Early Identification of Correlated Risk Factors can Improve the Prognosis of Patients with Postoperative Intracranial Infection

Abstract

Background In this retrospective study, we explore the clinical risk factors correlated to the prognosis of patients who suffered from central nervous system infection after a neurosurgical procedure.

Methods The study included 113 patients diagnosed with a postoperative intracranial infection. Several factors with clinical relevance were identified and analyzed by univariate analyses. The risk factors that showed any significant difference between the cases were analyzed by multivariate logistic regression analyses.

Results Here we show that the duration of the drainage before infection (measured in days; Beta [B]: –0.113; odds ratio [OR]: 0.893; 95% confidence interval [CI]: 0.805–0.991; p = 0.033), the number of antibiotics used for the treatment (B: –1.470; OR: 0.230; 95% CI: 0.072–0.738; p = 0.013), and the number of leucocytes in the cerebrospinal fluid (CSF; B: –0.016; OR: 0.984; 95% CI: 0.970–0.998; p = 0.027) are risk factors for the prognosis of patients with an intracranial infection. In contrast, the duration of antibiotic treatment (measured in days; B: 0.176; OR: 1.193; 95% CI: 1.063–1.339; p = 0.003) turned out to be a positive factor for recovery from infection.

Conclusions Our results suggest that early identification of the correlated risk factors can improve the prognosis of patients with intracranial infection after neurosurgery.

Keywords

intracranial infection - neurosurgery - risk factors - prognosis

Introduction

Intracranial infection is a common and serious complication of neurosurgery. The incidence of intracranial infection after neurosurgery can vary from 0.7 to 8.9%, as reported in different studies.[1] [2] [3] [4] This discrepancy may derive from the choice of different diagnostic criteria, the presence of multiple clinical factors that may interfere with the prognosis, and regional differences. China has the largest population in the world, and the highest number of craniotomies is performed in China. Retrospective studies conducted by Chinese groups reported that the incidence of intracranial infection is 7.4[5] to 8.6%.[6] Postoperative intracranial infection leads to longer hospitalization, multiple surgeries, and long-term usage of antibiotics, thus increasing the risks for the patients as well as the medical costs.[7] Severe infections may lead to neurologic dysfunctions or death.[8] The mortality rate of postoperative intracranial infections varies from 8 to 25% in the literature[9] [10] [11] [12] [13] and some medical centers reported a rate of 40.8%.[14] Only a few studies have examined the risk factors that may contribute to the prognosis of patients affected by a postoperative infection.[9] Therefore, this study aimed to further investigate the possible risk factors correlated to this clinical event and improve the prognosis for patients who suffer from infection after neurosurgery.

Materials and Methods

Study Population

This retrospective study was conducted at the People's Hospital of Anyang, Henan Province. The neurosurgery department of the hospital is a key medical unit in the Province of Henan and nearly 2,000 neurosurgical operations are performed every year. The study included data on 113 patients who were diagnosed with a postoperative intracranial infection after neurosurgical treatment between June 2018 and September 2021. The research protocol was approved by the hospital ethical committee (approval no. KY2018020), and the research was carried out in accordance with the ethical standards of the 1964 Helsinki Declaration and its subsequent amendments or similar ethical standards. All the patients enrolled in this study received distinct ethical approval from the hospital ethical committee to participate in the retrospective study.

Inclusion and Exclusion Criteria of Patients

The patients were considered eligible for the study according to the following criteria: (1) the patient underwent neurosurgery and (2) the patient developed a central nervous system infection after the operation. According to the Centers for Disease Control and Prevention Standard,[15] postoperative central nervous system infections (PCNSIs) include meningitis, ventriculitis, and intracranial abscess.[16] The patients were excluded from the study if they had severe open craniocerebral contaminated incisions or in case of incomplete clinical records that may affect the analyses.

Data Collection

Demographic information and clinical data of the patients were recorded. Demographic information included gender and age. Clinical data included the patient's primary disease, the surgical approach used, the duration of the infection-related surgery (in hours), the number of infection-related operations, if it was an emergency surgery or not, the duration of the drainage (in days), the method used for the drainage, the number of drainage tubes, presence of any leakage of the cerebrospinal fluid (CSF), the number of antibiotics used for treatment, the duration of usage of antibiotics (in days), the number of leucocytes in the CSF (×10⁶/l), the number of erythrocytes in the CSF (×10⁶/l), the erythrocytes-to-leucocytes ratio in the CSF, the mononuclear cell percentage in the CSF, the multinucleated cell percentage in the CSF, the amount of glucose in the CSF (mmol/l), the total amount of proteins in the CSF (mg/l), the amount of chlorine in the CSF (mmol/l), the bacteria responsible for the infection, the type of cultured bacteria (categorized), the time before the incurrence of the infection (in days), and the duration of infection (in days).

The number of infection-related operations refers to the number of operations that the patient underwent before the development of an intracranial infection during hospitalization. The duration of the infection-related surgery is the duration of the most relevant surgery before the infection. The duration of drainage refers to the length of time the drainage tube was kept in place before the incurrence of infection. CSF samples were taken at the time of diagnosis of the infection. The results from bacterial culture derive from samples taken after the development of infection. The duration of the infection refers to the time from the diagnosis to the time when the patient was considered cured of the infection or to the time of death or neurologic deterioration. The time of discharge from the hospital was selected as the clinical observation endpoint.

Statistical Analysis

To study the influence of the factors correlated to the prognosis of patients with intracranial infection, we analyzed each factor by univariate analysis. Specifically, two independent sample t-tests and two independent sample rank-sum tests (Mann–Whitney U test) were used for continuous variables, whereas the chi-squared test and Fisher's exact test were used for categorical variables. A difference of p < 0.05 was considered significant. A student's t-test was used to analyze age and glucose content in the CSF, given their normal distribution. Mann–Whitney U test was used to analyze several parameters, including the number of infection-related operations, duration of infection-related surgeries, number of drainage tubes placed before the infection, duration of drainage before infection, number of antibiotics used, duration of antibiotic treatment (in days), number leucocytes in the CSF, number of erythrocytes in the CSF, ratio between erythrocytes and leucocytes, percentage of monocytes, percentage of multinucleated cells, total protein content, chlorine content, number of bacteria, time before infection. A chi-squared test was used to analyze sex, emergency operations versus nonemergency operations, and the occurrence of CSF leakage. Fisher's exact test was used to analyze the primary disease, the surgical approach, the method of drainage, and the results of bacterial culture. All data were analyzed using the SPSS software (version 25.0). Multivariate logistic regression analyses were performed on the influencing factors that presented significant differences.

Results

Patient Demographics

Data on 113 patients, including 58 males (51.3%) and 55 females (48.7%), were collected and investigated. The minimum age of the patients was 15 years and the maximum age was 85 years, with an average age of 56.07 ± 12.65 years (see [Table 1] for details). These patients were affected by 15 primary diseases (see [Table 2] for details).

Table 1 Incidence and recovery rate in 113 patients with postoperative infection

Age group (y)	Infected patients	Proportion (%)	Cumulative ratio (%)	Cured patients	Cure ratio (%)
15∼	1	0.9	0.9	1	100
25∼	6	5.3	6.2	5	83.3
35∼	10	8.8	15.0	9	90
45∼	31	27.4	42.5	26	83.9
55∼	37	32.7	75.2	31	83.8
65∼	21	18.6	93.8	14	66.7
75–85	7	6.2	100	6	85.7

Table 2 Incidence and cure rate in 113 patients grouped by primary disease

Primary	Infected patients	Proportion (%)	Cured patients	Cure ratio (%)
Cerebral hemorrhage	58	51.3	43	74.1
Aneurysm	22	19.5	18	81.8
Glioma	8	7.1	8	100
Trigeminal neuralgia	6	5.3	6	100
Brain injury	4	3.5	3	75
Pituitary tumor	3	2.7	3	100
Facial spasm	2	1.8	2	100
Meningiomas	2	1.8	1	50
Acoustic neuroma	2	1.8	2	100
Arteriovenous malformation	1	0.9	1	100
Cavernous hemangioma	1	0.9	1	100
Craniopharyngioma	1	0.9	1	100
Ependymal tumor	1	0.9	1	100
Pineal tumor	1	0.9	1	100
Arachnoid cyst	1	0.9	1	100

Due to the diversity in etiology, pathology, and site of diagnosis, diagnosis of the primary diseases was divided into the following categories: 81 cases (71.7%) of spontaneous intracranial hemorrhage, 19 cases of intracranial tumor (16.8%), 4 cases of traumatic brain injury (3.5%), 6 cases of trigeminal neuralgia (5.3%), and others. Similarly, the types of surgeries that preceded the infection were classified according to the surgical method utilized: 38 cases of craniotomy (33.6%), 36 cases of ventricular drainage (31.9%), 13 cases of craniotomy plus ventricular drainage (11.5%), 9 cases of decompressive craniectomy (8.0%), 7 cases of lumbar drainage (6.2%), 5 cases of ventricular drainage plus lumbar drainage (4.4%), 4 cases of craniotomy plus lumbar drainage (3.5%), and 1 case (0.9%) of decompressive craniectomy plus ventricular drainage. Among all the surgeries performed, 75 cases (66.4%) were categorized as emergency surgeries and 38 cases (33.6%) as nonemergency surgeries (see [Table 3] for details).

Table 3 Incidence and cure rate in 113 patients grouped by surgical method

Surgical approach	Infected patients	Proportion (%)	Cumulative ratio (%)	Cured patients	Cure ratio (%)
Craniotomy	38	33.6	33.6	35	92.1
Ventricular drainage	36	31.9	65.5	26	72.2
Craniotomy and ventricular drainage	13	11.5	77.0	9	69.2
Decompressive craniectomy	9	8.0	85.0	7	77.8
Lumbar drainage	7	6.2	91.2	7	100.0
Ventricular drainage and lumbar drainage	5	4.4	95.6	4	80.0
Craniotomy and lumbar drainage	4	3.5	99.1	3	75.0
Decompressive craniectomy and ventricular drainage	1	0.9	100.0	1	100.0

Microbiology

Samples from 108 patients were collected for bacterial culture. Fifty-one cases (45.1%) were negative and 57 cases (48.7%) were positive for bacterial contamination, and 7 cases (6.2%) were not analyzed. Among the bacteria species detected, the most common bacteria were Acinetobacter baumannii (11.5% with 14 cases), Klebsiella pneumonia (7.1% with 8 cases), the gram-positive bacilli by smear (2.7% with 3 cases), and Pseudomonas aeruginosa (2.7% with 3 cases).

Risk Factors

After univariate analyses, the parameters that emerged as possible risk factors affecting the prognosis were whether the surgery was an emergency operation or not, the number of infection-related operations, the duration of the drainage (in days) before the infection, the number of antibiotics used for the treatment, the duration of antibiotic treatment (in days), the number of leucocytes in the CSF, and the glucose content in the CSF (mmol/l), the total protein content in the CSF (mg/l), the cultured bacteria, the number of cultured bacteria, and duration of infection (p < 0.05; see [Table 4] for univariate analysis results).

Table 4 Univariate analysis results

	Outcome		X 2/t/Z	p value
	Deteriorated (n = 21)	Cured (n = 92)
Sex
Female	9 (16.4%)	46 (83.6%)	0.349	0.555
Male	12 (20.7%)	46 (79.3%)
Age (y)	58.33 ± 11.45	55.55 ± 12.91	0.908	0.366
Primary disease
Intracranial hemorrhage	19 (23.5%)	62 (76.5%)	–	0.107
Intracranial trauma	1 (25.0%)	3 (75.0%)
Intracranial tumor and cysts	1 (5.0%)	19 (95.0%)
Mimic convulsion and trigeminal neuralgia	0	8 (100.0%)
Surgical approach
Craniotomy	3 (7.9%)	35(92.1%)	–	0.197
Decompressive craniectomy	2 (22.2%)	7(77.8%)
Ventricular drainage	10 (27.8%)	26 (72.2%)
Craniotomy + ventricular drainage	4 (30.8%)	9 (69.2%)
Decompressive craniectomy + ventricular drainage	0	1 (100.0%)
Lumbar drainage	0	7 (100.0%)
Craniotomy + lumbar drainage	1 (25.0%)	3 (75.0%)
Ventricular drainage + lumbar drainage	1 (20.0%)	4 (80.0%)
Emergency
No	3 (7.9%)	35 (92.1%)	4.324	0.038
Yes	18 (24.0%)	57 (76.0%)
Number of infection-related operations	2 (1, 2)	1 (1, 2)	–2.285	0.022
Duration of the infection-related surgery	1.00 (0.59, 3.71)	3.25 (1.00, 4.25)	–1.618	0.106
Type of drainage
No	0	18 (100.0%)	–	0.180
Ventricular drainage	11 (28.9%)	27 (71.1%)
Subcutaneous drainage	4 (16.0%)	21 (84.0%)
Lumbar drainage	1 (14.3%)	6 (85.7%)
Ventricular drainage + subcutaneous drainage	2 (15.4%)	11 (84.6%)
Ventricular drainage + lumbar drainage	2 (33.3%)	4 (66.7%)
Subcutaneous drainage + lumbar drainage	1 (20.0%)	4 (80.0%)
Ventricular drainage + subcutaneous drainage + lumbar drainage	0	1 (100.0%)
Number of tubes placed before infection	1.0 (1.0, 1.5)	1.0 (1.0, 1.0)	–1.378	0.168
Duration of the drainage before infection (days)	9 (4, 19)	4 (2, 8)	–2.914	0.004
CSF leakage
Yes	17 (18.5%)	75 (81.5%)	0.000	0.994
No	2 (14.3%)	12 (85.7%)
Number of antibiotics	2 (2, 2)	2 (1, 2)	–2.050	0.040
Duration of antibiotic treatment (in d)	10 (3, 18)	15 (9, 24)	–2.339	0.019
Leucocytes in CSF (106/l)	38.40 (15.25, 122.40)	13.30 (6.00, 24.85)	–3.126	0.002
Erythrocytes in CSF (106/l)	2,680 (160, 7,900)	2,370 (83, 22,660)	–0.532	0.595
Erythrocytes-to-leucocytes ratio	0.61 (0.02, 2.79)	1.65 (0.11, 11.06)	–1.613	0.107
Monocyte percentage	22.5 (20.0, 30.0)	22.5 (20.0, 30.0)	–0.370	0.712
Multinucleated cell percentage	77.5 (70.0, 80.0)	77.5 (70.0, 80.0)	–0.370	0.712
Glucose content (mmol/l)	1.12 ± 1.44	2.07 ± 1.17	–3.176	0.002
Total protein content (mg/l)	37.08 (21.35, 67.31)	19.77 (11.37, 34.06)	–2.964	0.003
Chlorine (mmol/l)	116.65 (110.23, 122.00)	119.10 (115.03, 124.00)	–1.466	0.143
Bacterial culture
Negative	2 (3.9%)	49 (96.1%)	–	0.000
Gram negative	14 (48.3%)	15 (51.7%)
Gram positive	1 (5.6%)	17 (94.4%)
Mixed bacteria	1 (16.7%)	5 (83.3%)
Candida albicans	1 (50.0%)	1 (50.0%)
Uncultivated	2 (28.6%)	5 (71.4%)
Number of bacteria	1 (1, 1)	0 (0, 1)	–2.958	0.003
Timespan before infection (in d)	9.0 (5.5, 21.0)	7.0 (4.3, 10.0)	–1.537	0.124
Duration of infection	10.0 (2.5, 16.5)	12.0 (8.0, 18.0)	–1.967	0.049

CSF; cerebrospinal fluid. Note: t-test: age and glucose content in CSF (mmol/l).

U test: Number of infection-related operations, duration of the infection-related surgery, number of tubes placed before the infection, duration of the drainage before the infection, number of antibiotics, duration of antibiotic treatment (in d), leucocytes in the CSF, erythrocytes in the CSF, erythrocytes-to-leucocytes ratio, monocyte percentage, multinucleated cell percentage, total protein content, chlorine content, number of bacteria, and timespan before infection.

Chi-squared test: sex, whether it was an emergency surgery or not, and CSF leakage.

Fisher's exact test: primary disease, surgical approach, drainage method, and results of bacterial culture.

The prognosis (cured/deteriorated: 1/0) was used as the dependent variable and the influencing factors in the univariate analysis were the independent variables. Multivariate logistic regression analysis was performed using the stepwise method (forward: Likelihood Ratio test [LR]). The results indicated that the independent risk factors affecting prognosis include the duration of drainage before infection, number of antibiotics used for treatment, duration of antibiotic treatment (in days), and the number of leucocytes in the CSF (×10⁸; p < 0.05). In particular, the duration of drainage (B: –0.113; odds ratio [OR]: 0.893; 95% confidence interval [CI]: 0.805–0.991; p = 0.033), the number of antibiotics used for treatment (B: –1.470; OR: 0.230; 95% CI: 0.072–0.738; p = 0.013), and the number of leucocytes in the CSF (B: –0.016; OR: 0.984; 95% CI: 0.970–0.998; p = 0.027) are all risk factors that inversely correlate with a positive prognosis for the patient. On the contrary, the duration of antibiotic treatment (B: 0.176; OR: 1.193; 95% CI: 1.063–1.339; p = 0.003) was shown to positively correlate with a good prognosis for patients affected by an intracranial infection. The results of the logistic meaningful analyses are shown in [Table 5].

Table 5 Logistic regression analysis results

	B	S.E.	Wald	df	Sig.	Exp(B)	95% CI for Exp(B)
							Lower	Upper
Drainage duration before infection	–0.113	0.053	4.567	1	0.033	0.893	0.805	0.991
Number of antibiotics	–1.470	0.595	6.104	1	0.013	0.230	0.072	0.738
Duration of antibiotic treatment	0.176	0.059	8.971	1	0.003	1.193	1.063	1.339
Leucocytes in CSF (108/l)	–0.016	0.007	4.893	1	0.027	0.984	0.970	0.998

Abbreviations: CI, confidence interval; CSF, cerebrospinal fluid; S.E., standard error.

Discussion

Postoperative Central Nervous System Infections (PCNSIs) are a serious complication of neurosurgery that needs further understanding. However, little is known about the clinical risk factors that may affect the prognosis of patients affected by a postoperative intracranial infection. In a retrospective study of 115 patients with gram-negative meningitis, it was reported that factors that correlated to a 30-day mortality or neurologic deterioration included the following: days from admission to meningitis development, consciousness at diagnosis, CSF glucose levels <50 mg/dL at diagnosis, higher creatinine levels, and blood glucose levels lower than 180 mg/dL.[9] In another retrospective study involving 3,580 patients after neurosurgery, the risk factors affecting the prognosis were low CSF glucose content (<20% of blood glucose), increased Acute Physiology and Chronic Health Evaluation III (APACHE III) score, and the presence of gram-negative bacteria.[17] In comparison, the results of multivariate logistic regression analyses performed in our study showed that the duration of the drainage before the development of infection (in days), the duration of the antibiotic treatment (days), the number of antibiotics used for treatment, and the number of leucocytes in the CSF are significantly different in patients with a positive or negative prognosis. Furthermore, the glucose content in the CSF (mmol/L) showed a significant difference between the two patient groups in the univariate analysis. However, the results of multivariate analysis showed that glucose content was not a risk factor for a poorer course of postoperative infection, which was inconsistent with the results presented in the aforementioned articles, where low levels of glucose were correlated to a deterioration in the prognosis. The discrepancy in the results may derive from the methodological differences, as in our study we regarded the CSF glucose content as a continuous variable, while in the previous articles it was analyzed in different range levels.

The duration of the antibiotic treatment (in days) was positively correlated with a good prognosis. Previous literature indicated that early treatment with antibiotics for intracranial infection is beneficial for a patient's prognosis,[18] and the duration of antibiotic treatment is mainly based on the patient's needs and on the types of pathogenic bacteria. It was previously reported that the duration of antibiotic application needs to meet relevant clinical indicators to ensure the achievement of a cure from the infection.[19]

The duration of drainage before the incurrence of infection (in days) is also a risk factor for a good prognosis. It was shown before that placement of the drainage tube and its duration are risk factors for intracranial infection after neurosurgery. In particular, the longer the duration of the drainage, the higher the rate of infection.[20] Interestingly, our data indicate that the duration of drainage before the infection is also a predictor of a poor prognosis, as the longer the duration of drainage, the worse the prognosis. Due to the limited sample size, an accurate prediction model on the duration of drainage has not been established. However, previous literature suggested that the risk of external ventricular drainage-related meningitis increases by 3.832-fold, if the drainage was used for 5 days, and that the risk of postoperative meningitis increases by 11.492-fold, if used for >7 days. .[20] Therefore, surgeons should pay special attention to patients with >5 days of external ventricular drainage or >7 days of lumbar drainage.

The number of leucocytes in the CSF (×10⁸/l) at the time of diagnosis of infection was also a risk factor against complete healing of the patients. To make the results of the logistic analyses meaningful, we convert units from 10⁶ to 10⁸/l. If the number of leucocytes is increased when the infection is diagnosed, the probability of recovery from infection becomes higher.

The number of antibiotics used for treatment represents the total number of antibiotics administrated to the patient from the time of diagnosis to the clinical observation endpoint. We found that when the number of antibiotics used increases, the prognosis is more likely to worsen. This was not previously reported in the literature. Further analyses of this group of patients revealed that these individuals were often seriously ill. As the infection was not easy to control, multiple bacterial cultures and several changes in the type of antibiotics were performed.

Diabetes is analyzed as a risk factor in some studies on intracranial infection after neurosurgery. A retrospective study of 115 patients with gram-negative meningitis conducted by Neuberger et al shows that blood glucose >180 mg/dL was associated with an unfavorable outcome on multivariate analysis.[9] In another retrospective study involving 3,580 patients after neurosurgery, the risk factors affecting the prognosis were low CSF glucose content, increased APACHE III score, and the presence of gram-negative bacteria. In this study, diabetes was not included in the risk factors analyzed. Unfortunately, there is no patient with diabetes and obesity enrolled in our study currently, so diabetes was not included in the risk factors analyzed. Indeed, the experience of surgeons is also a risk factor, which is not often considered in the literature, probably because the experience cannot be accurately quantified.

The main limitation of this study is that all the cases collected belonged to the same hospital center. Therefore, further analyses of patients coming from other centers are necessary to confirm our results.

Conclusions

According to our analyses, an increase in the duration of drainage before infection, the number of antibiotics used for treatment, and the number of leucocytes in the CSF are all factors correlated with a deterioration of the prognosis for patients with postoperative cranial infection. On the contrary, when the duration of antibiotic treatment increases, chances of recovery also become higher. This study will help clinicians to identify patients at risk of poor prognosis and, thus, improve the rate of recovery thanks to early intervention.

Conflict of Interest

None declared.

Disclosure Statement

The authors declare that they have no financial interest in relation to this article and its publication. All data in this article are available.

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Publication History

Received: 17 April 2022

Accepted: 01 September 2022

Accepted Manuscript online:
07 September 2022

Article published online:
16 January 2024