324
Table 6. Incidence Density and Resistance Rate of AMR Infections in Australia, 2014 Organism
Incidence per 1,000 Patient Days (95% UI)
E. coli BSI E. coli UTI E. coli RTI KP BSI KP UTI KP RTI PA BSI PA UTI PA RTI
Entero BSI Entero UTI SA BSI SA UTI SA RTI
0.61 (0.58–0.64) 7.85 (7.7–7.9) 0.10 (0.9–1.1)
0.14 (0.13–0.16) 1.3 (1.23–1.31) 0.12 (0.09–0.11) 0.11 (0.09–0.12) 1.03 (0.99–1.07) 0.72 (6.9–7.5)
0.02 (0.02–0.03) 0.11 (0.1–0.12) 0.39 (0.38–0.42) 0.26 (0.24–0.28) 0.46 (0.44–0.49)
Teresa M. Wozniak et al
Resistant Infections, No. (95% UI)
631 (520–752)
6,789 (6,333–7,252) 173 (119–237) 143 (90–209)
943 (805–1,091) 51 (22–94)
137 (87–198) 933(796–1,083)
2,306 (2,087–2,532) 131 (83–190)
906 (767–1050) 1,125 (975–1,285) 720 (601–856)
1,118 (966–1,282)
Resistance per 1,000 Patient Days (95% UI)
0.03 (0.3–0.4)
0.36 (0.34–0.38) 0.01 (0.07–0.1) 0.01 (0.005–0.01) 0.05 (0.04–0.06) 0.003 (0.001–0.01) 0.01(0.0–0.01) 0.05 (0.04–0.06) 0.12(0.11–0.13) 0.01 (0.01–0.011) 0.05 (0.04–0.06) 0.06 (0.05–0.07) 0.04 (0.03–0.05) 0.06 (0.05–0.07)
% Resistant (95% UI)
5.5 (4.5–6.5) 4.6 (4.3–4.9)
10.1 (6.8–13.2) 5.2 (3.6–7.7) 3.9 (3.4–4.5) 2.7 (1.5–5.1) 6.7 (4.6–9.8) 4.8 (4.1–5.5)
16.8 (15.3–18.3) 34.3(26.7–49.2) 42.6 (37.7–47.6) 15.2 (13.3–17.2) 14.6 (12.3–17.0) 12.9 (11.2–14.5)
Note. UI, uncertainty interval; BSI, bloodstream infection; UTI, urinary tract infection; RTI, respiratory tract infections; KP, K. pneumoniae; PA, P. aeruginosa; Entero, E. faecium; SA, S. aureus.
reporting the most recent data and that with the closest represen- tation to the Australian population and healthcare system was considered.
Data acquisition and calculation
Weused anAustralian survey of the clinicalmanagement of patients with a BSI caused by a resistant organism.23 From this publication, we extracted the antibiotic treatment (type of antibiotic, dose, and duration) and compared it against the treatment regimen for patients infected with a susceptible organism as described in the Australian Therapeutic guidelines (eTG)24 (Table 7 and Fig. 1). We calculated the difference in costs of antibiotics used to treat a single hypothetical patient with a resistant infection compared to a patient with a susceptible infection (cost of resistant infection minus the cost of a susceptible infection). Costs of antibiotics were obtained from the Queensland Department of Health lead pharmacist at a major metropolitan hospital using the 2017 pricing agreement for all Queensland hospital pharmacies. Excess LoS and mortality data were obtained from published
estimates identified in the literature review and are shown in Tables 1–5 for each of the 5 organisms. Accounting costs of a hos- pital bed used in our model was $1,839 per hospital bed day obtained from the Australian Independent Hospital Pricing Authority.25 The total annual cost of AMR was a product of the cost of excess treatment and excess hospital stay multiplied by the expected number of resistant infections in 2014.
Results Health burden
The most frequently occurring infections in our analysis were hospital-associated UTIs caused by E. coli (7.85 episodes per 1,000 patient days); these demonstrated a 10-fold higher rate than E. coli BSI (0.61 episodes per 1,000 patient days) (Table 6). Similar trends were evident for K. pneumoniae UTIs (1.3 UTI episodes per 1,000 patient days) compared with K. pneumoniae BSIs (0.14 BSI episodes per 1,000 patient days). Respiratory tract infections
(RTIs) caused by ceftazidime-resistant P. aeruginosa (0.12 episodes per 1,000 patient days; 95% uncertainty interval [UI], 0.11–0.13) also demonstrated rates that were 10-fold higher than P. aeruginosa BSIs. Across the 5 organisms included in our model, the proportion
of resistant isolates was highest in E. faecium, with 34.3% of BSIs and 42.6% UTIs testing positive for vancomycin resistance. However, incidence was amongst the lowest at 0.01 BSI episodes per 1,000 patient days and 0.05 UTIs per 1,000 patient days. Cost of antibiotics used to treat VRE was the highest across all
infections analyzed (Table 7). Linezolid prescribed intravenously 600 mg twice daily to treat VRE BSI23 resulted in an additional AUD$1,622 per infection and was ~20-fold more expensive than antibiotic treatment of MRSA (Table 7).
Attributable LoS and mortality
Estimates of additional hospital stay and mortality are presented in Tables 1–5. We identified high-quality studies that adjusted for time-dependent bias and reported measures of additional LoS and mortality for BSI patients for all selected organisms and excess LoS as reported for S. aureus and P. aeruginosa causing respiratory infections. High-quality studies that used a multistate modeling method to adjust for time-dependent bias reported excess morbid- ity and mortality of MRSA, E. coli, and K. pneumoniae BSIs.13 Cheah et al. (2013)16 and Lambert et al. (2011)14 did not use multi- state modeling methodology, but both groups controlled for time of infection at the analysis phase (medium-quality study). We did not identify any high-quality estimates for patients with UTIs for any of the included organisms. Except for a study from two Australian hospitals reporting additional LoS attributed to VRE infection,16 all other estimates of LoS and mortality were based on international data.13,14,17 All included studies were based on the general hospital ward population, with the exception of that by Lambert et al. (2011), which quantified attributable morbidity and mortality in patients infected with P. aeruginosa or respiratory MRSA from an intensive care unit.14
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