Treatment Of Traveler's Diarrhea Research Articles

Gut microbiome and antibiotic resistance effects during travelers' diarrhea treatment and prevention.

The travelers' gut microbiome is potentially assaulted by acute and chronic perturbations (e.g., diarrhea, antibiotic use, and different environments). Prior studies of the impact of travel and travelers' diarrhea (TD) on the microbiome have not directly compared antibiotic regimens, and studies of different antibiotic regimens have not considered travelers' microbiomes. This gap is important to be addressed as the use of antibiotics to treat or prevent TD-even in moderate to severe cases or in regions with high infectious disease burden-is controversial based on the concerns for unintended consequences to the gut microbiome and antimicrobial resistance (AMR) emergence. Our study addresses this by evaluating the impact of defined antibiotic regimens (single-dose treatment or daily prophylaxis) on the gut microbiome and resistomes of deployed servicemembers, using samples collected during clinical trials. Our findings indicate that the antibiotic treatment regimens that were studied generally do not lead to adverse effects on the gut microbiome and resistome and identify the relative risks associated with prophylaxis. These results can be used to inform therapeutic guidelines for the prevention and treatment of TD and make progress toward using microbiome information in personalized medical care.

Prescribing Patterns of Antibiotics for the Self-Treatment of Travelers' Diarrhea in Global TravEpiNet, 2009-2018.

BackgroundInternational travelers are often prescribed antibiotics for self-treatment of travelers’ diarrhea (TD), but the benefits and risks of antibiotics are debated. We assessed the prescribing patterns of empiric antibiotics for TD in international travelers evaluated at Global TravEpiNet (GTEN) sites (2009–2018). MethodsWe performed a prospective, multisite cross-sectional study regarding antibiotic prescriptions for the self-treatment of TD at 31 GTEN sites providing pretravel consultations to adult international travelers. We described traveler demographics, itineraries, and antibiotic(s) prescribed. We used multivariable logistic regressions to assess the association of year of consultation with antibiotic prescribing (yes/no) and class (fluoroquinolones vs azithromycin). We performed interrupted time-series analyses to examine differences in prescribing before and after the Food and Drug Administration (FDA) warning on fluoroquinolones (July 2016). ResultsAntibiotics were not prescribed in 23 096 (22.2%) of 103 843 eligible pretravel GTEN consultations; azithromycin and fluoroquinolones were most frequently prescribed. Antibiotic prescribing declined significantly each year between 2009 and 2018 (odds ratio [OR], 0.84; 95% CI, 0.79–0.89), as did fluoroquinolone prescribing, relative to azithromycin (OR, 0.77; 95% CI, 0.73–0.82). The rate of decline in fluoroquinolone prescribing was significantly greater after the FDA fluoroquinolone warning (15.3%/year) than before (1.1%/year; P < .001). ConclusionsEmpiric antibiotics for TD were prescribed in >75% of pretravel GTEN consultations, but antibiotic prescribing declined steadily between 2009 and 2018. Fluoroquinolones were less frequently prescribed than azithromycin, especially after the 2016 FDA fluoroquinolone warning. Emphasis on the risks of antibiotics may influence antibiotic prescribing by providers for empiric treatment of TD.

Diarrea del viajero

Traveller's diarrhoea (TD) is acquired primarily through ingestion of food and drinks contaminated with pathogens that cause diarrhoea. They can be bacteria, protozoa, helminths, and viruses. Globally, the most common causes of TD are two pathotypes of Escherichia coli (enterotoxigenic and enteroaggregative) and Campylobacter, although there are significant variations by geographic area visited. Most TD occurs in individuals traveling to low-middle income countries. The type of travel, length of stay, traveller's age, and the presence of certain underlying conditions are important risk factors to consider for the acquisition of TD. While TD is usually a mild and self-limiting disease, half of travellers with TD experience some limitation of activities during their trip, while up to 10% will experience persistent diarrhoea or other complications.The purpose of this article is to provide an updated microbiological, epidemiological, and clinical profile of traveller's diarrhoea, including known risk factors, as well as to make recommendations on the prevention and treatment of TD.

Structural signature of Ser83Leu and Asp87Asn mutations in DNA gyrase from enterotoxigenic Escherichia coli and impact on quinolone resistance

Enterotoxigenic Escherichia coli (ETEC) is among the most frequent microorganisms causing traveler's diarrhea (TD). Quinolones are potent antimicrobial agents used for the treatment of TD. Resistance to quinolones is typically caused by substitutions in QRDR region of gyrA subunit of DNA gyrase. The aim of this study was to seek insights into the effect of these substitutions at structural level and their association with observed quinolone resistance.Majority of the ETEC strains have gyrA mutations at amino acid position 83 and 87. To understand the quinolone resistance mechanism at molecular level, we have studied the interaction of wild type and mutant forms of ETEC gyrA with nalidixic acid and ciprofloxacin by molecular modeling using Discovery Studio and LeadIt.All the mutants had reduced affinity towards both ciprofloxacin and nalidixic acid relative to the wild type due to the mutations introduced in gyrA. Besides Ser83 and Asp87, for nalidixic acid binding Arg91 and His45 residues were observed to be critical while in ciprofloxacin binding Lys42 and Arg91 residues played a significant role.Amino acid substitutions contribute to the emergence of drug resistance in sensitive strains by causing structural alterations leading to reduced affinity of the drug towards receptor. Analysis of the effect of amino acid substitutions at structural level is of utmost importance to establish possible associations between mutations and the diseases. These studies accelerate the identification of pharmaceutical targets for relevant treatments and could also be helpful in guiding the design of further experimental research.

Acute Traveler’s Diarrhea: Initial Treatment

Diarrhea is the most common health issue affecting travelers to destinations across the world. This paper reviews the options for initial treatment of acute traveler’s diarrhea (TD). Its prevention, including but not limited to vaccines and safe travel and eating habits, is an important consideration but is beyond the scope of this paper. Treatment of TD has three arms: volume repletion, antibiotics, and antimotility/antisecretory agents. Patients should be advised to continue a diet that they can tolerate and maintain adequate fluid intake. In most cases, neither oral rehydration therapy nor dietary restrictions are likely to provide significant benefit. As yet, there is no evidence to support probiotic use for treatment of this type of diarrhea. Given that bacteria are the most frequent cause of TD, adult patients with moderate to severe disease should be treated empirically with a short course of antibiotics. In many instances, these will be prescribed pre-travel with instructions for proper usage when typical symptoms occur while abroad. However, such travelers should be advised to see a physician or seek emergency treatment if symptoms are severe or persist beyond 3 days. Antibiotic selection must take into account the epidemiology of resistant enteric pathogens. Fluoroquinolones are usually effective, although resistance of Campylobacter to this class of drugs in South and Southeast Asia warrants azithromycin as first-line empiric therapy in travelers to those regions. One day of therapy is often sufficient but can be extended to 3 days. Rifaximin is an alternative in non-invasive disease only. The antimotility agent loperamide is safe and effective and should be considered as adjunctive therapy in most cases of TD and can similarly be prescribed pre-travel. In non-pregnant adults, bismuth subsalicylate can also provide some symptomatic relief. Where available, racecadotril may be a safe alternative in both adults and children, although never specifically studied in TD. In cases of severe symptoms, or those lasting longer than 3 days, the patient should be evaluated for non-bacterial etiologies as well as possible Clostridium difficile infection. Certain travelers are more vulnerable to severe complications related to TD. Children, particularly infants, may need more aggressive fluid resuscitation with oral rehydration therapy. Several of the antidiarrheal agents must be avoided. Elderly patients and those with impaired cardiovascular reserve or immune-deficient states are more prone to complications as well. Treatment recommendations also differ for pregnant women. We generally advise adult non-pregnant travelers to follow smart eating and drinking practices and to bring a supply of bismuth subsalicylate and loperamide. We also prescribe an empiric antibiotic course (ciprofloxacin or azithromycin for up to 3 days) that is to be used for moderate to severe cases of TD.

A Randomized, Double Blind, Placebo‐Controlled Trial of an Oral Synbiotic (AKSB) for Prevention of Travelers' Diarrhea

Travelers' diarrhea (TD) is a significant problem for travelers. TD is treatable once it occurs, but few options for prevention exist. Probiotics have been studied for prevention or treatment of TD; however, very few combination probiotics have been studied. Therefore, the purpose of this study was to determine if prophylactic use of an oral synbiotic could reduce the risk of acquiring TD and reduce antibiotic use if TD occurred. Healthy subjects traveling to an area of the world with an increased risk of TD were eligible. All subjects received pre-travel counseling and were provided antibiotics and antidiarrheals (loperamide) for use only if TD developed. The subjects were blinded and randomized to take two capsules of placebo or oral synbiotic (a combination of two probiotics and a prebiotic) called Agri-King Synbiotic (AKSB) beginning 3 days prior to departure, daily while traveling, and for 7 days after return. All subjects kept symptom and medication diaries and submitted a stool sample for pathogen carriage within 7 days of return. The study was powered to detect a 50% reduction in the incidence of TD. Of the 196 adults (over 18 years of age) enrolled in the study, 54.3% were female and 80.9% were younger than 60 years. The study randomized 94 people to the AKSB arm and 102 to placebo. The incidence of TD was 54.5% in the overall group with 55.3% in the AKSB arm and 53.9% in the placebo (p = 0.8864). Among the subjects who experienced diarrhea (n = 107) there was no significant difference in the proportion of subjects that took antibiotics versus those that did not take antibiotics (35% vs 29%, p = 0.68). AKSB was safe with no difference in toxicity between the two arms. The prophylactic oral synbiotic was safe but did not reduce the risk of developing TD among travelers, nor did it decrease the duration of TD or the use of antibiotics when TD occurred.

Advances in the Treatment of Travelers’ Diarrhea

Diarrhea is the most common complaint reported by travelers from industrialized countries visiting developing nations. High-risk areas for travelers' diarrhea (TD) include South Asia, Sub-Saharan Africa, and Latin America, while moderate-risk areas include Southeast Asia, Middle East, Oceania and the Caribbean. Bacterial pathogens are the major cause of TD. Recent advances in the therapy for diarrhea include a better understanding of the potential benefit of symptomatic and antimicrobial therapy. The mainstay of treatment includes antibacterial therapy with one of three drugs, a fluoroquinolone, rifaximin, or azithromycin. Probiotics have been used in preliminary studies for both treatment and prevention of TD, but more studies are needed with these biologic agents. The aim of this review is to identify the recent advances in the therapy of TD and to provide recommendations for treatment during international travel.

In Vitro Activity and Single-Step Mutational Analysis of Rifamycin SV Tested against Enteropathogens Associated with Traveler's Diarrhea and Clostridium difficile

Rifamycin SV is a broad-spectrum, poorly absorbed antimicrobial agent that, when coupled with MMX technology, is being targeted for the oral treatment of traveler's diarrhea (TD) and Clostridium difficile-associated disease (CDAD). Rifamycin SV was tested for activity against 911 TD-associated enteropathogens and 30 C. difficile isolates collected from several global surveillance studies. Rifamycin SV demonstrated similar antimicrobial activity levels against the Enterobacteriaceae, with MIC₅₀ values ranging from 32 to 128 μg/ml for all but one strain (an enterotoxigenic Escherichia coli at >512 μg/ml). For non-Enterobacteriaceae strains, MIC₅₀ values ranged from 2 to 8 μg/ml, with the exception of Campylobacter spp., for which all strains had MIC values of >512 μg/ml. Rifamycin SV also demonstrated excellent activity (MIC₅₀ of ≤ 0.03 μg/ml) against most C. difficile strains (including one hypervirulent NAP1 strain), and this activity was even superior to the potency observed for vancomycin, metronidazole, and rifaximin. In mutational passaging studies, rifamycin SV induced stable resistance and showed a mutation frequency in E. coli similar to that of rifampin. This study presents the potency of rifamycin SV for enteropathogens commonly recovered from patients with TD and CDAD. Additional in vitro and in vivo studies appear necessary to determine the utility of rifamycin SV as an oral agent for the prevention and treatment of TD and CDAD.

Traveling Internationally: Avoiding and Treating Travelers' Diarrhea

Traveling Internationally: Avoiding and Treating Travelers' Diarrhea

Expert Review of the Evidence Base for Self‐Therapy of Travelers’ Diarrhea

The most frequent illness among people traveling from industrialized regions to developing countries is travelers’ diarrhea (TD). For all people entering areas known to pose a high risk for TD, medication should be included in the travel kit on trips, which can be taken for self‐therapy of resultant diarrheal illness. Drugs aimed at relief of symptoms, particularly loperamide, are the preferred standard treatment of TD by some professionals in Europe. Travel medicine experts in the United States and many in Europe feel that an antimicrobial agent that cures while shortening the duration of illness represents the mainstay of therapy. Loperamide combined with an appropriate antimicrobial agent will provide the most rapid relief of TD. In the following document, the authors used an evidence base when available to determine the strength and quality of evidence and when data were lacking, the panel of experts provided consensus opinion. Drugs used for symptomatic relief, including bismuth subsalicylate (BSS) and loperamide, decrease the number of unformed stools passed during a bout of TD but may not speed up illness recovery. The majority of authors of this document recommended that for all people traveling from low‐risk to high‐risk regions, one of the three antibacterial drugs should be transported with them for self‐treatment of diarrhea that occurs, given in respective order of development for TD therapy: a fluoroquinolone (ciprofloxacin or levofloxacin), rifaximin, or azithromycin. Azithromycin is preferred for treatment when diarrhea is complicated by dysentery (passage of grossly bloody stools) or by high fever and for use in children with TD. A number of experts would recommend additionally including loperamide in the travel kit for adults with TD as this may accelerate relief of the illness when used with an antimicrobial agent. An uncertain proportion of Europeans feel that it is sufficient to include loperamide alone …

Traveler’s Diarrhea: Updates for Pediatricians

Children who travel are at risk of developing the same illnesses that affect adult travelers. Treatment, etiology and actual risk of TD in children are not well defined. Prevention and self-treatment of TD should be discussed in great detail during pre-travel counseling. This includes information and instructions on various preventive measures as well as when to use medications and the potential adverse effects associated with these medications. A TD that is mild can be managed effectively by appropriate use of oral rehydration solutions. Families should be advised to carry ORS packets and start treatment in children as soon as the diarrhea begins. Self treatment with antibiotics such as azithromycin may be considered in children if diarrhea is moderate to severe. Caregivers should contact local health authorities if there is no improvement especially after self treatment with antibiotics.

Travelers’ Knowledge of Prevention and Treatment of Travelers’ Diarrhea

Information regarding the prevention and treatment of travelers' diarrhea (TD) is available to the public from various sources, such as medical personnel, travel clinics, personal contacts, and the Internet. This type of information may help travelers avoid this illness or help those afflicted minimize its duration. We collected questionnaire data from 104 travelers at departure gates for flights to Mexico from Calgary, Alberta on their knowledge of symptoms and treatment of TD and food risks associated with this illness and sources of information used. Almost half reported they received some information on travel-related diseases and on TD prior to the flight. When education level was controlled for, the mean score for people who had obtained information on TD was significantly higher than that for those who did not have such information. College or university-educated travelers scored better than did other travelers. A high proportion of travelers correctly identified risk levels associated with specific foods consumed during travel, and many recognize that they are at an increased risk of acquiring diarrheal illness while traveling in a developing country. Information on TD appears to improve the level of knowledge on its prevention and treatment among travelers from southern Alberta.

MSP017 Emergence of antibiotic resistance among S. pneumoniae and S. pyogenes strains isolated from the respiratory tract infections of children in Germany, 2002

Enterotoxigenic Escherichia coli (ETEC) is among the most frequent microorganisms causing traveler's diarrhea (TD). Quinolones are potent antimicrobial agents used for the treatment of TD. Resistance to quinolones is typically caused by substitutions in QRDR region of gyrA subunit of DNA gyrase. The aim of this study was to seek insights into the effect of these substitutions at structural level and their association with observed quinolone resistance.Majority of the ETEC strains have gyrA mutations at amino acid position 83 and 87. To understand the quinolone resistance mechanism at molecular level, we have studied the interaction of wild type and mutant forms of ETEC gyrA with nalidixic acid and ciprofloxacin by molecular modeling using Discovery Studio and LeadIt.All the mutants had reduced affinity towards both ciprofloxacin and nalidixic acid relative to the wild type due to the mutations introduced in gyrA. Besides Ser83 and Asp87, for nalidixic acid binding Arg91 and His45 residues were observed to be critical while in ciprofloxacin binding Lys42 and Arg91 residues played a significant role.Amino acid substitutions contribute to the emergence of drug resistance in sensitive strains by causing structural alterations leading to reduced affinity of the drug towards receptor. Analysis of the effect of amino acid substitutions at structural level is of utmost importance to establish possible associations between mutations and the diseases. These studies accelerate the identification of pharmaceutical targets for relevant treatments and could also be helpful in guiding the design of further experimental research.

In vitro antimicrobial susceptibility testing of bacterial enteropathogens causing traveler's diarrhea in four geographic regions.

The emergence of resistant enteropathogens has been reported worldwide. Few data are available on the contemporary in vitro activities of commonly used antimicrobial agents against enteropathogens causing traveler's diarrhea (TD). The susceptibility patterns of antimicrobial agents currently available or under evaluation against pathogens causing TD in four different areas of the world were evaluated. Pathogens were identified in stool samples from U.S., Canadian, or European adults (18 years of age or older) with TD during 1997, visiting India, Mexico, Jamaica, or Kenya. MICs of 11different antimicrobials were determined against 284 bacterial enteropathogens by the agar dilution method. Ciprofloxacin, levofloxacin, ceftriaxone, and azithromycin were highly active in vitro against the enteropathogens, while traditional antimicrobials such as ampicillin, trimethoprim, and trimethoprim/sulfamethoxazole showed high levels and high frequencies of resistance. Rifaximin, a promising and poorly absorbable drug, had an MIC at which 90% of the strains tested were inhibited of 32 microg/ml, 250 times lower than the concentration of this drug in the stools. Amdinocillin, nalidixic acid, and doxycycline showed moderate activity. Fluoroquinolones are still the drugs of choice for TD in most regions of the world, although our study has a limitation due to the lack of Escherichia coli samples from Kenya and possible bias in selection of the patients for evaluation. Azithromycin and rifaximin should be considered as promising new agents. The widespread in vitro resistance of the traditional antimicrobial agents reported since the 1980s and the new finding of resistance to fluoroquinolones in Southeast Asia are the main reasons for monitoring carefully the antimicrobial susceptibility patterns worldwide and for developing and evaluating new antimicrobial agents for the treatment of TD.

Treatment of gastrointestinal infections

Treatment of gastrointestinal infections continues to be complicated by expanding resistance to antibiotics. This has led to both new antibiotic treatments and to research on alternative therapies. In the case of Clostridium difficile colitis, interesting preliminary results have been obtained with both probiotic therapy and passive immunization strategies. The newer macrolides were found to be effective for multidrug-resistant Salmonella typhi and safe in the pediatric population. The efficacy of rifaximin, a nonabsorbed antimicrobial agent, was demonstrated in the treatment of travelers diarrhea in Mexico. The benefit of the proteolytic agent bromelain, which degrades enterocyte receptors for enterotoxigenic Escherichia coli, was shown in an experimental model of piglets challenged with this infection after bromelain prophylaxis. The potential value of zinc supplementation in infant diarrhea was shown in a study in India. The recently approved rotavirus vaccine is being withheld because of multiple reported cases of intussusception. Cryptosporidiosis continues to challenge old and new chemotherapeutic agents. The usefulness of paromomycin in Cryptosporidium infection was shown in both murine and piglet models. The cost effectiveness of prophylaxis for parasitosis in immigrants has been an area of investigation.

Treatment of traveller's diarrhoea. Economic aspects.

Traveller's diarrhoea (TD) is an enteric infective disease seen in 30 to 50% of the 30 million people who travel annually from the developed world to developing countries. It is the commonest disorder affecting international travellers. Although usually trivial, a significant minority of patients may develop a more protracted disease with an attendant increase in morbidity. This may then incur financial costs to the travellers themselves and to the healthcare systems of the host and origin countries. Advice regarding risk avoidance has so far proved ineffective in altering the behaviour of travellers and consequently the incidence of TD among them. Hard data are lacking on the cost effectiveness and cost benefit of prophylaxis and treatment of TD. Thus, we have attempted to quantify, as far as is possible, the total cost of TD and to set this against the potential savings from avoiding TD if prophylaxis or treatment options were universally employed. It must be noted that the financial benefit-cost ratio of an intervention may not be the most suitable measure of its desirability. However, such concepts as the success of travel are inherently difficult to quantify in economic terms. This analysis applies to travellers from the UK and economic variations between countries will after the outcomes obtained. Nevertheless, given these necessary constraints, all possible treatment options have a more favourable benefit-cost ratio than prophylaxis. In conclusion, the case for prophylaxis is not strong except in selected high risk groups, and limited self-treatment seems economically justified.