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Anti-diarrhoea antibiotics favour particularly resistant super bacteria

DiaorrheaAnti-diarrhoea antibiotics, especially in Africa, Asia and South America, not only render the tourist susceptible to an ESBL infection, but also lead to the most resistant strains of these bacteria, found a University of Helsinki study.

Every year, millions of travellers visit countries with poor hygiene, and approximately one third of them return home carrying antibiotic-resistant ESBL intestinal bacteria. Most of them remain unaware of this, as the bacteria cause no symptoms. High-risk areas for contracting ESBL bacteria are South and South-East Asia, Africa and Latin America.

Diarrhoea is the most common health complaint for people who travel to poor regions of the world. Those contracting diarrhoea have an increased risk of ESBL acquisition, and if they choose to they treat it with antibiotics, the risk becomes multiplied. A Finnish study led by Professor Anu Kantele and published two years ago showed that among people travelling to high-risk areas, those contracting diarrhoea and taking antibiotics, up to 80% brought ESBL super bacteria home with them.

A follow-up study led by Kantele at the University of Helsinki has now established that antibiotics taken while abroad not only render the tourist susceptible to an ESBL infection, but also lead to the most resistant strains of these bacteria being selected.

"ESBL bacteria are resistant to penicillins and cephalosporins, which is why infections caused by them are treated with antibiotics from other groups, such as fluoroquinolones (ciprofloxacin). When we analysed the patients with ESBL more closely, we found that among those who had not resorted to using antibiotics, 37% had an ESBL strain resistant to fluoroquinolone. As for the travellers who had taken fluoroquinolone, 95% had a strain of ESBL resistant to fluoroquinolone and, indeed, a variety of other antibiotics. Antibiotic use thus implies selecting ESBL strains with the broadest spectrum of resistance," Kantele explains.

"The finding makes sense. When we take an antibiotic, the bacteria that survive in our digestive system are those resistant to the treatment."

Antibiotic resistance can be transferred between bacteria through a package containing a variety of resistance genes, meaning that one package may contain resistance to several types of antibiotics. Indeed, most fluoroquinolone-resistant ESBL strains were also found resistant to certain other types of antibiotics the resistance to which is known to be transferred in the same gene packages that transfer ciprofloxacin resistance.

"In practice this means that travellers pick up the most resistant strains of ESBL, and we are left with dwindling treatment options for ESBL infections," states Kantele.

An ESBL infection rarely manifests through symptoms. Still, even a symptomless carrier can pass on the bacteria and, with ill luck, it can cause a severe, even life-threatening disease. Kantele emphasises that antibiotic resistance is one of the biggest threats to health care. If antibiotics loose their efficacy, many infectious diseases now treated successfully with antibiotics may become lethal again.

"The spread of resistant strains of bacteria makes the situation worse. Therefore, unnecessary use of antibiotics should be avoided also while travelling. diarrhea mostly remains mild or moderate, and no antibiotics are needed in such cases for healthy adults. They should just make sure to keep hydrated. And, if necessary, anti-motility medication can be taken in small amounts to alleviate the symptoms."

The study recruited Finnish travellers visiting the Travel Clinic at Aava Medical Centre as research subjects. The subjects gave a stool sample both before travel and immediately upon return, and answered questionnaire forms. A total of 90 people, all of whom had contracted an intestinal strain of ESBL bacteria while abroad, were selected to participate in the follow-up study. The susceptibility of the various strains to several different antibiotics was examined, and the results compared to such particulars as destination, age of traveller, travellers' diarrhoea, and antibiotic treatments used.

Background: One third of travellers to the poor regions of the (sub)tropics become colonized by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Co-resistance to non-beta-lactam antibiotics complicates the treatment of potential ESBL-PE infections.
Methods: We analysed co-resistance to non-beta-lactams among travel-acquired ESBL-PE isolates of 90 visitors to the (sub)tropics with respect to major risk factors of colonization: destination, age, travellers' diarrhoea (TD) and antibiotic (AB) use.
Results: Of the ESBL-PE isolates, 53%, 52%, 73%, and 2% proved co-resistant to ciprofloxacin, tobramycin, co-trimoxazole, and nitrofurantoin, respectively. The rates were similar among those with (TD+) or without (TD-) travellers' diarrhoea. Among fluoroquinolone-users vs. AB non-users, the co-resistance rates for ciprofloxacin were 95% versus 37% (p = 0.001), for tobramycin 85% versus 43% (p = 0.005), co-trimoxazole 85% versus 68% (p = 0.146), and nitrofurantoin 5% versus 2% (p = 0.147). In multivariable analysis co-resistance to ciprofloxacin was associated with increasing age, fluoroquinolone use, and tobramycin resistance.
Conlusions: While TD predisposes to ESBL-PE non-selectively, antimicrobial use favours strains resistant to drug taken and, simultaneously, any drug with resistance genetically linked to the drug used. Antibiotics taken during travel predispose to ESBL-PE with a high co-resistance rate.

Anu Kantele, Sointu Mero, Juha Kirveskari, Tinja Lääveri

[link url=""]University of Helsinki material[/link]
[link url=""]Travel Medicine and Infectious Disease abstract[/link]

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