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*For medical professionals only
, the article explains the rational application
of antimicrobials in neurological related diseases.
27 million
deaths due to bacterial antimicrobial resistance occurred in 2019.
The following is a brief summary of the use of antibacterial drugs (for bacteria and fungi) in neurological diseases for your reference
.
First, the classification of antibacterial drugs for neurological diseases
Preventive medication Preventive medication
is generally used to prevent infections
caused by specific pathogenic bacteria or that may occur in specific groups of people.
Such as the prophylactic application
of perioperative antibacterial agents in neurosurgery.
The purpose of prophylaxis is mainly to prevent surgical site infections, including superficial incision infections, deep incision infections, and organ/space infections involved in surgery, but does not include other site infections
that are not directly related to surgery and may occur after surgery.
Brain surgery (clean, no implants) is generally a class I incision, possible contaminating bacteria are Staphylococcus aureus, coagulase-negative staphylococcus, etc.
, it is generally recommended to use the first and second generation cephalosporins, for high-risk patients with high incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection can be used (norcomycin) vancomycin; Brain surgery through the sinuses, nasal cavity, oropharynx is a class II incision, and the possible contaminating bacteria are Staphylococcus aureus, streptococcus, oropharyngeal anaerobic bacteria (such as digestive streptococcus) It is generally recommended to use first- and second-generation cephalosporins± metronidazole, or clindamycin + gentamicin
.
■2.
Therapeutic medication
For patients with clinical diagnosis of bacterial or fungal infection, the use of antibacterial drugs is therapeutic medicine
。 The most common in neurology is central nervous system (CNS) infection, which is an acute or chronic infection
caused by various pathogens invading the brain parenchyma, membrane and blood vessels.
can be given first.
After the etiology test and drug susceptibility results are known, the medication plan is adjusted based on the previous treatment response; For patients with negative culture results, further treatment measures should be taken based on the response of empirical therapy and the patient's condition
.
Second, the application of neurological antibacterial drugs precautions
■ 1.
Drug selection
according to the characteristics of common pathogenic bacteria and drug resistance, for example, the common pathogenic bacteria of bacterial meningitis are meningococcus, Streptococcus pneumoniae and staphylococcus
.
Common pathogenic bacteria of brain abscess include streptococcus, enterobacteriaceae, and Staphylococcus aureus
.
.
(2) Streptococcus pneumoniae: penicillin-sensitive Streptococcus pneumoniae (MIC≤0.
06 mg/L) select penicillin G, penicillin-sensitive Streptococcus pneumoniae: when penicillin MIC≥0.
12 mg/L third-generation cephalosporin sensitivity and MIC<1 mg/L can be used ceftriaxone or cefotaxime; Vancomycin can be used in third-generation cephalosporin
insensitive (MIC≥1 mg/L).
(3) Haemophilus influenzae: Ampicillin is used for those who do not produce β-lactamase, and third-generation cephalosporins
are used for those who produce β-lactamase.
(4) Staphylococcus genus: MSSA uses oxacillin, cefazolin, MRSA uses vancomycin
.
(5) Enterobacteriaceae: non-ESBL-producing bacteria use third-generation cephalosporins, such as ceftriaxone or monocyclic aminotreonam; ESBL-producing bacteria can choose carbapenems, such as meropenem, etc.
(imipenem is generally not used for meningitis because it is easy to produce convulsions).
(7) Pseudomonas aeruginosa: cefepime or meropenem, alternative drugs are aztreonam or quinolones with anti-pseudomonas activity
.
■ 2.
Select drugs with higher concentrations in cerebrospinal fluid due to the presence of the blood-brain barrier,
The choice of anti-infective drugs for CNS infections must consider whether the drug can penetrate the blood-brain barrier
.
The distribution of drugs in CNS depends not only on the relative molecular weight, charge, lipophilicity, plasma protein binding rate, blood-brain barrier, etc.
of the drug, but also on
the host's own factors.
The third and fourth generation cephalosporins, aztreonam, carbapenems, sulfonamides, quinolones, vancomycin, rifampicin and isoniazid have high penetration of the blood-brain barrier and high concentrations in cerebrospinal fluid (Table 1).
■3.
Optimize the dosing regimen
according to the characteristics of antibacterial drug PK/PD Concentration-dependent drugs for bacterial meningitis can be increased in doses such as amikacin 15 mg/kg intravenously for bacterial meningitis caused by susceptible bacteria; High-dose intracyclofloxacin can be used in adult patients with Pseudomonas aeruginosa meningitis, 800~1200 mg/d, divided intravenous drip, 1 time/8 h or 12 h, can also be combined with aminoglycosides
.
■4.
The necessity of intrathecal injection of antibacterial drugs
Table 2 Recommendation, dosage and adverse reactions of intraventricular administration of antibacterial drugs[2]References[1]Revision Working Group of "Guidelines for the Clinical Application of Antimicrobials".
Guidelines for the clinical application of antimicrobials[M].
2015 Edition Beijing: People's Medical Publishing House, 2015: 5-8
Where to see more neurological clinical knowledge?
Come to the "doctor's station" and take a look 👇
, the article explains the rational application
of antimicrobials in neurological related diseases.
In May 2020, the World Health Organization, the Food and Agriculture Organization of the United Nations and the World Organisation for Animal Health met and decided to change the name "antimicrobial" to "antimicrobial" and designated thethird week of January and November as "World Antimicrobial Awareness Week"
.
This year, the theme of World Antimicrobial Awareness Week is "Preventing Antimicrobial Resistance Together
".
So what is antimicrobial resistance? It is thought that when bacteria, viruses, fungi and parasites change over time and no longer respond to drugs, antimicrobial resistance develops, making infections more difficult to treat and increasing the risk of
disease transmission, severe illness and death.
Infections become increasingly difficult or impossible to treat due to the development of drug resistance, which makes antibiotics and other antimicrobials ineffective
.
27 million
deaths due to bacterial antimicrobial resistance occurred in 2019.
The following is a brief summary of the use of antibacterial drugs (for bacteria and fungi) in neurological diseases for your reference
.
First, the classification of antibacterial drugs for neurological diseases
According to the purpose of medication, the application of antimicrobial drugs can be divided into prophylactic drugs and therapeutic drugs
.
Preventive medication Preventive medication
is generally used to prevent infections
caused by specific pathogenic bacteria or that may occur in specific groups of people.
Such as the prophylactic application
of perioperative antibacterial agents in neurosurgery.
The purpose of prophylaxis is mainly to prevent surgical site infections, including superficial incision infections, deep incision infections, and organ/space infections involved in surgery, but does not include other site infections
that are not directly related to surgery and may occur after surgery.
Brain surgery (clean, no implants) is generally a class I incision, possible contaminating bacteria are Staphylococcus aureus, coagulase-negative staphylococcus, etc.
, it is generally recommended to use the first and second generation cephalosporins, for high-risk patients with high incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection can be used (norcomycin) vancomycin; Brain surgery through the sinuses, nasal cavity, oropharynx is a class II incision, and the possible contaminating bacteria are Staphylococcus aureus, streptococcus, oropharyngeal anaerobic bacteria (such as digestive streptococcus) It is generally recommended to use first- and second-generation cephalosporins± metronidazole, or clindamycin + gentamicin
.
■2.
Therapeutic medication
For patients with clinical diagnosis of bacterial or fungal infection, the use of antibacterial drugs is therapeutic medicine
。 The most common in neurology is central nervous system (CNS) infection, which is an acute or chronic infection
caused by various pathogens invading the brain parenchyma, membrane and blood vessels.
CNS infection can be divided into bacterial, viral and fungal according to pathogens
.
According to the site, it can be divided into meningeal infection and brain parenchymal infection
.
The pathogenic organisms that cause intracranial infections often include viruses, bacteria, fungi, spirochetes, parasites, rickettsia, and prions
.
According to the patient's symptoms, signs, laboratory tests or radiological, ultrasound and other imaging results, patients diagnosed with bacterial and fungal infections should be indicated to use antibacterial drugs; Antibacterial drugs are also indicated for infections caused by pathogenic microorganisms such as Mycobacterium tuberculosis, Mycobacterium, Chlamydia, Spirochetes, Rickettsial and some protozoa; For viral infections that are ineffective with antimicrobials, appropriate antivirals
should be used.
can be given first.
After the etiology test and drug susceptibility results are known, the medication plan is adjusted based on the previous treatment response; For patients with negative culture results, further treatment measures should be taken based on the response of empirical therapy and the patient's condition
.
Second, the application of neurological antibacterial drugs precautions
■ 1.
Drug selection
according to the characteristics of common pathogenic bacteria and drug resistance, for example, the common pathogenic bacteria of bacterial meningitis are meningococcus, Streptococcus pneumoniae and staphylococcus
.
Common pathogenic bacteria of brain abscess include streptococcus, enterobacteriaceae, and Staphylococcus aureus
.
The following recommendations are made for the selection of antiinfective agents for common pathogenic organisms:
.
(2) Streptococcus pneumoniae: penicillin-sensitive Streptococcus pneumoniae (MIC≤0.
06 mg/L) select penicillin G, penicillin-sensitive Streptococcus pneumoniae: when penicillin MIC≥0.
12 mg/L third-generation cephalosporin sensitivity and MIC<1 mg/L can be used ceftriaxone or cefotaxime; Vancomycin can be used in third-generation cephalosporin
insensitive (MIC≥1 mg/L).
(3) Haemophilus influenzae: Ampicillin is used for those who do not produce β-lactamase, and third-generation cephalosporins
are used for those who produce β-lactamase.
(4) Staphylococcus genus: MSSA uses oxacillin, cefazolin, MRSA uses vancomycin
.
(5) Enterobacteriaceae: non-ESBL-producing bacteria use third-generation cephalosporins, such as ceftriaxone or monocyclic aminotreonam; ESBL-producing bacteria can choose carbapenems, such as meropenem, etc.
(imipenem is generally not used for meningitis because it is easy to produce convulsions).
(6) Acinetobacter species: meropenem should be applied to those who are sensitive to carbapenem; Carbapenem resistant patients should be given polymyxin and administered intraventricularly
.
(7) Pseudomonas aeruginosa: cefepime or meropenem, alternative drugs are aztreonam or quinolones with anti-pseudomonas activity
.
■ 2.
Select drugs with higher concentrations in cerebrospinal fluid due to the presence of the blood-brain barrier,
The choice of anti-infective drugs for CNS infections must consider whether the drug can penetrate the blood-brain barrier
.
The distribution of drugs in CNS depends not only on the relative molecular weight, charge, lipophilicity, plasma protein binding rate, blood-brain barrier, etc.
of the drug, but also on
the host's own factors.
The third and fourth generation cephalosporins, aztreonam, carbapenems, sulfonamides, quinolones, vancomycin, rifampicin and isoniazid have high penetration of the blood-brain barrier and high concentrations in cerebrospinal fluid (Table 1).
Table 1 Cerebrospinal fluid/plasma concentration of commonly used antibacterial drugs[2].
■3.
Optimize the dosing regimen
according to the characteristics of antibacterial drug PK/PD Concentration-dependent drugs for bacterial meningitis can be increased in doses such as amikacin 15 mg/kg intravenously for bacterial meningitis caused by susceptible bacteria; High-dose intracyclofloxacin can be used in adult patients with Pseudomonas aeruginosa meningitis, 800~1200 mg/d, divided intravenous drip, 1 time/8 h or 12 h, can also be combined with aminoglycosides
.
When time-dependent carbapenems are used to treat bacterial meningitis, the instillation time can be appropriately extended on the basis of the adequate dose to improve the efficacy, such as meropenem extending the instillation time to 3 hours, which can successfully treat meningitis
caused by drug-resistant gram-negative bacteria.
■4.
The necessity of intrathecal injection of antibacterial drugs
When systemic administration of CNS infection is not effective, intrathecal administration can be considered to give full play to the advantages of
topical administration.
Such as vancomycin 20 mg, once / day, ventricle administration
.
The concentration of cerebrospinal fluid in intravenous amphotericin B is extremely low, while AUCCSF/AUCS is as high as
100% during intrathecal administration.
Some scholars systematically evaluated 8769 cases of cryptococcal disease in China from 1985 to 2010, of which 2371 cases were CNS cryptococcal infection, and the case fatality rate of intrathecalin B administration was significantly lower than that of non-intrathecal injection
.
It is safe and effective
to use polymyxin intrathecal injection for CNS infection with pan-resistant gram-negative bacteria.
In the treatment of ventriculitis and meningitis caused by pan-resistant and fully resistant Acinetobacter baumannii, the success rate of 83 patients treated intrathecal polymyxin (adult dose was 1.
6~40 mg, pediatric dose was 0.
16 mg/kg, maximum 10 mg) was 89%.
The recommended regimen for intraventricular administration of antimicrobials is shown in Table 2
.
Table 2 Recommendation, dosage and adverse reactions of intraventricular administration of antibacterial drugs[2]References[1]Revision Working Group of "Guidelines for the Clinical Application of Antimicrobials".
Guidelines for the clinical application of antimicrobials[M].
2015 Edition Beijing: People's Medical Publishing House, 2015: 5-8
ZHANG Jing, LV Yuan, et al.
Expert consensus on the clinical application of pharmacokinetics/pharmacodynamics theory of antimicrobial drugs[J].
Chinese Journal of Tuberculosis and Respiratory, 2018, 41(06): 409-446.
HE Lixian, XIAO Yonghong, LU Quan, et al.
Guidelines for national antimicrobial therapy[M].
Beijing:People's Medical Publishing House, 2012.
Where to see more neurological clinical knowledge?
Come to the "doctor's station" and take a look 👇
