Study selection
A total of 9,973 records were retrieved in the initial literature search, and additional 102 studies were identified through manual reference screens. After removing 1,395 duplicates, 8,680 studies were retrieved. Titles and abstracts screening resulting in 603 records for full-text evaluation. Finally, 101 records were included. (Fig. 1)
Study Characteristics And Quality
Of the 101 eligible studies included in our review, 82 studies reported the prevalence of antibiotic utilization of children, including 34 studies on outpatient[32–65], 43 studies on inpatient[66–108], and one study on both outpatient and inpatient[109]. Moreover, four studies reported the prevalence of self-medication antibiotic utilization at home[110–113]. The majority of the studies were retrospective observational studies (n = 76), were published after 2011 year (n = 68), and were conducted in urban area (n = 75), and collected data from the Level 3 hospital (n = 50). The study data were obtained from 22 provinces in mainland China, with the largest number of studies from Guangdong province (n = 15), followed by Guangxi province (n = 9), and Jiangsu province (n = 7). A total of 50 studies collected data from the eastern economic zone, 19 studies from the western economic zone, 10 studies from the central economic zone, and three studies reported data from nationwide. In addition, 43 studies reported the risk factors for antibiotic utilization[20, 32, 33, 39, 42, 43, 49, 50, 55, 57, 64, 66, 68, 75, 77, 83–85, 91, 92, 99, 110–131], of which, five studies focused on children, 20 studies focused on physicians, 31 studies reported from caregivers, 11 studies reported from retail pharmacies, and one study reported from hospital.(Table S3, Table S4,Table S5,Table S6 in Appendix C).
Regarding the quality of included studies, for observational studies, 37 were with high quality and 58 were with moderate quality (Table S7 in Appendix D). For randomized studies, 2 were with high quality, 4 were with moderate quality. (Table S8 in Appendix D).
Prevalence Of Antibiotic Utilization In Chinese Children
The overall prevalence of antibiotic utilization among outpatients and inpatients were 63.8% (95%CI: 55.1–72.4%, I2 = 99.9%, P < 0.0001) (Fig. 2), and 81.2% (95% CI: 77.2–85.3%, I2 = 99.7%, P < 0.0001) (Fig. 3), respectively. In addition, the overall prevalence of caregiver’s self-medicating of antibiotics for children at home was 37.8% (95% CI: 7.9–67.6%, I2 = 99.8%, P < 0.0001) (Fig. 4).
In the subgroup analyses, the prevalence of combined use of antibiotic was 30.7% among outpatients, and 38.6% among inpatients. The prevalence of antibiotic utilization in eastern, central, and western economic zone were 59.8%, 80.0%, 70.0%, respectively, for outpatients, and 80.9%, 78.7%, 80.4%, respectively, for inpatients. A higher prevalence antibiotic utilization was found in urban, with 64.1% and 81.7% for outpatients and inpatients respectively. In addition, prevalence of antibiotic utilization in level 1, 2, 3 hospital were 66.4%, 59.1% 64.0%, respectively, among outpatients, and 85.5% in level 2 hospital, 79.6% in level 3 hospital among inpatients. (Table 1, Table 2).
Table 1
The prevalence of outpatient antibiotic utilization by antibiotic combination situation, economic zone, study setting, and hospital level.
| No. of studies (N) | n/N | Percentage (95% CI) (%) | P-value |
---|
Antibiotic combination situation (23) |
Single use of antibiotic | 23 | 27736/36751 | 69.3(58.2–80.3) | P < 0.0001 |
Combined use of antibiotic | 23 | 9015/36751 | 30.7(19.7–41.8) | P < 0.0001 |
Economic zone (34) | | | | |
Eastern | 24 | 68961/118022 | 59.8(49.3–70.2) | P < 0.0001 |
Central | 4 | 4363/5244 | 80.0(67.2–92.8) | P < 0.0001 |
Western | 7 | 5371/8540 | 70.0(56.1–83.9) | P < 0.0001 |
Study setting (34) | | | | |
Urban | 29 | 68961/118022 | 64.1(54.4–73.8) | P < 0.0001 |
Rural | 6 | 15489/30429 | 63.1(55.3–71.1) | P < 0.0001 |
Hospital level (34) | | | | |
Level 3 | 18 | 61551/103670 | 64.0(54.9–73.0) | P < 0.0001 |
Level 2 | 8 | 9086/21118 | 59.1(33.6–84.5) | P < 0.0001 |
Level 1 | 9 | 13813/23663 | 66.4(47.2–85.5) | P < 0.0001 |
N: Sample Size; n: Number of Children with Antibiotics; random-effect meta-analysis was used to calculate the overall pooled prevalence of antibiotic utilization. |
Table 2
The prevalence of inpatient antibiotic utilization by antibiotic combination situation, economic zone, study setting, and hospital level.
| No. of studies (N) | n/N | Percentage (95% CI) (%) | P-value |
---|
Antibiotic combination situation (34) |
Single use of antibiotic | 34 | 16230/26399 | 61.5(53.9–69.2) | P < 0.0001 |
Combined use of antibiotic | 34 | 10169/26399 | 38.6(31.0-46.2) | P < 0.0001 |
Economic zone (43) | | | | |
Eastern | 26 | 30201/36977 | 80.9(77.2–84.6) | P < 0.0001 |
Central | 9 | 17880/22341 | 78.7(71.6–85.9) | P < 0.0001 |
Western | 16 | 25156/34658 | 80.4(71.1–89.7) | P < 0.0001 |
Study setting (43) | | | | |
Urban | 43 | 46584/60478 | 81.7(77.4–85.9) | P < 0.0001 |
Rural | 2 | 219/296 | 76.3(77.2–85.3) | P < 0.0001 |
Hospital level (43) | | | | |
Level 3 | 33 | 42233/55692 | 79.6(74.6–84.6) | P < 0.0001 |
Level 2 | 13 | 4527/5039 | 85.5(81.6–89.5) | P < 0.0001 |
Level 1 | 1 | 43/45 | 95.6(-) | - |
N: Sample Size; n: Number of Children with Antibiotics; random-effect meta-analysis was used to calculate the overall pooled prevalence of antibiotic utilization. |
Risk Factors Of Antibiotic Utilization In Chinese Children
We explored the risk factors of antibiotic utilization in Chinese children using qualitative analysis from five aspects and 12 items (Table 3). The presentation of factors here is grouped into those at children level (e.g. distribution of disease, lack of skills and knowledge), and physician level (e.g. lack of skills and knowledge, pressure from patient, physician-patient relationship, economic incentive and profit from prescribing medicine, lack of pathogen detection or low pathogen detection rate), and caregiver level (e.g. lack of skills and knowledge, put pressure on physician to get antibiotics, behavior of self-medicating with antibiotics at home for children) and retail pharmacies level (e.g. sale antibiotics without prescription) and hospital level (e.g. ward capacity).
Table 3
Risk factors of antibiotic utilization in children in China.
| Risk factors | | No. of studies (N = 43) |
---|
Children | distribution of disease | The biological systems and organs of children are not well-developed, especially those of younger children, which make children more vulnerable. Children with upper respiratory tract infections (URTIs) are among the highest receivers of antibiotics. | 3(7.0%) |
| lack of skills and knowledge | Middle school students still have problems in medication adherence, the management of expired drugs and the antibiotics cognition. | 1(2.3%) |
Physicians | lack of skills and knowledge | Physicians consider antibiotics to be anti-inflammatory drugs is a common misconception. Doctors might overprescribe antibiotics due to lack of knowledge of its rational use. Gaps between reported knowledge and actual practice within antibiotic prescribing are commonly encountered. | 20 (46.5%) |
| pressure from patient | Majority of the village doctors would prescribe antibiotics if their patients stick to getting them. | 5(11.6%) |
| physician-patient relationship | Ineffective communication between patients and physicians may lead to the unnecessary prescription of antibiotics. | 2(4.7%) |
| economic incentive and profit from prescribing medicine | Retention of patients would increase physicians’ consultation fees. Doctors are able to make a profit from individual drug prescriptions, including antibiotics, and this may stimulate over-prescribing of antibiotics. | 5(11.6%) |
| lack of pathogen detection or low pathogen detection rate | Uncertainty in the etiological diagnosis is reported as one of the main causes of fear when prescribing in primary care settings. The doctor paid little attention to microbiological examination. | 8(18.6%) |
Caregivers | lack of skills and knowledge | Parents have considerable misunderstandings that may contribute to inappropriate antibiotic use. Most of parents believe that taking antibiotics in advance could protect children from common diseases. | 29(67.4%) |
| put pressure on physician to get antibiotics | Parents’ high expectations of quick relief of symptoms and recovery of their children would impose further pressure on doctors to prescribe antibiotic in order to make treatments more immediately effective. | 14(32.6%) |
| self-medicating with antibiotics at home for children | Most of the parents would use lower dose of antibiotics than required by the instruction with consideration of safety, and some parents would choose a higher dose. | 14(32.6%) |
Retail pharmacies | sale antibiotics without prescription | Although antibiotics sales in retail pharmacies are not within the jurisdiction of government regulation, retail pharmacy is still the main channel for parents to purchase antibiotics. | 11(25.6%) |
Hospitals | ward capacity | Newborn units with more than 100 beds have the highest rate of antibiotic use, compared to units with 50 or fewer beds, and those with 51–100 beds. | 1(2.3%) |
Distribution of disease in children has been regarded as a risk factor influencing antibiotic utilization by 7.0% (3/43) of studies. A study indicated that the reasons that lead physicians prescribe antibiotics were mainly clinical determinants such as severity of symptoms, immediate clinical issue[129]. Another survey on pediatric outpatient prescription found that respiratory infection was one of the diseases with the highest frequency, the most dosage of antibiotic utilization[86]. In addition, children lacking of skills and knowledge about antibiotics also influences antibiotic utilization. Although children knew that antibiotics were not antiviral drugs, they were less able to identify specific antibiotics[121].
A total of 46.5% (20/43) of studies suggested that physicians lacking of skills and knowledge was an important factor influencing antibiotic utilization of children. It was indicated that nearly 30% of pediatricians considered antibiotics to be anti-inflammatories[42], and some village doctors confused to select appropriate antibiotics for children[120]. Some studies explored that pressure from patient had an effect on antibiotic prescriptions. About 70% of the village doctors complied with the primary caregivers’ request even when they felt the antibiotics were unnecessary[120]. Physician-patient relationship was mentioned by 4.7% (2/43) of studies. Physicians wariness of medical disputes by dissatisfied patients might induce them to order unnecessary investigations and overprescribe antibiotics[77]. Economic incentives and profits from prescription also lead physicians to prescribe antibiotics. A study reported that inter-hospital competition was a driver of inappropriate prescribing, if patients did not have antibiotics they want, they will choose other hospital to purchase, leading to suffer financially[128]. A total of 18.6% (8/43) of studies reported that lacking of pathogen detection or low pathogen detection rate was also a risk factor. Through meta-analysis, we found that the overall pathogen detection rate among inpatients was 44.7% (95% CI: 29.7–59.7%, I2 = 99.7%, P < 0.0001), but there was no study on outpatients. (Fig. S1 in Appendix E).
A total of 67.4% (29/43) of studies reported that lacking of skills and knowledge from caregivers influences antibiotic utilization for children. Almost 66.3% of respondents mistakenly believed that antibiotics and anti-inflammatory drugs are the same drugs, 68.8% of respondents believed that antibiotics can cure infections caused by virus, 51.5% of respondents believed that antibiotics can be used to treat common cold, 69.9% of respondents believed that antibiotics can be used to treat pharyngitis or nonsuppurative tonsillitis, 37.9% of respondents didn’t know antibiotics should only be obtained with a doctor’s prescription, and 46.6% of respondents didn’t know inappropriate use of antibiotics can reduce the effectiveness of antibiotics (Table S9 in Appendix E). 32.6% (14/43) of studies reported put pressure on physician to get antibiotics was one of the risk factors influencing antibiotic utilization for children. A study reported that about half of the caregivers had requested antibiotics directly from physicians[117]. A total of 32.6% (14/43) of studies reported self-medicating with antibiotics at home for children was a risk factor of antibiotic utilization. A study reported that about 69.2% of caregivers would self-medication for children before visiting a doctor, in addition, to improve the effectiveness of treatment, they would increase the dosage arbitrarily[118].
For retail pharmacies, selling antibiotics without prescription has been regarded as a risk factor of antibiotic utilization for children. It was reported that individuals in most rural areas continue to have easy access to antibiotics[125]. The rate of antibiotic use was also associated with bed capacity, newborn units with more than 100 beds had the highest rate of antibiotic use, compared to units with 50 or fewer beds, and those with 51–100 beds[124].