Date Published: July 7, 2017
Publisher: Public Library of Science
Author(s): Aristine Cheng, Yu-Chung Chuang, Hsin-Yun Sun, Chia-Jui Yang, Hou-Tai Chang, Jia-Ling Yang, Wang-Huei Sheng, Yee-Chun Chen, Shan-Chwen Chang, Patrick CY Woo.
Acinetobacter species are not considered skin commensals and under-treatment is an overriding concern when caring for critically-ill patients who are mostly at risk of extensively drug-resistant Acinetobacter baumannii (XDRAB) infections. Hence even a single blood culture yielding XDRAB will tend to prompt intervention. However, field observations suggest that patients with single-positive blood cultures had milder disease and were more likely to be recruited in interventional studies than those with multiple-positive blood cultures, yet no distinction is made in current clinical or trial recruitment practices. To our knowledge, this is the first study to compare the clinical characteristics and outcomes of patients with single-positive versus multiple-positive blood cultures for XDRAB. In this multicenter prospective cohort study of XDRAB bacteremic patients from July 2010 to June 2015, only patients with at least two simultaneously drawn blood cultures were included. The patients were classified as having single-positive or multiple-positive blood cultures according to the number of positive blood cultures yielding XDRAB. The primary end-point was the 28-day mortality. Of a total of 155 patients enrolled, 69 had a single-positive and 86 had multiple-positive blood cultures. Leukopenia (37.2% vs. 16.2%; P = 0.004), thrombocytopenia (56.0% vs. 26.5%; P < 0.001), higher Pitt bacteremia scores (6.6 vs. 5.5, P = 0.03) and higher 28-day mortality rates (70.9% vs. 43.5%; P = 0.001) distinguished patients with multiple-positive from those with single-positive cultures. Multivariate logistic regression showed that multi-positivity independently predicted 28-day mortality (adjusted odds ratio, 2.34; 95% confidence interval (CI), 1.03–5.28; P = 0.04) and the Cox regression confirmed that multi-positivity (adjusted hazard ratio, 1.80; 95% CI, 1.13–2.85; P = 0.01) predicted rapid mortality. Patients with multiple versus single positive blood cultures yielding XDRAB had greater morbidity and mortality. Investigators and clinicians should be aware that the blood culture positivity rate impacts outcomes of XDRAB bacteremia.
Extensively drug-resistant Acinetobacter baumannii (XDRAB) bacteremia usually occurs in severely ill patients in the intensive care unit with limited therapeutic options [1, 2]. The associated crude and attributable mortality rates are high, ranging from 41% to 69% and 10% to 43%, respectively [3–7]. Several complicated risk factors relating to initial disease severity, antimicrobial resistance, host factors, and ineffective antimicrobial therapy have been identified [7–15]. However, few studies have focused on the impact of bacterial factors. Currently identified factors such as the Acinetobacter genospecies and serum OXA-51 DNA load require molecular tools too sophisticated for daily clinical practice [16, 17]. In contrast, the blood culture positivity rate is an easy observation that has proven to be a semi-quantitative measure of the magnitude of Staphylococcus aureus bacteremia and to predict mortality in such patients . However, the prognostic validity of the blood culture positivity rate is not universally applicable, as demonstrated by the similar clinical outcomes of patients with single versus multiple-positive blood cultures of enterococci or coagulase-negative staphylococci (CoNS) [19, 20].
A total of 155 patients were enrolled in the study period (July 2010–June 2015) (Fig 1). The mean (SD) age of the study cohort was 66.9 (17.4) years, the Pitt bacteremia score was 6.1 (3.3) points, the Charlson comorbidity index was 3.9 (3.0) points, and hospitalization duration before A. baumannii bacteremia onset was 31.7 (30.1) days. One hundred and four (67.1%) patients were male, 45 (29.0%) patients had underlying malignancy, and 30 (19.4%) patients received immunosuppressive therapy. The all-cause in-hospital mortality was 71.6%.
To our knowledge, this is the first study to compare the clinical outcomes of patients with single- versus multiple-positive blood cultures of XDRAB. Patients who had multiple sets of positive blood cultures for XDRAB differed significantly from those who had only one set of positive cultures out of multiple samples. Although single-positive bacteremia patients did not have negligible mortality, multiplicity of positive blood cultures independently predicted greater and more rapid mortality. These findings imply that the blood culture positivity rate can be used as a simple prognostic indicator in the context of XDRAB bacteremia and further studies to examine more efficient methods to detect contamination versus true infection in the context of a single-positive blood culture are needed.
In conclusion, the number of positive blood cultures is a prognostic indicator of the severity of XDRAB bacteremia. Multiple- compared to single-positive blood cultures for XDRAB is associated with rapidly fatal disease. In order to curb the alarming early mortality rates, prevention of multiple-positive XDRAB bacteremia by carbapenem stewardship might be a better strategy than attempts at curing the infection after culture results become known. Lastly, more research is needed to discern true infection and contamination among patients with single-positive cultures.