patients subjected to AP can serve to attenuate patient mortality during the initial phases. In our previous studies, a series of risk factors about to PNM have been evaluated, such as GCS scores [11], EVD [30], AMV[10], craniotomy and malignancy [9] and so on. This study evaluated two mortality risk factors, ICU admission and AMV. Both factors are known to have poor prognoses due to the severity of the underlying disease, making patients more susceptible to infection and leads to poor outcome.

In this investigation, we scrutinized two distinct treatment modalities for patients diagnosed with PNM. The initial approach involved AET, predominantly due to the delay in receiving antibiotic susceptibility test results. Consequently, a broad-spectrum antibiotic regimen was administered to ensure comprehensive coverage and mitigate any potential adverse consequences. Our findings revealed that the most frequently prescribed empirical antibiotic combination was Meropenem + Vancomycin, which may be associated with the severity of PNM and its higher propensity for unfavorable prognosis. The second approach entailed ADT, guided by the findings of antibiotic susceptibility testing. Similar to AET, the Meropenem + Vancomycin combination remained the predominant choice. This preference can be attributed to the widely accepted and efficacious nature of the Meropenem + Vancomycin clinical regimen for combating PNM. Additionally, a slightly lower proportion of patients received ADT compared to AET. This variation could be explained by the longer cultivation period (3–5 days) required for pathogen identification, allowing some PNM patients to recover within the timeframe of AET.

Insufficient investigation has been conducted regarding AP in the context of PNM. Firstly, single-center studies possess inherent limitations, and even with a sample size of over 1000 cases, single-center studies are less reliable than multi-center studies in terms of overall credibility. Secondly, the primary diseases causing PNM were not classified in detail, and only neurosurgical operations were analyzed as a category of disease. Lastly, the antibiotics used for AP at our center were limited, so we were only able to group them according to high level and low level antibiotics, which had certain limitations.

In summary, AP emerges as a pivotal determinant in the prognosis of PNM patients, exhibiting the potential to markedly enhance outcomes. Variations in antibiotic types exhibit negligible influence on patient mortality rates, thereby providing insights for antibiotic selection in clinical practice. Among all PNM patients receiving AP, ICU admission and AMV are independent risk factors for patient death, highlighting the need for vigilance in managing these factors by clinicians.