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. 2020 Dec 28;15(12):e0243868. doi: 10.1371/journal.pone.0243868

Antibiotic prescription practices among prescribers for children under five at public health centers III and IV in Mbarara district

Nelson Okello 1,2,*, Joseph Oloro 3, Catherine Kyakwera 1, Elias Kumbakumba 1, Celestino Obua 3
Editor: Mehreen Arshad4
PMCID: PMC7769467  PMID: 33370280

Abstract

Introduction

Rational use of medicines requires that patients receive medications appropriate to their clinical needs. Irrational prescription of antibiotics has been reported in many health systems across the world. In Uganda, mainly nurses and assistant medical officers (Clinical officers) prescribe for children at level III and IV primary care facilities (health center II and IV). Nurses are not primarily trained prescribers; their antibiotic prescription maybe associated with errors. There is a need to understand the practices of antibiotic prescription among prescribers in the public primary care facilities. We therefore determined antibiotic prescription practices of prescribers for children under five years at health center III and IV in Mbarara district, South Western Uganda.

Methods

This was a retrospective descriptive cross-sectional study. We reviewed outpatient records of children <5 years of age retrospectively. Information obtained from the outpatient registers were captured in predesigned data abstraction form. Health care providers working at health centers III and IV were interviewed using a structured questionnaire. They provided information on socio-demographic, health facility, antibiotic prescription practices and availability of reference tools. Data was analyzed using STATA software version 13∙0.

Results

There were 1218 outpatients records of children under five years reviewed and 35 health care providers interviewed. The most common childhood illness diagnosed was upper respiratory tract infection. It received the most antibiotic prescription (53%). The most commonly prescribed oral antibiotics were cotrimoxazole and amoxicillin, and ceftriaxone and benzyl penicillin were the commonest prescribed injectable antibiotics. Up to 68.4% of the antibiotic prescription was irrational. No prescriber or facility factors were associated with irrational antibiotic prescription practices.

Conclusion

Upper respiratory tract infection is the most diagnosed condition in children under five years with Cotrimoxazole and Amoxicillin being the most commonly prescribed antibiotics. Antibiotics are being prescribed irrationally at health centers III and IV in Mbarara District. Training and support supervision of prescribers at health centers III and IV in Mbarara district need to be prioritized by the district health team.

Introduction

Medicines play an integral part of healthcare delivery [1]. However, they are expensive commodities and account for a significant proportion of overall health expenditure in most countries. Rational use of medicines requires that patients receive medications appropriate to their clinical needs, in doses that meet their own individual requirements, for an adequate period of time and at the lowest cost to them and their community [2]. Irrational use of medicines described as the medically inappropriate and economically ineffective use of pharmaceuticals is a major challenge facing many health systems across the world [1].

Children represent a subset of the population who frequently receive antibiotics. Antibiotics are the most commonly prescribed drugs. It is particularly necessary after a confirmation culture and sensitivity studies, but structurally primary care units do not have facilities for microbial studies. Approximately three quarters of all outpatient antibiotic prescriptions given to children are for treatment of upper respiratory tract conditions [3]. Most children are seen in a primary health care setting by primary care givers, mainly nurses, assistant medical officers (clinical officers) and occasionally medical officers. Clinical officers are health cadres with diploma in medicine and community health, they work under supervision of holders of bachelor of medicine and bachelor of surgery (Medical officers/General Practioners).

Uganda's healthcare system works on a referral basis. Village health teams (VHT) work in the community at the lowest health care level where they provide referral of patients from the community; the second level of care often called health center II (dispensaries) are located at a parish level, health center IIIs and IVs are located at a sub county and a county level respectively. Health center III provide mainly maternal health and ambulatory care services. Health center IV has an operation room and provide in-patient and ambulatory services. Patients from a health center IV are referred to the district hospital, located at the district level. Regional and National Referral hospital are located at the Regional and National level respectively. Health centers III and IV (level III and IV) lack capacity to perform most of the investigations including culture/sensitivity testing and X-rays.

To address this and improve prescription practices, Uganda has a national clinical guideline (UCG) [4] last updated in 2016. It aimed at providing easy-to-use, practical, complete, and useful information on how to correctly diagnose and manage all common conditions in a primary care setting. The clinical guide should help in making the most appropriate use of scarce diagnostic and clinical resources, including medicines. The Regional Referral hospital and the district hospitals according to the Uganda health systems should be able to provide supervision role and mentorship to the lower health facilities within the district.

Health workers at health centers III and IV depend on their clinical skills and experience in making decision about antibiotic prescriptions. Nurses are not primarily trained as prescribers and thus their antibiotic prescription may be associated with errors. There is scarce information about the practice of antibiotic prescription among prescribers in public health centers III and IV in Mbarara District, South Western Uganda. We therefore evaluated pediatrics antibiotic prescription practices among the health workers caring for children under five years at the primary health care settings in Mbarara district.

Materials and methods

Study design

This was a descriptive cross-sectional study of antibiotic prescription practices among prescribers of children under five years at 17 public Health center III and IV in Mbarara District. This was conducted from February to May 2019.

Study setting

Mbarara district is found in the South-Western region of Uganda. It has a Regional Referral hospital, 13 Health Center III and four Health Centers IV. Most of these facilities are located in the rural and peri-urban areas and receive medical supplies from Uganda national medical store based on Uganda national essential drug list. The antibiotics supplied to these facilities is based on the level of care and must be on the essential drug list. They include among others, amoxicillin, erythromycin, azithromycin, cotrimoxazole, ampicillin, cloxacillin, ceftriaxone, benzyl penicillin and ciprofloxacin.

The health center III has about 19 health staff, headed by a Senior Clinical Officer (Senior assistant medical officer), it has an outpatient, laboratory and maternity services and serves about 23,969 people of which about 5033 (21%) are children under five [5]. Health centers IV serves a county or a parliamentary constituency, it is managed by two medical officers and other cadres; it serves a population of about 100,000 of which 21,000 (21%) are children under 5years of age. Health center III and IV facilities have limited investigation capacities, for instance, they do not have an X-ray machine and they have no facility for doing culture and sensitivity testing. Most often, prescribers at public health centers III and IV use the Uganda clinical guideline and manual for integrated management of newborn and childhood illnesses [6] for diagnosis and treatment of common childhood illnesses.

Study population

The study included 35 health care workers attending to children at Health center III and IV facilities and outpatient registers of children under five years treated with antibiotics within the last six months in the facilities.

Eligibility criteria

Prescribers (nurses, midwives, clinical officers and medical officers) at public health centers III and IV.

Records with complete entries.

Sample size and sampling procedure

The Cochran’s formula for sample size determination of a single population proportion [7], was used to calculate sample size for prescribers in this study. The prevalence of irrational antibiotic prescriptions among health care workers in lower health facilities in Mbarara was assumed at 50%. This was an arbitrary value given that there was no comparative data. 80% power and 95% confidence intervals were considered, and a sample size of 384 was realized for an infinite population, which was corrected for a finite population to 35. Participants were recruited consecutively until the sample size was reached. Each health center III and IV was visited once during data collection and two prescribers from each facility were interviewed using a structured questionnaire. In order to determine the common childhood illnesses treated with antibiotics in Health center III and IV, we systematically reviewed the facilities outpatients’ registers. The information obtained was entered into a data abstraction form. We classified the identified illnesses according to International Classification of Diseases 10 (ICD 10) [8] as indicated in the Uganda Clinical Guideline 2016. Conditions that matched integrated management of newborn and childhood illnesses protocol were classified based on the integrated management of Newborn and childhood illnesses manual [9].

In order to identify the most commonly prescribed antibiotics for common childhood illnesses in HC III and IV, we counted physically from the outpatient registers the number of children under five years of age who received antibiotic prescription for common childhood illnesses in the last 6 months using a predesigned data abstraction form. This included illnesses such as pneumonia, cough or cold, malaria, otitis media, urinary tract infection, diarrhea and dysentery as indicated on integrated management of newborn and childhood illnesses [9] manual. To decide whether the prescription was rational or not, we compared the diagnosis/classification with the standard guideline.

In order to establish health system and prescriber factors that affect antibiotic prescription practices, we conducted a face-to-face interview with each health unit in charge and health care providers who make prescription for children using a structured questionnaire in English. The interview covered areas of prescribers’ characteristics (level of education, last qualification attained, work experience and experience in pediatric care), availability and utilization of Uganda clinical guideline, availability of antibiotics and common childhood illnesses that require antibiotic prescription and utilization of laboratory services to test children for malaria before antibiotic prescription.

Quality control

A structured questionnaire guided by the Uganda clinical guideline 2016 was used in data collection. The Uganda clinical guideline 2016 is a validated tool used for primary care prescription [4]. Research assistants were trained on the data collection procedures, tools and ethical considerations of the study. Regular supervision was done to ensure consistency in the data being collected. Data check was done at the end of every day of data collection and stored for entry.

Ethics and consent

Study protocols and procedures were reviewed and approved by Mbarara University of Science and Technology (Ref. 15/11-18). The study received clearance from the Uganda National Council for Science and Technology (Ref. SS4924). We sought a written permission from the office of the District Health Officer (DHO), Municipal Health Officer Mbarara district local government to enable research in the district and municipal health facilities. We obtained written informed consent from the health care providers and the facility in-charge; this was done in the local language (Runyankole) for good understanding. Participants were assured of privacy and confidentiality of the information provided by them.

Data analysis

The data set was entered into Epi-Info software version 7∙2 database for both data set. These were imported into STATA software version 13∙0 for analysis.

We summarized baseline characteristics using frequencies and proportions for common childhood illnesses for which antibiotics was prescribed; common prescribed antibiotics. We also generated variables; rational and irrational prescriptions and compared with prescription guidelines. A univariate analysis, Chi-square test and fisher’s exact test was used to establish the relationships between the health system and prescriber factors with irrational antibiotic prescriptions for common childhood illnesses at significance level of 5%.

All factors with p-value <0.01 and those with a known biologically credible association with irrational antibiotic prescriptions were considered in the multivariate analysis which was performed to control confounding.

Results

Of the 1218 records, 65.6% were from HC III and most of which were for children aged 6 months and above. Only 8.1% of the records were for children below 6 months old. Records of females were more than males (53.1%5 vs 46.9%) (Table 1). Of the 35 prescribers interviewed, about sixty nine percent (68.6%) were from health center III with more females (74.3%). Most of the prescribers (77.1%) were either nurses or midwives, majority of whom (61.76%) had either diploma or degree. Majority (57.1%) of the prescribers interviewed were aged below 35 years and 42.9% of them were aged 35 years and above. The mean age was 36.5 years. Only 22.9% of the prescribers were clinicians (Clinical officers and Medical officers). Most of the prescribers (77.1%) had experience in childcare for five or more years and up to 45.7% of the prescribers had been in practice for 10years and above. Almost no prescribers had received any specific training on management of common childhood illnesses in the last 6 months (Table 2).

Table 1. Demographic characteristics of child from records, N = 1218.

Characteristics Frequency Percentage
Facility level
HC III 799 65.6
HC IV 419 34.4
Age in months, Mean (SD) 14.2
Age categories in months
0–5 98 8.1
6–11 237 19.5
12–23 360 29.6
24–59 523 42.9
Gender
Male 571 46.9
Female 647 53.1

Table 2. Table showing findings from prescribers’ interview, N = 35.

Characteristics Frequency (%)
Facility level
HC III 24 68.6
HC IV 11 31.4
Gender
Male 9 25.7
Female 26 74.3
Duration in paediatric care(years), mean (SD) 10.1 (7.3)
Duration in paediatrics care(years)
<5 8 22.9
5–9 11 31.4
> = 10 16 45.7
Designation
Medical officer 2 5.7
Clinical officer 6 17.1
Nurse/midwife 27 77.1
Highest level of training attained
Certificate 14 40
Diploma 18 51.4
Degree 3 8.6
Training received for management of specific childhood illness
Upper Respiratory Tract Infection 7 20.0
Pneumonia 8 22.9
Acute watery diarrhoea 8 22.9
Urinary Tract Infection 8 22.9
Otitis media 4 11.4
Bloody diarrhoea 6 17.1

Mostly Upper respiratory tract infection (URTI), Pneumonia and acute watery diarrhea received antibiotic prescription. Pneumonia was more likely to be diagnosed in HC IV (p < 0.05) while upper respiratory tract infection was more likely to be diagnosed in HC III (p = 0.01) (Fig 1).

Fig 1. Common childhood illnesses treated with antibiotics.

Fig 1

Cotrimoxazole and Amoxicillin were the most prescribed oral antibiotics while Benzyl penicillin and ceftriaxone were the most prescribed injectable antibiotic. Two (2) children received doxycycline, an antibiotic contraindicated in this age group (Fig 2).

Fig 2. Common antibiotic prescribed.

Fig 2

Almost all (97.1%) of the facilities had a reference tool, mainly Uganda Clinical Guideline and 62.9% had a Manual for Integrated Management of Neonatal and Childhood Illnesses (IMNCI 2012). Despite the presence of reference tools, 68.4% of the prescribed antibiotics was irrational as compared with the existing guideline. Irrational antibiotic prescriptions were more common at health centers III (73%) than in Health centers IV (59.8%) (P-value <0.05). Upper respiratory tract infection and acute watery diarrhea were the conditions that received most irrational antibiotic prescription (Fig 3).

Fig 3. Proportion of irrational antibiotic prescription based on the existing guideline.

Fig 3

Of the 35 prescribers interviewed, sixteen (16) reported having prescribed antibiotics for common childhood illnesses. Ten out of sixteen reported irrational antibiotic prescription, although there was no difference in prescription practices across prescribers/facility factors (Table 3).

Table 3. Relationship between irrational prescription and prescribers’/health facility factors, N = 16.

Prescribers Characteristics Irrational Prescription Freq (%) Rational Prescription Freq (%) Fisher’s Exact P-Value
Age (yrs.) 0.738
<35 (n = 10) 5 (50.0) 5 (50.0)
35–44 (n = 1) 1 (100) 0 (0.0)
> = 45 (n = 5) 4 (80.0) 1 (20.0)
Gender 0.588
Male (n = 5) 4 (80.0) 1 (20.0)
Female (n = 11) 6 (54.5) 5 (45.5)
Work experience 0.091
<5 (n = 4) 3 (75.0) 1 (25.0)
5–9 (n = 5) 1 (20.0) 4 (80.0)
> = 10 (n = 7) 6 (85.7) 1 (14.3)
Education level 0.604
Diploma or more (n = 12) 8 (66.7) 4 (33.3)
Certificate (n = 4) 2 (50.0) 2 (50.0)
Training 0.299
None (n = 11) 8 (72.7) 3 (27.3)
At least one (n = 5) 2 (40.0) 3 (60.0)
Facility level 1.00
III (n = 12) 7 (58.3) 5 (41.7)
IV (n = 4) 3 (75.0) 1 (25.0)
Reference guide 0.375
Not available (n = 1) 0 (0.0) 1 (100)
Available (n = 15) 10 (66.7) 5 (33.3)
Accessibility of the guide 1.00
Accessible (n = 15) 1 (6.7) 14 (93.3)
Not Accessible (n = 1) 1 (100) 0 (0.0)
Drug stock out 0.588
Stock out (n = 11) 6 (54.5) 5 (45.5)
No stock out (n = 5) 4 (80.0) 1 (20.0)

Discussion

This study was conducted to determine the antibiotic prescription practices of prescribers for children under five years at public health centers III and IV in Mbarara District. Results showed that Upper respiratory tract infection contributed more than half of the common childhood illness in Health centers III and IV. It also received the most antibiotic prescription. It is thought that Upper respiratory tract infection is mainly viral and antibiotic has no role in its management [10], a few cases could be due to a bacterial etiology. Our finding could be because diagnosis at this level of care is mainly clinical but also due to the fact that majority of the prescribers in our study were either nurses or midwives. A health cadre not primarily trained to make diagnosis and prescription. This might have led to a misclassification of illnesses. This is similar to findings of the studies in Ghana [11] and India where acute tonsillitis and otitis media (AOM) were as common as upper respiratory tract infection and represented more than 69% of all indications for prescribing antibiotics [12]. Our finding was however contrary to findings in United States, where two thirds of the viral upper respiratory tract infection was treated with antibiotics [13]. A lower prevalence of 38% was observed in Netherlands [14].

Cotrimoxazole and Amoxicillin were prescribed in the majority of childhood illnesses such as acute watery diarrhoea in which antibiotic is not recommended [15] (Uganda Clinical Guideline, pages 335–336 & 383–385) [4]. This could be because Amoxicillin is a common medicine and it is generally cheap, therefore easily prescribed. Amoxicillin and Cotrimoxazole were more available in these facilities and prescribers were more likely to make prescription of what they had in stock. The over prescription of amoxacillin and cotrimoxazole in our study is not surprising. These medicines are recommended for management of uncomplicated bacterial infection in children. They are preferred first line and are readily available. It was however surprising that these antibiotics were also prescribed for acute watery diarrhea, a condition that is mainly viral. Similarly, in Ghana, Prah (2017) found amoxicillin prescription was at 22.5% [11]. While Kibuule (2016) in Uganda found amoxicillin over use of about 30 percent. Amoxacillin prescription in children is lower in some parts of the world. In Albania, Mihani and Kelici (2018) found a lower proportion of amoxicillin prescription of only 19.4% [16]. This could be due to the fact that in their setting, diagnostic confirmation is done before antibiotic prescription unlike in the Ugandan case where most prescription for out patients are made on an empirical basis. Although injectable antibiotic use in outpatients was also noted in our study, their prescription was generally low compared to that of oral antibiotics. This means that the prescribers in these facilities makes prescription from the essential drug list for Uganda, a practice that should be encouraged. Doxycicline was prescribed for children below 5 years of age. This drug is generally contra indicated in this age group due to its side effect of enamel hypoplasia and tooth pigmentation [17].This could be due to knowledge gap among the prescribers, considering that majority of the prescribers in our study were either nurses or midwives. These health care cadres are not primarily trained to prescribe according to the Ugandan guidelines.

About two-thirds of the prescribed antibiotic was irrational, yet all the facilities had the guideline that were accessible. Upper respiratory tract infection and or acute watery diarrhea were irrationally treated with antibiotics. These childhood illnesses are caused mainly by viruses and can be managed supportively [9]. This finding indicates lack of knowledge on the classification and management of common childhood illnesses, it could also reflect poor adherence to the guideline. This could be explained by the fact that majority of the prescribers in our study were not primarily trained as prescribers. It appears that the prescribers in our study made their prescriptions based on their previous experience or by copying others. Guidelines were not utilized in making antibiotic prescription. This finding was comparable to a Ghanaian and Chinese study by Prah (2017) and Song (2018) where more than half of antibiotic prescription was irrational. In Netherlands and Korea, irrational antibiotic prescription was generally low [18].

We did not find any relationship between prescription practices and prescribers/facility factors. This was surprising given the fact that most of our prescribers were either nurses or midwives who were not trained prescribers. This could be explained by the fact our study was not powered to assess the relationship or associations. The irrational antibiotic prescription was noted across the prescribers’ and facility factors. This was contrary to a study done by A. Kotwani (2012) on factors influencing primary care physicians to prescribe antibiotics in Delhi-India [3]. They found diagnostic uncertainty, lack of time due to overcrowding, consideration about suitability, laxity in regulation for prescribing and dispensing, self-medication and doctors’ shopping among others were the main reason for irrational antibiotic prescription in India [3].

Study limitation

It was not possible to link prescribers to the records retrieved. This level of care may have more challenge with antibiotic prescription. We did not assess diagnostic accuracy especially for upper respiratory tract infection; this might have resulted into over reporting of this condition and antibiotic prescription. We did not explore all the components of irrational prescription. Our sample size for the prescribers was not enough to establish the relationship between prescribers’/facilities factors and prescription practices.

Conclusions

Antibiotics were mainly prescribed for the treatment of viral respiratory infections and acute watery diarrhea in children, conditions mainly caused by viruses making the antibiotic prescription irrational. We recommend regular refresher courses on regarding management of common childhood illness and, technical support supervision on adherence to antibiotic prescription guideline, and a qualitative study to explore factors influencing irrational antibiotic prescription practices.

Supporting information

S1 Dataset

(XLSX)

S2 Dataset

(XLS)

Acknowledgments

1) District Health Officer and Municipal Health Officer, Mbarara who permitted the study to be done in the District and Municipality respectively.

2) Prescribers who were the study respondents.

3) Department of Pediatrics and Child Health, Mbarara University of Science and Technology.

Abbreviations

EDL

Essential Drug List

HC

Health Center

IMNCI

Integrated Management of Newborn and Childhood Illnesses

LHD

Local Health District

MAK

Makerere University

MOH

Ministry of Health

MUST

Mbarara University of Science and Technology

SIDA

Swedish International Development Cooperation Agency

UCG

Uganda Clinical Guideline

URTI

Upper Respiratory Tract Infection

VHT

Village Health Team

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

This study was funded by Makerere University – Swedish International development Agency (SIDA) research scholarship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of manuscript.

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Decision Letter 0

Mehreen Arshad

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28 Jul 2020

PONE-D-20-10851

Antibiotic Prescription Practices Among Prescribers for Children under fives at Public Health Centers IIIs and IVs in Mbarara District.

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The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: No

Reviewer #3: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. Correct minor typographical errors (examples, page 12, line 12: 53.1 %5; on page 14, line 14: "contra indicated") and inconsistencies (e.g. capitalization of some diseases and drugs but not others)

2. The Uganda Clinical Guidelines 2016 and the WHO-IMNCI guidelines 2018 were referenced in the text, but not included in the references section

3. Statements are made in the text that URIs and acute watery diarrhea are mainly viral. Some readers may be aware that bacterial pathogens are occasionally implicated (e.g. Group A Strep or catarrhal Pertussis for URIs; ETEC, Shigella, etc. for diarrhea). To avoid confusion, it is recommended to cite the specific guidelines in the UCG 2016 (e.g. pages 777-778 for diarrhea in children), and what the recommendation is (e.g. erythromycin or ciprofloxacin for severe diarrhea or dysentery). This will help avoid confusion for readers who are not familiar with the prescribing guidelines, and give insight onto the findings of the study.

4. It may be worth mentioning in the text, when discussing the irrational prescribing of antibiotics for watery diarrhea, that a rotavirus vaccine campaign was undertaken in 2018.

5. In figure 2, it is recommended that the authors avoid using abbreviations for drugs and use full antibiotic names instead (e.g. Xpen, PPF are abbreviations that not all readers may recognize)

Reviewer #2: Thank you for the opportunity to review this paper. This study describes irrational antibiotic prescription within health centers in Uganda. The study design was a retrospective cross-sectional design and data was collected through a data extraction form and a questionnaire that was filled by investigators. As the study aims to “Our study aimed at determining antibiotic prescription practices of prescribers for children under five years at public health center IIIs and IVs in Mbarara District.” The adds to implementation of guidelines and describes antibiotic practices in Uganda. However, some concerns are raised in the reporting of the methodology of the paper, that requires major revisions. Additional information should be provided to fulfill the objective of this study.

1. In the abstract, page 7: “This may be associated with errors in antibiotic prescription. This practice has not been studied in our setting.”

This is better reformulated to clarify what “This” reflects.

2. Page 7: The term “health workers” is broad and is not accurate for describing antibiotic prescribing, since not all health workers prescribe them

3. Abstract, methods: This section needs to be reformulated, since it is not clear how the study was done. For example: “An interviewer administered questionnaire were used to collect health” looks like a third questionnaire different that the one introduced when interviewing health workers.

4. What is the difference between these “clinical officers and occasionally medical officers.”? The sentence starts with nurses being a profession then presumably compared to medical doctors?

5. Page 8: “to the lower health facilities within the district.” Why are these facilities considered lower?

6. The background introduction benefit from additional details on the availability of any studies antibiotic prescribing practices in Mbarara district or its health centers. If no previous studies exist, it should be highlighted as a gap in the literature.

7. In the entire methods section , it is better to separate the study into first 2 sections, one related to the reviewed records and with all its details, and the second related to the interviewed health providers and all its details. The authors switch back and forth with the two sections, which confuses the reader.

8. In the study limitations: “The data may not relate to the prescribers we interviewed”. The data in this case may be the data extracted from the records. However, the authors also interviewed the prescribers, and have data from the answers filled when they were interviewed them. I think this limitation is not of importance since they objective is not to link the two sources, rather each source should help in studying certain aspects of antibiotic prescribing.

9. It is mentioned in the study that health center 3 has a laboratory, shouldn’t it be capable of performing cultures? Please clarify

10. Since the authors did not cover all components of irrational drug prescribing (ex: cost), it cannot be concluded that prescribing was irrational, rather it should be described according to how irrational was measured: ex: inappropriate dose, indication, duration or period of use. These details on how the prescription was judged as irrational can be detailed if available in the data. The specific domains that were used to judge on how rational prescribing was should be mentioned. Also, since the objective of the study is to describe prescription practices, this should be present in the results; currently it is only reported that 68.4% of prescriptions are irrational.

Reviewer #3: There is significant quality research published in antibiotic resistance among children and its irrational use. Specific diseases have been highlighted and the overall antibiotic resistance has also been covered from low and middle income country settings. There is very little that the manuscript adds to existing knowledge base and is of little interest to wider readership. Examples of some recent literature include:

Tekleab AM, Asfaw YM, Weldetsadik AY, Amaru GM. Antibiotic prescribing practice in the management of cough or diarrhea among children attending hospitals in Addis Ababa: a cross-sectional study. Pediatric health, medicine and therapeutics. 2017;8:93.

Tasawer Baig M, Akbar Sial A, Huma A, Ahmed M, Shahid U, Syed N. Irrational antibiotic prescribing practice among children in critical care of tertiary hospitals. Pakistan journal of pharmaceutical sciences. 2017 Jul 2;30.

Hameed A, Naveed S, Qamar F, Alam T, Abbas SS, Sharif N. Irrational use of antibiotics. Different Age Groups of Karachi: a wakeup call for antibiotic resistance and future infections. J Bioequiv Availab. 2016;8:242-5.

Ilić K, Jakovljević E, Škodrić-Trifunović V. Social-economic factors and irrational antibiotic use as reasons for antibiotic resistance of bacteria causing common childhood infections in primary healthcare. European journal of pediatrics. 2012 May 1;171(5):767-77.

Sebsibie G, Gultie T. Retrospective assessment of irrational use of antibiotics to children attending in Mekelle general hospital. Sci J Clin Med. 2014 Jun 12;3(3):46-51.

Moreover, the manuscript is poorly written with weak references. Please note that the style of referencing for the journal is Vancouver style of referencing.

The article draws weak conclusions and is based on a study design which is lower in the hierarchy of evidence.

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6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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PLoS One. 2020 Dec 28;15(12):e0243868. doi: 10.1371/journal.pone.0243868.r002

Author response to Decision Letter 0


20 Aug 2020

RESPONSE TO THE REVIEWERS

I would like to appreciate very much all your comments and guidance offered concerning my submission. I would therefore like to respond as follows;

REVIEWER 1

1. Typing error corrected as highlighted on page 12 line 12, page 14 line 14

2. Uganda Clinical Guideline 2016 (UCG 2016) and WHO – IMNCI 2012 included in the reference section as advised.

3. Statement about etiology of upper respiratory tract infections and acute watery diarrhea revised to indicate the possibility of bacterial etiology occasionally necessitating antibiotic therapy.

4. Statement concerning Rota viral vaccine campaign to mitigate diarrhea has been added to the text.

5. Abbreviations have been removed from figure 2

REVIEWER 2

1. The statement on page 7 of the abstract has been reformulated.

2. I have revised the statement “health worker” so that it accurately describes the prescribers as highlighted.

3. The method section has been made clearer to indicate what we actually did as highlighted in the text.

4. In Uganda, Clinical officer is a title given to health cadres who completed a 3-year course leading to award of diploma in medicine and community health. They are the primary care prescribers in health centre IIIs, IVs, outpatient departments of District and Regional hospitals. Medical officers on the other hand are holders of Bachelor of Medicine and Bachelor of Surgery. In Uganda, Medical officers are employed at the level of health centre IVs and above. They work in both outpatient and inpatient departments.

5. Page 8. In Uganda, there is a policy on the level of care and referral systems. The lowest level being the Village Health Team (VHT), they provide home based care for malaria and pneumonia. VHTs identify and refer patients who may need further care to either Health centre II or III. Health centre II mainly handles vaccination and uncomplicated antenatal care. They refer their patient to health centre IIIs. Health centre IIIs refer to health centre IVs. Both health centre IIIs and IVs have basic laboratory services like microscopy and complete blood count only. Health centre IIIs and IVs can refer to a district hospital. The next level of care in the hierarchy are regional and national referral hospitals, they have capacity to offer specialized care. So, in Uganda from the level IV down to VHTs are referred to as lower level facility since they lack facilities for investigations.

6. There is no any study on antibiotic prescription practices in Mbarara and Uganda in general. This has already been highlighted as a gap that necessitated our study.

The method section has been separated to reflect records and prescribers’ interview as advised.

One limitation has been removed as suggested.

Health centre IIIs and IVs in Uganda have only basic laboratory services, they cannot perform microbiological studies including blood culture.

The conclusion that prescription of antibiotic was irrational in this setting has been revised to reflect components of irrationality assessed in our study.

Reviewer 3

I absolutely agree with you that a lot of literature exist on antibiotic resistance and irrational prescription. We however did not see any published article on antibiotic prescription practices in a rural setting of Uganda. We thought this study was necessary as a baseline for a bigger study with a better design which would inform policy on control and prevention of antibiotic resistance.

Attachment

Submitted filename: Response to the reviewers.docx

Decision Letter 1

Mehreen Arshad

1 Oct 2020

PONE-D-20-10851R1

Antibiotic Prescription Practices Among Prescribers for Children under fives at Public Health Centers IIIs and IVs in Mbarara District.

PLOS ONE

Dear Dr. Okello,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please read the comments below carefully. There appear to be many grammatical errors which need to be corrected. The references also appear to be in the wrong format. 

Please submit your revised manuscript by Nov 15 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Mehreen Arshad, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

Thank you for responding to the reviewer comments. In reviewing further there are several other clarifications that need to be as well. Please also read through the entire manuscript carefully. There are many grammatical errors that need to be corrected.

1. Introduction para 2: please explain the different clinical officer and medical officer

2. Intro para 4: please explain the difference between HC IIIs and IVs

3. Methids: Sample size and sampling procedure: Please read through this paragraph carefully, there are many grammatical errors in it

4. It is unclear why there are 2 paragraphs under the heading 'Results from prescribers’ interview' under the tables and figures section.

5. The legends for the tables and the figures need to be made more concise. They should not describe what is already noted in the table/figure. Also the legends appear to be referencing the figures incorrectly. For eg. the legend above figure 2 references figure 3.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

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Reviewer #1: No

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

PLoS One. 2020 Dec 28;15(12):e0243868. doi: 10.1371/journal.pone.0243868.r004

Author response to Decision Letter 1


5 Nov 2020

1. Introduction para 2: In Uganda, Clinical officer is a title given to health cadres who completed a 3-year course leading to award of diploma in medicine and community health. They are the primary care prescribers in health centre IIIs, IVs, outpatient departments of District and Regional hospitals. They literally work as assistant medical officers. Medical officers on the other hand are holders of Bachelor of Medicine and Bachelor of Surgery. In Uganda, Medical officers are employed at the level of health centre IVs and above. They work in both outpatient and inpatient departments.

2. Introduction para 4: In Uganda, there is a policy on the level of care and referral systems. The lowest level being the Village Health Team (VHT), they provide home based care for malaria and pneumonia. VHTs identify and refer patients who may need further care to either Health centre II (level 2) or III (level 3). Health level 2 mainly handles vaccination and uncomplicated antenatal care. They refer their patients to health centre IIIs (level 3). Health centre IIIs refer to health centre IVs (level 4). Both health centre IIIs (level 3) and IVs (level 4) have basic laboratory services like microscopy and complete blood count only. Health centre IIIs and IVs can refer to a district hospital. The next level of care in the hierarchy are regional and national referral hospitals, they have capacity to offer specialized care. So, in Uganda from the level IV down to VHTs are referred to as lower level facility since they lack facilities for investigations.

3. Methods: I have addressed the grammatical errors noted under method section, refer to page 4 and 5 in the text.

4. The double heading ‘Results’ and legends for tables and figures have been revised to avoid repetition.

5. The citations style has been changed to ‘plos’ format

Attachment

Submitted filename: Response to the reviewers.docx

Decision Letter 2

Mehreen Arshad

30 Nov 2020

Antibiotic Prescription Practices Among Prescribers for Children under fives at Public Health Centers IIIs and IVs in Mbarara District.

PONE-D-20-10851R2

Dear Dr. Okello,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

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Kind regards,

Mehreen Arshad, M.D.

Academic Editor

PLOS ONE

Acceptance letter

Mehreen Arshad

11 Dec 2020

PONE-D-20-10851R2

Antibiotic Prescription Practices Among Prescribers for Children under five at Public Health Centers III and IV in Mbarara District.

Dear Dr. Okello:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Mehreen Arshad

Academic Editor

PLOS ONE

Associated Data

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    Attachment

    Submitted filename: Response to the reviewers.docx

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    Submitted filename: Response to the reviewers.docx

    Data Availability Statement

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