| BackgroundCommon neurosurgical diseases such as severe craniocerebral injury,spontaneous intracerebral hemorrhage,aneurysmal arachnoid hemorrhage,acute ischemic stroke,cerebral arteriovenous malformation and other serious conditions often require neurosurgical intervention and long-term intensive care unit（ICU）treatment.In addition to craniocerebral operation and long-term ICU treatment,blood-brain barrier disruption,bedside invasive operation,indwelling external drainage tube and other factors greatly increase the risk of central nervous system infection（CNSI）,which may lead to longer hospital stay,higher medical costs and more severe neurological dysfunction or even death,with the mortality rate as high as 15% ～ 30%.Early definitive diagnosis,identification of causative pathogens,and targeted selection of reasonable anti-infective drugs are key factors to improve the prognosis of patients with CNSI.At present,traditional cerebrospinal fluid culture is most commonly used in clinical practice as a method for CNSI pathogen identification.However,traditional cerebrospinal fluid culture cannot test viruses,parasites,etc.,with limited pathogen coverage,and is susceptible to interference by factors such as pathogen content,external environment,use of antibacterial drugs and pathogen death,resulting in low positive rate.At the same time,it also has the disadvantages of wasting long time,which cannot satisfy the clinical needs.Although other traditional detection methods such as immunological tests and molecular biology can quickly identify common CNSI pathogens,including viruses,the defect is still obvious due to the need for staff to make predictions under the premise of a priori cognition and the limited coverage of pathogens.Metagenomic second-generation sequencing（mNGS）technology uses the principle of shotgun sequencing to perform high-throughput sequencing of all DNA or RNA in all microorganisms in patient specimens,getting rid of the limitation of pure culture of microbial isolation.Without relying on a priori cognition,it only needs the nucleic acid extracted from a small amount of samples to determine the nucleic acid sequence of all microorganisms in the samples and identify pathogenic,colonizing,rare and unknown pathogens.Unlike the shortcomings of traditional detection methods,such as long time,limited pathogen coverage,low sensitivity,and many interfering factors,mNGS is compatible with the concept of "rapid and accurate diagnosis and treatment" while having high sensitivity.ObjectiveTo explore the pathogen detection ability,diagnostic efficacy,and clinical utility of mNGS in neurosurgery patients at perioperative period with central nervous system infection.MethodEighty patients with suspected CNSI during perioperative period admitted to the Neurosurgery Intensive Care Unit（NSICU）of Henan Provincial People’s Hospital from October 2019 to January 2022 were prospectively and consecutively included,and the collected cerebrospinal fluid samples were simultaneously subjected to mNGS and traditional cerebrospinal fluid culture;1.the pathogenic pathogens of CNSI patients were determined by three professionals in combination with mNGS detection report,cerebrospinal fluid culture results,patient clinical characteristics,and relevant auxiliary examinations to compare the pathogen detection ability of mNGS and traditional culture;2.the sensitivity,specificity,positive predictive value,negative predictive value and youden index number of mNGS and traditional culture were calculated and compared using the clinical diagnosis of CNSI as the "gold standard",while the diagnostic efficacy of mNGS and traditional culture was analyzed using receiver operating characteristic（ROC）curve;3.the time taken from obtaining cerebrospinal fluid samples to feedback the results to clinicians was compared by mNGS and traditional culture methods.To evaluate the performance of the two methods in terms of clinical timeliness;4.describe the anti-infective drug adjustment in patients with CNSI according to the mNGS detection report to guide the clinical practice and preliminarily assess the clinical application value of mNGS;5.to evaluate the clinical intervention performance of mNGS according to the three major indicators of "clinical recognition","clinical nonrecognition",and "unclear significance" and further assess the clinical application value of mNGS;6.the number of pathogen reads detected by mNGS in patients with confirmed CNSI was stratified to compare the length of NSICU stay,14-day mortality,and 90-day mortality between different groups of patients,in aim at analyzing the relationship between the number of pathogen sequences and the length of hospital stay and mortality of patients.Result1.A total of 80 patients with suspected CNSI were included,all of whom were empirically treated with antibiotics（100%）,and 41 cases were finally clinically diagnosed,including 25 cases of bacterial infection（8 Gram-positive bacteria and 17 Gram-negative bacteria）,6 cases of viral infection,3 cases of fungal infection,4 cases of mixed infection（1 bacterial + viral + fungal,2 bacterial + viral,and 1 fungal + viral）,and 3 cases of infection with unidentified pathogens.Of the 41 patients with CNSI,38 were positive by mNGS,and 29 different pathogens were successfully detected,including bacteria,viruses,and fungi;only 10 were positive by traditional culture,and 5 different pathogens were detected,all of which were gram-negative bacilli.Among all detected pathogens,gram-negative bacteria had the highest constituent ratio（41.46%）,all of which were gram-negative bacilli;followed by gram-positive bacteria（19.51%）,most of which were gram-positive cocci;virus constituent ratio was14.63%,of which the most common was human herpesvirus;fungi had the lowest constituent ratio of 7.32%,of which the most common was Candida albicans;besides,9.76% and 7.32% of patients had mixed infection and unknown pathogen infection.2.The sensitivity,specificity,positive predictive value,and negative predictive value of mNGS for detecting cerebrospinal fluid were 92.7%,92.3%,92.7%,and 31.1%,respectively;the sensitivity,specificity,positive predictive value,and negative predictive value of traditional cerebrospinal fluid culture were 24.4%,100.0%,95.1%,and 26.0%,respectively.The Youden indices of the two methods were 0.850 and 0.244,respectively.ROC curve analysis showed that the AUC of mNGS for the diagnosis of CNSI was 0.925（95% CI: 0.858 ～ 0.992,P < 0.001）;the AUC of traditional cerebrospinal fluid culture for the diagnosis of CNSI was 0.622（95% CI: 0.499 ～ 0.745,P = 0.061）.3.From the collection of cerebrospinal fluid samples for examination to the feedback of results to clinicians,the average time of mNGS detection feedback was（30.21 ± 5.40）h,and the average time of traditional culture was（107.14 ± 11.62）h.There was a significant statistical difference between the two groups（P<0.001）.In terms of detecting bacterial positivity,the average feedback time of mNGS detection results was（29.81 ± 5.65）h,and the average time of traditional culture was（98.36 ± 12.60）h,with a significant statistical difference between the two groups（P = 0.006）.4.Of the 41 patients with CNSI,the initial anti-infective regimen was adjusted in 25（60.98%）patients.Twenty-three patients（56.10%）were upgraded to the anti-infective regimen,of which 14 patients（34.15%）added one anti-infective drug,3 patients（7.32%）added two anti-infective drugs,and 6 patients（14.63%）replaced antibiotics;2 patients（4.88%）were downgraded to antibiotics,all of which were reduced by one antibiotic.5.Finally,the effect of mNGS intervention was evaluated as clinically recognized in a total of 69 cases,clinically disrecognized in a total of 6 cases,and unclear in 5 cases;the proportion of cases with positive effect of mNGS detection was 86.3%,and the proportion of cases with negative effect was 7.5%.6.Of the 41 patients with CNSI,the initial anti-infective regimen was adjusted in 25（60.98%）patients.Twenty-three patients（56.10%）were upgraded to the anti-infective regimen,of which 14 patients（34.15%）added one anti-infective drug,3 patients（7.32%）added two anti-infective drugs,and 6 patients（14.63%）replaced antibiotics;2 patients（4.88%）were downgraded to antibiotics,all of which were reduced by one antibiotic.ConclusionFor neurosurgical patients with CNSI during perioperative period,mNGS has good diagnostic efficacy and clinical application value,which can effectively make up for the lack of traditional cerebrospinal fluid culture,and is worthy of more extensive clinical application and more in-depth study. |
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