Time to Burn? Characteristics of Hydroxocobalamin Administration in an Academic Medical Center.

Background/Objective: Hydroxocobalamin is indicated for cyanide poisoning and its package insert states it should be given "without delay". We sought to evaluate time to administration and clinical characteristics when hydroxocobalamin was administered in a quaternary care academic medical center. Methods: All hydroxocobalamin administrations from January 1, 2007 to December 31, 2018 were analyzed. Data points recorded were: carboxyhemoglobin, cyanide and methemoglobin levels, hospital time and course, time and dose of hydroxocobalamin administration, lactate and bicarbonate levels, initial and nadir pH, initial heart rate, and initial and lowest systolic blood pressure. Results: Fifty-six cases were identified. One case was excluded as hydroxocobalamin was administered for nitroprusside toxicity. Among 55 cases analyzed, 93% (n = 51) were adults. Median hospital length of stay was 4.3 days (IQR 2.5 to 12). Burn, inhalation injury, and smoke inhalation were 80% of admitting diagnoses. Median time to hydroxocobalamin administration was 208 minutes (IQR 62.5 to 330). Eleven of 55 cases died. Hydroxocobalamin was given within 60 minutes of arrival in 12 cases, of which 3 died. All adults received 5 g of hydroxocobalamin. Time to hydroxocobalamin administration was longer in death cases [median: 221 minutes (IQR 119 to 594)] vs survivors [median: 184.5 minutes (IQR 62.8 to 315)]. Seventeen cases had cyanide levels drawn, with 9 being measurable, but none were toxic. Conclusions: Significant delay in hydroxocobalamin administration was seen in this study. Cases that resulted in death had significantly longer times to hydroxocobalamin administration. Further studies are warranted to identify reasons for delays in hydroxocobalamin administration.

Convergence of plasmid architectures drives emergence of multi-drug resistance in a clonally diverse Escherichia coli population from a veterinary clinical care setting.

The purpose of this study was to determine the plasmid architecture and context of resistance genes in multi-drug resistant (MDR) Escherichia coli strains isolated from urinary tract infections in dogs. Illumina and single-molecule real-time (SMRT) sequencing were applied to assemble the complete genomes of E. coli strains associated with clinical urinary tract infections, which were either phenotypically MDR or drug susceptible. This revealed that multiple distinct families of plasmids were associated with building an MDR phenotype. Plasmid-mediated AmpC (CMY-2) beta-lactamase resistance was associated with a clonal group of IncI1 plasmids that has remained stable in isolates collected up to a decade apart. Other plasmids, in particular those with an IncF replicon type, contained other resistance gene markers, so that the emergence of these MDR strains was driven by the accumulation of multiple plasmids, up to 5 replicons in specific cases. This study indicates that vulnerable patients, often with complex clinical histories provide a setting leading to the emergence of MDR E. coli strains in clonally distinct commensal backgrounds. While it is known that horizontally-transferred resistance supplements uropathogenic strains of E. coli such as ST131, our study demonstrates that the selection of an MDR phenotype in commensal E. coli strains can result in opportunistic infections in vulnerable patient populations. These strains provide a reservoir for the onward transfer of resistance alleles into more typically pathogenic strains and provide opportunities for the coalition of resistance and virulence determinants on plasmids as evidenced by the IncF replicons characterised in this study.

Phylogenomic approaches to determine the zoonotic potential of Shiga toxin-producing Escherichia coli (STEC) isolated from Zambian dairy cattle.

This study assessed the prevalence and zoonotic potential of Shiga toxin-producing Escherichia coli (STEC) sampled from 104 dairy units in the central region of Zambia and compared these with isolates from patients presenting with diarrhoea in the same region. A subset of 297 E. coli strains were sequenced allowing in silico analyses of phylo- and sero-groups. The majority of the bovine strains clustered in the B1 'commensal' phylogroup (67%) and included a diverse array of serogroups. 11% (41/371) of the isolates from Zambian dairy cattle contained Shiga toxin genes (stx) while none (0/73) of the human isolates were positive. While the toxicity of a subset of these isolates was demonstrated, none of the randomly selected STEC belonged to key serogroups associated with human disease and none encoded a type 3 secretion system synonymous with typical enterohaemorrhagic strains. Positive selection for E. coli O157:H7 across the farms identified only one positive isolate again indicating this serotype is rare in these animals. In summary, while Stx-encoding E. coli strains are common in this dairy population, the majority of these strains are unlikely to cause disease in humans. However, the threat remains of the emergence of strains virulent to humans from this reservoir.