This study demonstrated that ICU patients with BSIs in Taiwan had significantly worse clinical outcomes and higher economic burden than ICU patients without ICU-acquired infections from the same population. For example, the patients with BSI exhibited 1.66-fold and 1.41-fold increases in in-hospital and 14-day mortality rates. Per case, the patients with BSI had an excess hospital stay of 12.77 days and cost of 7,646 US dollars. Furthermore, a similar clinical and economic impact was observed among all of the causative pathogens examined.
BSIs have been associated with higher mortality and morbidity, contingent on the causative pathogen involved.1,3,13-16 For example, worse clinical outcomes have been reported for patients with BSIs caused by A. baumannii,16,17 P. aeruginosa,15,16 S. aureus,1,4,15,16 Enterobacteriaceae,4,16 and Candida spp.1,16,18 In contrast, controversial results have been obtained regarding the mortality of patients affected by enterococcal bacteremia. While some authors have argued that Enterococcus spp. represents a low virulence pathogen1 and is not associated with increased mortality unless in the presence of endocarditis,19 other authors have reported contrasting results.5,6,16,18 In the present study, significantly higher mortality was observed for patients with enterococcal bacteremia, and this may be due to vulnerability of the hosts examined, increased resistance, and a larger study population.
The high healthcare burden of BSIs reported in previous literature3,13,20 and in the present study underscores the importance of preventing ICU-acquired BSIs by infection control measurements. Furthermore, the results of these studies help to assess cost effectiveness of infection control measurements in the process of policy-making. For example, patients with ICU-acquired BSIs during the 9-year period cost Taiwan an estimated 298 million US dollars and 495,222 days (supplementary Table 5). A policy that reduced the rate of infection by 10%21 would translate into a savings of 30 million US dollars and 4,952 patient-days saved.
Drug resistance has been found to be correlated with higher medical costs due to the need for second-line antimicrobials for treatment, as well as additional diagnostic and treatment tools.22, 23 In the present study, the costs for MDR bacteria included extra 85 million US dollars and 140,923 days over nine years (Supplementary Table 5). However, cost differences between susceptible and resistant strains were not determined in the present study. Drug-susceptible strains were not included as controls due to differences in testing methods, drugs, and breakpoints for these strains which could lead to mis-assignments of drug-resistant pathogens as susceptible pathogens.
Candidemia poses a great threat to ICU patients due to its excessive medical burdens,16,18,20 and C. albicans is the most common pathogen. However, in some countries, the prevalence of non-albicans Candida exceeds that of C. albicans.24 For those infected with non-albicans Candida, higher rates of mortality,24,25 longer hospitalization stays, and increased hospital costs have been described;25-27 although other studies have reported contradicting findings.28,29 These discrepancies may be due to host factors and differences in the virulence and resistance patterns24 of non-albicans Candida. In the present study, the crude 14-day and in-hospital mortality rates of 958 patients infected with C. albicans were 38.10% and 56.16%, respectively. In comparison, among 704 patients infected with non-albicans Candida, these rates were 34.94% and 52.98%, respectively. While the hospital costs and length of stay were higher in the non-albicans Candida group compared to the C. albicans group, the 95% CI overlapped for the two groups (Table 4). These data suggested that the clinical and economic outcomes of these two groups did not greatly differ. However, the present study was not designed to specifically compare the outcomes of those infected with C. albicans versus non-albicans Candida. Therefore, additional studies with a larger number of patients, adjustment for host factors, and consideration of antifungal drugs, incubation time, and treatment duration are needed to clarify the impact of each Candida species.
The large number of patients examined in this study and the use of propensity score matching represent two major strengths of the present study. These aspects also allowed the impact of each pathogen group to be discerned. However, there were also several limitations associated with the present study which merit discussion. First, the exact cost after the index date could not be retrieved from the NHIRD. Therefore, the high total cost shown in this study may be due to costs incurred prior to the onset of a BSI. It is possible that matching of the duration before the index date and comorbidity may have reduced overestimations of healthcare costs due to time-dependent bias.30 Second, confounding factors associated with clinical impact, such as APACHE II or Pitt Bacteremia scores, were not included in this study. Instead, other clinical risk factors (Charlson Comorbidity Index score, number of organ failures, use of inotropic agents, and receipt of invasive procedures) were incorporated in our model. Third, our study is inherently limited by its retrospective design, which includes a dependence on the accuracy of the ICD codes used and unmeasurable bias.31,32 In addition, the prolonged hospitalization may have been due to a change in patient management in response to a BSI, rather than increased morbidity due to a BSI.15