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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
2
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.

Opportunism

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.

1https://​www​.san​tepubliq​ue​france​.fr/​m​a​l​a​d​i​e​s​-​e​t​-​t​r​a​u​m​a​t​i​s​m​e​s​/​i​n​f​e​c​t​i​o​n​s​-​a​s​s​o​c​i​e​e​s​-​a​u​x​-​s​o​i​n​s​-​e​t​-​r​e​s​i​s​t​a​n​c​e​-​a​u​x​-​a​n​t​i​b​i​o​t​i​q​u​e​s​/​r​e​s​i​s​t​a​n​c​e​-​a​u​x​-​a​n​t​i​b​i​o​t​i​q​u​e​s​/​d​o​n​nees/
2https://​www​.pnas​.org/​c​o​n​t​e​n​t​/​1​1​9​/​8​/​e​2​1​1​3​9​47119