Congressional testimony by the Surgeon General of the United States, 1969

1. EMERGENZE INFETTIVE DAL 1970 It is time to “close the book on infectious diseases.” Surgeon General William H. Stewart Congressional testimony by the Surgeon General of the United States, 1969

5. 16 antimicrobial compounds in late-stage clinical development Eight compounds have activity against gram-positive organisms Eight compounds have activity against both gram-positive and gram-negativeorganisms From these 13 pharmaceutical leaders,just 3 new compounds are in advanced clinical development, thus reflecting the companies’ decreased investment in this therapeutic area

6. Compounds with activity against both Gram-positive and Gram-negativeorganisms

7. Pharmacogenomics, 2008 Non-antibiotic coumpounds

8. Pharmacogenomics, 2008 Non-antibiotic coumpounds

10. Hand washing Full-barrier precautions during catheter insertion Cleaning the skin with clorexidine Avoiding femoral site if possible Removing unnecessary catheters

11. Multifaceted interventions Introduction of VAP bundle Measure of compliance and feedback Cocanour CS et al. J Trauma 2006

12. “despite the advance in diagnostic technology, it has been necessary to maintain proficiency at the reference laboratory in “old school” microbiology skills such as culture, identification, and susceptibilities testing of bacteria, fungi, parasites, and viruses” Very advanced diagnostic technology.. Very rapid turnaround time (15 min).. Bed-side diagnosis..

13. Molecular test versusstandard culture RR (95% CI) 0.87 (0.61-1.24)

14. Molecular test versusno screening Incidence of MRSA BSI RR (95% CI) 0.54 (0.41-0.71) Incidence of MRSA SSI RR (95% CI) 0.69 (0.46-1.01)

15. Multi-drug resistant organisms control in hospitalAlert systems and IC Task Force • Diagnosis of infection OR colonization • Appropriate antibiotic therapy • Application of infection control measures • Education of HCWs • Follow-up

16. Policlinico A. Gemelli 114 Alerted case from May to October 2009 49% from medicine wards 20% from ICU 18% from surgery 13% from rehabilitation and geriatrics

17. HIV

18. LIVER Factors Affecting Concentration of Antiviral Drug at its Site of Action Absorption Metabolism CYPs P-gp Oral AdministrationDrug (tablet/capsule) Dissolution GI MUCOSA CYP3A4/5 CYP2B6 CYP2C19 P-gp SYSTEMIC CIRCULATION PIs NNRTIs ProteinBoundDrug FreeDrug Distribution TISSUES Bound Drug Free Drug • TARGET CELL • NRTIs (Intracellular Phosphorylation) • Protease Inhibitors • NNRTIs Excretion URINE NRTIs

19. Toxicity Efficacy TDM

20. Predictors of 48 weeks virological failure Therapeutic drug levels independently associated with a lower risk of virological failure Fabbiani M. et al. JAC 2009

21. The 50 Best Inventions of 2009 From a rocket of the future to a $10 million lightbulb, here are TIME's picks for the best new gadgets and breakthrough ideas of the year

22. Lights and shadows of clinical trials of HIV vaccines • The first three Phase III clinical trials have been discontinued for safety reasons, having more infections among the vaccinated than the placebo group. • Recently the Phase III clinical trial performed in Thailand using a priming with recombinant canarypox vector (ALVAC-HIV) plus two booster injections of a recombinant glycoprotein 120 subunit vaccine (AIDSVAX B/E) showed a 30% reduced infections in the vaccinated group. Published on October 20, 2009 N Engl J Med 2009;361.

24. Our “shock and kill” technique infected cells uninfected cells high intracellular glutathione levels “Shock” Addition of an HDAC inhibitor low Addition of buthionine sulfoximine “Kill” Cells survive treatment Cells die

25. Scaffold Medicine

26. Diversity-Oriented Synthesis: un approccio alla diversità strutturale

27. Molecular modeling preliminare

28. HLA B*5701 e Abacavir

29. CYP2B6 e Efavirenz

30. HLA, CYP2B6, ABCB1 e NEVIRAPINA

31. UGT1A1 e Atazanavir

32. Individualized Medicine

34. INTELLIGENT TECHNOLOGY

35. Interventional trialTREAT wards vs controlsTreatment costs P = 0.007 Euros

36. All laboratories analysis of all patients of the hospital are stored into the central database. Periodically a procedure extracts analysis for all patients present in the database server and stores them into a shared directory on the server machine. SecureODBC on Internet An Open Source ETL (Extraction Transformation and Load) tool is installed server-side. An automated process extracts analysis from the shared directory, applies several transformations in order to make analysis fit physicians’ needs and stores them into the analysis table. The chemical analysis mask, with de-normalized data (one exam = one column) ETL tool loads data into a relational database, built with normalized structure and exposed on Internet/intranet via secure ODBC connection. Analysis structure is de-normalized in real-time during physicians db exploration and is shown in user friendly forms. User authentication provides access control and strict db privileges management. …read/write… Hematological analysis Chemical analysis Microbiological analysis Physicians’ home Virolab offices

37. Results: GRT vs. DHby therapy line There is an increase in performance by increasing the therapy line: i.e. all models predict better when there is a long known therapy history On the other hand, subsequent therapy lines are likely to be more unsuccessful

38. HEALTH TECHNOLOGY ASSESSEMENT