title: Out-of-pocket health expenditures and antimicrobial resistance in low-income and middle-income countries: an economic analysis.
abstract: BACKGROUND
  The decreasing effectiveness of antimicrobial agents is a growing global public health concern. Low-income and middle-income countries are vulnerable to the loss of antimicrobial efficacy because of their high burden of infectious disease and the cost of treating resistant organisms. We aimed to assess if copayments in the public sector promoted the development of antibiotic resistance by inducing patients to purchase treatment from less well regulated private providers.
  
  
  METHODS
  We analysed data from the WHO 2014 Antibacterial Resistance Global Surveillance report. We assessed the importance of out-of-pocket spending and copayment requirements for public sector drugs on the level of bacterial resistance in low-income and middle-income countries, using linear regression to adjust for environmental factors purported to be predictors of resistance, such as sanitation, animal husbandry, and poverty, and other structural components of the health sector. Our outcome variable of interest was the proportion of bacterial isolates tested that showed resistance to a class of antimicrobial agents. In particular, we computed the average proportion of isolates that showed antibiotic resistance for a given bacteria-antibacterial combination in a given country.
  
  
  RESULTS
  Our sample included 47 countries (23 in Africa, eight in the Americas, three in Europe, eight in the Middle East, three in southeast Asia, and two in the western Pacific). Out-of-pocket health expenditures were the only factor significantly associated with antimicrobial resistance. A ten point increase in the percentage of health expenditures that were out-of-pocket was associated with a 3·2 percentage point increase in resistant isolates (95% CI 1·17-5·15; p=0·002). This association was driven by countries requiring copayments for drugs in the public health sector. Of these countries, moving from the 20th to 80th percentile of out-of-pocket health expenditures was associated with an increase in resistant bacterial isolates from 17·76% (95% CI 12·54-22·97) to 36·27% (31·16-41·38).
  
  
  CONCLUSIONS
  Out-of-pocket health expenditures were strongly correlated with antimicrobial resistance in low-income and middle-income countries. This relation was driven by countries that require copayments on drugs in the public sector. Our data suggest cost-sharing of antimicrobials in the public sector might drive demand to the private sector in which supply-side incentives to overprescribe are probably heightened and quality assurance less standardised.
  
  
  BACKGROUND
  National Institutes of Health.
authors.affiliation: Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA; National Bureau of Economic Research, Cambridge, MA, USA. Electronic address: malsan@stanford.edu.
authors.forename: Marcella
authors.initials: M
authors.lastname: Alsan
authors.affiliation: Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA.
authors.forename: Lena
authors.initials: L
authors.lastname: Schoemaker
authors.affiliation: Shorenstein Asia-Pacific Research Center, Stanford University, Stanford, CA, USA; National Bureau of Economic Research, Cambridge, MA, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Eggleston
authors.affiliation: Gandhi Medical College and Hospital, Department of Microbiology, Secunderabad, India.
authors.forename: Nagamani
authors.initials: N
authors.lastname: Kammili
authors.affiliation: Gandhi Medical College and Hospital, Department of Microbiology, Secunderabad, India.
authors.forename: Prasanthi
authors.initials: P
authors.lastname: Kolli
authors.affiliation: Center for Health Policy and the Center for Primary Care and Outcomes Research, Stanford University, Stanford, CA, USA; National Bureau of Economic Research, Cambridge, MA, USA.
authors.forename: Jay
authors.initials: J
authors.lastname: Bhattacharya
mesh_terms: D000890:Anti-Infective Agents / Q000627:therapeutic use*; D003906:Developing Countries; D024881:Drug Resistance, Bacterial; D004363:Drug Utilization; D014943:Global Health; D005102:Health Expenditures / Q000706:statistics & numerical data*; D006801:Humans
chemical_list: D000890:Anti-Infective Agents