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Bacteraemias in tropical Australia: changing trends over a 10-year period
Diagnostic Microbiology and Infectious Disease 75 (2013) 266–270
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Bacteraemias in tropical Australia: changing trends over a 10-year period☆ Selina Porter a, b, Natkunam Ketheesan a, c, Robert Norton a, b, d,⁎ a b c d
School of Medicine and Dentistry, James Cook University, Douglas, Queensland 4811, Australia Townsville Hospital, Townsville, Queensland 4811, Australia School of Veterinary and Biomedical Sciences, James Cook University, Douglas, Queensland 4811, Australia Pathology Queensland, Townsville Hospital, Townsville, Queensland 4811, Australia
a r t i c l e
i n f o
Article history: Received 4 September 2012 Received in revised form 31 October 2012 Accepted 11 November 2012 Available online 29 December 2012 Keywords: Bacteraemia Tropical Australia
a b s t r a c t Bacteraemia is an important cause of morbidity and mortality worldwide. This is the largest reported study of bacteraemias in Australia. The presence of organisms endemic to the tropical region and the changing trends described have significant implications for empirical antibiotic therapy. This retrospective study examined 8976 blood cultures from Townsville Hospital, a regional Australian hospital located in the tropics over a 10year period. The rate of bacteraemic episodes during the study period was 10.12 per 1000 admissions. Intravenous devices (18.7%), immunosuppressive therapy (16.1%), and urinary tract infections (16.1%) were important sources for bacteraemia. The most common organisms were Staphylococcus aureus (20.9%) and Escherichia. coli (15.6%). A significant reduction was observed in S. aureus susceptibility to clindamycin (P b 0.05) and in E. coli susceptibility to gentamicin. Organisms isolated that were of relevance to the tropics of Australia included Burkholderia pseudomallei, Group A streptococcus, and Brucella suis. Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved.
1. Introduction In Australia, the incidence of bacteraemia has been reported to be between 4.6 and 8.1 per 1000 admissions (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993; Oldfield et al., 1982). The profile of causative pathogens differs across the world and is influenced by climate, population demographics, and the endemicity of pathogens (Al-Ajlan et al., 2011; Chierakul et al., 2004; Currie et al., 2000). Clinically significant bacteraemia is treated with antibiotics which may be confounded by microbial resistance. A comprehensive knowledge of the local pathogen profile is essential to ensure appropriate empirical therapy, thereby minimising bacterial resistance and disease (Collignon, 2002). The majority of studies of bacteraemia, including those conducted in Australia, examine a single organism or patient population and are often conducted in areas of temperate climate (Girard and Ely, 2007; Laupland et al., 2003). A few Australian studies have provided an insight into bacteraemia (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993; Oldfield et al., 1982), of which only one was conducted in tropical Australia (Douglas et al., 2004). Studies of bacteraemia conducted in tropical countries are limited to reports from developing countries with limited resources. The high preva-
☆ This study was carried out by SP partly under the School of Medicine MBBS Honours Programme of James Cook University, in collaboration with The Townsville Hospital. ⁎ Corresponding author. Tel.: +61-7-4433-1111; fax: +61-7-4433-2415. E-mail address: [email protected] (R. Norton).
lence of HIV and TB in those countries and the absence of comprehensive immunisation programs result in a microbial profile which may be unsuitable for comparison to the wider tropical Australian population (Archibald and Reller, 2001; Brent et al., 2006; Douglas et al., 2004). The Townsville Hospital is the main tertiary referral centre for North Queensland. The tropical savannah climate of the area includes monsoonal rains resulting in seasonal flooding. At the time of the 2006 census, 211,736 people resided in the Townsville Health Service District, with Indigenous Australians accounting for 6.6% of the total population. This is more than twice the national average.
2. Methods This was a retrospective study which examined 64,126 consecutive blood samples provided for culture to the Pathology Department at the Townsville Hospital over a 10-year period (1 January 2000 to 31 December 2009). In this study, bacteraemia was defined as blood culture isolates deemed to be responsible for clinical illness, while contaminant isolates were considered as isolates deemed not responsible for clinical illness (Gosbell et al., 1999). The source of bacteraemia was defined as the clinical focus of infection that was considered by the treating medical team to be the source of bacteraemia in a patient with positive blood cultures (Douglas et al., 2004). The isolation of a pathogen from a patient in whom the focus of infection was not identified was defined as an unknown source (Gosbell et al., 1999).
0732-8893/$ – see front matter. Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.diagmicrobio.2012.11.017
S. Porter et al. / Diagnostic Microbiology and Infectious Disease 75 (2013) 266–270
Consecutive blood cultures from the same individual with the same organism identified within 5 days of initial isolation were regarded as a single bacteraemic episode (Douglas et al., 2004). A database was created which included patient identifiers, laboratory number, the date of sampling, the organisms detected, the likely source, and clinical significance of the bacteraemia. The clinical significance of a culture was determined by a clinical microbiologist who conferred with the treating physician. Blood cultures which were of unknown significance or that did not have the significance recorded were excluded from analysis. Occupied bed days and admissions to the hospital during the study period were obtained from the hospital administration. The data were analysed to identify
267
the frequencies of clinically significant cultures, bacteraemia, contaminant cultures, and the prevalence of pathogens detected in culture. The most common sources for clinically significant bacteraemia were also assessed. Ethics approval for this study was provided by the Townsville Health Service District Human Research Ethics Committee (HREC/05/QTHS/3). 2.1. Detection of bacteraemia Blood cultures were processed using the BacT/ALERT® automated microbial detection system (Organon Teknika, Durham, NC, USA). Blood cultures which signalled positive were subjected to a Gram
Table 1 Organisms detected in significant bacteraemias. Organisms Gram-positive organisms S. aureus Coagulase-negative staphylococci S. pneumoniae Streptococcus (Group A) E. faecalis Streptococcus viridans group Streptococcus (Group B) Streptococcus spp. Bacillus spp. Streptococcus (Group G) Corynebacterium spp. Streptococcus (Group C) Micrococcus spp. Enterococcus spp. Clostridium spp. C. perfringens Streptococcus (Group F) Other Gram-positive species Gram-negative organisms E. coli K. pneumoniae P. aeruginosa E. cloacae S. maltophilia A.baumannii P. mirabilis S. marcescens Bacteroides spp. Salmonella spp. B. pseudomallei Pseudomonas spp. Acinetobacter spp. B. fragilis H. influenza K. oxytoca E. aerogenes N. meningitidis M. morganii Chryseobacterium spp. Citrobacter spp. S. paucimobilis Achromobacter spp. F. oryzihabitans Pantoea spp. Providencia spp. Aeromonas spp. Escherichia spp. B. suis Other Gram-negative species Fungi Candida albicans Candida spp. Cryptococcus neoformans Other fungi species
2000 (n = 443)
2001 (n = 506)
2002 (n = 428)
2003 (n = 395)
2004 (n = 447)
2005 (n = 452)
2006 (n = 434)
2007 (n = 391)
2008 (n = 527)
2009 (n = 513)
2000 to 2009 (n = 4536)
111 (25.1) 62 (14.0)
115 (22.7) 109 (21.5)
96 (22.4) 67 (15.7)
80 (20.3) 95 (24.1)
97 (21.7) 81 (18.1)
98 (21.7) 101 (22.4)
79 (18.2) 90 (20.7)
85 (21.8) 81 (20.7)
95 (18.0) 135 (25.6)
96 (18.7) 120 (23.4)
952 (21.0) 941 (20.8)
37 (8.4) 15 (3.4) 6 (1.4) 7 (1.6) 5 (1.1) 6 (1.4) 4 (0.9) 8 (1.8) 3 (0.7) 1 (0.2) 0 (0.0) 1 (0.2) 1 (0.2) 0 (0.0) 0 (0.0) 6 (1.4)
34 (6.7) 15 (3.0) 6 (1.2) 9 (1.8) 3 (0.6) 5 (1.2) 5 (1.0) 3 (0.6) 3 (0.6) 0 (0.0) 0 (0.0) 2 (0.4) 1 (0.2) 1 (0.2) 0 (0.0) 2 (0.4)
24 (5.6) 14 (3.3) 12 (2.8) 6 (1.4) 12 (2.8) 6 (1.4) 7 (1.6) 4 (0.9) 2 (0.5) 2 (0.5) 0 (0.0) 2 (0.5) 1 (0.2) 1 (0.2) 1 (0.2) 9 (2.1)
24 (6.1) 5 (1.3) 15 (3.8) 9 (2.3) 8 (2.0) 7 (1.8) 3 (0.8) 2 (0.5) 1 (0.3) 1 (0.3) 2 (0.5) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (0.8)
19 (4.3) 9 (2.0) 8 (1.8) 9 (2.0) 6 (1.3) 7 (1.6) 7 (1.6) 3 (0.7) 7 (1.6) 3 (0.7) 7 (1.6) 4 (0.9) 1 (0.2) 4 (0.9) 0 (0.0) 6 (1.3)
18 (4.0) 15 (3.3) 17 (3.8) 10 (2.2) 7 (1.6) 6 (0.4) 9 (2.0) 6 (1.3) 7 (1.6) 2 (0.4) 2 (0.4) 1 (0.2) 0 (0.0) 0 (0.0) 1 (0.2) 9 (2.0)
16 (3.7) 17 (4.0) 7 (1.6) 10 (2.3) 11 (2.5) 7 (1.6) 3 (0.7) 3 (0.7) 2 (0.5) 2 (0.5) 2 (0.5) 4 (0.9) 0 (0.0) 2 (0.5) 0 (0.0) 3 (0.7)
14 (3.6) 15 (3.8) 15 (3.8) 12 (3.1) 14 (3.6) 7 (1.3) 0 (0.0) 3 (0.8) 4 (1.0) 3 (0.8) 1 (0.3) 0 (0.0) 0 (0.0) 1 (0.3) 1 (0.3) 3 (0.8)
16 (3.1) 19 (3.6) 20 (3.8) 11 (2.1) 9 (1.7) 9 (1.5) 6 (1.1) 5 (1.0) 2 (0.4) 5 (1.0) 6 (1.1) 2 (0.4) 3 (0.6) 0 (0.0) 0 (0.0) 10 (6.1)
19 (3.7) 12 (2.3) 14 (2.8) 9 (1.8) 12 (2.3) 10 (1.6) 8 (1.6) 3 (0.6) 2 (0.4) 2 (0.4) 1 (0.2) 3 (0.6) 3 (0.6) 0 (0.0) 1 (0.2) 4 (3.1)
221 136 120 92 87 70 52 40 33 21 21 19 10 9 4 55
(4.9) (3.0) (2.7) (2.0) (1.9) (1.5) (1.2) (0.9) (0.7) (0.5) (0.5) (0.4) (0.2) (0.2) (0.1) (1.2)
57 (12.9) 24 (5.4) 21 (4.8) 8 (1.8) 6 (1.4) 5 (1.1) 8 (1.8) 2 (0.5) 3 (0.7) 4 (0.9) 11 (2.5) 5 (1.1) 1 (0.2) 4 (0.9) 2 (0.5) 3 (0.7) 2 (0.5) 1 (0.2) 2 (0.5) 2 (0.5) 1 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (0.7) 2 (0.5) 1 (0.2) 0 (0.0) 5 (1.1)
80 (15.8) 26 (5.1) 24 (4.7) 17 (3.4) 8 (1.6) 6 (1.2) 7 (1.4) 6 (1.2) 0 (0.0) 5 (1.0) 3 (0.6) 2 (0.4) 2 (0.4) 3 (0.6) 2 (0.4) 1 (0.2) 1 (0.2) 3 (0.6) 1 (0.2) 4 (0.8) 1 (0.2) 1 (0.2) 1 (0.2) 0 (0.0) 2 (0.4) 1 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) 12 (2.4)
54 (12.6) 32 (7.5) 26 (6.1) 10 (2.3) 6 (1.4) 5 (1.2) 7 (1.6) 6 (1.4) 1 (0.2) 8 (1.9) 5 (1.2) 4 (0.9) 4 (0.9) 4 (0.9) 2 (0.5) 2 (0.5) 1 (0.2) 5 (1.2) 0 (0.0) 1 (0.2) 1 (0.2) 1 (0.2) 0 (0.0) 1 (0.2) 0 (0.0) 1 (0.2) 1 (0.2) 0 (0.0) 1 (0.2) 9 (2.1)
74 (18.7) 23 (5.8) 20 (5.1) 11 (2.8) 7 (1.8) 3 (0.8) 5 (1.3) 4 (1.0) 1 (0.3) 3 (0.8) 1 (0.3) 2 (0.5) 2 (0.5) 6 (1.5) 1 (0.3) 5 (1.3) 3 (0.8) 2 (0.5) 3 (0.8) 1 (0.3) 1 (0.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (1.3)
69 (15.4) 30 (6.7) 30 (6.7) 13 (2.9) 14 (3.1) 10 (2.2) 2 (0.5) 3 (0.7) 2 (0.5) 7 (1.6) 9 (2.0) 6 (1.3) 1 (0.2) 4 (0.9) 0 (0.0) 2 (0.5) 3 (0.7) 1 (0.2) 2 (0.5) 1 (0.2) 1 (0.2) 3 (0.7) 0 (0.0) 3 (0.7) 1 (0.2) 0 (0.0) 1 (0.2) 0 (0.0) 0 (0.0) 16 (3.6)
64 (14.2) 25 (5.5) 27 (6.0) 17 (3.8) 6 (1.3) 11 (2.4) 5 (1.1) 7 (1.6) 8 (1.8) 2 (0.4) 6 (1.3) 0 (0.0) 9 (2.0) 0 (0.0) 4 (0.9) 4 (0.9) 0 (0.0) 4 (0.9) 1 (0.2) 1 (0.2) 3 (0.7) 1 (0.2) 1 (0.2) 4 (0.9) 0 (0.0) 0 (0.0) 1 (0.2) 1 (0.2) 3 (0.7) 19 (4.2)
76 (17.5) 36 (8.3) 20 (4.6) 11 (2.5) 10 (2.3) 9 (2.1) 7 (1.6) 6 (1.4) 8 (1.8) 3 (0.7) 0 (0.0) 4 (0.1) 4 (0.1) 0 (0.0) 4 (0.1) 3 (0.7) 1 (0.2) 1 (0.2) 1 (0.2) 2 (0.5) 3 (0.7) 3 (0.7) 0 (0.0) 2 (0.5) 0 (0.0) 1 (0.2) 2 (0.5) 4 (1.0) 0 (0.0) 11 (2.5)
55 (14.1) 18 (4.6) 21 (5.4) 10 (2.6) 2 (0.5) 5 (1.9) 4 (1.0) 2 (0.5) 0 (0.0) 5 (1.3) 0 (0.0) 4 (1.0) 3 (0.8) 4 (1.0) 3 (0.8) 2 (0.5) 1 (0.3) 1 (0.3) 1 (0.3) 2 (0.5) 0 (0.0) 3 (0.8) 4 (1.0) 0 (0.0) 1 (0.3) 1 (0.3) 0 (0.0) 0 (0.0) 0 (0.0) 15 (3.8)
86 (16.3) 17 (3.2) 24 (4.6) 15 (2.9) 11 (2.1) 11 (2.1) 4 (0.8) 10 (1.9) 7 (1.3) 3 (0.6) 4 (0.8) 4 (0.8) 3 (0.6) 0 (0.0) 2 (0.4) 1 (0.2) 6 (1.1) 1 (0.2) 4 (0.8) 2 (0.4) 2 (0.4) 0 (0.0) 3 (0.6) 0 (0.0) 3 (0.6) 1 (0.2) 2 (0.4) 0 (0.0) 0 (0.0) 15 (2.9)
92 (17.9) 25 (4.9) 17 (3.3) 8 (1.6) 4 (0.8) 2 (0.4) 3 (0.6) 5 (1.0) 16 (3.1) 4 (0.8) 3 (0.6) 4 (0.8) 0 (0.0) 0 (0.0) 5 (1.0) 2 (0.4) 4 (0.8) 3 (0.6) 3 (0.6) 1 (0.2) 0 (0.0) 0 (0.0) 1 (0.2) 0 (0.0) 3 (0.6) 2 (0.4) 0 (0.0) 0 (0.0) 0 (0.0) 17 (3.3)
707 256 230 120 74 67 52 51 46 44 42 35 29 25 25 25 22 22 18 17 13 12 10 10 10 10 9 6 4 124
(15.6) (5.6) (5.1) (2.7) (1.6) (1.5) (1.2) (1.1) (1.0) (1.0) (0.9) (0.8) (0.6) (0.6) (0.6) (0.6) (0.5) (0.5) (0.4) (0.4) (0.3) (0.3) (0.2) (0.2) (0.2) (0.2) (0.2) (0.1) (0.1) (2.7)
4 (0.9) 7 (1.6) 0 (0.0) 0 (0.0)
5 (1.0) 9 (1.8) 2 (0.4) 0 (0.0)
5 (1.2) 4 (0.9) 0 (0.0) 0 (0.0)
2 (0.5) 4 (1.0) 1 (0.3) 0 (0.0)
4 (0.9) 7 (1.6) 0 (0.0) 1 (0.2)
3 (0.7) 8 (1.8) 0 (0.0) 1 (0.2)
2 (0.5) 6 (1.4) 0 (0.0) 0 (0.0)
11 (2.8) 8 (2.1) 0 (0.0) 0 (0.0)
3 (0.1) 11 (0.2) 0 (0.0) 0 (0.0)
4 (0.8) 8 (1.6) 0 (0.0) 1 (0.2)
43 72 3 3
(1.0) (1.6) (0.1) (0.1)
Values are shown as n (%). Total pathogens detected in significant bacteraemias are greater in number than that of significant bacteraemias as some bacteraemic episodes were polymicrobial.
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S. Porter et al. / Diagnostic Microbiology and Infectious Disease 75 (2013) 266–270
stain and were subcultured onto appropriate media and incubated aerobically or anaerobically at 37 °C. Identification was done using standard methods. 2.2. Antibiotic susceptibility Antibiotic susceptibility testing was done using Clinical Laboratory Standards Institute or National Committee for Clinical Laboratory Standards methods. Antibiotic susceptibility data for the 5 most prevalent causative pathogens of bacteraemia were obtained from cumulative antibiograms. The percentage susceptibility of these pathogens to relevant antibiotics was collated by year, and trends in susceptibility for the 10-year study period assessed. 2.3. Statistical analysis Pearson's correlation coefficient (r) was employed to assess time trends of bacteraemia frequency per 100,000 bed days for the 10 most prevalent pathogens between 2000 and 2009. Pearson's correlation coefficient was also used to assess time trends for the percentage susceptibility of the 5 most prevalent pathogens across the study period. Statistical analysis was conducted using SPSS version 19, and a P value of less than 0.05 was considered statistically significant.
Fig. 1. Decreasing trends in bacteraemia due to Staphylococcus aureus and Streptococcus pneumoniae. Over the 10-year period, there was a significant decrease in bacteraemia caused by Staphylococcus aureus (r = −0.90; P b 0.01) and Streptococcus pneumoniae (r = −0.92; P b 0.01).
A total of 64,126 blood samples were cultured at the Townsville Hospital laboratory during the 10-year period. There were 9047 (14.1%) positive blood cultures with 246 different organisms or species detected. Of these positive blood cultures, 71 (0.78%) records were found to be incomplete and therefore excluded from analysis. These included those with an unknown significance or source. Contaminants accounted for 28% of all positive blood cultures and for 3.9% of all blood cultures conducted during the study period. This remained relatively consistent over the study period. A significant decrease in the total number of bacteraemias per year was observed over the study period (r = −0.813; P = 0.004). Gram-positive and Gram-negative organisms comprised 53.5% and 44.1%, respectively, with 2.4% fungal isolates. Overall bacteraemia accounted for 10.12 per 1000 admissions.
(20.9%) significant bacteraemic episodes; of these, 204 (21.4%) were methicillin-resistant S. aureus (MRSA). Rates of S. aureus bacteraemia decreased across the study period from 92.23/100,000 bed days in the year 2000 to 51.92/100,000 bed days in the year 2009, representing a significant negative trend (P b 0.01) (Fig. 1). There was no significant trend detected in the overall incidence of MRSA over the study period. Multi-resistant MRSA (mrMRSA) exhibited a significant reduction during this period (r = −0.651; P = 0.042). Although there was an increase in non–multi-resistant MRSA over the 10-year study period, this was not statistically significant (P = 0.125). The Group A streptococcus (GAS) and Group B streptococcus (GBS) were detected in 3% (n = 136) and 1.9% (n = 87) of cultures of bacteraemias, respectively. Although an increasing trend in isolation of GBS was observed over the study period, this was not found to be significant (r = 0.306; P = 0.389). There was a significant reduction in Streptococcus pneumoniae isolations. Rates of S. pneumoniae fell from 30.74 bacteraemias/100,000 bed days in the year 2000 to 10.28 bacteraemias/ 100,000 bed days in 2009 (Fig. 1). This represented a significant negative trend over the study period (P b 0.01). Coagulase-negative staphylococci were detected in 15.41% (699) of bacteraemias; this comprised a group which included 19 different organisms. Burkholderia pseudomallei was detected in approximately 1% (n = 43) of bacteraemias over the study period. A few isolates of Brucella suis were also isolated over the 10-year study period (n = 4).
3.2. Significant bacteraemia
3.3. Source of bacteraemia
Detailed percentages of specific pathogens isolated are given in Table 1. A comparison of the 5 most common isolates obtained in this study with other published Australian studies is given in Table 2. The most prevalent pathogen was Staphylococcus aureus, detected in 952
Staphylococcus aureus was a leading pathogen from many different sources (Table 3), including central lines, cellulitis, septic arthritis, dialysis, and wounds. Escherichia coli bacteraemias were largely due to urinary and intra-abdominal sources. Coagulase-negative staphylococci
Table 2 Comparative proportions of major groups of pathogens isolated from patients with bacteraemia in Australia.
Table 3 The 10 most common categories of sources of bacteraemia.
3. Results 3.1. Assessment of blood cultures
S. aureus E. coli K. pneumoniae P. aeruginosa S. pneumoniae Total numbers (n) Reference
Current Darwin study (%) (%)
Sydney (%)
Newcastle (%)
Canberra (%)
21.0 15.6 5.6 5.0 4.9 4536
22.2 34
25 19.7 6.8 9.1 5.3
24.2 22.6 5.5 6.8 4.2 317
21.8 19.4 5 6.1 6.1 257
12.5 4.2 498
Douglas Gosbell Oldfield McGregor and et al., 2004 et al., 1999 et al., 1982 Collignon, 1993
Values for each pathogen are expressed as a percentage proportion of the identified pathogen.
Source
Frequency % (n⁎ = 3891)
Central venous catheter Urinary tract Immunosuppressant Neonates Intra-abdominal Respiratory tract Dialysis patients Cellulitis Localised skin infection Osteomyelitis Other causes
17.2 14.5 14.5 10.4 9.4 8.7 8.1 7.7 2.4 2.2 6.5
(602) (565) (565) (405) (367) (337) (315) (299) (94) (85) (254)
n = Number of bacteraemias attributed to specific source or category of patients.
S. Porter et al. / Diagnostic Microbiology and Infectious Disease 75 (2013) 266–270
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Table 4 Time trend analyses for the percentage susceptibilities of major pathogens to selected antibiotics.
Ampicillin Augmentin Ceftriaxone Ciprofloxacin Clindamycin Erythromycin Flucloxacillin Gentamicin Meropenem Penicillin Timentin
S. aureus (methicillin susceptible)
E. coli
r
r
P
−0.127
0.726
−0.246 −0.246
−0.664
−0.733 0.126 0.290
P
K. pneumoniae
P. aeruginosa
r
P
0.493 0.493
0.182 0.497 0.354
0.616 0.144 0.315
0.036a
0.509
0.133
r
S. pneumoniae P
0.649
0.042a
0.579 0.406
0.080 0.244
−0.181
0.617
r
P
0.616
0.058
0.016a 0.729 0.416
A significant decrease in the susceptibility of S. aureus to clindamycin and E. coli to Gentamicin is shown. A significant increase in P. aeruginosa susceptibility to ciprofloxacin is also demonstrated. Blank cells = Not tested; r = correlation coefficient; P = P value. a P b 0.05.
were the leading pathogens in line-associated bacteraemias, immunosuppressed patients, and neonatal patients. 3.4. Antibiotic susceptibilities Detailed results of time trend analyses for the percentage susceptibilities of major pathogens to selected antibiotics are given in Table 4. Methicillin-susceptible S. aureus (MSSA) susceptibility to erythromycin and flucloxacillin remained stable throughout the study period; however, susceptibility to clindamycin exhibited a significant negative trend over the study period. E. coli was observed to have a significant reduction in susceptibility to gentamicin. No significant trend was observed in susceptibility of E. coli to ampicillin, ciprofloxacin, or ceftriaxone. No significant trend was observed in the percentage susceptibility of Klebsiella pneumoniae to augmentin, gentamicin, ciprofloxacin, or ceftriaxone. 4. Discussion This is the largest reported review of bacteraemias in Australia. Gram-positive pathogens predominated in bacteraemias in our study, which is consistent with other studies conducted within Australia (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993) and overseas (Shorr et al., 2006; Skogberg et al., 2008; Weinstein et al., 1997). Advances in medical technology and medical practices have been identified as the reason behind a shift from a predominance of Gram-negative to a predominantly Gram-positive profile of bacteraemic pathogens over the past several decades (Weinstein et al., 1997). This contrasts with findings in the United Kingdom and Europe where Gram-negative isolates predominate (Ispahani et al., 1987; Panceri et al., 2004; Reacher et al., 2000; Wilson et al., 2011). This is likely due to a rise in extended spectrum β-lactamase (ESBL)–producing strains of E. coli which are resistant to cephalosporin antibiotics and a general increase in the use of urinary catheters (Wilson et al., 2011). As observed in this study and by others (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993; Oldfield et al., 1982; Weinstein et al., 1997; Reacher et al., 2000; Wilson et al., 2011) S. aureus and E. coli were the most prevalent pathogens responsible for bacteraemia (Tables 1 and 2). There was a significant decrease in the incidence of S. aureus, (Fig. 1), which represented a greater than 40% decrease in standardised rates over the 10-year period and was an unexpected finding as similar studies in other centres in Australia did not report such trends (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993). A recent study of bacteraemia in the United Kingdom also detected a significant
decrease in S. aureus over a 4-year period from 2004 to 2008. This was attributed to a reduction in MRSA as a result of national initiative programmes targeted at MRSA bacteraemia in England since 2004 (Wilson et al., 2011). In our study, we also observed a significant decrease in the incidence of mrMRSA over the study period; however, the overall incidence of MRSA remained stable inferring that the negative trend in S. aureus bacteraemia was attributable to a reduction in MSSA. The reasons for the decrease observed in S. aureus, K. pneumoniae, and Pseudomonas aeruginosa numbers are not known. However, it is possible that it is a true decrease due to greater awareness of risk groups and risk factors that has enabled more efficient infection control. It is also possible that the decrease could have been due in part to early administration of antibiotic therapy prior to the drawing of blood cultures. The significant decrease in S. pneumoniae over the study period (Fig. 1) can be largely attributed to the introduction of pneumococcal vaccination programs in North Queensland. These programs resulted in a substantial decline in invasive pneumococcal disease, particularly in Indigenous children, following their implementation (Hanna et al., 2006, 2010). GAS is a pathogen that causes considerable morbidity and mortality particularly amongst the Indigenous population (Norton et al., 2004). In the current series, GAS was detected in 3% of all bacteraemia. This contrasts with studies conducted in temperate climates where the incidence of GAS is lower (1.8%) (2–4). The stability in rates of GAS observed in our study is consistent with a recent study of β-haemolytic streptococcal bacteraemia in North Queensland (Harris et al., 2011). Although we observed an increasing trend in the incidence of GBS bacteraemia, it was not statistically significant. B. pseudomallei, the aetiologic agent of melioidosis, is endemic to northern Australia. This organism was detected in only 1 other Australian study of bacteraemia which was conducted in Darwin and reported B. pseudomallei to be the cause of 6% of all bacteraemia over a 12-month study period (Douglas et al., 2004). The lower incidence in Townsville reflects the relatively lower average rainfall in the area as compared to Darwin and the positive correlation between incidence and severity of melioidosis with intensity of rainfall (Currie and Jacups, 2003). Brucella suis, the causative pathogen of brucellosis, is a zoonotic disease which is transmitted via direct contact with contaminated aerosols from the reservoir of feral pigs (Eales et al., 2010). This organism has an Australia-wide incidence of 0.2 per 100,000 population, 80% of which occur in Queensland. B. suis was not reported in other Australian studies of bacteraemia (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon 1993; Oldfield et al., 1982). The identification of the source of bacteraemia (Table 3) would be one of the limitations of this study. This was a subjective judgement
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made by a clinician when the blood culture first signalled positive, and the initial assessment might not always reflect the final diagnosis (Al Dahouk and Nockler, 2011). Increasing bacterial resistance to antimicrobial agents is a serious concern (Levy and Marshall, 2004). Surveillance studies of bacteraemia have reported increasing trends in many organisms globally, including MRSA, vancomycin-resistant enterococci, ESBL-producing, and multidrug-resistant enterobacteriaceae (Bell and Turnidge, 2003; Reacher et al., 2000; Reynolds et al., 2004). In our study, we also observed a significant reduction in susceptibilities of E. coli to gentamicin and of S. aureus to clindamycin. This likely reflects prescribing practices in the region. Conversely, the significant increase in the susceptibility of P. aeruginosa to ciprofloxacin could be attributed to the restriction of quinolone usage. Consistent with other Australian studies, no record of bacteraemia due to vancomycinresistant enterococci was observed (Douglas et al., 2004). In conclusion, our study demonstrates the unique profile of the causative pathogens of bacteraemia in tropical Queensland. When compared with other international and Australian data, major differences were observed in organisms endemic to the region such as GAS, B. pseudomallei, and B. suis. Some similarities were observed in pathogen profile with that reported from Darwin, reflecting comparable aspects in climate and demographic profile in both cities. This study has served to confirm the value of continued local surveillance of pathogen prevalence and antibiotic susceptibilities in guiding regional prescribing practices. References Al Dahouk S, Nockler K. Implications of laboratory diagnosis on brucellosis therapy. Expert Rev Anti Infect Ther 2011;9(7):833–45. Al-Ajlan HH, Ibrahim AS, Al-Salamah AA. Comparison of different PCR methods for detection of Brucella spp. in human blood samples. Pol J Microbiol 2011;60(1): 27–33. Archibald LK, Reller LB. Clinical microbiology in developing countries. Emerg Infect Dis 2001;7(2):302–5. Bell J, Turnidge J. SENTRY Antimicrobial Surveillance Program Asia-Pacific Region and South Africa. Commun Dis Intell 2003;27(Suppl.):S61–6. Brent AJ, Ahmed I, Ndiritu M, Lewa P, Ngetsa C, Lowe B. Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study. Lancet 2006;367(9509):482–8. Chierakul W, Rajanuwong A, Wuthiekanun V, Teerawattanasook N, Gasiprong M, Simpson A. The changing pattern of bloodstream infections associated with the rise in HIV prevalence in northeastern Thailand. Trans R Soc Trop Med Hyg 2004;98(11):678–86. Collignon PJ. Antibiotic resistance. Med J Aust 2002;177(6):325–9. Currie BJ, Jacups SP. Intensity of rainfall and severity of melioidosis, Australia. Emerg Infect Dis 2003;9(12):1538–42.
Currie BJ, Fisher DA, Howard DM, Burrow JN, Lo D, Selva-Nayagam S. Endemic melioidosis in tropical northern Australia: a 10-year prospective study and review of the literature. Clin Infect Dis 2000;31(4):981–6. Douglas MW, Lum G, Roy J, Fisher DA, Anstey NM, Currie BJ. Epidemiology of community-acquired and nosocomial bloodstream infections in tropical Australia: a 12-month prospective study. Trop Med Int Health 2004;9(7):795–804. Eales KM, Norton RE, Ketheesan N. Brucellosis in northern Australia. Am J Trop Med Hyg 2010;83(4):876–8. Girard TD, Ely EW. Bacteremia and sepsis in older adults. Clin Geriatr Med 2007;23(3): 633–47. Viii. Gosbell IB, Newton PJ, Sullivan EA. Survey of blood cultures from five community hospitals in south-western Sydney, Australia, 1993–1994. Aust N Z J Med 1999;29(5):684–92. Hanna JN, Humphreys JL, Murphy DM. Invasive pneumococcal disease in Indigenous people in north Queensland, 1999–2004. Med J Aust 2006;184(3):118–21. Hanna JN, Humphreys JL, Murphy DM, Smith HV. Invasive pneumococcal disease in non-Indigenous people in north Queensland, 2001-2009. Med J Aust 2010;193(7): 392–6. Harris P, Siew DA, Proud M, Buettner P, Norton R. Bacteraemia caused by betahaemolytic streptococci in North Queensland: changing trends over a 14-year period. Clin Microbiol Infect 2011;17(8):1216–22. Ispahani P, Pearson NJ, Greenwood D. An analysis of community and hospital-acquired bacteraemia in a large teaching hospital in the United Kingdom. Q J Med 1987;63(241):427–40. Laupland KB, Church DL, Mucenski M, Sutherland LR, Davies HD. Population-based study of the epidemiology of and the risk factors for invasive Staphylococcus aureus infections. J Infect Dis 2003;187(9):1452–9. Levy SB, Marshall B. Antibacterial resistance worldwide: causes, challenges and responses. Nat Med 2004;10(12 Suppl):S122–9. McGregor AR, Collignon PJ. Bacteraemia and fungaemia in an Australian general hospital—associations and outcomes. Med J Aust 1993;158(10):671–4. Norton R, Smith HV, Wood N, Siegbrecht E, Ross A, Ketheesan N. Invasive group A streptococcal disease in North Queensland (1996–2001). Indian J Med Res 2004;119(Suppl.):148–51. Oldfield GS, Duggan JM, Ghosh HK. Septicaemia in a general hospital. Med J Aust 1982;1(4):169–72. Panceri ML, Vegni FE, Goglio A, Manisco A, Tambini R, Lizioli A. Aetiology and prognosis of bacteraemia in Italy. Epidemiol Infect 2004;132(4):647–54. Reacher MH, Shah A, Livermore DM, Wale MC, Graham C, Johnson AP. Bacteraemia and antibiotic resistance of its pathogens reported in England and Wales between 1990 and 1998: trend analysis. BMJ 2000;320(7229):213–6. Reynolds R, Potz N, Colman M, Williams A, Livermore D, MacGowan A. Antimicrobial susceptibility of the pathogens of bacteraemia in the UK and Ireland 2001–2002: the BSAC Bacteraemia Resistance Surveillance Programme. J Antimicrob Chemother 2004;53(6):1018–32. Shorr AF, Tabak YP, Killian AD, Gupta V, Liu LZ, Kollef MH. Healthcare-associated bloodstream infection: a distinct entity? Insights from a large U.S. database. Crit Care Med 2006;34(10):2588–95. Skogberg K, Lyytikainen O, Ruutu P, Ollgren J, Nuorti JP. Increase in bloodstream infections in Finland, 1995–2002. Epidemiol Infect 2008;136(1):108–14. Weinstein MP, Towns ML, Quartey SM, Mirrett S, Reimer LG, Parmigiani G. The clinical significance of positive blood cultures in the 1990s: a prospective comprehensive evaluation of the microbiology, epidemiology, and outcome of bacteremia and fungemia in adults. Clin Infect Dis 1997;24(4):584–602. Wilson J, Elgohari S, Livermore DM, Cookson B, Johnson A, Lamagni T. Trends among pathogens reported as causing bacteraemia in England, 2004–2008. Clin Microbiol Infect 2011;17(3):451–8.
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Bacteraemias in tropical Australia: changing trends over a 10-year period☆ Selina Porter a, b, Natkunam Ketheesan a, c, Robert Norton a, b, d,⁎ a b c d
School of Medicine and Dentistry, James Cook University, Douglas, Queensland 4811, Australia Townsville Hospital, Townsville, Queensland 4811, Australia School of Veterinary and Biomedical Sciences, James Cook University, Douglas, Queensland 4811, Australia Pathology Queensland, Townsville Hospital, Townsville, Queensland 4811, Australia
a r t i c l e
i n f o
Article history: Received 4 September 2012 Received in revised form 31 October 2012 Accepted 11 November 2012 Available online 29 December 2012 Keywords: Bacteraemia Tropical Australia
a b s t r a c t Bacteraemia is an important cause of morbidity and mortality worldwide. This is the largest reported study of bacteraemias in Australia. The presence of organisms endemic to the tropical region and the changing trends described have significant implications for empirical antibiotic therapy. This retrospective study examined 8976 blood cultures from Townsville Hospital, a regional Australian hospital located in the tropics over a 10year period. The rate of bacteraemic episodes during the study period was 10.12 per 1000 admissions. Intravenous devices (18.7%), immunosuppressive therapy (16.1%), and urinary tract infections (16.1%) were important sources for bacteraemia. The most common organisms were Staphylococcus aureus (20.9%) and Escherichia. coli (15.6%). A significant reduction was observed in S. aureus susceptibility to clindamycin (P b 0.05) and in E. coli susceptibility to gentamicin. Organisms isolated that were of relevance to the tropics of Australia included Burkholderia pseudomallei, Group A streptococcus, and Brucella suis. Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved.
1. Introduction In Australia, the incidence of bacteraemia has been reported to be between 4.6 and 8.1 per 1000 admissions (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993; Oldfield et al., 1982). The profile of causative pathogens differs across the world and is influenced by climate, population demographics, and the endemicity of pathogens (Al-Ajlan et al., 2011; Chierakul et al., 2004; Currie et al., 2000). Clinically significant bacteraemia is treated with antibiotics which may be confounded by microbial resistance. A comprehensive knowledge of the local pathogen profile is essential to ensure appropriate empirical therapy, thereby minimising bacterial resistance and disease (Collignon, 2002). The majority of studies of bacteraemia, including those conducted in Australia, examine a single organism or patient population and are often conducted in areas of temperate climate (Girard and Ely, 2007; Laupland et al., 2003). A few Australian studies have provided an insight into bacteraemia (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993; Oldfield et al., 1982), of which only one was conducted in tropical Australia (Douglas et al., 2004). Studies of bacteraemia conducted in tropical countries are limited to reports from developing countries with limited resources. The high preva-
☆ This study was carried out by SP partly under the School of Medicine MBBS Honours Programme of James Cook University, in collaboration with The Townsville Hospital. ⁎ Corresponding author. Tel.: +61-7-4433-1111; fax: +61-7-4433-2415. E-mail address: [email protected] (R. Norton).
lence of HIV and TB in those countries and the absence of comprehensive immunisation programs result in a microbial profile which may be unsuitable for comparison to the wider tropical Australian population (Archibald and Reller, 2001; Brent et al., 2006; Douglas et al., 2004). The Townsville Hospital is the main tertiary referral centre for North Queensland. The tropical savannah climate of the area includes monsoonal rains resulting in seasonal flooding. At the time of the 2006 census, 211,736 people resided in the Townsville Health Service District, with Indigenous Australians accounting for 6.6% of the total population. This is more than twice the national average.
2. Methods This was a retrospective study which examined 64,126 consecutive blood samples provided for culture to the Pathology Department at the Townsville Hospital over a 10-year period (1 January 2000 to 31 December 2009). In this study, bacteraemia was defined as blood culture isolates deemed to be responsible for clinical illness, while contaminant isolates were considered as isolates deemed not responsible for clinical illness (Gosbell et al., 1999). The source of bacteraemia was defined as the clinical focus of infection that was considered by the treating medical team to be the source of bacteraemia in a patient with positive blood cultures (Douglas et al., 2004). The isolation of a pathogen from a patient in whom the focus of infection was not identified was defined as an unknown source (Gosbell et al., 1999).
0732-8893/$ – see front matter. Crown Copyright © 2013 Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.diagmicrobio.2012.11.017
S. Porter et al. / Diagnostic Microbiology and Infectious Disease 75 (2013) 266–270
Consecutive blood cultures from the same individual with the same organism identified within 5 days of initial isolation were regarded as a single bacteraemic episode (Douglas et al., 2004). A database was created which included patient identifiers, laboratory number, the date of sampling, the organisms detected, the likely source, and clinical significance of the bacteraemia. The clinical significance of a culture was determined by a clinical microbiologist who conferred with the treating physician. Blood cultures which were of unknown significance or that did not have the significance recorded were excluded from analysis. Occupied bed days and admissions to the hospital during the study period were obtained from the hospital administration. The data were analysed to identify
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the frequencies of clinically significant cultures, bacteraemia, contaminant cultures, and the prevalence of pathogens detected in culture. The most common sources for clinically significant bacteraemia were also assessed. Ethics approval for this study was provided by the Townsville Health Service District Human Research Ethics Committee (HREC/05/QTHS/3). 2.1. Detection of bacteraemia Blood cultures were processed using the BacT/ALERT® automated microbial detection system (Organon Teknika, Durham, NC, USA). Blood cultures which signalled positive were subjected to a Gram
Table 1 Organisms detected in significant bacteraemias. Organisms Gram-positive organisms S. aureus Coagulase-negative staphylococci S. pneumoniae Streptococcus (Group A) E. faecalis Streptococcus viridans group Streptococcus (Group B) Streptococcus spp. Bacillus spp. Streptococcus (Group G) Corynebacterium spp. Streptococcus (Group C) Micrococcus spp. Enterococcus spp. Clostridium spp. C. perfringens Streptococcus (Group F) Other Gram-positive species Gram-negative organisms E. coli K. pneumoniae P. aeruginosa E. cloacae S. maltophilia A.baumannii P. mirabilis S. marcescens Bacteroides spp. Salmonella spp. B. pseudomallei Pseudomonas spp. Acinetobacter spp. B. fragilis H. influenza K. oxytoca E. aerogenes N. meningitidis M. morganii Chryseobacterium spp. Citrobacter spp. S. paucimobilis Achromobacter spp. F. oryzihabitans Pantoea spp. Providencia spp. Aeromonas spp. Escherichia spp. B. suis Other Gram-negative species Fungi Candida albicans Candida spp. Cryptococcus neoformans Other fungi species
2000 (n = 443)
2001 (n = 506)
2002 (n = 428)
2003 (n = 395)
2004 (n = 447)
2005 (n = 452)
2006 (n = 434)
2007 (n = 391)
2008 (n = 527)
2009 (n = 513)
2000 to 2009 (n = 4536)
111 (25.1) 62 (14.0)
115 (22.7) 109 (21.5)
96 (22.4) 67 (15.7)
80 (20.3) 95 (24.1)
97 (21.7) 81 (18.1)
98 (21.7) 101 (22.4)
79 (18.2) 90 (20.7)
85 (21.8) 81 (20.7)
95 (18.0) 135 (25.6)
96 (18.7) 120 (23.4)
952 (21.0) 941 (20.8)
37 (8.4) 15 (3.4) 6 (1.4) 7 (1.6) 5 (1.1) 6 (1.4) 4 (0.9) 8 (1.8) 3 (0.7) 1 (0.2) 0 (0.0) 1 (0.2) 1 (0.2) 0 (0.0) 0 (0.0) 6 (1.4)
34 (6.7) 15 (3.0) 6 (1.2) 9 (1.8) 3 (0.6) 5 (1.2) 5 (1.0) 3 (0.6) 3 (0.6) 0 (0.0) 0 (0.0) 2 (0.4) 1 (0.2) 1 (0.2) 0 (0.0) 2 (0.4)
24 (5.6) 14 (3.3) 12 (2.8) 6 (1.4) 12 (2.8) 6 (1.4) 7 (1.6) 4 (0.9) 2 (0.5) 2 (0.5) 0 (0.0) 2 (0.5) 1 (0.2) 1 (0.2) 1 (0.2) 9 (2.1)
24 (6.1) 5 (1.3) 15 (3.8) 9 (2.3) 8 (2.0) 7 (1.8) 3 (0.8) 2 (0.5) 1 (0.3) 1 (0.3) 2 (0.5) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (0.8)
19 (4.3) 9 (2.0) 8 (1.8) 9 (2.0) 6 (1.3) 7 (1.6) 7 (1.6) 3 (0.7) 7 (1.6) 3 (0.7) 7 (1.6) 4 (0.9) 1 (0.2) 4 (0.9) 0 (0.0) 6 (1.3)
18 (4.0) 15 (3.3) 17 (3.8) 10 (2.2) 7 (1.6) 6 (0.4) 9 (2.0) 6 (1.3) 7 (1.6) 2 (0.4) 2 (0.4) 1 (0.2) 0 (0.0) 0 (0.0) 1 (0.2) 9 (2.0)
16 (3.7) 17 (4.0) 7 (1.6) 10 (2.3) 11 (2.5) 7 (1.6) 3 (0.7) 3 (0.7) 2 (0.5) 2 (0.5) 2 (0.5) 4 (0.9) 0 (0.0) 2 (0.5) 0 (0.0) 3 (0.7)
14 (3.6) 15 (3.8) 15 (3.8) 12 (3.1) 14 (3.6) 7 (1.3) 0 (0.0) 3 (0.8) 4 (1.0) 3 (0.8) 1 (0.3) 0 (0.0) 0 (0.0) 1 (0.3) 1 (0.3) 3 (0.8)
16 (3.1) 19 (3.6) 20 (3.8) 11 (2.1) 9 (1.7) 9 (1.5) 6 (1.1) 5 (1.0) 2 (0.4) 5 (1.0) 6 (1.1) 2 (0.4) 3 (0.6) 0 (0.0) 0 (0.0) 10 (6.1)
19 (3.7) 12 (2.3) 14 (2.8) 9 (1.8) 12 (2.3) 10 (1.6) 8 (1.6) 3 (0.6) 2 (0.4) 2 (0.4) 1 (0.2) 3 (0.6) 3 (0.6) 0 (0.0) 1 (0.2) 4 (3.1)
221 136 120 92 87 70 52 40 33 21 21 19 10 9 4 55
(4.9) (3.0) (2.7) (2.0) (1.9) (1.5) (1.2) (0.9) (0.7) (0.5) (0.5) (0.4) (0.2) (0.2) (0.1) (1.2)
57 (12.9) 24 (5.4) 21 (4.8) 8 (1.8) 6 (1.4) 5 (1.1) 8 (1.8) 2 (0.5) 3 (0.7) 4 (0.9) 11 (2.5) 5 (1.1) 1 (0.2) 4 (0.9) 2 (0.5) 3 (0.7) 2 (0.5) 1 (0.2) 2 (0.5) 2 (0.5) 1 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (0.7) 2 (0.5) 1 (0.2) 0 (0.0) 5 (1.1)
80 (15.8) 26 (5.1) 24 (4.7) 17 (3.4) 8 (1.6) 6 (1.2) 7 (1.4) 6 (1.2) 0 (0.0) 5 (1.0) 3 (0.6) 2 (0.4) 2 (0.4) 3 (0.6) 2 (0.4) 1 (0.2) 1 (0.2) 3 (0.6) 1 (0.2) 4 (0.8) 1 (0.2) 1 (0.2) 1 (0.2) 0 (0.0) 2 (0.4) 1 (0.2) 0 (0.0) 0 (0.0) 0 (0.0) 12 (2.4)
54 (12.6) 32 (7.5) 26 (6.1) 10 (2.3) 6 (1.4) 5 (1.2) 7 (1.6) 6 (1.4) 1 (0.2) 8 (1.9) 5 (1.2) 4 (0.9) 4 (0.9) 4 (0.9) 2 (0.5) 2 (0.5) 1 (0.2) 5 (1.2) 0 (0.0) 1 (0.2) 1 (0.2) 1 (0.2) 0 (0.0) 1 (0.2) 0 (0.0) 1 (0.2) 1 (0.2) 0 (0.0) 1 (0.2) 9 (2.1)
74 (18.7) 23 (5.8) 20 (5.1) 11 (2.8) 7 (1.8) 3 (0.8) 5 (1.3) 4 (1.0) 1 (0.3) 3 (0.8) 1 (0.3) 2 (0.5) 2 (0.5) 6 (1.5) 1 (0.3) 5 (1.3) 3 (0.8) 2 (0.5) 3 (0.8) 1 (0.3) 1 (0.3) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 5 (1.3)
69 (15.4) 30 (6.7) 30 (6.7) 13 (2.9) 14 (3.1) 10 (2.2) 2 (0.5) 3 (0.7) 2 (0.5) 7 (1.6) 9 (2.0) 6 (1.3) 1 (0.2) 4 (0.9) 0 (0.0) 2 (0.5) 3 (0.7) 1 (0.2) 2 (0.5) 1 (0.2) 1 (0.2) 3 (0.7) 0 (0.0) 3 (0.7) 1 (0.2) 0 (0.0) 1 (0.2) 0 (0.0) 0 (0.0) 16 (3.6)
64 (14.2) 25 (5.5) 27 (6.0) 17 (3.8) 6 (1.3) 11 (2.4) 5 (1.1) 7 (1.6) 8 (1.8) 2 (0.4) 6 (1.3) 0 (0.0) 9 (2.0) 0 (0.0) 4 (0.9) 4 (0.9) 0 (0.0) 4 (0.9) 1 (0.2) 1 (0.2) 3 (0.7) 1 (0.2) 1 (0.2) 4 (0.9) 0 (0.0) 0 (0.0) 1 (0.2) 1 (0.2) 3 (0.7) 19 (4.2)
76 (17.5) 36 (8.3) 20 (4.6) 11 (2.5) 10 (2.3) 9 (2.1) 7 (1.6) 6 (1.4) 8 (1.8) 3 (0.7) 0 (0.0) 4 (0.1) 4 (0.1) 0 (0.0) 4 (0.1) 3 (0.7) 1 (0.2) 1 (0.2) 1 (0.2) 2 (0.5) 3 (0.7) 3 (0.7) 0 (0.0) 2 (0.5) 0 (0.0) 1 (0.2) 2 (0.5) 4 (1.0) 0 (0.0) 11 (2.5)
55 (14.1) 18 (4.6) 21 (5.4) 10 (2.6) 2 (0.5) 5 (1.9) 4 (1.0) 2 (0.5) 0 (0.0) 5 (1.3) 0 (0.0) 4 (1.0) 3 (0.8) 4 (1.0) 3 (0.8) 2 (0.5) 1 (0.3) 1 (0.3) 1 (0.3) 2 (0.5) 0 (0.0) 3 (0.8) 4 (1.0) 0 (0.0) 1 (0.3) 1 (0.3) 0 (0.0) 0 (0.0) 0 (0.0) 15 (3.8)
86 (16.3) 17 (3.2) 24 (4.6) 15 (2.9) 11 (2.1) 11 (2.1) 4 (0.8) 10 (1.9) 7 (1.3) 3 (0.6) 4 (0.8) 4 (0.8) 3 (0.6) 0 (0.0) 2 (0.4) 1 (0.2) 6 (1.1) 1 (0.2) 4 (0.8) 2 (0.4) 2 (0.4) 0 (0.0) 3 (0.6) 0 (0.0) 3 (0.6) 1 (0.2) 2 (0.4) 0 (0.0) 0 (0.0) 15 (2.9)
92 (17.9) 25 (4.9) 17 (3.3) 8 (1.6) 4 (0.8) 2 (0.4) 3 (0.6) 5 (1.0) 16 (3.1) 4 (0.8) 3 (0.6) 4 (0.8) 0 (0.0) 0 (0.0) 5 (1.0) 2 (0.4) 4 (0.8) 3 (0.6) 3 (0.6) 1 (0.2) 0 (0.0) 0 (0.0) 1 (0.2) 0 (0.0) 3 (0.6) 2 (0.4) 0 (0.0) 0 (0.0) 0 (0.0) 17 (3.3)
707 256 230 120 74 67 52 51 46 44 42 35 29 25 25 25 22 22 18 17 13 12 10 10 10 10 9 6 4 124
(15.6) (5.6) (5.1) (2.7) (1.6) (1.5) (1.2) (1.1) (1.0) (1.0) (0.9) (0.8) (0.6) (0.6) (0.6) (0.6) (0.5) (0.5) (0.4) (0.4) (0.3) (0.3) (0.2) (0.2) (0.2) (0.2) (0.2) (0.1) (0.1) (2.7)
4 (0.9) 7 (1.6) 0 (0.0) 0 (0.0)
5 (1.0) 9 (1.8) 2 (0.4) 0 (0.0)
5 (1.2) 4 (0.9) 0 (0.0) 0 (0.0)
2 (0.5) 4 (1.0) 1 (0.3) 0 (0.0)
4 (0.9) 7 (1.6) 0 (0.0) 1 (0.2)
3 (0.7) 8 (1.8) 0 (0.0) 1 (0.2)
2 (0.5) 6 (1.4) 0 (0.0) 0 (0.0)
11 (2.8) 8 (2.1) 0 (0.0) 0 (0.0)
3 (0.1) 11 (0.2) 0 (0.0) 0 (0.0)
4 (0.8) 8 (1.6) 0 (0.0) 1 (0.2)
43 72 3 3
(1.0) (1.6) (0.1) (0.1)
Values are shown as n (%). Total pathogens detected in significant bacteraemias are greater in number than that of significant bacteraemias as some bacteraemic episodes were polymicrobial.
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stain and were subcultured onto appropriate media and incubated aerobically or anaerobically at 37 °C. Identification was done using standard methods. 2.2. Antibiotic susceptibility Antibiotic susceptibility testing was done using Clinical Laboratory Standards Institute or National Committee for Clinical Laboratory Standards methods. Antibiotic susceptibility data for the 5 most prevalent causative pathogens of bacteraemia were obtained from cumulative antibiograms. The percentage susceptibility of these pathogens to relevant antibiotics was collated by year, and trends in susceptibility for the 10-year study period assessed. 2.3. Statistical analysis Pearson's correlation coefficient (r) was employed to assess time trends of bacteraemia frequency per 100,000 bed days for the 10 most prevalent pathogens between 2000 and 2009. Pearson's correlation coefficient was also used to assess time trends for the percentage susceptibility of the 5 most prevalent pathogens across the study period. Statistical analysis was conducted using SPSS version 19, and a P value of less than 0.05 was considered statistically significant.
Fig. 1. Decreasing trends in bacteraemia due to Staphylococcus aureus and Streptococcus pneumoniae. Over the 10-year period, there was a significant decrease in bacteraemia caused by Staphylococcus aureus (r = −0.90; P b 0.01) and Streptococcus pneumoniae (r = −0.92; P b 0.01).
A total of 64,126 blood samples were cultured at the Townsville Hospital laboratory during the 10-year period. There were 9047 (14.1%) positive blood cultures with 246 different organisms or species detected. Of these positive blood cultures, 71 (0.78%) records were found to be incomplete and therefore excluded from analysis. These included those with an unknown significance or source. Contaminants accounted for 28% of all positive blood cultures and for 3.9% of all blood cultures conducted during the study period. This remained relatively consistent over the study period. A significant decrease in the total number of bacteraemias per year was observed over the study period (r = −0.813; P = 0.004). Gram-positive and Gram-negative organisms comprised 53.5% and 44.1%, respectively, with 2.4% fungal isolates. Overall bacteraemia accounted for 10.12 per 1000 admissions.
(20.9%) significant bacteraemic episodes; of these, 204 (21.4%) were methicillin-resistant S. aureus (MRSA). Rates of S. aureus bacteraemia decreased across the study period from 92.23/100,000 bed days in the year 2000 to 51.92/100,000 bed days in the year 2009, representing a significant negative trend (P b 0.01) (Fig. 1). There was no significant trend detected in the overall incidence of MRSA over the study period. Multi-resistant MRSA (mrMRSA) exhibited a significant reduction during this period (r = −0.651; P = 0.042). Although there was an increase in non–multi-resistant MRSA over the 10-year study period, this was not statistically significant (P = 0.125). The Group A streptococcus (GAS) and Group B streptococcus (GBS) were detected in 3% (n = 136) and 1.9% (n = 87) of cultures of bacteraemias, respectively. Although an increasing trend in isolation of GBS was observed over the study period, this was not found to be significant (r = 0.306; P = 0.389). There was a significant reduction in Streptococcus pneumoniae isolations. Rates of S. pneumoniae fell from 30.74 bacteraemias/100,000 bed days in the year 2000 to 10.28 bacteraemias/ 100,000 bed days in 2009 (Fig. 1). This represented a significant negative trend over the study period (P b 0.01). Coagulase-negative staphylococci were detected in 15.41% (699) of bacteraemias; this comprised a group which included 19 different organisms. Burkholderia pseudomallei was detected in approximately 1% (n = 43) of bacteraemias over the study period. A few isolates of Brucella suis were also isolated over the 10-year study period (n = 4).
3.2. Significant bacteraemia
3.3. Source of bacteraemia
Detailed percentages of specific pathogens isolated are given in Table 1. A comparison of the 5 most common isolates obtained in this study with other published Australian studies is given in Table 2. The most prevalent pathogen was Staphylococcus aureus, detected in 952
Staphylococcus aureus was a leading pathogen from many different sources (Table 3), including central lines, cellulitis, septic arthritis, dialysis, and wounds. Escherichia coli bacteraemias were largely due to urinary and intra-abdominal sources. Coagulase-negative staphylococci
Table 2 Comparative proportions of major groups of pathogens isolated from patients with bacteraemia in Australia.
Table 3 The 10 most common categories of sources of bacteraemia.
3. Results 3.1. Assessment of blood cultures
S. aureus E. coli K. pneumoniae P. aeruginosa S. pneumoniae Total numbers (n) Reference
Current Darwin study (%) (%)
Sydney (%)
Newcastle (%)
Canberra (%)
21.0 15.6 5.6 5.0 4.9 4536
22.2 34
25 19.7 6.8 9.1 5.3
24.2 22.6 5.5 6.8 4.2 317
21.8 19.4 5 6.1 6.1 257
12.5 4.2 498
Douglas Gosbell Oldfield McGregor and et al., 2004 et al., 1999 et al., 1982 Collignon, 1993
Values for each pathogen are expressed as a percentage proportion of the identified pathogen.
Source
Frequency % (n⁎ = 3891)
Central venous catheter Urinary tract Immunosuppressant Neonates Intra-abdominal Respiratory tract Dialysis patients Cellulitis Localised skin infection Osteomyelitis Other causes
17.2 14.5 14.5 10.4 9.4 8.7 8.1 7.7 2.4 2.2 6.5
(602) (565) (565) (405) (367) (337) (315) (299) (94) (85) (254)
n = Number of bacteraemias attributed to specific source or category of patients.
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269
Table 4 Time trend analyses for the percentage susceptibilities of major pathogens to selected antibiotics.
Ampicillin Augmentin Ceftriaxone Ciprofloxacin Clindamycin Erythromycin Flucloxacillin Gentamicin Meropenem Penicillin Timentin
S. aureus (methicillin susceptible)
E. coli
r
r
P
−0.127
0.726
−0.246 −0.246
−0.664
−0.733 0.126 0.290
P
K. pneumoniae
P. aeruginosa
r
P
0.493 0.493
0.182 0.497 0.354
0.616 0.144 0.315
0.036a
0.509
0.133
r
S. pneumoniae P
0.649
0.042a
0.579 0.406
0.080 0.244
−0.181
0.617
r
P
0.616
0.058
0.016a 0.729 0.416
A significant decrease in the susceptibility of S. aureus to clindamycin and E. coli to Gentamicin is shown. A significant increase in P. aeruginosa susceptibility to ciprofloxacin is also demonstrated. Blank cells = Not tested; r = correlation coefficient; P = P value. a P b 0.05.
were the leading pathogens in line-associated bacteraemias, immunosuppressed patients, and neonatal patients. 3.4. Antibiotic susceptibilities Detailed results of time trend analyses for the percentage susceptibilities of major pathogens to selected antibiotics are given in Table 4. Methicillin-susceptible S. aureus (MSSA) susceptibility to erythromycin and flucloxacillin remained stable throughout the study period; however, susceptibility to clindamycin exhibited a significant negative trend over the study period. E. coli was observed to have a significant reduction in susceptibility to gentamicin. No significant trend was observed in susceptibility of E. coli to ampicillin, ciprofloxacin, or ceftriaxone. No significant trend was observed in the percentage susceptibility of Klebsiella pneumoniae to augmentin, gentamicin, ciprofloxacin, or ceftriaxone. 4. Discussion This is the largest reported review of bacteraemias in Australia. Gram-positive pathogens predominated in bacteraemias in our study, which is consistent with other studies conducted within Australia (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993) and overseas (Shorr et al., 2006; Skogberg et al., 2008; Weinstein et al., 1997). Advances in medical technology and medical practices have been identified as the reason behind a shift from a predominance of Gram-negative to a predominantly Gram-positive profile of bacteraemic pathogens over the past several decades (Weinstein et al., 1997). This contrasts with findings in the United Kingdom and Europe where Gram-negative isolates predominate (Ispahani et al., 1987; Panceri et al., 2004; Reacher et al., 2000; Wilson et al., 2011). This is likely due to a rise in extended spectrum β-lactamase (ESBL)–producing strains of E. coli which are resistant to cephalosporin antibiotics and a general increase in the use of urinary catheters (Wilson et al., 2011). As observed in this study and by others (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993; Oldfield et al., 1982; Weinstein et al., 1997; Reacher et al., 2000; Wilson et al., 2011) S. aureus and E. coli were the most prevalent pathogens responsible for bacteraemia (Tables 1 and 2). There was a significant decrease in the incidence of S. aureus, (Fig. 1), which represented a greater than 40% decrease in standardised rates over the 10-year period and was an unexpected finding as similar studies in other centres in Australia did not report such trends (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon, 1993). A recent study of bacteraemia in the United Kingdom also detected a significant
decrease in S. aureus over a 4-year period from 2004 to 2008. This was attributed to a reduction in MRSA as a result of national initiative programmes targeted at MRSA bacteraemia in England since 2004 (Wilson et al., 2011). In our study, we also observed a significant decrease in the incidence of mrMRSA over the study period; however, the overall incidence of MRSA remained stable inferring that the negative trend in S. aureus bacteraemia was attributable to a reduction in MSSA. The reasons for the decrease observed in S. aureus, K. pneumoniae, and Pseudomonas aeruginosa numbers are not known. However, it is possible that it is a true decrease due to greater awareness of risk groups and risk factors that has enabled more efficient infection control. It is also possible that the decrease could have been due in part to early administration of antibiotic therapy prior to the drawing of blood cultures. The significant decrease in S. pneumoniae over the study period (Fig. 1) can be largely attributed to the introduction of pneumococcal vaccination programs in North Queensland. These programs resulted in a substantial decline in invasive pneumococcal disease, particularly in Indigenous children, following their implementation (Hanna et al., 2006, 2010). GAS is a pathogen that causes considerable morbidity and mortality particularly amongst the Indigenous population (Norton et al., 2004). In the current series, GAS was detected in 3% of all bacteraemia. This contrasts with studies conducted in temperate climates where the incidence of GAS is lower (1.8%) (2–4). The stability in rates of GAS observed in our study is consistent with a recent study of β-haemolytic streptococcal bacteraemia in North Queensland (Harris et al., 2011). Although we observed an increasing trend in the incidence of GBS bacteraemia, it was not statistically significant. B. pseudomallei, the aetiologic agent of melioidosis, is endemic to northern Australia. This organism was detected in only 1 other Australian study of bacteraemia which was conducted in Darwin and reported B. pseudomallei to be the cause of 6% of all bacteraemia over a 12-month study period (Douglas et al., 2004). The lower incidence in Townsville reflects the relatively lower average rainfall in the area as compared to Darwin and the positive correlation between incidence and severity of melioidosis with intensity of rainfall (Currie and Jacups, 2003). Brucella suis, the causative pathogen of brucellosis, is a zoonotic disease which is transmitted via direct contact with contaminated aerosols from the reservoir of feral pigs (Eales et al., 2010). This organism has an Australia-wide incidence of 0.2 per 100,000 population, 80% of which occur in Queensland. B. suis was not reported in other Australian studies of bacteraemia (Douglas et al., 2004; Gosbell et al., 1999; McGregor and Collignon 1993; Oldfield et al., 1982). The identification of the source of bacteraemia (Table 3) would be one of the limitations of this study. This was a subjective judgement
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made by a clinician when the blood culture first signalled positive, and the initial assessment might not always reflect the final diagnosis (Al Dahouk and Nockler, 2011). Increasing bacterial resistance to antimicrobial agents is a serious concern (Levy and Marshall, 2004). Surveillance studies of bacteraemia have reported increasing trends in many organisms globally, including MRSA, vancomycin-resistant enterococci, ESBL-producing, and multidrug-resistant enterobacteriaceae (Bell and Turnidge, 2003; Reacher et al., 2000; Reynolds et al., 2004). In our study, we also observed a significant reduction in susceptibilities of E. coli to gentamicin and of S. aureus to clindamycin. This likely reflects prescribing practices in the region. Conversely, the significant increase in the susceptibility of P. aeruginosa to ciprofloxacin could be attributed to the restriction of quinolone usage. Consistent with other Australian studies, no record of bacteraemia due to vancomycinresistant enterococci was observed (Douglas et al., 2004). In conclusion, our study demonstrates the unique profile of the causative pathogens of bacteraemia in tropical Queensland. When compared with other international and Australian data, major differences were observed in organisms endemic to the region such as GAS, B. pseudomallei, and B. suis. Some similarities were observed in pathogen profile with that reported from Darwin, reflecting comparable aspects in climate and demographic profile in both cities. This study has served to confirm the value of continued local surveillance of pathogen prevalence and antibiotic susceptibilities in guiding regional prescribing practices. References Al Dahouk S, Nockler K. Implications of laboratory diagnosis on brucellosis therapy. Expert Rev Anti Infect Ther 2011;9(7):833–45. Al-Ajlan HH, Ibrahim AS, Al-Salamah AA. Comparison of different PCR methods for detection of Brucella spp. in human blood samples. Pol J Microbiol 2011;60(1): 27–33. Archibald LK, Reller LB. Clinical microbiology in developing countries. Emerg Infect Dis 2001;7(2):302–5. Bell J, Turnidge J. SENTRY Antimicrobial Surveillance Program Asia-Pacific Region and South Africa. Commun Dis Intell 2003;27(Suppl.):S61–6. Brent AJ, Ahmed I, Ndiritu M, Lewa P, Ngetsa C, Lowe B. Incidence of clinically significant bacteraemia in children who present to hospital in Kenya: community-based observational study. Lancet 2006;367(9509):482–8. Chierakul W, Rajanuwong A, Wuthiekanun V, Teerawattanasook N, Gasiprong M, Simpson A. The changing pattern of bloodstream infections associated with the rise in HIV prevalence in northeastern Thailand. Trans R Soc Trop Med Hyg 2004;98(11):678–86. Collignon PJ. Antibiotic resistance. Med J Aust 2002;177(6):325–9. Currie BJ, Jacups SP. Intensity of rainfall and severity of melioidosis, Australia. Emerg Infect Dis 2003;9(12):1538–42.
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