key: cord-0868958-6xlnnsmi
authors: Leblebicioglu, Hakan; Rodriguez-Morales, Alfonso J.; Rossolini, Gian Maria; López-Vélez, Rogelio; Zahar, Jean-Ralph; Rello, Jordi
title: Management of infections in critically ill returning travellers in the intensive care unit—I: considerations on infection control and transmission of resistance()
date: 2016-04-28
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2016.04.019
sha: e60d298dcd915defe348f16660ed1cd16d865e12
doc_id: 868958
cord_uid: 6xlnnsmi

Depending on their destinations and activities, international travellers are at a significant risk of contracting both communicable and non-communicable diseases. On return to their home countries, such travellers may require intensive care. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and more recently Ebola haemorrhagic fever, has highlighted the risks. Other well-known communicable pathogens such as methicillin-resistant Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae have been described previously. However, malaria remains by far the most important cause of death. The issues related to imported antibiotic resistance and protection from highly contagious diseases are reviewed here. Surveillance strategies based on epidemiological data (country visited, duration of travel, and time elapsed since return) and clinical syndromes, together with systematic search policies, are usually mandatory to limit the risk of an outbreak. Single-bed hospital rooms and isolation according to symptoms should be the rule while awaiting laboratory test results. Because person-to-person contact is the main route of transmission, healthcare workers should implement specific prevention strategies.

Resistance Infection control Traveller ICU Migrant

Depending on their destinations and activities, international travellers are at a significant risk of contracting both communicable and non-communicable diseases. On return to their home countries, such travellers may require intensive care. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), and more recently Ebola haemorrhagic fever, has highlighted the risks. Other well-known communicable pathogens such as methicillin-resistant Staphylococcus aureus and carbapenemase-producing Enterobacteriaceae have been described previously. However, malaria remains by far the most important cause of death. The issues related to imported antibiotic resistance and protection from highly contagious diseases are reviewed here. Surveillance strategies based on epidemiological data (country visited, duration of travel, and time elapsed since return) and clinical syndromes, together with systematic search policies, are usually mandatory to limit the risk of an outbreak. Single-bed hospital rooms and isolation according to symptoms should be the rule while awaiting laboratory test results. Because person-to-person contact is the main route of transmission, healthcare workers should implement specific prevention strategies. healthcare settings, and the high mortality rates associated with invasive infections. 2 In principle, any of these pathogens can be encountered, either as colonizers or as infecting agents, in travellers returning from areas of endemicity and in patients repatriated from foreign healthcare facilities. Acquisition may be the consequence of exposure to contaminated food or environments, of close contact with colonized individuals, or of admission to hospitals and exposure to medical practices either for unexpected reasons (e.g., trauma, acute diseases) or for medical tourism (e.g., specialized surgery, organ transplantation). As has been clearly documented, the transmission of MRSA has increased with the growth of international travel, resulting in either asymptomatic colonization or clinically significant MRSA infections. 3, 4 Some evidence is also available for the international dissemination of VRE via transfer/ repatriation of patients from hospitals located in endemic areas. 5 Concerning Gram-negative organisms, the impact of international travel has been firmly established in the dissemination of MDR Enterobacteriaceae, including high-risk clones producing ESBLs (especially enzymes of the CTX-M type) and/or carbapenemases of various types (e.g., KPC, OXA-48, NDM, VIM). [6] [7] [8] The risk of the spread of MDR strains of Enterobacteriaceae in this situation includes not only Escherichia coli, Klebsiella spp, and Enterobacter spp, but also classical enterobacterial pathogens such as Salmonella enterica and Shigella spp, with evidence of imported cases of typhoid fever and shigellosis caused by MDR strains. 8, 9 The transmission of MDR Acinetobacter has been documented following the international transfer of patients from intensive care units (ICUs) in countries with high-level endemicity, 10 and the repatriation of evacuees involved in military operations in endemic areas. 11 Less evidence is available for the travel-related dissemination of MDR/XDR P. aeruginosa strains, but this is clearly a possibility following the transfer of colonized patients from ICUs where these strains are endemic or are causing outbreaks. 12 The admission to the ICU of patients colonized or infected by MDR/XDR pathogens is a matter of concern, since it may be followed by cross-infections and outbreaks in the ICU setting unless suitable infection control practices are enforced immediately. Moreover, infections caused by MDR/XDR pathogens may require different antimicrobial treatments from those routinely used in the ICU, which are based on the local epidemiology; this may result in inappropriate empiric treatment and thus increased morbidity and mortality.

Therefore, the possibility of carriage or infection by an MDR/ XDR pathogen should always be considered for critically ill returning travellers admitted to the ICU. A risk assessment should be performed, considering the area of provenance, the history of the patient, and the presence of additional risk factors for carriage or infection by similar resistant pathogens. 2, 12 The epidemiology of MDR/XDR pathogens may vary according to geographical area. The proportion of MRSA among S. aureus isolates remains very high in some European countries, the USA, Latin America, and the Far East, but is considerably lower in other European countries such as the Netherlands and the Scandinavian countries. 13 ESBL-producing Enterobacteriaceae are now disseminated worldwide, with very high rates detected among ICU patients in Latin America, the Asia-Pacific region, and the Middle East. 14 For their part, CPE have achieved a notable level of endemicity in some areas of Europe (e.g., Greece and Italy), the Middle East (e.g., Turkey, Israel), South America (e.g., Colombia), and China. 15 Travellers/patients from areas of high endemicity for MDR/XDR pathogens have a higher risk of exposure to these pathogens, and the possibility of being infected or colonized by these agents at the time of repatriation should always be considered. When consulting sources of information regarding resistance and endemicity (such as ProMED-mail, http://www. promedmail.org), clinicians should consider that (1) for several countries (especially low-income settings) epidemiological information is scarce or lacking, and (2) the epidemiology of MDR/XDR pathogens can change rapidly. So this information should be considered partial and should be updated regularly.

Exposure to medical practices in facilities from endemic areas, either unanticipated or scheduled, is an additional risk factor for carriage/infection by MDR/XDR pathogens. 16 Recommendations for ICUs, based on the current evidence, include the following:

(1) Carrying out a risk assessment for carriage/infection by MDR/ XDR pathogens for all ICU admissions of patients returning from international travel or transferred from foreign hospitals. 

Depending on their destinations and activities, international travellers are at a significant risk of contracting both communicable and non-communicable diseases. 17 The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and more recently Ebola haemorrhagic fever, has highlighted the risks. However, other well-known communicable pathogens such as MRSA 18 and CPE 19, 20 have been described previously. ICU patients, because of the severity of illness, the workload, and the antibiotic selection pressure, are important potential reservoirs of dangerous microorganisms. The most important challenges for ICU practitioners are first to identify admissions with the highest risk of communicable disease, and second to rapidly implement preventive measures in order to avoid nosocomial transmission.

Surveillance strategies for the early detection of unusual infectious disease events should be the rule. Syndromic surveillance can help to reduce the identification time. All patients transferred from hospitals in high-risk countries (Table 1) should be considered as potential carriers of MDR or highly drug-resistant microorganisms. All of these patients should be screened for rectal carriage at admission and a few days after any antibiotic therapy. 21 While awaiting screening results, the patient should be hospitalized in a single-bed room. Contact and body fluid precautions should be added. All patients with fever and clinical or radiographic evidence of pneumonia or acute respiratory distress syndrome, and with a history of travel from countries in or near the Arabian Peninsula (Bahrain, Iraq, Iran, Israel, the West Bank and Gaza, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, Syria, the United Arab Emirates, and Yemen) within 14 days before symptom onset, or close contact with a symptomatic traveller who developed fever and acute respiratory illness within 14 days after travelling from countries in the region, should be considered as potentially infected by MERS-CoV. 22 Viral haemorrhagic fever should be suspected in selected patients coming from Sub-Saharan Africa with fever and bleeding disorders, depending on the geographical origin and local epidemiological situation. A general syndromic approach to tropical infections in the ICU is described in Table 2 . 23 Although many imported infectious diseases may require ICU admission, the most frequent ones are relatively few in number. In a descriptive analysis of acute and potentially life-threatening tropical diseases among 82 825 ill Western travellers reported to GeoSentinel from 1996 to 2011, 3655 patients (4.4%) with 13 diseases were identified; falciparum malaria (76.9%), enteric fever (18.1%), and leptospirosis (2.4%) were the most frequent. Ninety-one percent of patients had fever. The median time from travel to presentation was 16 days. Thirteen (0.4%) patients died: 10 with falciparum malaria, two with melioidosis, and one with severe dengue. Falciparum malaria was mainly acquired in West Africa, enteric fever on the Indian subcontinent, and leptospirosis, scrub typhus, and murine typhus in Southeast Asia. 24 

Emergency departments at general hospitals are the first units to deal with an unknown highly contagious tropical infectious disease and they should be prepared for this eventuality (a heavy price was paid during the SARS outbreak). In an endemic area, MERS-CoV infection is more likely to be acquired in healthcare facilities than in the community: in the 2014 outbreak in Jeddah, Saudi Arabia, more than four out of five exposures were at healthcare facilities, mainly due to poor and insufficient isolation measures at admission. 25 Patients with suspected highly contagious tropical infectious diseases should be placed directly in an emergency department isolation room (if available) and should be examined and assessed as soon as possible. Standard precautions and cough and respiratory etiquette should be applied systematically. During admission, these patients should avoid any contact with other patients, and unprotected healthcare workers should avoid contact with them. If possible, point-of-care bedside laboratory tests should be used for sampling, or all analyses should be done in a biosafety level 3/4 laboratory. Samples should be inactivated (with formalin) before testing in a routine laboratory. Transfer to the ICU or to a high-level isolation unit must be carried out in a secure manner.

Many organisms are present in the ICU, but only a few are involved in person-to-person transmission. An overview of the precautions recommended for selected tropical infections and conditions is shown in Table 3 . 

ICUs attend patients who are severely ill and in some way immunocompromised because of underlying diseases and the use of invasive medical devices and technology in their care. Consequently, person-to-person transmission of pathogens may be frequent. Intensive care therapy should be performed in collaboration with the infectious disease team. The unit should be subjected to negative pressure if available. The duration of manual ventilation during resuscitation procedures should be kept to a minimum. Non-invasive positive pressure ventilation should be used instead of facial mask aerosol therapy when possible. Endotracheal intubation and cardiopulmonary resuscitation have been associated with increased SARS-CoV transmission among physicians and nurses in the ICU. Endotracheal intubation should be performed with rapid sequence induction by the most skilled person available, who should wear personal protective equipment. Meticulous infection control measures must be followed.

Invasive procedures should be avoided unless absolutely essential. Chest radiography, ultrasonography, bronchoscopy, and gastrointestinal endoscopy should be performed at the bedside, avoiding moving the patient unnecessarily; if not possible, these procedures should be performed in an air-controlled environment. Patients who require dialysis at their bedside should receive either peritoneal dialysis or haemodialysis, and dedicated haemodialysis machines and decontaminated dialysate should be designated as infectious waste.

Detailed tutorials and guidelines have been produced by the US Centers for Disease Control and Prevention (CDC), 26 the European Centre for Disease Prevention and Control (ECDC), 27 and the European Network for Infectious Diseases (EUNID). 28 There are also other guidelines focused on specific diseases such as Ebola virus disease (CDC) and Crimean-Congo haemorrhagic fever. 29, 30 New definitions of sepsis have different implications when applied in low-income and middle-income countries, 31 and a new paradigm for management should be developed. A research agenda highlighting the differences in approach between high-income and poor-resource scenarios is required.

Funding: None. Conflict of interest: The authors have no conflicts of interest to report.

JR and HL designed the manuscript: ARM and GMR prepared the section on emerging resistance. RLV and JRZ wrote the section on infection control. JR wrote the final version. The final version was approved by all authors.

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