Contro i batteri killer, eradicazione precoce e ricerca di nuovi antibiotici

Dove va la ricerca FFC – Giovanni Taccetti è un medico con specializzazione in pediatria, dedicato alla fibrosi cistica e in particolare alla infettivologia FC.

Dal 1992 lavora all’ospedale Meyer di Firenze nel Centro Fibrosi Cistica: è quotidianamente impegnato nell’assistenza ai pazienti ma riesce anche a realizzare importanti progetti di ricerca clinica riguardanti la terapia delle infezioni batteriche in FC. I primi finanziamenti ricevuti da FFC risalgono al 2003, grazie al progetto FFC 9/2003, a cui collaborò con l’obiettivo di identificare le diverse specie che compongono la famiglia Burkholderia cepacia complex. Da allora ha approfondito le proprie conoscenze e ha sperimentato protocolli terapeutici per Staphylococus aureus meticillino-resistente (MRSA) e soprattutto Pseudomonas aeruginosa.
Come è nato il suo interesse per la ricerca infettivologica?
«Al Dipartimento di Pediatria della Clinica Universitaria dell’Ospedale Meyer di Firenze, dove si è svolta la mia formazione, mi è stato insegnato che gli ospedali migliori sono quelli in cui viene svolta anche attività di ricerca.
Dal 1992 mi sono occupato di fibrosi cistica. Al Meyer esistevano già allora competenze microbiologiche
particolarmente qualificate e sono state queste che hanno indirizzato la mia attività in campo clinico. Nel tempo, l’attività di assistenza quotidiana ai pazienti mi ha messo sotto gli occhi come la prima causa di morte fossero le infezioni respiratorie: di lì lo stimolo per conoscere di più i batteri in causa e migliorarne gli schemi di trattamento antibiotico».

Lei è uno dei pochi clinici italiani che è riuscito a portare a termine trial di ricerca clinica multicentrica. Perché in Italia è così difficile realizzarli?
«è difficile ovunque, in Italia così come in altre parti del mondo. Molti ostacoli dipendono dalle  caratteristiche stesse della FC, malattia con espressione clinica estremamente variabile. Per realizzare un trial clinico è necessario individuare un problema rilevante, usare un corretto approccio metodologico e collaborare fattivamente con altri colleghi per studiare un numero consistente di pazienti, facendo così raggiungere allo studio la necessaria potenza statistica. è molto importante che le procedure per l’esecuzione di indagini ed esami siano del tutto uguali nei vari centri, altrimenti i risultati del trial non saranno utilizzabili. Tutto questo richiede un grande impegno e ha un costo elevato in termini di risorse e impiego di personale. E poi c’è l’aspetto della valutazione del progetto da parte dei Comitati Etici presenti in ogni ospedale: purtroppo le norme regolatorie per la corretta conduzione degli studi sono palesemente più complesse in Italia rispetto ad altri Paesi».

In particolare lei ha indagato la possibilità di eradicazione precoce di Pseudomonas e Staphylococcus: qual è il razionale alla base di questi trial e fino a che punto si possono eradicare questi batteri? Il trattamento è praticato in maniera simile in tutti i Centri?
«Il razionale alla base di questi studi è l’eliminazione del patogeno in fase iniziale, prima che si adatti all’ambiente polmonare e cronicizzi (progetti FFC 18/2004 e FFC 17/2007). L’eradicazione determina il ritardo della cronicizzazione dell’infezione, che è di notevole importanza clinica per il paziente. Attualmente l’esperienza nel campo dell’eradicazione di P. aeruginosa è molto più consistente rispetto al trattamento eradicante nei confronti di altri patogeni. Il protocollo di trattamento può variare e finora non ne è emerso uno più efficace degli altri.
Comunque, nei vari studi finora condotti, la percentuale di eradicazione del germe dalle vie aeree è analoga, purché la terapia sia iniziata entro breve tempo dal primo isolamento del batterio dalle vie aeree del paziente.
Il trattamento eradicante di P. aeruginosa è diventato uno standard di cura in tutta Europa per i pazienti FC e, laddove adottato, ha portato a una notevole riduzione della prevalenza dell’infezione cronica da P. aeruginosa.
Oggi si pensa anche di andare a scovare P. aeruginosa in particolari sedi dell’albero respiratorio che possono servire da nicchia e serbatoio di riserva, come naso e seni paranasali, e trattarli in modo da interrompere il passaggio alle basse vie: a questo scopo la Fondazione ha finanziato il progetto FFC 30/2015, ancora in via di svolgimento. Inferiori sono la conoscenza e l’esperienza di eradicazione di
Staphylococus aureus meticillino-resistente (MRSA) (progetto FFC 20/2012) ma i risultati preliminari sembrano già interessanti».

Che cosa vede all’orizzonte?
«All’orizzonte ci sono nuovi antibiotici, che saranno probabilmente frutto della ricerca in un campo più grande della FC e in un secondo momento potranno essere testati in pazienti FC, con un particolare sviluppo delle formulazioni adatte alla via inalatoria. La disponibilità di nuovi antibiotici andrà probabilmente in parallelo con lo sviluppo di farmaci attivi sul difetto di base, frutto di una ricerca  condotta direttamente in campo FC. I nuovi farmaci dovrebbero riuscire nell’intento di modificare le caratteristiche delle secrezioni bronchiali FC e rendere il polmone un ambiente meno predisposto all’infezione cronica.
Certo non verrà meno il bisogno di terapie antibiotiche! Ma c’è da aspettarsi che in futuro la malattia sia diversa e abbia una differente evoluzione».

Di
Flaminia Malvezzi
Pubblicato in “FFC” n. 46 – Settembre 2016

 

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