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    Home > Active Ingredient News > Infection > In children with "high fever and cephalosporin resistance", how to choose antibacterial drugs for this infection?

    In children with "high fever and cephalosporin resistance", how to choose antibacterial drugs for this infection?

    • Last Update: 2021-06-04
    • Source: Internet
    • Author: User
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    Only for medical professionals to read and refer to Enterobacter cloacae infection, how to choose the right antibacterial drug? Recently, the Center for Drug Evaluation of the National Medical Products Administration opened a "Children's Drug Column" on its official website.

    Screenshot of the official website of the Center for Drug Evaluation of the State Drug Administration.
    The State Drug Administration also pays more attention to the use of children's drugs.
    Recently, it has issued several announcements on the revision of children-related drug inserts.

    For details on the screenshots of the official website of the State Food and Drug Administration, please scan the QR code to see that there is nothing trivial about children's medication! Today, Jie Xiaoyao talks about the rational use of drugs in pediatrics through a case of bacterial infection.

    Case review A 2-year-old child was admitted to the hospital because of "recurrent abdominal pain, fever and vomiting for 9 days".

    After the operation was admitted to the hospital, a laparotomy was performed urgently to perform laparotomy, incision and debridement of the abscess around the ascending colon, enhanced suture of the ascending colon diverticulum, and biopsy of the mass around the ascending colon + appendectomy.

    Suddenly, the pus was taken during the operation and Escherichia coli was detected.
    The drug sensitivity test showed that the test drug was fully sensitive; but the child still developed a high fever.
    After the use of piperacillin/tazobactam, the fever again occurred.
    Mipenem/cilastatin is anti-infection.

    After the treatment, Enterobacter cloacae was detected in the abdominal drainage fluid.
    The drug sensitivity result is shown in Figure 1.
    The clinician consults the clinical pharmacist if it is necessary to replace the antibacterial drug.

    Figure 1 The results of drug susceptibility in children Enterobacter cloacae infection and drug resistance ▎ What is Enterobacter cloacae? Enterobacter cloacae, belonging to the genus Enterobacteriaceae, is a Gram-negative Brevibacterium vulgaris.
    It has flagella, no spores, facultative anaerobic, low nutritional requirements, and can form large and moist mucus on ordinary culture media.
    Like colonies.

    It does not hemolyze on the blood agar plate, and can ferment lactose on the intestinal selective medium to form red colonies.

    Pathogenic mechanism: endotoxin is the pathogenic factor of Enterobacter cloacae.

    ▎Why does antibiotic resistance occur? The main mechanisms of Enterobacter cloacae resistance to antibiotics are as follows: ① production of inactivating enzymes or inactivating enzymes; ② drug resistance involving movable genetic elements such as plasmids and integrons; ③ quinolone antibiotic resistance (qnr) gene mediation ④The permeability of the outer membrane is decreased; ⑤The active efflux pump is enhanced; ⑥The formation of biofilm.

    Among them, inactivated enzymes are the most important drug resistance mechanism.
    The inactivated enzymes produced mainly include extended-spectrum β-lactamases (ESBLs) and cephalosporinase (AmpC enzyme).
    A small number of Enterobacter cloacae can produce carbon blue Mycoenzyme.

     ESBLs are plasmid-mediated hydrolysis of penicillins, oxyimino cephalosporins (including third and fourth generation cephalosporins), and monocyclic amide aztreonam, but do not hydrolyze carbapenems and cephalosporins.
    Drugs, but can be inhibited by β-lactamase inhibitors (enzyme inhibitors mainly refer to clavulanic acid, sulbactam, tazobactam, and avibactam.

    Drug susceptibility tests routinely detect this enzyme ).

    AmpC enzyme is chromosome-mediated and can hydrolyze penicillins, cephalosporins (including third-generation cephalosporins, but generally not fourth-generation cephalosporins), cephalosporins and monocyclic β-lactams, carbocyanines Mycoene antibacterial drugs are stable to it.

    In general, ESBL inhibitors are not effective against AmpC enzymes, especially clavulanic acid.

    The incidence of AmpC enzyme is lower than that of ESBLs, and the level of attention in China is not as high as that of ESBLs.
    Routine testing is not done on the drug susceptibility test list, but we can observe whether the cephalosporins are resistant and whether the fourth-generation cephalosporins are resistant.
    Sensitive to judge whether it exists.

       .
    What kind of medicine do you consider to treat this infection? The treatment plan for ESBLs and AmpC-producing Enterobacter cloacae is generally shown in the following table: ▎A-enzyme-producing Enterobacteriaceae bacterial infection treatment plan Table 1 A-enzyme-producing Enterobacteriaceae bacteria infection pathogenic treatment plan ▎E-enzyme producing intestine Treatment plan for Bacterial infections Table 2 Pathogen treatment plan for infections caused by E-enzyme-producing Enterobacteriaceae bacteria The drug susceptibility results of Enterobacter cloacae detected in this case showed resistance to cefotetan and third-generation cephalosporins, while enzyme inhibitors Compound preparation, fourth-generation cephalosporin sensitive.

    Therefore, it is speculated that the bacteria produced ESBLS and AmpC enzymes at the same time.

    Antibacterial drugs that are resistant to these two inactivating enzymes include carbapenems, tigecycline, polymyxin, and amikacin.

    ▎How do you consider the medication? Although cefepime is sensitive, in the absence of therapeutic drug monitoring (TDM monitoring), there is a risk of failure in the treatment of ESBLs-producing Enterobacter, and it is not recommended.

    Although amikacin is sensitive, it is not suitable for children, elderly patients, and patients with lung infections.
    It is mostly one of the combination drugs in the second option.

     Therefore, in combination with drug effectiveness, safety, and economy, the most cost-effective drugs are carbapenem drugs, such as imipenem/cilastatin and meropenem.

    Imipenem/cilastatin has already been used, and the medication can be continued.

    Two days after using imipenem/cilastatin, the patient's body temperature gradually returned to normal (see Figure 2 for details).

    Figure 2 The temperature change of a child.
    Reference materials: [1] Wang Minggui.
    Handbook of diagnosis and treatment of drug-resistant gram-negative bacteria infection[M].
    People's Medical Publishing House, 2015.
    [2] Zhou Hua, Li Guanghui, Chen Baiyi, etc.
    Chinese Supermarket Expert consensus on response strategies for broad-spectrum β-lactamase enterobacteriaceae infection[J].
    Chinese Medical Journal, 2014, 94(024):1847-1856.
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