Significant Reduction of Antibiotic Consumption and Patients’ Costs after an Action Plan in China, 2010–2014
Significant Reduction of Antibiotic Consumption and Patients' Costs after an Action Plan in China, 2010-2014
Lidao Bao 0
Rui Peng 0
Yi Wang 0
Ruilian Ma 0
Xianhua Ren 0
Wenbin Meng 0
Fusheng Sun 0
Junxia Fang 0
Ping Chen 0
Yang Wang 0
Qiuhong Chen 0
Jian Cai 0
Jian Jin 0
Jinhui Guo 0
Shucheng Yang 0
Xiaomei Mo 0
Enjing Zhang 0
Yuerong Zhang 0
Zhaoxin Lu 0
Binbin Chen 0
Xiujuan Yue 0
Meijun Zhu 0
Yingying Wang 0
Xinchao Li 0
Yuan Bian 0
Shaoshan Kong 0
Wenfei Pan 0
Qian Ding 0
Jun Cao 0
Rupin Liu 0
Nan Chen 0
Xuelian Huang 0
Agula B 0
Haijun Lyu 0
0 Academic Editor: Andrew C Singer, NERC Centre for Ecology & Hydrology, UNITED KINGDOM
Funding: This study was financially supported by
Nature Science Fund from Inner Mongolia
Autonomous Region to Lidao Bao (2013MS1224),
Scientific Project Fund from Affiliated Hospital of
Inner Mongolia Medical University to Yi Wang
(NYFY2010YB006), Youth Innovation Fund from
Inner Mongolia Medical University to Lidao Bao
(NY2010QN002), and Key Scientific Fund from
Affiliated Hospital of Inner Mongolia Medical
University to Ruilian Ma (NYFYZD20130158). The
funders had no role in study design, data collection
On July 1, 2011, the Chinese government launched a national Action Plan for antibiotic
stewardship targeting antibiotic misuse in public hospitals. The aim of this study was to
evaluate the impacts of the Action Plan in terms of frequency and intensity of antibiotic utilization
and patients costs in public general hospitals.
Competing Interests: The authors of this study
declare that no conflicting interests exist.
Administrative pharmacy data from July 2010 to June 2014 were sampled from 65 public
general hospitals and divided into three segments: (1) July 2010 to June 2011 as the
preparation period; (2) July 2011 to June 2012 as the intervention period; and (3) July 2012 to
June 2014 as the assessment period. The outcome measures included (1) antibiotic
prescribing rates; (2) intensity of antibiotic consumption; (3) patients costs; and (4) duration of
peri-operative antibiotic treatment in clean surgeries of thyroidectomy, breast, hernia, and
orthopedic procedures. Longitudinal and cross-sectional analyses were conducted.
Longitudinal analyses showed significant trend changes in the frequency and intensity of
antibiotic consumption, the patients costs on antibiotics, and the duration of antibiotic
treatment received by surgical patients undergoing the 4 clean procedures during the
intervention period. Cross-sectional analyses showed that the antibiotic prescribing rates were
reduced to 35.3% and 12.9% in inpatient and outpatient settings, that the intensity of
antibiotic consumption was reduced to 35.9 DDD/100 bed-days, that patients costs on antibiotics
were reduced significantly, and that the duration of peri-operative antibiotic treatment
received by surgical patients undergoing the 4 types of clean procedures decreased to less
than 24 hour during the assessment period.
The Action Plan, as a combination of managerial and professional strategies, was effective
in reducing the frequency and intensity of antibiotic consumption, patients costs on
antibiotics, and the duration of peri-operative antibiotic treatment in the 4 clean surgeries.
The increasing prevalence of antibiotic resistance has been recognized as a public health threat
worldwide, especially in China . The prevalence of methicillin-resistant Staphylococcus
aureus (MRSA), extended-spectrum -lactamase-producing Escherichia coli, imipenem-resistant
Pseudomonas aeruginosa, and imipenem-resistant Acinetobacter baumannii accounted for
50% to 70% of nosocomial infections in China in 2010 . Antibiotic overuse and misuse are
major contributing factors for antibiotic resistance [3,4]. An epidemiological research found
that antibiotics were prescribed for 68.9% of hospitalized patients, among whom 37.0% of the
patients were subject to a combination of multiple antibiotics treatment, and that the average
intensity of antibiotic consumption was 80.1 Defined Daily Doses/per 100 patient-days (more
than twice of the average value worldwide) in China in 2010 .
According to recommendations from the World Health Organization (WHO), healthcare
authorities should put emphasis on four aspects to contain antibiotic resistance, including (1)
establishment of a national system to address antibiotic resistance; (2) legislation followed by
enforcement to prevent illegal sales or marketing of prescription drugs targeting microbial
infections; (3) education and stewardship on rational antibiotic use; and (4) strict adherence to
guidelines aiming to prevent infections in the entire healthcare facilities . Collectively,
WHO suggests that antibiotic resistance should be addressed by administrative strategies
together with professional strategies at national, regional, and institutional levels.
Implementation and enforcement of a holistic antibiotic stewardship program have shown positive effects
in combating antibiotic resistant pathogens, as was reported in a recent meta-analysis of 89
studies . On July 1, 2011, the Chinese government initiated a national public health
campaign targeting antibiotic resistance . The campaign was a national antibiotic stewardship
action plan (hereafter referred to as the Action Plan) in a series of government regulations over
the past decade by incorporating administrative and professional strategies into an overall
antibiotic stewardship program. Since its inception, the rampant antibiotic consumption driven by
multifaceted factors have been reduced as a result of enforced antibiotic management and
optimized antibiotic prescribing in China [1,9]. However, there are few researches evaluating the
overall impact of the Action Plan due to practical and methodological challenges.
The aim of this Research Article was to bridge the gap by examining the pharmacoeconomic
impacts of the Action Plan. Administrative pharmacy data and electronic medical records were
extracted from the hospital information systems in 65 public general hospitals across China.
The impacts of the Action Plan on antibiotic consumption and economic costs were analyzed
using segmented regression analysis of interrupted time series (ITS).
Policy interventions by the Action Plan
The Action Plan for combating antibiotic resistance officially took into effect on July 1, 2011
. Since compulsory participations from secondary and tertiary public hospitals
(corresponding to Class II and III hospitals according to Chinas hospital classification system) were
dictated by the Ministry of Health, a separate control group characterized by a randomized control
trial was not feasible. Therefore, we decided to evaluate the impact of the Action Plan using
segmented regression analysis of ITS as well as cross-sectional analyses to provide a whole
picture. Before the initiation of the Action Plan, 3 guidelines that had effects on antibiotic
prescribing had been enacted by the Ministry of Health: (1) Regulations on Prescription
Management issued on February 10, 2010, which highlights pharmacy validation by clinical
pharmacists on medication use, especially on antibiotic prescribing ; (2) Regulations on
pharmacy administration in medical institutions issued on January 30, 2011, which underscores
the key roles of Drug and Therapeutics Committees (DTCs) and clinical pharmacists in
formulary control, concurrent prescribing monitoring, and pharmacy validation ; and (3) Action
Plan for Antibiotic Stewardship in Clinical Application issued on April 25, 2011, which outlines
the key elements in developing and implementing a framework for antibiotic stewardship in
public hospitals . In our study, the 3 major policy changes mentioned above were considered
as a preparation phase prior to the official initiation of the Action Plan started on July 1, 2011.
The Action Plan dictated: (1) that the chief administrators (leaders groups) of the hospital
should be responsible for patient outcomes and cost-effectiveness of antibiotic utilization; (2)
that the prescription evaluation system should be enforced with manifested disciplinary actions
against infringement ; (3) that a functional infectious disease department and microbiology
department should be enforced to work in collaboration with clinical pharmacists and other
professionals with routine responsibilities of infection control; and (4) that a structured
(nonrestricted, restricted, and very-restricted) antibiotic use policies should be established and
clinicians should be trained and accredited before being assigned the level-of-use antibiotic
prescribing or dispensing privileges. Non-restricted (first-line) antibiotics refer to those with
proven efficacy, relatively low price and little effect on antibiotic resistance; restricted
antibiotics (second-line) refer to those with proven efficacy, relatively high price and greater effect on
antibiotic resistance; and very-restricted antibiotics refer to those with known adverse effects
and a tendency to cause antibiotic resistance. As a managerial tool, specific goals were set by
the Action Plan: (1) the proportion of patients receiving antibiotic prescription (hereafter
referred to as antibiotic prescribing rates) should be less than 60% for hospitalized patients or
less than 20% for outpatients; (2) the intensity of antibiotic consumption should be less than
40 DDD/100 bed-days; (3) the proportion of patients receiving antibiotic prophylaxis for clean
surgeries should be less than 30%; and (4) antibiotic prophylaxis should be administered 30 to
120 minute prior to surgical incision and the duration of the prophylaxis should not extend
beyond 24 hour.
Apart from regular dissemination sessions through routine DTC meetings in respective
hospitals, the Ministry of Health regularly held national education programs for physicians and
managerial personnel. Supervision on the compliance with the Action Plan was conducted
twice a year by the healthcare authorities. These measures are an ongoing process, so is the
refinement of the guidelines for prescribing antibiotics. On May 8, 2012, the Chinese MoH issued
a revised version of antibiotic guidelines entitled Regulations on Clinical Applications of
Antibiotics , aiming to improve rational antibiotic utilization in all medical units with detailed
listings of indications, contraindications, dose, form, route, frequency and duration of
administration on antibiotics in the formulary of public hospitals.
Conceived by the first author in May 2014, a research on the pharmacoeconomic impacts of
the Action Plan was discussed by peers on a professional clinical pharmacist community
(http://www.clinphar.cn/). The inclusion criteria required the completeness and availability of
administrative pharmacy data and electronic medical records from all medical units, excluding
the departments of pediatrics and hematology, over the past 4 years (July 2010 to June 2014).
By stratified sampling based on classification (i.e., secondary or tertiary) of public general
hospitals, the research protocols were sent to the pharmacy departments of 300 public general
hospitals. Among the 152 hospitals that responded, 65 hospitals (30 tertiary hospitals and 35
secondary hospitals) were selected depending on the inclusion criteria. The stratification of
sampling was based on the ratio of the total number of medical encounters in tertiary hospitals
to the number in secondary hospitals in 2011 (898 million in tertiary hospitals vs. 992 million
in secondary hospitals) . This research was approved by the Ethics Committee of the
Affiliated Hospital of Inner Mongolia Medical University. The Ethics Committees of the 65 hospitals
approved this research on condition of not being identified.
Since 3 major policy changes mentioned above had occurred before the initiation of the
Action Plan on July 1, 2011, we chose data points of 12 months prior to the initiation. The
coauthors of our study agreed to identify this time period as a preparation period. Further, it was
reasonable to postulate that there were lagged effects of the Action Plan as disseminating and
implementing the Action Plan occurred during an extended period of time. After preliminary
data analysis on the collected data, the study period was divided into 3 segments characteristic
of the segmented regression analysis, including Segment 1: the preparation period (July 2010 to
June 2011); Segment 2: the policy intervention period (July 2011 to June 2012); and Segment 3:
the assessment period (July 2012 to June 2014).
Outcome measures and data collection
The outcome measures were the managerial goals set by the Action Plan, as described above.
Antibiotic consumption data were collected from the administrative pharmacy data and
electronic medical records in the 65 hospitals using a self-developed program, by which the
consumed medication including antibiotics (ATC code: J01J05) were converted into the ATC/
DDD system (WHO, version 2013) . Antibiotic prescribing rates were calculated for
inpatient, outpatient, and emergency settings in the 65 hospitals. The data of the antibiotic
consumption were normalized to DDD/100 bed-days for inpatients, and to DDD/1000
outpatientdays for outpatients. Inpatients costs (including the costs on hospital study, medication,
antibiotics, and very-restricted antibiotics) were extracted from inpatients discharge records.
Outpatients costs on medication, antibiotics, and very-restricted antibiotics were collected from
hospital information systems. The patients costs were then converted into U.S. dollars (1 U.S.
dollar = 6.15 CNY). The average duration of hospital stay as well as peri-operative antibiotic
treatment received by patients undergoing 4 types of clean surgeries (thyroidectomy, breast
surgery, hernia, or orthopedic procedures) were extracted. Finally, the collected data were
aggregated as evenly-spaced average monthly data characteristic of time series data points.
Segmented regression analysis of ITS was conducted to analyze the aggregated monthly data of
interest from indicated hospitals. The data points were then divided into 3 segments
corresponding to the preparation period, policy intervention period, and assessment period. Two
parameters define each segment of a time series: (1) level, which is the value of a time series at a
beginning of a given times series (e.g., the y-intercept); and (2) trend, which is the rate of
change of an outcome measure of interest (e.g., the slope). Segmented regression analysis of
interrupted time series allows us to assess, in statistical terms, how much an intervention changed
an outcome of interest, immediately and over time; instantly or with delay; transiently or
longterm . Model 1 below can be used to evaluate the changes in level and trend caused by a
single intervention. Model 2 below can be used to evaluate the changes in time series with
more than one change points which are characterized by lagged effects and/or interventions
that occur over an extended period of time . Given the lagged effects revealed by
preliminary analysis and multiple interventions occurred during the policy intervention period, Model
2 was the statistical model used in this study:
time after interventiont et
time after interventiont
In Model 2, 0 estimates the level of the outcome during the preparation period; 1 estimates
the trend during the preparation period; 2 estimates the level change during the policy
intervention period; 3 estimates the trend change during the policy intervention period; 4
estimates the level change during the assessment period; 5 estimates the trend change during the
assessment period. Yt is the average monthly value of the outcome measure of interest at
month t; time is a continuous variable indicating time in months at time t starting from the
preparation period (time 0); intervention is an indicator for time t occurring before
(intervention = 0) or after (intervention = 1) the policy intervention which was implemented at month
13 (e.g., July 2011); time after intervention is a continuous variable counting the month after
the policy intervention at time t, coded 0 before the policy intervention or 136 after the policy
intervention; assessment is an indicator for time t occurring before (assessment = 0) or after the
assessment (assessment = 1) which was implemented at month 25; time after assessment is a
continuous variable counting the months after the assessment at time t, coded 0 before the
assessment or 124 after the assessment. The last term in Model 2 is the error term et,
representing variation unexplained by the segmented regression model. The error term et is assumed
to be comprised of a Gaussian random error (white noise) and an potential error term at time t
that may be correlated to errors (the autoregressive component) or shocks (the moving-average
component) at preceding or subsequent time points . To avoid overestimating the
significance of effect of the policy intervention, the error term et is reduced to a white noise by fitting
an ARMA model to the error term et .
Statistics were analyzed using Statistics Analysis System (SAS; version 9.2). The effects of
policy intervention are expressed as changes in level and trend and their corresponding
standard errors. Segmented Regression analysis of ITS was conducted using PROC ARIMA of SAS.
In addition, the impacts of the Action Plan were evaluated by whether the managerial goals on
antibiotic consumption had been achieved during the assessment period; therefore,
crosssectional analyses were conducted on the average yearly values of outcome measures during
the 3 periods using PROC MIXED of SAS. Bar charts were plotted for data visualization, with
error bars representing standard deviations. Normality was checked by Shapiro-Wilk test, and
homoscedasticity was checked using plots of residuals against the predicted values. The
significance level was 0.05.
The impacts of the Action Plan on antibiotic consumption in the 65 general hospitals are
shown in Fig. 1. The changes of level and trend with respects to antibiotic prescribing rates
during the preparation, intervention, and assessment periods are summarized in Table 1. Fig. 1A
shows that the average antibiotic prescribing rates declined by 2.27% (se = 0.22; p < 0.001), by
1.07% (se = 0.37; p = 0.004), and by 1.31% (se = 0.19; p < 0.001) per month in the inpatient,
outpatient and emergency settings during the intervention period, respectively (Table 1).
Cross-sectional analyses showed that the average prescribing rate was reduced significantly
from 62.9% during the preparation period to 35.3% during the assessment period in the
inpatient settings (p < 0.001; Fig. 1D). Similar reductions in prescribing rates were observed in
both outpatient (26.4% vs. 12.9%; p < 0.001) and emergency (44.2% vs. 28.4%; p < 0.001)
settings during the assessment period compared with the preparation period (Fig. 1E and 1F).
Fig. 1B and 1C show that the average intensity of antibiotic consumption decreased per
month by 2.23 DDD/100 bed-days (se = 0.30; p < 0.001) in the inpatient settings, and by 1.31
DDD/1000 outpatient-days (se = 0.14; p < 0.001) in the outpatient settings during the
intervention period (Table 1). Cross-sectional analyses showed that the average intensity of
inpatients antibiotic consumption dropped from 76.6 DDD/100 bed-days during the preparation
period to 35.9 DDD/100 bed-days during the assessment period (p < 0.001; Fig. 1G), and that
the intensity of outpatients antibiotic consumption declined from 25.7 DDD/1000
outpatientdays during the preparation period to 14.9 DDD/1000 outpatient-days during the assessment
period (p < 0.001; Fig. 1H).
Changes in patients costs on hospital stay, medication, antibiotics
including the very-restricted antibiotics
The average patients costs during the 3 periods are shown in Fig. 2. In the inpatient settings,
the total costs on hospital stay remained practically unchanged (slope = -0.71; se = -2.88;
p = 0.804) during the intervention period, whereas the average costs on medication showed a
Fig 1. Changes in antibiotic prescribing rates and intensity of antibiotic consumption. Time series of average monthly value of the antibiotic
prescribing rates (A) were plotted for inpatient (IN), outpatient (OUT), and emergency (EM) settings. The data on intensity of antibiotic consumption were
plotted for the inpatient (B) and outpatient settings (C). Cross-sectional analyses were conducted by comparing the average yearly data on antibiotic
prescribing rates in inpatient (D), outpatient (E) and emergency (F) settings as well as the intensity of consumption in the inpatient (G) and outpatient (H)
settings. P: preparation; I: intervention; A: assessment; *significant difference in intervention/assessment vs. preparation; #significant difference in
assessment vs. intervention.
Changes in level and slope in antibiotic prescribing rates in inpatient (RATE_I), outpatient (RATE_O) and emergency (RATE_E) settings in the 65 general
hospitals were analyzed using segmented regression analysis of ITS. The intensity of antibiotic consumption was expressed as DDD/100 bed-days for
inpatient settings (DDD_I) or DDD/1000 outpatient-days for outpatient settings (DDD_O). The parameters of 1 to 5, expressed as Mean (SE), were
described in the Methods.
*p < 0.05;
**p < 0.01;
***p < 0.001.
significant decrease (level = -41.2; se = 17.7; p < 0.05) at the start of the intervention period
(Table 2). The average costs on antibiotics decreased by $6.95 (se = 1.57; p < 0.001) per month
during the intervention period for hospitalized patients (Table 2). Similarly, the costs for
hospitalized patients on the very-restricted antibiotics showed a significant reduction (slope = -2.08;
se = 0.42; p < 0.001) per month during the intervention period (Table 2). Cross-sectional
analyses showed significant decreases in the average costs on hospital stay ($1396.2 vs. $1382.2;
p = 0.041), medication ($606.7 vs. $541.8; p < 0.001), antibiotics ($203.7 vs. $95.4; a reduction
of 53%; p < 0.001), and on the very-restricted antibiotics ($51.3 vs. $6.9; a reduction of 87%;
p < 0.001) for hospitalized patients during the assessment period compared with the
preparation period (Fig. 2C2F).
In the outpatient settings (Fig. 2B), the average patients costs on medication, antibiotics,
and on the very-restricted antibiotics decreased significantly by $0.49 (se = 0.12; p < 0.001),
$0.81 (se = 0.12; p < 0.001), and $0.14 (se = 0.02; p < 0.001) per month during the intervention
period, respectively (Table 2). Cross-sectional analyses showed significant decreases in the
average outpatients costs on medication ($51.7 vs. $39.1; p < 0.001), antibiotics ($18.3 vs. $6.7; a
reduction of 63%; p < 0.001), and on the very-restricted antibiotics ($2.9 vs. $1.1; a reduction
of 62%; p < 0.001) during the assessment period compared with the preparation period
Changes in hospital stay as well as duration of peri-operative antibiotic
treatment in the 4 types of clean surgeries
The average duration of hospital stay as well as peri-operative antibiotic treatment for patients
receiving the 4 types of clean surgeries of thyroidectomy, breast surgery, hernia, or orthopedic
procedures in the 65 general hospitals are shown in Fig. 3. The average duration of hospital
stay decreased by 0.16 day (se = 0.03; p < 0.001) per month during the intervention period; the
duration of peri-operative antibiotic treatment received by the surgical patients decreased by
0.19 day (se = 0.02; p < 0.001) per month during the intervention period (Table 3).
Cross-sectional analyses showed significant decreases in the duration of hospital stay (6.41 vs. 5.27 day; p
< 0.001) and the duration of peri-operative antibiotic treatment (3.97 vs. 0.96 day; p < 0.001)
during the assessment period compared with the preparation period (Fig. 3B and 3C).
Fig 2. Changes in patients costs. The stack plots represent the average monthly data of costs for inpatients (A) and outpatients (B) during the preparation,
intervention, and assessment periods. The costs are summarized as the costs on hospital stay (TO), medication (ME), antibiotics (AN), and very-restricted
antibiotics (VR). Cross-sectional analyses were conducted by comparing the average yearly data on patents costs on hospital stay, medication, antibiotics,
and very-restricted antibiotics (Very-Restricted) for both inpatients (CF) and outpatients (GI). P: preparation; I: intervention; A: assessment; *significant
difference in intervention/assessment vs. preparation; #significant difference in assessment vs. intervention.
In summary, the impacts of a national action plan for antibiotic stewardship in China were
evaluated with reference to the goals set by the Action Plan, including the frequency and
intensity of antibiotic consumption as well as the duration of antibiotic prophylaxis in clean
surgeries of thyroidectomy, breast, hernia, and orthopedic procedures. A total of 65 public general
hospitals were included, and data were extracted from pharmacy modules of respective hospital
information systems. Longitudinal analyses were conducted on the average monthly data by
regression analysis of ITS; cross-sectional analyses were conducted on the average yearly data
using the mixed model. Regression analyses of ITS revealed consistent and significant trend
antibiotics, and the duration of antibiotic treatment received by surgical patients undergoing
the 4 clean procedures during the intervention period (Tables 1, 2, and 3). Cross-sectional
Changes in level and slope in patients costs on medications (ME), antibiotics (AN), and on the very-restricted (VR) antibiotics were analyzed for both
analyses show that the antibiotic prescribing rates during the assessment period were reduced
to 35.3% and 12.9% (Fig. 1D and 1E) in inpatient and outpatient settings respectively,
indicating that the goals set by the Action Plan were achieved (60% for inpatients and 20% for
outpatients as described in the Methods). During the preparation period, the average yearly intensity
of antibiotic consumption was 76.6 DDD/100 bed-days (Fig. 1G) in inpatient settings, which
was comparable to the previously reported data (80.1 DDD/100 bed-days) . In contrast, the
intensity was reduced to 35.9 DDD/100 bed-days (Fig. 1G) during the assessment period,
which was lower than the goal set by the Action Plan (40 DDD/100 bed-days). Meanwhile,
patients costs on antibiotics were reduced significantly by 53% (Fig. 2E) and 62% (Fig. 2H) in
Fig 3. Changes in hospital, duration of peri-operative antibiotic treatment. Time series of duration of hospital stay (dHS) and peri-operative antibiotic
treatment (dAT) for patients undergoing 4 types of clean procedures of thyroidectomy, breast, hernia, and orthopedic procedures were plotted (A).
Crosssectional analyses were conducted by comparing the duration of patients hospital stay (B) and the duration of peri-operative antibiotic treatment (C) received
by the surgical patients during the 3 study periods. P: preparation; I: intervention; A: assessment; *significant difference in intervention/assessment vs.
preparation; #significant difference in assessment vs. intervention.
inpatient and outpatient settings during the assessment period compared with the preparation
period, respectively. In effect, the duration of hospital stay were analyzed for all hospitalized
patients as well, showing that there were no significant differences during the 3 periods
investigated (data not shown); therefore, we selected a homogeneous subset of clean surgeries to
evaluate the impacts of the Action Plan. The duration of peri-operative antibiotic treatment
received by surgical patients undergoing the 4 types of clean procedures decreased to less than
24 hour (< 24 hour set by the Action Plan) during the assessment period, which was
concomitant with a slight yet significant decrease in the duration of hospital stay (Fig. 3B and 3C).
The purpose of the Action Plan as a combination of professional and administrative
strategies was to promote rational antibiotic utilization to contain the prevalence of antibiotic
resistance and patients costs. The Action Plan focused on the managerial strategies. The
effectiveness and efficiency of the managerial strategies can be attributed, at least partially, to
the organizational structure in Chinas public hospitals. The chief administrators are appointed
jointly by higher healthcare administrations and cadre authorities, taking full responsibilities of
day-to-day performance, including procurement of medicines and employment decisions .
Healthcare professionals working in public hospitals are subject to civil service rules as well as
the supervision from cadre authorities , meaning that disciplinary actions caused by
infringement on the antibiotic guidelines lead to the cessation of the prescribers medical career.
In implementing the strategies initiated by the Action Plan, members of DTC and directors of
all relevant departments hold weekly meetings, by which issues in antibiotic administration
were identified and discussed and prescribers in question are interviewed. In routine practice,
clinical pharmacists are conferred with more power to participate in daily ward-rounds and
concurrent pharmacy validation. Furthermore, as a managerial tool, healthcare authorities
conduct two supervision sessions each year, during which the hospitals performances relating
to antibiotics are inspected. All the members of our research team agree that prescribers and
clinical pharmacists are working under more pressure from the management and peers.
Since Chinas private hospitals, which handled about 5% of total outpatient and inpatient
services , are privately funded and operated for profit with more autonomy, the Action
Plan of antibiotic stewardship concentrated on public hospitals, which are roughly divided into
national, provincial, municipal, and county-level hospitals. Our pilot study on the national and
county-level public hospitals showed larger variation in the collected data; therefore, they were
excluded from this study to achieve statistical homogeneity. Though statistical analyses showed
slight yet significant differences between secondary and tertiary hospitals, separate data
analyses using hospital category as a factor reached the same conclusions as they were analyzed as a
whole (data not shown). Besides, only 65 out of 300 hospitals were admitted in this study,
which was mainly due to three reasons: (1) the lack of a fully-functional pharmacy
management system in certain hospitals that were excluded from this study; (2) the concern for release
of sensitive medical data; and (3) the stratified sampling method, which required a ratio of the
number of tertiary hospitals to the number of secondary hospitals equaling about 9/10. A
computerized pharmacy management system plays important roles in pharmacy validation and
concurrent prescription monitoring with improved patient outcomes . However, more
than 50 hospitals that could not participate in this study lacked a functional pharmacy module
in their hospital information systems during the study periods, especially in 2010. Although
the avoidance of acquiring sensitive data, such as standardized mortality rates, was manifested
in our research protocols, more than 100 of hospitals that refused to participate concerned the
release of medical information on patients costs, resulting in the relatively lower response rate
(152/300), which was confirmed in our follow-up calls. In addition, the impacts of the Action
Plan on the duration of antibiotic treatment in clean surgeries were evaluated in only 4 types of
clean surgeries of thyroidectomy, breast, hernia, and orthopedic procedures, since these 4
surgeries could be identified as clean procedures from the available data. We examined the
duration of antibiotic treatment other than the duration of antibiotic prophylaxis, since whether the
antibiotic treatment was for prophylactic purpose or for therapeutic purpose could not be
identified from the collected data in the year of 2010. The compliance of administering antibiotic
prophylaxis 30 to 120 minute prior to surgical incision was not evaluated quantitatively in this
study, since recording the timing of prophylactic antibiotic administration electronically
required technical issues of modifying the pharmacy management systems, which occurred
differentially in the investigated hospitals.
Along with the antibiotic stewardship program in public hospitals, the Chinese government
began to strengthen antibiotic utilization policy specific to primary healthcare institutions in
the community and in rural clinics, which will be evaluated in our future studies. We hope that
the fundamental changes prompted by the Action Plan can gradually turn into institutionalized
and standardized clinical practice in all healthcare institutions so as to effectively address the
global threatantibiotic resistance.
In conclusion, the antibiotic stewardship in China was effective in reducing the frequency and
intensity of antibiotic use in public hospitals. Furthermore, segmented regression analysis of
ITS reveals how these changes in antibiotic prescriptions changed in different settings in
various types of hospitals, which will provide evidence for healthcare policy makers when for future
policy interventions on antibiotic stewardship.
Conceived and designed the experiments: LB RP Yang Wang RM XR AB HL. Performed the
experiments: WM FS JF PC Yang Wang QC J. Cai JJ JG SY XM EZ YZ ZL BC XY MZ Yingying
Wang XL YB SK WP QD J. Cao RL NC XH. Analyzed the data: LB RP WB AB HL.
Contributed reagents/materials/analysis tools: WM FS JF PC Yang Wang QC J. Cai JJ JG SY XM EZ YZ
ZL BC XY MZ Yingying Wang XL YB SK WP QD J. Cao RL NC XH. Wrote the paper: LB RP
AB HL. Contributed to the selection of statistics of interest investigated: LB Yi Wang WM FS
JF PC Yang Wang QC J. Cai JJ JG SY XM EZ YZ ZL BC XY MZ Yingying Wang XL YB SK WP
QD J. Cao RL NC XH.
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