The percentage of patients that do not respond to existing commonly used antibacterials is difficult to estimate on a nationwide as well as on an indication basis. Antimicrobial resistance varies widely by hospital and geographic region, depending on local resistance patterns and standard prescribing practices.
Published estimates of indication-specific antimicrobial resistance are scarce. Evans, et al. (2007) find that out of 604 surgical admissions treated for at least one Gram-negative rod (GNR) infection in a university hospital surgical intensive care unit and ward, 137 (23 percent) were due to infections with GNR resistant to at least one major class of antibacterial drugs (rGNR). In a later study, Roberts, et al. (2009) report that in a sample of 1,391 patients in a Chicago area hospital, 188 (13.5 percent) had antibacterial drug-resistant infections.11 According to a 2009 report by the European Center for Disease Prevention and Control (ECDC) and the European Medicines Agency (EMEA), resistance to antibacterial drugs is high among Gram-positive and Gram-negative bacteria that cause serious infections in humans and reaches 25 percent or more in several EU Member States.12
One expert interviewed for the study estimated that roughly a third of all hospital-acquired infections are resistant to standard antibacterial drugs but that resistance is increasing more slowly in the outpatient setting. The expert further speculated that if approximately 30 percent of infections are resistant to antibacterial drugs in hospitals, the rate of resistance in the outpatient settings might range from 10 percent to 15 percent. A large pharmaceutical executive noted that resistance to commonly used antibacterial drugs currently ranges from 20 percent to 25 percent according to internal research conducted by his company.
Table 16 summarizes the antimicrobial resistance data available for the model estimate. As can be observed from the table, reported estimates of antimicrobial resistance are highly varied. Based on the collective body of evidence available, we use 20 percent as the average percentage of patients not responding to existing commonly used antibacterial drugs in the U.S., independent of type of indication. For sensitivity analysis, we assume that the parameter follows a uniform probability distribution with a lower limit of 10 percent and an upper limit of 25 percent.
11 In the study, an infection was defined as antibacterial resistant if the implicating organism(s) fell into one of four subgroups: (1) methicillin-resistant Staphylococcus aureus, (2) vancomycin-resistant enterococci, (3) Escherichia coli resistant to fluoroquinolones or third-generation cephalosporins or Klebsiella species resistant to third-generation cephalosporins (AREK), and (4) amikacin- or imipenem-resistant Enterobacter, Pseudomonas, or Acinetobacter species (AIR).
12 In the study, the antibacterial resistant gram-positive bacteria included Staphylococcus aureus, Enterococcus spp. (e.g., Enterococcus faecium), and Streptococcus pneumoniae. The gram-negative bacteria included Enterobacteriaceae (Escherichia coli and Klebsiella spp.), and Non-fermentative Gram-negative bacteria (Pseudomonas aeruginosa).