Infezioni da microorganismi multi-resistenti: dove abbiamo

sbagliato, come possiamo rimediare

Antonio Cascio

Università di Palermo

il batterio è stato individuato lo scorso mese nelle urine di una donna della Pennsylvania di 49 anni

• MDR: non -susceptibility to at least one agent in three or more antimicrobial categories.

• XDR: non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories).

• PDR: non -susceptibility to all agents in all antimicrobial categories (i.e. no agents tested as susceptible for that organism).

Magiorakos et al,Clin Microbiol Infect 2012; 18: 268–281

• Critical priority: – Pseudomonas aeruginosa, carbapenem-resistant – Enterobacteriaceae, carbapenem-resistant, ESBL-producing – Acinetobacter baumannii, carbapenem-resistant

• High priority:

– Enterococcus faecium, vancomycin-resistant – Staphylococcus aureus, methicillin-resistant, vancomycin-intermediate and resistant – Helicobacter pylori, clarithromycin-resistant – several species of Campylobacter, fluoroquinolone-resistant – Salmonellae, fluoroquinolone-resistant – Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant

• Medium priority:

– Streptococcus pneumoniae, penicillin-non-susceptible – Haemophilus influenzae, ampicillin-resistant – several species of Shigella, fluoroquinolone-resistant

Executive order.

Combacting antibiotic resistant Bacteria

• Con l’autorità conferitami come Presidente dalla Costituzione e dalla legislazione degli Stati Uniti d’America, ordino quanto segue: – -------

• La lotta ai batteri resistenti agli antibiotici rappresenta una priorità di sicurezza nazionale. Lo staff del Consiglio di Sicurezza Nazionale, in collaborazione con l’Ufficio di Politica Scientifica e Tecnologica, con il Consiglio di Politica Interna, e con l’Ufficio di Gestione e Bilancio, dovrà coordinare lo sviluppo e l’attuazione delle politiche del Governo Federale per la lotta ai batteri resistenti agli antibiotici tra cui le attività, le relazioni e le raccomandazioni della Task Force per la lotta alla resistenza agli antibiotici prevista nella sezione 3 della presente ordinanza.

• Migliorare l’Antibiotic Stewardship • Potenziamento degli sforzi nazionali di sorveglianza per i batteri resistenti • Prevenzione e risposta alle infezioni e ai focolai epidemici da organismi

antibiotico-resistenti • Promuovere lo sviluppo di antibiotici e di tecniche diagnostiche di nuova

generazione

Antimicrobial resistance concern clinicians

• Treatment options are limited and sometimes nonexistent;

• Resistance has spread widely on several fronts;

• Dissemination and acquisition may be silent and pose significant challenges for infection control;

• Infections are associated with increased mortality and economic costs.

Antibiotic resistance

• Mutation of existing DNA;

• Uptake of foreign DNA by means

of:

– transformation

– phage-mediated transduction

– Conjugation (DNA exchange

directly from other bacteria).

• Old and new antibiotics vary in their impact on the emergence and spread of resistant bacteria

Dove abbiamo

sbagliato?

• Targeted metagenomic analyses of rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost sediments and the identification of a highly diverse collection of genes encoding resistance to b-lactam, tetracycline and glycopeptide antibiotics.

• Structure and function studies on the complete vancomycin resistance element VanA confirmed its similarity to modern variants.

• These results show conclusively that antibiotic resistance is a natural phenomenon that predates the modern selective pressure of clinical antibiotic use.

• Viable multidrug-resistant bacteria were cultured from the Lechuguilla Cave in NewMexico even though it has been totally isolated for >4 million years.

• These bacteria were resistant to at least 1 antibiotic and often 7–8 antibiotics, including β-lactams, aminoglycosides, and macrolides, as well as newer drugs such as daptomycin, linezolid, telithromycin, and tigecycline

• Despite their isolation, presumably for >11,000 years since

their ancestors arrived in South America, and no known exposure to antibiotics, they harbor bacteria that carry functional antibiotic resistance (AR) genes, including those that confer resistance to synthetic antibiotics and are syntenic with mobilization elements.

• Eighty percent of antibiotics sold in the US are for use in animals, primarily for growth promotion and infection prophylaxis, without adequate data supporting efficacy

• It is suggested that nearly half of the 210,000 tonnes of antibiotics produced in China are deployed in food animals.

• Some studies give data on what antibiotics are found in waterways and manure in China, which gives an indirect idea of both that the amounts used and types of antibiotics are used. However this is still all only based on relatively limited sample sizes.

• From the information available, it suggests high volumes of sulphonamides, tetracyclines and fluoroquinolones (enrofloxacin, fleroxacin and norfloxacin) are widely used in the agriculture sector there.

Ecologia delle malattie

• Tutte le patologie emergenti degli ultimi 30-40 anni sono da ritenere il risultato delle modifiche nella demografia mondiale e degli sconfinamenti dell'uomo in terre non abitate in precedenza.

• Poor-quality medicines present a serious public health problem, particularly in emerging economies and developing countries, and may have a significant impact on the national clinical and economic burden.

• Attention has largely focused on the increasing availability of deliberately falsified drugs, but substandard medicines are also reaching patients because of poor manufacturing and quality-control practices in the production of genuine drugs (either branded or generic).

• Substandard medicines are widespread and represent a threat to health because they can inadvertently lead to healthcare failures, such as antibiotic resistance and the spread of disease within a community, as well as death or additional illness in individuals.

• Antibiotics at sublethal concentrations can promote genetic exchanges through multiple pathways involving various stress responses.

Fleming in reference to Penicillin

• The public will demand [the drug and]…then will begin an era… of abuses. The microbes are educated to resist penicillin and a host of penicillin‐fast organisms is bred out which can be passed to other individuals…In such a case the thoughtless person playing with penicillin treatment is morally responsible for the death of the man who finally succumbs to infection with penicillin‐resistant organism. I hope the evil can be averted.

Fleming A. Penicillin’s finder assays its future. New York Times. 1945; 21

Come possiamo

rimediare

• Addressing antibiotic abuse in farm animals;

• Methods to implement prevention of nosocomial infections;

• Stewardship to improve hospital-based antibiotic use; – ….

– Avoid inappropriate antibacterial use for viral infections;

– Resisting the urge to treat colonization rather than true infection;

– Discontinuing use of antimicrobials when infection is cured or unlikely ;

• Diagnostic methods that can transform the management of infectious diseases;

• Methods to promote antibiotic development

Decrease in Nonhuman Use of Antimicrobials.

• Currently, only the European Union has banned (since 2006) the use of antibiotics for nontherapeutic uses in farm animals.

• It has been estimated that 80% of antimicrobial use in the United States is for nontherapeutic uses in livestock.

• Further inroads globally should be made into regulating such use because this has been linked to antimicrobial resistant human infections.

Infection Control and Antimicrobial Stewardship.

• Multidisciplinary teams (involving physicians, pharmacists, microbiologists, and nurses).

• Antimicrobial stewardship should extend beyond inpatients to the outpatient setting (including emergency departments), where most patients are seen.

Prevention of nosocomial infections

• Awareness

• Hand hygiene

• Contact Isolation – Gloves + Gowns – Equipment dedicated to room – Disinfect personal equipment used in room

• Limit HCW exposure

Active Surveillance and Interrupting the Chain of Transmission

• Early detection, isolation and cohorting, and skin decontamination in select patient groups (eg, daily chlorhexidine bathing) can help interrupt the chain of transmission.

• Novel approaches may help in decreasing environmental contamination (eg, adenosine triphosphate bioluminescence or UV monitoring for effectiveness of environmental cleaning, hydrogen peroxide vapor decontamination, and use of coppercoated surfaces);

• Laboratories, depending on local hospital epidemiology, should determine the optimal method for CPGNB screening and be aware that no one method is perfect (molecular methods only detect resistance targets identified in the assay, whereas phenotypic methods may be less sensitive overall and are generally more labor intensive).

Regional or National and International Level

Information Sharing.

• Given the potential for rapid regional dissemination of resistant GNB with increased interfacility transfers for medical care, novel methods to accurately identify patients who are at risk of or who are known CPGNB carriers during transfer of care will help ensure that appropriate infection control measures will be continued.

• Regional antimicrobial surveillance networks, such as the Healthcare-Associated Infections-Community Interface, European Antimicrobial Resistance Surveillance Network, and Asian Network for Surveillance of Resistant Pathogens, play an important role in providing necessary data for policy making and resource allocation.

• The ID specialty should be seen as an essential component in modern healthcare.

• The money used to create an effective ID service is well-invested, since ID specialists will decrease the risk of dissemination of infections within hospitals and within society.

• Also, by optimising antibiotic treatment, in terms of choice of drugs, dosages and treatment times, these specialists can contribute to a reduction in the incidence of antimicrobial resistance, the consumption of such medicines and the risk of nosocomial infections caused by resistant bacteria.

• To be optimally efficient, the ID specialist must work in close cooperation with clinical microbiologists and hospital hygiene specialists.

• When outbreaks occur, cooperation with public health organisations is also necessary, as well as with national infection control agencies and with international organisations such as the European Centre for Disease Prevention and Control and the WHO

The impact of infectious diseases

consultation on oncology practice

67

•428 batteriemie, 850 letti

•Terapia antibiotica indirizzata su

blood colture o su IDS

•Empirica appropriata nel 63%

sale al 78% con IDS

•IDS più rapido shift a orale e

meno largo spettro

The Value of Infectious Diseases Consultation in

Staphylococcus aureus Bacteremia

56% reduction in moratlity

Proposte

• Assumere infettivologi

• Presenza di almeno un infettivologo per ospedale

• Possibilmente istituire un servizio di infettivologia in ogni ospedale (tale servizio dovrebbe essere in rete con gli altri servizi di infettivologia e dipendere dalla UOC di malattie infettive più vicina)

• This article will detail the available data supporting the value of infectious diseases specialists in their roles of directing antimicrobial-management and infection-control programs, maintaining health care workers’ well-being, and minimizing exposure

Steward: definition

a person and especially a

man whose job is to serve

meals and take care of

passengers on a train,

airplane, or ship

Antimicrobial Stewardship Programs

ASPs are designed

• To optimize antimicrobial therapy,

• To improve patients’ outcomes,

• To ensure cost-effective therapy and

• To reduce adverse effects associated with

antimicrobial use, including antimicrobial

resistance

MacDougall C et al. Clin Microbiol Rev 2005; 18; 638–656

Lesprit P et al. Curr Opin Infect Dis 2008:21; 344–349

Kaki R et al. J Antimicrob Chemother 2011; 66: 1223–1230

•“The reductions in antimicrobial utilization associated with

stewardship interventions have not been associated with any

worsening in nosocomial infection rates, length of stay or

mortality among intensive care patients.”

“Stewardship interventions were associated with … fewer antibiotic adverse events.”

IMPACT OF STEWARDSHIP ON SAFETY?

Alla Regia Centrale Regionale (RCR) dovranno pervenire: • i dati del consumo degli antibiotici (i farmacisti

invieranno il consumo mensile degli antimicrobici separati per UOC sia al CIO che alla RCR)

• i dati relativi agli isolamenti di germi MDR (possibilmente in tempo reale). (I microbiologi invieranno i dati al sia CIO di competenza che alla RCR)

• I dati relativi agli indici occupazionali e i DRG delle UOC coinvolte (calcolo del numero di paz ricoverati/giorno). Le Direzioni Sanitarie invieranno i dati con cadenza mensile

• I risultati delle indagini di prevalenza puntuale delle ICA (eseguiti ogni 4 mesi)

Necessario fare rete

BUONA POLITICA

BUONI TECNICI

Regia Centrale Regionale

• Funzione di coordinamento dei CIO • Coordina interventi omogenei nelle diverse

aziende (metodologie che garantiscano l’ottenimento di risultati condivisibili) relativi a – Prevalenza/incidenza di infezioni nosocomiali – Consumo di singoli antimicrobici per UOC – Prevalenza/incidenza di microrganismi sentinella

• Raccoglie in tempo reale i dati forniti dai CIO e li analizza provando anche a correlare i dati del consumo degli antibiotici con quelli della prevalenza dei microrganismi MDR

Regia Centrale Regionale

Igienista/i

Infettivologo/i

Microbiologo/i

Braccio operativo

Igienista/i

Infettivologo/i

Microbiologo/i

Alla Regia Centrale Regionale (RCR) dovranno pervenire: • i dati del consumo degli antibiotici (i farmacisti

invieranno il consumo mensile degli antimicrobici separati per UOC sia al CIO che alla RCR)

• i dati relativi agli isolamenti di germi MDR (possibilmente in tempo reale). (I microbiologi invieranno i dati al sia CIO di competenza che alla RCR)

• I dati relativi agli indici occupazionali e i DRG delle UOC coinvolte (calcolo del numero di paz ricoverati/giorno). Le Direzioni Sanitarie invieranno i dati con cadenza mensile

• I risultati delle indagini di prevalenza puntuale delle ICA (eseguiti ogni 4 mesi)

Consumo Antibiotici

Farmacie Aziende

UOC Microbiolog

Isolamenti microorg. MDR

Direz. Sanit. Indici occupazionali

e DRG

CIO Risultati indagini di point prevalence

Audit e feedback

CIO CIO CIO CIO CIO CIO CIO

Servizio 5 - Qualità, governo clinico e sicurezza dei pazienti del Dipartimento per le Attività Sanitarie e Osservatorio Epidemiologico (D.A.S.O.E.)

UOC Microbiologia Riferimento Regionale

UOC Microbiologia Riferimento Regionale

UOC Microbiologia di Riferimento

• Istituzione di n.2 UOC di Microbiologia di riferimento regionale – Sicilia occidentale - Palermo (Prof.ssa Anna Giammanco) – Sicilia Orientale - Catania (Prof.ssa Stefania Stefani)

• Funzione – Collettori dei microrganismi MDR provenienti dai

laboratori dei relativi bacini • Tipizzazione microrganismi MDR • Antibiogramma con MIC • Saggio di antibiotici in combinazione in caso di infezioni difficili (su

espressa richiesta del clinico) • archiviazione ed elaborazione dei dati • Invio dei dati alla Regia Centrale con cadenza semestrale

Costi

• Implementazione UOC di Riferimento (strumentazione e personale tecnico specializzato)

• Laboratory Information System

• Database e manutenzione dello stesso

• Epidemiologo/microbiologo/infettivologo addetto alla gestione dei dati