Neither Single nor a Combination of Routine Laboratory Parameters can Discriminate between Gram-positive and Gram-negative Bacteremia

Abstract

Adequate early empiric antibiotic therapy is pivotal for the outcome of patients with bloodstream infections. In clinical practice the use of surrogate laboratory parameters is frequently proposed to predict underlying bacterial pathogens; however there is no clear evidence for this assumption. In this study, we investigated the discriminatory capacity of predictive models consisting of routinely available laboratory parameters to predict the presence of Gram-positive or Gram-negative bacteremia. Major machine learning algorithms were screened for their capacity to maximize the area under the receiver operating characteristic curve (ROC-AUC) for discriminating between Gram-positive and Gram-negative cases. Data from 23,765 patients with clinically suspected bacteremia were screened and 1,180 bacteremic patients were included in the study. A relative predominance of Gram-negative bacteremia (54.0%), which was more pronounced in females (59.1%), was observed. The final model achieved 0.675 ROC-AUC resulting in 44.57% sensitivity and 79.75% specificity. Various parameters presented a significant difference between both genders. In gender-specific models, the discriminatory potency was slightly improved. The results of this study do not support the use of surrogate laboratory parameters for predicting classes of causative pathogens. In this patient cohort, gender-specific differences in various laboratory parameters were observed, indicating differences in the host response between genders.

Routine laboratory biomarkers used to predict Gram-positive or Gram-negative bacteria involved in bloodstream infections

“…Among BSI-GP, the highest frequency was S. aureus (43.7%), whose mortality was 30.4%. The present data corroborates the literature 9 , 11 , 19 – 21 , demonstrating a greater difficulty in the treatment of BSI-GN, sometimes related to the specific characteristics of this bacterial group, such as the known lipopolysaccharide with an endotoxin specific to GN 21 – 23 ; or the higher resistance to antibacterial drugs of clinical use, mainly found in A. baumannii and P. aeruginosa, which increases their mortality rate 24 , 25 .…”

“…The knowledge of the bacterial group involved in the bacteremia process favors the early initiation of the most appropriate empirical therapy and increases patients' chances of survival 4 . Although many RLB have been reported as predictors of bacteremia, sepsis or mortality, they are not commonly used to distinguish between BSI-GN or BSI-GP 5 , 6 , 8 , 10 , 11 , 15 – 17 . Of the 68 RLB evaluated in this study, we set up a new statistical model with 4 covariates, predicting BSI-GN with an AUC of 0.69 a precision of 0.64, a sensitivity of 0.61 and a specificity of 0.67, which could assist clinicians in choosing the antimicrobial before the final BC result (Table 4 , Fig.…”

“…This model involves multiple analyzes where the predictor variables are analyzed simultaneously, so that the effect of each variable is adjusted to the effect of the others. Some of these biomarkers have already been proposed in other studies to predict BSI or the bacterial group involved in BSI, but few have shown good sensitivity and specificity as an independent test 9 , 11 , 14 , 17 .…”

“…Ratzinguer et al evaluated a large number of biomarkers with statistical analysis and did not obtain a satisfactory result 11 . However, Lin et al and Li et al demonstrated that some biomarkers, when associated, had the potential to predict the bacterial group involved in BSI 12 , 13 .…”

Prospects for the Management of Sepsis in an Era of Personalised Medicine

“…At one end of the spectrum is the belief that knowing the microbial cause of the sepsis is largely irrelevant, other than for epidemiological purposes. In this view, sepsis is the final common pathway of tissue injury and is essentially similar, irrespective of whether the infection was caused by Escherichia coli or Staphylococcus aureus [15]. Broad-spectrum antibiotics can eventually be tailored once the organism has been isolated, but given the need for early intervention and the risks of antimicrobial resistance, many doubt the need to be too concerned about the diagnosis.…”