Our retrospective study, which assessed the difference of the drug intensity and functional outcome of patients with CNS infection between groups performed with or without mNGS tests, identified a better prognosis and lower intensity of medication in patients who underwent mNGS tests. The improvement of medication intensity and prognosis due to the application of mNGS was significant in individuals with worse consciousness on admission or in people with CNS bacterial infection.
CNS infection is a life-threatening disease responsible for severe disability or death. CNS infections may depend on the therapeutic resources, including timely access to anti-infection therapy, appropriate antibiotic or antiviral drugs usage(5, 7, 16, 17). Several studies reported the superiority of mNGS for diagnosing pathogens in infectious diseases, comparing to conventional methods. Our data confirmed the high sensitivity and specificity of mNGS in the detection of pathogens, which were consistent with previous studies of mNGS (7, 18-20), as we found the sensitivity of the mNGS reached 91.67% compared to culture, and the specificity was 88.24% in contrast of final diagnosis. In addition, the extra-detection rate of mNGS was as high as 39.8% compared to culture. This study also revealed that mNGS was of excellent application value in the diagnosis of CNS infections.
Moreover, previous studies have confirmed the guidance role of mNGS in clinical treatment, as Hu et al. declared a considerable modification of infection diagnoses based on mNGS (21). Besides, another research showed that, among patients with suspected infection undergoing immunosuppressive corticosteroid therapy, mNGS played a role in optimizing antibiotic regimes (22). However, these studies have failed to locate the study population on CNS infections accurately but have generally explored the role of mNGS in guiding clinicians to use drugs. Our study has uniquely evaluated the intensity of drug usage and its adjustment due to mNGS tests among patients with CNS infections. We revealed a difference in the intensity of anti-infection drugs used between participants performed with mNGS and those who did not, which confirmed that the application of mNGS could effectively reduce the medication intensity. We further evaluated the patients without co-infection and compared with the TraE Group; the CDI and DDI value of the mNGS Group still showed a noticeable reduction. As we excluded the confounding factors of co-infection, the benefit of mNGS on reducing drug intensity was further confirmed.
We also found that the application of mNGS might have a more significant impact on patients with bacterial CNS infection. As the data showed that in the bacterial and fungal infection subgroups, the CDI value of the mNGS Group was lower than that of the TraE Group, while the patients performed with mNGS tests in the viral and bacterial infection subgroups had lower DDI values. The reasons are as follows: Firstly, In the treatment of bacterial infections, the de-escalation of broad-spectrum antibiotics might bring more remarkable changes to the intensity of medication. Secondly, the clinical manifestations were typical; thus, the clinician's empirical judgments were more accurate; therefore, the intensity of medication showed less fluctuation. Thirdly, we generally did not diagnose patients as fungal infections when there was no etiological evidence. Most of them were performed with antibiotics empirically. The clinician might change the medication to fungal drugs after obtaining the mNGS reports; therefore, the intensity of the drug tended to increase.
Moreover, the people with the worst (Grade 3) and mildest (Grade1) neurological function seemed to be more likely to benefit from the mNGS examination, that was, reducing the length of hospitalization and drug use. It was possibly due to the reduction of medication and unnecessary hospitalizations based on the mNGS reports among patients with the mildest symptoms and patients in severe condition acquired optimized and targeted medications regimes, which speeded up the recovery of patients and reduced unnecessary medications. Therefore, we could draw to a conclusion that, for critical patients with CNS infection, the application of mNGS may be more valuable and instructive in diagnosis and treatment.
In total, we reported 49% of altered medication and 24.7% of decreased drug usage, reflecting the potential value of mNGS in guiding the clinical medication plan and benefiting the precise use of antibiotics. We further analyzed the reasons for decreased drug intensity, and the reduction of drugs counted for the most, counting 57.14%. It can be easily explained that the patients might be treated with multiple drugs simultaneously on admission due to the unclear etiology diagnosis. However, later, the clinician could identify the target pathogen with mNGS tests and exclude previously suspected pathogen, therefore reduced the types of drugs. Moreover, there were other reasons for the decrease of drug intensity such as drug adjustment, drug downgrade, and reduction of drug dose, since, with the report of mNGS, clinicians might find the pathogenic type targeted by the empirical medication was different from the actual type of infection, then the type of medication was changed. Furthermore, narrow-spectrum anti-infection drugs might be used precisely according to the target pathogen reported by mNGS. The previous study of Filmarray meningitis/encephalitis Panel has shown that it could, to some extent, improve the antibiotic regimens on CNS infection patients (10, 23, 24); however, the research focused on the bacterial meningitis patients, without an overall population of CNS infected patients restricted by the limited scope of its pathogen examination and the study design itself.
We used the mRS to assess the patient's self-care ability and neurological impairment at the time of discharge. We found that the patients' probability of being included in the poor prognosis (Level 3) would decrease from 26.5–17.3% result of mNGS application, showing the ability of mNGS in improving the results of patients with CNS infections. The conclusion could be reached that the application of mNGS in CNS-infected populations improved patients' prognosis and optimized the drug intensity of patients during hospitalization. The previous study reported a better improvement rate among patients who adjusted medication according to mNGS than those performed with medication empirically (22). We speculate that the mNGS’ rapid, accurate, and broad pathogen detection characteristics precisely identified pathogens types, thus accelerating the workup and treatment. Besides, CNS infection is a severe and dangerous infectious disease, demanding timely therapy, while CSF culture has difficulty giving timely feedback due to its low positive rate and time-consuming characteristics. Therefore, the application of the mNGS test would promote the implementation of the optimal treatment, thus leading to rapid remission of the disease and a better prognosis.
Our study has several strengths, as our retrospective research analyzed a group of patients with high homogeneity of the CNS infection, ensuring that the same group of doctors made their medication plan, thus reflecting the changes in medication usage and prognosis accurately under the influence of mNGS. Our study also has limitations inherent to its retrospective design. The relatively small sample size of parasite CNS infections and unclassified ones in our study, and therefore we could not yet conclude the value of clinical medication guidance of mNGS in these groups. In addition, the results of mNGS may be interfered with by many factors, thus in the future, a larger sample size, multi-center, and prospective study are needed to verify the application value of mNGS in CNS infections.