We report the emergence of non-susceptibility to cefiderocol from a subpopulation of Pseudomonas aeruginosa recovered from a patient without history of cefiderocol exposure. Whole genome sequencing identified mutations in major iron transport pathways previously associated with cefiderocol uptake. Susceptibility testing should be performed before therapy with siderophore cephalosporins.

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Background:Rhinocerebral mucormycosis occurs in immunocompromised hosts with uncontrolled diabetes, solid organ transplants, and hematologic malignancies. Primary disease is in the paranasal sinuses but often progresses intracranially, via direct extension or angioinvasion. Rhinocerebral mucormycosis is rapidly fatal with a mortality rate of 85%, even when maximally treated with surgical debridement, antifungal therapy, and correction of underlying processes.Methods:We performed a retrospective chart review of patients with rhinocerebral mucormycosis from 2011 to 2014. These patients were analyzed for symptoms, surgical and medical management, and outcome. We found four patients who were diagnosed with rhinocerebral mucormycosis. All patients underwent rapid aggressive surgical debridement and were started on antifungal therapy on the day of diagnosis. Overall, we observed a mortality rate of 50%.Results:An early aggressive multidisciplinary approach with surgical debridement, antifungal therapy, and correction of underlying disease have been shown to improve survivability in rhinocerebral mucormycosis.Conclusion:A multidisciplinary approach to rhinocerebral mucormycosis with otolaryngology, neurosurgery, and ophthalmology, infectious disease and medical intensivists can help reduce mortality in an otherwise largely fatal disease. Even despite these measures, outcomes remain poor, and a high index of suspicion must be maintained in at-risk populations, in order to rapidly execute a multifaceted approach.

Based on our findings, daily 1 DS TMP/SMX prophylaxis did not appear to provide reliable protection against nocardiosis. However, we could not state definitely that TMP/SMX prophylaxis was or wasn't protective because of lack control group. None of the Fisher's exact tests revealed associations between the tested risk factors and either disease dissemination or mortality. This could be due to a true lack of association between the variables in each pair. However, it is also likely that our relatively small sample size limited our power to detect underlying relationships that may be present. Compared with other studies, 1-year mortality was lower at our institution (11% vs 16%).