Impact of Multidrug-resistant Pseudomonas aeruginosa Infection on Patient Outcomes

Elizabeth B Hirsch; Vincent H Tam


Expert Rev Pharmacoeconomics Outcomes Res. 2010;10(4):441-451. 

In This Article

Economic Impact

Literature investigating the economic impact of HAIs and attributable costs of antibiotic-resistant infections appears to be on the rise.[65] This may be due, in part, to the current era of increasing resistance rates and lack of novel antimicrobials in the development stages.[66] Economic data reporting on the burden of Gram-positive resistance are more extensive than Gram-negative resistance; however, the association with increased hospital costs and lengths of stay is evident.[67–71]

Few studies have attempted to quantify the direct costs attributed to MDR P. aeruginosa infections and increased costs are not consistently demonstrated. Again, the difficulties in direct comparison of these studies include varied definitions of resistance and economic evaluation methods. Harris and colleagues published a case series of 22 patients with MDR P. aeruginosa recovered from any clinical culture hospitalized from August 1994 to December 1997.[72] They classified a MDR isolate as one with intermediate susceptibility or resistance to ceftazidime, ciprofloxacin, imipenem and piperacillin. The mean cost of hospitalization during which the first MDR isolate was cultured was US$54,081 (mean length of stay = 18 days) compared with a mean of US$22,116 cost of hospitalization for patients with susceptible P. aeruginosa infections. In total, 17 out of 22 patients required surgery to treat their infection (five required amputations), which could increase both hospital charges and length of hospital stay. In the cohort of patients with fluoroquinolone-resistant P. aeruginosa infections, median hospital charges were significantly higher compared with patients with fluoroquinolone-susceptible infection (US$62,325 [inter-quartile range: US$22,129–188,979] and US$48,733 [US$18,760–124,829], respectively; p = 0.008).[56] Although these patients had fluoroquinolone-resistant isolates, cross-resistance in P. aeruginosa to other antimicrobial classes was common.[73] In the third study of patients with imipenem-resistant P. aeruginosa isolates, median hospital costs (inter-quartile range) were US$81,330 (US$28,549–228,174) for case patients compared with US$48,381 (US$19,148–131,144) for control patients (p < 0.001).[59] Increased hospitalization costs were at least partly owing to increased lengths of stay for those patients with imipenem-resistant isolates (15.5 median days vs 9 days; p = 0.02). The last study published in 1999 was a cohort of 489 hospitalized patients with clinical cultures of P. aeruginosa.[64] Hospital charges were studied in 309 of these patients admitted between April 1995 and July 1996. A total of 217 patients had a baseline isolate susceptible to all four study agents (piperacillin, ceftazidime, ciprofloxacin and imipenem), 92 patients had a baseline isolate resistant to at least one study agent, and 17 had emergence of resistance (defined as subsequent detection of P. aeruginosa with at least a fourfold increase in MIC relative to baseline). Neither resistance at baseline nor emergence of resistance was associated with a significant increase in daily hospital charges (multiplicative effects, 1.04 and 1.1, respectively; p = 0.41 and p = 0.43). The adjusted effects of resistance at baseline and emergence of resistance were similar for daily charges in a multivariate model (RR: 1.0 and 1.1, respectively; p = 0.41 and p = 0.43). The authors also estimated the effect of emergence of resistance by combining daily charge and length of stay analyses. Using a matched cohort study design of 15 patients in whom resistance emerged, the cumulative hospital charge was US$7340 higher than that for matched controls (p = 0.14). Although these authors did not find a significant difference in hospital charges, their definition of a resistant isolate was resistance to only one agent. Had they used a more stringent definition of resistance (i.e., to all four antipseudomonal agents), a more significant difference in charges might have been found.

Although the existing literature demonstrates increased costs owing to resistant Gram-negative infections, data focusing on P. aeruginosa are limited and somewhat inconsistent. Well-designed studies are needed to fully appreciate the direct cost burden associated with MDR P. aeruginosa infections.