Economic Burden and Health Consequences of Antibiotic Resistance in Patients at a Tertiary Care Hospital, Vellore, South India Sujith J Chandy (1,2), Thomas Kurien(1), T Nalloor(1), V Balaji(1), S. Christopher(1), Cecilia Stalsby Lundborg(2) 1.Christian Medical College, Vellore, India 2.Karolinska Institutet, Stockholm, Sweden

Background India is a large low middle income (LMIC) country with over 1.2 billion people Infections continue to occupy a prominent place in the spectrum of disease both in the hospital and the community. This invariably means a high use of antibiotics and emergence of resistance. Due to resistance therefore, many extra costs may be incurred by the patient such as more expensive antibiotics, investigations, complications, and extra days in the hospital.

Background In a country like India where many patients cannot afford basic hospital treatment, it would be very important to study how much extra cost does the patient bear due to bacterial resistance. This information could convince policy makers about the need for stricter guidelines and awareness programs on rational use of antibiotics. It could also serve as a public health message about the economic and health consequences of resistance.

Aim To estimate the economic burden and health consequences due to antibiotic resistance in hospital inpatients in a tertiary care hospital at Vellore, South India.

Study Area Vellore district, in the state of Tamil Nadu, South India. This district has an area of 5920 sq.km and a population of 3.5 million people according to the last census in 2001 The overall literacy is 72.6%. The male and female populations approximately similar in number. Agriculture is the main occupation.

Setting Christian Medical College, Vellore - Tertiary care hospital with 1957 beds and 4500 outpatients per day. It also has primary care outreach programmes in 3 rural areas and the urban area inside the city

Methodology Design: Descriptive Cost Analysis Period of Study: A 12 month period (2010). Study Population: Inpatients of Dept of Medicine at Christian Medical College Hospital, Vellore. Eligibility: Patients admitted during the study period with: - a diagnosis of septicaemia - prescribed an empirical antibiotic - a culture and sensitivity test report

Resistance Assessment Bacterial resistance was assessed by antibiotic susceptibility testing performed on isolates from patients by the disk diffusion method at the Microbiology Department of CMC Hospital, Vellore. The susceptibility breakpoints for each drug were defined according to National Committee for Clinical Laboratory Standards (NCCLS-CLSI) guidelines. The Microbiology Department at CMC Hospital is a National Reference Laboratory

Data Collection Baseline information on sociodemographic characteristics, admission details and diagnostic condition were collected through medical charts. Microbiological confirmation of culture reports were obtained from lab register Medication information was available on the pharmacy computer system. Hospital accounting data was used to assess the costs of antibiotics, specific costs and overall cost.

Analysis To assess the economic burden of resistance, the overall cost in patients when empirical antibiotic therapy is effective (causative bacteria being susceptible) was compared with the overall cost in patients whom the empirical antibiotic has been changed due to ‘resistance’ (the culture and sensitivity test reporting bacterial resistance to the empirical antibiotic). The two groups were also compared for antibiotic costs, medicine costs, length of stay, intensive care admissions and mortality. Wilcoxon Two Sample test was applied to detect the significance of difference in costs between resistant and susceptible groups

Results 1 Organisms In Patient Groups

Results 2 Top Ten Antibiotics used in Patients

Results 3 Resistant GroupSusceptible Group Mean Age51.5 years52 years Average Number of Co-morbidities Mean Length of Hospital Stay 17 days15 days ICU Admissions4022 Mortality52 Comparison of Health Consequences between Groups

Results 4 Comparison of Antibiotic and Overall Costs among Groups Median25 th Percentile 75 th Percentile P>Z Antibiotic Cost in Rs. Resistant Group Susceptible Group Overall Cost in Rs. Resistant Group Susceptible Group

Results 5 Comparison of Specific Costs (Rupees) between Groups

Summary - 1 Main organism isolated in blood culture - E.coli in 39% of patients. Main antibiotic administered - piperacillin-tazobactam in 37% of patients. ICU admissions in the resistant group were 80% more than that in the susceptible group Mortality was low in both groups but more twice the number in the resistant group Length of stay was approximately similar between the two groups (17 vs. 15 days)

Summary - 2 Specific, overall and antibiotic costs are all higher in resistant group. Specific costs such as lab, ICU and ward charges were all higher the resistant group Overall costs for patients in the resistant group were 44% more than for those in the susceptible group. Antibiotic costs were significantly higher for the resistant group Bacterial resistance has a significant impact on the cost burden to patients and their health consequences as evidenced by this study

Implications and Conclusions An agricultural worker (majority of the Indian workforce) earns a daily wage of Rs. 65/- (1 Euro). (Ref: A difference of Rs. 20,959/- per patient in overall cost between resistant and susceptible groups therefore translates to approximately 320 days of income. This loss to a person in addition to other health consequences, family burden and loss of working income is a catastrophic burden to the individual, the family and the society.

Implications and Conclusions The burden of resistance as evidenced by this study and the message thus generated, needs to be used through advocacy, media and academic forums to : impact regulations in antibiotic misuse raise the profile of rational antibiotic use raise awareness of the health consequences and financial costs of resistance.

Acknowledgements EMECW Lot 15 scholarship was granted to investigator. All Co-investigators for their support and partnership CMC Vellore IRB for ethical permit Staff, colleagues and faculty at Karolinska Institutet, Stockholm, Sweden and Christian Medical College, Vellore, India for their assistance with the study