Antimicrobial resistance Brief reminder about global problem

WHO key facts Antimicrobial resistance (AMR) threatens the effective prevention and treatment of an ever- increasing range of infections caused by bacteria, parasites, viruses and fungi. It is an increasingly serious threat to global public health that requires action across all government sectors and society. AMR is present in all parts of the world. New resistance mechanisms emerge and spread globally. In 2012, there were about 450 000 new cases of multidrug-resistant tuberculosis (MDR-TB). Extensively drug-resistant tuberculosis (XDR-TB) has been identified in 92 countries. MDR-TB requires treatment courses that are much longer and less effective than those for non-resistant TB.

Resistance to earlier generation antimalarial drugs is widespread in most malaria-endemic countries. Further spread, or emergence in other regions, of artemisinin- resistant strains of malaria could jeopardize important recent gains in control of the disease. There are high proportions of antibiotic resistance (ABR) in bacteria that cause common infections (e.g. urinary tract infections, pneumonia, bloodstream infections) in all regions of the world. A high percentage of hospital- acquired infections are caused by highly resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) or multidrug-resistant Gram-negative bacteria. Patients with infections caused by drug-resistant bacteria are generally at increased risk of worse clinical outcomes and death, and consume more healthcare resources than patients infected with the same bacteria that are not resistant.

Without urgent, coordinated action, the world is heading towards a post- antibiotic era, in which common infections and minor injuries, which have been treatable for decades, can once again kill.

History of antibiotic discovery and concomitant development of antibiotic resistance. History of antibiotic discovery and concomitant development of antibiotic resistance. The dark ages, the preantibiotic era; primordial, the advent of chemotherapy, via the sulfonamides; golden, the halcyon years when most of the antibiotics used today were discovered; the lean years, the low point of new antibiotic discovery and development; pharmacologic, attempts were made to understand and improve the use of antibiotics by dosing, administration, etc.; biochemical, knowledge of the biochemical actions of antibiotics and resistance mechanisms led to chemical modification studies to avoid resistance; target, mode-of-action and genetic studies led to efforts to design new compounds; genomic/HTS, genome sequencing methodology was used to predict essential targets for incorporation into high-throughput screening assays; disenchantment, with the failure of the enormous investment in genome-based methods, many companies discontinued their discovery programs. Other milestones in this history include the creation of the FDA Office of New Drugs after the thalidomide disaster led to stricter requirements for drug safety, including the use of antibiotics. This slowed the registration of novel compounds. Before antibiotics were discovered, Semmelweis advocated hand washing as a way of avoiding infection; this practice is now strongly recommended as a method to prevent transmission. Davies J , and Davies D Microbiol. Mol. Biol. Rev. 2010;74:417-433

Chloroquine resistance

More reasons to avoid unnecessary antibiotics Antibiotic-associated diarrhea (clostridium difficile) Especially associated with wide spectrum cephalosporins like ceftriaxon and fluoroquinolones Likelihood of resistance also in the patient treated increases, not just in population Increased likelihood of urinary track and candida infections among women Importance of gut flora to health (for example metabolic and immunity functions)

What accelerates AMR? Inappropiate use of antimicrobial drugs Antimicrobial drugs used when not truly needed Use of wrong antibiotics or too short treatment Poor infection prevention Hand hygiene in hospitals!!! Poor diagnostic facilities for communicable diseases Use of antimicrobial drugs in animal husbandry Loose policy of sharing antimicrobial drug In many countries available without prescription Financial benefits and possible sanctions encouraging doctors to overprescribe antimicrobial drugs

Everyday life in health care Many working hours spent convincing patients that they don’t need antibiotics for common cold or other minor conditions Autoimmune diseases partly due to too high level of hygiene More fatal and bigger variety of communicable diseases HIV and other conditions decreasing immunity More limited diagnostic facilities FINLAND TANZANIA

Lessons to learn Despite presence of malaria, HIV, tuberculosis etc. all the communicable illnesses are not fatal In bronchitis there is fewer, productive cough and chest pain, but in many cases the causing agent is virus and because of that antibiotics don’t help Majority of diarrheas heal without antibiotics, guidelines of treatment in Finland recommend antibiotic just to Shigella, EIEC, typhoid fewer and cholera (+more severe forms of bacterial diarrhea) Follow up is also treatment option

Suggestions for development More cooperation with other staff Check the national treatment of guidelines and internet resources (provide WLAN that functions) More consultation Nobody knows perfectly medicine immediately after graduating, better to ask stupid questions than to give obviously wrong treatment Medicine is not science of geniuses (Dr. House), but group intelligence Consultation hours especially for the newly graduated to discuss more difficult cases Guidelines of treatment for the hospital Radiological meetings

More development Lectures given by local staff including clinical officers to encourage studying Diagnostic facilities don’t improve fast, but culture for consultation and learning can be enhanced with less money More organized structure for meetings and consultation would make the 6 week visit of foreign doctors more beneficial Continuity in patient files to avoid many identical cures for example suspected helicobacter infection