June 29, 2022

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Diagnosis of intracranial infection in critical neurological patients

Diagnosis and Treatment of intracranial infection in critical neurological patients


Diagnosis and Treatment of intracranial infection in critical neurological patients. Critical neurological patients include severe head injury, severe cerebral hemorrhage, large-area cerebral infarction, and neurosurgery critically ill patients after large tumor surgery.

Diagnosis of intracranial infection in critical neurological patients


These patients have severely damaged brain tissue, poor brain function, impaired consciousness, multiple organ dysfunction, long-term bed rest, reduced resistance, and are very prone to or complicated with intracranial infection, aggravate the primary injury, reduce the patient’s prognosis, and increase The morbidity and mortality of critically ill patients, and the attributable mortality of central nervous system infections can be as high as 15% to 30%, and the patient and socioeconomic burdens.

Intracranial infections after neurosurgery craniotomy mainly include meningitis, ventriculitis, subdural abscess and brain abscess. The infection rate after craniotomy is about 0.3% to 8.9%. It is reported in the literature that the postoperative infection rate of neurosurgery is as high as 30% to 80%; the postoperative infection rate of contaminated surgery, including open skull fractures and scalp lacerations, is 10% to 25%; clean-contaminated surgery, postoperative The infection rate was 6.8% to 15.0%; the infection rate of clean surgery was 2.6% to 5.0%. Two domestic single-center retrospective case studies showed that post-operative central nervous system infection (PCNSI) rates after neurosurgery craniotomy were 7.4% and 8.6%, respectively.

Common pathogens of intracranial infections are Gram-positive Staphylococcus (Staphylococcus aureus, coagulase-negative Staphylococcus, Enterococcus, MASA), Acinetobacter baumannii, Enterobacter, Pseudomonas aeruginosa, Klebsiella pneumoniae Bacteria etc. There are few reports on the epidemiology of intracranial infection in critically ill patients in domestic and foreign literature. Neurocritical patients in the intensive care unit are critically ill, have low resistance, and are at high risk of infection by resistant bacteria. It can be inferred from clinical experience that the incidence of intracranial infection in critically ill patients may be higher than that of conventional elective craniotomy.

A domestic investigation of intracranial infection in patients after craniotomy in the intensive care unit showed that 12 out of 160 patients had intracranial infection, and the infection rate was 7.5%. A large foreign case report from a single center showed that in the neurosurgery intensive care unit (NICU), the incidence of nosocomial infection was 3.65%, of which the incidence of shunt infection and acquired meningitis was about 0.85%. A statistical report of hospital infections in the NICU of Heidelberg University Hospital in Germany showed that meningitis (0.4%) and ventriculitis (0.8%) in the NICU Hospital of Traditional Chinese Medicine accounted for about 1.2%.

1. High risk factors

Under normal circumstances, brain tissue is protected by multiple protections such as the scalp, skull, dura mater, and blood-brain barrier. The blood-brain barrier can restrict the passage of macromolecular substances, so the central nervous system infection rate is low under normal circumstances. However, the cerebrospinal fluid lacks complement and antibody IgM, has fewer phagocytic cells, and once the bacteria invades the barrier caused by trauma or surgery, and the cerebrospinal fluid is a good medium suitable for bacterial growth and reproduction, it is difficult to control intracranial infections. Common risk factors for intracranial infection include: advanced age, long operation time, multiple operations, cerebrospinal fluid leakage, open wounds, glucocorticoids, diabetes or stress-induced hyperglycemia, massive blood loss, ventricular drainage tube or lumbar drainage tube placement time More than 72h, mechanical ventilation, total parenteral nutrition, etc.

Neurologically critically ill patients are in critical condition, bedridden for a long time, resistance and immunity are low, long-term use of antibiotics causes dysbiosis, lung or intestinal drug-resistant bacteria infection, resulting in the patient’s risk of infection during surgery, wound dressing, lumbar puncture, etc. increase.

2. Diagnosis

The diagnostic criteria for intracranial infection are divided into pathogenic diagnostic criteria and clinical diagnostic criteria. For details, see the standards listed in the “Expert Consensus on the Diagnosis and Treatment of Infection in Critically Ill Patients in China Neurosurgery (2017)”.

2.1 The detection of cerebrospinal fluid etiology and related biomarkers is also of great significance for the diagnosis of bacterial intracranial infection:

lumbar puncture and cerebrospinal fluid examination is of great significance for the diagnosis and treatment of intracranial infection, including general characteristics, cerebrospinal fluid routine, biochemistry, and cerebrospinal fluid bacterial culture And drug sensitivity test, etc. Cerebrospinal fluid cell count, sugar, and protein are not reliable indicators for the diagnosis of infection. Normal cerebrospinal fluid cell count, sugar, and protein cannot exclude the presence of infection. Negative cerebrospinal fluid Gram staining cannot exclude the presence of infection, especially in those who have been treated with antibiotics (weak, Intermediate recommendation).

Positive bacterial culture of cerebrospinal fluid, pus, secretions or tissue specimens, shunt catheters is the gold standard to confirm the diagnosis (strong, advanced recommendation). Should try to save the cerebrospinal fluid before applying antibiotics for culture and drug sensitivity test. In patients with cerebrospinal fluid shunt or external drainage, if the initial culture is negative, specimens should be sent again within at least 10 days. Those with negative cerebrospinal fluid culture can perform molecular biology examination to find the pathogen. The literature reports that the methods to improve the positive rate of cerebrospinal fluid smear and culture include microscopy after differential centrifugation, pretreatment of bacteria collection, and shaking culture method.

2.2 The research progress of biochemical markers that are helpful for diagnosis:

In addition to the pathogenic detection of cerebrospinal fluid, the detection of biochemical markers of cerebrospinal fluid is also of great significance for the diagnosis of intracranial infection.

(1) Cerebrospinal fluid lactic acid:

Elevated cerebrospinal fluid lactate has certain value for the diagnosis of intracranial infection. Cerebrospinal fluid lactic acid concentration greater than 3.5-4.2mmol/L is common in bacterial meningitis. Meta-analysis reports show that elevated cerebrospinal fluid lactic acid has an advantage over cerebrospinal fluid white blood cell count, sugar, and protein in distinguishing bacterial inflammation from aseptic inflammation. It is also one of the commonly used biochemical indicators for clinical identification of bacterial infections and viral infections. Model analysis of elevated cerebrospinal fluid lactate combined with serum PCT can diagnose bacterial meningitis with a very high probability.

The 2017 American Society of Infectious Diseases Clinical Practice Guidelines also pointed out that elevated cerebrospinal fluid lactate and/or elevated cerebrospinal fluid proealcitonin (PCT) can help diagnose medical-related bacterial meningitis and ventriculitis (weak, intermediate) recommend). The Bacterial Ventritis Chapter of the American Clinical Neuromedicine (HCN) Manual recommends that all postoperative neurosurgery patients with cerebrospinal fluid lactic acid concentration ≥4.0mmol/L should be given empirical antibacterial treatment.

(2) Procalcitonin (PCT):

Plasma PCT detection is useful in assessing patients’ central nervous system infections and distinguishing bacterial and viral meningitis infections, while the value of cerebrospinal fluid PCT detection in diagnosing intracranial infections and judging treatment effects is still controversial.

(3) Cerebrospinal fluid protein:

Heparin-binding protein (HBP) is a serine protease secreted by polymorphonuclear neutrophils. It has significant bactericidal activity, chemotactic properties and inflammation regulation. HBP in cerebrospinal fluid is an ideal indicator to assist in the diagnosis of bacterial intracranial infection. A prospective study showed that the sensitivity of cerebrospinal fluid HBP>20mg/ml in the diagnosis of bacterial meningitis reached 100%, and the specificity reached 99.2%.

HBP is of great significance for distinguishing bacterial intracranial infection from non-bacterial intracranial infection, and the increase is related to the severity of infection and the prognosis of the disease. Non-invasive detection of serum HBP can also be used as an ideal potential marker for acute bacterial meningitis, and it has differential diagnostic significance even for treated patients. For critically ill patients with meningitis, further research and close monitoring of HBP plasma levels are recommended, which is expected to replace the current clinically commonly used repeated lumbar puncture to monitor changes in bacterial meningitis.

(4) Other markers under experimental research

Other markers under experimental researchinclude cerebrospinal fluid enzymes, immunological markers, and cerebrospinal fluid cytokines, etc., which have auxiliary value for the identification of intracranial infection pathogens, but due to low specificity, cumbersome detection, and low cost performance. It is far from clinical practical application.

3. Treatment

The central nervous system has special anatomical and pathophysiological characteristics: there is a blood-brain barrier and a lack of lymphatic system. In the case of intracranial infection, antibiotics that can easily pass through the blood-brain barrier and reach an effective bactericidal concentration in the cerebrospinal fluid should be used. The treatment principles recommended by the latest Chinese expert consensus are as follows:

(1) When a central nervous system infection is suspected, empirical antimicrobial therapy should be started as soon as possible, and the treatment plan can be adjusted in time according to the results of drug sensitivity;

(2) First choose antibacterial drugs that easily penetrate the blood-brain barrier, and intravenous route is recommended for drug treatment;

(3) The maximum drug dosage allowed by the instructions and possible long-term treatment;

(4) Empirical antimicrobial therapy> 72 hours with poor efficacy should consider adjusting the treatment plan. The treatment of intracranial infection in critically ill patients has the following aspects.

3.1 Etiological treatment:

If patients with severe neurological illness are suspected of intracranial infection, they should receive empirical treatment immediately. Early antimicrobial treatment is positively correlated with a good prognosis. For details of the empirical treatment drug selection plan, please refer to the consensus of Chinese experts. The choice of antibacterial drugs can first cover gram-positive bacteria and gram-negative bacteria.

Gram-positive bacteria:

Common coagulase-negative staphylococci, staphylococcus aureus and enterococcus. When the risk of bacterial resistance is low, choose nafcillin or oxacillin. When the risk of resistance is high (such as methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus), vancomycin is the first choice, and linezolid is the second choice. Vancomycin can be used locally to increase the effective concentration of the drug.

Gram-negative bacteria:

Common Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Carbapenem-resistant Enterobacter, etc. The first choice for anti-infective treatment of gram-negative bacteria is third-generation cephalosporin; if it is a widely drug-resistant gram-negative bacteria infection, the first choice is meropenem, which has the advantages of easy penetration of the blood-brain barrier and low central and renal toxicity. It has been reported in the literature that the intravenous 1gq6h and 2gq8h dosing regimens of meropenem have a higher degree of cerebrospinal fluid penetration than the intravenous 1gq8h dosing regimen. Higher doses and shorter dosing intervals are more helpful in removing pathogens.

For drug-resistant Acinetobacter baumannii infection, intravenous polymyxin combined with intrathecal injection or intracerebroventricular administration is considered to be a more effective anti-infective treatment. There are many treatment options for Candida infection in the central nervous system. Amphotericin B [0.5~0.7mg/(kg·d)] or amphotericin B liposome alone or combined with flucytosine is recommended. Fluconazole 400~800mg (6~12mg/kg) daily alone or in combination with flucytosine is the second choice, which is suitable for patients who cannot tolerate amphotericin B or have relatively mild disease.

3.2 Route of administration:

Topical medication is based on rational intravenous medication, through intrathecal injection, intraventricular administration and other methods to increase the concentration of cerebrospinal fluid drugs, which directly act on the area of ​​infection and inflammation, and the drug residence time is 15-60 minutes. Consider giving intraventricular antimicrobial therapy in the following situations:

  • (1) Systemic application of antibiotics cannot achieve a sufficiently high cerebrospinal fluid drug concentration under non-toxic doses;
  • (2) Those whose cerebrospinal fluid culture results continue to be positive after 48-72 hours of systemic application of antibiotics and other anti-infective treatment measures.

Still cautious about intrathecal injection of antibacterial drugs through lumbar puncture. Because lumbar puncture injection of drugs can cause serious complications such as increased intracranial pressure, osmotic pressure gradient, uneven drug concentration, and chemical inflammation leading to spinal canal adhesions.

After intrathecal injection, the head can be kept low to increase drug diffusion and increase local drug concentration. Antibacterial and antifungal drugs that can be used for intrathecal injection include gentamicin, tobramycin, netilmicin, amikacin, streptomycin, polymyxin (colistin, polymyxin B), glycopeptides (vancomycin, teicoplanin), tigecycline, amphotericin B, caspofungin, etc.

3.3 Long treatment duration:

Expert consensus recommends that anti-infective treatment of the central nervous system should be long-term treatment. The treatment time for typical infections is 4-8 weeks. Anti-infective treatment should be continued for 1 to 2 weeks after meeting the clinical cure criteria. Generally, three consecutive CSF tests are normal and the bacterial culture is negative as the clinical cure standard. It is recommended to give the maximum drug dose and a long course of treatment. Long-term drug concentration in the cerebrospinal fluid exceeding the minimum bactericidal concentration is the key to successful treatment. The total course of anti-infective treatment for patients with subdural empyema is generally 3 to 6 weeks, and the total course of anti-infective treatment for patients with brain abscess is generally 6 to 8 weeks.

3.4 Surgical treatment:

Use ventricular drainage or lumbar cistern drainage to smooth cerebrospinal fluid drainage to promote cerebrospinal fluid inflammation. If there are clear infection foci, such as subdural empyema, brain abscess, skin and soft tissue infection, etc., the wound should be thoroughly debrided. Artificial materials (artificial dura mater, skull repair materials, Ommaya capsule, etc.) should be removed as soon as possible. Patients with intraventricular empyema can be flushed under ventriculoscopy.

Abscess puncture and aspiration is feasible after the formation of brain abscess package. Brain abscess puncture and aspiration can isolate the lesion, reduce the volume of the abscess and learn the type of pathogenic bacteria. It is recommended for brain abscesses with known pathogens, diameter <2.5mm and deep location Antibiotics alone should not be used for brain abscesses in patients with brain abscesses complicated by meningitis, ventriculitis or low intracranial pressure. Patients with subdural empyema can be operated to drain the pus.

3.5 Symptomatic and supportive treatment:

Symptomatic and supportive measures such as dehydration and lowering of intracranial pressure, anti-epileptic, analgesia, and nutritional support can be given according to the patient’s clinical symptoms and imaging findings to reduce complications, enhance the patient’s body resistance, and shorten the course of the disease.

3.6 Prevention of intracranial infection in critically ill patients:

The attributable fatality rate of intracranial infection is relatively high, about 15-30% reported in the literature. In particular, drug-resistant bacterial infection significantly increases the difficulty of treatment, prolongs the course of the disease, and reduces the prognosis. Critically ill patients are in the intensive care unit environment, and good quality control of the sense of hospitality is of great significance for reducing the occurrence of nosocomial infections (including intracranial infections).

Using antibiotics cautiously and rationally, strictly following the principle of “empirical medication-bacterial drug sensitivity experiment”, and reducing the emergence of drug-resistant bacteria are the overall measures to actively prevent intracranial infections. In clinical diagnosis and treatment, surgery and operations should strictly follow the principle of aseptic to minimize the risk of intracranial infection.

(source:internet, reference only)

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