Why is the Herd Protection Level Higher in the UK than in Belgium after the Introduction of the Rotavirus Vaccine?

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(RR 1.03; 0.90-1.16), moxifloxacin (RR 1.02; 0.93-1.16) and amoxicillin-clavulanate (RR 0.93; 0.80-1.08) in the ITT population.  Conclusions: This study highlights that in adults with moderate-to-severe CAP, ceftaroline fosamil could provide an acceptable level of efficacy compared with ceftriaxone and was comparable to levofloxacin, moxifloxacin and amoxicillin-clavulanate in the ITT population. The overall findings from this review support ceftaroline fosamil as an alternative antibiotic in hospitalised adults with moderate-to-severe CAP. PIN7 Zinforo (Ceftaroline Fosamil) Versus other Empiric Initial IV Antibiotics for Complicated Skin and Soft Tissue Infections (CSSTI): A Network Meta-Analysis Rao N1, Gibson E1, Lawson RW2, Goodall JJ3 Heath, UK, 2AstraZeneca, Gaithersburg, MD, USA, 3AstraZeneca, Luton, UK 1Wickenstones, Goring

Objectives: The mainstay of treatment for complicated skin and soft tissue infections (cSSTI) continues to be empiric antimicrobial therapy combined with appropriate surgical intervention. Due to the ongoing emergence of antibiotic-resistant pathogens, contributing to treatment failure and increasing costs of treatment, there is a growing need for effective, advanced-spectrum antibacterial agents. This research aims to estimate the relative efficacy and adverse event (AE) profile of Zinforo™ (ceftaroline fosamil) a fifth-generation cephalosporin against initial IV antibiotics in methicillin-resistant staphylococcus aureus(MRSA)-suspected cSSTI.  Methods: A systematic literature review was conducted in Medline, Medline-In-Process and Cochrane to identify all published RCTs in MRSA-suspected cSSTI between 2011 and 2015. These data supported an update to an existing NMA, conducted using netmetapackage in the R project programme, where both random and fixed-effect (relative risk [RR]) models were outputted. The primary outcomes were clinical cure rate at test of cure visit (TOC), AEs/serious AEs and mortality, in the intent-to-treat (ITT), clinically evaluable (CE) and microbiologically evaluable (ME) populations.  Results: The systematic literature review identified seven relevant studies which supported the NMA. In the ITT population, the pairwise relative effects and the relative treatment effects of ceftaroline fosamil versus other antibiotics (linezolid, vancomycin, tigecycline and daptomycin) for clinical cure rates at TOC were comparable to linezolid (RR 0.96; 0.91-1.02), vancomycin (RR 1.00; 0.971.04) and tigecycline (RR 1.01; 0.93-1.07), and ceftaroline fosamil was numerically less favourable than daptomycin (RR 0.79; 0.55-1.14).  Conclusions: This study highlights that in cSSTI, ceftaroline fosamil is comparable to all comparators in the ITT population. The overall findings from this review support ceftaroline fosamil as a comparable alternative to other antibiotics used to treat MRSA-suspected cSSTI. PIN8 Hepatitis C – Real World Effectiveness of HCV Treatment in Poland Plisko R, Wladysiuk M, Miazga P, Bebrysz M HTA Consulting, Krakow, Poland

Objectives: HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. In the last years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective on SVR rates, well tolerated, allow for shorter treatment regimens based on clinical data. In 2015 year 4 new regims have been introduced to Polish reimbursement system to tread HCV for genotyp 1 (ombitasvir / paritaprevir / ritonavir / dasabuvir or sofosbuvir / ledipasvir), 1B (daklatascir / asunaprevir), 2 (sofosbuvir with ribavirin or sofosbuvir / peginterferon / ribavirin), 3 (sofosbuvir with ribavirin or sofosbuwir with with peginterferon and ribavirin), 4 (ombitasvir / paritaprevirm / ritonavir / dasabuvir or sofosbuvir / rybavirin or sofosbuvir with ribavirin or sofosbuvir / peginterferon / ribavirin), 5 (sofosbuvir with ribavirin or sofosbuvir / peginterferon / ribavirin). The first result will be obtaind from patients treated by new therapies and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication.  Methods: Retrospective patients data collection in 4 hospitals with the highest contract with NHF have begun on April 2016. We will collect: number of patients treated, characteristics of patients, ETR, SVR24, safety, reason of preliminary cessation of treatment.  Results: The data collection will be finished at the end of July 2016.  Conclusions: The aim of study is to compare real world evidence data in Polish drug programs with data from clinical trials. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. PIN9 Therapeutic Indication of Lyophilized Hydrocortisone to the Treatment of Trichinosis with Neurological and / or Myocardial Involvement Zanghelini F1, Rego MJ1, Oliveira MD1, Andrade CA1, Pereira MC1, Nunes TR1, Galdino-Pitta MR2, Viana DC3, Cardoso PR3, Pitta MG1 1Universidade Federal de Pernambuco, Recife, Brazil, 2UFPE, Recife, Brazil, 3Avenida Professor Moraes Rego, Recife, Brazil

Objectives: To evaluate the therapeutic indication of 100mg and 500mg injectable lyophilized powder hydrocortisone to the treatment of trichinosis with neurologic and / or infarct involvement. Methods: The review was carried out in March 2015 on four databases: I) BMJ - Best Practice; II) Dynamed; III) UpToDate and IV) Micromedex. The search adopted the vocabulary of structured Descriptors in Health Sciences (DeCS) and Medical Subject Headings (MeSH). Indexed descriptors used in the research were: “Trichinosis,” “Trichinellosis” and “hydrocortisone”.  Results: Base I) The treatment of trichinosis presenting systemic symptoms (including manifestations of the central nervous system, cardiac or pulmonary involvement) is the antiparasitic therapy (anthelmintic) associated with corticosteroid. However,

the corticosteroid found in the evidence was prednisolone in a dose of 0.5 to 1mg/ kg a day, administered orally, with a maximum dose of 60mg a day. The use of corticosteroids in triquinolose is based only on expert opinion and the treatment cycle is 10-15 days. Base II) The hydrocortisone sodium succinate is indicated for treatment of triquinolose presenting neurological or infarct involvement. In adults, the usual dosage is 100mg to 8g daily, and its initial therapy is 100-500mg every 2-10 hours as needed. Base III) Found evidence synthesis demonstrates that the treatment of patients with trichinosis presenting neurologic or infarct involvement should be performed with antiparasitic therapy (anthelmintic) associated with corticosteroids (prednisolone, 30-60mg a day for 10-15 days). Base IV) Hydrocortisone sodium succinate can be used in adults to treat trichinosis presenting neurologic and/or infarct involvement.  Conclusions: According to the synthesis of selected evidence hydrocortisone can be used in the treatment of trichinosis presenting neurological or infarction involvement. PIN10 Evaluation of the Number Needed to Vaccinate (NNV) with Gardasil9 in order to Avert 1 Case of Human Papillomavirus (HPV)-Related Anogenital Disease in France Uhart M, Largeron N, Drury R, Soubeyrand B Sanofi Pasteur MSD, Lyon, France

Objectives: Gardasil9 is indicated for active immunisation of individuals from the age of 9 years against precancers and cancers affecting the cervix, vulva, vagina, anus and genital warts caused by specific HPV-types 6/11/16/18/31/33/45/52/58. Gardasil9 is anticipated to prevent approximately 90% of cervical, vulvar, vaginal and anal HPV-related cancers as well as 90% of genital warts and 75-85% of highgrade cervical intraepithelial neoplasia (CIN2/3). The study objective was to estimate the NNV to prevent a case of disease by vaccinating 12 year old girls in France with Gardasil9.  Methods: The NNV was defined as NNV= 1/(r0–rv) where r0 represents the risk of the disease in the absence of vaccination and rv represents the risk of the disease in vaccinees with Gardasil9 over a fixed period of time. rv is defined as rv= r0*(1–VE) where VE represents the vaccine efficacy for each considered disease as listed in the SmPC. We assume the epidemiology of HPV related diseases and the current sceening context of cervical cancer remain stable over the time, vaccination of a cohort of 12 years old girls(i.e. HPV-naïve individuals) and a lifetime vaccine protection. Disease incidences and proportion of cases attributed to the HPV-types included in the vaccine were retrieved from Hartwig et al. 2015 and Monsonego et al. 2007.  Results: NNV estimates to prevent a case of cervical, anal, vaginal, and vulvar cancer were respectively 126, 683, 2744 and 3162. Regarding precancers, NNV estimates were 10, 2843, 1168 and 186 respectively to avert a case of CIN2/3, AIN2+, VaIN2+ and VIN2+. Last, the estimated NNV to avert a case of genital wart was 8. Overall, NNV to prevent one case of any indicated cancer is 99; 9 to prevent any indicated precancer and 4 to prevent any indicated disease.  Conclusions: The low NNV illustrate the important benefits expected from the Gardasil9 vaccination program. PIN11 Susceptibility Pattern of Pseudomonas Aeruginosa Isolates to Carbapenem Antibiotics Zubair M1, Hussain T2 1Peshawar Medical and Dental College, Peshawar, Pakistan, 2National University of Sciences and Technology, Islamabad, Pakistan

Objectives: Pseudomonas aeruginosa is one of the most common pathogens responsible for nosocomial infections. Multidrug resistant isolates of P. aeruginosa pose significant health risks to hospitalized patients. Carbapenems are prescribed as the last resort antibiotics against the multidrug resistant isolates. The aim of this study was to assess the susceptibility pattern of clinical isolates of P. aeruginosa to carbapenems, and to obtain baseline information for empirical therapy.  Methods: One hundred and twenty two multidrug resistant P. aeruginosa isolates were collected from indoor patients in the Khyber Teaching Hospital (KTH) in Peshawar, Pakistan during January to June 2016. Kirby-bauer disc diffusion tests were used to check susceptibility of the isolates to carbapenem antibiotics (imipenem, meropenem, doripenem).  Results: Twenty three percent of the isolates (n= 28) were found resistant, with varying resistance level to the tested carbapenems such as imipenem (23%), meropenem (15%) and doripenem (11%).  Conclusions: This study confirms that resistance is emerging in P. aeruginosa isolates to carbapenems- the last resort antibiotics. Prevalence of such a high resistance to carbapenems is very alarming and urgently requires implementation of infection control measures in order to prevent the spread of carbapenem resistance among bacterial communities. Resistance is potentially linked to the injudicious use of antibiotics. A strict antibiotics treatment policy is required to preserve antibiotics and protect humans from the drug-resistant deadly infectious diseases. PIN12 Why is the Herd Protection Level Higher in the UK than in Belgium after the Introduction of the Rotavirus Vaccine? Standaert B1, Schecroun N2, Lorenc S3 1GSK Vaccines, Wavre, Belgium, 2Keyrus Biopharma C/O GSK, Wavre, Belgium, 3Bartech Belgium SA C/O GSK, Wavre, Belgium

Objectives: Belgium and the UK have introduced rotavirus vaccination as a universal mass vaccination (UMV) program. There was an impressive herd protection effect measured among the unvaccinated at-risk children (1-5 years old [y]) expressed through reduced hospitalization rates for the disease during the 2 epidemic periods following the vaccine introduction. Surprisingly, the herd protection level was higher in the UK than in Belgium. Is there an explanation?  Methods: A semi-dynamic population model was developed to estimate the proportion of vaccinated children during the rotavirus epidemic period following the start of the UMV at different time points. It is assumed that the children < 1y, if unvaccinated, are the ones who mainly spread the virus around. As the starting date of the UMV was different between the



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two countries, calculating the estimated vaccinated proportion of children during the first epidemic season post-vaccine introduction per country, allows an estimation of the difference in herd protection. The latter data were then compared with observed data.  Results: Belgium started its UMV 2 months before the following epidemic rotavirus-season while the UK started 6 months before. It resulted in an estimated difference in the proportion of vaccinated children < 1y during the following epidemic period about 45% (UK proportion 90%, Belgium 45%). The resulting difference in herd protection in terms of avoided hospitalizations is about 25% and is in line with the observed difference in reduction of hospitalizations in the 1st year (87% for the UK versus 62% for Belgium).  Conclusions: For obtaining a maximum benefit in rotavirus vaccination with a strong herd protection effect early on, the start of the UMV should occur with a high uptake and at an optimal period of the year, e.g. 6 months before the following rotavirus season. Only then will this strategy enable the gain of the full economic benefit the vaccine can give. PIN13 Prediction of the Morbidity with Bacterial Purulent Meningitis of Various Origin with Consideration of the Existing Vaccine Prevention Procedures Ryazhenov VV1, Gorokhova SG2 First Moscow State Medical University, Moscow, Russia, 2Research Clinical Center of JSC Russian Railways, Moscow, Russia

1I.M. Sechenov

Objectives: To analyze the morbidity with bacterial purulent meningitis (BPM) in the population of Russian patients. To create a predictive model of the number of patients with BPM and the probability of clinical outcomes dependent on the applied tactics of vaccine prevention.  Methods: On the initial stage, we searched for the data on the morbidity with BPM caused by various serogroups of Neisseria meningitidis. Next, we developed clinical and statistical model of patients with generalized forms of meningitis (GFM) with consideration of serogroups of infectious agents.  Results: The analysis of patients with GFM caused by Neisseria meningitides revealed that 624 Russian patients before 17 y.o. will be diagnosed with this infectious agent, including 531 children of 0-4 y.o. In Moscow, the number of GFM patients < 17 y.o. will be 88-132, including 74-112 before 5 y.o. The analysis of the distribution of patients by serotypes of Neisseria with consideration of the morbidity in Russia revealed that 219 will have A serotype, 194 — B serotype, 294 — C serotype, and 24 — other serotypes. In Moscow, 26-39 patients will have A serotype of Neisseria meningitides, 23-35 — B serotype, and 35-53 — C serotype. The introduction of Menactra vaccine to the immunization schedule will change the morbidity with Neisseria meningitides. In Moscow, it will reduce from 74-112 cases to 13-20 cases. The mortality will also change. Actual mortality in Moscow among patients of 0-4 y.o. with confirmed diagnosis of Neisseria meningitides is 13-19 cases. The use of Menactra vaccine will reduce this value to 2-4 cases.  Conclusions: Introduction of Menactra vaccine is a rational strategy of BPM prevention. It helps to reduce both morbidity and the probability of lethal outcomes. PIN14 Burden of Medically Attended Acute Gastroenteritis in England: A Cohort Study in CPRD Ferreira G1, Lopman BA2, Tam C3, Harris J4, Bollaerts K1, Cattaert T1, Riera M1, Vestraeten T1 1P95 Pharmacovigilance and Epidemiology Services, Leuven, Belgium, 2National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Preventiion, Atlanta, GA, USA, 3National University of Singapore, Singapore, Singapore, 4University of Liverpool, Liverpool, UK

Objectives: Medically attended acute gastroenteritis (MAAGE) is due to multiple causes including viruses, bacteria and parasites. The objective was to assess the episode rates of MAAGE to inform the cause-specific MAAGE burden of disease.  Methods: Patients registered in general practices contributing to Clinical Practice Research Datalink (CPRD) from January 2006 to December 2014 and eligible for Hospital Episode Statistics (HES) Inpatient linkage data were included. Cases were defined based on MAAGE related Read and ICD-10 codes. Episodes were defined as events separated by a minimum 14-day disease-free period. Episode rates with 95% CIs were calculated by calendar year and month, age group (< 1, 1-4, 5-9, 10 -17, 18-64, 65-74, 75-84 and 85+ years old), gender, region, healthcare setting (GP care only or requiring hospitalization) and aetiology.  Results: A total of 5 124 812 subjects (50.9% female) were included in the study with a median follow-up time in CPRD of 7.6 years. 273 774 cases were identified with at least one MAAGE episode, representing an overall episode rate of 12.95 per 1000 person-years (95%CI: 12.9012.99). The highest burden was observed in < 1 years old, 1-4 years old, and 85+ years old, with episode rates of 95.57 (94.38-96.76), 39.26 (38.89-39.62) and 36.02 (35.56-36.49) respectively. Episode rates were stable year-on-year with marked winter seasonality. Episode rates requiring GP care only vs. requiring hospitalization were 7.43 (7.40-7.47) and 5.52 (5.49-5.55) respectively. The episode rate with aetiology unspecified was 11.81 (11.77-11.86)  Conclusions: Burden of MAAGE is high in the CPRD population with the highest episode rates in children and elderly. In order to assess cause-specific burden of MAAGE further statistical modelling development is required to attribute the high proportion of cause-unspecified MAAGE. ISAC protocol 16_063R. PIN15 Findings of a Literature Review in Support of a Patient Count Model (PCM) for Hepatitis C Virus (HCV) in the EU5 Gueron B1, Nalpas C1, Maiese BA2, Cadarette SM2, Campbell DJ2, Arvin-berod C3, Duchesne I4 1Janssen Pharmaceuticals, Paris, France, 2Xcenda, Palm Harbor, FL, USA, 3Xcenda Switzerland GmbH, Bern, Switzerland, 4Janssen EMEA, Beerse, Belgium

Objectives: A literature review was performed to support the development of an HCV PCM in the EU5 from 2017-2021. Methods: MEDLINE, via PubMed (2010-January 2016) and recent conferences (2014-2016) were searched for stud-

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ies on the epidemiology of HCV and related clinical/patient factors.  Results: The literature review identified 51 studies that included HCV epidemiology outcomes potentially pertinent for inclusion in the PCM. However, several key data gaps were identified among the more recently-published literature. For example, data on HCV prevalence in the general population were not found for Italy or the UK, and estimates for other countries were not well-aligned with other data sources such as continent-wide surveillance reports. Data on HCV prevalence in subgroups were more readily available, including for people who inject drugs: 50.5% in the UK (data years: 2004−09) to 81.1% in Italy (2000; 2005−2007); HIV/HCV co-infected patients: 16.4% in France (2011) to 31.0% in a multi-country study (year NR); and prisoners: 4.8% in France (2010) to 25.3% in Spain (2004−05). No population-level incidence data were identified. Only 2 studies reported information regarding HCV diagnosis rates, with 35−65% of patients unaware of HCV-positive status. Additional limitations include the lack of data on the impact of migration to Europe from areas with endemic HCV.  Conclusions: The literature review identified recent key parameters across multiple subpopulations that may be required for parameterization of a PCM. However, limited recent incidence, prevalence, and other important epidemiologic data may require the use of older data sources for the PCM, highlighting the need for newer epidemiological studies in this rapidly changing disease area. Additionally, sources other than primary literature may be utilized. For example, where peer-reviewed primary studies are not available, secondary sources such as reviews, surveillance reports, health technology assessments and other policy documents, and expert opinions may be consulted to complete PCM parameterization.

INFECTION – Cost Studies PIN16 Managing Healthcare Resources: Estimated Budget Impact On The National Health Service (England) Of Introduction Of Antimicrobial Sutures Edmiston CEJr 1, Holy CE2, Leaper DJ3 1Medical College of Wisconsin, Milwaukee, WI, USA, 2Johnson & Johnson, New Brunswick, NJ, USA, 3Institute of Skin Integrity and Infection Prevention, Huddersfield, UK .

Objectives: Despite a large number of randomized trials and reviews evaluating the effectiveness of antimicrobial sutures (AMS), the clinical and cost impact of using AMS vs. non-coated sutures (NCS) are not well documented and were therefore evaluated in this study.  Methods: A systematic review and meta-analysis of all published evidence comparing AMS to NCS from 01/01/2005 to 02/2016 was conducted. Surgical site infection (SSI) was the primary outcome. A sub-analysis further evaluated risk of SSI based on surgical wound classification (SWC), as defined by the Centers for Disease Control and Prevention. For this sub-analysis, studies were categorized as: Group 1: Clean, Group 2: Clean/contaminated, Group 3: Contaminated and Dirty-infected, Group 4: Undefined or including a mix of wound types. The results of the meta-analysis were used in a decision-tree deterministic and stochastic cost model, using United Kingdom (UK)-based cost of SSI and sutures.  Results: From an initial 66 citations, 32 unique data points from 28 distinct manuscripts were included in the final assessment. Of the 28 studies, 68% were randomized and 61% reported blinding of physicians and evaluators. The odds ratio (OR) for SSI in the TCS vs control was significant at 0.617 (95% confidence interval (CI): 0.526 to 0.724, p= 0.029). There was significant heterogeneity (I2=  33%). Whereas there was a clear trend of increased effectiveness by SWC type, a meta-regression did not identify SWC as a significant predictor of SSI, most likely because of the small number of studies in Group 3. Using these estimates of SSI risks, the average savings per surgery ranged from £122.0 (95% CI: £66.6 to £190.3 for clean wound to £411.54 (95% confidence interval: £202.1 to £677.8) for dirty wound surgeries.  Conclusions: Using UK-based healthcare costs and published rates of SSI, use of AMS result in significant savings for all surgical wound types. PIN17 Budget Impact Analysis Of Ceftolozane/Tazobactam (Zerbaxa) For The Treatment Of Complicated Intra-Abdominal Infections And Complicated Urinary Tract Infections In The Italian Setting Barbieri M1, Crocchiolo D2, Veneziano MA2 for Health Economics, University of York, York, UK, 2MSD Italy, Rome, Italy

1Centre

Objectives: Antibiotic-resistant Gram-negative bacteria prevalence in Italy is one of the highest in Europe, causing the need of new therapeutic options effective on resistant strains. The aim of this study is to estimate the budget impact following the introduction of Zerbaxa in the treatment of complicated intra-abdominal infections (cIAIs) and complicated urinary tract infections (cUTIs) both for the Italian National Health Service (NHS) and at a regional level.  Methods: A budget impact model was developed over a 3-year time horizon using local epidemiological data. We used real data of market consumption (IMS data, year 2015-2016) to estimate the relative share of products used in the Italian setting (flouroquinolones, penicillins, cephalosporins, carbapenems) for the treatment of cUTIs and CIAIs. Market penetration of Zerbaxa was based on manufacturer’s assumptions. Data were validated by three experts which received questionnaires. Unit costs were taken from Italian standard sources. Univariate sensitivity analyses were conducted on key model parameters.  Results: A total of 11,009 cIAIs infections and 16,325 cUTIs infections were considered as model population at the first year, with an assumed 16.8% annual growth rate. The introduction of Zerbaxa over the next 3 years, assuming a market share of 0.76%, 3.26% and 12.16% respectively for the first, second and third year for cIAIs and 1.10%, 4.71% and 17.57% for cUTIs would lead to a total of approximately € 12.1 million cost increase to the Italian NHS (4.9 million for cIAIs and 7.2 million for cUTIs). At a regional level, cost increase ranged from approximately € 25k for Valle d’Aosta region to € 2 million for Lombardia region.  Conclusions: This analysis suggests that the use of Zerbaxa for the treatment of cIAIs and cUTIs would lead to an increase in cost to the Italian NHS lower than 5% over three years of total expenses for treating these infections.