Elongation factor P (EF-P) is posttranslationally modified at a conserved lysyl residue by the coordinated action of two enzymes, PoxA and YjeK. We have previously established the importance of this modification in Salmonella stress resistance. Here we report that, like poxA and yjeK mutants, Salmonella strains lacking EF-P display increased susceptibility to hypoosmotic conditions, antibiotics, and detergents and enhanced resistance to the compound S-nitrosoglutathione. The susceptibility phenotypes are largely explained by the enhanced membrane permeability of the efp mutant, which exhibits increased uptake of the hydrophobic dye 1-N-phenylnaphthylamine (NPN). Analysis of the membrane proteomes of wild-type and efp mutant Salmonella strains reveals few changes, including the prominent overexpression of a single porin, KdgM, in the efp mutant outer membrane. Removal of KdgM in the efp mutant background ameliorates the detergent, antibiotic, and osmosensitivity phenotypes and restores wild-type permeability to NPN. Our data support a role for EF-P in the translational regulation of a limited number of proteins that, when perturbed, renders the cell susceptible to stress by the adventitious overexpression of an outer membrane porin.

BackgroundIn the management of bacteremia, positive repeat blood cultures (persistent bacteremia) are associated with increased mortality. However, blood cultures are costly and it is likely unnecessary to repeat them for many patients. We assessed predictors of persistent bacteremia that should prompt repeat blood cultures.MethodsWe conducted a retrospective cohort study of bacteremias at an academic hospital from April 2010 to June 2014. We examined variables associated with patients undergoing repeat blood cultures, and with repeat cultures being positive. A nested case control analysis was performed on a subset of patients with repeat cultures.ResultsAmong 1801 index bacteremias, repeat cultures were drawn for 701 patients (38.9 %), and 118 persistent bacteremias (6.6 %) were detected. Endovascular source (adjusted odds ratio [aOR], 7.66; 95 % confidence interval [CI], 2.30-25.48), epidural source (aOR, 26.99; 95 % CI, 1.91-391.08), and Staphylococcus aureus bacteremia (aOR, 4.49; 95 % CI, 1.88-10.73) were independently associated with persistent bacteremia. Escherichia coli (5.1 %, P = 0.006), viridans group (1.7 %, P = 0.035) and β-hemolytic streptococci (0 %, P = 0.028) were associated with a lower likelihood of persistent bacteremia. Patients with persistent bacteremia were less likely to have achieved source control within 48 h of the index event (29.7 % vs 52.5 %, P < .001), but after variable reduction, source control was not retained in the final multivariable model.ConclusionsPatients with S. aureus bacteremia or endovascular infection are at risk of persistent bacteremia. Achieving source control within 48 h of the index bacteremia may help clear the infection. Repeat cultures after 48 h are low yield for most Gram-negative and streptococcal bacteremias.

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Our objective was to evaluate whether patients with bacteraemic urinary tract infection (UTI) who receive inadequate empirical therapy have worse outcomes than those with adequate therapy. This was a retrospective cohort study of patients with bacteraemic UTI. The exposure variable was adequate versus inadequate empirical antibiotic therapy (AEAT versus IEAT) within 24 h of culture collection. Primary endpoint was time to cure. The primary analysis used propensity score models with inverse probability of treatment weights. A secondary Cox proportional hazards modelling approach was used to test the robustness of this finding, and to evaluate other patient and pathogen predictors of time to cure. Of 469 patients with bacteraemic UTI, 368 (78.5%) received AEAT. There was no significant difference in mortality between those receiving AEAT and those receiving IEAT (adjusted OR 0.86, 95%CI 0.47e1.58). Receipt of AEAT had no association with time to cure (HR 0.93, 95%CI 0.73e1.19, p 0.55) or time to normalization of individual clinical variables. Cox proportional hazards modelling revealed that longer time to cure was associated with liver disease (HR 0.25, 95%CI 0.08e0.76, p 0.015), prior stroke (HR 0.73, 95%CI 0.54e0.99, p 0.044), empirical receipt of piperacillinetazobactam (HR 0.77, 95%CI 0.59e0.99, p 0.044), qSOFA score >1 (HR 0.68, 95%CI 0.55e0.84, p < 0.001), and hospital-onset UTI (HR 0.53, 95%CI 0.39e0.71, p < 0.001). In conclusion, we found no association between AEAT and time to cure for patients with bacteraemic UTI. It may be appropriate to accept a higher risk threshold when choosing empirical antibiotic regimens, even in centres with high rates of resistant uropathogens.