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Study Notes Failure of Oral Third Generation Cephalosporins to Treat Shigellosis

Oral third-generation cephalosporins failed to treat Shigella sonnei infections despite in vitro susceptibility in 4 cases.

Failure of oral third-generation cephalosporins to treat Shigella sonnei infections highlights the need for a review of recommended treatments amid increasing antibiotic resistance, a new study found.

The study, published in Open Forum Infectious Diseases, examined 4 cases of shigellosis reported to the US Centers for Disease Control and Prevention (CDC) by state health departments in Massachusetts, New Jersey, Rhode Island and Tennessee.

“We describe four patients with Shigella sonnei infection who experienced treatment failure with oral third-generation cephalosporin antibiotics, even though their isolates were susceptible in vitro,” Jennifer Collins, MD, an epidemiologist in the CDC’s Enteric Diseases Prevention Branch and the lead author, told Contagion®.

“These cases highlight the need for prospective studies comparing oral third-generation cephalosporins with recommended antibiotics. This is particularly important given increasing antibiotic resistance among Shigella.”

The study noted that groups at higher risk of infection include young children, travelers to developing countries, men who have sex with men, and immunocompromised persons.

The cases examined in the study included a 51-year-old man with poorly controlled HIV infection, a 32-year-old man who had reported sexual contact with men, a 41-year-old man with HIV infection, and a 22-year-old woman who developed symptoms while visiting Ireland.

“Two patients who received IV ceftriaxone had protracted infections, even though their isolates were susceptible to this,” Collins Contagion®.

“As we discuss in the paper, this may have been related to host factors, severe illness, or short duration of therapy. However, it is concerning given ceftriaxone is the third-generation cephalosporin recommended for treatment of shigellosis in clinical guidelines.”

Case 1 received 4 days of IV ceftriaxone, then was transitioned to oral cefpodoxime. His symptoms recurred and he was given 4 weeks of IV ceftriaxone. Case 2 received oral ciprofloxacin, which was changed to oral azithromycin, and then oral cefixime, before a 5-day course of IV ceftriaxone was administered.

Case 3 took ciprofloxacin for 7 days. Symptoms recurred and he received a 10-day course of oral cefdinir, and 5-weeks later, a 7-day course of outpatient ceftriaxone. Case 4 started with oral ciprofloxacin and improved, but symptoms recurred and she was given 5 days of oral cefixime, followed by a second 5-day round of cefixime.

“We want providers to be aware of the potential for clinical and microbiological treatment failure when oral third-generation cephalosporins are used to treat shigellosis,” Collins told Contagion®.

The CDC’s National Antimicrobial Resistance Monitoring System laboratory will continue to collaborate with state health departments to monitor antibiotic resistance trends.

“We hope researchers will implement prospective studies comparing oral third-generation cephalosporins with recommended antibiotics,” Collins said.

Drug-resistant Shigella was listed among pathogens that pose serious threats, according to the CDC’s “biggest threats” report on antibiotic-resistant pathogens. A Failure of oral third-generation cephalosporins to treat Shigella sonnei infections highlights the need for a review of recommended treatments amid increasing antibiotic resistance, a new study found.

The study, published in Open Forum Infectious Diseases, examined 4 cases of shigellosis reported to the US Centers for Disease Control and Prevention (CDC) by state health departments in Massachusetts, New Jersey, Rhode Island and Tennessee.

“We describe 4 patients with Shigella sonnei infection who experienced treatment failure with oral third-generation cephalosporin antibiotics, even though their isolates were susceptible in vitro,” Jennifer Collins, MD, an epidemiologist in the CDC’s Enteric Diseases Prevention Branch and the lead author, told Contagion®.

“These cases highlight the need for prospective studies comparing oral third generation cephalosporins with recommended antibiotics. This is particularly important given increasing antibiotic resistance among Shigella.”

The study noted that groups at higher risk of infection include young children, travelers to developing countries, men who have sex with men, and immunocompromised persons.

The cases examined in the study included a 51-year-old man with poorly controlled HIV infection, a 32-year-old man who had reported sexual contact with men, a 41-year-old man with HIV infection, and a 22-year-old woman who developed symptoms while visiting Ireland.

“Two patients who received IV ceftriaxone had protracted infections, even though their isolates were susceptible to this,” Collins Contagion®.

“As we discuss in the paper, this may have been related to host factors, severe illness, or short duration of therapy. However, it is concerning given ceftriaxone is the third-generation cephalosporin recommended for treatment of shigellosis in clinical guidelines.”

Case 1 received 4 days of IV ceftriaxone, then was transitioned to oral cefpodoxime. His symptoms recurred and he was given 4 weeks of IV ceftriaxone. Case 2 received oral ciprofloxacin, which was changed to oral azithromycin, and then oral cefixime, before a 5-day course of IV ceftriaxone was administered.

Case 3 took ciprofloxacin for 7 days. Symptoms recurred and he received a 10-day course of oral cefdinir, and 5-weeks later, a 7-day course of outpatient ceftriaxone. Case 4 started with oral ciprofloxacin and improved, but symptoms recurred and she was given 5 days of oral cefixime, followed by a second 5-day round of cefixime.

“We want providers to be aware of the potential for clinical and microbiological treatment failure when oral third-generation cephalosporins are used to treat shigellosis,” Collins told Contagion®.

The CDC’s National Antimicrobial Resistance Monitoring System laboratory will continue to collaborate with state health departments to monitor antibiotic resistance trends.

“We hope researchers will implement prospective studies comparing oral third-generation cephalosporins with recommended antibiotics,” Collins said.

Drug-resistant Shigella was listed among pathogens that pose serious threats, according to the CDC’s “biggest threats” report on antibiotic-resistant pathogens. A 2016 study of 32 clusters of Shigella infection in reported between 2011 and 2015 found antimicrobial resistance in 9 clusters, including 2 resistant to ceftriaxone, 7 to azithromycin and 3 to ciprofloxacin.

of 32 clusters of Shigella infection in reported between 2011 and 2015 found antimicrobial resistance in 9 clusters, including 2 resistant to ceftriaxone, 7 to azithromycin and 3 to ciprofloxacin.