RECOMMENDATIONS FOR AN
EFFECTIVE STRATEGY ON
ANTIMICROBIAL RESISTANCEFROM PREVENTION BY VACCINATION TO THE
DEVELOPMENT AND USE OF NOVEL ANTIBIOTICS

June 2022

THE DOCUMENT WAS SIGNED BY:
AIPO - Associazione Italiana Pneumologi Ospedalieri [Italian Association of Hospital
Pneumologists]
AMCLI - Associazione Microbiologi Clinici Italiani [Association of Italian Clinical Microbiologists]
CITTADINANZATTIVAFADOI - Società Scientifica di Medicina Interna [Federation of Associations of Hospital Doctors
on Internal Medicine]
FIMMG - Federazione Italiana Medici di Famiglia [Italian Federation of General Practitioners]
FIMP - Federazione Italiana Medici Pediatri [Italian Federation of Paediatricians]
FOFI - Federazione Ordini Farmacisti Italiani [Federation of Italian Pharmacists’ Associations]
GISA - Gruppo Italiano Stewardship Antimicrobica [Italian Antimicrobial Stewardship Working
Group]SIAARTI - Società Italiana di Anestesia, Analgesia, Rianimazione e Terapia
Intensiva [ItalianSociety of Anesthesia, Analgesia, Resuscitation and Intensive Care]
SIF - Società Italiana di Farmacologia [Italian Society of Pharmacology]
SIFO - Società Italiana di Farmacia Ospedaliera e dei Servizi Farmaceutici [Italian Society of
Hospital Pharmacy and Pharmaceutical Services]
SIHTA - Società Italiana di HTA [Italian Society of HTA]SIM - Società Italiana di Microbiologia [Italian Society of Microbiology]
SIMG - Società Italiana di Medicina Generale e delle Cure Primarie [Italian Society of General
Medicine and Primary Care]
SIMIT - Società Italiana di Malattie Infettive e Tropicali [Italian Society of Infectious and Tropical
Diseases]
SIP - Società Italiana di Pediatria [Italian Society of Paediatrics]
SIP - Società Italiana di Pneumologia [Italian Society of Pneumology]
SITA - Società Italiana di Terapia Antinfettiva, Antibatterica, Antivirale, Antifungina [Italian Society ofAnti-infective, Antibacterial, Antiviral and Antifungal Therapy]
SITI - Società Italiana di Igiene Medicina Preventiva e Sanità Pubblica [Italian Society of Hygiene,
Preventative Medicine and Public Health]initiative organized by

FOREWORD
The year 2025 will mark ten years since the adoption of the WHO Global
Action Plan on antimicrobial resistance (AMR) and, despite the progress
made so far, a solid and effective action is still required to eradicate thisphenomenon.
Farmindustria has decided to promote the establishment of amultidisciplinary Task Force to pool the know-how and experience ofexperts on the subject, with a view to providing recommendations on
critical aspects in the fight against AMR.
Task Force members include representatives from the medical andscientific community, the academic world, citizens and patientsassociations, pharmacists organizations and the pharmaceuticalindustry.
The discussions between these experts resulted in this document
consisting of three chapters regarding, respectively:

The role of vaccination as a prevention tool against antimicrobial
resistance
Value, access and innovation of novel antibiotics against bacterial
resistanceAppropriate use of antibiotics

These three topics were discussed during three parallel work sessions
involving the various experts and further feedback and information wereobtained through a survey sent to all participants. The document wasshared with the whole Task Force panel of experts each step of the way.
3

In drafting the document, attempts were made to focus attention on thespecific issues requiring solutions that are sustainable in the long termand effective planning, and for which a direct and solid recommendation
can be made.
The recommendations proposed are intended as a complementary tool
to those provided by existing technical and institutional panels.

THE ROLE OF VACCINATION AS A PREVENTION TOOL AGAINSTANTIMICROBIAL RESISTANCE
The number of scientific publications that support the positive roleof vaccination in the prevention of antimicrobial resistancephenomenon grows from one year to the next. This fundamental role
has been recognized by the European Commission, European
Parliament and European Council and the WHO has recently adopted
a more decisive stance on this issue2.
Vaccines are able to reduce antimicrobial resistance through various
mechanisms by:a) directly protecting vaccinated individuals, who will not become
infected and will therefore not have to use antibiotics;b) reducing viral infections, consequently lowering any
associated secondary bacterial infections, and also
inappropriate use of antibiotics3,4;c)

reducing the possibility of the illness being transmitted tothe unvaccinated population, and therefore reducing the
likelihood of the pathogen being transmitted. And since inpediatric and/or geriatric patients in particular, infection
often leads to hospitalization, controlling infection (bothviral and bacterial) reduces bacterial circulation in hospitalsettings, therefore preventing the diffusion of resistantbacteria;d) also protecting the microbiome from the changes induced
by wide-spectrum antibiotics and therefore the developmentof resistant bacterial species resulting from the acquisitionof resistance genes from other organisms present in the
microbiome.
4

All vaccinations, including those contemplated in the Italian National
Immunization Program (NIP) can potentially play an important direct orindirect role in the prevention of antimicrobial resistance and its
consequences, not least the economic and social ones.
However, it is also important to promote research into new specificvaccines for multiresistant micro-organisms, particularly nosocomial
ones that can play a significant clinical role in terms of frequency, severity
and therapeutic difficulties.
In order to maximize the impact of vaccinations, it is fundamental, on the
one hand, to achieve the coverage targets established in the NIP and, on
the other, that the Ministry of Health and Scientific Societies raiseawareness on the role of these vaccinations.

RECOMMENDATIONS
1. National Immunization Information System
Complete the National Immunization Information System assoon as possible and make it available nationwide. This is afundamental tool for planning vaccination campaigns for all
preventable diseases, for managing vaccine administration andfor the prompt sourcing of enough vaccines to satisfy the
population’s health demand.
It will also contribute to the acquisition of data and evidence on
the positive role vaccinations play in preventing AMR, and aid theRegional Authorities in implementing Electronic Health Records,
with the entry of the vaccinations administered.
2. Vaccinations and diagnostic and therapeutic pathways
Incorporate all vaccinations, including those in the NIP calendar,
into diagnostic and therapeutic pathways in a standard manner
nationwide to protect individuals with one or more healthconditions from the risk of contracting infectious diseases thatcan be prevented by vaccination.
3. Vaccination culture

5

Favor healthcare professional training on the issue, particularly
the mechanisms by which vaccines are able to prevent the
spread of antibiotic resistance, and promote awarenessinitiatives in order to generate a vaccination culture, also witha view to countering antimicrobial resistance, in order to meetthe vaccination coverage targets set in the NIP.

4. National Action Plan on Antimicrobial Resistance and National
Immunization Program
Raise awareness of the fundamental role of vaccination inpreventing AMR both in the new National Action Plan on
Antimicrobial Resistance (NAP-AMR) and in the new National
Immunization Program, which are both currently being preparedby the Italian Ministry of Health.
5. Scientific society consensus
Draft an official Scientific Society consensus statement on therole in preventing antibiotic resistance played by thevaccinations included in the NIP calendar, in order to promote
the value of vaccination through a multidisciplinary approach.

VALUE, ACCESS AND INNOVATION OF NOVELANTIBIOTICS AGAINST BACTERIAL RESISTANCE5
Research on and identification of innovative antibiotics able to getaround the current mechanisms of bacterial resistance are an unmet
clinical need of great importance for being able to effectively reducethe morbidity and mortality of nosocomial infections from multidrugresistant (MDR) Gram-negative bacteria.
The pharmaceutical industry has played a fundamental role in thedevelopment of antimicrobials, and although research has recently
picked up again, there are still several barriers to investments in thistherapeutic area.
Despite the significant attention this issue has received over the past
decade from important international organizations, such as theWorld Health Organization and the World Bank, national
governments have made little progress in promoting thedevelopment of new antimicrobials and particularly new antibiotics,
leading to a few pilot projects that have been launched in somecountries in recent years. The European Commission has alsoemphasized the lack of measures able to attract significant
investments in this area, by highlighting this issue in its
Pharmaceutical Strategy for Europe6.
In this context, while maintaining actions to support exploratory
research thanks to public investments, and hopefully implementing
them through the opportunities included in the Italian National

6

Recovery and Resilience Plan (NRRP), it is necessary to create afavorable environment that can attract investments by thepharmaceutical industry and other investors, especially to provide
economic support for the more advanced phases of clinicaldevelopment.
In order to achieve this objective, some countries have started testing
new measures, known as Pull incentives7,8, both separately and incombination with one another, such as new assessment methods
that also analyze aspects other than the therapeutic benefit fortreated patients or ad hoc reimbursement schemes (e.g., thesubscription model tested in the United Kingdom). As a matter offact, most Health Technology Assessment (HTA) systems now
primarily focus on assessing the therapeutic and economic benefits
solely from an NHS perspective (improvement in patient health andimpact in terms of direct health costs).
However, even at international level, several organizations havestressed the need to define a specific value framework for new
antimicrobials against resistant strains that takes into consideration
also the social and ecological costs (impact in terms of indirect andsocial security costs).

RECOMMENDATIONS
1. Methodology for evaluating new antibiotics against resistantbacterial strains
Adapt current methodologies for establishing the value ofantibiotics to the characteristics of these medicinal products,
considering their life-saving role, taking into account that this will
require a wider perspective and the analysis of scenarios andevidence beyond those needed for current marketing authorization
applications.
2. Criteria for granting ‘innovative’ status to new antibiotics against
resistant bacterial strains
7

Use specific indicators able to effectively measure the degree ofinnovation of new antibiotics, adapting, if necessary, the current
elements of assessment supporting applications for innovative
status (therapeutic need based on the indicators published eachyear by the ECDC on antibiotic-resistant pathogens, added
therapeutic value on pathogens resistant to available antibiotics

and robustness of scientific evidence by adapting the GRADE
method to suit the specific characteristics of the new antibiotics,
also taking into account their capacity to effectively counter themain mechanisms of bacterial resistance with innovative
mechanisms).
3. Ad-hoc reimbursement models for new antibiotics effective
against bacterial resistanceAs antimicrobial stewardship imposes restrictions on the use of
new antibiotics in the treatment of infections caused by resistantstrains in order to reduce the likelihood of new forms of resistancedeveloping, it is necessary to identify new methods ofreimbursement that guarantee developers economic returns
such as to increase and maintain investments in R&D in this area.

APPROPRIATE USE OF ANTIBIOTICS
Appropriate use is considered one of the main tools for preventing
the selection and spread of resistant microorganisms in thecommunity and in healthcare facilities and, consequently, thetransmission of infection by resistant bacteria.
In establishing the short-term rules regarding appropriate use of
new antibiotics and training, the National Action Plan on
Antimicrobial Resistance (NAP-AMR) stresses the importance ofpromoting healthcare professional training initiatives on theappropriate use of all antibiotics, and on the prevention and control
of infections, including healthcare-associated infections (HAIs),
involving all stakeholders, as part of a holistic approach.
The NAP-AMR also aims to assure mechanisms for the governanceof these medicinal products when they are placed on the market.
So far, these objectives have been only partially achieved and it istherefore necessary to increase investments in antimicrobial
stewardship programs to overcome the remaining deficits.
In particular, in emergency/urgency settings (e.g., sepsis in the ICU,
severe infections in onco-hematology) for which it is essential to havetimely access to antibiotic therapy, it is not always possible to obtainan infectious disease consultation, which at present can only beprovided by an infectious diseases specialist or other specialist, with8

specific expertise, identified by the Hospital Infection Control
Committee.
In addition, the AIFA product information sheets on new antibiotics
are an objective impediment to the use in emergency situations ofthese potentially life-saving medicinal products. As a matter of fact,
these information sheets are in accordance with the authorization
indications that define the settings for use and posology and that
predominantly refer to syndromic situations (pneumonia, urinary
tract infections, abdominal infections), rather than etiological ones,
therefore forcing infectious diseases specialists to use them off-label
when prescribing them empirically or on the basis of a confirmed orsuspected aetiology.
Lastly, empirical use by other specialists in critical patients, with risk
factors, epidemiological setting, colonization, is not currently
considered or permitted.
Although rapid molecular diagnosis is considered fundamental for
reducing the inappropriate use of antibiotics and therefore in thecontrol of resistant infections, to date, antimicrobial stewardshipprograms have not been fully integrated with diagnostic stewardshipprograms.

RECOMMENDATIONS
1. Healthcare facilities
Use the resources allocated to the “Health” mission of the Italian
National Recovery and Resilience Plan (NRRP) to overcome thestructural, technological and organizational deficiencies that have so
far constituted hindrances to the full implementation of the actions
set forth in the PNCAR.
2. Healthcare professional training
9

Guarantee that the funds allocated by the NRRP to organize
extraordinary training initiatives on healthcare-associatedinfections to all healthcare professionals and non-medical
hospital staff, as well as primary-care staff, are directed towards
specific programs on antimicrobial stewardship and infection
control.

3. Multidisciplinary teams
Guarantee the presence of a multidisciplinary team (specialists,
microbiologists, hospital pharmacists, etc.) within healthcare
facilities charged with the responsibility of defining and applying
stewardship programs.
4. Governance of new antibiotics
Guarantee timely access to new antibiotics in urgent and emergency
conditions, extending the possibility of prescribing these new “lifesaving” drugs to other specialists with specific expertise on the useof antibiotics (intensive care specialists, hematologists, etc.), bymaking provision for it in antimicrobial stewardship programs.
In addition, in the context of precise therapeutic recommendations
it may be useful to consider a “free and regulated access window”
to allow patients to receive the necessary treatment promptly in thedecisive earliest few hours.

5. Integration between antibiotic stewardship and diagnostic
stewardship
Develop antibiotic stewardship programs closely integrated withdiagnostic stewardship in the definition of diagnostic, therapeuticand care pathways in a standard manner across the country,
involving all healthcare professionals, especially those working in
the community medicine setting.
Promote the use of first-level diagnostic devices (e.g. pharyngeal
swab for GABHS, PCR testing, urine dipsticks, pneumatic
otoscopy, etc.) that, in primary care settings, allow greater
diagnostic precision and consequent greater prescriptive
appropriateness.
6. Information for citizens

Promote communication campaigns addressing the generalpublic on appropriate and well-informed use of antibiotics, aimed
at improving awareness among the citizens.

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PANEL OF EXPERTS WHO TOOK PART IN AMR TASKFORCE PROJECT
The role of vaccination as a prevention tool against
antimicrobial resistance
Coordinator:
Gaetano Privitera (Società Italiana di Igiene - SITI [Italian Society of Hygiene,
Preventative Medicine and Public Health])
Elena Bozzola (Società Italiana di Pediatria - SIP [Italian Society of Paediatrics])
Mauro Carone (President, Associazione Italiana Pneumologi Ospedalieri - AIPO [Italian
Association of Hospital Pneumologists])
Paolo D'Ancona (participated as an independent expert)
Paola Faverio (Associazione Italiana Pneumologi Ospedalieri - AIPO [Italian
Association of Hospital Pneumologists])
Tommasa Maio (Federazione Italiana Medici di Medicina Generale - FIMMG [ItalianFederation of General Practitioners])
Domenico Martinelli (Università di Foggia, participated as an independent expert)
Gianni Rezza (participated as an independent expert)
Alessia Squillace (Cittadinanzattiva, [Active citizenship Network])

Value, access and innovation of novel antibiotics against
bacterial resistance
Coordinator:
Francesco Saverio Mennini (President, Società Italiana di HTA - SIHTA [Italian Societyof HTA])

11

Matteo Bassetti (President, Società Italiana di Terapia Antinfettiva, Antibatterica,
Antivirale, Antifungina - SITA [Italian Society of Anti-infective, Antibacterial, Antiviraland Antifungal Therapy])
Arturo Cavaliere (President, Società Italiana di Farmacia Ospedaliera e dei Servizi
Farmaceutici - SIFO [Italian Society of Hospital Pharmacy and Pharmaceutical
Services])
Americo Cicchetti (Director, Alta Scuola di Economia e Management in Sanità ALTEMS [School of Healthcare Economics and Management])
Annamaria De Luca (Società Italiana di Farmacologia - SIF [Italian Society of
Pharmacology])
Ignazio Grattagliano (Società Italiana di Medicina Generale e delle Cure Primarie SIMG [Italian Society of General Medicine and Primary Care])
Giorgio Racagni (President, Società Italiana di Farmacologia - SIF [Italian Society of
Pharmacology])
Stefania Stefani (President, Società Italiana di Microbiologia - SIM [Italian Society ofMicrobiology])
Stefano Vella (Università Cattolica del Sacro Cuore, participated as an independent
expert)Appropriate use of antibiotics
Coordinator:
Francesco Menichetti (President, Gruppo Italiano Stewardship Antimicrobica - GISA
[Italian Antimicrobial Stewardship Working Group])

Pierangelo Clerici (President, Associazione Microbiologi Clinici Italiani - AMCLI[Association of Italian Clinical Microbiologists])
Claudio Cricelli (President, Società Italiana di Medicina Generale e delle Cure
Primarie - SIMG [Italian Society of General Medicine and Primary Care])Antonio D’Avino (President, Nazionale Federazione Italiana Medici Pediatri – FIMP
[Italian Federation of Paediatricians])
Mattia Doria (Federazione Italiana Medici Pediatri - FIMP [Italian Federation ofPaediatricians])
Antonello Giarratano (President, Società Italiana di Anestesia, Analgesia,
Rianimazione e Terapia Intensiva – SIAARTI [Italian Society of Anesthesia, Analgesia,
Resuscitation and Intensive Care])
Francesco Luzzaro (Associazione Microbiologi Clinici Italiani - AMCLI [Associationof Italian Clinical Microbiologists])
Dario Manfellotto (President, Federazione delle Associazioni dei Dirigenti OspedalieriInternisti - FADOI [Federation of Associations of Hospital Doctors on Internal
Medicine])
Walter Marrocco (Federazione Italiana Medici di Medicina Generale - FIMMG [ItalianFederation of General Practitioners])
Claudio Mastroianni (President, Società Italiana di Malattie Infettive e Tropicali SIMIT [Italian Society of Infectious and Tropical Diseases])
Maurizio Pace (Federazione degli Ordini dei Farmacisti Italiani - FOFI [Federation of
Italian Pharmacists’ Associations)Angelo Pan (ASST di Cremona [Cremona Local Health Authority], participated as anindependent expert)
Federico Pea (Società Italiana di Farmacologia - SIF [Italian Society of
Pharmacology])
Nicola Petrosillo (Fondazione Policlinico Universitario Campus Bio-Medico,
participated as an independent expert)
Luca Richeldi (Società Italiana di Pneumologia - SIP [Italian Society of Pneumology])
Claudio Santini (Federazione delle Associazioni dei Dirigenti Ospedalieri Internisti FADOI [Federation of Associations of Hospital Doctors on Internal Medicine])
Marcello Tavio (Società Italiana di Malattie Infettive e Tropicali - SIMIT [Italian Societyof Infectious and Tropical Diseases])
One Task Force meeting on “Value, access and innovation of novel antibiotics against
bacterial resistance” was also attended by a representative of the AIFA (Dr Maria
Paola Trotta).
The Farmindustria Working Group on antimicrobial resistance, composed of Andrea
Pitrelli (Group leader), Loredana Bergamini, Marzena Bochenska, Giovanni
Checcucci Lisi, Tiziana Di Paolantonio, Monica Gori, Federico Marchetti, Marina
Panfilo, Maria Adelaide Bottaro and Mauro Racaniello, also contributed to the Task
Force project and the drafting of this document.

12Notes1 WHO Global Action Plan (2015)
https://www.who.int/publications-detail-redirect/9789241509763.
2 Leveraging Vaccines to Reduce Antibiotic Use and Prevent Antimicrobial Resistance:
A World Health Organization Action Framework – Clinical Infectious Diseases 2021
https://pubmed.ncbi.nlm.nih.gov/33493317/.
3 Klein EY, et al. The frequency of influenza and bacterial co-infection: a systematic review
and meta-analysis. Influenza and Other Respiratory Viruses. Early View June 24, 2016.
4 Madhi SA, Klugman KP, the Vaccine Trialist Group. A role for Streptococcus pneumoniae
in virus-associated pneumonia. Nature Medicine 2004; 10: 811 – 813.
5 Ceppi batterici resistenti identificati dalla sorveglianza nazionale dell’antibioticoresistenza AR-ISS coordinata dall’Istituto Superiore di Sanità. Dai dati 2019 risultano
sotto sorveglianza i seguenti 8 patogeni: Staphylococcus aureus, Streptococcus
pneumoniae, Enterococcus faecalis, Entecoccus faecium, Escherichia coli, Klebsiellapneumoniae, Pseudomonas aeruginosa e Acinetobacter species
6 https://eur-lex.europa.eu/legal-content/IT/TXT/PDF/?uri=CELEX:52020DC0761&from=EN
7 Antimicrobial Resistance: Tackling the Gap in R&D Resources with Pull Incentives - incollaboration with Wellcome Trust | World Economic Forum (weforum.org).
8 Cama, J., et al.. To Push or To Pull? In a Post-COVID World, Supporting and Incentivizing
Antimicrobial Drug Development Must Become a Governmental Priority. ACS infectious
diseases, (2021) https://doi.org/10.1021/acsinfecdis.0c00681.
9 Dutescu, I. A., & Hillier, S. A. (2021). Encouraging the Development of New Antibiotics:
Are Financial Incentives the Right Way Forward? A Systematic Review and Case Study.
Infection and drug resistance, 14, 415–434. https://doi.org/10.2147/IDR.S287792.

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