1. Innovating for the healthcare needs of today and tomorrow

2. At war against healthcare associated infections
The Economist May 2016
First reported U.S. case of bacterial infection resistant to last resort antibiotic
Superbugs now present on all continents
When people hear about antibiotic resistance creating “superbugs”, they tend to think of new diseases and pandemics spreading out of control. The real threat is less flamboyant, but still serious: existing problems getting worse, sometimes dramatically. Infections acquired in hospital are a prime example. They are already a problem, but with more antibiotic resistance they could become a much worse one. Elective surgery, such as hip replacements, now routine, would come to carry what might be seen as unacceptable risk. So might Caesarean sections. The risks of procedures which suppress the immune system, such as organ transplants and cancer chemotherapies, would increase.
For the first time, researchers have found a person in the United States carrying bacteria resistant to antibiotics of last resort, an alarming development that the top U.S. public health official says could mean “the end of the road” for antibiotics.
The antibiotic-resistant strain was found last month in the urine of a 49-year-old Pennsylvania woman.
Colistin is the antibiotic of last resort for particularly dangerous types of superbugs, including a family of bacteria known as CRE, which health officials have dubbed “nightmare bacteria.” In some instances, these superbugs kill up to 50 percent of patients who become infected. The Centers for Disease Control and Prevention has called CRE among the country’s most urgent public health threats.
It’s the first time this colistin-resistant strain has been found in a person in the United States. In November, public health officials worldwide reacted with alarm when Chinese and British researchers reported finding the colistin-resistant strain in pigs and raw pork and in a small number of people in China. The deadly strain was later discovered in Europe and elsewhere.

3. The global health scare
The global nightmare…….
11.5%
17.1%
11.3%
9.2%
Most gov’s spend ~10% of GDP on healthcare
World Bank data 2014
Healthcare costs are high:
It doesn’t matter if you are Angela Merkel, the newly elected Swedish Prime Minister Stefan Löfvén, Dilma Roussef or Christina Kirchner, they all spend close to 10% of GDP on healthcare and if you are Barack Obama the bill is as high as 18% of GDP.
Chile: 7.2%
Mexico: 6.1%
The challenges are the same across the world:
Higher living standards mean that we live longer and require more healthcare.
At the same time there is intense pressure on government spending. Hospitals have been close in Greece, Spain; protugal etc. And I am sure that the situation is no differenct in for example Argentina where the ecenomic and financial crisis is severe.
To break the negative trend, we need to be innovative and creative . In other words: focus more on healthcare, than sick care.
9.1%
11.9%
4.7%
Breaking the trend requires innovation and creativity

4. How big is the problem? Healthcare associated infections (HAI)
Leading causes of death
Cause of death
Rank
Cardiovascular diseases incl. stroke 1 2
Cancer 3
HAI
Medical devices, for example catheters, are accountable for approx % of HAI cases
Nearly 6 million HAI cases in the US and EU annually – causing 150,000 deaths
Average prevalence in the EU is 7% and the average in developing countries is 15%
USD 36-45bn annually in added healthcare cost in the US alone
Healthcare associated infections (HAI) also referred to as “nosocomial” or “hospital acquired” infections are acknowledged as the most frequent adverse event in healthcare. According to the World Health Organization (WHO) the prevalence of HAI varies between 5–19% in different countries with an average of over 10% worldwide. HAI is a leading cause of morbidity and mortality in patients seeking medical care; in fact it is the third largest cause of death in developed countries. Medical devices, for example catheters, account for over 50% of all HAI cases.
Apart from the suffering of the patients, this also causes enormous cost for the healthcare systems across the world.

5. Healthcare associated infections
Antibiotics and multiresistant bacteria
”Multiresistant bacteria is a greater threat to mankind than climate change – but no one talks about it…”
Professor Hans Rosling, Karolinska Institutet
of the bacteria that cause HAI are resistant to at least one relevant antibiotic
70%
Hans Rosling

6. Antibiotic resistance and healthcare associated infections at the top of the political agenda
Global consumption of antibiotics increased by 30 percent between 2000 and 2010, from approximately 50 billion to 70 billion standard units, based on data from 71 countries.
CDDEP report ”The State of the World’s Antibiotics 2015” September 2015
”Antimicrobial resistance is so serious that it threatens modern medicine. A post-antibiotic era in which common infections and minor injuries can kill – is a very real possibility for the 21st century.”
WHO Global report on antimicrobial resistance, 2014
Infection prevention is a crucial element when tackling antimicrobial resistance as it reduces the need for antimicrobials. We will support initiatives that strengthen infection prevention within our countries.
Declaration of the G7 Health Ministers meeting in Berlin in October 2015

7. Travel increases risk of multiresistant bacteria
More people travel than ever before
Travelers are exposed to increased infection risk
50 percent of travelers returning from South Asia to Europe, carry multiresistant bacteria*
Seeking medical care in a country with a high level of multiresistant bacteria increases the risk even more
Religious travel is increasing every year
*Antimicrobials Predispose to ESBL-PE, 15 March 2015
50 percent of travelers returning from South Asia (46%), including India, carry multi resistant bacteria, according to a Finnish study “Antimicrobials Increase Travelers Risk of Colonization by Extended-Spectrum Betalactamase-Producing Enterobacteriaceae” According to the same study, one in three travelers returning from Southeast Asia (33%) and North Africa (33%) carry multi resistant bacteria.
According to the WHO, there is a 1 in risk of being injured in an aircraft accident. In comparison, there is a 1 in 300 chance of a patient being harmed in health care.
“These kind of bacteria can in some cases not be treated at all since they are resistant to all available antibiotics”, says Johan Tham Infectious Disease Specialist. (På den här sortens bakterier biter absolut ingenting, säger Johan Tham)
HAI results in extra patient days, at a cost of 6.5 billion SEK annually. Studies show that about 30 percent of all HAI can be prevented according the Swedish National Board of Health and Welfare (Socialstyrelsen) “Lägesrapport inom patientsäkerhetsområdet 2015”
Reducing the number of HAI with 30%, would save patient days and free up resources for an amount of approx. 2 billion SEK annually. (“Vårdrelaterade infektioner, framgångsfaktorer som föerbygger” SKL 2014)
In Europe HAI requires 16 million extra patient days to a cost of approx. 7 billion Euro annually. The costs for HAI in the US is approx. 10 billion USD annually (”Vårdrelaterade infektioner, framgångsfaktorer som förebygger” SKL 2014)

8. Antibiotic discovery void
Antimicrobial resistance and HAI

9. Deaths attributable to AMR
Compared to other major causes of death
”Ten million people at risk if
antimicrobial resistance is
not tackled”
”The spread of AMR is expected to reduce global GDP by 2 – 3.5 percent”
During 2014 the problem of HAI and AMR got tremendous attention - ignited by the WHO report before the summer. The problem of AMR is now widely considered as one of the biggest threats to human health globally and is often mentioned together climate change as one of the two biggest issues that need to be tackled on a global basis.
One of the most recent reports on the topic is the so called O’Neil report commissioned by the UK Prime Minister. The report looks at both the health and macroeconomic consequences if we do not seriously tackle this problem.
In 35 years AMR will be one of the top killers globally with 10 million deaths yearly, as a comparsion 8 million die from cancer globally and 1,2 million in traffic. When it comes to effects on the economy the report estimates that the spread of AMR is expected to reduce global GDP by 2-3,5%.
Review on Antimicrobial Resistance (AMR), Tackling drug-resistant infections globally,
December 2014

10. To prevent device related healthcare associated infections:
Bactiguard’s mission
To prevent device related healthcare associated infections:
Reduce healthcare cost
Reduce the use of antibiotics – to prevent spread of multi-resistant bacteria
Save lives

11. BIP products (Bactiguard Infection Protection)
Where does HAI occur?
Products
Produkter
BIP Foley Catheter
USA
Hospitalized patients’ exposure to different risk factors in Sweden
(Share of patients’ exposure to risk factor)
Riskfaktorer för patienter på svenska sjukhus
BIP ETT
The green colored pie charts illustrate the areas in the body, most expesed to HAI, where Bactiguard has a correlationg product. The data in this chart is from the US, but can be applied for most of developed countries.
The lower graph show risk factors that patients in Swedish hospitals at a given time are exposed to, that increases the risk to develop a HAI. As an example 24% of patients receive a Foley catheter, one of the most common causes of infection. An even larger portion of patients are treated with antibiotics, which by itself is a risk factor.
BIP CVC
Antibiotics
Surgical site
Urological
catheter
Central venous
Immuno-
surpressed
Mechanic ventilation
Multiple risk factors
SKL

12. Example of blood stream infections by standard CVC
A dangerous and painful state for the patient, and costly for the hospital

13. Consequences of VAP
Ventilator associated pneumonia, caused by endotracheal tubes
The relative risk of VAP in a ventilated patient is up to 25 %1-3
VAP adds a estimated cost of more than $40,000 to a typical hospital admission
30-50%
The mortality is between 30–50% 4-5.
BIP ETT is a new product and the clinical data is limited. I will guide you through why we belive that BIP ETT will have great potential to reduce VAP and the clinical data we have availble right now.
1. Ibrahim EH et al. Chest. 2001;120(2):
2. Craven DE et al. Infect. 1996;11(1):32-53.
3. Rello J et al. Chest. 2002;122(6):
4. Kollef MH et al. Chest. 2005; 128 (6):
5. Stijn Blot et al. Critcal Care Medicine, March (2014) 42:3

14. Prevention of microbial adhesion and biofilm formation
Our mechanism of action
Microbes adhere and multiply.
When enough have developed, they form a biofilm.
Uncoated surface
Less microbes adhere to and colonize on the surface, preventing biofilm formation and subsequent infection.
Bactiguard
coated surface

15. How does it work? The galvanic effect – effective and safe Bactiguard
coated surface
Bactiguard
coated surface
Release of substances, such as silver ions, chlorhexidine or antibiotics, killing microbes.
Short effect due to release
Potential harm to tissue
Releasing coatings
The Bactiguard Infection Protection (BIP) technology is based on applying an extremely thin noble metal coating, consisting of gold, silver and palladium, to medical devices. The Bactiguard® coating is firmly bound to the
surface of the device and reduces the adhesion and growth of microbes.
The three noble metals in the Bactiguard coating – gold, silver and palladium, cause a galvanic effect which leads to a micro current that prevent the bacteria to adhere to the surface.
The solution is unique. As opposed to coating technologies, which depend on the release of toxic substances e.g. silver ions or antibiotics, the Bactiguard coating is non-toxic and non-pharmacologic. To date, more than130 million Bactiguard® coated urinary catheters have been sold for patient use, with no reported adverse events related to the coating.
The noble metals Au, Ag and Pd cause a galvanic effect when in contact with fluid. The micro current on the surface create an unfavorable environment for microbial adhesion.
No toxic release of antimicrobial agents
Tissuefriendly
Biocompatible

16. The Bactiguard® coating
The patients are exposed to harmless amounts of metals
Use of products with Bactiguard® coating,
exposes the patient to the equivalent of
SILVER Ag
A glass of milk contains equivalent amount
3–4 μg
PALLADIUM Pd
2 μg
A patient using a BIP product is only exposed to very small amounts of metals. This is due to the fact that the coating is very sustainable, very little relase and very small absolute amounts of metals are being used.
This illustrates the amounts of different noble metals that a patient is exposed to if using a BIP Foley. The levels are normally times below toxicological safety limits at chronic use.
GOLD Au
A portion of potatoes
contains equivalent amount
0,2–0,3 μg

17. 150 million Foley catheters have been used since 1995
Clinical evidence
150 million Foley catheters have been used since 1995
No adverse events
have been reported, associated with the coating
36%
of weighted average reduction is proven in clincial studies of symptomatic CAUTI, but in some studies up to 90%
Permanent catheter
Several reports of successful patient cases with permanently catheterized patients
52%
reduction of catheter related blood
infections with BIP CVC and indications for decreased risk of thrombosis
67%
reduction of ventilator associated pneumonia with BIP ETT
As Bactiguard coated Foleys have been used since 1995 in the USA, the products are well documented and studied. In fact approximately 50% of all Foley catheters used in the USA today are coated with Bactiguard. 130 millions of those have been sold since 1995.
A large amount of clinical test and studies have been performed involving over patients. No adverse events have been reported related to the coating.
Most studies related to Bactiguard coating are made with Foleys, where you can see an weighted average reduction of 36%. But on certain patient groups, the reduction can be up to 70%.
Bactiguard coated CVCs have shown to reduce bloodstream infections by 50%
BIP ETT has shown to reduce VAP by 67% in a study presented as poster at Euroanasthesia 2015.

18. Bactiguard Infection Protection
Effective prevention of healthcare associated infections, through reduction of microbial adherence and growth to medical devices.
Reduces the need for antibiotics, and can so limit the spread of multiresistant bacteria.
The Bactiguard coating is proven to be a tissue friendly and safe technology.
To summarize our offer:
- Effective prevention of healthcare associated infections, through reduction of microbial adherence and growth to medical devices.
- Reduces the need for antibiotics, and can so limit the spread of multiresistant bacteria.
- The Bactiguard coating is proven to be a tissue friendly and safe technology.

19. BIP Foley Catheter

20. Do you recognize any of this?
The catheters needs to be changed earlier than expected due to problems?
Cloudy urine?
Recurring UTIs with certain patients?
The staff needs to
rinse the catheter?
Do you recognize these challenges? What problems do you mostly see with your patients?
Smelly urine?
Crystals on the catheter?
Clogging catheters?

21. In vitro data BIP Foley Catheter
This is the most recent in vitro data, showing that BIP Foley catheters reduce ESBL producing Klebsiella bacteria.
*MRSA tested for Silicone only

22. Reduction of biofilm in clinical use
37 long term catheterized urological-surgical patients (>30 days)
58% reduction of biofilm occurrence on BIP Foleys
BIP Foley Catheter
Standard Foley
No of patients 18 19
Biofilm
6 (33%)
15 (79%)
Mazzoli S.*, Meacci F.*, Cai T.§, Bartoletti R.
*STDs Center, Santa Maria Annunziata Hospital, ASL 10 Florence, Italy
Urology Unit, Santa Maria Annunziata Hospital, University of Florence, Florence, Italy
Poster, “Eurobiofilms 2009” conference, Rome (Sept 02-05, 2009).

23. Clinical evidence BIP Foley Catheter
Author (year)
Type of study
Number of patients
Site
# days catheterized
Incidence-reduction
(p value)
Aljohi A (2016)
RCT 60
ICU, Saudi Arabia 3
90%
(p=0.006)
Hidalgo F (2015)
116
Cardiology, Spain
4 mean
38%
(p=0.037)
Lederer (2014)
Before-after
853
7 hospitals, hospital-wide, US
8 mean
58%
(p<0.0001)
Pickard (2012)
1224*
24 hospitals, surgical care, UK
3-10 days*
19%*
(p=0.157)
Seymour (2006)
117
One acute general hospital, UK
> 2 days
71%
Gentry (2005)
133
Medical and surgical wards, US
7-10 days
34%
Newton (2002)
1757
Burn unit ICU, US
5-8 days
32%
(p=0.029)
These are the 6 studies that give the weighted average of 36%. They have been selected by us in colloboration with KOLS as they comply with the stricter critera from CDC since 2009:
Peer-reviewed studies
Measure symptomatic CAUTI (sCAUTI) specifically, not a mix of asymptomatic and symptomatic
>2 days catheterization time in majority of patients
As you can see there is a spread, so dependent on study design, baseline of infection incidence and patient population amongs other things you may get different results.
* 4241 in total, including patients catheterized for 1-2 days
Weighted average 36%
These peer-reviewed studies:
Measure symptomatic CAUTI (sCAUTI), not bacteriuria
Majority of patients >2 days catheterized
Aljohi AA, et al, Urol Ann 2016;8:423-9.
Hidalgo F et al, Enferm Intensiva 2015; 26(2):54-62
Lederer JW et al, J WOCN 2014; 41(5):1-8
Pickard et al, The Lancet, Nov 5, 2012
Seymour C, British Journal of Nursing, 2006; 15(11):
Gentry H et al, Nursing Standard. 2005; 19, 50, 51-54
NewtonT et al, Infection Control and Hospital Epidemiology; 2002; 23(1): 217-8

24. Clinical evidence Foleys
150 million Foley catheters have been used since 1995
No adverse events
have been reported, associated with the coating
36%
of weighted average reduction is proven in clincial studies of symptomatic CAUTI (catheter associated urinary tract infections),
but in some studies up to 90%
Permanent catheter
Several reports of successful patient cases with permanently catheterized patients
As Bactiguard coated Foleys have been used since 1995 in the USA, the products are well documented and studied. In fact approximately 50% of all Foley catheters used in the USA today are coated with Bactiguard. 130 millions of those have been sold since 1995.
A large amount of clinical test and studies have been performed involving over patients. No adverse events have been reported related to the coating.
Most studies related to Bactiguard coating are made with Foleys, where you can see an weighted average reduction of 33%. But on certain patient groups, the reduction can be up to 70%. The studies we have used to calculate this average are the more high qualitative studies meaning they are peer-reviewed, they look specifically at symptomatic CAUTI (in line with the CDC guidelines updated in 2009 to disregard bacteremia since it is not treated) and include majority of patients having a catheter more than 2 days (which corresponds to our recommendation on which patient to use it on).
In addition to this, the largest study on patients showed a reduciton of 32% in both symptomatic and asymptomatic CAUTI and reduction of urosepsis by 44%
Even though the BIP technolgoy is primarily a preventive method, there are also patient cases on permantly catheterized patients that have been ”cured” from their UTI (during the study period) when using a BIP Foley. One case as been publised (Estores, USA) and a second case from Sweden will be published shortly.

25. Cost savings with BIP Foley Catheter
BIP Foley Catheter has been shown to reduce CAUTI in a cost effective way. The costs savings are present in a wide variety of reimbursement systems1,2,3. Several health economic evaluations have been conducted in Europe and USA12,16,17. In one of these, a large, prospective, randomized study of almost patients, Bactiguard coated catheters were shown to offer significant annual cost savings when considering the excess cost of CAUTI1. In another 2-year prospective surveillance study of 10 patient care units, the introduction of a Bactiguard coated urinary catheter was associated with a significant decline in CAUTI and led to reduced costs2.
BIP Foley Catheters are associated with lower length of hospital stay costs, treatment costs and improved patient quality of life1. The graph to the right is based on a Bactiguard health economy model using Saint et al
1. Karchmer TB et al, Arch Intern Med Nov 27;160(21):3294–8
2. Rupp ME et al. AJIC. 2004; 32(8):
3. Saint S. et al. Arch Intern Med. 2000; 160:
Saint S. et al. Arch Intern Med. 2000; 160:

26. Clinical evidence BIP Foley Catheter:
Aljohi et al. 2016
Patients
60 patients in ICU
(medical and surgical critical ICU)
Design
Randomized (30 Standard, 30 BIP Foley)
single center, single-blinded, prospective, controlled
Site
King Fahad Hospital, University of Dammam, Saudi Arabia
Catheterization time
3 days
Primary endpoint
Symptomatic CAUTI
(sCAUTI) according to CDC definition
Secondary endpoints
Bacteriuria
Bacteremia
Polyuria
Oliguria
After 3 days of catheterization
-90%
p=0.006
p=0.24
p=0.13
p=1.0
After the catheterization period of 3 days, ten cases of CAUTI were recorded in the standard catheter group while only one case of CAUTI occurred in the noble metal alloy catheter group meaning the risk reduction was 90% (33% vs. 3.3% per catheter days). The upper graph shows it in percentage of patients that developed CAUTI, Secondary bacteremia, Polyuri and Oliguria whereas the lower graph shows the number of cases.
When it comes to bacteremia, there were 9 cases in the standard group, but no additional cases were observed in the noble metal alloy catheter group. Three of the 9 bacteremia cases were considered to be secondary bacteremic UTI since they were positive for the same strains of microorganism in both blood and urine, suggesting that this microbe(s) originated from the urinary tract.
-90%
Aljohi AA, Hassan HE, Gupta RK. The efficacy of noble metal alloy urinary catheters in reducing catheter-associated urinary tract infection. Urol Ann 2016;8:423-9.

27. Clinical evidence BIP Foley Catheter
Hidalgo F et al. 2015
Number of patients
116
Patients
Cardiac surgery post-
operative patients
Design
Prospective randomized
Hospital/Country
Spain
Primary outcome
UTI confirmed by 105 CFU/ml microorganisms in urine
Microbiology
Most common species were E-coli (30%) and Klebsiella Pneumonia (30%)
Health economy
The use of BIP Foley Catheter was shown cost effective
-38%
OR=2.22, p=0.037
Hidalgo F et al; Incidence of urinary tract infections after cardiac surgery: comparative study according to catheterization device. Enferm Intensiva, 21 March 2015

28. Clinical evidence BIP Foley Catheter:
Lederer et al. 2014
No patients
853
Design
Multicenter Surveillance study
Site
USA (acute care hospitals)
Primary outcome
Symptmatic CAUTI (sCAUTI) according to
Clinical diagnosis
CDC definition
Other
Antibiotic use
p<0.0001
p<0.0001
CDC criteria for a Catheter-related UTI:
• The patient shall be catheterized for > 2 days, • Diagnosis during catheterization or within 2 days after removal Center for Disease Control, USA
The latest published study is by Lederer et al in the US, where sCAUTI rates was prepared between uncoated and Bactiguard coated Foleys. From 7 acute care hospitals, 853 patients were recruited.
First the sCAUTI prevalence was measured at each hospital during at least 3 months with standard (uncoated) Foleys, then there was a switch to the Bactiguard coated.
To compare the outcomes, they used both the more strict CDC definition (Centre for Disease Control) but also the clinical diagnosis. With both methods to measure results, a reduction of approximately 50% in sCAUTI incidence could be observed.
Antibiotic use was also measured, where a 60% reduction could be obersved with the Bacitiguard coated group (less patients, and shorter treatments)
Lederer JW, Multicenter Cohort Study to Assess the Impact of a Silver-Alloy and Hydrogel-Coated Urinary Catheter on Symp- tomatic Catheter-associated Urinary Tract Infections. J Wound Ostomy Continence Nurs Jun 11
Antibiotic days/patient
Lederer JW et al, J WOCN 2014; 41(5):1-8

29. Clinical evidence BIP Foley Catheter
Karchmer et al. 2000
Reduction CAUTI
–32%
–21%
–44%
No patients
27 800
Patient type
All patients except psychiatry and pediatrics
Design
Prospective, ward randomized, cross-over
Site
University Hospital of Virginia, U.S.
Primary outcome
Symptomatic and asymptomatic UTI
In the year of 2000, before the more strict CDC definitions of CAUTI where introduced in 2009, Karchmer et al performed the largest study comparing both symptomatic and asymptomatic CAUTI on patients at the University Hospital of Virginia in the USA. The study was designed as a prosepctive , ward randomized cross over study over 12 months. The products used in the standard group where silicone coated latex and then Bactiguard coated latex (Bardex IC).
The study showed a reduction of CAUTI per 100 catheters with 32% and a reduction of CAUTI per 1000 catheter days by 21%, as well as a reduction of urosepsis by 44% (not statistically significant due to low numbers of urosepsis)
Karchmer TB et al, A randomized crossover study of silver-coated urinary catheters in hospitalized patients. Arch Intern Med Nov 27;160(21):3294-8
p=0.001
p=0.04
p=0.42
Karchmer TB et al, Arch Intern Med Nov 27;160(21):3294-8

30. Clinical evidence BIP Foley Catheter
Patient case, Sweden (not yet published)
No patients 1
Patient type
Permanently catheterized, suprapubic, neurologic bladder dysfunction with urine retention, recurrent UTI every month
Design
22 months follow up
cross-over (switch to BIP Foley Catheter month 10)
Site
Centralsjukhuset Hospital Karlstad, Sweden
Primary outcome
CAUTI
Antibiotic use
Other
outcomes
Comfort (patient)
Handling properties (nurse)
Another interesting study, soon to be published, from Sweden is a patient case with a permanently catheterized patient with on a monthly basis recurring UTIs in need of antibiotic treatment. After switching from a silver releasing catheter to Bactiguard in May 2013, the patient has not had any UTI over 2 years.
Data on file

31. BIP Foley Catheter features
Bactiguard coating inside and outside
Hydrophilic coating for less friction at insertion
Approved for up to 90 days use
Material: Latex or Silicone core
Transurethral or suprapubic use
Tissue friendly and safe for patient use
2-way and 3-way catheters
The BIP Foley Catheter is approved for use during 90 days, and is available in a range of sizes in both latex and silicone. Except for the Bactiguard coating they are also coated with a hydrophilic coating to ease insertion. The BIP technology is proven tissue friendly and safe for patient use, due to its low levels of metals and its mechanism of action.
Hydrophilic coating
Bactiguard-coating
Latex/Silicone material

32. Pre-wetting BIP Foley Catheter
The hydrophilic coating is a premium feature of the Bactiguard Foley catheters, providing more ease of insertion for the health care professional and comfort for the patient.
Pre-wett the catheter with sterile water or NaCI before inserting the catheter

33. BIP Foley Catheter patient segments
The risk of CAUTI increases with every day the patient has a catheter
BIP Foley Catheter is recommended for patients who require a catheter >2 days
Such patient segments include, but is not exclusive to:
ICU patients – critically ill
Neurological patients
Stroke
Dementia
Spinal cord injured
Urology patients
Prostate cancer
Bladder cancer,
BPH/TURP
Other chronically catheterized patients
Immunosuppressed patients
As the risk for infections increase with every day the patients carries the catheter, and biofilm formation takes at least approximately 48 hours – we recommende BIP Foley Catheters for patients expected to have the catheter for more than two days.
Which patient segements in your care unit has a Foley >2 days?
These are some patient segments that we have identfied through published date, expert interviews with over 60 doctors and data from the Swedish healthcare system considering prevalence of UTI, average catherization time and sensibility to infections.

34. BIP Central Venous Catheter (BIP CVC)

35. CLABSI/CRBSI Prevalence and cost of complications due to CVCs
Catheter related blood stream infection (CRBSI) is the most frequent complication and risk associated with the use of CVCs
Prevalence ranges from 4-6% and a mortality between 12 to 25%
One case of CRBSI costs in average dollar
Morbidity and Mortality Weekly Report (MMWR), Vital Signs: Central Line--Associated Blood Stream Infections --- United States, 2001, 2008, and 2009, CDC
Wolf HH, et all; Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Central venous catheter-related infections in hematology and oncology : guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol Nov;87(11): [Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ, Fraser VJ .Attributable cost of catheter-associated bloodstream infections among intensivecare patients in a nonteaching hospital. Crit Care Med Aug;34
CLABSI Central Line Associated Blood Stream Infection
CRBSI Catheter Related Blood Stream Infection

36. Catheter related thrombosis has the same prevalence as CLABSI and is life threatening4%
CLABSI 4-6%
Mortality
12-25%
3 terms:
pro-thrombotic – create clots and gives risk of thrombosis (all devices inserted into blood are pro-thrombotic)
Non-thrombotic – do not create clots, do not give risk for thrombosis
Anti-thrombotic – dissolves present clots, decrease risk for thrombosis
Morbidity and Mortality Weekly Report (MMWR), Vital Signs: Central Line--Associated Blood Stream Infections --- United States, 2001, 2008, and 2009, CDC
Wolf HH, et all; Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Central venous catheter-related infections in hematology and oncology : guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO). Ann Hematol Nov;87(11):
[Warren DK, Quadir WW, Hollenbeak CS, Elward AM, Cox MJ, Fraser VJ .Attributable cost of catheter-associated bloodstream infections among intensivecare patients in a nonteaching hospital. Crit Care Med Aug;34

37. In vitro data BIP CVC
Average % reduction
In vitro data 3 relevant microbial strains reduction of bacterial adhesion BIP CVC compared to uncoated CVC

38. Clinical evidence BIP CVC
Goldschmidt et al.
Reduction in catheter related infections
No patients
236
Patient type
Haematologic and oncologic diseases
Median time for catheterization : 13,3/12,7 days
Design
Prospective, randomized
Site
University of Heidelberg, Germany
Primary outcome
Catheter related infection
Other
Local catheter infection
Catheter related bacteremia
Additionally
The risk for thrombosis was evaluated by Harter et al who found no increased risk in the Bactiguard group
52%
50%
44%
Goldschmidt et al at the University Hospital in Heidelberg Germany, compared the infections rates on oncology and hematology patients using a CVC. During the 17 month study time, 233 CVCs were evaluated of which 113 were standard (uncoated) and 120 were coated with Bactiguard coating. They found that patients with the Bactiguard coated CVC only developed half has many infections as the uncoated CVC group.
In an analysis by Harter et al, it was also concluded that the Bactiguard coated group (1 case) had no increased risk of trombosis vs the standard group ( 3 cases), but the cases were to few for statisitcal significance.
To summarize, the Bactiguard coated catheter showed a decreased risk for infection, while no increased risk for trombosis.
Goldschmidt H, et al. Prevention of catheter-related infections by silver coated central venous catheters in oncological patients. Zentralbl Bakteriol. 1995
Dec;283(2):
Harter et al Catheter-related infection and thrombosis of the internal jugular vein in hematologic-oncologic patients undergoing chemotherapy: A prospective comparison of silver-coated and uncoated catheters. Cancer. 94 (1): (2002).
Goldschmidt H.et al., Zbl. Bakt.1995; 233:

39. Clinical evidence BIP CVC: Risk of thrombosis
Harter et al
Results- Catheter Related Thrombosis
No patients
236
Patient type
Haematologic oncologic diseases
Median time for catheterization : 13,3/12,7 days
Design
Prospective, randomized
Site
University of Heidelberg, Germany
Primary outcome
Thrombosis prevalence
Harter et al, Cancer 94(1): (2002)

40. Thrombosis- TAT as surrogate markers in clinical study
Trombin-Antitrombin complex (TAT)
 Increased TAT formation is correlated to activation of coagulation and are surrogate markers for thrombosis
Thrombosis is when a blood clot is formed in a vein. This is a serious condition, since the bloood clot can seal of the vessel. The blood clot can break apart, travel throughout the body, and cause blockages in the heart, brain, or lungs, leading to heart attack, stroke, or pulmonary embolism depending on where it ends up. To evaluate the blood compatible properties in the lab, we measure TAT, which is a surrogate marker for thrombosis.

41. BIP CVC: Ex Vivo assessment of Blood Compatibility
Vafa Homann et al. 2015
Problem
Catheter related Thrombosis – develops in around 4% of the patients and forms life threatening blood clots
Methods
Blood from 23 healthy volunteers was examined for compatibility with BIP CVC and standard catheter in the Chandlers- loop model
Primary outcome
BIP CVC showed less TAT = less activation of coagulation = lower thrombotic risk than non-coated CVC
Other
BIP CVC showed no hemolysis, while another anti-infective CVC* showed extensive hemolysis. Thus, BIP CVC is unique being both anti-infective and tissue-friendly.
*Chlorhexidine Silver Sulfadiazine CVC
Tendency to less thrombosis has been seen in vitro, using surrogate marker TAT, and visually
Hydrocath Assure – BD Medical
Careflow – BD Medical
The results of the study revealed that the Bactiguard noble metal alloy coating used for the BIP CVC has potentially improved blood compatibility properties of the catheter in terms of risk of thrombosis compared to a standard uncoated product. The BIP CVC was also superior to the other coated CVC with respect of non-hemolytic properties. This, together with prevention of microbial adhesion and biofilm formation on the catheter, suggests that the Bactiguard coating can be a key approach to battle healthcare associated infections in general and bloodstream infections in particular, in a tissue friendly way.
”Tendency
to less Thrombosis”
*TAT= Thrombin–Anti-Thrombin complex, depends on activation of coagulation and is used as marker for thrombotic risk
Vafa Homann et al Improved Ex vivo blood compatibility of Central Venous Catheters with noble metal coating. J of Biomaterial Research Karolinska Institutet, Danderyd Hospital, Bactiguard

42. Soft tip
The superior geometric soft tip design couple with unique soft blended bio-compatible material make insertion safe and easy.

43. Needles Straight Y valve
The BIP CVC kits are available with either straight or the more specialized Y-Valve needle which allows for easy guide-wire insertion while minimizing air embolism and backflow of blood as you can leave the syringe in one of the needle insertion sites while using the other one for the guidewire. It is a very popular and rare feature, often much appreciated by doctors.
Straight
Y valve

44. Kink resistant guidewire
The guidewire of the BIP CVC has a Nitinol core, preventing it from kinking. If you bend it and then release, it will return to its original shape. This prevents it from getting stuck in the catheter during the insertion procedure.

45. High flow catheter 703 - Lumen Size is 16G/18G/18G
Distal = 16G (1.041 mm)
Middle = 18G
Proximal = 18G
713 - Lumen Size is 14G/18G/18G
Distal = 14G (1.20 mm)
14G > 16G
Gauge
A special article amongst the BIP CVC products in the product 713 which just as the 703 is a 7 French catheter with 3 lumen. It has however a larger distal lumen, 14G instead of 16G, allowing for more rapid and high volume of fluids & Medication Administration. It is our high flow catheter and very popular.
This should not be confused with a high pressure catheter, which is something else and not available in the BIP CVC range of products today.

46. BIP CVC features Short term (<30 day) use
Polyurethane with Bactiguard coating on the outside
Y- and straight valve needle options
No increased risk for thrombosis
Tissue friendly and safe for patient use
Catheter size
French
(Fr/Ch)
Lumen Gauge (G)
Length
(cm)
4 Fr 1 lumen
4 Fr 18
16, 20
4 Fr 2 lumen
22/22
6, 10, 16
5 Fr 1 lumen
5 Fr 16
5 Fr 2 lumen
5,5 Fr
18/18
10, 16, 20
5 Fr 3 lumen
20/20/22
8, 13, 30
7 Fr 1 lumen
7 Fr 14
7 Fr 2 lumen
16/16
16, 20, 30
7 Fr 3 lumen
16/18/18
10, 16, 20, 30
14/18/18
8,5 Fr 2 lumen
8,5 Fr
14/16/16
8,5 Fr 3 lumen
8,5 Fr 4 lumen
14/16/18/18
The BIP CVC is approved for use up to 30 days and available in several sizes. 5FR 3 lumen and kinkresistent guidewire will be launched during 2016.

47. BIP Endotracheal Tube (ETT)

48. Bacteria causing VAP and longer stay
Early onset <4 days Community acquired bacteria
Late onset >4 days Antibiotic – resistant nosocomial organisms (gram negative, aerobes)
If the symptoms start before 4 days it is probably a community acquired bacteria
If it starts after 4 days it is probably a nosocomial infection by antibiotic-resistent organisms, often gram negative aerobes.
Some authors use the cut off point 2 days, and some use 4 days.
VAP is associated with increasing the number of days the patients’ needs to stay in the ICU. Studies show that patients ventilated more than 5 days, stay up to 22 days in the ICU and in the hospital in general up to 25 days longer.

49. Risk factors for VAP Recent hospitalization
Admission from a chronic care environment
Current hemodialysis
Immunocompromised state
Prior use of antimicrobial agents during current period of hospital stay
The risk factors for VAP include the following.
Recent hospitalization
Admission from a chronic care environment
Current hemodialysis
Immunocompromised state
Prior use of antimicrobial agents during current period of hospital stay

50. Reduce micro aspiration (=subglottic secretion drainage)
VAP Prevention
Keep the head of the patient’s bed raised
Check the patient’s ability to breathe on his or her own
Hand hygiene
Clean the inside of the patient’s mouth on a regular basis.
Reduce micro aspiration (=subglottic secretion drainage)
Limit bacterial colonization
So what can be done to prevent VAP. These are common guidelines to prevent it:
To keep the patients head high.
Extubate if possible
Hand hygiene; if the health care professional touches the ETT, bacteria can move down the tube.
Routine cleaning of patients mouth.
Reduce micro aspiration, meaning removing fluid or mucose that is stuck above the cuff. This is usually done through a suction lumen, a feature that Bactiguard offers through the BIP ETT Evac – Evac being short for evacuation lumen. This feature is often also called subglottic secretion drainage.
Another important way is to limit bacterial growth and biofilm formation – which we are adressing with our coating.

51. BIP ETT Evac- A dual approach to VAP prevention
Bactiguard coating preventing infections through less microbial adhesion
Subglottic secretion drainage (SSD)
Reducing VAP by 67%2
Reducing VAP by 50%1
The solution – A dual approach with BIP Endotracheal Tube Evac
It has been specifically designed to reduce ventilator associated pneumonia (VAP). It combines the known VAP reducing feature of subglottic secretion drainage with the clinically proven ability to reduce microbial adhesion and prevention of biofilm formation of the Bactiguard noble metal alloy coating.
It is still to be proven in clinical studies what the reduction of the combination of these two features can bring, but I think you can agree with me it looks very promising.
1 Haas CF et al. Respir Care. 2014; Jun; 59(6):933-52
2 Tincu R et al. Poster Euroanasthesia June (2015) 32

52. In vitro data BIP ETT
Average % reduction
The table shows In vitro data for 5 relevant bacterial strains and their reduction compared to uncoated ETT.
1. Data on file

53. Clinical evidence, BIP ETT
Bucharest Clinical Emergency Hospital, University of Medicine and Pharmacy “Carol Davila”, Critical Care Toxicology Unit, Bucharest, Romania
Clinical evidence, BIP ETT
Tincu et al (Poster, Euroanasthesia 2015)
No of patients
100
Patient type
Come due to drug poisoning
Design
Prospective, randomized, controlled, independent, cross-over
Site
Bucharest, Rumania
Primary outcome
VAP rates, length of stay
Other outcomes
Microbiological findings, Antibiotic use
67%
“ ~70% less antibiotics per VAP case (p=0.05)”
50 patients randomized into either standard or BIP group

54. BIP ETT Evac features Approved for 30 day use For oral intubation
High volume, low pressure cuff
PVC with Bactiguard coating on both inside and outside
Reduces bacterial growth in vitro by >90%1
Tissue friendly and safe for patient use
The BIP ETT Evac is approved for oral intubation up to 30 days. It is available in the most commonly used sizes from 6Fr to 9Fr.
It has a high volume, low pressure cuff – I will come back to this in a couple of slides. ’
The tube itself is made out of PVC with Bactiguard coating on both inside and outside, which has proved to reduce bacterial adhesion by over 90% in vitro.
The tube is also proven to be perfectly safe for patient use.
1. Data on file

55. BIP ETT features Approved for 30 day use
For both oral/nasal intubation
High volume, low pressure cuff
PVC with Bactiguard coating on both inside and outside
Reduces bacterial growth in vitro by >90%1
Tissue friendly and safe for patient use
The BIP ETT is approved for use up to 30 days and available in a broad range of sizes, from pediatric 3Fr up to 10Fr.
It can be used for wither oral or nasal intubation and has a high volume, low pressure cuff.
The tube itself is made out of PVC with Bactiguard coating on both inside and outside, which has proved to reduce bacterial adhesion by over 90% in vitro.
The tube is also proven to be perfectly safe for patient use.
1. Data on file

56. Support slides

57. Policy, laws & regulations
Our vision
Our Vision
Defining the universal standard of care for prevention of Healthcare Associated Infections (HAI) together with policy makers, academia and healthcare
Policy, laws & regulations
Surveillance
Prevention
Adequate treatment
Implementation
New Standards of Care
Our new location is great when it comes to realizing our long term vision of ”defining the new standards of care for the prevention of HAI”
Our technology and products is only one part of the solution consiting of three main building blocks. In order to reduce HAI you need:
Surveilance (a system for measuring the level of HAI
Prevention (next building block prevention - hygiene routines, training of staff, technology)
Adequate treatment (use antibiotics sensibly)
New standards of care need to be devloped together with healthcare providers and researchers. Which we are now located very close to

58. Built on a Swedish Innovation
From technology provider to medical device manufacturer

59. Headquarter
Huvudkontor i Flemingsberg Life Science Park,
i anslutning till Karolinska Sjukhuset Huddinge
Forskning & Utveckling, Produktion och Företagsledning under samma tak
Headquarter in Flemingsberg Life Science Park, close to Karolinska Hospital Huddinge
Research & Development, Production and
management in the same building
Bactiguards headquarter is located close to Karolinska Hospital in Stockholm, where R&D, production and management are based.

60. Antibiotic use The global health scare
Netherlands Estonia Latvia Romania Germany Sweden Slovenia Austria Hungary Norway Denmark
Czech Republic
United Kingdom
Lithuania
Bulgaria
Finland
Spain (b)
Poland
Iceland (b)
Ireland
Portugal
Malta
Slovakia
Italy
Luxembourg
France
Belgium
Cyprus (a)
Greece
Penicillins (J01C)
Cephalosporins and other beta-la
Tetracyclines (J01A)
Macrolides, lincosamides and streptogramins (J01F)
Quinolones (J01M)
Sulfonamides and trimethoprim (J01E)
Other J01 Classes
Source ECDC: Surveillance report 2011 on antimicrobial consumption in Europe

61. Antibiotic resistance in the EU
The global health scare
<1%
1%- <5%
5%- <10%
10%- <25%
25%- <50%
>50%
No data reported or less than 10 isolates
Not included
Liechtenstien
Luxembourg
Malta
Source: ECDC

62. CAUTI Definition (CDC)
Asymptomatic bacteriuria
105 CFU/ml and no clinical symptoms; max 2 microbial species (excluded in 2009)
Symtomatic UTI
Bacteria in urine (bacteriuria) as above
AND
Clinical symptoms (fever / super pubic tenderness / urgency etc.)
ABUTI (Asymptomatic Bacteremic UTI)
105 CFU/ml and no clinical symptoms
Bacteria in blood culture, with at least 1 matching microbial species
Urosepsis
(Bacteremic UTI)
Bacteria in the blood stream originating from the urinary tract infection; systemic symptoms
CDC criteria for CAUTI
- During catheterization OR within 48 hours after withdrawal
- Urinary catheter was in place for >2 calendar days on the date of event

63. CLABSI/CRBSI - definition CDC definition:
At least one symptom (fever >38°C, chills, hypotension)
Recognized CLABSI pathogen from blood sample
Organism is NOT related to infection from other site
Patients catheterized for >2 days
During catheterization or on the 1st day after withdrawal
CLABSI - Central Line Associated Blood Stream Infection
CRBSI – Catheter Related BSI

64. Why do the studies say ”silver-alloy” if its not a ”silver technology?
FDA
Approved 1995

65. In vitro testing of microbial adhesion
Ahearn test and SEM
Bactiguard coating prevents bacterial adhesion and biofilm formation
Foley without coating
An Ahearn test is an in vitro test to evaluate the adhesion of microorganisms to device surfaces. In this test we allow bacteria to grow on an uncoated Foley and a Bactiguard coated Foley, then shake off the bacteria on an Agar plate to quantify the bacteria.
In the images to the left we see the same thing through a scanning electron microscope (SEM).
Foley with Bactiguard coating
Gram negative bacteria

66. Minimal release of metals from the Bactiguard coating
Tests with BIP Foley Catheter in artificial urine during 90 days show minimal release of metals
The amount of metals that are being released are far below toxic levels
The BIP technologiy mechanism of action is not to release substances to kill off bacteria, only to prevent adhesion.
The graphs show test with the BIP Foley Catheter in artificial urine during 90 days and prove the very limited release of metals. On the x-axis different catheter sizes are shown and on the y axis the remainder of the 3 noble metals after 90 days exposure to urine. On the latex catheter almost 100% is still attached to the surface, and on the silicone %.
Except the low percentage that is release, the absolute numbers are far below toxic safety levels for chronic use ( x). This means that that the patient is not exposed to risks.
TD, Report for simulated 3 months of use for BIP Foley Latex and Silicon

67. The Bactiguard coating lowers the natural cytotoxicity of latex
Levels of Urethral Damage
Results of Implantation
The effect of different materials on the rat urethral mucosa. Strips of catheters of different materials and coating were inserted into the urethra of 100 rats. After 72h the damage was assessed using a 4-graded scale. The Bactiguard®/Hydrogel was as biocompatible as the control. Data on file.
1 Oskadd
2 Delvis skadad
3 Lätt skadad
4 Allvarligt skadad
0.5 1
1.5 2
2.5 3
3.5 4
Rubber
Latex
Latex/Hydrogel
Latex/Bacti-Guard
Latex/Bacti-Guard/
Hydrogel
Control – Cystotomy only
I this study by Liedberg et al, different material cytotoxic properties have been assesed on urethral mucosa (rat). Results show that Bactiguard and hydrogel coated latex (like BIP Foley Catheter) is significantly less aggressive to the tissue compared to rubber, latex, hydrogel coated latex etc. on a scale 1-4 on how much damage could be observed in a microsope.
Bactiguard coating seems to recude the toxic properties of latex, and is so more tissue friendly.
H. Liedberg, P. Ekman, L. Nordling, T. Lundeberg ”The effect of different catheter material on the urethral mucosa”

68. The Bactiguard® coating in comparison to releasing technologies
For exampel: Traditional silver release technology
Surface coating
Silver Ag
Many healthcare professionals are familiar with tradtional coating technologies that depend on release of substances, for example large amounts of silver ions, antibiotics or chlorhexidine. This is a very different mechanism of action than the Bactiguard technology. As an example a ”silver catheter” can have 5-10 times more silver than a Bactiguard coated catheter, even if also the latter contains some silver. The mechanism of action with the silver technologies, as opposed to BIP, is that large amounts of silver ions are being released from the surface to actively kill bacteria. The downside is that the effect is not sustaining as the coating is being released, and it can be very aggresive to surrounding tissue – even causing inflammatory responses itself.
The FDA and other authorities have issued several warnings related to these type of coatings.
Silver ions are released from
the surface, killing bacteria.
5 to 10 times thicker layer than a surface with Bactiguard coating, then becomes thinner over time.

69. Small amount of noble metals in Bactiguard coating
Silver (Ag)1
Normal case exposure: at least 1 000x below toxicological safety limits for chronic use
Gold (Au) 2
Normal case exposure: – x below toxicological safety limits for chronic use
Palladium (Pd) 3
Normal case exposure: at least 1 000x below toxicological safety limits for chronic use
Also when used chronically, BIP Foley Catheter and BIP CVC are safe to use from the perspective of patients being exposed to silver, gold and palladium.
1.reference-dose of chronic, oral administration (RfD) United States Environmental Protection Agency: mg/kg/day)
2. Permitted Daily Exposure (PDE) derived from NOAEL-values, by the CHMP (Committee for Medicinal Products for Human Use) at EMA, PDE for chronic use, the parenteral administration-route for palladium: 10 μg/day
3. The calculated safety limit for gold exposure, based on the lowest recommended therapeutic dose for Auranofin (a gold salt) and adjusted with an uncertainty factor of 10 for the administration route: 87 µg /day
1. Reference-dose of chronic, oral administration (RfD) United States Environmental Protection Agency: mg/kg/day)
2. Permitted Daily Exposure (PDE) derived from NOAEL-values, by the CHMP (Committee for Medicinal Products for Human Use) at EMA PDE for chronic use, the
parenteral administration-route for palladium: 10 μg/day
3. The calculated safety limit for gold exposure, based on the lowest recommended therapeutic dose for Auranofin (a gold salt) and adjusted with an uncertainty factor of 10 for the administration route: 87 µg /day