Preliminary Results of Antibiotic Utilization Studies Using Point Prevalence Survey In Botswana

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Preliminary Results of Antibiotic Utilization Studies Using Point Prevalence Survey In Botswana Bene D Anand Paramadhas, Joyce Kgatlwane, Celda Tiroyakgosi, Matshediso Matome, Amos Massele, Jaran Eriksen, Lars L Gustafsson, Arno Muller, Brian Godman

BACKGROUND Bacterial resistance to antibiotics is a recognized emerging public health problem. A burden for public health systems. Threatens the progress in achieved health gains of countries. Inappropriate and indiscriminate use and disposal of antibiotics across human and veterinary health sectors and by industry are the main factors that promote evolution of bacterial resistance. The extent and appropriateness of antibiotic use in Botswana remains unknown. Countries are expected to develop a national action plan as per recent WHA resolution ------------------------ Ventola CL, 2016. The antibiotic Resistance Crisis. Pharmacy and Therapeutics 20(4) 277-283

OBJECTIVES To describe the extent and appropriateness of antibiotic use in hospitalized patients; and Assess the structural capacity for promotion of appropriate antibiotic use in hospitals

METHODOLOGY Study design is quantitative observational descriptive. Study method involved a structured point prevalence survey to describe the extent and appropriateness of antibiotic use and to assess the institutional capacity for promotion of appropriate antibiotic use. Study variables had categorical and discrete at hospital, ward and patient levels. Study settings included 9 public and 1 private for profit hospitals representing all geographical regions of the country offering primary, secondary, tertiary and specialized care services. Sampling frame involved medical records of all inpatients that remained admitted overnight on the date of survey in the above 10 hospitals Study sample involved medical records of all patients or an authorized person who provided a voluntary verbal informed consent.

METHODOLOGY Inclusion Criteria Medical records of all inpatients that remained admitted overnight on the date of survey Exclusion Criteria Medical records of: Patients or authorized persons who do not grant consent Accident & emergency outpatients Consulted outpatients Patients kept in observation after chemotherapy or minor procedures who did not stay overnight Discharged patients lodging in ward due to lack of transport to their facility or homes Patients in labour ward Psychiatric in-patients and Inpatients who are exclusively on TB treatment.

METHODOLOGY Definitions Extent of antibiotic use is the description of the pattern of antibiotic prescriptions made in reference to the various settings, patient and disease characteristics. Appropriateness of antibiotic use is the assessment of antibiotic prescriptions against the current national antimicrobial guidelines for adherence. Structural capacity means the ability of the hospitals to provide for the needs to promote appropriate antimicrobial use for achieving appropriate outcomes. Point Prevalence measures the prevalence of antibiotic use during an hospitalization episode (not what is prescribed on the date of survey)

METHODOLOGY Ethical Considerations Ethical consent granted by the Health Research and Development Division (13/18/1 X(560) and by all hospital research and ethics committees or managements. Hospital employees who were trained by MURIA & University of Botswana on Principles in Research Ethics and on the Structured Data Collection Tool. Patients or authorized persons were explained about the study and assurance of confidentiality through anonymizing collected data, clarified their doubts to receive verbal voluntary informed consent. All collected data were de-identified by data collectors at their hospitals to anonymize data before emailed to investigators. Investigators assured of results to be shared with their respective hospitals.

METHODOLOGY Data Collection Data collected through hospital employees who were trained by MURIA & University of Botswana on Principles in Research Ethics and on the Structured Data Collection Tool. Communication support provided through telephonic and email communications to clarify any doubts. Data collected in hard copies of the tool and captured on the standardized Excel template with dropdown menus. Data collected in 30 working days in 10 hospitals (3 rd May to 14 th June 2017) Data collection took1day for Primary and Specialized hospitals with 1 and 5 data collectors respectively; 3 to 5 days in District hospitals with 1 to 2 data collectors and 10 days in referral hospital with 2 data collectors. Data was reviewed to verify any typographical errors, incorrect identification and to recognize the missing values in preparation for the analysis. Data presented with frequency and percentages.

RESULTS & DISCUSSION Patient Population (N=773) Admissions Consented % Consented No of Hospitalizations in Primary Hospital 69 67 97,10 No. of Hospitalizations in District Hospital 330 280 84,85 No. of Hospitalizations in Referral Hospital 311 307 98,71 No. of Hospitalizations in Specialized Hospital 63 57 90,48 Total no. of Hospitalizations & Consent 773 711 92,37

RESULTS & DISCUSSION Ward Admissions & Consent (N=773) Admissions Consented % Consented Paediatric Intensive Care Unit (PICU) 6 6 100,00 Obstetrics & Gynaecology (OBGY) 209 199 95,22 Adult Medical Ward (AMW) 207 192 92,75 Adult Surgical Ward (ASW) 177 164 92,66 Paediatric Surgical Ward (PSW) 34 31 91,18 Adult Intensive Care Unit (AICU) 19 17 89,47 Paediatric Medical Ward (PMW) 68 59 86,76 Neonatal Intensive Care Unit (NICU) 53 43 81,13

RESULTS & DISCUSSION Gender Distribution N=711 433 (60.90%) 278 (39,10%) Males Females

RESULTS & DISCUSSION Total Age (Median) Standard Deviation Adult (Years) 627 38.79 22.28 Children (Years) 21 10.48 1.29 Infants (Months) 22 3.95 2.26 Neonates (Days) 41 4.83 6.95 Total 711

% of Patients RESULTS & DISCUSSION 45.00 40.00 35.00 30.00 25.00 20.00 15.00 10.00 5.00 0.00 Employment Status (%) 21.57 22.06 Males (N=204) Employed Unemployed 23.70 40.91 Females (N=308)

% of Patients RESULTS & DISCUSSION Risk Factors for use of Antibiotics 50.00 45.00 40.00 35.00 30.00 25.00 20.00 15.00 10.00 5.00 0.00 42.90 Transferred In Patients (N=697) 12.70 Previous Hospitalizations (N=614) 2.54 Malaria Positive (N=118) 5.01 Malnourished (N=599) 25.40 TB Positive (N=126)

% of Patients RESULTS & DISCUSSION Risk Factors -Catheter Use (%) 60.00 50.00 53.02 44.16 40.00 30.00 20.00 10.00 0.00 Peripheral (N=314) 7.45 Urinary (N=53) 1.41 1.27 1.27 0.00 Hamodialysis (N=10) Central Venous (N=9) Other (N=9) Peritonial No Catheter

% of Patients RESULTS & DISCUSSION 100.00 90.00 80.00 70.00 Risk Factors - Intubation (%) 90.15 60.00 50.00 40.00 30.00 20.00 10.00 0.00 6.89 3.94 3.94 0.00 0.28 Endotracheal (N=28) Gastroduodenal (N=0) Tracheostomy (N=2) Nasogastric (N=49) Suction (N=28) No Intubation (N=641)

% of Patients RESULTS & DISCUSSION 70 60 50 40 30 20 10 0 61.74 Community Accuired (N=439) Type of Infections (%) 8.44 0.42 Hospital Acquired (N=60) Home Based Care (N=3) Non-Infectious Conditions (N=209) 29.4

RESULTS & DISCUSSION HIV Status Among Hospitalized Admissions Tested Positive Negative On HAART Total 711 462 185 277 158 Percentage 100 64,97 40,04 59,95 85,40

Cefotaxime Amoxycillin Metronidazole Oral Erythromycin Cotrimoxazole Metronidazole Ampicillin Cloxacillin Ceftriaxone Gentamycin Nalidixic Acid Doxycycline Amoxycillin + Cefradine Benzylpenicillin Cefppodoxime Vancomycin Chloramphenicol Benzathinebenzylp Clarithromycin Azithromycin Amikacin Phenoxymethylpe Ampicillin + Cefuroxime Cefditoren Imipenem + Meropenem Ciprofloxacin Levofloxacin % OF PATIENTS RESULTS & DISCUSSION 8.00 7.00 6.00 5.00 4.00 3.00 2.00 1.00 0.00 Previous Antibiotic Exposure N=134 (%) 6.76 6.23 4.27 4.09 3.38 2.49 2.31 2.31 2.14 1.42 1.25 0.89 0.89 0.89 0.53 0.53 0.53 0.36 0.36 0.36 0.36 0.36 0.18 0.18 0.18 0.18 0.18 0.18 0.18 0.18

No.of days RESULTS & DISCUSSION 18.00 16.00 14.00 12.00 10.00 8.00 6.00 4.00 2.00 0.00 Mean Duration of Pre-hospitalization Exposure of Antibiotics 16.25 12.00 11.0010.22 10.00 9.50 8.00 7.35 7.20 7.00 6.00 6.00 5.85 5.56 5.53 5.00 4.44 4.33 4.00 4.00 3.80 3.40 3.08 3.00 3.00 1.70 1.00 1.00 1.00

% OF PATIENTS RESULTS & DISCUSSION 14.00 12.00 13.22 Admission Diagnosis as Per ECDC Diagnosis Codes (%) N=339 10.00 8.00 8.72 7.59 6.00 4.00 2.00 0.00 3.52 2.81 2.67 2.25 1.41 1.41 1.13 0.98 0.98 0.98 0.70 0.28 0.14 0.14 0.14 0.00 0.00 OBGY PNEU SST GI CNS CSEP BRON BJ ENT CYS CVS FN PYE UND EYE GUM IA SIRS ASB BAC DIAGNOSIS PER SITE OF INFECTION

No. of Missed Doses RESULTS & DISCUSSION 60 Missed Doses 50 40 30 20 10 0 0 200 400 600 800 1000 1200 No. of Prescriptions

RESULTS & DISCUSSION Primary District Tertiary Specialty Total No. of Antibiotic Prescriptions 77 283 541 81 No. of Medical Records Reviewed (Consented) No. of Admissions for Bacterial Infection/ Surgical Prophylaxis 67 280 307 57 59 155 114 14 Antibiotic Prescribing Ratio Per Patient 1.31 1.83 4.75 5.79

RESULTS & DISCUSSION Prevalence of: Specialist (%) N=57 Tertiary (%) N=307 District (%) N=280 Primary (%) N=67 Injectable antibiotic use 136.84 121.82 60.00 67.16 Oral antibiotic use 5.26 54.40 40.36 47.76

RESULTS & DISCUSSION Duration of Surgical Prophylaxis Specialist (%) N=27 Tertiary (%) N=58 District (%) N=31 Primary (%) N=2 1 dose Surgical Prophylaxis 25.93 0.00 6.45 0.00 1 day Surgical Prophylaxis 7.41 0.00 3.23 0.00 > 1day Surgical Prophylaxis 66.67 100.00 90.32 100.00

RESULTS & DISCUSSION CST Indicators Specialist (%) N=57 Tertiary (%) N=307 District (%) N=280 Primary (%) N=67 Culture & Sensitivity Ordered Culture & Sensitivity reported Antibiotic therapy consolidated 29.82 2.61 3.57 22.39 58.82 50.00 70.00 26.67 100.00 100.00 0.00 100.00

ASSESSMENT OF INSTITUTIONAL CAPACITY FOR PROMOTION OF ANTIMICROBIAL STEWARDSHIP

LIMITATIONS No on-site support for data collectors Committed time for staff in service to collect data was difficult though released from work due to staff shortages. Confusion with several terminologies for diagnosis: Impression, Assessment, Query??? Rule out.. Etc. No standard template used for taking patient history; information may not be available, a times to search volumes of notes. E.g. previous hospitalization, medication history etc Some tests are not indicated for the admitted condition; therefore TB, Malaria, CD4 counts or HIV wasn t tested. Difficult to confirm a HAI as not recorded as the diagnosis and not elaborately defined in data collection tools. Field for Antibiotic Stop date was not provided Discrepant prescription orders: Electronic prescriptions when stopped; it wasn t stopped in drug administration sheets the later used for the study as nurses use this to administer medications. Obtaining consent at some settings difficult due to participant bias (Moms of Paediatric and Neonatal)

ACKNOWLEDGEMENTS Ministry of Health and Wellness Botswana Health Research and Development Unit MOHW Botswana University of Botswana Hospital managements and Research & Ethics Committees. All ln-service staff who extended their valuable service time for Data Collection