CRE and CRPA treatment principles are clarified in one article!

It is only for medical professionals to read and refer to.
We hope that through various efforts, we can make fewer resistant bacteria and make patients safer
.

Bacterial resistance is one of the major challenges in global public health, and carbapenem-resistant bacteria, especially carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Pseudomonas aeruginosa The infection problem caused by (CRPA) poses a great threat to human health
.

Faced with this worldwide problem, what measures have clinical experts taken to deal with the challenges posed by drug-resistant bacteria? I believe that the "Expert Consensus on Diagnosis, Treatment, Prevention and Control of Carbapenem-resistant Enterobacteriaceae in China" (hereinafter referred to as "CRE Consensus") successfully held not long ago can bring many new ideas to the clinic.
The conference is organized by Zhejiang Professor Yu Yunsong of Run Run Run Run Run Shaw Hospital Affiliated to University School of Medicine and Professor Wang Minggui of Huashan Hospital Affiliated to Fudan University co-chaired, and a number of experts came to the scene to focus on CRE epidemic, detection, colonization and infection, treatment principles, drug selection, diagnosis and treatment of various systems, Discussion and sharing of prevention and control and CRPA treatment strategies
.

 CRE precision medication? Laboratory and clinical collaboration, Hu Fupin, director of Huashan Hospital affiliated to Fudan University, first pointed out that the 2020 data of the National Bacterial Resistance Surveillance Network showed that the isolation rate of Klebsiella pneumoniae is on the rise, and it has jumped to second place.
The drug resistance rate can even be as high as 30.
2% [1]
.

 The main mechanisms of Enterobacteriaceae resistance to carbapenem antibiotics include carbapenemase production, high production of AmpC enzyme or extended-spectrum β-lactamase combined with loss of outer membrane porin and/or high efflux pump Expression.
Among them, the KPC-producing carbapenemase is the main drug resistance mechanism in adults, and metalloenzymes are the main mechanism in children.
At this time, the available sensitive treatment drugs are limited, and it is necessary to treat them separately and guide the clinical medication accurately
.

 The risk of death of patients after CRE infection is extremely high (>30%).
It is necessary to pay attention to the colonization and infection risks of key departments such as intensive care unit (ICU), blood, and transplantation.
Early detection, early isolation, and early prevention are the key to treatment
.

At this time, the laboratory and the clinic need to communicate closely, work together, and carry out screening to intervene in advance
.

 In addition, in order to quickly update the understanding of CRE, laboratories also need to keep pace with the times, and should promptly understand the mechanism of CRE enzyme mutations and different solutions
.

So that when CRE infection occurs, initial effective anti-infective treatment can be carried out, and the plan can be adjusted quickly according to bacterial changes
.

 For example, a joint drug susceptibility test can be conducted to provide a more precise medication plan for the clinic, protect the existing effective treatment plan, and promote the rational application of antibacterial drugs while detecting the resistance of bacteria, and effectively curb the spread of drug-resistant strains
.

 What does the consensus say about CRE treatment principles? When talking about the CRE prevention and control principles in the consensus, Du Xiaoxing, director of the Run Run Run Run Run Run Run Hospital, Zhejiang University School of Medicine, pointed out that CRE isolated from clinical specimens are mostly pathogenic bacteria, and CRE isolated from non-sterile body fluids needs to be distinguished between colonization and infection , It is also necessary to select sensitive antibacterial drugs according to different infection sites and minimum inhibitory concentration (MIC) values
.

The drug treatment strategies for infections in each system should be adjusted according to the penetration of the drug tissue concentration, and different administration methods can be considered to increase the drug concentration in the tissue and reduce side effects
.

 In addition, Director Du Xiaoxing emphasized in his speech that "enzyme type affects future CRE treatment decisions", and the new enzyme inhibitor compound formulations that have been marketed in China can be used to treat most of the CRE infections mainly producing KPC carbapenemase.
Well, the side effects are also smaller than traditional solutions
.

According to the characteristics of metalloenzymes that do not hydrolyze aztreonam, aztreonam can be used in combination with CRE infections that produce metalloenzymes
.

 Professor Chen Baiyi from the First Affiliated Hospital of China Medical University believes that in the CRE prevention and control strategy, prevention of occurrence, treatment of infection, and control of transmission are all important
.

On the basis of drug susceptibility, follow up the source of infection by paying attention to the infection of different parts and give targeted treatment
.

For CRE isolated from lower respiratory tract specimens, it is necessary to distinguish between contamination, colonization and infection
.

Site colonization is only one step away from infection.
It is necessary to focus on the patient's immune function, which is also an important reference for formulating treatment plans for the next infection
.

Due to the limited choice of therapeutic drugs, it is also necessary to select appropriate antibacterial drugs based on the pharmacokinetics/pharmacodynamics (PK/PD) and MIC values ​​of different drugs in different parts, while optimizing the route of administration
.

(For details of CRE infections in each system, please refer to CRE consensus [2]) Choosing drug susceptibility-based combination therapy, CRPA patients will benefit more, Director Zhou Hua of the First Affiliated Hospital of Zhejiang University School of Medicine pointed out when talking about the challenges brought by CRPA , A variety of mechanisms cause Pseudomonas aeruginosa to be aggressive and will resist, escape or overcome the host's immune defense system
.

In recent years, its drug-resistant phenotype has changed a lot.
KPC-producing Pseudomonas aeruginosa has become an important clone in East China.
Therefore, the treatment of CRPA also requires further clinical attention
.

 Different from the CRE treatment plan based on enzyme-based decision-making, due to multiple drug resistance mechanisms such as enzyme production, lack of membrane porins, and high expression of efflux pump, for CRPA, the choice of drug sensitivity-based combination therapy will benefit patients more significantly
.

 The data suggests that there is no difference in infection-related mortality and bacterial clearance between polymyxin monotherapy and unverified combination therapies
.

The drug sensitivity-based combined treatment group showed lower infection-related mortality, higher bacterial clearance, and better safety
.

 Based on the changes in CRPA resistance mechanisms, the clinical evidence and applications of new enzyme inhibitors are also worthy of attention
.

The in vitro sensitivity of ceftazidime/avibactam to Pseudomonas aeruginosa reached 86.
9%, and the in vitro sensitivity to CRPA reached 64.
3% [3]
.

In addition, although both ceftazidime/avibactam and polymyxin are alternative drugs for CRPA, they are safer than polymyxin and have no heterogeneous drug resistance; compared with aminoglycosides, It has the advantages of more precise curative effect and fewer side effects [4]
.

 Summary At the end of the meeting, Professor Yunsong Yu and Professor Minggui Wang concluded that the prevention and control of CRE is an issue that clinicians attach great importance to.
The release of this consensus will help clinicians better respond to CRE, and reemphasize that its diagnosis and treatment need to be based on prevention and treatment of infections.
Three strategies for controlling communication are carried out
.

 "Prevention of production" requires good multidisciplinary cooperation between clinical and laboratory departments to guide the rational use of antibiotics; "treatment of infection" requires analysis of the resistance mechanism of CRE, attention to enzyme-producing enzymes, guidance of treatment decisions, and prevention of new bacteria Mutations; and "controlling transmission" requires departments such as the intensive care unit and transplantation ward to do a better job in prevention and control
.

 For CRPA, due to its complex resistance mechanism, it is necessary to guide the combination medication based on the results of drug sensitivity
.

For the KPC-producing Pseudomonas aeruginosa that is prevalent in some regions, clinicians are required to update their treatment decision-making cognition and provide treatment that keeps pace with the times
.

 All in all, I hope that through various efforts, there will be fewer resistant bacteria and make patients safer
.

References: [1]http:// China Expert Consensus Compilation Group on Diagnosis, Treatment, Prevention and Control of Carbapenem-resistant Enterobacteriaceae Bacterial Infections, China Medical Education Association Infection Disease Professional Committee, Chinese Medical Association Bacterial Infection and Drug Resistance Prevention and Control Professional Committee.
Expert consensus on diagnosis, treatment, prevention and control of carbapenem-resistant Enterobacteriaceae bacterial infection in China[J].
Chinese Medical Journal, 2021, 101(36): 11.
[3]Yang Y, Guo Y, Yin D, Zheng Y, Wu S, Zhu D, Hu F.
In Vitro Activity of Cefepime-Zidebactam, Ceftazidime-Avibactam, and Other Comparators against Clinical Isolates of Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii: Results from China Antimicrobial Surveillance Network (CHINET) in 2018.
Antimicrob Agents Chemother.
2020 Dec 16;65(1):e01726-20.
[4]Cai B, Cai Y, Liew YX, Chua NG, Teo JQ , Lim TP, Kurup A, Ee PL, Tan TT, Lee W, Kwa AL.
Clinical Efficacy of Polymyxin Monotherapy versus Nonvalidated Polymyxin Combination Therapy versus Validated Polymyxin Combination Therapy in Extensively Drug-Resistant Gram-Negative Bacillus Infections.
Antimicrob Agents Chemother.
2016 Jun 20;60(7):4013-22.
Swipe down to view the information for medical and scientific reference only.
It is not recommended to use this product in any way that is inconsistent with the prescription information approved by your country.