The rational use of antimicrobial drugs is an important measure to cope with the global crisis of bacterial drug resistance, and in the technical system of rational use of antimicrobial drugs, various guiding principles and guidelines are of great value.In 2004, the Ministry of Health of China, together with the State Administration of Traditional Chinese Medicine and the Ministry of Health of the General Logistics Department of the People’s Liberation Army, promulgated the Guiding Principles for the Clinical Application of Antimicrobial Drugs (hereafter referred to as the Principles), which has played a positive role in guiding The promulgation of the Principles has played a positive role in guiding the rational use and management of clinical antimicrobial drugs and achieved outstanding results, and has also promoted the construction of a series of systems for the rational use of antimicrobial drugs since then. Jie Shenghua, Department of Infection, Wuhan Union Medical College Hospital
Due to the development of bacterial drug resistance, research and development of new antibacterial drugs, and more importantly, the achievement of research results in the treatment of various infectious diseases, the Principles that have been in use for 10 years are bound to have certain deficiencies and even possible errors.
On the occasion of the release of the 2015 edition of the Principles, based on the purpose of careful study, the author compared the changes in the 2015 edition of the Principles with the 2004 edition and analyzed the main revisions as follows. This article is only a brick to draw in the jade, and the majority of clinical workers to discuss.
I. The overall revision of the 2015 edition of the Principles
The 2015 edition of the Principles basically continues the writing style of the 2004 edition of the Principles, and the overall layout and content have not been greatly adjusted. However, in terms of overall content, the 2015 edition of the Principles has the following changes.
1. Content improvement
The 2015 version of the Principles has increased the overall length, including the first part of the content of preventive medicine (including surgical and non-surgical parts) and the clinical application of antibacterial drugs management content, the third part mainly increased a variety of new antibacterial drugs and antifungal drugs marketed in recent years, and the fourth part of the empirical treatment of various bacterial infections more prominent and clear.
2. Emphasis on new achievements
In the past decade, research on the treatment of bacterial infections has progressed relatively rapidly, and new theories, new drugs, and new research results have begun to be applied in the clinical setting, and various infection guidelines have been well received by the clinic, which are reflected in the 2015 edition of the Principles. For example, the PK/PD concept is widely recognized in clinical practice, and the 2015 edition of the Principles introduces the PK/PD classification of the relevant drugs when describing them. Similarly, the 2015 edition of the Principles also defines some new names, such as “sepsis” and “deep fungal infections” in the 2004 edition of the Principles. For example, the terms “sepsis” and “deep fungal infection” in the 2004 edition of the Principles have been replaced by “bloodstream infection” and “invasive fungal infection”.
3. More attention to the issue of drug resistance
The 2015 edition of the Principles pays much attention to bacterial drug resistance and the management of drug-resistant bacteria. and resistant. In the drug recommendation also pay attention to the drug resistance situation, such as for Neisseria gonorrhoeae no longer recommended quinolones, the application of macrolides in respiratory tract infections is also recommended to be decided with reference to the local drug resistance situation.
4. Empirical treatment of bacterial infections section highlights empirical treatment
In the 2004 edition of the Principles, the treatment of bacterial infections was more recommended for various bacteria and less empirical treatment was recommended, which made the guidelines face difficulties in clinical application; the 2015 edition of the Principles, in addition to retaining the original pathogenic treatment recommendations, substantially increased the recommendations for empirical treatment, making it more relevant to clinical practice and more operable.
5. The content is more specific and operable
Compared with the 2004 version of the Principles, the 2015 version of the Principles is more specific in the description of clinical indications and risk factors, for example, in the route of administration of therapeutic antibacterial drugs, oral administration is mainly recommended for mild to moderate infections, and intravenous injection is mainly limited to six clear situations; similarly, the empirical treatment of various bacterial infections is also very clear in the disease stratification.
6. Consistency with relevant regulations
Since 2004, China’s health administration has promulgated more regulations on the rational use of antibacterial drugs, such as the Measures for the Administration of Clinical Application of Antibacterial Drugs and the Notice on Further Strengthening the Management of Clinical Application of Antibacterial Drugs, etc. The relevant contents are better integrated into the 2015 version of the Principles, for example, there are more management contents in the second part, and the emphasis in the preventive use of surgical drugs is Strictly control the application of fluoroquinolones, etc.
Second, the basic principles of clinical application of antibacterial drugs
The “basic principles of clinical application of antibacterial drugs” should be the core part of the “Principles”, which has a guiding and leading role for the entire “Principles”. The 2015 version of the Principles of the therapeutic application of antimicrobial drugs has not changed much, and the main change is to highlight the content of “empirical treatment”, which is in line with clinical practice. Various infectious diseases require active treatment after diagnosis, and cannot wait for the results of bacterial examination, i.e., the positive rate of microbiological examination is not 100% clinically compatible, and there is also the possibility that specificity is not fully guaranteed, which all require empirical treatment of infectious diseases. Clarifying the status of empirical treatment is also necessary for the rational use of antimicrobial drugs.
The 2015 edition of the Principles has a large increase in the preventive application of antimicrobial drugs. Specific recommendation tables for antimicrobial drugs for non-surgical infection prophylaxis, surgical prophylaxis, and invasive operation prophylaxis have been added. In the section on perioperative prophylaxis in surgery, it is clarified that the purpose of prophylaxis is to “prevent surgical site infections …… excluding other postoperative site infections that are not directly related to surgery”, and the 2004 version of the Principles was deleted. The content of “possible systemic infections” in the 2004 version of the Principles was deleted to avoid the possibility of clinical confusion. In the classification of surgical incisions according to four categories (I~IV), which is different from the 2004 version of the Principles, the relevant differences are also explained.
In the schedule of prophylaxis, the 2015 edition of the Principles has made major changes to the previous recommendations: for example, ceftriaxone has been eliminated as a prophylactic choice in brain surgery, and cefoperazone/sulbactam has been eliminated as a prophylactic recommendation in liver surgery and transendoscopic retrograde cholangiopancreatography (ERCP); on the contrary, the recommendation of cephalosporins has been added in surgery with the possibility of luminal contamination, and in MRSA-prone units may also consider vancomycin as a prophylactic agent. These changes are consistent with the epidemiology of bacteria infecting the surgical site and avoid clinical medication errors. Schedule 1 regarding oral penicillin should refer to oral penicillin V or amoxicillin and requires attention. The partial non-recommendation of antimicrobial agents for infection prevention in various invasive procedures requires education of clinicians to correct existing incorrect practices, even if these recommendations are inconsistent with those of various specialties, but should prevail.
The 2015 edition of the Principles has few changes in the section on antimicrobial drug use in special populations. The use of tetracyclines and quinolones in neonates has been changed from “prohibited” to “avoided”, while the use of tetracyclines in pediatric patients is “not to be used in children under 8 years of age”, which requires attention in clinical This needs to be noted in the clinical application (debatable). In the various tables of antimicrobial drug use for special populations, some recently listed antimicrobial drugs and anti-infective drugs, such as tigecycline, daptomycin, micafungin, etc., have been added.
III. Management of clinical application of antibacterial drugs
Since 2004, China has strengthened the management of the rational use of clinical antimicrobial drugs, issued a series of relevant management regulations, carried out special rectification work on the clinical application of antimicrobial drugs, and especially promulgated the Measures for the Administration of Clinical Application of Antimicrobial Drugs (hereinafter referred to as “Measures”) in 2012, providing a legal basis for the management of the rational use of antimicrobial drugs and has formed a good management system.
Based on these 10 years of management experience, the 2015 edition of the Principles has made substantial additions to the 2004 edition regarding the management of the rational use of antimicrobial drugs, which mainly emphasizes the need for medical institutions to establish a management system for the clinical application of antimicrobial drugs (including working groups, technical teams and support systems), and establishes the status of hierarchical management of antimicrobial drugs as a core management strategy (including hierarchical criteria, It also makes corresponding provisions for medical institutions to carry out microbiological testing, hospital infection control and personnel training.
This part is actually a streamlining and compressing of the Measures, with emphasis on the main management content and methods. Compared with the Approach, this part is limited and relatively simple, while the legal efficiency of the Approach is stronger than the 2015 version of the Principles, so in practice the Approach will be more valuable. If used as technical principles, this part of the 2015 version of the Principles can be omitted in future revisions.
Fourth, the indications and precautions for various types of antibacterial drugs
Since 2004, the main progress of antimicrobial drugs lies in the marketing of some new drugs and the promotion and application of the concept of PK/PD classification of relevant antimicrobial drugs. In view of this, the main revision of the 2015 edition of the Principles in this part is to clarify the PK/PD classification of various types of antimicrobial drugs, increase the content of new antimicrobial drugs, and pay attention to the introduction of relevant drug resistance. The added antimicrobial drug categories include cephalosporins, penicillins, oxycephalenes, glycylcyclines, polymyxins, cyclic lipopeptides, oral oxazolidinones, and echinocandins. In addition, ertapenem, rifapentine, voriconazole, posaconazole and mycoplasma are also added drugs. Also deleted anti-Mycobacterium leprae drugs.
In the introduction of specific drugs, the focus was on bacterial resistance. For example, “ampicillin/sulbactam and cefoperazone/sulbactam have antibacterial activity against Mycobacterium avium. Cefoperazone/sulbactam and ticarcillin/clavulanic acid are also active against Stenotrophomonas maltophilia”.
The introduction of carbapenems also mentions issues regarding resistance to carbapenems against immobile and enterobacteria, quinolones not recommended for gonorrhea treatment and strict restrictions as surgical prophylaxis. However, overall, common clinical questions about streptococcal resistance to macrolides, the situation of ESBL-producing enterobacteria, the prevalence of MRSA, and pneumococcal resistance to penicillin were not reflected in the corresponding sections.
There are also some minor changes in drug use, such as the notes on penicillin encephalopathy and the fact that penicillin cannot be given intrathecally were removed, and the recommendation that penicillin should be discontinued in lactating women is not fully consistent with general clinical practice; the description that aminoglycosides can be given once a day in the basic principles section has also not been established in our clinic.
The 2015 edition of the Principles describes the content of individual drugs more specifically, such as the description of the indications for lincosamides and glycopeptides, and the description of precautions for quinolones, antituberculosis drugs and antifungal drugs has also increased; at the same time, the tips for the use of a variety of drugs (such as penicillin, cephalosporins, aminoglycosides, etc.) during lactation have increased more.
V. Principles of empirical antimicrobial therapy for various bacterial infections
The most prominent feature of this section is the integration of various domestic and international guidelines in recent years, the addition of empirical drug recommendation tables, and the distinction between drug-resistant and non-drug-resistant conditions in the section on etiologic therapy. The names of individual diseases have been revised, for example, the terms “sepsis” and “deep fungal infection” have been changed to “bloodstream infection” and “invasive fungal infection”. For example, “sepsis” and “deep fungal infection” were changed to “bloodstream infection” and “invasive fungal infection”, the description of “granulocytopenia infection” was added, and “cervicitis” was described only by “purulent cervicitis”. The term “pelvic inflammatory disease” was changed directly to “pelvic inflammatory disease”.
The increase in empirical treatment was mainly in respiratory infections (acute exacerbation of chronic obstructive pulmonary disease [AECOPD], bronchiectasis co-infection, pneumonia), cystitis and pyelonephritis, prostatitis, abdominal infections, and skin and soft tissue infections; there were also some adjustments in the original pathogenic treatment, such as an increase in the diagnostic criteria for AECOPD (graded according to the severity of the disease), and macrolide The treatment of Mycoplasma pneumoniae infection needs to refer to local drug sensitivity results, the pathogenic characteristics and drug selection of early-onset and late-onset hospital-acquired pneumonia, the distinction between pregnant and non-pregnant women for urinary tract infections, the increase in the content of infectious diarrhea and the explicit non-use of antibacterial drugs for enterohemorrhagic Escherichia coli infection, and the empirical treatment of bacterial meningitis and brain abscess are introduced one by one according to various clinical conditions (especially for The treatment of Streptococcus pneumoniae infections needs to be treated differently depending on the degree of sensitivity to penicillin).
The adherence to the guidelines is reflected in the treatment of various infectious diseases, especially the Infectious Diseases Society of America guidelines, such as community pneumonia and intra-hospital pneumonia recommendations and guidelines are consistent, and more content is also included in the invasive fungal infections section, distributed in the treatment of MRSA infections in the treatment of various sites of infectious pathogens is also consistent with the guidelines. This change is more easily accepted by the clinic and is not beneficial to the rational use of antimicrobial drugs.
In the pathogenic treatment, most of the therapeutic drug recommendations are treated according to drug-resistant and non-drug-resistant bacteria, such as the classification of Escherichia coli into ESBL-producing or not, Staphylococcus aureus into MRSA and non-MRSA, and Streptococcus pneumoniae focusing on penicillin resistance characteristics; the therapeutic drug selection on the one hand increases the new drugs marketed in recent years, such as linezolid and daptomycin for MRSA treatment, for multi
Vancomycin combined with fosfomycin is mentioned in several places regarding the treatment of severe MRSA infection, which is not completely consistent with the general guideline recommendations. The description of the treatment regimen for tuberculosis is more detailed than the 2004 version of the Principles, giving specific dosing regimens and regimens, while there are few modifications to the treatment of statutory infections.
VI. Conclusion
The 2015 edition of the Principles has been promulgated and implemented, and the overall content has been increased compared with the 2004 edition. It is believed that the 2015 edition of the Principles will play a positive role in promoting the rational use of clinical antimicrobial drugs in China.
Article author: Xiao Yonghong
International Journal of Epidemiology Infectious Diseases Vol. 42, No. 5, October 2015