Professor Tang Kejing
While strengthening clinical drug management and controlling bacterial resistance, the implementation of the national centralised procurement policy for antibiotics offers challenges and opportunities.
Centralised procurement with volume-based procurement (referred to as “procurement”) is one of the important measures to promote the supply-side reform of medical services, and has played an important role in improving the well-being of individuals, promoting the reform of the tripartite linkage of medical care and promoting the healthy development of the medical industry. With the normalisation and institutionalisation of procurement work, increasingly more antibiotics have been included in the procurement scope, bringing new opportunities and challenges to the clinical application management of antibiotics in medical institutions.
Recently, “Medical Forum” invited Professor Tang Kejing of the First Affiliated Hospital of Sun Yat-Sen University to discuss the clinical application of antibiotics under the management model of ‘centralized procurement’ of antibiotics.
Q1. Under the context of the national policy of drug procurement, and the specific nature of the clinical application of antimicrobial drugs, – such as being a determinant of the prognosis of infectious diseases, the severe situation of microbial resistance, and different clinical requirements for individual antimicrobial drugs – what do you think should be done to strengthen the management of antimicrobial drugs, curb bacterial resistance, and actively implement the national policy of antimicrobial drug procurement?
Since the State Council issued the “Pilot Scheme for National Organisation of Drug Centralised Procurement and Use” in 2019, the national organisation of drug procurement has expanded from partial regional pilot programs to nationwide implementation, with the coverage of drug varieties continuously expanding, effectively reducing drug prices and significantly alleviating the burden of medication costs for patients.
With the normalisation and institutionalisation of drug procurement, an increasing number of antimicrobial drugs have been included in the procurement category. While the cost of antimicrobial treatment has significantly decreased, physicians are facing new problems and challenges in the clinical application management of antimicrobial drugs. Unlike antihypertensive or antidiabetic drugs that need to be taken for a lifetime for chronic disease treatment, the treatment course of antimicrobial drugs is often short, – generally no more than two weeks – and is aimed at achieving timely and significant anti-infection effects. A reasonable antimicrobial regimen is a decisive factor in effectively improving the prognosis of bacterial infection in patients, while inappropriate antimicrobial therapy often further elicits the occurrence of bacterial resistance, leading to worsening of infection or even death.
Therefore, under the severe bacterial resistance situation in China, medical institutions need to actively implement the national policy of antimicrobial drug procurement, complete the agreed procurement volume of antimicrobial drugs, and continuously strengthen the management of antimicrobial drugs to ensure antimicrobial efficacy and curb the occurrence of bacterial resistance. Specifically, the following aspects can be considered:
Firstly, in the process of implementing the collective procurement policy for antibiotics, attention should be paid to adjusting and optimising the variety of existing antibiotics in the hospital to ensure the scientific rationality of the hospital’s antibiotic catalogue and meet the clinical needs of patients.
Secondly, while making the collective procurement of the preferred options of antibiotics, drugs in the current catalogue that are meeting clinical needs should be retained. Especially for large-scale tertiary hospitals and national medical centers, the supply of ‘original’ drugs should be guaranteed for patients with special needs, such as critically ill patients, in order to achieve smooth recovery.
Thirdly, when selecting drugs in collective procurement, try to choose generic drugs that have passed a one-time evaluation. If the generic drug fails to pass the one-time evaluation, its clinical effectiveness cannot be guaranteed, and its use should be reconsidered, especially in the case of antibiotics.
Next, the estimation of the quantity of collective procurement of antibiotics should be treated with greater caution. Due to the very low drug prices under the collective procurement policy, medical institutions may overestimate the amount of antibiotics that are needed, resulting in irrational use of antibiotics and the occurrence of drug resistance events, which not only endangers the personal health of patients, but also causes serious public health problems.
Finally, the application and management of clinical antibiotics should be strengthened. Medical staff need to strengthen the review, evaluation, and corresponding rectification of clinical drug prescriptions to avoid the phenomenon of irrational use of antibiotics in clinical practice (such as for conditions without indications for antibiotics, inappropriate selection of antibiotic varieties, overdose, over-treatment, and inappropriate combinations of antibiotics).
Q2. What do you think is the status and value of clinical pharmacists in the management of antimicrobial agents in medical institutions? What are the ways for clinical pharmacists to participate in the management of the clinical application of antimicrobial agents?
With the implementation of drug procurement policies, the status and value of clinical pharmacists in the management of antimicrobial agents in medical institutions are highlighted. Clinical pharmacists participate in the management of the clinical application of antimicrobial agents in the following ways:
First, clinical pharmacists participate in the selection and evaluation of antimicrobial agents in medical institutions, ensuring that antimicrobial agents with strong antimicrobial activity, superior pharmacokinetic/pharmacodynamic (PK/PD) parameters, fewer adverse reactions, optimal cost-effectiveness, a stronger evidence base, and greater recommendations by authoritative guidelines can be included in the antimicrobial agent list of the hospital.
Second, clinical pharmacists actively participate in the calculation of the number of antimicrobial agents purchased through centralised procurement and the task decomposition of the antimicrobial agents purchased through centralised procurement.
In terms of calculating the amount of antimicrobial agents purchased through centralized procurement, usually the amount of drugs under the same generic name purchased by the medical institution in the previous year, and the trend of use in the past year, are used as the basis for calculation, combined with factors such as changes in disease types, updates in evidence-based medicine, changes in medical insurance attributes, the impact of similar drugs, changes in bacterial resistance, and the diagnosis and treatment of infectious diseases, to estimate future use.
Owing to the special nature of antimicrobial agents and the differences in management, it is not appropriate to adopt a uniform task decomposition method for all antimicrobial agents. It is recommended to have a “tailored approach, use only when necessary, and strictly prevent misuse” policy. The specific clinical applications of each centrally-procured antimicrobial agent should be analysed to develop a reasonable implementation plan.
Third, effectively monitor and manage the clinical application of antimicrobial agents. For example, clinical pharmacists at the First Affiliated Hospital of Sun Yat-Sen University actively participate in the multidisciplinary team (MDT) consultations of critically ill patients with severe infections, etc., by strengthening publicity and education, ensuring that clinical doctors understand the relevant policies of centralised procurement, and strengthening the knowledge of surgical doctors and others regarding the variety and application of antimicrobial agents.
Fourth, review and evaluate drug prescriptions, promptly discovering and correcting instances of drug use without indication, inappropriate drug selection, overdosing, and prolonged medication use.
Fifth, effectively monitor and manage the clinical usage indicators of antimicrobial agents. This objective can be achieved by tracking monthly statistics and analysing indicators, with a focus on monitoring the usage rate of antimicrobial agents, the intensity of antimicrobial agent use in hospitalised patients, and the usage rate of antibiotic prophylaxis for class I incision.
Sixth, strengthen the monitoring of adverse reactions to antimicrobial agents, and analyse and evaluate the monitoring results of adverse reactions. In addition, work together with clinical doctors to improve the ability to detect suspected adverse reactions, actively report adverse reactions to antimicrobial agents, and facilitate the reporting and management of centrally-procured antimicrobial agents in hospitals.
Seventh, make full use of the real-world data of medical and health institutions at all levels to carry out scientific and standardised comprehensive evaluation of the clinical application of antimicrobial agents in accordance with the “Guidelines for Comprehensive Evaluation and Management of Drug Clinical Trials (Trial Implementation 2021 Edition)” and attach importance to quality evaluation and transformation application of evaluation results to promote the rational use of centrally-procured antimicrobial agents.
Q3. Since the downgrading of epidemic prevention and control measures in December 2022, there have been huge challenges for the standardised use of antibacterial drugs. When some COVID-19 patients exhibit symptoms such as yellow purulent sputum, elevated white blood cell counts, and multiple diffuse infiltrates in the lungs on chest CT scans, initial empirical anti-infective treatment will be initiated in clinical practice, and many hospitals recommend antibacterial regimens mainly consisting of oral respiratory quinolones and second-generation cephalosporins. Could you please talk about the application value of respiratory quinolones (such as levofloxacin, moxifloxacin, and ciprofloxacin) in the context of the new situation of anti-infection during COVID-19?
Some COVID-19 patients may exhibit symptoms such as yellow purulent sputum, elevated C-reactive protein (CRP) levels, and imaging features suggestive of viral pneumonia, but these are not indications for the use of antibacterial drugs. Although patients with comorbidities such as bronchitis, emphysema, and other conditions are likely to have bacterial infections concurrent with COVID-19 infection, differential diagnosis should be considered before initiating anti-infective treatment during the COVID-19 pandemic, to distinguish between viral infections, bacterial infections, and mixed infections.
A viral and bacterial co-infection may be considered in COVID-19 patients when they exhibit obvious increases in white blood cell counts, diffuse infiltrates in both lungs, present with small patchy and consolidated shadows visible on lung CT scans, and have pathogenic bacteria detected in sputum cultures. After completing comprehensive clinical microbiological examinations, rational use of antibacterial drugs can be initiated.
In terms of the convenience of clinical use and the breadth of the antibacterial spectrum, respiratory quinolones have demonstrated significant advantages in outpatient treatment. Most respiratory quinolones, including levofloxacin, moxifloxacin, and ciprofloxacin, only need to be taken once a day and have high oral bioavailability, which is very beneficial for outpatient antibacterial treatment.
Respiratory quinolones have a broad antibacterial spectrum and can cover not only common pathogens such as Streptococcus pneumoniae and Klebsiella pneumoniae, but also atypical pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae. In addition, respiratory quinolones have good antibacterial efficacy against some Gram-negative rods and Gram-positive cocci known to have strong drug resistance. For example, ciprofloxacin has very good antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA.
In clinical practice, COVID-19-infected patients with underlying diseases (especially the elderly) are often infected with multiple types of pathogenic bacteria when they have bacterial infections, such as Escherichia coli, Pseudomonas aeruginosa, and some atypical pathogens. In this situation, respiratory quinolones, as antibacterial drugs with a wider coverage, can achieve better anti-infective treatment effects.