Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

Chapter 11 Posttravel Evaluation

Antimicrobial Resistance

D. Cal Ham, Joseph Lutgring, Aditya Sharma

Antimicrobial resistance enables microbes to avoid or diminish the effects of antimicrobial agents and is acquired either through mutation or the acquisition of resistance genes. Antimicrobial-resistant organisms can cause infections that are difficult to treat, often requiring the use of expensive, less effective, or more toxic alternative medications (www.cdc.gov/drugresistance/about.html). Resistance can occur in viral, bacterial, fungal, and parasitic pathogens. The epidemiology of resistant organisms often varies globally from that seen in the United States. Travelers and medical professionals should be aware of the risk of acquisition of resistant organisms during international travel and consider travel history when caring for patients, both to identify effective treatment for infections and to ensure infection control interventions are in place to prevent spread of antimicrobial resistance.

The focus of this section is on resistant bacteria and an emerging fungal pathogen; neither are covered in pathogen-specific chapters. These microbes can be acquired both from health care and community exposures during international travel, causing illness or asymptomatic colonization. Additional information about organism-specific resistance can be found in the disease specific sections of Chapter 4, Travel-Related Infectious Diseases, and in Chapter 9, Medical Tourism.

INFECTIOUS AGENTS AND EPIDEMIOLOGY

Antimicrobial-Resistant Organisms of Concern in the Community

Globally, use of health care services, use of anti­microbials in agriculture, and inadequate sanitation and water purification systems are associated with the emergence and spread of resistance at the community level. Resistance in the community can take many forms. Two categories of importance to travelers are the microorganisms that cause diarrhea and those that result in long-term intestinal colonization and sometimes extraintestinal infections.

Bacteria that cause diarrhea include a variety of enteric pathogens such as Escherichia coli O157, Campylobacter jejuni, Salmonella spp., and Shigella spp. Resistance to first-line anti­microbials among these enteric pathogens has risen worldwide in recent years, posing new challenges for treatment decisions. Please refer to Chapter 4, for further details of antimicrobial resistance in specific bacteria.

Intestinal colonization with bacteria is influenced by diet, exposure to agents (such as antibiotics) that disrupt the microbial flora, interaction with other humans or animals, and contact with the environment. Enterobacteriaceae, such as Escherichia coli and Klebsiella pneumoniae, commonly inhabit the human gut and can be transmitted silently between close contacts, including household members. Intestinal colonization with Enterobacteriaceae is usually asymptomatic; however, these bacteria may also cause a range of extraintestinal infections—most commonly urinary tract infections and less frequently bacteremia.

Enterobacteriaceae resistant to critically important antibiotics, such as extended-spectrum cephalosporins, carbapenems, and colistin, have been isolated from a wide range of community sources, including healthy people, animals, produce, meat, and drinking water. Consumption of foods prepared by street vendors, taking an antibiotic during travel, and travelers’ diarrhea have been associated with intestinal colonization with antimicrobial-resistant Enterobacteriaceae. People with certain comorbidities, such as chronic bowel disease, are also more likely to become colonized with resistant Enterobacteriaceae during travel. Extraintestinal infections caused by Enterobacteriaceae resistant to extended-spectrum cephalosporins, carbapenems, or colistin may be more difficult to treat. Additionally, travelers colonized with antimicrobial-resistant Enterobacteriaceae can transmit these bacteria or their mechanisms of antimicrobial resistance to close contacts upon return to their countries of origin. The duration of intestinal colonization with antimicrobial-resistant Enterobacteriaceae after travel ranges from 1 month to >1 year.

The risk of intestinal colonization with antimicrobial-resistant Enterobacteriaceae during travel is related to the prevalence of resistant organisms in the country visited. Studies of returning travelers have identified a high risk of colonization with Enterobacteriaceae resistant to extended-spectrum cephalosporins when returning from countries in South America, Southeast Asia, South Asia, East Africa, northern Africa, and the Middle East; the risk of acquisition was highest after travel to Vietnam, India, and Peru. Acquisition of carbapenem-resistant Enterobacteriaceae (CRE) has been reported in travelers returning from South Asia and Southeast Asia. Colonization with E. coli resistant to the last-resort antibiotic colistin has been reported from travelers returning from countries in Europe (Portugal), the Caribbean, the Middle East, South America, Southeast Asia, East Asia, and northwest Africa.

Antimicrobial-Resistant Organisms of Concern in Health Care Settings

A patient history of recent hospitalization outside the United States has been associated with colonization or infection with antimicrobial-resistant organisms that are rare in the United States. This section describes organisms of concern for travelers with overseas health care exposures, such as hospitalization or surgery.

Gram-negative bacteria with resistance to broad-spectrum antibiotics, such as extended-spectrum cephalosporins, carbapenems, and colistin, cause infections that are difficult to treat and are of particular concern in health care settings because they have the potential for rapid spread to other patients. Resistance mechanisms of particular concern are extended-spectrum β-lactamases (ESBLs), carbapenemases, and mobile colistin resistance (MCR) genes, which confer resistance to extended-spectrum cephalosporins, carbapenems, and colistin, respectively. ESBL-producing gram-negative bacteria were originally described in health care settings but now have disseminated into communities globally, including in the United States. Carbapenemase-producing bacteria are often highly resistant to treatment. Although 1 carbapenemase, K. pneumoniae carbapenemase (KPC), emerged in the United States, other carbapenemases, which can be found in CRE, Pseudomonas aeruginosa, and Acinetobacter baumannii, have historically been associated with hospitalizations outside the United States.

Notably, there have been recent case reports of carbapenemase-producing CRE acquisition in travelers to South and Southeast Asia who did not have health care exposure; the rates of carbapenemase-producing CRE acquisition among healthy travelers are currently unknown. Bacteria harboring an MCR gene (such as mcr-1) appear to be primarily community associated and are often associated with ESBL-producing Enterobacteriaceae, although Enterobacteriaceae harboring MCR and carbapenemases have been reported from Asia and Europe.

Two hospital-based outbreaks of K. pneumoniae with MCR have been reported, from China and Portugal; the strain in the Portugal outbreak also produced a carbapenemase. Emergence of MCR in carbapenemase-producing CRE may result in rapid spread of strains with extremely limited treatment options in health care settings.

Antimicrobial-resistant gram-positive bacteria are a significant cause of health care–associated infections. Methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci (VRE) are endemic in the United States, and travelers hospitalized outside the United States may also become colonized or infected by these organisms. Transmissible linezolid resistance has been identified in gram-positive bacilli, including Staphylococcus aureus, coagulase-negative Staphylococcus, and Enterococcus spp. from several countries worldwide, particularly in South America. This resistance is of particular concern in VRE, for which treatment options are limited.

The fungal pathogen Candida auris has rapidly emerged worldwide, and multiple US patients with C. auris have reported prior health care exposures in countries with documented C. auris transmission. Cases have been reported in >20 countries and broader spread is suspected (www.cdc.gov/fungal/candida-auris/index.html). C. auris is distinct from other Candida species in its tendency to cause outbreaks in health care facilities, long duration of asymptomatic colonization of the skin, environmental persistence, and unusual levels of resistance to antifungals. Strains resistant to all 3 main classes of antifungal agents have been found in several countries but have not yet been identified in the United States. C. auris is frequently misidentified by routine laboratory diagnostics, which likely contributes to underdetection both domestically and outside the United States. Any Candida species isolated from patients who have received health care in the previous year in a country with documented C. auris transmission should be identified to the species level. Providers should notify public health agencies and implement infection control measures if suspected or confirmed C. auris is identified.

PREVENTION DURING TRAVEL

Community

In many countries, antibiotics may be readily available without prescription. Advise travelers seeking care for medical conditions while overseas, that although antibiotics may be procured easily, high-quality medical advice from a licensed practitioner is strongly suggested for assessing treatment options, including whether antibiotic treatment is indicated. Management of mild cough, upset stomach, diarrhea, and other simple ailments usually does not require an antibiotic. Over-the-counter medications for these minor health events should be included in the travel health kit for an international traveler. Use of antibiotics can predispose travelers to acquiring resistant bacteria.

Travelers and the clinicians treating them should be aware that common bacterial infections in destination countries may be resistant to first-line antimicrobials typically used in the United States. For example, enteric pathogens that cause travelers’ diarrhea in the Caribbean and South Asia are commonly resistant to fluoroquinolones. Therefore, if antibiotics are needed for treatment, an alternative antibiotic may be required. Evidence regarding effective therapies to prevent colonization or infection with a resistant organism in travelers is lacking; probiotics and bismuth-containing compounds are under investigation for this purpose.

Contaminated water may serve as a source of enteric bacteria, including E. coli, Salmonella spp., and Shigella spp. Drinking contaminated water confers a risk of transmission of enteric bacteria, including those that are resistant to antimicrobials. General safe water use recommendations apply to prevention of waterborne organisms. See Chapter 2, Water Disinfection, for CDC recommendations regarding water treatment.

Foods prepared under poor hygienic condi­tions may also be a source of enteric bacteria. Making safe food choices and paying careful attention to good hand hygiene can reduce the risk of exposure to these pathogens, including those that harbor antimicrobial resistance. See Chapter 2, Food & Water Precautions, for recommendations regarding food consumption and guidance on hand hygiene.

Health Care Settings

Patients admitted to health care facilities outside the United States, especially in low- and middle-income countries, may be at higher risk for acquiring antimicrobial-resistant organisms. These exposures may be facilitated by inadequate hand hygiene practices, insufficient environmental cleaning of health facilities, and irregular supply or use of personal protective equipment by health care workers. These gaps are more common in low-resource settings.

Information about infection prevention and control services in international health care settings is often limited. However, patients and health care workers traveling overseas, particularly in low- and middle-income countries, may reduce risk by choosing health facilities with active infection prevention and control programs. Travelers may also consider visiting health care facilities that have been accredited for infection prevention and control by national and international bodies. A health care facility accredited by an external body may have better-developed infection control practices than a nonaccredited facility. However, accreditation does not guarantee absence of risk of pathogen transmission in health care.

POSTTRAVEL CONSIDERATIONS

Some patients returning from international travel may be at higher risk for colonization and infection with resistant organisms depending on the location of their travel. Obtain an international travel history going back at least 12 months from all patients presenting for care. This information can play an important role in their clinical care and in the infection control practices employed during their clinical encounter.

Health Care Provider Guidance for Returning Travelers

CDC has pathogen-specific guidance for CRE and C. auris in patients who had a recent overnight stay in a health care facility outside the United States. Recommendations for CRE include:

  • When CRE is identified in a patient with a history of an overnight stay in a health care facility outside the United States in the past 6 months, the CRE isolate should be sent for confirmatory susceptibility testing and to determine the carbapenem resistance mechanism.
  • For patients admitted to health care facilities in the United States after hospitalization in facilities outside the United States within the past 6 months, consider rectal screening to detect CRE colonization and place patients in contact precautions while awaiting these screening cultures.

Additional recommendations for patients infected or colonized with CRE can be found in the CRE Toolkit (www.cdc.gov/hai/pdfs/cre/CRE-guidance-508.pdf) and https://stacks.cdc.gov/view/cdc/25250/cdc_25250_DS1.pdf.

Recommendations for C. auris

  • All isolates of Candida collected from the bloodstream or other normally sterile sites should be identified to the species level. Species identification for Candida isolates from nonsterile sites should be considered when the patient has had an overnight stay in a health care facility outside the United States in the previous year in a country with documented C. auris transmission.
  • Patients being treated for C. auris should be closely monitored for treatment failure.

Additional recommendations for providers caring for patients infected or colonized with C. auris can be found at www.cdc.gov/fungal/diseases/candidiasis/health-professionals.html.

BIBLIOGRAPHY

  1. Arcilla MS, van Hattem JM, Haverkate MR, Bootsma MCJ, van Genderen PJJ, Goorhuis A, et al. Import and spread of extended-spectrum β-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study. Lancet Infect Dis 2017;17:78–85.
  2. CDC. Antibiotic resistance threats in the United States, 2013. Atlanta, GA. Available from: www.cdc.gov/drugresistance/threat-report-2013.
  3. Chen L, Todd R, Kiehlbauch J, Walters M, Kallen A. Notes from the field: pan-resistant New Delhi Metallo-beta-lactamase-producing Klebsiella pneumoniae—Washoe County, Nevada, 2016. MMWR Morb Mortal Wkly Rep. 2017;66:33.
  4. Friedman DN, Carmeli Y, Walton AL, Schwaber MJ. Carbapenem-resistant Enterobacteriaceae: a strategic roadmap for infection control. Infect Control Hosp Epidemiol. 2017;38:580–94.
  5. George DB, Manges AR. A systematic review of outbreak and non-outbreak studies of extraintestinal pathogenic Escherichia coli causing community-acquired infections. Epidemiol Infect. 2010;138:1679–90.
  6. Liu YY, Wang Y, Walsh TR, Yi LX, Zhang R, Spencer J, et al. Emergence of plasmid-mediated colistin resistance mechanism MCR-1 in animals and human beings in China: a microbiological and molecular biological study. Lancet Infect Dis. 2016;16:161–8.
  7. Peirano G, Bradford PA, Kazmierczak KM, Badal RE, Hackel M, Hoban DJ, et al. Global incidence of carbapenemase-producing Escherichia coli ST131. Emerg Infect Dis. 2014;20:1928–31.
  8. Vincent C, Boerlin P, Daignault D, Dozois CM, Dutil L, Galanakis C, et al. Food reservoir for Escherichia coli causing urinary tract infections. Emerg Infect Dis. 2010;16:88–95.
  9. Woerther PL, Andremont A, Kantele A. Travel-acquired ESBL-producing Enterobacteriaceae: impact of colonization at individual and community level. J Travel Med. 2017;24:S29–34.
  10. World Health Organization. Antimicrobial resistance: global report on surveillance 2014. World Health Organization, Geneva, Switzerland. [cited 2018 Nov 6]. Available from: www.who.int/drugresistance/documents/surveillancereport/en.
TOP