Nosocomial Infections The need for new gram-negative drugs

ABOUT DATAMONITOR HEALTHCARE
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About the Infectious Diseases and Respiratory (ID&R) pharmaceutical analysis team
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CHAPTER 1 EXECUTIVE SUMMARY
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Scope of the analysis
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Datamonitor insight into the nosocomial infections market
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CHAPTER 2 DISEASE BACKGROUND
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Disease definition
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Epidemiology
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Modes of acquisition
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Surgical site infections
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Causative pathogens
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General incidence
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Pathogenesis
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Bloodstream infections
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Causative pathogens
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General incidence
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Intravascular catheter-related infections account for the majority of BSIs
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Pathogenesis
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Urinary tract infections
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Causative pathogens
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General Incidence
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The majority of hospital acquired UTIs are associated with contaminated urinary catheters
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Pathogenesis
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Pneumonia
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Causative pathogens
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General incidence
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Mechanical ventilation increases the risk of HAP
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Pathogenesis
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CHAPTER 3 ETIOLOGIC AGENTS
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Bacterial pathogens
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Bacterial resistance
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Gram-positive bacteria
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Staphylococcus aureus
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Enterococci
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Clostridium difficile
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Gram-negative bacteria
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Escherichia coli
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Klebsiella pneumoniae
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Pseudomonas aeruginosa
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Acinetobacter baumannii
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Viral pathogens
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Fungal pathogens
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CHAPTER 4 TREATMENT OPTIONS
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Hospital antibacterial market
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The overall value in terms of patient numbers
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Size of the market in terms of sales
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Classes of antibacterials
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Cephalosporins
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Penicillins
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Fluoroquinolones
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Carbapenems
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Macrolides and ketolides
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Glycopeptides
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Empiric management of nosocomial infections
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Cost of therapy by site of infection
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Surgical site infections
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Antibiotic prophylaxis prior to surgical operations
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Post-operative treatment
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Bloodstream infections
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Urinary tract infections
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Hospital acquired pneumonia
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Pathogen specific therapy
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Gram-positive pathogens
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Staphylococcus aureus (including MRSA)
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Enterococci
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Clostridium difficile
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Gram-negative pathogens
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Klebsiella pneumoniae
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Pseudomonas aeruginosa
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Acinetobacter baumannii
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Factors influencing physician decision-making
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CHAPTER 5 FUTURE TRENDS AND IMPROVING TREATMENT OUTCOMES
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New product development
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Effective gram-negative drugs is the greatest unmet need
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The financial burden of multidrug-resistant gram-negative organisms
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Majority of newly introduced compounds and compounds in late-stage development target gram-positive pathogens
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Tigecycline
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Daptomycin
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Dalbavancin
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Telavancin
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Doripenem
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Ceftobiprole
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Preventative strategies to help combat spread of infections in hospitals
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Surveillance
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Combating bacterial resistance
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Financial burden of nosocomial infections
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BIBLIOGRAPHY
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Books
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Press releases
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Websites
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Datamonitor reports
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Contributing experts
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Disclaimer
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List of Tables

Table 1: Most common pathogens isolated from hospital acquired bloodstream infections, US
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Table 2: Incidence rates and distribution of pathogens most commonly isolated from monomicrobial bloodstream infections and associated crude mortality rates for all patients, patients in intensive care units (ICUs) and patients in non-ICU wards
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Table 3: Staphylococcus aureus-related discharge diagnoses in the US by patient age and infection site, 1999-2000
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Table 4: The number of invasive S. aureus (SAU) isolates and the proportion resistant to methicillin in the five major EU markets, 2005
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Table 5: Prolonged stay and mortality rate from Acinetobacter infections in the US
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Table 6: Overall cost of therapy in the US by site of infection
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Table 7: Overview of recently launched antibacterials and antibacterials in late stage development, 2007
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List of Figures

Figure 1: The four major types of nosocomial infections
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Figure 2: Percentage of four main types of nosocomial infections of all nosocomial infections
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Figure 3: Endogenous and exogenous routes of acquisition
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Figure 4: Infections associated with invasive devices and procedures
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Figure 5: Types of Surgical Site Infections (SSI)
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Figure 6: Diagrammatic representation of types of SSI
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Figure 7: Incidence density (/1000 patient days) of registered SSI by surgical procedure (overall) and 95% confidence intervals
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Figure 8: Incidence density (overall) mean of registered surgical site infection by NNIS risk index and by surgical procedure
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Figure 9: Cumulative incidence of SSI in hospitals in England and Wales, 1997-2005
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Figure 10: Adjusted SSI rates,1997-2005
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Figure 11: Definition of Bloodstream infection (BSI)
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Figure 12: Incidence rates and distribution of pathogens most commonly isolated from monomicrobial bloodstream infections and associated crude mortality rates for all patients, patients in intensive care units (ICUs) and patients in non-ICU wards
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Figure 13: Estimated number of deaths caused by nosocomial BSIs each year in the US, 2001
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Figure 14: Mean rates of BSI across ICUs in NNIS hospitals, 2004
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Figure 15: The urinary tract
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Figure 16: Mean rate of UTI per 1000 urinary catheter days in NNIS hospitals, 2004
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Figure 17: Classification of Urinary Tract Infections (UTI)
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Figure 18: Classification of Hospital-acquired pneumonia
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Figure 19: Mean rate of VAP per 1000 ventilator-days in NNIS hospitals, 2004
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Figure 20: Endotracheal intubation
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Figure 21: Distribution of outbreaks of hospital infections by pathogen, 1997-2002
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Figure 22: Gram-negative and gram-positive bacteria
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Figure 23: Distribution of type of bacteria in hospital infections
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Figure 24: Percentages of gram-negative and gram-positive organisms by site of infection from 1986-2003
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Figure 25: Selected antimicrobial-resistant pathogens associated with nosocomial infections in ICU hospitals, comparison of resistance rates from January-December 2003 with rates for 1998-2002
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Figure 26: Methicillin (oxacillin)-resistant Staphylococcus aureus (MRSA) among ICU patients, 1995-2004
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Figure 27: Staphylococcus aureus: proportion of invasive isolates resistant to oxacillin (MRSA) in Europe, 2005
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Figure 28: Staphylococcus aureus: trends of methicillin-resistance in the 5 major European markets, 1999-2005
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Figure 29: Vancomycin-resistant Enterococci among ICU patients in the US, 1995-2004
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Figure 30: Proportion of invasive Enterococcus faecalis isolates resistant to aminoglycosides in Europe, 2005
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Figure 31: Proportion of invasive Enterococcus faecium isolates resistant to vancomycin in Europe, 2005
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Figure 32: National estimates of US short-stay hospital discharges with Clostridium difficile listed as primary or as any diagnosis, 1996-2003
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Figure 33: C. difficile reports from patients aged 65 years and over, received under the mandatory reporting scheme in England during 2004 and 2005
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Figure 34: US states with the NAP1 strain C. difficile confirmed by the CDC as of September 2006
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Figure 35: Escherichia coli: trends of amino-penicillin resistance in the five major Euripean markets 1999-2005
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Figure 36: Escherichia coli: trends of fluoroquinolone resistance in the five major Euripean markets 1999-2005
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Figure 37: Third generation cephalosporin-resistant Klebsiella pneumoniae among ICU patients in NNIS participating hospitals in the US,1995-2004
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Figure 38: Proportion of invasive Klebsiella pneumoniae isolates resistant to 3rd generation cephalosporins, carbapenems, fluoroquinolones and aminoglycosides in Europe, 2005
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Figure 39: Fluoroquinolone-resistant Pseudomonas aeruginosa among ICU patients in the US, 1995-2004
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Figure 40: Proportion of invasive Pseudomonas aeruginosa isolates resistant to carbapenems, ceftazidime, fluoroquinolones and aminoglycosides in Europe, 2005
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Figure 41: Total number of patients developing nosocomial infections in an average year in the US
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Figure 42: Antibacterial sales across the seven major markets by sales and volume, 2001-05
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Figure 43: Sales and volume use in the hospital versus the community market, excluding Japan, 2001-05
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Figure 44: Sales of hospital antibacterials in the six major markets, excluding Japan, 2005
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Figure 45: Percentage share of overall hospital antibacterial sales by class in the six major markets, excluding Japan, 2005
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Figure 46: Cost of antibiotic therapy per patient by site of infection (US average wholesale prices)
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Figure 47: Share of each type of infection of overall expenditure on antibacterials to treat nosocomial infections, US
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Figure 48: Summary of management strategies for patients with suspected HAP, VAP and HCAP
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Figure 49: Empiric management of HAP, HCAP, VAP
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Figure 50: Initial antibiotic therapy for patients with no known risk factors for multidrug resistant pathogens, early onset and any disease severity
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Figure 51: Initial therapy for hospital-acquired pneumonia in patients with late-onset disease or risk factors for multidrug resistant pathogens and all disease severity
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Figure 52: Initial intravenous adult doses of antibiotics for empiric therapy of HAP, HCAP and VAP in patients with late-onset disease or risk factors for multidrug-resistant pathogens
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Figure 53: Treatment options for CDAD
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Figure 54: Summary of the factors influencing prescription choice from KOL research
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Figure 55: Patient stratification by risk factors
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Figure 56: Prevention strategies by risk factor
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Figure 57: Antibiotic resistance: a vicious cycle
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Figure 58: A schematic representation of the costs associated with HAI
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