A methodological comparison of risk scores versus decision trees for predicting drug-resistant infections: A case study using extended-spectrum beta-lactamase (ESBL) bacteremia.

BACKGROUND: Timely identification of multidrug-resistant gram-negative infections remains an epidemiological challenge. Statistical models for predicting drug resistance can offer utility where rapid diagnostics are unavailable or resource-impractical. Logistic regression-derived risk scores are common in the healthcare epidemiology literature. Machine learning-derived decision trees are an alternative approach for developing decision support tools. Our group previously reported on a decision tree for predicting ESBL bloodstream infections. Our objective in the current study was to develop a risk score from the same ESBL dataset to compare these 2 methods and to offer general guiding principles for using each approach. METHODS: Using a dataset of 1,288 patients with Escherichia coli or Klebsiella spp bacteremia, we generated a risk score to predict the likelihood that a bacteremic patient was infected with an ESBL-producer. We evaluated discrimination (original and cross-validated models) using receiver operating characteristic curves and C statistics. We compared risk score and decision tree performance, and we reviewed their practical and methodological attributes. RESULTS: In total, 194 patients (15%) were infected with ESBL-producing bacteremia. The clinical risk score included 14 variables, compared to the 5 decision-tree variables. The positive and negative predictive values of the risk score and decision tree were similar (>90%), but the C statistic of the risk score (0.87) was 10% higher. CONCLUSIONS: A decision tree and risk score performed similarly for predicting ESBL infection. The decision tree was more user-friendly, with fewer variables for the end user, whereas the risk score offered higher discrimination and greater flexibility for adjusting sensitivity and specificity.

Carbapenem Resistance Caused by High-Level Expression of OXA-663 ß-Lactamase in an OmpK36-Deficient Klebsiella pneumoniae Clinical Isolate.

Carbapenem resistance is mainly mediated by carbapenemases or extended-spectrum ß-lactamases (ESBL) plus a loss of porins. However, we have identified a Klebsiella pneumoniae clinical isolate that contains neither carbapenemases nor ESBLs. Instead, we found that high-level expression of a novel blaOXA-10-derived ß-lactamase gene, blaOXA-663, in conjunction with OmpK36 deficiency results in high-level carbapenem resistance. This finding demonstrates the combinatorial complexity of factors, including ß-lactamase activity, its expression levels, and porin activity, that yield carbapenem resistance.

Risk factors, outcomes and genotypes of carbapenem-nonsusceptible Klebsiella pneumoniae bloodstream infection: a three-year retrospective study in a large tertiary hospital in Northern China.

OBJECTIVE: To investigate the independent risk factors, outcomes and genotypes associated with carbapenem-non-susceptible K. pneumoniae bloodstream infections (BSIs) in northern China from 2014 to 2016. METHODS: Over a three-year period, a total of 289 K. pneumoniae BSI patients were identified. Medical records were extracted to obtain the clinical information. Polymerase chain reactions (PCRs) were performed to analyse the multilocus sequence typing (MLST) types, Klebsiella pneumoniae carbapenemase (KPC) and metallo-ß-lactamases (MBL) genes, for replicon typing of the 10 randomly selected carbapenem-non-susceptible K. pneumoniae. RESULTS: A total of 59 carbapenem-non-susceptible K. pneumoniae strains were identified. Resistance rates to imipenem, meropenem, ertapenem and amikacin were low. Multivariate analyses showed that a central venous catheter odds ratio (OR) of 4.021 (CI 1.002-16.134); mechanical ventilation of 7.587 (2.856-20.156); Pitt bacteraemia score of 1.481 (CI 1.218-1.800); hospitalization prior to culture of 1.026 (CI 1.001-1.053); and some antibiotic use 30 days prior to K. pneumoniae bacteremia, including carbapenem of 9.123 (CI 2.995-27.791), aminoglycoside of 34.079 (2.091-555.396), and tigecycline of 5.065 (CI 1.261-20.339) were associated with carbapenem-non-susceptible K. pneumoniae bacteremia. Sequence type 11 (ST11) was the most predominant MLST type, which accounted for 50% of the isolates. Eighty per cent of the isolates harbored the KPC-2 gene. The overall 28-day mortality rates of carbapenem-non-susceptible and carbapenem-susceptible K. pneumoniae were 54.24% and 19.56%, respectively. CONCLUSION: Central venous catheter, mechanical ventilation, high Pitt bacteraemia score, hospitalization prior to culture, and prior antibiotic use (carbapenem, aminoglycoside and tigecycline) were identified as independent risk factors for carbapenem-non-susceptible K. pneumoniae BSI, which was mostly caused by KPC-2 in northern China.

Dietary supplementation with omega-3 polyunsaturated fatty acids ameliorates acute pneumonia induced by Klebsiella pneumoniae in BALB/c mice.

The immune benefits associated with the optimal intake of dietary fatty acids are widely known. The objective of the present investigation was to elucidate the role of omega-3 polyunsaturated fatty acids (n-3 PUFA) food source on acute pneumonia induced by Klebsiella pneumoniae. Three different n-3 PUFA preparations (cod liver oil, Maxigard, and flaxseed oil) were orally supplemented and infection was induced in different groups of experimental mice. Mice fed olive oil and normal saline served as oil and saline controls, respectively. After 2 weeks of fatty acid feeding, no effect on the establishment of infection was observed when acute pneumonia was induced in animals. On the other hand, 6 weeks of n-3 PUFA administration was found to improve resistance in mice, as reduced lung bacterial load coupled with significant improvement in pathology was seen in infected mice. Alveolar macrophages collected from all 3 groups of mice fed n-3 PUFA exhibited a significant decrease in the level of apoptosis following infection with K. pneumoniae and an enhanced in vitro phagocytic potential for the pathogen. Lower lung levels of nitric oxide, malondialdehyde, and lactate dehydrogenase were associated with a decrease in the severity of tissue damage. There was a significant increase in the lung levels of pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß)). No significant change was observed in the levels of interleukin-10 (IL-10). This study highlights that dietary n-3 PUFA supplementation exerts an overall beneficial effect against acute experimental pneumonia. This mechanism is operative through upregulation of nonspecific and specific immune defenses of the host.

Role of Klebsiella and collagens in Crohn's disease: a new prospect in the use of low-starch diet.

Crohn's disease is suggested to result from a microbially triggered immune-mediated autoimmune process, involving mainly the terminal ileum and ileo-caecal junction. Klebsiella pneumoniae shares certain molecular structures present in pullulanase pulA and pulD secretion enzymes with various self-antigens present in collagens and HLA-B27 molecules, respectively. A link exists between high dietary starch intake and the growth of intestinal microflora, involving especially Klebsiella microbes. Increased exposure to Klebsiella in the gut as the result of high starch intake would lead to high production of antiKlebsiella antibodies as well as autoantibodies to the cross-reactive self-antigens with the resultant inflammation at the pathological sites. Eradication of these microbes from the gut in patients with Crohn's disease with the use of low-starch diet and antibacterial agents as well as immunomodulatory measures could be beneficial in the management of this disease.

The improved survival of experimental animals fed with fish oil is suppressed by a leukotriene inhibitor.

Fish oil is believed to alter the immune response and improve survival after infections in experimental animals. This effect may be due to altered production of the leukotrienes (LT). We, therefore, performed a study in order to evaluate whether the effect of fish oil on the immune response of experimental animals is mediated through altered production of the LT. Female NMRI mice in four groups were fed with fish oil, fish oil with 5-lipoxygenase (5-LO) inhibitor (Zileuton, Abbott Laboratories, Chicago, IL, USA), corn oil or corn oil with 5-LO inhibitor. After 6 weeks, the mice were infected with Klebsiella pneumoniae and the survival was monitored. The experiment was performed twice. Analysis was performed mainly on data pooled from both experiments. The survival of the groups fed with fish oil was increased, compared to that of all the other groups and when compared to the groups fed with fish oil with 5-LO inhibitor (log-rank test) the difference was significant (P = 0.007). It has been postulated that the effect of fish oil on the immune system is mediated through altered production of LT. In our study, blocking of the production of the LT eliminated the beneficial effects of fish oil. Our results are in concord with the hypothesis that the effect of fish oil is, at least partly, mediated through altered production of LT.

Pathogenesis of seronegative arthritis.

The concept of seronegative spondarthritis, linking several diseases around ankylosing spondylitis, has received considerable clinical and genetic support, especially through the discovery of a high frequency of HLA-B27 in these disorders. Exogenous factors would appear to be responsible for some manifestations of the disease, but the role of Klebsiella micro-organisms is equivocal, and dietary control does not affect clinical manifestations. Increased serum and salivary IgA antibodies in active ankylosing spondylitis patients tend to suggest that IgA may act as an acute-phase reactant.