PNG Med J 2012 Mar-Dec;55(1-4): 5-11
Bloodstream infections caused by resistant bacteria in surgical patients admitted to Modilon Hospital, Madang Henao Asa1, Moses Laman2,3, Andrew R. Greenhill2, Peter M. Siba2, Timothy M.E. Davis3, John Maihua1 and Laurens Manning3,4 Modilon General Hospital, Madang, Papua New Guinea, Papua New Guinea Institute of Medical Research, Madang and School of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, Australia SUMMARY In view of the dearth of information relating to antibiotic resistance in communityand hospital-acquired bacterial infections in Papua New Guinea (PNG), we carried out a prospective, hospital-based observational study of surgical patients between October 2008 and October 2009. In a sample of 115 patients (median age 30 years; 55% males) suspected of having a bloodstream infection, blood cultures were positive in 11 (10%) and a significant pathogen was isolated in 9 (8%). Staphylococcus aureus was isolated in 4 patients (44%) and 3 were methicillin resistant; all these isolates were considered community acquired because cultures were performed within 48 hours of admission. Of the remaining 5 isolates, 4 were Gram-negative organisms with at least intermediate resistance to chloramphenicol that were grown from blood taken >48 hours post-admission and thus considered nosocomially acquired. These data suggest two distinct patterns of bacterial infection in PNG surgical inpatients that have implications for national antibiotic prescription guidelines. Introduction
that causes skin, soft tissue, bone, joint and bloodstream infections (2) and is a leading cause of morbidity and mortality worldwide, including tropical countries (4-6).
In many developing countries, diagnostic microbiology facilities for invasive bacterial infections are not given priority due to their cost, a shortage of trained laboratory staff and the heavy burden of other diseases such as HIV/AIDS (human immunodeficiency virus/ acquired immune deficiency syndrome), malaria and tuberculosis (1,2). In some of these countries, empiric use of broadspectrum antibiotics is widespread and paralleled by high rates of infections caused by multiresistant organisms. One pertinent example is the recent report of the dissemination of a metallo-beta-lactamase (NDM-1) carried by a Klebsiella pneumoniae from India. Bacteria that acquire NDM-1 are resistant to all but the last line of antibiotics (3). Methicillin-resistant Staphylococcus aureus (MRSA) is another multiresistant organism
In Papua New Guinea (PNG), reports of MRSA are limited to a single case report (7) and a mortality audit which identified only two infected children (8). Similarly, to the best of our knowledge, there have been only two studies within the last 15 years describing the local epidemiology of multiresistant Gramnegative bacteria in PNG (9,10). In view of unregulated antibiotic use in the community and the lack of hospital laboratory facilities that are needed to identify and thus help restrict the spread of resistant bacteria, we hypothesized that community-acquired MRSA (CA-MRSA) and Gram-negative infections resistant to currently used antibiotics might be important causes of infection in hospitalized
1 Modilon General Hospital, PO Box 2030, Madang, Madang Province 511, Papua New Guinea 2 Papua New Guinea Institute of Medical Research, PO Box 378, Madang, Madang Province 511, Papua New Guinea 3 S chool of Medicine and Pharmacology, University of Western Australia, Fremantle Hospital, PO Box 480, Fremantle, Western Australia 6959, Australia 4 C orresponding author
[email protected]
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children at Modilon Hospital (MRAC 08.13). Written informed consent was obtained from individual patients before participation. Clinical data were entered into case report forms that included demographic information, examination findings, surgical diagnosis, investigations and outcome. Data were analysed using Stata (version 8). Univariate comparisons between patients with positive and negative blood cultures were performed using Mann-Whitney U and chi-squared tests for continuous and categorical variables, respectively. A level of significance of p ≤0.05 was used throughout.
surgical patients in PNG. Patients and Methods We performed a prospective, hospital-based observational study of surgical patients at Modilon General Hospital, the referral hospital in Madang Province. Patients were recruited over a 12-month period between October 2008 and October 2009, and were considered eligible for inclusion if they were suspected of having bloodstream infections on clinical grounds including an axillary temperature >37.5oC. Patients were classified as having i) a community-acquired bloodstream infection if a positive blood culture was obtained within 48 hours of admission, and ii) a nosocomial infection if the positive culture was from blood taken more than 48 hours after admission (11).
Results Blood cultures were performed on 115 surgical patients suspected of having a bloodstream infection. The median age was 30 years (interquartile range [IQR] 2834) and 55% were male. Trauma was the leading cause of admission, accounting for 40 patients (35%). Soft tissue injury (10 patients), fractures (10 patients), knife wounds (8 patients), head injury (4 patients), penetrating abdominal wounds (2 patients) and animal bites (2 patients) accounted for the majority of trauma cases. Other causes of admission included appendicitis (21%), malignancy (12%), abscesses (6%), burns (6%), ulcers (5%), other focal infections (5%), paraplegia (3%), hernia (3%) and others (4%).
Venous blood samples were drawn for blood culture, full blood count (Coulter Ac•T diff, Beckman Coulter, Brea, USA) and malaria microscopy. For adults, blood (5-10 ml) was placed into commercially prepared aerobic and anaerobic blood culture bottles whilst, for children, a single paediatric bottle (2-3 ml) was used. After incubation in an automated blood culture system (Bactec 9050 Becton-Dickinson, Franklin, New Jersey, USA), isolates were inoculated on to either chocolate agar plates or, for Gram-negative organisms, MacConkey agar and further incubated in a candle jar under 5% CO2 for 72 hours as previously described (12). Gram’s stain, catalase, coagulase and oxidase tests were performed for preliminary identification of organisms. Bacterial isolates were then stored in skim milk broth at -80oC until formal identification and antibiotic susceptibility testing could be performed at a reference laboratory. Antibiotic susceptibility testing was undertaken by the Kirby-Bauer disc diffusion method using antibiotic-impregnated discs (Oxoid, UK) and minimum inhibitory concentrations (MICs) were determined using e-tests (AB Biodisk, Sweden). All susceptibility break points were defined using standard guidelines (13). Coagulasenegative staphylococci, bacillus species and corynebacteria species were considered contaminants.
Blood cultures were positive in 11 patients (10%) and a significant pathogen was isolated in 9 (8%); 2 contaminants (2%, both coagulasenegative staphylococci) were identified during the study. These data are summarized in Figure 1. The clinical features, risk factors and outcomes of patients with and without bloodstream infections are shown in Table 1. Prior use of antibiotics and malignancy were significantly associated with a higher risk of a positive blood culture. Mortality was also significantly higher in patients with a positive blood culture (33% versus 6.7%, p = 0.012). The organisms isolated and their antibiotic susceptibility patterns are shown in Figure 1 and Table 2, respectively. Staphylococcus aureus was isolated in 4 patients (44%) and 3 of these were MRSA. Whilst the MRSA isolates were resistant to oxacillin and therefore methicillin and flucloxacillin, they remained sensitive to second-line antibiotics including chloramphenicol. All S. aureus isolates were considered community acquired
This study was conducted as part of good-quality clinical care and bacteriology investigations were done concurrently with a severe illness study of Papua New Guinean 6
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Figure 1. Consort diagram outlining study recruitment and positive blood culture results. CA-MRSA = community-acquired methicillin-resistant Staphylococcus aureus
because blood cultures were performed within 48 hours of admission. 2 of the 3 patients with CA-MRSA were admitted with abscesses and the other had septic arthritis. Two were treated with flucloxacillin and one with flucloxacillin plus chloramphenicol and one patient had surgical debridement. All patients with CAMRSA survived. One patient absconded during recovery thereby precluding follow-up.
to cotrimoxazole, 2 to gentamicin and 1 to ciprofloxacin. Formal screening for extended-spectrum beta-lactamases was not performed, nor was the susceptibility to ceftriaxone determined. None of the 5 patients with Gram-positive infections died compared with 3 of the 4 patients with Gram-negative nosocomial infections (Fisher’s exact test, p = 0.048) Discussion
Of the remaining 5 isolates, 4 were Gram-negative and considered nosocomial infections. They included Klebsiella pneumoniae (2 isolates), Pseudomonas aeruginosa (1 isolate) and Alcaligenes spp. (1 isolate). The final isolate was identified as Streptococcus pneumoniae that was cultured 6 days after the patient’s admission following ear trauma. Although this patient was likely to have had prior carriage of Streptococcus pneumoniae, he was also considered to have a nosocomial infection.
This study demonstrates that multiresistant organisms are prevalent in PNG and that they cause severe community- and hospitalacquired surgical infections. In addition, two broad patterns of invasive bacterial disease emerged. First, there was a predominance of CA-MRSA in invasive S. aureus infections. Second, nosocomial infections were mostly caused by Gram-negative bacteria that were resistant to chloramphenicol (CMP).
Of the 4 Gram-negative organisms, all showed resistance or intermediate resistance to tetracycline, 3 to chloramphenicol, 3
Despite the small size of the present study and the possibility of ascertainment bias due to recruitment of patients who had 7
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Table 1 Clinical and laboratory features, risk factors and outcome in surgical patients who had blood cultures performed. Data are presented as median [interquartile range] or percent (%) Positive blood culture (n = 9)
Negative blood culture (n = 106)*
p value**
28 [10.6-39.7]
30 [28-34]
0.5
Male sex (%)
50
65
0.46
Prior antibiotic use (%)
60
23.8
0.014
44.4
50
1.00
38.8 [38.1-39.2]
38.5 [38.5-38.7]
0.48
100.5 [75.5-122.1]
100 [98-101]
0.90
20 [16.6-28]
19 [18-20]
0.49
Malignancy (%)
20
4.8
0.05
Recent surgery (%)
50
32.4
0.26
Intravenous catheter in situ (%)
70
75.2
0.72
Indwelling urinary catheter in situ (%)
20
17.1
0.82
94.5 [78.9-131.1]
98 [87-105]
0.51
10.8 [4.2-13.6]
8.5 [7.8-8.9]
0.46
226 [15.5-325.8]
199 [172.4-248.6]
0.45
0
8.6
0.34
15 [6-37]
11 [8-14]
0.45
33
6.7
0.012
Age (years)
Blood culture performed
