The present survey assessed the status of PK/PD knowledge among Chinese ICU physicians. The results showed that approximately half of the participants passed the exam, especially for questions on the adjustment of antibiotics for sepsis and the adjustment of antibiotics under organ support. Additionally, hospitals with different grades and physicians with different job titles exhibited different degrees of PK/PD knowledge. What surprises us is that the passing rate of resident physicians is the highest, which seems unreasonable, because generally the higher the working years, the higher the theoretical knowledge and professional level. At the same time, the average score of chief physician and ICU physician who has worked for more than 15 years is the highest, but the average score is the highest, which indicates that there is "polarization" in the mastery level of PK / PD among physicians with the same Title, and the mastery situation is quite different. However, the total number of participants in this study is small, accounting for only about 1% of the total number of ICU practitioners in China. At the same time, the number of deputy chief physicians and chief physicians is small, which may have some bias. At the same time, combined with the results of 5C training, whether to accept continuing education training also has a certain impact on the test results. However, in general, the mastery of PK / PD knowledge of Chinese ICU doctors is unsatisfactory.
In addition to Chinese ICU physicians, those in other countries also lack acceptable of knowledge of PK/PD. A study conducted in Europe showed that European ICU professionals do not have a satisfactory level of PK knowledge[19]. Even though the theoretical knowledge is available in China, combined with the results of the current survey, we found that PK/PD knowledge has not been valued by clinicians. Given the high mortality rate of sepsis and increasing antibiotic resistance, methods to improve ICU physicians’ PK/PD knowledge need to be further studied.
Sepsis is a common reason for admission to ICUs, and early correct antibiotic use is an important measure to reduce mortality due to sepsis[9]. On the one hand, patients with sepsis may also have organ dysfunction, resulting in drug accumulation and adverse reactions. On the other hand, insufficient dose of antibiotics may lead to treatment failure and drug resistance[28]. Additionally, organ support may significantly influence PK/PD[29]. Therefore, for patients with sepsis, an optimal antibiotic administration strategy is essential to minimize the occurrence of adverse reactions and drug resistance while ensuring efficacy.
TDM of antimicrobials, even those with a wide therapeutic index, is becoming more common, whilst TDM for “traditional” drugs, such as aminoglycosides and glycopeptides, is continually being studied for further improvement. In the case of in vitro drug susceptibility testing with known pathogenic bacteria and minimum inhibitory concentration, TDM is carried out by monitoring changes in serum concentration combined with PK/PD target attainment. An antibiotic-based adjustment programme remarkably improves treatment efficiency[30], reduces the occurrence of antibiotic adverse reactions, and reduces the mortality of septic patients[31, 32]. A recent TDM-based study[33] demonstrated that TDM should be routinely carried out for monitoring β-lactam antibiotics and aminoglycosides, while linezolid, teicoplanin, and vancomycin need to be monitored by TDM for critically ill patients. Using artificial intelligence-based methods such as Bayesian theory, PK/PD-relevant parameters can be calculated by combining blood drug concentration and patient's personal information, to achieve individualized antibiotic treatment[34–37]. Studies have shown that Bayesian theory combined with TDM can accurately monitor the dosage of antibiotics[38, 39].
At the same time, multidisciplinary cooperation can also optimize the antibiotic dosing regimen; strengthening the cooperation of clinicians, nurses, pharmacists, infection departments, microbiology rooms, and other departments can greatly improve the efficiency of drug delivery. Richter et al.[40] pointed out that implementation of TDM in sepsis patients under the premise of multidisciplinary cooperation can improve the stability of plasma antibiotic levels, shorten the treatment time, and improve treatment effectiveness. After multidisciplinary cooperation, clinicians’ decision-making efficiency was elevated by 90%[41]. Another study on the multidisciplinary cooperative administration of aminoglycosides showed that ensuring the effective concentration of aminoglycosides also reduces the toxicity and side effects of drugs [42].
At present, the best method for ICU physicians to optimize antibiotic delivery is to enhance their PK/PD-based knowledge. Our survey suggested that ICU physicians’ PK/PD knowledge was not satisfactory in China. The distribution of antibiotics mainly depends on the volume of distribution (Vd) and the binding rate of plasma protein (PB). Vd is a theoretical volume affected by infection, protein level, and renal function[43]; comprehension of Vd is challenging for ICU physicians. The plasma protein binding rate is closely associated with the protein level in patients[44]. The efficacy of high binding rate is often affected, but it does not attract ICU physicians’ attention. The half-life of antibiotics is affected by the apparent volume of distribution and drug clearance. Due to the complicated condition, it is difficult to calculate the half-life of drugs in patients with sepsis in clinical practice; thus, the rate of correct usage of antibiotics is low. Additionally, there are several other factors that affect PK in septic patients, and it is critical to understand the characteristics of antibiotics and comprehensively analyse the pathophysiological changes in septic patients.
Training is one of the most important approaches to enhance ICU physicians’ PK/PD knowledge. Our previous research revealed that the success of COVID-19 treatment is related to whether medical staff received professional training[45]. In the present survey, the advantages of professional training programmes for ICU physicians were discussed. The greater the number of participants in training programme, the greater the knowledge of PK/PD. However, there are remarkable gaps between the 5C training programme and knowledge-based PK/PD in different regions of mainland China. These results indicate that further attention should be paid to enhance ICU physicians’ knowledge about PK/PD.
This study has some limitations. First, the sample size was small, and only 1% of the total Chinese ICU staff were included. Second, ICU physicians who participated in the survey were from tertiary hospitals, and the number of physicians belonging to secondary hospitals was relatively limited. Third, the participants were mainly from the developed regions of eastern China, and there were fewer participants from western regions.