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    Home > Active Ingredient News > Infection > Ninofloxacin has been on the market for 5 years and uses data to tell the Chinese story of antibacterial treatment

    Ninofloxacin has been on the market for 5 years and uses data to tell the Chinese story of antibacterial treatment

    • Last Update: 2021-04-23
    • Source: Internet
    • Author: User
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    As a national class 1.
    1 new antibacterial drug, nanofloxacin has put "scientific rigor" in the first place, both from its research and development and its clinical research for more than 10 years before the market, and it has carried out targeted indications of community-acquired pneumonia (CAP) and target pathogens.
    Corresponding clinical research, and prospectively integrating patient population pharmacokinetic studies into phase II and III clinical trials, obtained a lot of clinical data to guide clinical medication.

    Since its listing in 2016, nanofloxacin has gone through five years of clinical application.
    Zhejiang Medicine has always maintained a scientific and rigorous attitude, actively carried out clinical re-evaluation after the listing of nanofloxacin, and encouraged domestic experts in various fields to carry out basic and scientific research.
    Clinical research has achieved more research results.

    In 2019, nanofloxacin entered the national medical insurance catalog; at present, nanofloxacin injection has all passed the national review and will be launched soon, laying the foundation for subsequent sequential clinical therapy.

    What data has been obtained from the evaluation of nanofloxacin in the past five years? What experience has been in clinical application in the past 5 years? How to choose nanofloxacin reasonably and conduct professional management? On April 9th, at the expert seminar on clinical re-evaluation of the fifth anniversary of the listing of nanofloxacin, experts from the fields of respiratory, infection, severe disease, microbiology, clinical pharmacology and pharmacy conducted in-depth exchanges and experience sharing.

    Expert discussion site Professor Zhang Jing gave a report entitled "Nanofloxacin's 5th Anniversary Basic and Clinical Research Review" The development of nanfloxacin for more than ten years 01 Excellent results in re-evaluation of CAP common pathogens in the past 5 years Sensitivity to nanofloxacin is still maintained.
    In May 2018, the National Medical Products Administration officially issued the "Guidelines for Antibacterial Drug Breakpoint Research Technology", which clearly stipulates that new antibacterial drugs must have antimicrobial drug sensitivity breakpoints before they are approved for marketing.
    (Such as epidemiological cut-off value).Therefore, after the listing of nanofloxacin, Professor Hu Fupin from the Institute of Antibiotics of Huashan Hospital first carried out a study on the epidemiological threshold of different bacteria against nanofloxacin.
    The study established the Enterobacteriaceae, Pseudomonas aeruginosa, and grapevine.
    The epidemiological cut-off values ​​of Coccus, Streptococcus pneumoniae, and Haemophilus influenzae cover the main pathogens of CAP, as well as Enterobacteriaceae bacteria, laying the foundation for the expansion of subsequent urinary tract infection indications.

    At the same time, nanofloxacin entered the National Bacterial Resistance Surveillance (CARST) network to monitor bacterial resistance and carry out in vitro antibacterial activity testing.

    Research data shows that from 2017 to 2018, nanofloxacin still maintains strong antibacterial activity against common CAP pathogens such as Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis.
    The MIC90 for cocci and group β streptococcus is 0.
    12 mg/L and 1 mg/L, respectively, and for Staphylococcus aureus and Staphylococcus epidermidis are 1 mg/L and 0.
    5 mg/L, which is 1/2 of other quinolone drugs.
    1/64.

    The antibacterial activity against atypical pathogens is similar to other quinolones.

    There is almost no antibacterial effect on Mycobacterium tuberculosis (MTB).

    Pharmacokinetic data is gradually complete.
    Patients with mild to moderate hepatorenal dysfunction do not need to adjust the dose.
    70% of nanofloxacin is mainly excreted through the kidneys and is not metabolized by P450 enzymes, with very low liver metabolites.

    However, there is a lack of relevant evidence on whether there is an impact on patients with hypohepatic function.

    Therefore, in the post-marketing re-evaluation study, a parallel controlled study was conducted between normal populations and patients with mild to moderate hepatic impairment (Child-Pugh B) to compare the pharmacokinetic parameters of nanofloxacin after oral administration of 500 mg.

    The results showed that the ratio of AUC0-72h in the moderate liver function group/AUC0-72h in the control group was 1.
    15, and there was no significant difference between the two groups.

    It is suggested that there is no need to adjust the dose for patients with mild or moderate liver function decline, and the adjustment of the dosage regimen for patients with severe liver function needs further study.
    At present, this part of the population needs close follow-up safety during medication. Patients with severe renal insufficiency need to extend the interval between medications.
    What is the usage and dosage of CAP patients with mild renal insufficiency in the instructions of nanofloxacin, and how about the usage and dosage of patients with moderate and severe renal insufficiency? Extrapolation based on the previous population pharmacokinetic model of CAP patients showed that the drug exposure of patients with severe renal impairment has doubled.

    To this end, a head-to-head verification study was carried out between patients with severe renal impairment (eGFR=16.
    9 ml·min-1·1.
    73m-2) and normal people (eGFR=107.
    3 ml·min-1·1.
    73m-2).

    The results showed that the drug exposure of patients with severe renal dysfunction was indeed significantly increased, and the ratio of the increased AUC was almost similar to the extrapolation result, and the ratio of AUC0-72h between the two groups was 1.
    93.

    The urine excretion rate has also been reduced.
    According to the drug's PK/PD characteristics, it is a concentration-dependent antibacterial drug.
    After further PK/PD analysis, it is recommended that severe renal function decline (eGFR≤30 ml·min-1·1.
    73m-2) The dose for patients without dialysis remains unchanged at 0.
    5 g, and the dosing interval can be extended to 36 h to 48 h.

    Good tissue and body fluid penetrability Preclinical animal experiments have shown that nanofloxacin is widely distributed in tissues, and has good tissue penetrability in the prostate, bladder, and lungs.

    But there is no human body data.

    To this end, first conducted research on the penetration of body fluids in lung tissues.
    The preliminary results showed that nanofloxacin has good penetration of body fluids in bronchial mucosa tissues, which is more than twice the plasma drug concentration in the same period.

    The clinical research efficacy and safety of adult CAP in the expanded population has been further certified.
    After the listing of nanofloxacin, it will further verify its clinical and microbiological efficacy and safety in the treatment of CAP in a wider population.
    It is in 69 research centers such as Huashan Hospital of Fudan University.
    A multi-center, one-arm, open study was carried out, and 465 subjects were enrolled.
    There was no upper limit on the age of subjects, and the population including elderly subjects was expanded. The results show that the clinical cure rate can reach more than 94%.
    In terms of microbial clearance rate, although the number of pathogenic bacteria strains obtained is not many, those with positive bacterial culture (15 cases) were cured clinically, including Mycoplasma pneumoniae, Chlamydia pneumoniae, and pneumophila The clinical cure rate of patients with positive serological tests such as Legionella is nearly 100%.

    The safety results are consistent with the Phase III study, mainly for some mild gastrointestinal adverse reactions.

    Another retrospective, single-center clinical study included a total of 337 outpatient CAP patients who received nanofloxacin oral 500 mg once a day monotherapy.

    The results showed that the average medication time was 8.
    24 days.

    After 3 days of treatment, the symptom improvement rate was 61.
    3%.

    After the treatment, 98.
    14% of patients improved or cured.

    The incidence of adverse events was 1.
    86%.

    The follow-up results showed that 93.
    5% of patients were satisfied with the treatment effect.

    Research on new indications explores the respiratory system: The 2021 edition of the Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease recommends that nanofloxacin can be used for the antibacterial treatment of acute exacerbations of mild to moderate chronic obstructive pulmonary disease.

    In other fields, 70% of nanoxacin is excreted through the kidneys in its original form after oral administration, and the effective urine concentration is maintained for a long time.
    Animal studies have shown that it has good tissue distribution in the bladder and prostate, and has potential in urinary tract infections and other urinary systems.
    The value of treatment is worthy of discussion and research.

    Another open, single-arm, multi-center study initially explored the efficacy, safety and PK/PD of nanofloxacin in the treatment of diabetic foot infection (DFI).

    The 25 patients with mild or moderate DFI enrolled in the study were given nanofloxacin orally 750 mg qd for 7 to 14 days.
    As a result, the clinical cure rate was 95%, and the microbiological effective rate was over 82%.

    PK/PD analysis showed that nanofloxacin was quickly absorbed and distributed to soft tissues after oral administration.
    The tissue penetration rate was high.
    The concentration of nanofloxacin in soft tissues was more than 2.
    5 times that in plasma. In addition, studies evaluating the effects of nanofloxacin and fosfomycin on vancomycin's anti-methicillin-resistant Staphylococcus aureus (MRSA) activity and anti-drug resistance mutations have shown that nanofloxacin can enhance vancomycin in vitro Antibacterial activity and anti-drug resistance mutation ability, after vancomycin is combined with nanofloxacin, the MIC and MPC values ​​of vancomycin are significantly reduced.

    Nenoxacin and levofloxacin gavage treatment of rabbit tissue cage community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection model animal studies showed that the bacterial concentration of the levofloxacin group decreased significantly during the treatment process and then resumed growth.
    Treatment Different degrees of drug resistance occurred during the process; the bacteria in the nanofloxacin group decreased rapidly during the treatment, and the bacteria did not resume growth after the end of the treatment, and there was no drug resistance.

    02Experts’ discussion focus 1: The strong antibacterial activity of nanofloxacin against the main target pathogens, such as Streptococcus pneumoniae and Staphylococcus aureus, the MIC value is above the MPC value, and the mutation selection window (MSW) Narrow, low resistance mutation rate in vitro.

    It further explained the characteristics of nanofloxacin maintaining strong antibacterial activity under the monitoring of drug resistance.

    Focus 2: Clinical antibacterial efficacy and safety are widely recognized.
    In addition to the similar drug properties of quinolones, nanofloxacin is ineffective against tuberculosis, and its sensitivity to CA-MRSA is an important feature.

    For patients with CAP suspected of tuberculosis, taking nanofloxacin does not have to worry about the delayed diagnosis of tuberculosis.

    Regarding the clinical experience of nanfloxacin, experts have said that nanfloxacin is safe, has no obvious adverse reactions, and has no obvious gastrointestinal side effects.
    It can be used after meals.

    For some patients with MRSA infection, such as thrombocytopenia after using linezolid during sequential treatment, try to switch to nanofloxacin.

    Nenofloxacin has a good antibacterial effect on gram-positive bacterial infections.
    Some experts have used nanofloxacin to treat gram-positive bacterial infections after abdominal aortic stents and monitored inflammatory indicators and found that PCT and C-reactive protein were all reduced , The patient has a good prognosis.

    Focus 3: Indications for skin and soft tissue infections and prostate infections deserve attention.
    Nenoxacin has a high concentration in skin and soft tissues, has good antibacterial activity against gram-positive bacteria, and does not produce cross-resistance with levofloxacin and moxifloxacin. The skin and soft tissue infections are mostly Gram-positive bacterial infections.
    Therefore, the antibacterial treatment of nanofloxacin on skin and soft tissue infections is worthy of further study.

    The treatment of prostate infection is a difficult clinical problem.
    At present, the treatment effect of many drugs is not good.

    Nenoxacin has a high penetration rate in the prostate, so the treatment of prostate infection is also worthy of further clinical research.

    If you consider the skin and soft tissue infections caused by Staphylococcus aureus for diabetic feet, you can choose nanofloxacin treatment, but considering mixed infections with anaerobic bacteria, combination medications should be taken.

    Focus 4: It is recommended to include restricted levels in the classification management of drugs.
    At present, many provinces and cities have successively updated the "Classified Management Catalog for Clinical Application of Antimicrobial Drugs".
    Experts believe that it is more reasonable to list nanofloxacin as restricted.

    On the one hand, nanofloxacin has accumulated 5 years of clinical drug experience, and its safety is good; on the other hand, after entering the medical insurance list, the daily treatment cost of nanofloxacin is 32.
    4 yuan, which is relatively affordable; in addition, it is used as an oral Medicine is more applicable and convenient in outpatient clinics.

    (In no particular order) Typesetting: Huang Lingling, Qiu Jia, Editor: Qiu Jia, Review: Xu Fengyan, "Physician Daily" Contribution Public E-mail: yishibao2017@163.
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