π Health and biotech
How science is preparing for antibiotic resistance

Antibiotic resistance in the shadow of opportunistic infections

Agnès Vernet, Science journalist
On March 16th, 2022 |
4 mins reading time
Antibiotic resistance in the shadow of opportunistic infections
Thierry Naas
Thierry Naas
Associate Professor in Medical Microbiology at the Faculty of Medicine, University of Paris 11
Key takeaways
  • Antibiotic resistance is a major public health problem, accounting for over 5,000 deaths in France in 2015. This phenomenon can also affect benign bacteria, causing opportunistic infections.
  • For example, the infamous Escherichia coli, a benign bacterium of our digestive system, can now be resistant to the reference treatment for urinary tract infections, which it causes in 25% of cases.
  • This resistance develops through regular contact with antibiotics. Molecules active in the environment favour the selection of resistance among soil bacteria and thus their overall prevalence.
  • Better use and prescription of antibiotics would limit this “acclimatisation” of bacteria.

From a clin­i­cal point of view, not all path­o­gen­ic bac­te­ria are alike. We can dis­tin­guish between path­o­gen­ic bac­te­ria, such as sal­mo­nel­la or shigel­la, which always make their car­ri­ers ill, and oppor­tunis­tic bac­te­ria, which exist in our diges­tive tract, skin or nasal cav­i­ties and can become infec­tious through a wound or a weak­ened immune system.


An exam­ple of the lat­ter is Escherichia coli, a bac­teri­um that lives in per­fect sym­bio­sis with our body (it is said to be com­men­sal). This bac­te­r­i­al species par­tic­i­pates in the home­osta­sis of the diges­tive tract and pro­duces vit­a­mins. Home­osta­sis is a reg­u­la­to­ry process by which the body bal­ances its var­i­ous inter­nal con­stants. But this species is also respon­si­ble for 25% of uri­nary tract infec­tions. Gen­er­al­ly sen­si­tive to all antibi­otics, this bac­teri­um is now resis­tant to the stan­dard treat­ment for uri­nary tract infec­tions, the 3rd gen­er­a­tion cephalosporins, in about 3% of cas­es1. A com­men­sal and benign bac­teri­um of our diges­tive sys­tem can thus be an infec­tious threat to the kid­ney if not treat­ed effectively.

Unlike oth­er dis­eases, these com­pli­ca­tions do not appear sud­den­ly. You can live with antibi­ot­ic-resis­tant bac­te­ria for years. They remain silent as long as the immune sys­tem and oth­er com­men­sal bac­te­ria keep them in check.

Dur­ing a stress­ful peri­od or a viral ill­ness, for exam­ple, the immune sys­tem can weak­en and a bac­te­r­i­al infec­tion can occur. The major­i­ty of the patients we care for suf­fer from can­cer, are in inten­sive care or have had a trans­plant. Oppor­tunis­tic infec­tion sit­u­a­tions are now more com­mon than those caused by resis­tant pathogens.

The increas­ing preva­lence of infec­tions due to mul­ti-antibi­ot­ic-resis­tant bac­te­ria is caused by both the overuse of antibi­otics and their mis­use in clin­i­cal and vet­eri­nary set­tings. On farms, these treat­ments have been used not only to treat infec­tions but also to pre­vent them. Since using them as a pre­ven­ti­tive mea­sure con­sid­er­ably facil­i­tates ani­mal growth, many farm­ers start­ed using them as growth-pro­mot­ers. Until 1996, pigs in France were treat­ed pre­ven­tive­ly with gly­copep­tides, a class of “last-resort” antibi­otics used in the treat­ment of staphy­lo­coc­ci. This prac­tice is now banned in Europe, but it con­tin­ues in the Unit­ed States and is con­tribut­ing to the increase in bac­te­r­i­al resis­tance on a glob­al scale.

A global and worldwide problem

The use of antibi­otics in the envi­ron­ment is not lim­it­ed to farm­ing prac­tices, how­ev­er. A recent study has shown that med­ica­tions are present in all Euro­pean rivers2. Releas­ing active mol­e­cules into the envi­ron­ment encour­ages the selec­tion of resis­tance among soil bac­te­ria and thus their over­all prevalence.

These bac­te­ria encounter the com­men­sal flo­ra of the diges­tive tract, through unwashed hands or veg­eta­bles, and can exchange genet­ic mate­r­i­al. Antibi­ot­ic treat­ments will then encour­age the spread of resis­tance or its appear­ance. These drugs must there­fore be pre­scribed and tak­en conscientiously.

Antibi­ot­ic presc­it­pi­on also needs to be con­sid­ered in its social con­text. In India, peo­ple buy treat­ments accord­ing to their finan­cial means. A rich patient will take a broad-spec­trum antibi­ot­ic, i.e. one that can kill many bac­te­ria, while a poor patient will have to make do with mol­e­cules that are effec­tive on few­er bacteria.

In Europe, the ther­a­peu­tic options are more mea­sured. How­ev­er, it is impor­tant to take into account the vari­a­tions in effec­tive­ness of an antibi­ot­ic depend­ing on the tis­sue being treat­ed. It is also essen­tial to respect the dosage. When a patient takes an antibi­ot­ic, they often expe­ri­ence a rapid improve­ment in their symp­toms, some­thing that may lead them to stop their treat­ment ear­ly. But, just because the signs of infec­tion have gone away does not mean that the bac­te­ria have dis­ap­peared. In gen­er­al, treat­ment not fol­lowed to the let­ter con­tributes to the devel­op­ment of resistance.

Imported and indigenous cases

Our lab­o­ra­to­ry has been asso­ci­at­ed with the Nation­al Ref­er­ence Cen­tre (NRC) for Car­bapen­em Resis­tant Enter­obac­te­ri­aceae (CRE) for 10 years. Car­bapen­ems are last-resort antibi­otics used, in par­tic­u­lar, in inten­sive care units to treat seri­ous infec­tions. Resis­tance to these mol­e­cules is a pub­lic health con­cern as treat­ment of infec­tions is being restrict­ed to the use of col­istin. This is the last active mol­e­cule, but it has seri­ous side effects such as irre­versible dam­age to kid­ney function.

When it was cre­at­ed in 2012, the CNR observed car­bapen­em-resis­tant strains main­ly in trav­ellers, in par­tic­u­lar those who had vis­it­ed the Maghreb or India. Peo­ple who trav­el to these coun­tries have a two out of three chance of acquir­ing an enter­obac­teri­um resis­tant to one or more antibi­otics. These bac­te­ria are not nec­es­sar­i­ly path­o­gen­ic, but if the patients are tem­porar­i­ly immuno­com­pro­mised, they can cause an infec­tion that is dif­fi­cult to treat.

Today, more than 60% of the cas­es we treat are indige­nous, involv­ing patients who have nev­er trav­elled out­side Europe and who have there­fore acquired resis­tance in their home­land. The scale of the prob­lem is grow­ing and is there­fore no longer lim­it­ed to low-income countries.

In the city and in the hospital

Pre­vent­ing the spread of these resis­tances is now an active bat­tle for the med­ical com­mu­ni­ty. Some hos­pi­tals have devel­oped active poli­cies that encour­age the rea­son­able pre­scrip­tion of antibi­otics by pub­lish­ing rec­om­men­da­tions for the use of these mol­e­cules accord­ing to the pathol­o­gy in ques­tion, with the sup­port of infec­ti­ol­o­gists for spe­cif­ic cas­es. How­ev­er, there is still room for improve­ment. France is the third largest con­sumer of antibi­otics in Europe. The devel­op­ment of rapid tests to dis­tin­guish between viral and bac­te­r­i­al infec­tions, par­tic­u­lar­ly for sore throats, is a lever for reduc­ing their mis­use in our coun­try and else­where. The aim is to guar­an­tee the effec­tive­ness of avail­able antibi­otics for as long as pos­si­ble. Research and devel­op­ment of new ther­a­peu­tic solu­tions will not be enough to curb the cri­sis. Very rough­ly speak­ing, the phar­ma­ceu­ti­cal indus­try needs 20 years to devel­op a new antibi­ot­ic, where­as it only takes 24 hours for a bac­teri­um cul­ti­vat­ed in the lab­o­ra­to­ry to become resis­tant. Prop­er use, in the right dos­es and for the right rea­sons, will allow us to safe­guard these pre­cious mol­e­cules while wait­ing for new ther­a­pies, such as phagother­a­py, immunother­a­py, or antimi­cro­bial pep­tides, and of course new, more effec­tive antibiotics.