Stewardship / Resistance Scan for Jan 14, 2022

Fosfomycin for UTIs
Candida auris resistance

Mixed results in trial of fosfomycin for bacterimic urinary tract infections

A randomized clinical trial found that fosfomycin did not demonstrate noninferiority to comparator antibiotics for bacteremic urinary tract infections (bUTIs) caused by multidrug-resistant (MDR) Escherichia coli, but it could remain an option for select patients, researchers reported yesterday in JAMA Network Open.

In the trial, which included patients recruited from 22 Spanish hospitals from June 2014 through December 2018, investigators randomly assigned 70 participants to receive intravenous fosfomycin disodium and 73 to receive ceftriaxione or meropenem (if the infection was resistant to ceftriaxone). The primary outcome was clinical and microbiologic cure (CMC) 5 to 7 days after finalization of treatment. The noninferiority margin was 7%.

The rates of CMC were 68.6% in the fosfomycin group and 78.1% in the comparator group (difference, –9.4 percentage points). While fosfomycin failed to achieve noninferiority criteria, the study authors note that it was not due to lack of efficacy. Clinical failure rates were lower in the fosfomycin patients (14.3% vs 19.7%; difference, –5.4 percentage points). And among patients with severe sepsis, the CMC rate was higher in the fosfomycin group (86.7%) than in the comparator group (72.7%), a finding the authors say reinforces the idea that fosfomycin is efficacious in this infection.

In addition, an exploratory analysis of 38 patients who underwent rectal colonization studies found that none of the patients treated with fosfomycin acquired a new ceftriaxone- or meropenem-resistant gram-negative bacterial infection, compared with 23.5% in the comparator group.

However, six patients in the fosfomycin group had to discontinue treatment, four of them because of heart failure.

"Fosfomycin did not demonstrate noninferiority in the treatment of bUTI caused by MDR E coli," the authors wrote. "However, the data suggest that the drug is effective and may be considered among selected patients, particularly those without previous heart disease and with low risk of sodium overload–related problems." 

The authors of an accompanying commentary conclude that the results suggest that fosfomycin, a drug discovered more than 50 years ago, may have utility as a carbapenem-sparing strategy for extended-spectrum beta-lactam E coli infections, and should be further explored.
Jan 13 JAMA Netw Open study
Jan 13 JAMA Netw Open commentary


Rising echinocandin resistance found in NY Candida auris isolates

A study of clinical Candida auris isolates from New York shows increasing resistance to echinocandins, researchers reported this week in Antimicrobial Agents and Chemotherapy.

The researchers looked at clinical C auris isolates from healthcare facilities in New York and New Jersey, which together accounted for 55% of US C auris cases reported from 2016 through 2020. Among the 1,148 isolates from 697 patients in New York, all were resistant to fluconazole from 2016 through 2019, with resistance dropping slightly in 2020 (99.6%). Amphotericin B resistance fell from 82.1% in 2016 to 45.3% in 2019.

There was no resistance to echinocandins among the 2016 isolates, but echinocandin resistance rose to 4% by 2020. Ten isolates were found to be resistant to all three antifungals.

Among the 134 isolates from 121 patients in New Jersey, all were resistant to fluconazole, none were resistant to echinocandins, and amphotericin B resistance fell from 66.7% in 2017 to 31.1% in 2020.

The study authors said the precise mechanism behind differences in echinocandin resistance and pan-resistance between the New York and New Jersey isolates is unclear. "The observed resistance pattern might reflect intraregional differences in antifungal treatment practices, but further investigations are needed for confirmation," they wrote.

In its most recent update last fall, the Centers for Disease Control and Prevention (CDC) reported a total of 938 confirmed C auris infections in 21 states from September 2020 through August 2021, along with 3,034 patients colonized with the organism. The MDR yeast, which spreads easily in healthcare settings and can cause severe and deadly invasive infections in immunocompromised patients, was first identified in Japan in 2009 and first appeared in the United States in 2013.
Jan 10 Antimicrob Agents Chemother abstract
Oct 27 CDC Candida auris update

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