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Abstract

Introduction:

Correct reconstitution and administration is mandatory in obtaining the adequate concentration of an antibacterial at the site of infection.

Objective:

The objective was to evaluate the reconstitution and administration practice adopted by a cohort of mothers in administering paediatric antibacterial suspensions.

Methods:

A cross-sectional descriptive study carried in Jaffna district Sri Lanka, teachers (n = 685) were selected as representative of cohort of mothers. Two-stage stratified cluster sampling technique was used; first, 4 educational zones were selected. Cluster were assigned proportionately. Antibacterial pack was given to participant to reconstitute and measure using a preferred measuring device. Questionnaire and scorecard were used. None followed all the steps of the reconstitution and administration practices correctly. Volume measured by about participants (30%) differed by over 20% than the correct volume.

Conclusion:

Practice of reconstitution and administration of antibacterial agents by a cohort of educated mothers was found to be unsatisfactory.

Keywords

children antibacterial reconstitution

Introduction

Liquid dosage forms still remain popular for children in many low and middle income countries. They offer some unique advantages such as dose flexibility, ease of administration, wide availability and relatively less expensive over the new paediatric oral dosage forms such as orodispersible tablets. However, ensuring the stability of liquid dosage forms throughout their shelf-life is not easy.

Most of the antibacterials are formulated as dry powders¹ which had to be reconstituted into suspension before use. Studies have reported that errors are more frequent with these dry powder for reconstitution than ready-to-use liquid dosage forms.² Caregivers face difficulties in reconstituting the dry powder, and in accurately measuring the required volume.² A Taiwanese study reported that only 2% of caregivers properly identified the steps to reconstitute antibiotic suspensions after reading the medication leaflets.³ Studies have documented errors due to usage of different liquid measuring devices with errors occurring in 50% to 80% instances.^4
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Rate of antibacterial resistance is rising to dangerously high levels in all parts of the world. Antibacterial resistance is accelerated by misuse and overuse of antibacterials.⁷ Improper reconstitution and administration of antibacterial suspension can contribute to emergence and spread of antibacterial resistance². Hence, the objective of this study was to critically appraise the reconstitution, measurement and administration practice adopted by mothers in administering paediatric antibacterial suspension.

Methods

This cross-sectional descriptive study was conducted in Jaffna district which is 1 of the 5 districts of the Northern Province of Sri Lanka during 2019 to 2020.

Subject Cohort

Teachers were selected as the study population as they are expected to possess reasonable education.

Inclusion Criteria

Female teachers employed in a school at the time of the study who had at least 1 child under the age of 6 years were included in the study.

Exclusion Criteria

Teachers who had health care professionals in the family, who had children with long-term illnesses requiring frequent visits to hospital, or who had a past employment history as a health care professional or social worker, were excluded from the study. Teachers who had participated in similar studies or educational programmes were also excluded.

Sample Size

Sample size was calculated as 685.Percentage of dosing errors was used to calculate the sample size as dosing errors would be the serious outcome of incorrect practices of reconstitution and measurement (Administration error was considered as dosing error and the errors occurring during the reconstitution process). Dosing errors from the literature varies from 10 % to 50 % depending on the measuring tools used.⁸ Prevalence was taken as 50% since it will give the maximum sample size. Study used a 2 stage stratified cluster sampling method. To minimise the error due to clustering effect a correction for the design effect was used.⁹

Selection of Sample

A 2-stage stratified cluster sampling technique was used to select the required sample. A cluster was a group of school teachers from a single educational zone in the Jaffna district. In the first stage of sampling, 4 of the 5 educational zones, in the Jaffna district were selected randomly by drawing lots. The cluster size was set at 8 as the number of teachers that likely to be mothers in a cluster was taken as 10. Therefore, 86 clusters were required to satisfy the sample size of 685. The 86 clusters were allocated proportionately among the 4 education zones based on the number of teachers in each zone. Number of clusters allocated to Jaffna, Valikamam, Vadamarachi and Thenmarachchi zones are shown in Table 1.

Table 1.

Number of Teachers Selected for the Study in the 4 Educational Zones.

Educational zone	Number of teachers in schools	Proportion of school teachers (%)	Number of clusters needed to be selected from each zone
Jaffna	2515	35.8	31
Valikamam	2137	30.5	26
Vadamarachi	1417	20.2	17
Thenmarachhi	945	13.5	12
Total	7014	100.0	86

Source: Northern province education sector vital statistics 2015.

These clusters were randomly selected from each zone. Eight numbers of teachers who are mothers from each clusters were selected using the eligibility criteria.

Study Instruments

An interviewer administered questionnaire and scorecard were used for this study. We designed the first draft of the score card based on literature and expertise of the research team. The draft scorecard was sent to experts in the pharmacy field. Each expert rated each step in the score card on a 9 point Likert scale for necessity criteria for each step in the first draft. When the overall panel median score of ≥7 with agreement within the panellists and when no more than 2 panel members rating the statement outside a 3-point distribution around the median, that step was considered as appropriate. The final score card comprising 21 steps (Table 2) was checked for inter-rater reliability. A kappa value above 0.7 was considered as good agreement. A guideline to give the scores also was prepared based on the scorecard.

Table 2.

Proportion of Participants Adhering to Correct Steps in Reconstitution, Measurement and Administration of Oral Antibacterial Suspension.

No	Step	No of participants who scored correctly (%) 95% CI [ ]
01	Shake the bottle before opening to loosen the powder.	45(6.6) [4.8-8.7]
02	Check whether the powder is loosened.	20(2.9) [1.8-4.5]
03	Check for the marked level in the bottle.	685(100) [ 99.6]
04	Add sufficient water, close the lid and shake well to disperse.	158(23.1) [20.0-26.4]
05	Check whether all powder are dispersed well if not shake again.	117(17.1) [14.4-20.1]
06	Top up to the marked level.	659(96.2) [94.5-97.5]
07	Close the lid and shake again.	654(95.5) [93.6-96.9]
08	Check if the volume is correct if it’s not repeat step 6& 7.	416(60.7) [57.0-64.4]
Select the correct measuring device.
09	Oral syringe/measuring cup/measuring spoon (2.5 mL).	685(100) [ 99.6]
10	Oral syringe/measuring cup /measuring spoon.(3.75 mL)	685(100) [ 99.6]
11	Oral syringe/measuring cup /measuring spoon (5 mL).	685(100) [ 99.6]
12	Shake the bottle well.	14(2)[1.1-3.0]
Measure the volume.
13	2.5 mL	685(100) [ 99.6]
14	3.75 mL	685(100) [ 99.6]
15	5.0 mL	685(100)[ 99.6]
Check for correctness of the volume.
16	2.5 mL	685(100) [ 99.6]
17	3.75 mL	685(100) [ 99.6]
18	5.0 mL	685(100) [ 99.6]
Volume measured (dosing error - within 10% of the target volume).
19	2.5 mL	277(40.4) [36.7-44.2]
20	3.75 mL	318 (46.4) [42.6-50.2]
21	5.0 mL	462(67.4) [63.8-70.9]

Interviewer Administered Questionnaire

The questions were on age, highest education achieved, number of children, previous experience in using a measuring device and pervious experience in using antibacterial formulations were obtained.

Data Collection, Entry and Analysis

Each participant was given an amoxicillin pack and instructed to reconstitute the antibacterial powder with the provided water as if they were to administer the dose to a child. Participants were also requested to measure the volumes of 2.5, 3.75, and 5 mL of liquid prepared by using a suitable measuring device. Multiple options of measuring devices namely dosing cup, measuring spoon, kitchen spoon and syringe were provided. The accuracy of the volume was measured by the weight of the measured dose (tool weight containing parents measured dose minus pre assessment tool weight) compared with the reference weight (like as for 5 mL dose, average weight of 5 mL measured by 2 senior pharmacists using a syringe).⁸ Scores were given according to the scorecard with correct and incorrect steps, respectively, getting a score of 1 and zero. Dosing error was defined when the mean volume was

Within ±10% as ‘no error’

Between ±11% to 20% as ‘mild error’

When it was ±≥20% as ‘moderate error’

Not adhering to even 1 step in the score card was defined as administration error. P < .05 was considered as the limit for testing significance.

Primary Outcome Measures

Correct and incorrect steps and the accuracy of the volume

Approvals

Ethical approval was obtained from the Ethics Review Committee, Faculty of Medicine, University of Colombo (EC-18-006.). Administrative approval was obtained from the Director, Department of Education, Jaffna, relevant Directors of Zonal education branches and the relevant school principals.

Study Findings

Basic Characteristics of the Study Participants

Of the 685 participants, 61.2% were in the age group of 30 to 40 years with 37.8% having a graduate and 30.9% a postgraduate degree: 97% and 76%, respectively have used a measuring device and antibacterial formulations before. Table 2 shows the scores obtained by the participants: None got all 21 steps correct with 49.3% getting at least 15 steps correct.

All have got the following steps correct; checking the marked level, selecting correct measuring device, measuring the volume and checking the correctness of the volume by checking the volume mark at their eye level. However, a considerable number of participants failed to shake the bottle before opening and before measuring the required volumes and to check whether the powder is loosened before adding water.

A higher proportion of participants have measured 5 mL (67%) correctly than 2.5 mL (40%) and 3.75 mL (45%; Table 3). More than 30% have measured the volume ≥20% ending in making moderate error.

Table 3.

Volume Errors made by Participants When Measuring the Liquid Antibacterial Using Different Devices.

Device	Volume measured
	2.5 mL				3.75 mL				5 mL
	No error[%]	Mild error[%]	Moderate error[%]	Total[%]	Noerror[%]	Mild error[%]	Moderate error[%]	Total[%]	No error[%]	Mild error[%]	Moderate error[%]	Total[%]
Os	23[32]	9[12]	41[56]	73[100]	121[46]	40[15]	102[38.8]	263[100]	45[56.2]	4[5]	31[38.8]	80[100]
Mc	239[41]	157[27]	181[31]	577[100]	151[47]	57[18]	115[35.6]	323[100]	395[69]	119[20.8]	58[10.1]	572[100]
Ms	14[41]	8[44]	12[35]	34[100]	18[0.4]	11[24]	16[35.6]	45[100]	20[64.5]	6[19.3]	5[16.1]	31[100]
Os + Mc	0	0	0	0	1[50]	1[50]	0	2[100]	1[100]	0	0	1[100]
Os + Ms	0	0	0	0	1[33]	0	2[66.6]	3[100]	1[100]	0	0	1[100]
Mc + Ms	1[100]	0	0	1[100]	26[53]	11[22]	12[24.5]	49[100]	0	0	0	0

Percentages may not sum to 100% due to rounding of numbers.

Mc, measuring cup; Ms, measuring spoon, Os, oral Syringe.

There was no significant associate between the age (P = .257), education level (P = .416), number of children (P = .488), measuring device used before (P = .075) and the marks scored by the participants, but we observed a significant association between prior experience of antibiotic use (P = .001) and the total marks scored.

Measuring Device Used by the Participants When Measuring the Volumes

Oral syringe has been used more to measure 3.75 mL (38.4%) when compared 5 mL (11.7%) and 2.5 mL (10.7%). Measuring cup was the preferred measuring device to measure all 3 volumes followed by oral syringe. Spoons have been less preferred when measuring all 3 volumes.

Table 3 shows the volume errors made by participants when using different devices. There was no relationship between the measuring device used and volume errors (for 2.5 mL the P value was .249, for 3.75 mL it was .823 and for 5 mL P value was .156).

Reading the Instruction

Only 8% of the participants read the reconstitution instructions on the package and checked the expiry date.

Storage and Duration of Use

Majority of the participants knew about the place to store the reconstituted liquid antibacterials (68%) and the duration to store the reconstituted liquid dosage form (96.1%).

Discussion

Children depend on their caregivers for their medications, but caregivers often do not understand the importance of precisely administrating paediatric dosage forms. This could lead to medication errors predisposing to treatment failure, development of antimicrobial resistance and harmful effects. The rate of parental error in dosing liquid dosage forms has been reported to be as high as 63%, even after receiving verbal instructions.¹⁰

Children often get their medications as oral liquid dosage forms, but some of them are manufactured in a powder form and reconstituted into suspension before use because of stability issue¹: Many oral liquid antibacterials for children including amoxicillin, amoxicillin and clavulanic acid, cephalexin, cefuroxime and azithromycin are manufactured as dry powder.

Reconstitution of dry powder would cause more errors than ready-to-use liquid dosage forms. Errors may arise in any of the stages involved in the reconstitution of the dry power, including the process of reconstitution, the volume and temperature of the reconstituted liquid, the medication shelf-life, storage conditions and dosing. This is a poorly documented component in rational use of antibacterials. Hence we critically appraised the reconstitution, measurement and administration practice adopted in administering paediatric antibacterial suspensions.

Majority (76%) of the participants in our cohort reported prior experience of giving antibacterial formulation which come in dry powder form. This is similar to Nigerian study where 91% have reported using at least one time.¹¹ Although, our cohort was exclusively teachers, only 8% has read the instructions, a very low figure compared to the figures reported in other studies.⁵ Having the instructions only in English might have deterred the participants from reading. Reasons for an educated cohort failing to read the instructions need to be explored further.

Our findings have revealed that the practices adopted by mothers who are reasonably educated with regard to reconstitution, measurement and administration of antibacterial dry powder was far from ideal. About 93% of participants did not shake the bottle to loosen the powder which is in agreement with the Nigerian study (27%).¹¹

Only about a fourth (23%) followed the correct practice of adding water in 2 steps. Adding water in 2 steps has its advantages: It will help to get the lumps out.¹²

Correct dosing involves shaking the bottle before measuring the required volume, and using accurate measuring device. It was very disappointing to note that only 2% participants actually shook the bottle before taking the required volume. This was unexplainable because many tend to do this for many non-medicine liquids. Some might ignore this practice as insignificant step, dosing errors occur when suspensions were administered without shaking.¹³ They documented that the drug sediments at the bottom of the bottle if it is not shaken before use, and the measured volume contains a diluted solution of the antibiotic. This not only leads to treatment failure, but predisposes to emergence of antibacterial resistance as well.

In our study none of the participants considered household teaspoon as the most accurate device for dose administration with everyone choosing either the oral syringe or measuring cup or measuring spoon. This is a big change because a study done 30 years ago in Sri Lanka reported that only 21% (N = 140) had used the measuring devices packed with the medicine.¹⁴ A Ghanaian study done 10 years ago reported that 95.0% of the participants used household spoons.¹⁵ Issues related to administering medicines to children have come to the attention only very recently which has led manufactures to supply the measuring device with liquid medicines. This would have led the participants to select the measuring device packed with the medicine and not the household spoons.

Oral syringe is considered as a suitable measuring device,¹³ and manufacturers are expected to supply oral syringe when there is a need to measure the volume which is not multiple of 5 mL.¹⁶ However, oral syringes are not infallible: Studies, including our current study have reported dosing (volume) errors with oral syringes.⁸ Lack of familiarity might have caused the volume errors with syringes as they are not used commonly for other purposes compared to cups and spoons. Participants have measured 5 mL more accurately than 2.5 and 3.75 mL. There was no 3.75 mL mark in the measuring device provided, but this may not be the sole reason for the error because many did not measure 2.5 mL also accurately despite it was marked.

Although participants were educated teachers the knowledge regarding storage was not optimum and they did not read the instructions on the package and did not look for the expiry date. According to most of manufacturers’ directions antibiotic suspensions should be discarded after 10 days of reconstitution. This fact was known to 96% of participants which is better than another study where it was revealed that parents (15%) gave left over antibiotic suspension to their children.¹⁷

A one-fifth reported that they will be keeping the reconstituted antibacterial formulation on the table or shelves: Storage requirements of medicines had to be followed accurately as medicines are chemicals which can react with external environment. Getting exposed to humidity and heat reduces the concentration and therapeutic effect. A study had revealed that paediatric antibiotic suspensions stored at room temperatures had rapidly degraded and lost the potency over a period of 1 week.¹⁸ A Palestinian study revealed that 70% of the reconstituted suspensions were stored outside the refrigerator.¹⁹ Olorukooba et al recorded that 62% of the mothers did not keep the reconstituted suspension inside the refrigerator¹¹. Pharmacists should provide adequate directions to mothers on how to store medications properly. In addition, social media, clinic visits and printed educational materials should be utilised to educate the parents. If this is the practice by participants who are reasonably educated, 75% of mothers in Sri Lanka have studies up to upper secondary education and their practice could be still lower. This study was done only on teachers with a reasonable educational background who are mothers. We did not evaluate the effectiveness on mothers with other levels of education. Time was an impending factor for teachers. Teachers had work commitments which may have made them to finish the process quickly. Our results may be influenced by the fact that this study was carried out in schools and not in a patient’s home under actual conditions.

Conclusions

Practices adopted in reconstituting and administering antibacterial suspension by a cohort of reasonably educated mothers appear to be very low. Of the assessed determinants namely age, education, number of children, previous experience in using measuring device or an antibacterial agent, only previous experience of antibacterial use was significantly associated with correct practice. Volume error was not dependent on the choice of the measuring device. Measuring cup was the preferred device to measure the all 3 volumes (5, 3.75 and 2.5 mL) with domestic spoons being the least preferred. The use of syringe has not contributed in measuring the volume accurately. The majority of participants knew where to store and reconstitute liquid antibacterial formulation, even if few of them read the reconstitution instructions on the container and looked up the expiration date.

Footnotes

We thank the Director of Education,Jaffna Province,principals and teachers of the schools who gave all the support during my study.

List of abbreviations

Mc: Measuring cup;Ms: Measuring spoon,Os: Oral Syringe.

ORCID iDs

Nadeshkumar Abarna

Manoji Gitanjali Sathiadas

Ethical Considerations

Ethical approval was obtained from the Ethics Review Committee,Faculty of Medicine,and University of Colombo. (Ethical approval No EC-18-006). Permissions/ approval will be obtained from relevant administrative authorities. Informed consent was obtained from the participants.

Author Contributions

NA: Contributed to conception and design;Contributed to acquisition;analysis;or interpretation;Drafted the manuscript;critically revised the manuscript;Gave final approval;Agrees to be accountable for all aspects of work ensuring integrity and accuracy. MGS: Contributed to conception and design;Contributed to interpretation;critically revised the manuscript;Gave final approval;Agrees to be accountable for all aspects of work ensuring integrity and accuracy. NG: Contributed to conception and design;Contributed to analysis;or interpretation;critically revised the manuscript;Gave final approval;Agrees to be accountable for all aspects of work ensuring integrity and accuracy. SRS: Contributed to conception and design;Contributed to analysis;or interpretation;critically revised the manuscript;Gave final approval;Agrees to be accountable for all aspects of work ensuring integrity and accuracy.

Funding

The author(s) received no financial support for the research,authorship,and/or publication of this article.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research,authorship,and/or publication of this article.

Data Availability Statement

This is part of a large study hence the dataset generated and/or analysed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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An Evaluation of Reconstitution,Measurement and Administration Practices Adopted by Mothers in Administering Paediatric Antibacterial Suspensions