ABSTRACT
BACKGROUND: In 2018, the Centers for Disease Control and Prevention and the Vermont Department of Health investigated an outbreak of multidrug-resistant Shigella sonnei infections in a retirement community that offered a continuum of care from independent living through skilled nursing care. The investigation identified 24 culture-confirmed cases. Isolates were resistant to trimethoprim-sulfamethoxazole, ampicillin, and ceftriaxone, and had decreased susceptibility to azithromycin and ciprofloxacin. METHODS: To evaluate clinical and microbiologic response, we reviewed inpatient and outpatient medical records for treatment outcomes among the 24 patients with culture-confirmed S. sonnei infection. We defined clinical failure as diarrhea (≥3 loose stools per day) for ≥1 day after treatment finished, and microbiologic failure as a stool culture that yielded S. sonnei after treatment finished. We used broth microdilution to perform antimicrobial susceptibility testing, and whole genome sequencing to identify resistance mechanisms. RESULTS: Isolates contained macrolide resistance genes mph(A) and erm(B) and had azithromycin minimum inhibitory concentrations above the Clinical and Laboratory Standards Institute epidemiological cutoff value of ≤16 µg/mL. Among 24 patients with culture-confirmed Shigella infection, 4 were treated with azithromycin; all had clinical treatment failure and 2 also had microbiologic treatment failure. Isolates were susceptible to ciprofloxacin but contained a gyrA mutation; 2 patients failed treatment with ciprofloxacin. CONCLUSIONS: These azithromycin treatment failures demonstrate the importance of clinical breakpoints to aid clinicians in identifying alternative treatment options for resistant strains. Additionally, these treatment failures highlight a need for comprehensive susceptibility testing and systematic outcome studies, particularly given the emergence of multidrug-resistant Shigella among an expanding range of patient populations.
Subject(s)
Dysentery, Bacillary , Shigella , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Azithromycin/pharmacology , Azithromycin/therapeutic use , Ciprofloxacin/pharmacology , Ciprofloxacin/therapeutic use , Disease Outbreaks , Drug Resistance, Bacterial/genetics , Dysentery, Bacillary/drug therapy , Dysentery, Bacillary/epidemiology , Humans , Macrolides/therapeutic use , Microbial Sensitivity Tests , Retirement , Shigella sonnei/genetics , Treatment Outcome , VermontABSTRACT
Ceftriaxone-resistant Salmonella enterica serotype Typhi (Typhi), the bacterium that causes typhoid fever, is a growing public health threat. Extensively drug-resistant (XDR) Typhi is resistant to ceftriaxone and other antibiotics used for treatment, including ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole (1). In March 2018, CDC began enhanced surveillance for ceftriaxone-resistant Typhi in response to an ongoing outbreak of XDR typhoid fever in Pakistan. CDC had previously reported the first five cases of XDR Typhi in the United States among patients who had spent time in Pakistan (2). These illnesses represented the first cases of ceftriaxone-resistant Typhi documented in the United States (3). This report provides an update on U.S. cases of XDR typhoid fever linked to Pakistan and describes a new, unrelated cluster of ceftriaxone-resistant Typhi infections linked to Iraq. Travelers to areas with endemic Typhi should receive typhoid vaccination before traveling and adhere to safe food and water precautions (4). Treatment of patients with typhoid fever should be guided by antimicrobial susceptibility testing whenever possible (5), and clinicians should consider travel history when selecting empiric therapy.
Subject(s)
Ceftriaxone/pharmacology , Disease Outbreaks , Drug Resistance, Microbial , Salmonella typhi/drug effects , Travel-Related Illness , Typhoid Fever/epidemiology , Typhoid Fever/microbiology , Adolescent , Adult , Aged , Ceftriaxone/therapeutic use , Child , Child, Preschool , Female , Humans , Infant , Iraq/epidemiology , Male , Middle Aged , Pakistan/epidemiology , Typhoid Fever/drug therapy , United States/epidemiology , Young AdultABSTRACT
A large outbreak of extensively drug-resistant (XDR) Salmonella enterica serotype Typhi infections is ongoing in Pakistan, predominantly in Sindh Province. Here, we report the sequencing and characterization of five XDR Salmonella Typhi isolates from the Punjab province of Pakistan that are closely related to the outbreak strain and carry the same IncY plasmid.
