In 2019, there were an estimated 4.95 million fatal cases worldwide associated with multiple antibiotic-resistant (MDR) bacterial strains, 1.27 million of which were directly attributable to MDR infections

Rapid action is therefore needed to prevent deaths reaching 10 million per year by 2050.

The MDR bacteria are: Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Streptococcus pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa.

Italy, according to the European Centre for Infection Control (ECDC), is the European country with the highest incidence of cases (201,584 in 2015) and deaths (10,762 in 2015) from infections with MDR bacteria.

The WHO, as part of the programme to combat antibiotic resistance initiated in 2015 and shared in 2017 by the European Commission, publishes, on 18 November, ‘the WHO AWaRe Antibiotic Book’

The book contains clinical recommendations for the management of more than 30 infectious diseases of adults and children contracted both locally and in hospital.

In particular, the book clearly defines clinical situations in which antibiotics, based on scientific evidence, are not necessary because they are unnecessary and to avoid the selective pressure that favours the emergence of resistant strains.

It is also stipulated that the duration of antibiotic treatment, according to the new guidelines, must be much shorter than previously recommended, but sufficient to achieve clinical recovery in mild and medium severity forms.

To prevent the emergence and spread of resistant strains, it is essential to adopt dosages capable of reaching sufficient concentrations at the site of infection to exert a lethal effect on the bacteria.

The book, to support clinicians in prescribing first- and second-line antibiotics for the most common infections in order to reduce the risk of adverse reactions and the development of resistance, refers to the classification into 4 groups called AWaRe.

First-line antibiotics (Access group), those to be used in case of failure or more severe forms (Watch) and those to be left as a reserve (Reserve) for intractable cases.

The fourth group lists those never to be used (not recommended).

Access antibiotics are narrow-spectrum, have a good safety profile and a generally low risk of inducing resistance

They are recommended for empirical therapy (as first- or second-choice options) of the most common infections.

The WHO has set a target for 2023 that at least 60% of global antibiotic consumption at national level should come from the Access group.

This list includes, among others, amoxicillin, amoxicillin/clavulanic acid, cefazolin, doxycycline, metronidazole, nitrofurantoin, sulfamethoxazole/trimethoprim.

It should be noted that fluorquinolones and macrolides are absent as resistance to these two classes of antibiotics has reached such high rates that their use is not recommended in the first instance.

Watch list antibiotics are broader spectrum

They have a higher risk of inducing resistance and are recommended as first-choice options only in patients with more severe clinical presentations or for infections whose aetiological agent is most likely resistant to Access group antibiotics.

This list includes, among others, azithromycin and the macrolides, cefepime, cefixime, cefoxitin, ceftriaxone, minocycline, the fluoroquinolones, oral fosfomycin, carbapenems, oral and EV neomycin, netilmycin, piperacillin/tazobactam, rifampin, rifaximin, teicoplanin, oral and EV vancomycin.

Finally, the Reserve list includes antibiotics to be used as a last resort in the event of clinical and microbiological failure or to treat life-threatening infections with germs resistant to multiple antibiotics.

The Reserve list includes, among others, aztreonam, cefiderocol, ceftaroline-fosamil, ceftazidime/avibactam, ceftolozane/tazobactam, dalbavancin, dalfopristin/quinupristin, daptomycin, eravacyclin, fosfomycin EV, imipenem/cilastatin/relebactam, linezolid, meropenem/vaborbactam.

The WHO book also includes infographics on the 10 syndromes most commonly observed by both GPs and paediatricians of free choice (community pneumonia, UTI, bronchitis, COPD, sinusitis, pharyngitis, bacterial lymphadenitis, otitis, pharyngitis, tooth/mouth infections) translated and adapted to our epidemiological reality by AIFA-OPERA and collected in a booklet that will be sent to all doctors.

The booklet is a valuable and concise pocket-sized aid containing antibiotic therapy recommendations based on the latest scientific evidence for physicians working in the field and in nursing homes.

An ‘app’ to download to one’s smartphone or other electronic device containing all the material included in the documents is also being developed.

Also available are the first ‘AIFA-OPERA Recommendations on the targeted treatment of infections with Gram-negative bacteria resistant to multiple antibiotics’, (OPERA: Optimisation of Antibiotic PrEscRtion), drawn up on the basis of the latest scientific evidence and evaluated using the GRADE-Adolopment method, to combat the MDR bacteria most frequently isolated in Italy in hospitalised patients and in the territory (Enterobacterales resistant to 3rd generation cephalosporins, Enterobacterales resistant to carbapenems, Acinetobacter baumannii resistant to carbapenems and Difficult-to-Treat [DTR] Pseudomonas spp. ).

All documents and applications will be periodically updated on the basis of new evidence as it becomes available.

The difficult epidemiological moment we are going through clearly highlights the relevance of the information and education project that AIFA, taking up the WHO project, is proposing on a subject that needs a fast turnaround for the good of the population.

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FNOMCEO