Serum procalcitonin monitoring for differential diagnosis of ventriculitis in adult intensive care patients

The objective of our study was to assess the value of serum procalcitonin (PCT) monitoring in the differential diagnosis of ventriculitis in adult intensive care (ICU) patients. We analyzed 15 consecutive patients with ventriculitis in which a ventricular catheter had been inserted and contrasted these data with the observations in 10 patients with community-acquired bacterial meningitis. Cerebrospinal fluid (CSF) and blood samples were collected daily to assess serum PCT, C-reactive protein (CRP) and CSF leukocyte count. PCT levels were normal or slightly elevated in patients with ventriculitis with either positive or negative CSF bacterial culture but elevated in patients with bacterial meningitis. A PCT cut-off value of 1.0 ng/ml or more showed a specificity of 77% and a sensitivity of 68% for ventriculitis with positive CSF bacterial culture. Serum PCT levels reflected more accurately the time phases of disease during therapy. We conclude that the monitoring of serum PCT alone is not helpful for the differential diagnosis of ventriculitis, in contrast to that of bacterial meningitis. The value of PCT as an additional marker with which to assess the efficacy of therapy in ventriculitis is suggested, but requires further assessment.     

Cerebrospinal fluid tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 as diagnostic markers of cerebrospinal fluid infection in neurosurgical patients

OBJECTIVE: To evaluate whether cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-8 may be used as diagnostic markers for the differential diagnosis of aseptic vs. bacterial meningitis and/or ventriculitis in neurosurgical patients. DESIGN: Prospective, observational study. SETTING: University teaching hospital. SUBJECTS: A total of 112 cerebrospinal fluid samples from 14 asymptomatic patients with normal cerebrospinal fluid after neurosurgery, 27 asymptomatic and 19 symptomatic patients with postneurosurgical aseptic meningitis, 32 patients with postneurosurgical cerebrospinal fluid infection, and 20 with severe subarachnoid and/or cerebral hemorrhage. MEASUREMENTS AND MAIN RESULTS: Specific ELISA kits were used to analyze TNF-alpha, IL-1beta, IL-6, and IL-8 concentrations on cerebrospinal fluid samples. Elevations in cerebrospinal fluid concentrations of TNF-alpha, IL-1beta, IL-6, and IL-8 were induced by different diseases or neurosurgical procedures, but cerebrospinal fluid bacterial infection induced the highest concentrations. To discriminate between aseptic cerebrospinal fluid pleocytosis and cerebrospinal fluid infection with a specificity of 95%, cerebrospinal fluid leukocyte count >1700/mL, TNF-alpha >150 pg/mL, and IL-1beta >90 pg/mL showed sensitivities of 51%, 74%, and 90%, respectively. Sufficiently sensitive and specific cutoff points could not be found for cerebrospinal fluid IL-6 or IL-8. CONCLUSION: Cerebrospinal fluid IL-1beta appears to be the best biochemical marker of cerebrospinal fluid infection in neurosurgical patients.     

Serum procalcitonin levels in bacterial and abacterial meningitis

OBJECTIVES: To test the hypothesis that serum procalcitonin (PCT) levels are elevated in patients with bacterial meningitis and remain within normal limits in patients with abacterial meningitis. DESIGN: Prospective case series. SETTING: Tertiary care center. PATIENTS: A total of 30 patients (13 men and 17 women) with a mean age of 52 yrs, having acute bacterial (n = 16) or abacterial (n = 14) meningitis. INTERVENTIONS: Blood and cerebrospinal fluid samples. MEASUREMENTS AND MAIN RESULTS: Patients with abacterial meningitis were younger and had a shorter hospital stay. Of 16 patients with bacterial meningitis, 14 were in a septic condition at admission, but only 5 of 14 patients with abacterial meningitis were in a septic condition at admission. At discharge, 12 patients were without symptoms, 9 patients were moderately disabled, and 9 were severely disabled. No patient died. At admission, PCT, C-reactive protein, white blood cell and cerebrospinal fluid leukocyte counts, and cerebrospinal fluid protein and lactate levels were higher and the serum/cerebrospinal fluid glucose quotient was lower in patients with bacterial meningitis as compared with those with abacterial meningitis (p < .001). PCT was the variable with the highest specificity for bacterial infections (100%), but there were false-negative findings in five patients with bacterial meningitis (a sensitivity of 69%). Persistently elevated or increasing PCT levels after 2 days were associated with an unfavorable clinical course. CONCLUSIONS: Our results indicate that PCT is a useful additional variable for distinguishing bacterial from abacterial meningitis. In patients with abacterial meningitis, PCT levels do not increase even in cases of viral sepsis. Elevated PCT levels indicate a bacterial origin with high specificity, but false-negative results can occur.     

Correction of ventricular cerebrospinal fluid (CSF) samples for blood content does not increase sensitivity and specificity for the detection of CSF infection

BACKGROUND: Blood contamination is commonly observed in ventricular cerebrospinal fluid (CSF) samples from patients with extraventricular drainage systems. Because the introduction of blood may interfere with the white blood cell count as a useful marker for the diagnosis of an infection, correction for blood content would be desirable. METHODS: In a retrospective study, we analysed the use of correction formulas in 724 blood-contaminated ventricular CSF samples. RESULTS: Using a standard correction method the white blood cell count was not normalised in most CSF samples, with pleocytosis indicating an inflammatory stimulus set by the blood itself or by the foreign body. When correcting white blood cell counts in the CSF of culture-positive patients, some samples were normalised or overcorrected. In addition, correction of the CSF white blood cell count did not increase sensitivity and specificity for the detection of culture-positive CSF samples. CONCLUSIONS: Correction is not necessary when using the white blood cell count as a parameter to predict CSF infection in ventricular CSF samples.     

Predictors of extraventricular drain–associated bacterial ventriculitis

Purpose

Bacterial ventriculitis (BV) may develop in patients requiring external ventricular drains (EVDs). The purpose of this study was to determine predictors of EVD-associated BV onset.

Materials and Methods

A retrospective review of Duke University Hospital patients with EVD device placement between January 2005 and May 2010 was conducted. Subject data were captured for predefined variables. Outcomes included in-hospital mortality, length of stay, and neurologic status at discharge.

Results

In 410 subjects with 420 EVDs, the BV rate was 10.2%. Univariate analysis indicated that age, sex, positive blood culture, duration of EVD placement, and the number of cerebrospinal fluid (CSF) samples taken were associated with BV. Of these, the number of CSF samples and sex retained significance in multivariable modeling (female: odds ratio, 0.47 [confidence interval, 0.23-0.97]; CSF samples: odds ratio, 1.08 [confidence interval 1.01-1.17]; P = .04; c index = 0.69). In this model, each CSF sample taken expanded the likelihood of BV by 8.3%. The most common pathogens were Staphylococcus or proprioniobacter (n = 26). Bacterial ventriculitis was associated with an increase in hospital length of stay (33 ± 22.9 days vs 24.6 ± 20.4 days; P = .04) but not mortality.

Conclusion

An association exists between CSF sampling frequency and the development of EVD-associated BV. Larger prospective studies should be aimed at identifying causal relationships between these variables.     

脑脊液与血清降钙素原、C-反应蛋白在中枢神经系统感染诊断中的应用价值

目的 探讨血清降钙素原(PCT)、C-反应蛋白(CRP)在中枢神经系统感染(ICNS)诊断中的应用价值。方法 选取我院2016年1月-2020年12月收治的ICNS患者72例为观察组,按感染类型分为化脓性感染亚组(44例)与病毒性感染亚组(28例),另选取同期接受脑外科手术并未发生ICNS的患者80例为对照组。比较各组脑脊液、血清CRP、PCT水平。结果 观察组脑脊液、血清PCT、CRP均高于对照组(P<0.05);化脓性感染亚组患者脑脊液、血清PCT、CRP均高于病毒性感染亚组(P<0.05);ROC曲线分析显示,脑脊液CRP(AUC=0.823)、脑脊液PCT(AUC=0.890)以及血清CRP(AUC=0.729)、血清PCT(AUC=0.793)均是预测ICNS的重要因素(P<0.01)。结论 脑脊液、血清PCT、CRP可作为诊断ICNS病情的指标,其中脑脊液PCT的诊断效能较高。     

脑脊液置换联合脑室外引流治疗自发性脑室出血的临床探讨

目的探讨脑脊液置换在脑室出血治疗中的应用。方法52例自发性脑室出血患者随机分为两组,治疗组28例,采用单侧或双侧脑室外引流术、尿激酶灌注,同时给予腰大池持续外引流或反复腰穿置换脑脊液;对照组24例,采用延长脑室外引流时间及尿激酶灌注治疗。结果侧脑室外引流尿激酶灌注加脑脊液置换术提高了自发性脑室出血患者存活率,减少了颅内感染和脑积水等并发症的发生率。结论联合应用侧脑室外引流、尿激酶灌注和脑脊液置换术治疗自发性脑室出血,方法简单,疗效确切。     

CD62L on neutrophil granulocytes,a useful,complementary marker for the prediction of ventriculitis in blood-containing CSF

ObjectivesPresence of residual blood is a common problem in cerebrospinal fluid (CSF) diagnostics of ventriculitis. We hypothesised that neutrophil granulocytes in infected, blood-containing CSF lose CD62L expression. Therefore CD62L expression on neutrophils may present a complementary marker to distinguish between patients with residual blood and infection.Designs and methodsEvaluation was performed in 64 ventricular CSF samples sent to the laboratory for diagnostic investigation. Cell count, microbiological culture, total protein and flow cytometric analysis of CSF were performed.ResultsCell counts and CD62L expression were significantly different between the culture positive and negative group. ROC-analysis revealed a significant predictive value for cell count and CD62L expression. Optimal cut-offs were calculated and a decision tree was established to predict a positive culture.ConclusionsCell count and CD62L expression were predictive for a positive culture and the combination helped to increase specificity and sensitivity for the detection of ventriculitis in blood-containing CSF.     

脑脊液中肝素结合蛋白、总蛋白、降钙素原检测在鉴别细菌性与非细菌性颅内感染疾病中的临床应用

目的探讨脑脊液中肝素结合蛋白(HBP)、总蛋白、降钙素原(PCT)检测在鉴别细菌性与非细菌性颅内感染疾病中的临床应用价值。方法我院收治的颅内感染患者248例,分为细菌性颅内感染142例(细菌组)和非细菌性颅内感染106例(非细菌组),选取同期无颅内感染住院患者85例为对照组。比较三组血白细胞计数(WBC)、血清PCT以及脑脊液WBC、HBP、总蛋白、PCT水平。绘制ROC曲线计算灵敏度、特异度。结果细菌组血WBC、血清PCT及脑脊液WBC、HBP、总蛋白、PCT水平均高于非细菌组与对照组(P<0.05)。各指标鉴别细菌性与非细菌性颅内感染脑脊液HBP的截断值为21.30 ng/ml,灵敏度为75.35%,特异度为79.25%。脑脊液总蛋白的截断值为1054.50 mg/L,灵敏度为83.10%,特异度为70.75%。脑脊液PCT的截断值为0.16 ng/ml,灵敏度为88.03%,特异度为89.62%。结论脑脊液中HBP、总蛋白、PCT检测在鉴别细菌性与非细菌性颅内感染具有较高的价值,可与传统指标血WBC、脑脊液WBC以及血清PCT等联合应用,辅助临床诊断。     

Analysis of the brain bioavailability of peripherally administered magnesium sulfate: A study in humans with acute brain injury undergoing prolonged induced hypermagnesemia

OBJECTIVE: Based on preclinical investigations, magnesium sulfate (MgSO4) has gained interest as a neuroprotective agent. However, the ability of peripherally administered MgSO4 to penetrate the blood-brain barrier is limited in normal brain. The current study measured the passage of intravenously administered Mg into cerebrospinal fluid in patients with brain injury requiring ventricular drainage. DESIGN: A prospective evaluation of the cerebrospinal fluid total and ionized magnesium concentration, [Mg], during sustained hypermagnesemia was performed. SETTING: Neurosciences intensive care unit at a major teaching institution. PATIENTS: Thirty patients with acute brain injury secondary to subarachnoid hemorrhage, traumatic brain injury, primary intracerebral hemorrhage, subdural hematoma, brain tumor, central nervous system infection, or ischemic stroke were studied. INTERVENTIONS: Patients underwent 24 hrs of induced hypermagnesemia during which total and ionized cerebrospinal fluid [Mg] was measured. Serum [Mg] was adjusted to 2.1-2.5 mmol/L. Cerebrospinal fluid [Mg] was measured at baseline, at 12 and 24 hrs after onset of infusion, and at 12 hrs following infusion termination. MEASUREMENTS AND MAIN RESULTS: At baseline, total (1.25 +/- 0.14 mmol/L) and ionized (0.80 +/- 0.10 mmol/L) cerebrospinal fluid [Mg] was greater than serum total (0.92 +/- 0.18 mmol/L) and ionized (0.63 +/- 0.07 mmol/L) [Mg] (p < .05). Total (1.43 +/- 0.13 mmol/L) and ionized (0.89 +/- 0.12 mmol/L) cerebrospinal fluid [Mg] was maximally increased by 15% and 11% relative to baseline, respectively, during induced hypermagnesemia (p < .05). CONCLUSIONS: Hypermagnesemia produced only marginal increases in total and ionized cerebrospinal fluid [Mg]. Regulation of cerebrospinal fluid [Mg] is largely maintained following acute brain injury and limits the brain bioavailability of MgSO4.     

Evaluation of procalcitonin as a marker of infection in a nonselected sample of febrile hospitalized patients

The level of procalcitonin is undetectable in healthy individuals and slightly increased in viral infections and noninfectious inflammatory responses. It has been described to be notably increased in bacterial, parasitic, or fungal infections. Procalcitonin has been reported to be a reliable marker for severe bacterial infections, although it has mainly been studied in specific entities or in selected groups of patients. We prospectively determined the procalcitonin level in 103 unselected febrile hospitalized patients. Most of them had a proven (39) or probable bacterial infection (44). Procalcitonin was more frequently positive in bacteremic patients (p = 0.01), in patients with a proven bacterial infection (p < 0.01), and in those with a high sepsis score (p < 0.005), however; when cases with proven bacterial infection were considered as a reference, the sensitivity of the test was only 54% and the specificity 70%. Procalcitonin determination should not be included systematically in the screening of febrile hospitalized patients.     

A multidisciplinary approach to end external ventricular drain infections in the neurocritical care unit

External ventricular drain (EVD) placement is a common practice in neurocritical care units. The EVDs are the "gold" standard and the most cost-effective treatment for intracranial hypertension and hydrocephalus caused by a variety of neurological conditions. The EVD drains excess cerebrospinal fluid in an attempt to maintain balance within the cranial vault and provides intermittent monitoring of intracranial pressure. This invasive procedure, as with any other procedures, carries an increased risk of a device-related infection that can lead to devastating consequences such as meningitis, ventriculitis, and death. This article will discuss how Riverside Methodist Hospital, which is located in Central Ohio, identified an increase in the rate of EVD infections in 2007 and responded with changes in procedure and processes. The implementation of the improvement plan has resulted in 25 months without an EVD infection, a triumph for the patients, staff, and the hospital system.     

血清降钙素原在小儿上呼吸道感染疾病中的检测意义

目的探讨血清降钙素原检测在小儿上呼吸道感染早期诊断中的意义。方法对2010年1月-5月100例门诊就诊4—12岁小儿上呼吸道感染患者，检测血常规及血清降钙素原。结果降钙素原检测对于细菌与非细菌感染存在显著差异。结论降钙素原检测可显著提高细菌性感染诊断的敏感性及特异性。     

Intraventricular levels of amikacin after intravenous administration.

Serum and ventricular fluid pharmacokinetic data for amikacin were evaluated prospectively in 10 hydrocephalic children with suspected ventriculitis. After the fourth or fifth intravenous 7.5-mg/kg dose of amikacin given every 8 h, mean peak serum levels were 24.3 +/- 3.2 microgram/ml (achieved at 0.5 h) with a calculated half-life of 2.2 +/- 1.1 h. Mean peak ventricular fluid levels in five patients with bacterial infection were 6.1 +/- 2.0 microgram/ml (achieved at 3 h). In the remaining five patients without bacterial ventriculitis, very low levels (less than or equal to 0.7 microgram/ml) of amikacin were detected. Ventricular fluid pleocytosis was directly correlated and glucose levels were inversely correlated with penetration of amikacin. Systemic therapy with amikacin may be the treatment of choice for children with ventriculitis meningitis caused by bacteria which are highly susceptible to this drug, thereby permitting the avoidance of the potentially hazardous intraventricular route of administration.     

Penetrance of nafcillin into human ventricular fluid: correlation with ventricular pleocytosis and glucose levels.

Fourteen hydrocephalic pediatric patients with suspected shunt infections were studied for penetrance of nafcillin into the ventricular fluid after intravenous administration. In seven patients with bacterial ventriculitis, the concentration of nafcillin in ventricular fluid was 0.8 to 20.4% of the peak concentration in serum. In the remaining seven patients without bacterial ventriculitis, ventricular fluid levels ranged between less than or equal to 0.02 to 4% of peak serum concentrations. Although the degree of pleocytosis correlated poorly with penetrance, ventricular fluid glucose levels correlated inversely with penetrance of nafcillin (r = -0.7275, P less than 0.001).     

Conspicuous endoscopic appearance of ventriculitis caused by coagulase-negative staphylococci

To date, reports about the macroscopic appearance of ventriculitis have been rare, consisting only of a few autopsy cases. A patient in our hospital had ventriculitis caused by coagulase-negative staphylococci, and under neuroendoscopy we obtained clear findings of granular ependymitis. A 44-year-old man was admitted for disturbance of consciousness caused by progressive hydrocephalus. He had experienced subarachnoid hemorrhage (SAH) from a left vertebral dissecting aneurysm, and had subsequently received a ventriculoperitoneal shunt against post-SAH hydrocephalus. After admission, he was found to have retrograde shunt infection from peritonitis caused by cholecystitis. Coagulase-negative staphylococci were detected in cerebrospinal fluid (CSF), and the infection persisted even with intrathecal administration of gentamycin, and intravenous administration of vancomycin and arbekacin. Endoscopic rinsing was performed, and multiple small yellowish microgranulations, less than 1 mm in diameter, were observed in the lateral ventricles and the third ventricle. Rinsing of the CSF after intensive antimicrobial treatment resulted in a cure. Because there have been no reports of endoscopic observations of bacterial ventriculitis, we were unable to be certain about the origin or significance of the microgranulations. However, whether or not the microgranulations were bacterial colonies, infection did not recur during a 2-year follow-up period.     

腰穿脑脊液置换对蛛网膜下腔出血患者神经系统功能恢复的影响

Background: Death and disability of subarachnoid hemorrhage(SAH) are caused by lesions of cerebral hernia, spasm of cerebral blood vessels, injuries the blood brain barrier, or communicating hydrocephalus.Cerebrospinal fluid displacement through lumbar puncture can clear the bloody cerebrospinal fluid and reduce the blood pollution of the cerebrospinal fluid, shorten xanthochromia time, reduce the intracranial pressure early and meninges stimulation. Intrathecal injection of dexamethasone can reduce defense reaction of the meninges, tissue adhesion and organization at the same time.     

脑积水脑室腹腔分流相关性脑室炎治疗方案的探讨

目的探讨脑积水脑室腹腔分流相关性脑室炎的治疗方法。方法对临床怀疑有脑脊液分流管性感染的患者,先拔除原分流管．同时行脑室外引流术．取脑室内脑脊液行细菌培养和抗生素敏感试验检查。术后,在获得细菌培养结果前．每日经脑室外引流管注入万古霉素25～50mg;在获得细菌培养结果后,确定或调整使用抗生素的种类。在脑室炎治愈后,根据需要最终对脑积水给予合理的治疗。结果11例患者中感染凝固酶阴性或表皮葡萄球菌及金黄色葡萄球菌者共9例,其中1例感染阴沟杆菌、克雷伯杆菌和产气肠杆菌;1例感染链球菌;1例感染牛粪杆菌。药敏试验表明：9例患者感染的球菌对万古霉素均敏感,但其中仅1例对庆大霉素敏感。1例感染链球菌和2例感染杆菌者,均有各自敏感的抗生素。在临床治疗中,万古霉素实际有效者8例;抗生素治疗疗程为16～36d。11例患者全部存活,其中9例神经功能明显改善。结论①脑室内注入抗生素是一种治疗脑室炎可靠而有效的方法。②万古霉素是治疗脑室炎的首选药物,少数患者需要加用或改用其他抗生素。③系统性抗生素治疗的作用尚不能肯定,可在感染表现期辅助使用。④脑室炎的诊断和治疗还涉及很多问题,有待广泛而深入的研究。     

Novel applications for serum procalcitonin testing in clinical practice

Introduction: Procalcitonin has emerged as a reliable marker of acute bacterial infection in hospitalized patients and the assay has recently been incorporated into several clinical algorithms to reduce antimicrobial overuse, but its use in patients with end-organ dysfunction is controversial.

Areas covered: In this review, the authors examine what is known about procalcitonin testing in patients with organ dysfunction, including those with end-stage renal disease, congestive heart failure, chronic obstructive pulmonary disease, and cirrhosis, and explore how the assay is now being used in the management of non-infectious diseases.

Expert commentary: Procalcitonin holds tremendous promise to identify a diverse set of medical conditions beyond those associated with acute bacterial infection, including post-surgical anastomotic leaks, acute kidney injury, and complications after intracerebral hemorrhage. The authors review recent studies examining procalcitonin in these areas and explore how the assay might be used to guide diagnosis and prognosis of non-infectious diseases in the near future.     

Fibrinolytic therapy in intraventricular hemorrhage.

OBJECTIVE: To review the literature concerning intraventricular administration of fibrinolytic agents to treat patients with intraventricular hemorrhage (IVH). DATA SOURCES: An extensive literature search (MEDLINE, EMBASE, Conference Proceedings) was conducted to identify articles in English published between 1966 and May 2000 pertaining to the pathophysiology of IVH and its treatment by intraventricular administration of recombinant tissue plasminogen activator (alteplase) or urokinase (u-PA). The bibliographies of selected identified articles were also screened for publications not found in the computerized search. STUDY SELECTION: All pertinent publications were reviewed and considered. Those describing the intraventricular administration of fibrinolytic agents to patients with IVH were included. DATA SYNTHESIS: IVH has a poor prognosis, partly due to the mass effect of blood clots on the ventricular walls. The cerebrospinal fluid has a limited fibrinolytic system. Therefore, clots may remain in the ventricles for months after a hemorrhage. The management of IVH is primarily directed at controlling intracranial pressure through an external ventricular drain, but this catheter often becomes occluded by coagulated blood. To overcome this problem, and to dissolve the residual blood clot, investigators have administered alteplase or u-PA directly into the ventricles of patients with IVH. Complications of this therapy include infection and possible rebleeding. Clinical studies of fibrinolytic therapy for IVH have found a 30-35% reduction in mortality with treatment, but to date, have not clearly documented improved neurologic outcome of the survivors. CONCLUSIONS: Fibrinolytic therapy with alteplase or u-PA may be life-saving in severe cases of IVH. Yet many technical issues remain to be resolved, such as the optimal dose, frequency, method, timing, and duration of administration of the agent. Additional randomized, double-blind, placebo-controlled studies need to be performed so that the true value of this therapy can be assessed.