Case Presentation: 34 year old lady with AML presented with diarrhea of 2 days duration and was found to be positive for Salmonella on GI PCR, which was subsequently confirmed on stool culture.She was started on Ciprofloxacin for treatment and discharged. Returned 2 days later with resolved diarrhea but was febrile and now found to have blood culture positive for non typhi Salmonella over the next 3 days.Overall, patient had been on ciprofloxacin for at least 5 days with persistent positive culture for Salmonella.Patient’s isolate was consistently reported positive with ciprofloxacin MIC reported as ≤0.5 (Sensitive). Is this really susceptible?

Discussion: Drug resistant non typhi salmonella poses a serious threat level according to the CDC. There are over 1200,000 salmonella infections reported per year of which over 100,000 are drug resistant. Resistance to a first line agent is defined as resistance to one or more of the following agents :Ampicillin,ceftriaxone,ciprofloxacin and/or bactrim.Compared with stool isolates, blood isolates are associated with resistance to more than one agent,often more than 3 drug classes,including first line agents.Ceftriaxone resistance increased significantly for blood isolates,doubling from 2.5% to 5% between 1996-2007 and Ciprofloxacin resistance stands at 4.5%.
Salmonella bacteremia is more common in drug resistant than susceptible infections and fluoroquinolone resistance is associated with >3 fold increased risk of invasive illness or death within 90 days.Historically,high level Fluoroquinolone resistance is defined as MIC >4, however over the past decade strains of salmonella with decreased ciprofloxacin susceptibility (DCS) have emerged,defined as MICs of 0.12-1.0 while sensitive strains aka Wild type salmonella have MICs 0.008-0.06.Due to emergence of FQ resistance,in 2012 CLSI approved <0.06 as susceptibility breakpoint for salmonella typhi and all extraintestinal isolates of salmonella, including non typhi serovars.The discrepancy in reported sensitivities in our case arose from the fact that most US labs use FDA breakpoints which groups non typhi salmonella with other Enterobacteraciae with sensitive MIC of <1.When tested according to the CLSI breakpoints,the MIC of our isolate was 0.4,consistent with a reduced susceptibility strain rather than a truly susceptible strain.The patient then cleared blood culture after switching antibiotics to Ertapenem.

Conclusions: For all extraintestinal non typhi serovars of Salmonella,it is appropriate to use CLSI breakpoints of FQ sensitivity to guide treatment.Sensitive CLSI breakpoints are substantially lower at <0.06 compared to FDA breakpoints of MIC < 1.Therefore reportedly sensitive strains may actually have reduced susceptibility and present as antibiotic failure in spite of treatment.It is appropriate to use an alternate agent in these cases.