Investigation of Amoxicillin Use in Fever Clinic Patients: Standardized Application of Antibiotics is Still Challenging : Infectious Microbes & Diseases

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Letter

Investigation of Amoxicillin Use in Fever Clinic Patients: Standardized Application of Antibiotics is Still Challenging

Yu, Dong-Shan#; Gao, Zhen#; Ai, Mao-Xing; Wu, Yu-Chan; Xi, Wen-Na*

Editor(s): van der Veen, Stijn

Author Information
Infectious Microbes & Diseases 4(1):p 41-43, March 2022. | DOI: 10.1097/IM9.0000000000000081

Abstract

Amoxicillin has been a widely prescribed antibiotic in primary care settings since the 1970s. It is a semisynthetic penicillin with enhanced activity against a variety of Gram-positive and Gramnegative bacteria, such as Streptococcus species, Listeria monocytogenes, Clostridium species, and Escherichia coli.1,2 In China, almost every pharmacy sells amoxicillin without the need for a prescription, which brings great convenience to people, but also poses striking challenges to keeping development of drug resistance under control.3,4 Here, we investigated the clinical impact of non-prescribed amoxicillin usage in patients before attending the fever clinic of the Second Affiliated Hospital of Nanchang University from March 1, 2020 to March 31, 2021. We aimed to understand the basic situation of amoxicillin usage to provide support for the prevention and control of antibiotic abuse.

According to medical records, a total of 9093 patients went to the fever clinic of the Second Affiliated Hospital of Nanchang University from March 2020 to March 2021. Investigation of amoxicillin usage in these patients showed that 446 patients (4.9%) admitted taking amoxicillin and no other antibiotics before going to the fever clinic. Among these patients, 100 cases were selected by adopting a simple random sampling method for further investigation. As the control group, another 100 cases were randomly selected with the same method from patients who did not take any antibiotics. Clinical manifestations, including febrile symptoms, signs, laboratory tests, amoxicillin usage, and primary diagnosis, were included in the statistics to compare the amoxicillin and control groups. Medical laboratory data were collected, including a complete blood cell count (white blood cells, neutrophils, lymphocytes) and C-reactive protein (CRP) levels. All medical laboratory data were generated from the Department of Clinical Laboratory of the Second Affiliated Hospital of Nanchang University. As shown in Table 1, more than half of the patients were initially diagnosed with upper respiratory tract infections, and the duration of amoxicillin use was basically similar as the duration of fever. Patients from the amoxicillin group and the control group displayed no marked differences in terms of age, sex, and symptoms, including the duration of fever, temperature, chills, cough, expectoration, swelling of tonsils, acute pharyngeal discomfort, gastrointestinal distress, and urinary tract discomfort. In laboratory tests, there were no significant differences between the groups in counts of total white blood cells, neutrophils and lymphocytes, or the levels of CRP. Besides the primary diagnoses of upper respiratory tract infections (59%), lung infections (11%), acute gastroenteritis (9%), and urinary tract infections (5%) were also common. There was no significant difference in the primary diagnosis between the amoxicillin group and the control group. The pathogenesis of upper respiratory tract infections involves complex interactions between bacterial and viral pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, respiratory syncytial virus, Bocavirus and Adenovirus, and the host inflammatory responses.5 Therefore, it is inappropriate to choose oral amoxicillin therapy or other antibiotics without evidence of etiology, or blood routine and inflammatory markers. Our data indicates that amoxicillin is extensively used by the investigated population at an alarming rate, while it does not achieve the aimed antiinfective effects.

Table 1 - Baseline characteristics and laboratory findings of 200 patients

Basic characteristics and laboratory findings

All patients (n = 200)

Amoxicillin group (n = 100)

Control group (n =100)

P value

Age, years

32 (25, 45)

29 (19, 47)

25 (21, 45)

0.38

Sex

Women

95 (47%)

46 (46%)

49 (49%)

-

Men

105 (53%)

54 (54%)

51 (51%)

-

Course of amoxicillin, days

-

2.2 (1.0, 3.8)

-

-

Signs and symptoms

Duration of fever, days

2.6 (4.8,18.3)

3.1 (1.0, 5.4)

2.2 (1.0, 3.7)

0.28

Temperature, °C

37.3-38.0

70 (35%)

22 (22%)

48 (48%)

-

38.1-39.0

88 (44%)

51 (51%)

37 (37%)

-

>39.0

42 (21%)

27 (27%)

15 (15%)

-

Chills

42 (21%)

27 (27%)

15 (15%)

0.29

Cough

85 (43%)

45 (45%)

40 (40%)

0.74

Expectoration

72 (36%)

42 (42%)

30 (30%)

0.42

Swelling of tonsil

43 (22%)

28 (28%)

15 (15%)

0.30

Acute pharyngeal discomfort

131 (66%)

62 (62%)

69 (69%)

0.57

Diarrhea

27 (14%)

12 (12%)

15 (15%)

0.50

Stomachache

11 (6%)

7 (7%)

4 (4%)

0.11

Nausea

13 (7%)

6 (6%)

7 (7%)

0.52

Vomiting

9 (5%)

4 (4%)

5 (5%)

0.70

Frequent micturition, urgent urination and/or odynuria

6 (3%)

3 (3%)

3 (3%)

0.86

Laboratory findings

White blood cell count, × 109/L

9.5 (5.8, 12.7)

9.4 (6.0, 13.1)

9.6 (5.7, 11.6)

0.72

Neutrophil count, × 109/L

8.5 (4.1, 9.9)

9.5 (3.7, 10.1)

7.2 (4.3, 8.9)

0.47

Lymphocyte count, × 109/L

1.5 (0.9, 1.8)

1.5 (0.9, 1.8)

1.4 (0.9, 1.9)

0.35

C-reactive protein, mg/L

26.1 (2.3, 38.3)

21.0 (5.5, 38.9)

11.8 (0.5, 15.7)

0.06

Primary diagnosis

Upper respiratory infection

118 (59%)

53 (53%)

65 (65%)

0.32

Lung infection

21 (11%)

13 (13%)

8 (8%)

0.07

Acute gastroenteritis

17 (9%)

7 (7%)

10 (10%)

0.45

Urinary tract infection

10 (5%)

6 (6%)

4 (4%)

0.50

Others

34 (17%)

21 (21%)

13 (13%)

0.17

Categorical data were summarized as frequencies (%) and compared by x2 test or Fisher exact test between groups when applicable. Continuous variables were described as median and interquartile range (IQR) values and compared with the Mann-Whitney U test. All analyses were performed with GraphPad Prism 8 (GraphPad Software, UK). Differences with P < 0.05 between group means were considered statistically significant.

Overall, our study highlights the extensive use of amoxicillin among fever patients, while therapeutic effects appear unsatisfactorily. This phenomenon is probably associated with the following reasons: (1) Amoxicillin is a well-known and inexpensive antibiotic, which is available in almost every pharmacy in China and can be purchased under a real-name registration system, even without a prescription. In addition, many Chinese families keep a supply of medicines, including antibiotics, in case of an emergency. (2) Having been used extensively for many years, the rate of amoxicillin resistance has increased significantly. For example, the reported frequency of amoxicillin resistance was 85.7% for Salmonella isolates, while E. coli and Staphylococcus aureus displayed resistance to amoxicillin in more than 13% and 90% of the isolates, respectively.6,7 (3) The use of amoxicillin was inappropriate because either the course of treatment was of insufficient length or dose, or this antibiotic was not recommended to target the specific etiological agent of the infection. An antibiotic treatment course usually takes 3-7 days. However, our data indicated that the median time of amoxicillin usage in this study was 2.2 days, which was short in course and therefore might limit the therapeutic effect of the antibiotic. Furthermore, pathogens of upper respiratory tract infections are complex.5 When people purchase medicines in pharmacies, they may get unsuitable antibiotics due to limited knowledge and a lack of necessary pathogen evidence.

In summary, irregular use of antibiotics is still a serious problem. Standardized application of antibiotics not only needs to be carried out in hospitals, but also needs to be supervised in clinics and pharmacies. Therefore, it is imminent to educate the public about the scientific application of antibiotics.

Acknowledgments

The authors thank the patients for complying with the epidemic regulations and going to the fever clinic.

References

[1]. Brogden RN, Carmine A, Heel RC, Morley PA, Speight TM, Avery GS. Amoxycillin/clavulanic acid: a review of its antibacterial activity, pharmacokinetics and therapeutic use. Drugs 1981;22(5):337-362.
[2]. Chen Y, Sun L, Ba X, et al. Epidemiology, evolution and cryptic susceptibility of methicillin-resistant Staphylococcus aureus in China: a whole-genome-based survey. Clin Microbiol Infect 2021;28(1):85-92.
[3]. Jacobs MR. Extended release amoxicillin/clavulanate: optimizing a product for respiratory infections based on pharmacodynamic principles. Expert Rev Anti Infect Ther 2005;3(3):353-360.
[4]. Rodríguez EC, Bautista AM, Montaño LA, Ovalle MV, Correa FP. Laboratory-based surveillance of Shigella spp. from human clinical cases in Colombia, 1997-2018. Biomedica 2021;41(1):65-78.
[5]. Pettigrew MM, Gent JF, Pyles RB, Miller AL, Nokso-Koivisto J, Chonmaitree T. Viral-bacterial interactions and risk of acute otitis media complicating upper respiratory tract infection. J Clin Microbiol 2011;49 (11):3750-3755.
[6]. Wu G, Gong S, Cai H, Ding Y. The availability, price and affordability of essential antibacterials in Hubei province, China. BMC Health Serv Res 2018;18(1):1013.
[7]. Zhang SX, Zhou YM, Tian LG, et al. Antibiotic resistance and molecular characterization of diarrheagenic Escherichia coli and non-typhoidal Salmonella strains isolated from infections in Southwest China. Infect Dis Poverty 2018;7(1):53.
Keywords:

amoxicillin; fever clinic; standardized application; popularization education; challenge

Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.