Mortality and associated risk factors in consecutive patients admitted to a UK NHS trust with community acquired bacteraemia.

PURPOSE: Within the UK, there is lack of contemporary data on clinical outcomes in patients admitted to hospital with severe community acquired infection. The purpose of this study was to determine outcomes and risk factors associated with mortality in consecutive patients admitted to a UK NHS trust with community acquired infections that cause bacteraemia. METHODS: From September 2007 to August 2008, demographic, clinical and microbiological data were collected on patients with laboratory confirmed bacteraemia. Multivariate logistic regression was used to determine the association between predicted variables and likelihood of death. RESULTS: 686 bacteraemic episodes occurred in 681 patients. The most common sites of infection were non-catheter associated urinary tract infections (140, 20.4%) and biliary tract infections (62, 9.1%). The most common organisms were Escherichia coli (238, 34.7%), Staphylococcus aureus (84, 12.2%) and Streptococcus pneumoniae (40, 5.8%). Of the E coli infections, extended spectrum ß-lactamase (ESBL) producers accounted for 21/238 (8.8%), and of the S aureus infections, methicillin resistant S aureus (MRSA) accounted for 14/84 (16.7%). 124 (18.2%, 95% CI 15.3% to 21.1%) people died within 7 days and 170 (25.0%, 95% CI 21.7% to 28.2%) within 30 days. Age (OR 2.17, 95% CI 1.54 to 3.06), Charlson comorbidity index (OR 1.21, 95% CI 1.10 to 1.34), and Pitt score (OR 1.49, 95% CI 1.32 to 1.67) were highly significantly associated with 30 day mortality (p<0.001). Delay in appropriate antibiotic treatment (OR 1.35, 95% CI 1.05 to 1.75) and an undefined site of infection (OR 2.05, 95% CI 1.19 to 3.53) were less significantly associated with 30 day mortality (p<0.05). CONCLUSION: The 30 day mortality rate in consecutive patients with community acquired bacteraemic infection was 25.0%. These figures could be used as performance indicators to compare outcomes in different UK NHS trusts. With the exception of delay in appropriate antibiotic treatment, predictors of mortality at 30 days were non-modifiable.

Activation of JNK in sensory neurons protects against sensory neuron cell death in diabetes and on exposure to glucose/oxidative stress in vitro.

Diabetes activates all three groups of MAP kinases in sensory ganglia. Inhibition of this activation for the ERK and p38 groups prevents nerve damage, and agents that improve neuronal function in diabetic rats-antioxidants and aldose reductase inhibitors-also inhibit activation of ERK and p38 in dorsal root ganglia (DRG). However, these same treatments consistently increase activation of JNK. Thus, in DRG from rats with streptozotocin (STZ)-induced diabetes of 12-week duration, the p54/56 isoforms of JNK were activated by 2.75 compared to controls (P <.05). In DRG from diabetic rats treated with a gamma-linolenic acid and alpha-lipoic acid diester (GLA/LA), the activity of the p54/56 isoform was 3.75 that of controls and the p46 isoform was also increased to 1.75 that of controls (both P <.05 compared to both controls and untreated diabetics). We therefore tested the hypothesis that JNK activation is protective. Exposure of rats to diabetes increased activation of JNK in DRG, but treatment with GLA/LA increased this effect (P <.05). Specific inhibition of JNK in primary cultures of DRG neurons using a peptide inhibitor of JNK (JNKi1, 159-600-R100, 7.5 micro M, Alexis Biochemicals) increased the release of LDH and reduced MTT staining; both findings indicate an increase in neuronal damage. Taken together these findings indicate that multiple isoforms of JNK were activated in sensory neurons of diabetic rats, probably by a combination of raised glucose and oxidative stress, and that this activation of JNK serves to protect the neurons from damage.