Interim guidance on management of infections with a multidrug-resistant strain of Salmonella Newport

An Advisory Committee Statement (ACS)
Committee to Advise on Tropical Medicine and Travel (CATMAT)

Publication date: January 2023

Table of contents

• Preamble
• Key points
• Objective
• Patient management recommendations
• Patient education recommendations
• Additional resources and useful links
• Acknowledgements
• Conflict of interest
• References

Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides the Public Health Agency of Canada with ongoing and timely medical, scientific, and public health advice relating to tropical infectious disease and health risks associated with international travel. The Agency acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers.

Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.

Key points

• The Public Health Agency of Canada and multiple global authorities have observed an increase in antibiotic-resistant Salmonella infections among travellers returning from Mexico. The Salmonella causing these infections is a strain of multidrug-resistant Salmonella serotype Newport (MDR Salmonella Newport).
• MDR Salmonella Newport should be suspected in any patient with a >48 hour history of acute febrile diarrhoea and a recent travel history to Mexico.
• MDR Salmonella Newport shows broad resistance to most orally-provided antibiotics, including azithromycin, that is, the therapy often recommended for treatment of travel-related Salmonella Newport infections.
• Antibiotic treatment is not indicated for most cases of travel-associated diarrhea, but rather is ideally restricted to persons with severe bacteria-associated illness, and/or who are considered to be at relatively higher likelihood for poor outcomes if infected, such as, immunosuppressed, very young or old.
• MDR Salmonella Newport is unlikely to respond to oral antibiotics commonly used as empiric treatment for travellers' diarrhea. Suspected cases should have cultures done for confirmation early in the course of illness and empiric treatment, if needed, should be with broad spectrum intravenous antibiotics.

Objective

This statement provides guidance to health care providers for the management of patients with known or suspected MDR Salmonella Newport infection after travel to or from Mexico. CATMAT also aims to remind clinicians of management practices that apply to travellers' diarrhea more generally.

The recommendations made on this page are based on expert opinion. A formal evidence appraisal, such as Grading of Recommendations, Assessment, Development and Evaluation (GRADE), was not done.

For recommendations related to the prevention of travellers' diarrhea see the CATMAT statement on prevention of travellers' diarrhea.

Patient management recommendations

Consider MDR Salmonella Newport infection in the differential diagnosis of patients with symptoms compatible with salmonellosis (such as, diarrhea, fever, and abdominal cramps) and who have returned from Mexico in the 7 days preceding illness onset.

For most patients with Salmonella and other travel-related diarrheal illnesses, including MDR Salmonella Newport, treatment with antibiotics is of limited clinical value and may cause antibiotic-related harms, including prolonged asymptomatic Salmonella carriage, disturbance of the microbiome and selection for/colonization with drug resistant bacteria. Overuse of antibiotics is also considered one of the major global public health hazards^{Footnote 1}.

Routine use of antibiotics for treatment of travellers' diarrhea, including for patients potentially infected with MDR Salmonella Newport, should be avoided.

Antibiotic treatment is indicated for patients who are considered at greatest risk for poor outcomes, including people:

• with severe disease, bacteremia, extra-intestinal infections, and those with manifestations of sepsis. Severe disease has not been systematically defined in studies, but could include many bowel movements per day with evidence of dehydration, high fever persisting over several days, or signs of complicated enteritis such as cholecystitis or appendicitis.
• at relatively higher likelihood for invasive disease, such as:
  • infants younger than 3 months of age. Some experts would consider treatment for children below 12 months of age.
  • older adults. Although there is no clear evidence for an age threshold for complicated disease, age above 65 years has been suggested.
  • people with known vascular disease, or valvular or endovascular abnormalities (for example, grafts, prosthetic heart valves, cardiac valve disease)
  • people with immunosuppression from any cause, HIV infection, or sickle cell disease^{Footnote 2}
  • people with other conditions associated with invasive salmonellosis, such a large joint disease, recent malaria anemia, or RBC-transfusion dependence

Unfortunately, the relative risk of infection-associated complications in these groups remains poorly defined. However, we believe early antibiotic therapy in these populations is likely to reduce the risk for such complications.

Most MDR Salmonella Newport isolates from this travel-associated strain are not susceptible in vitro to antibiotics generally recommended for oral treatment.

If you're considering antibiotic treatment for a patient with known or suspected MDR Salmonella Newport infection following (within the last 7 days) travel to Mexico, we suggest the following approach be applied:

Diagnosis

• Among people possibly infected with MDR Salmonella Newport isolates as defined above, obtain appropriate cultures (for example, stool, urine, blood) for those with risk factors for invasive disease listed above. Severely ill patients should be tested promptly. Confirmation of MDR Salmonella, with full antibiogram results, typically has a turnaround time of 72 hours.
• Antibiotic susceptibility testing may not be routinely performed for gastrointestinal isolates. Consider contacting your laboratory to request antimicrobial susceptibility testing of any Salmonella isolate to guide the choice of antibiotic if antibiotic treatment is needed.

Treatment

• Limit use of antibiotics for patients with an acute diarrheal illness to those with clinical indications (see antibiotic treatment above).
• For empiric therapy when indicated, consider the resistance profile of this strain of MDR Salmonella Newport when selecting empiric treatment for patients who traveled to Mexico in the 7 days before illness began. The antibiotics commonly used for empiric treatment of diarrhea, such as azithromycin and fluoroquinolones, are likely to be ineffective.
• Ceftriaxone or alternative broad spectrum intravenous agent should be considered for empiric treatment.
  • Most isolates are susceptible to ceftriaxone.
  • Most isolates are resistant to ampicillin, ciprofloxacin, and trimethoprim-sulfamethoxazole.
  • Azithromycin may not be effective for treating this strain and should be used with caution. Most isolates carry a macrolide resistance gene and show an elevated minimum inhibitory concentration (>32 µg/ml) on laboratory testing. While clinical breakpoints to determine resistance in non-Typhi Salmonella strains have not been established for azithromycin, an epidemiologic cut-off value of 16ug/uL has been established for invasive non-typhoidal Salmonella in a multi-country study^{Footnote 3},^{Footnote 4}.
  • Cefixime and rifaximin may be active in vitro for this strain of Salmonella, but clinical data are currently lacking.
• Given the sporadic occurrence of unrelated cases of MDR Salmonella (various serogroups) in Canada, which are known to be resistant to ceftriaxone, critically ill patients with documented salmonellosis potentially unrelated to the strain reported here should receive an agent with little or no described resistance, such as a carbapenem, pending results of susceptibility testing^{Footnote 5}.
• Tailor antibiotic treatment to the results of antimicrobial susceptibility testing when possible.
• Consider consulting an infectious disease specialist for management of patients with MDR or complicated Salmonella infections.
• Advise patients about returning to work based on provincial health recommendations. Some provinces may require a negative stool test before a person can return to work in a high-risk setting (such as food preparation, childcare, or healthcare) after a Salmonella infection.

Patient education recommendations

Advise patients that they can take steps to prevent the spread of disease. People with diarrhea should:

• wash their hands thoroughly with soap and water for at least 20 seconds especially before and after eating, handling raw meat, petting an animal or after using the toilet. The benefits of hand washing.
• not share their food with others
• not prepare food for others
• follow provincial public health recommendations and occupational health guidance regarding return to higher risk occupations after Salmonella infections
• not swim or soak in shared bodies of water – including in pools, hot tubs, lakes, ponds, or the ocean – until they have fully recovered
• avoid sexual activities at increased risk for feco-oral transmission of Salmonella as these activities have been shown to increase the risk of person-person transmission of enteric pathogens
• be diligent about practicing good hygiene for at least several weeks after diarrhea ends; people with salmonellosis (and some other diarrheal illnesses) might continue to shed the bacteria in stool after symptoms resolve

Advise travellers that vaccination against Salmonella Typhi (that is, typhoid vaccine) does not protect against infection with Salmonella Newport or other similar strains. Travellers should always eat and drink safely abroad.

These habits can help protect travellers against other travel-associated illnesses, including travellers' diarrhea, typhoid, and paratyphoid fever.

Additional resources and useful links

• CATMAT - Statement on travellers' diarrhea
• CATMAT - Statement on international travellers and typhoid
• Health Canada - Salmonellosis (Salmonella)
• WHO – Salmonella (non-typhoidal)
• Eat and drink safely abroad
• Hand washing and staying healthy

Acknowledgements

This statement was prepared by the MDR Salmonella (Newport) Working Group: Libman M (Chair), Bui Y, Lagacé-Wiens P, Schofield S, and the CATMAT Secretariat and was approved by CATMAT.

CATMAT would like to thank Dr. Cédric Yansouni (external consultant) for his contribution to the statement. CATMAT also acknowledges the technical and administrative support from the Centre for Border and Travel Health at the Public Health Agency of Canada for the development of this statement.

CATMAT members: Libman M (Chair), Acharya A, Bogoch I, Bui Y, Greenaway C, Khatib A, Lagacé-Wiens P, Lee J, Plewes K, Vaughan S.

Liaison members: Angelo K (Centers for Disease Control and Prevention), Pernica J (Association of Medical Microbiology and Infectious Disease Canada), Viel-Thériault I (Canadian Paediatric Society).

Ex officio members: Marion D (Department of National Defence), Rossi C (Department of National Defence), Schofield S (Department of National Defence), and Zimmer R (Biologics and Radiopharmaceutical Drugs Directorate, Health Canada).

Conflict of Interest

None declared.