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    Home > Active Ingredient News > Infection > Professor Wang Sheng: CRKP infection treatment challenges are severe, don’t forget the carbapenem combination treatment plan

    Professor Wang Sheng: CRKP infection treatment challenges are severe, don’t forget the carbapenem combination treatment plan

    • Last Update: 2022-01-09
    • Source: Internet
    • Author: User
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    *It is only for medical professionals to read about Klebsiella pneumoniae infection and drug resistance, and look forward to the status and prospects of carbapenem drugs
    .

    Klebsiella pneumoniae is a common pathogenic enterobacteria.
    With the widespread application of carbapenem drugs, the detection rate of carbapenem-resistant Klebsiella pneumoniae (CRKP) continues to rise, becoming a global Public health issues of concern
    .

    In 2017, the World Health Organization (WHO) listed CRKP as one of the most important drug-resistant pathogens in the 21st century, which poses a huge challenge to infection control
    .

    Therefore, the "medical community" specially invited Professor Wang Sheng from the Tenth People's Hospital of Tongji University to introduce the current status of CRKP infection, share treatment measures, and look forward to treatment prospects
    .

    Uncovering the mystery of Klebsiella pneumoniae Klebsiella pneumoniae (referred to as lung grams) was first reported by Carl Friedlander in 1882.
    It belongs to the Enterobacteriaceae of Gram-negative bacilli and belongs to the genus Klebsiella.
    Important member
    .

    The microscopically showed Brevibacterium vulgaris, which has a capsule, and has both O antigen and K antigen (ie, bacterial antigen and capsular antigen)
    .

    Professor Wang Sheng introduced Road, Klebsiella pneumoniae is a common respiratory tract colonization, in addition can also be found in many other parts of the body, such as urinary tract, digestive tract, reproductive tract, blood and nervous system
    .

    Klebsiella pneumoniae is a common pathogenic bacteria in clinical conditions, the most common is respiratory tract infection, and it is also very easy to cause sepsis, meningitis, urinary system infection, peritonitis and so on
    .

    In recent years, due to the increasingly serious abuse of antibiotics, the widespread resistance of antibiotics has brought great challenges to the anti-infection work, directly increasing the difficulty of clinical treatment of such bacterial infections, and the resistance of Klebsiella pneumoniae The high fatality rate caused by the medicine poses a serious threat to the life safety of patients
    .

    Interpretation of the resistance mechanism and detection rate of CRKP The resistance mechanism of CRKP is quite complicated and has not been fully elucidated.
    The more clear mechanisms are currently considered to be: carbapenemase production, deletion or mutation of outer membrane protein, overexpression of efflux pump, and Variations of penicillin binding proteins, the most important of which is carbapenemase production.
    Carbapenemase production can also be subdivided into KPC enzyme production, metalloenzyme production, OXA production and so on
    .

    Bacterial mobile genetic elements (such as plasmids) can carry resistance genes to transfer and spread among the same or different strains, accelerating the resistance of Klebsiella pneumoniae to clinical antibacterial drugs and the dissemination of resistant bacteria, thereby forming multiple Drug-resistant bacteria bring great difficulties to treatment
    .

    The 2018 National Bacterial Resistance Surveillance Report showed that the average resistance rate of patients with Klebsiella pneumoniae infection to carbapenem drugs was 10.
    1%.
    In the intensive care unit (ICU), patients with Klebsiella pneumoniae infection were resistant to carbon.
    The resistance rate of penicillene drugs is even higher, which has exceeded 60%
    .

    In China, the more developed areas, such as the southeast coast, Beijing and Tianjin, the higher the resistance rate of Klebsiella pneumoniae.
    This may be related to the earlier application and popularization of high-grade antibiotics in developed areas
    .

    Professor Wang Sheng also emphasized that the detection rate of CRKP is showing an upward trend year by year.
    According to the dynamic monitoring of China Antimicrobial Resistance Surveillance Network (CHINET) in 2020, CRKP has ranked first in the detection rate of drug-resistant bacteria, and the pathogenicity rate of CRKP , The fatality rate is high, and the challenges faced by clinicians are becoming more severe
    .

    An important weapon for the treatment of CRKP-carbapenem-containing combination therapy options.
    Currently, CRKP has limited options for treatment of antibiotics.
    Existing studies generally believe that combination therapy is better than monotherapy.
    Domestic and foreign guidelines suggest that combination therapy is a response to CRKP infection.
    Effective measures
    .

    Professor Wang Sheng pointed out that CRKP belongs to carbapenem-resistant bacteria.
    With the advent of some new antibacterial drugs that have antibacterial effects on CRKP, its brilliance seems to be overwhelmed by carbapenem drugs, but meropenem is used as a Representative carbapenem drugs still occupy an important position in the treatment of CRKP
    .

    Clinical studies have shown that adding carbapenem drugs to the combined treatment regimen will relatively increase the effective rate
    .

    The 2017 European Society for Infection and Clinical Microbiology (ESCMID) survey showed that the carbapenem combination (combined with polymyxin or tigecycline) is one of the most commonly used dual combination programs
    .

    Based on pharmacokinetics/pharmacodynamics (PK/PD) and minimum inhibitory concentration (MIC) values ​​to optimize the dosing regimen and combination medications, the existing antibacterial drugs can exert their greatest effect
    .

    In terms of MIC value, Professor Wang Sheng believes that if the MIC is less than 8 mg/L, carbapenem drugs are indispensable in the combined treatment plan; if the MIC is greater than 8 mg/L, the curative effect of carbapenem drugs may be relatively limited, but In actual clinical operations, when the MIC reaches 32 mg/L, or even 64 mg/L, the combined treatment plan with carbapenem-containing drugs is also effective
    .

    As long as the effective rate of the combined treatment plan reaches 30%, it can also increase the patient's chance of cure.
    The combined treatment plan is a treatment option worth trying
    .

    In terms of PK/PD, Professor Wang Sheng suggested that the dose of carbapenem drugs can be increased for CRKP patients.
    Taking meropenem as an example, patients with severe infections can try to increase the dose to 2.
    0g, q8 h.
    The clinical findings can be correct.
    Some patients with CRKP can play a role
    .

    Since carbapenems are time-dependent antibiotics, Professor Wang Sheng tried to use a continuous pump for prolonged infusion administration.
    In theory, the longer the infusion time, the higher the effective concentration of the drug and the better the effect, but in clinical practice It was found that the curative effect did not meet expectations, and further research is needed
    .

    Foreign researchers are trying to use a combination of two carbapenem drugs, Professor Wang Sheng called "saturation attack", the theory of this strategy is to use a carbapenem drug to curb the resistance of CRKP The drug ability allows another carbapenem drug to give full play to its curative effect.
    However, the theory is good, and the results did not meet expectations.
    It is expected that domestic and foreign scientific researchers will continue to carry out evidence-based medical research and verify it
    .

    Face the challenge and look to the future.
    Finally, Professor Wang Sheng looked forward to the future research direction of CRKP treatment.
    Combination therapy is currently an effective measure for the treatment of CRKP.
    However, there is currently no large-scale multicenter randomized controlled study to provide a combination treatment plan.
    The selection provides a strong basis, and the guidance of therapeutic drugs is basically based on empirical and retrospective research
    .

    Moreover, for patients who need to use two or more antibacterial drugs at the same time, in vitro combined drug sensitivity test should be performed.
    However, at least 95% of domestic hospital microbiology rooms do not have combined drug sensitivity test
    .

    Therefore, the choice of combination therapy is worthy of further in-depth study
    .

    CRKP is more difficult in clinical treatment.
    Facing such severe challenges, Professor Wang Sheng put forward the following suggestions and ideas: CRKP strains can be preserved, the distribution characteristics of drug-resistant genes can be analyzed through gene sequencing, and the resistance of each strain can be determined.
    Drug gene profile, conduct in vitro and clinical tests, and provide recommended antibiotic combination treatment plans
    .

    Similar to gene chips, a combination treatment plan is determined according to the expression characteristics of drug-resistant genes, in order to improve the cure rate of CRKP patients
    .

    At present, there are various mechanisms that lead to CRKP resistance, and research on resistance mechanisms will play an important role in the management and treatment of CRKP in the future
    .

    Therefore, it is possible to in-depth study of the resistance mechanism and develop a new antibiotic that is not affected by the existing resistance genes, which can smoothly enter the CRKP strain, play a bactericidal effect and reduce patient mortality
    .

    The increase in the degree of bacterial resistance also indicates the importance of infection prevention and control.
    Strengthening the construction of related work and building a more solid line of defense for infection control is one of the most important development directions of China's medical system in recent years
    .

    Targeted formulation of reasonable and effective prevention and control measures will help effectively prevent the emergence and spread of multi-drug resistance of Klebsiella pneumoniae
    .

    Expert profile Wang Sheng Tongji University professor, chief physician, doctoral tutor, director of the Department of Critical Care Medicine, the Tenth People's Hospital of Tongji University
    .

    Member of the Critical Care Physician Branch of the Chinese Medical Doctor Association, deputy chairman of the Critical Care Branch of the Shanghai Society of Traditional Chinese Medicine, member of the Critical Care Professional Committee of the Shanghai Medical Association, and member of the Critical Care Physician Branch of the Shanghai Medical Association
    .

    Editorial board member of Journal of Emergency and Critical Care Medicine and Chinese Journal of Critical Care Medicine, National Natural Science Foundation of China, Ministry of Education Fund for Returned Overseas Students, and Shanghai Science and Technology Commission Project Review Expert, Shanghai Pujiang Talents Program and Shanghai Health System Young Talent "Silver Snake" Award" winner
    .

    Specializes in the comprehensive treatment of severe infections, extracorporeal cardiopulmonary support technology (ECMO) and enteral nutrition support treatment.
    He has presided over more than 10 projects at all levels including the Ministry of Science and Technology 863 Program and the National Natural Science Foundation of China.
    He has published more than 60 papers and is included in SCI.
    More than 30 papers
    .

    This article is only used to provide scientific information to medical and health professionals, and does not represent the platform’s position.
    Review of previous highlights: 1.
    Carbapenem-resistant Enterobacteriaceae bacterial infections make treatment more difficult, and what are the advantages of combined treatment ? 2.
    How effective is the combination of antibiotics for carbapenem-resistant gram-negative bacteria in vitro? See what this review says? 3.
    What is the modified qSOFA score used to predict the severity of adult patients with sepsis? Let's take a look at its "past and present lives"! 4.
    Why is it advocated to shorten the course of antibiotics for acute infections? 5.
    The demand for combined application of antibacterial drugs is becoming more and more urgent.
    Do you know all of these 4 in vitro combined drug sensitivity tests? 6.
    Meropenem and therapeutic drug monitoring, these issues are worth understanding! 7.
    The use of antibacterial drugs and the monitoring of therapeutic drugs in severe infections are worthy of attention! 8.
    The monitoring report of in vitro antibacterial activity of meropenem is here! Let's take a look at the latest monitoring data 9.
    The PK/PD target system helps optimize the antibiotic clinical medication plan
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