Post-neurosurgical Meningitis Research Articles

Clinical, microbiological profile and treatment response to intraventricular antibiotics in the Management of Post-Neurosurgical Meningitis: A single center experience.

Introduction Post-Neurosurgical Meningitis (PNM) is a serious medical condition with high mortality and morbidity caused by organisms like Staphylococcus aureus and Gram-negative organisms like Acinetobacter baumannii. Optimum concentration of antibiotics in the cerebrospinal fluid (CSF) to treat these infections are difficult to achieve. Intraventricular antibiotic administration bypasses the blood-brain barrier and can achieve high CSF concentration without causing systemic toxicity. Methods Retrospective review of all patient records were done to identify patients who developed post-neurosurgical meningitis and received intraventricular antibiotic therapy during the period of July 2017 to December 2022. Demographic and clinical data along with type of antibiotic, route, dose and duration of administration was collected. CSF parameters before and after intraventricular antibiotic administration were collected and analyzed. Results 26 patients with post-neurosurgical meningitis received intraventricular antibiotic therapy. Intracranial tumors were the most common underlying pathology followed by aneurysms. 17/26 patients had received vancomycin and 9/26 patients had received colistin. External ventricular drain was used in 17/26 cases and Ommaya reservoir was used in 9/26 cases. 6 cases showed growth of organism in CSF before starting intraventricular antibiotics, 1 case remained culture positive despite treatment. 3/26 patients died despite treatment. There were significant changes in the CSF parameters after intraventricular antibiotic therapy. Conclusion Intraventricular administration of antibiotic provides an alternative therapeutic option in the management of patients who are not responding or poorly responding to systemic antibiotics.

Clinical significance of cerebrospinal fluid presepsin as adjunctive biomarker for postneurosurgical meningitis: A single-center prospective observational study.

Postneurosurgical meningitis (PNM) is a serious complication in neurocritical care patients, leading to clinical deterioration and worsening outcomes. Accurate diagnosis of PNM is often difficult due to the lack of definitive diagnostic criteria. This study investigates the potential utility of cerebrospinal fluid (CSF) presepsin (PSP), blood PSP, and the CSF/blood PSP ratio as adjunctive biomarkers for the diagnosis of PNM. We conducted a single-center prospective observational study at Nara Prefecture General Medical Center in Nara, Japan, from April 2020 to March 2022. The postoperative neurosurgical patients with suspected PNM were included in the study and divided into PNM and non-PNM groups. We evaluated the sensitivity, specificity, area under curves (AUCs), positive predictive value (PPV), and negative predictive value (NPV) for the diagnosis of PNM with CSF PSP, blood PSP, and CSF/blood PSP ratio compared in the two groups. We screened 241 consecutive patients with postoperative neurosurgery. Diagnosis of PNM was suspected in 27 patients, and the clinical diagnosis was confirmed in nine patients. The results of CSF PSP (cutoff: 736 pg/mL) for the diagnosis of PNM were sensitivity 89%, specificity 78%, PPV 67%, NPV 93%, AUC 0.81 (95% confidence interval [CI], 0.60-1.00), blood PSP (cut-off: 264 pg/mL) was 56%, 78%, 56%, and 78%, 0.65 (95% CI, 0.42-0.88), and those of CSF/blood PSP ratio (cutoff: 3.45) was 89%, 67%, 57%, and 92%, 0.83 (95% CI, 0.65-1.00). Elevated CSF PSP and CSF/blood PSP ratio may be associated with PNM and could serve as valuable adjunctive biomarkers for improving diagnostic accuracy.

Diagnostic and Monitoring Value of β-2 Transferrin and Transferrin for Intracranial Infection After Neurosurgery.

After neurosurgery, intracranial infection is a common complication with high rates of clinical impairment and death. Traditional diagnostic approaches are time-consuming. Early and correct diagnosis improves infection control, treatment success, and survival. Novel markers are used to diagnose and classify post-neurosurgical meningitis (PNM) to overcome the difficulties of diagnosing postoperative intracranial infections and avoid the drawbacks of existing diagnostic measures. The objective was to investigate the diagnostic value of β-2 transferrin (β-2TF) and transferrin (TF) in the cerebrospinal fluid (CSF) for the identification of intracranial infection after neurosurgery. Owing to their symptoms and laboratory results, 168 patients with suspected intracranial infection after neurosurgery were divided into 3 groups: post-neurosurgical bacterial meningitis (PNBM; n = 61), post-neurosurgical aseptic meningitis (PNAM; n = 45), and non-PNM (n = 62). We measured lactate (LA), β-2TF, and TF levels in the CSF. CSF LA levels were significantly higher in the PNM, PNBM, and PNAM groups compared with the non-PNM group ( P < .05). The CSF β-2TF level in PNM, PNBM, and PNAM were statistically higher than those in non-PNMs ( P < .05). CSF TF levels in the PNBM group were statistically higher than those in the PNAM and non-PNM groups ( P < .05). The PNBM and non-PNM receiver operating curve (ROC) analysis indicates that the cutoff values for the combination (LA, β-2TF, TF) was 0.349, and the area under the curve (AUC) was 0.945 ( P < .0001), with 92.86% sensitivity and 92.98% specificity. The PNAM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, β-2TF, TF) was 0.346, and the AUC was 0.962 ( P < .0001), with 89.29% sensitivity and 90.24% specificity. The PNM and non-PNM ROC analysis indicates that the cutoff values for the combination (LA, β-2TF, TF) was 0.609, and the AUC was 0.941 ( P < .0001), with 96.36% sensitivity and 82.83% specificity. A Glasgow Coma Scale score ≤8, LA, β-2TF/TF ratio, length of hospital stay, intensive care unit admission, poor surgical wound, and craniotomy were associated with poor outcomes ( P < .05). LA and β-2TF were independent risk factors for intracranial infection. Postoperative cerebral infections can be identified using CSF β-2TF as a particular marker protein. CSF TF helps distinguish PNBM from PNAM. Combining CSF LA with them improves diagnostic speed, sensitivity, and accuracy. LA and β-2TF were independent risk factors for cerebral infection.

The value of elevated cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis

Bacterial meningitis is a serious complication after neurosurgery and has a high mortality rate. Early diagnosis and timely treatment are crucial or will have disastrous consequences. The classic triad of bacterial meningitis lacks sensitivity and specificity. Therefore, the diagnosis of post-neurosurgical bacterial meningitis relies on cerebrospinal fluid. But traditional cerebrospinal fluid parameters are not completely reliable in diagnosing post-neurosurgical bacterial meningitis. Previous studies have found that CSF lactate concentration is related to bacterial meningitis. But, after the craniocerebral operation, the cerebrospinal fluid of most patients is bloody. Whether red blood cells interfere with diagnosing PNBM based on lactate concentration is limited. In the current study, we further analysis on whether red blood cells interfere with diagnosing PNBM based on lactate concentration. This study aimed to investigate the value of cerebrospinal fluid lactate concentrations in post-neurosurgical bacterial meningitis. A prospective observational study was performed on 62 patients at Kunshan First People’s Hospital’s intensive care unit affiliated with Jiangsu University. We found that erythrocytes do not affect cerebrospinal fluid lactate, and elevated lactate concentrations can be used as a marker for postoperative bacterial meningitis.

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

AimsTo evaluate the effect of antibiotic prophylaxis(AP) in the prognosis of Post-neurosurgical meningitis(PNM) patients.MethodsA cohort analysis was performed using the clinical database in Beijing Tiantan Hospital and Capital Medical University. Data were collected on patients with the diagnosis of PNM (n = 3931) during 2012.01 to 2022.04. The microbial distribution, types of AP, and 42 and 90 days survival analysis of AP patients were evaluated using probable statistical methods. Independent risk factors for mortality were established by constructing a logistic regression analysis.ResultA total of 1,190 patients were included in this study, Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus occupied the highest proportion. Of them, 929 cases received AP, cefuroxime and ceftriaxone are the most frequent used antibiotics. In addition, We found that PNM patients without AP significantly increased the 42 days and 90 days all-cause mortality rates. The use of different levels of AP did not improve patient outcomes, and ICU admission and assisted mechanical ventilation (AMV) were identified as independent mortality risk factors for PNM patient received AP.ConclusionsAP plays an important role in the prognosis of PNM patients and has a significant function in improving prognosis. The prevention of PNM with antibiotics prior to neurosurgery should be emphasized in clinical practice, and appropriate selection of antibiotics is necessary to prevent the occurrence of infection and inhibit the emergence of antibiotic-resistant bacteria.

Empirical cefepime+vancomycin versus ceftazidime+vancomycin versus meropenem+vancomycin in the treatment of healthcare-associated meningitis: results of the multicenter Ephesus study

BackgroundHerein, we analyzed the efficacy of main antibiotic therapy regimens in the treatment of healthcare-associated meningitis (HCAM).Materials/methodsThis retrospective cohort study was conducted in 18 tertiary-care academic hospitals Turkey, India, Egypt and Romania. We extracted data and outcomes of all patients with post-neurosurgical meningitis cases fulfilling the study inclusion criteria and treated with empirical therapy between December 2006-September 2018.ResultsTwenty patients in the cefepime + vancomycin-(CV) group, 31 patients in the ceftazidime + vancomycin-(CFV) group, and 119 patients in the meropenem + vancomycin-(MV) group met the inclusion criteria. The MV subgroup had a significantly higher mean Glasgow Coma Score, a higher rate of admission to the intensive care unit within the previous month, and a higher rate of antibiot herapy within the previous month before the meningitis episode (p < 0.05). Microbiological success on Day 3–5, end of treatment (EOT) clinical success (80% vs. 54.8%% vs 57.9%), and overall success (EOT success followed by one-month survival without relapse or reinfection 65% vs. 51.6% vs. 45.3%), EOT all cause mortality (ACM) and day 30 ACM (15% vs. 22.6% vs. 26%) did not differ significantly (p > 0.05) among the three cohorts. No regimen was effective against carbapenem-resistant bacteria, and vancomycin resulted in an EOT clinical success rate of 60.6% in the methicillin-resistant staphylococci or ampicillin-resistant enterococci subgroup (n = 34).ConclusionsOur study showed no significant difference in terms of clinical success and mortality among the three treatment options. All regimens were ineffective against carbapenem-resistant bacteria. Vancomycin was unsuccessful in approximately 40% of cases involving methicillin-resistant staphylococci or ampicillin-resistant enterococci.

Diagnosis of post-neurosurgical bacterial meningitis in patients with aneurysmal subarachnoid hemorrhage based on the immunity-related proteomics signature of the cerebrospinal fluid.

Post-neurosurgical bacterial meningitis (PNBM) is a serious complication for patients who receive neurosurgical treatment, but the diagnosis is difficult given the complicated microenvironment orchestrated by sterile brain injury and pathogenic infection. In this study, we explored potential diagnostic biomarkers and immunological features using a proteomics platform. A total of 31 patients with aneurysmal subarachnoid hemorrhage (aSAH) who received neurosurgical treatment were recruited for this study. Among them, 15 were diagnosed with PNBM. The remaining 16 patients were categorized into the non-PNBM group. Proteomics analysis of the cerebrospinal fluid (CSF) was conducted on the Olink platform, which contained 92 immunity-related molecules. We found that the expressions of 27 CSF proteins were significantly different between the PNBM and non-PNBM groups. Of those 27 proteins, 15 proteins were upregulated and 12 were downregulated in the CSF of the PNBM group. The receiver operating characteristic curve analysis indicated that three proteins (pleiotrophin, CD27, and angiopoietin 1) had high diagnostic accuracy for PNBM. Furthermore, we also performed bioinformatics analysis to explore potential pathways and the subcellular localization of the proteins. In summary, we found a cohort of immunity-related molecules that can serve as potential diagnostic biomarkers for PNBM in patients with aSAH. These molecules also provide an immunological profile of PNBM.

Clinical Value of Glycan Changes in Cerebrospinal Fluid for Evaluation of Post-Neurosurgical Bacterial Meningitis with Hemorrhagic Stroke Patients.

Post-neurosurgical bacterial meningitis (PNBM) is one of the severe complications in patients receiving neurosurgical procedures. Recent studies have found microbe-related glycans play important roles in adhesion, invasion, and toxicity toward innate immunological reactions. In this study, we aimed to investigate the glycomic profile and its potential diagnostic efficacy in post-neurosurgical bacterial meningitis (PNBM) patients with hemorrhagic stroke. A total of 136 cerebrospinal fluid (CSF) samples were recruited and divided into a PNBM group and a non-PNBM group based on the clinical diagnostic criteria. A lectin biochip-based method was established for the detection of glycans in CSF. The clinicopathological data and biochemical parameters in CSF from all patients were analyzed. Two models for multivariate analysis investigating glycan changes in the CSF were conducted, aiming at determining the specific expression and diagnostic efficacy of lectin-probing glycans (LPGs) for PNBM. In univariate analysis, we found that 8 out of 11 LPGs were significantly correlated with PNBM. Model 1 multivariate analysis revealed that PNA (p = 0.034), Jacalin (p = 0.034) and LTL (p = 0.001) were differentially expressed in the CSF of PNBM patients compared with those of non-PNBM patients. Model 2 multivariate analysis further disclosed that LTL (p = 0.021) and CSF glucose (p &lt; 0.001) had independent diagnostic efficacies in PNBM, with areas under the curve (AUC) of 0.703 and 0.922, respectively. In summary, this study provided a new insight into the subject of CSF glycomics concerning bacterial infection in patients with hemorrhagic stroke.

Characteristics of Post-Neurosurgical Nosocomial Bacterial Meningitis in Adults: a retrospective Cross-Sectional Study

Aim: To analyze the characteristics of Post-neurosurgical nosocomial bacterial meningitis in adults Study design: A retrospective cross-sectional study Place and duration: Riyadh Care Hospital/ National Care Hospital, from July 2005 to June 2010 then 2013 to 2018. Methodology: Over ten years, sixty-two patients above the age of 16 years who suffered from Post-neurosurgical nosocomial bacterial meningitis were evaluated by collecting clinical data. The cases were divided into two categories, the first one from July 2007 to June 2012 and second one from August 2013 to July 2018. Results: Among the 62 patients, there were 43 males and 19 females with post-neurosurgical nosocomial bacterial meningitis. It was recorded in the first group that the percentage of post-neurosurgical nosocomial meningitis in all culture-proven adult bacterial meningitis was 12 percent and for the second group it was seen to be 27 percent. The most constant clinical characteristics were fever and gradual consciousness disruption, which may be related to various postoperative neurosurgery issues. The most prevalent pathogens were recorded to be pseudomonas aeruginosa, staphylococcus aureus, coagulase-negative staphylococcus, Acinetobacter baumannii, and lastly, Escherichia coli. During the second era, there was a rise in polymicrobial illnesses and multi antibiotic resistance. Mortality was 22% in the first group of the study and 36% in the second group of the study. Conclusion: The selection of appropriate empirical antibiotics is complex and is necessary to be guided by knowledge of the comparative ratio of multiple diseases as well as the rising prevalence of resistant strains. To increase the likelihood of survival, early diagnosis is suggested with optimal antibiotic selection based on in vitro susceptibility testing, epidemiologic patterns, and lastly, metabolic derangement treatment to be advised and required. Keywords: Bacterial Meningitis, adults, post-neurosurgery

Intelligent Clinical Lab for the Diagnosis of Post-Neurosurgical Meningitis Based on Machine-Learning-Aided Cerebrospinal Fluid Analysis.

Post-neurosurgical meningitis (PNM) often leads to serious consequences; unfortunately, the commonly used clinical diagnostic methods of PNM are time-consuming or have low specificity. To realize the accurate and convenient diagnosis of PNM, herein, we propose a comprehensive strategy for cerebrospinal fluid (CSF) analysis based on a machine-learning-aided cross-reactive sensing array. The sensing array involves three Eu3+-doped metal-organic frameworks (MOFs), which can generate specific fluorescence responding patterns after reacting with potential targets in CSF. Then, the responding pattern is used as learning data to train the machine learning algorithms. The discrimination confidence for artificial CSF containing different components of molecules, proteins, and cells is from 81.3 to 100%. Furthermore, the machine-learning-aided sensing array was applied in the analysis of CSF samples from post-neurosurgical patients. Only 25 μL of CSF samples was needed, and the samples could be robustly classified into "normal," "mild," or "severe" groups within 40 min. It is believed that the combination of machine learning algorithms with robust data processing capability and a lanthanide luminescent sensor array will provide a reliable alternative for more comprehensive, convenient, and rapid diagnosis of PNM.

Nomogram Analysis of Clinical Characteristics and Mortality Risk Factor of Non-Fermentative Gram-Negative Bacteria-Induced Post-Neurosurgical Meningitis.

To explore the clinical characteristics of post-neurosurgical meningitis (PNM) patients infected with nonfermenting Gram-negative bacilli (NFGNB) and to evaluate the related mortality risk factors. A cohort analysis of PNM patients infected with NFGNB in Beijing Tiantan Hospital and Capital Medical University from 2012.1 to 2020.12. The microbial distribution, antimicrobial sensitivity and genotypes were tested, and potential mortality risk factors were evaluated using Mann-Whitney U or chi-squared tests. Independent risk factors for mortality were established by constructing a logistic model. A total of 2940 PNM patients were enrolled in this study, of whom 207 (17.1%) were infected with NFGNB. Among these patients, 29 died of NFGNB meningitis, with an overall mortality rate of 14.0%. The top three NFGNBs were Acinetobacter baumannii (105 cases, 50.7%), Pseudomonas aeruginosa (29 cases, 14.0%) and Acinetobacter lwoffii (20 cases, 9.7%). Nomogram analysis revealed that hypertension (OR 4.551, 95% CI: 1.464-14.154, P = 0.009), external ventricular drainage (EVD) (OR 3.944, 95% CI: 1.286-12.095, P = 0.016), and assisted mechanical ventilator (AMV) (OR 6.192, 95% CI: 1.737-22.081, P = 0.005) were independent risk factors for mortality. In addition, antibiotic prophylaxis was shown to play a vital role in NFGNB-induced PNM therapy. PNM patients infected with NFGNB have a high mortality rate. Hypertension, EVD and AMV were independent mortality risk factors, and clinical attention should be paid to their prevention and treatment.

Current diagnosis and potential obstacles for post-neurosurgical bacterial meningitis.

Despite the guidance of aseptic technology applied, bacterial meningitis seems to be an unavoidable obstacle in the process of neurosurgery, with high rates of disability and mortality. The diagnosis of post-neurosurgical bacterial meningitis (PNBM) mainly depends both on clinical symptoms and laboratory outcomes. Due to the excessive neuro-inflammatory reactions which are evoked by the primary brain disease or the craniotomy operation, the symptoms derived from the infection and aseptic may not be easily distinguished. On the other hand, the low positive rate and time-consuming character restrict the clinical practical values of bacterial culture. Therefore, it is always difficult to make a definite diagnosis of post-neurosurgical bacterial meningitis. Here, we reviewed the established literature about the diagnostic biomarkers for the PNBM and analyzed the potential obstacles in both clinical and scientific studies. Given the obstacle which has negative impacts on further investigation about the biology of PNBM, we only find relatively small numbers of study on PNBM. In this review, we summarize the established diagnostic methods and biomarkers for PNBM. Meanwhile, we also propose some potential investigation prospects. This review may help to better understand the character of PNBM in both clinical diagnosis and scientific investigations.

4-Hydroxyphenyllactic Acid in Cerebrospinal Fluid as a Possible Marker of Post-Neurosurgical Meningitis: Retrospective Study.

The search for new potential biomarkers for the diagnostics of post-neurosurgical bacterial meningitis is required because of the difficulties in its early verification using results of the routine laboratory and biochemical analyses of the cerebrospinal fluid (CSF). The goal of the study was to determine the contents of the aromatic metabolites and biomarkers in the CSF samples of the post-neurosurgical patients (n = 82) and their potential diagnostical significance for the evaluation of the risk of post-neurosurgical meningitis. Patients with signs of post-neurosurgical meningitis (n = 30) had lower median values of glucose and higher values of cell count, neutrophils, lactate, protein, 3-(4-hydroxyphenyl)lactic acid (p-HPhLA), and interleukin-6 (IL-6) than patients without signs of post-neurosurgical meningitis (n = 52). ROC analysis for IL-6 and p-HPhLA resulted in 0.785 and 0.734 values of the area under the ROC curve, with sensitivity 96.30 and 66.67%; specificity 54.17 and 82.69%, respectively. IL-6 should be considered as a non-specific biomarker, in contrast to the microbial metabolite p-HPhLA. If the concentration of p-HPhLA was more or equal to 0.9 µmol/L, the risk of bacterial complications was 9.6 times higher. p-HPhLA is a promising marker for the prognosis of post-neurosurgical meningitis, and its determination on a larger group of post-neurosurgical patients can subsequently prove its diagnostic significance for the verification of CNS infections.

Current Perspectives on the Diagnosis and Management of Healthcare-Associated Ventriculitis and Meningitis.

Ventriculitis or post-neurosurgical meningitis or healthcare-associated ventriculitis and meningitis (VM) is a severe infection that complicates central nervous system operations or is related to the use of neurosurgical devices or drainage catheters. It can further deteriorate patients who have already presented significant neurologic injury and is associated with high morbidity, mortality, and poor functional outcome. VM can be difficult to distinguish from aseptic meningitis, inflammation that follows hemorrhagic strokes and neurosurgical operations. The associated microorganisms can be either skin flora or nosocomial pathogens, most commonly, Gram-negative bacteria. Classical microbiology can fail to isolate the culprit pathogen. Novel cerebrospinal fluid (CSF) biomarkers and molecular microbiology can fill the diagnostic gap and expedite pathogen identification and treatment. The pathogens may demonstrate significant resistant patterns and their antibiotic treatment can be difficult, as many important drug classes, including the beta-lactams and the glycopeptides, hardly penetrate to the CSF, and do not achieve therapeutic levels at the site of the infection. Treatment modifications, such as higher daily dose and prolonged or continuous administration, might increase antibiotic levels in the site of infection and facilitate pathogens clearance. However, in the case of therapeutic failure or infection due to difficult-to-treat bacteria, the direct antibiotic instillation into the CSF, in addition to the intravenous antibiotic delivery, may help in the resolution of infection. However, intraventricular antibiotic therapy may result in aseptic meningitis and seizures, concerning the administration of aminoglycosides, polymyxins, and vancomycin. Meanwhile, bacteria form biofilms on the catheter or the device that should routinely be removed. Novel neurosurgical treatment modalities comprise endoscopic evacuation of debris and irrigation of the ventricles. VM prevention includes perioperative antibiotics, antimicrobial impregnated catheters, and the implementation of standardized protocols, regarding catheter insertion and manipulation.

Whole-Genome Analysis of KPC-Producing Klebsiella Pneumoniae Isolates from Hospital Acquired Post-Neurosurgical Meningitis

Whole-Genome Analysis of KPC-Producing Klebsiella Pneumoniae Isolates from Hospital Acquired Post-Neurosurgical Meningitis

Post-neurosurgical meningitis; gram negative bacilli vs. gram positive cocci.

Background:Post-neurosurgical meningitis is a significant cause of mortality and morbidity. In this study we aimed to compare the differences of clinical, laboratory features and outcomes between the post-neurosurgical meningitis caused by gram-negative bacilli (GNB) and gram-positive cocci (GPC).Methods:Cases of post-neurosurgical meningitis (with positive CSF culture) were included. After classifying patients as GNB and GPC groups, clinical and paraclinical data were compared.Results:Out of 2667 neurosurgical patients, CSF culture was positive in 45 patients. 25 (54.3%) were GNB, 19 (41.3%) GPC. The most common microorganisms were Klebsiella pneumoniae (n=14, 31.1%), Coagulase negative staphylococcus (n=8, 17.8%), Staphylococcus aureus (n=6, 13.3%), Acinetobacter baumannii (n=4, 8.9%), Pseudomonas aeruginosa (n=2, 4.4%), and Escherichia coli (n=2, 4.4%). There were no correlation between CSF Leakage, Surgical site appearance, presence of drain, Age and GCS between two groups (P=0.11, P=0.28, P=0.06, P=0.86, P=0.11 respectively). The only different laboratory indexes were ESR (86.8 mm/h vs. 59.5 mm/h, P=0.01) and PCT (13.1 ng/ml vs. 0.8 ng/ml, P=0.02) which were higher in GNB cases. 20% (n=5) of patients with GNB meningitis received preoperative corticosteroid, while none of GPC cases received (P=0.03). The median length of hospitalization for GNB and GPC cases was 56 and 44.4 days respectively (P=0.3).Conclusion:The GNB antibiotic coverage should be designed more carefully in post-neurosurgical meningitis especially in patients with recent corticosteroid therapy and elevated ESR and procalcitonin.

1111. Therapeutic Drug Monitoring of Colistin in Cerebrospinal Fluid in the Treatment of Neurosurgical Meningitis caused by Pseudomonas aeruginosa and KPC-producing Enterobacterales

BackgroundCentral nervous system (CNS) infections caused by carbapenem-resistant Enterobacterales (CRE) and Difficult-to-treat resistant (DTR)-P. aeruginosa (PA) present a therapeutic dilemma. Therapies are limited due to antibiotic resistance and inadequate CNS diffusion. Intraventricular polymyxins are utilized in this setting despite a lack in pharmacokinetic data after CNS injection. We describe the utilization of intravenous and intrathecal polymyxin E [colistimethate (CMS)] therapeutic drug monitoring (TDM) in 3 cases of post-neurosurgical meningitis. MethodsBacterial identification and susceptibility testing were performed using MicroScan. TDM was employed by dosing CMS at 125,000 IU (i.e., 4.1 mg CBA or 10 mg) administered via external ventricular drain twice daily and 4.5 MIU (133.2 CBA or 360 mg) CMS administered over 30 minutes IV twice daily. Four pairs of CSF and blood samples were collected for each patient (Table 1). Samples were placed on ice to minimize in-vitro conversion of CMS to Colistin. Colistin binding in plasma and CSF was measured using ultracentrifugation. Concentrations of CMS and Colistin in CSF and human plasma were determined by liquid chromatography/mass spectrometry. Patients A, B and C received 20, 15, and 12 doses of CMS, respectively, prior to TDM.ResultsBacterial cultures revealed DTR PA, blaKPCE. cloacae and blaOXA-48K. pneumoniae for patients A, B and C, respectively. Colistin minimum inhibitory concentrations (MIC) were 0.5 µg/ml, 0.125 µg/ml, and 0.125 µg/ml, respectively. The measured CSF and plasma concentrations of CMS, Colistin, and binding are shown in Table 1. Clinical resolution and microbiological cure were attained in all patients. Therapeutic Drug Monitoring of Unchanged CMS and Formed Colistin in CSF samples for patient A, B, and C Therapeutic Drug Monitoring of Unchanged CMS and Formed Colistin in Plasma Samples for patient A, B, and C ConclusionFavorable concentrations of formed Colistin and CMS in CSF were achieved in 3 patients with complicated CNS infection. To the best of our knowledge, this is the first study to report the binding of Colistin in CSF in humans. A TDM method was effectively applied to demonstrate that Colistin achieves and maintains the PK/PD target (fAUC/MIC) [ratio of area under the plasma concentration curve of unbound drug to MIC] that best correlates with killing activity. Overall, our results support intraventricular polymyxins for treating DTR Gram-negative CNS infections.Disclosures Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

Characteristics of Post-Neurosurgical Nosocomial Bacterial Meningitis in Adults: A retrospective Cross-Sectional Study

Aim: To analyze the characteristics of Post-neurosurgical nosocomial bacterial meningitis in adults Study design: A retrospective cross-sectional study Place and duration: Riyadh Care Hospital/ National Care Hospital, from July 2005 to June 2010 then 2013 to 2018. Methodology: Over ten years, sixty-two patients above the age of 16 years who suffered from Post-neurosurgical nosocomial bacterial meningitis were evaluated by collecting clinical data. The cases were divided into two categories, the first one from July 2007 to June 2012 and second one from August 2013 to July 2018. Results: Among the 62 patients, there were 43 males and 19 females with post-neurosurgical nosocomial bacterial meningitis. It was recorded in the first group that the percentage of post-neurosurgical nosocomial meningitis in all culture-proven adult bacterial meningitis was 12 percent and for the second group it was seen to be 27 percent. The most constant clinical characteristics were fever and gradual consciousness disruption, which may be related to various postoperative neurosurgery issues. The most prevalent pathogens were recorded to be pseudomonas aeruginosa, staphylococcus aureus, coagulase-negative staphylococcus, Acinetobacter baumannii, and lastly, Escherichia coli. During the second era, there was a rise in polymicrobial illnesses and multi antibiotic resistance. Mortality was 22% in the first group of the study and 36% in the second group of the study. Conclusion: The selection of appropriate empirical antibiotics is complex and is necessary to be guided by knowledge of the comparative ratio of multiple diseases as well as the rising prevalence of resistant strains. To increase the likelihood of survival, early diagnosis is suggested with optimal antibiotic selection based on in vitro susceptibility testing, epidemiologic patterns, and lastly, metabolic derangement treatment to be advised and required. Keywords: Bacterial Meningitis, adults, post-neurosurgery

Predictive Value of Cerebrospinal Fluid Lactate Level for the Diagnosis of Bacterial Meningitis following Cranial Surgery

Background:To distinguish post-neurosurgical bacterial meningitis (PNBM) from aseptic meningitis is difficult. Inflammatory and biochemical cerebrospinal fluid (CSF) changes mimic those classically observed after CNS surgery. CSF lactate assay has therefore been proposed as a useful PNBM marker. Objective:To determine the value of cerebrospinal fluid (CSF) lactate level for the identification of bacterial meningitis following cranial surgery. Methods:Between January 2016 and December 2016, a prospective clinical study was done in Department of Neurosurgery, in which all patients with clinical suspicion of PNBM were enrolled. Patients with clinical suspicion of bacterial meningitis BM were categorized, according to preset criteria, into 3 groups: (1) proven BM; (2) presumed BM, and (3) nonbacterial meningeal syndrome. CSF markers were plotted in a receiver operating curve (ROC) to evaluate their diagnostic accuracy. Results:The study included 70 patients. We obtained 65 CSF samples from patients with clinical suspicion of BM by CSF analysis. 20 corresponded to proven BM, 7 to probable BM and 38 to excluded BM. Mean lactate in CSF was: 8.4 ±3.0 mmol /l for proven BM, 4.8 ± 0.99 mmol /l for probable BM and 2.08 ± 0.822 mmol/l for excluded BM (P &lt; .001). Conclusion: CSF lactate level has good predictive value to distinguish BM from aseptic meningitis with sensitivity of 90% and specificity: 87% at cut-off value: 4.0 mmol/l.

Using Therapeutic Drug Monitoring to Treat KPC-Producing Klebsiella pneumoniae Central Nervous System Infection With Ceftazidime/Avibactam.

This report describes the treatment of Klebsiella pneumoniae carbapenemase (KPC)–3–producing multidrug-resistant K. pneumoniae with ceftazidime/avibactam (CAZ-AVI) in a patient who developed postneurosurgical meningitis and bacteremia. Therapeutic drug monitoring of cerebrospinal fluid and blood samples demonstrated CAZ-AVI concentration levels 20-fold greater than the minimum inhibitory concentration in the first 60 minutes postinfusion, providing evidence for the utility of CAZ-AVI in treating KPC–Klebsiella pneumoniae central nervous system infections.