Original research
Assessment of inpatient antibiotic use in teriary referral hospital in Eritrea: A retrospective study

Nebyu Daniel Amha1*, Yohana Haile Berhe2

1Department of Pharmacology, School of Pharmacy, Asmara College of Health Sciences, Asmara, Eritrea.
2Department of Pharmaceutics, School of Pharmacy, Asmara College of Health Sciences, Asmara, Eritrea.
*Corresponding Author:
Email addresses:
NDA: [email protected]
YHB: [email protected]

Abstract
Background
The aim of this study is to investigate antibiotic use among hospitalized patients in Halibet teaching referral hospital in Asmara, using prescribing, hospital and patient care indicators.
Methods
All patients (n=3678) admitted to Halibet hospital from 1st January 2017 until 31st December 2017 and had their medications dispensed from the inpatient pharmacy were included in the study population. Using systematic random sampling one hundred cases were selected, their medical card retrieved and data was collected manually using standard forms. Prescribing, hospital and patient care indicators were measured using formulas developed by World Health Organization (WHO) and Strengthening Pharmaceutical Services.
Results
Data on prescribing indicators showed 79% of hospitalizations had at least one antibiotic prescribed, the average number of antibiotics per hospitalization was 1.22; percentage of prescribing one antibiotic was 77%, two antibiotics (17%), three antibiotics (6%); 97% were prescribed by generic names; all (100%) of antibiotics were prescribed from the Eritrean National List of Medicines (ENLM). On average an antibiotic was prescribed for 6.36 days (SD=6.02). Ampicillin was the most commonly prescribed antibiotic (42.2%) followed by benzylpenicillin (13.7%), gentamycin (9.8%), and cloxacillin (8.8%). Parenteral was the most common route of administration prescribed (81.4%), while capsules (13.7%). tablets (3.9%), syrup (1%). Data on hospital indicators showed key antibiotics were out of stock on average for 78.18 days; 87.5% of key antibiotics were available on the day of the study and 25.8% of the medicines hospital budget was spent on antimicrobial. Data on patient care indicator showed patients taking antibiotics stayed in the hospital for 9.72 days (SD=). Laboratory test was performed on 1% of the cases.
Conclusions: Antibiotic use rate was high (79%), prescribing using generic name of antibiotic was 97% and prescribing from essential medicines list was 100%. Lack of standard treatment guidelines for infectious diseases is the major obstacle in the rational use of antibiotics in this hospital. Parenteral route of administration is high (81.4%) therefore switching to oral antibiotics should be sought whenever applicable. The urgent need of standardization of treatment in this hospital should be addressed promptly.
Keywords: Antibiotic use, Inpatient, Eritrea, Prescribing indicators, Facility indicators

Background
Inappropriate use of antibiotics in primary care and hospital settings is a major contributing factor to the spread of antibiotic resistance 1. World Health Organization (WHO) has classified antibiotic resistance as a public health threat of growing concern requiring immediate attention 1-3. More than 700, 000 deaths per year are currently attributed to antibiotic resistance and if no action is taken it is projected to take 10 million lives and cost US $ 100 trillion by 2050 4. Antibiotics are the most frequently prescribed drugs in hospitalized patients 1, 5-8. Latest figures in the United States show that more than half of patients received an antibiotic during their hospital stay and one third of the antibiotic prescriptions involved irrational use 9, 10.
Causes for inappropriate drug use in hospitalized patients are unnecessary use of antibiotic, inappropriate dose, inadequate regulation and monitoring, over or under prescribing 9, 11-13. Lack of standard treatment guidelines (STGs), protocols for rational drug use, weak or absent drug therapeutic committees (DTCs) in less developed countries exacerbates the inappropriate antibiotic use 14. About 70% of hospital-acquired bacterial infections are resistant to at least one antibiotic 15.
WHO has developed key indicators to measure antibiotic use in health facilities 16 and many studies 17-25 have reported using or based upon these WHO indicators. These indicators however are geared towards the outpatient prescriptions and do not reflect the antibiotics use in hospitalized patients, for example dispensing time is not applicable in hospital wards, percentage of injectable drugs and number of drug encountered would be expected to be higher than outpatients. Furthermore the indicators do not address factors like duration of hospital stay or type of disease being treated which influence antibiotic use 26. Thus the WHO core drug use indicators were modified to the inpatient setting. (Table 1)
Table 1: Inpatient antibiotic use indicators
Inpatient core drug use indicators
Prescribing indicators
Percentage of hospitalizations with one or more antimicrobials prescribed
Average number of antimicrobials prescribed per hospitalization in which antimicrobials were prescribed
Percentage of antimicrobials prescribed consistent with the hospital formulary list
Average duration of prescribed antimicrobial treatment
Percentage of antimicrobials prescribed by generic name
Hospital indicators
Percent of key antimicrobials available on study day
Average number of days that a set of key antimicrobials is out of stock
Expenditure on antimicrobials as a percentage of total hospital medicine costs
Patient care indicator measurement

Average duration of hospital stay of patients who receive antimicrobials
Note: These indicators are obtained from Strengthening Pharmaceutical Systems (SPS) and World Health Organization 16
Although high rate of antibiotic use has been reported in Eritrea 27 published research on antibiotic use in hospitals is meager 3. The aim of this hospital-wide antibiotic use study is to describe the antibiotic use in hospitalized patients in Halibet Referral Hospital (HRH) using a standard method designed by Strengthening Pharmaceutical Systems (SPS) and to identify problems in the antibiotic use.
Methods:
Setting
The study was conducted at Halibet Referral Hospital (HNRH), Asmara, Eritrea. HRH is a 150 bed government owned, teaching hospital with surgical, medical, orthopedic, burn and emergency wards. HRH receives on average 7,000 admissions per year.
Study design
A cross sectional, retrospective study design was used to evaluate three key drug use indicators viz. hospital indicators, prescribing indicators and patient care indicator. The methods for collecting and evaluating these indicators were adopted from the Strengthening Pharmaceutical Systems Program 26 after studying the feasibility and appropriateness of the indicators to the hospital environment. For purposes of this study an antibiotic is defined as a drug which has a J01 or J04 code according to the Anatomical Therapeutic Chemical (ATC) classification system 28.

Eligibility criteria
Patients admitted from January 1, 2017 until 31 December 2017 and had their medication dispensed from the in-hospital satellite pharmacy, irrespective of their age, gender and diagnosis were included. Because antituberculosis drugs were excluded according to the WHO recommendation since they are used for long periods in high number, frequency and cost.
Sample size and data collection
A total of 3654 hospitalized patients took medications from the satellite pharmacy were included in the total eligible population and using a systematic random sampling 100 cases were selected. The complete patient chart for these samples was obtained from the record office. The data was collected by two pharmacists from March 2 to April 2 using standard data collection forms (supplement).
Formulas for calculating the indicators
Prescribing indicators
1. Percentage of hospitalizations with one or more antibiotics prescribed = (Number of patient hospitalizations with one or more antibiotics prescribed / Total number of hospitalizations studied) X 100
2. Average number of antibiotics prescribed per hospitalization in which antibiotics were prescribed = Number of antibiotics prescribed for all hospitalizations / Total number of hospitalizations with antibiotics prescribed
3. Percentage of antibiotics prescribed consistent with the hospital formulary list = (Number of antibiotics prescribed that are on the formulary list / Number of antibiotics prescribed ) X 100
4. Average duration of prescribed antibiotic treatment = Total number of days on antibiotic treatment / Total number of antibiotics prescribed
5. Percentage of antibiotics prescribed by generic name = (Total number of antibiotics prescribed by generic name / Total number of antibiotics prescribed) X 100
Hospital indicators
Sixteen antibiotics were selected to be key antibiotics. These antibiotics have a vital drug designation in the Eritrean National List of Medicines. Vital drugs are lifesaving drugs which should be available at all times 29. The hospital indicators were calculated using the following formulas:
1. Percent of key antibiotics available on study day = ( Number of key antibiotics actually in stock / Number of key antibiotics that should be available) X 100
2. Average number of days that a set of key antibiotics is out of stock = Number of days that each key antibiotic is out of stock / Number of key antibiotics in the review
3. Expenditure on antibiotics as a percentage of total hospital medicine costs = (Total cost of all antibiotics purchased / Total cost of all medicines purchased) X 100

Patient care indicator
1. Average duration of hospital stay of patients who receive antibiotics = Total number of days of hospitalization for patients receiving antibiotics / Number of patients receiving antibiotics.
Statistical analysis
After checking for data completion, the necessary computations were performed according to the formulas given. Additional statistical analysis such as frequencies, percentage and averages were carried out using Statistical Package for Social Sciences (SPSS) version 20.
Results
Table 2: Summary of inpatient drug use indicators in Halibet referral hospital in 2017
Inpatient antibiotic use indicator Result (SD)
Prescribing Indicators
Percent of hospitalization with one or more antibiotics prescribed 79%
Average number of antibiotics prescribed per hospitalizations 1.22
Percent of antibiotics from National or Hospital Formulary 100%
Average number of days antibiotic treatment was prescribed 6.36 (6.02)
Percent of antibiotics prescribed by generic name 97%
Hospital indicators
Existence of STG* for infectious diseases No
Existence of approved Hospital Formulary or EML* No
Percentage of key antibiotic available on day of study 87.5%
Average number of days that a set of key antibiotic is out of stock 78.18
Expenditure on antimicrobials as a % of total hospital medicine cost 25.8%
Patient care indicator
Average number of days of patients who received antibiotics stayed in hospital 9.72

Table 3: Most commonly prescribed antibiotics (excluding Metronidazole)

Ampicillin Benzylpenicillin 3 M Gentamycin Cloxacillin Ceftriaxone Ciprofloxacin
% 42.1 % 13.7% 9.8% 8.8% 5.9% 4.9%

Table 4: Antibiotic treatment days

treatment groups
1-7 days 7-14 days 15-20 days > 21 days
74.74% 18.2.% 4.03% 3.03%

Table 5: Antibiotic route of administration
Injection Tablet Capsule Syrup
81.4% 3.9% 13.7% 1.0%

Table 6 Number of antibiotics prescribed per hospitalization
One Two Three Four or greater
77% 17% 6% 0%

Discussion
Prescribing indicators
We found that 79 % of patients received at least one antibiotic for systemic use during their hospital stay. This figure is lower than a specialty hospital study which focused in antibiotic use in three wards in Ethiopia (73.7%) 8. Other ward specific inpatient antibiotic use studies reported lower percentages, Ethiopia (64.7%) 6 , (73.68%) 30, India (66%) 31. A point-prevalence antibiotic use study in 11 hospitals in Democratic Republic of Congo was 68% 32. A The WHO recommendation for antibiotic prescribing per encounter is 20.0-26.8% 13 but this value is not completely applicable in hospital wards where the patients are more dilapidated and are in need of more antibiotics. Furthermore, the percentage of antibiotic use differs in one hospital from ward to ward based on the type of patients and reasons for admission. Medical wards are expected to have more antibiotic use than emergency wards. A study focusing on surgical ward antibiotic use in HRH found antibiotic use to be 69%, with 30% preoperative and 39% postoperative 33. Since all the hospitalized patients had an equal chance of being included in the study, we chose to follow the recommendation of SPS and took random 100 cases to represent all the hospitalized patients. (SPS) Our finding suggests that general antibiotic use in HRH is high but future studies should focus antibiotic use on specific wards.
On average 1.29 antibiotics were prescribed per hospitalization, lower than a study in 11 hospitals in DRC in which 1.4 antibiotics were prescribed per patient 32 and 2.1 in a specialty hospital in Ethiopia 8. All (100%) of the prescribed antibiotics were in the ENLM. HRH is a government hospital and adherence to essential medicines and prescribing by generic name is higher in public hospitals than private hospitals 17, 31. Other studies found Lesotho (79%) 34, Pakistan (98.8%) 13, India (99.8%) 18. Almost all (97%) of antibiotics were prescribed using their generic names. This could be attributed to the centralized drug procuring system in HRH and scarcity of competing brands in the market. Reports of prescribing by generic names show Ethiopia (90.6 %) 17, Brazil (72.8%) 23, Pakistan (56.6%) 13, Lesotho (35.6%) 34.
Except in few situations for most bacterial infections the average number of antibiotic treatment days is 7-10. An antibiotic was prescribed on average for 6.6 days (SD 6.02) however 12.7% of patients were prescribed antibiotics longer than 10 days while 6.86 % stayed on antibiotics longer than 14 days with 2.94% staying longer than 20 days.
Ampicillin was the most commonly prescribed drug (42%) similar to DRC (35%) 32, in Turkey 5 as ampicillin-salbatam in 19% cases; other studies of most commonly prescribed antibiotic reported ceftriaxone (27.5%) in Ethiopia 6, cefotaxime (32%) India 7. A recent study 35 in Orotta Hospital in Asmara found that ampicillin has developed resistance to many microorganisms; E.coli (87.5%), Klebsiella spp (75%), Citrobacter (100%), Pseudomonas (81.8%), Salmonella (100%) 35.The prescription of ampicillin should be seen in the light of these microorganisms’ sensitivity. Culture tests are an important part to confirm microorganisms and design an appropriate therapy. However laboratory tests were performed on 1% of the cases, lower than Lesetho (2%) 34 and Ethiopia (3.8%) 8.
Our study found injection as the most common route of administration 81.4% similar to a study in Ethiopia (82.4%) 8 but higher than in DRC (68.2%) 32. Injectable medicine overprescribing and prescribing outside treatment guidelines are some causes of inappropriate antibiotic use 13, 36. According to the WHO core drug use indicators 13, the ideal percent of injectable per patient encounter is 13.4-24.1%, this value does not reflect their actual use and is expected to be higher in hospitalized patients where IV line is more common. Switching to oral route of administration is associated with lower treatment cost, catheter related infections, hospital stay and burden for nursing staff 37. We believe ampicillin as the most commonly prescribed antibiotic, might have increased the percentage of injection first because it isn’t available in other dosage form save injection and the prescriber can’t switch to oral ampicillin once the patient has improved, thus increasing the percentage of injectables.
Out of the 77% patients on antibiotics 17% were on two antibiotics and 6% were taking three antibiotics. Our finding is lower than a study in an Ethiopian hospital found patients on two antibiotics (42%), three antibiotics (23%) 6 and from a study in DRC which reported two antibiotics were prescribed in 30.3% cases 32.
Hospital care indicators
On the day of study 16 key antibiotics (87.5%) were available in stock. Similar studies done in developing countries found 72.4% and 65.7% of key antibiotics were available in stock in Pakistan 13 and Ethiopia 25 respectively. Our finding although better than what Atif 13and Gidebo25 found, it still is less than ideal because key drugs should be available at all times.
The availability of key antibiotics is an important factor because lack of access to key antibiotics forces prescribers to make less appropriate drug choices with higher costs and more risk of side effects and antibiotic resistance. Selected key antibiotics were out of stock for an average 78.18 days per year much higher than the 30 days in Ethiopia 17.
From the total cost of medicines 25.59% was spent on antimicrobial (antimicrobial in this context is includes antibacterial, antiviral, antifungal, antiparasite). A study in Lesetho 34 found 69% of medicine expenditure was spent on antibiotics. This lower percentage could be because Halibet is a non-specialty general hospital which provides services to miscellaneous patients. For example when antidiabetic drugs are taken out, the percentage spent on antibiotics increases to 35.63% and when antihypertensives are further taken out, the percentage spent on antibiotics reaches 41.70 %. Antibiotics generally take up 20-40 percent of hospital budget spent on medicines 26.
Patient care indicators
The average number of hospital stay for patients was 10.5 days. Over half of the patients (%) stayed for less than 10 days while 8.86% patients who stayed more than 20 days. Other studies found hospital stay to be average 6 days in a private hospital in India 31. Staying longer than 10 days is 3.086 times more likely to result in antibiotic use problems than when staying less than 10 days 38. Prolonged hospital stay is associated with higher treatment costs, increased risk of nosocomial infections, emergence of resistant microorganisms, increased number of drug prescription which increases the risk of ADR and drug-drug interaction 26, 38, 39.
Limitations of the study
The percentage of antibiotics actually administered was not calculated due to incomplete nurses’ data. We didn’t calculate appropriateness of therapy because neither a national nor a hospital standard treatment guideline is currently available to prescribers.
Conclusion
Antibiotic use in Halibet hospital was high and is in need of standardization. The empirical use of antibiotics needs to follow either a hospital or a national guideline which are currently none existent. Ampicillin selection as a treatment choice needs to be investigated. Parenteral route of administration was therefore switching to oral antibiotics should be sought whenever applicable. The urgent need of standardization of treatment in this hospital should be addressed promptly.
Abbreviations
SPS: Strengthening Pharmaceutical Services
EML: Essential Medicines List
ENLM: Eritrean National List of Medicines
STG: Standard Treatment Guideline
DTC: Drug and Therapeutic Committee
WHO: World Health Organization
CDC: Center for Disease Control
HNRTH: Halibet National Referral Teaching Hospital
Acknowledgements
The authors would like to thank the medical director of HNRTH for allowing us to conduct this research, head and members of record office at the HNRTH for helping us retrieve data.
Funding
Not available.
Availability of data and materials
The data of this study are available from the corresponding author on reasonable request,
Authors’ contributions
NDA and YHB designed the study. NDA collected data and literature review. NDA and YHB analyzed and interpreted the data. NDA drafted the manuscript and critically reviewed it. All authors read and approved the final version of the manuscript.
Ethics approval and consent to participate
Approval to conduct the study was obtained from the medical director of the hospital.
Competing interests
The authors declare that they have no competing interests.

Author details
1Department of Pharmacology, School of Pharmacy, Asmara College of Health Sciences, Asmara, Eritrea. 2Department of Pharmaceutics, School of Pharmacy, Asmara College of Health Sciences, Asmara, Eritrea.
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