1. Line associated infections and bacteraemia Dr. Brian O’Connell

2. Adapted from Bone et al. Chest 1992; 101: 1644-55

3. Gram negative cell wall

4. Diagram of a Gram-positive bacterial cell-wall

5. Microbial triggers of sepsis Bacteraemia/fungaemia – Positive blood cultures are more common the more severe the disease More likely to have positive blood cultures in patients with septic shock Severe local infections associated with greater mortality Endotoxaemia – lipopolysaccharide Other bacterial toxins – Bacterial superantigens (e.g. TSST-1, streptococcal pyrogenic exotoxins)

6. Diagnosis of Sepsis No bedside or laboratory test provides a definitive diagnosis Clinical evidence of SIRS (tachycardia, tachypnea, leucocytosis, fever) with altered mental status, hyperbilirubinaemia, acidosis, thrombocytopenia Non-infective causes include: – Burns, pancreatitis, trauma, adrenal insufficiency, malignant hyperthermia, heat-stroke, hypersensitivity reactions)

8. Bacteraemia/Blood-stream Infection (BSI) Primary cause majority of hospital-acquired BSI (64%) most are due to infected intravascular catheters remainder have bacteraemia with no identifiable source Secondary Secondary infections are related to severe infections at other sites, such as the urinary tract, lung, postoperative wounds, and skin. Cause the majority of community-acquired BSI

9. Patterns of bacteraemia 3 patterns of bacteraemia 1.Transient – Lasts minutes to hours – Instrumentation of contaminated mucosal surface Tooth brushing, dental procedures, cystoscopy – manipulation of infected tissue 2.Intermittent Usually from un-drained infection 3.Continuous – Usually from an endovascular infection Endocarditis, infected aneurysm,

10. Diagnosis of bacteraemia Blood culture – Take two sets from different sites Should be performed on all hospitalised patients with fever (≥38ºC) combined with leucocytosis or leucopaenia before the use of parenteral or systemic antimicrobial therapy Systemic and localized infections including suspected acute sepsis, meningitis, osteomyelitis, arthritis, acute untreated bacterial pneumonia, or fever of unknown origin in which abscess or other bacterial infection is suspected or possible

12. Taking a blood culture from a central line Taking a blood culture from a Peripheral vein

13. Blood cultures Take at least 10 ml per set

14. What are the most common organisms recovered from blood?

15. Different groups of patients Traditional divisions :2 broad groups hospital acquired community acquired New divisions:3 groups Hospital acquired Health-care association Non health-care association / Unknown

16. Definitions Hospital acquired (HA): isolate recovered from inpatient > 48 h in hospital Health care associated (HCA): isolate recovered from patient with one of the following risk factors inpatient in SJH in previous 90 days outpatient in SJH in previous 30 days referred or transferred from another hospital resident in nursing home Non Hospital or Healthcare associated (NHCA): isolate from patient not defined as HA or HCA

17. Top 5 Bacteraemia isolates in SJH during 2006 HA n = 658 CNS 315 (48%) S. aureus 78 (12%) E. coli 60 (9%) E. faecium 30 (5%) E. faecalis 22 (3%) HCA n = 279 CNS 122 (44%) E. coli 35 (13%) S. aureus 24 (9%) S. pneumoniae 17 (6%) S. maltophilia 7 (3%) NHCA n = 274 CNS 142 (52%) E. coli 39 (14%) S. aureus 1 8 (7%) S. pneumoniae 11 (4%) BHS Gp.A 7 (3%)

18. Micro-organisms causing bacteraemia Overall change from predominantly Gram-negative infection to Gram-positive infection

19. Single organism bacteraemias in EORTC trials of febrile neutropenia

20. What are the common sources of blood- stream infection? Hospital-acquired – Central line – Urinary tract – Intra-abdominal Community-acquired – Urinary tract – Intra-abdominal – Respiratory tract

21. Table 2. Distribution of Systemic Response, Antibiotic Choice, and Outcome by Sources in 339 Episodes of Community-Acquired BSI in Adult Critically Ill Patients * SourceOverallDeath Inappropriate Treatment Sepsis Severe Sepsis Septic Shock Secondary BSI Lower respiratory tract70 (20.6) 19 (27.1)17 (24.3)34 (48.6) 31 (44.3)6 (8.6) Intra-abdominal68 (20.1) 12 (17.6) 9 (13.2) 47 (69.1) 30 (44.1)9 (13.2) Genitourinary tract67 (19.8) 6 (9.0) 17 (25.4) 44 (65.7) 23 (34.3)5 (7.5) Other35 (10.3) 13 (37.1)4 (11.4)18 (51.4) 13 (37.1)8 (22.9) Primary BSI99 (29.2) 36 (36.4)22 (22.2)41 (41.4) 44 (44.9)21 (21.2) Overall 339 (100)86 (25)69 (20)184 (55) 141 (41.5)49 (14.5) Chest. 2003;123:1615-1624

22. Management 1.Antimicrobial therapy –Early appropriate antimicrobial therapy improves survival 2.Surgical drainage –Important to look for and drain sources of infection 3.IV- fluids, blood transfusion, pressors 4.Nutrition 5.Other possible therapies –Steroids –vasopressin –Anti-inflammatory drugs –Anticoagulants

23. Empiric antimicrobial therapy choice depends upon institutional spectrum of infections, susceptibility pattern of infecting micro-organisms and individual clinical situation

24. Catheter-related infections Intravascular catheters are indispensable in modern- day medical practice Infections associated with intravascular catheters are a major cause of morbidity & mortality

27. Infectious complications of central venous catheters (CVCs) Local site infection Catheter-related blood stream infection (CRBSI) Septic thrombophlebitis – Endocarditis – Metastatic infection – e.g. endocarditis, lung abscess, brain abscess, osteomyelitis & endopthalmitis

28. Appearance of a central venous catheter associated with bacteraemia. Note the minimal surrounding erythema and purulence at the insertion site

29. Incidence of catheter-related infection varies:- Type of catheter - non-tunnelled vs. tunnelled Site of catheter – int. jugular > subclavian Number of catheter days Frequency of catheter manipulation Setting of catheter placement i.e. emergency/elective

30. Incidence of catheter-related infection varies: Hospital size Hospital service/unit Patient-related factors e.g. underlying disease and acuity of illness

31. Pathogenesis of catheter-related blood-stream infection

32. Scanning electron micrograph of a Staphylococcus biofilm. Emerging Infectious Diseases 2001; 7: 277-281

33. Epidemiology In the U.S., 15 million catheter days occur in ICUs each year Average rate of catheter associated bacteraemias is 5.2 per 1,000 catheter days So, approximately 78,000 catheter associated infections occur in ICUs in the US each year 250,000 cases annually if entire hospitals assessed rather than exclusively ICUs

34. Consequences Significant increase in patient morbidity & mortality Significant increase in hospital costs Significant increase in duration of hospitalisation

35. Morbidity & Mortality Meta-analysis of 2573 CRBSIs Case fatality rate – 14% Directly attributable to CVC – 19% Mortality rate highest for S. aureus bacteraemia – 8.2% overall

36. Cost In ICU studies, cost per infection is an estimated $34,500 - $56,000 Annual cost of caring for patients with CRBSIs estimated at up to $2.3 billion

37. Common pathogens isolated in CRBSIs Pathogen1986 – 1989 (%)1992 – 1999 (%) Coagulase negative Staphylococci 2737 Staphylococcus aureus 16 13 (>50% MRSA isolated) Enterococcus spp. 8 (0.5% VRE) 13 (25.9% VRE) Gram-negative rods E.coli Enterobacteraciae P. aeruginosa K. pneumoniae 19 6 5 4 14 2 5 4 3 Candida spp. 88

38. Catheter- Related Blood stream infection (CRBSI) Definition Essential Criteria: Peripheral blood culture positive Clinical signs and symptoms of infection (Temp>=38ºC or rigors/chills or hypotension) No other obvious source of sepsis And one of the following: 1.  15 CFU on line tip 2. > 2 h differential time to positivity (Central vs. Peripheral) Guidelines for prevention of Intra-vascular Catheter Related infections MMWR August 9,2002/Vol.51/No.RR-10

39. Tunnelled CVC-related blood stream infection Complicated infection Tunnel infection or port abscess Septic thrombosis, endocarditis, osteomyelitis Remove CVC/ID & treat with antibiotics for10–14 days Remove CVC/ID & treat with antibiotics for 4 – 6 weeks, 6 – 8 weeks for osteomyelitis Management of Catheter-related blood-stream infection

40. Tunnelled CVC-related blood stream infection Uncomplicated infection Coagulase negative Staphylococcus S. aureus May retain CVC & use systemic antibiotic for 7 days plus antibiotic lock therapy for 10 – 14 days Remove CVC if there is clinical deterioration or persisting or relapsing bacteraemia Remove CVC & use systemic antibiotic for 14 days if TOE –ve For CVC salvage, if TOE –ve use systemic & antibiotic lock therapy for 14 days Remove CVC if there is clinical deterioration, persisting or relapsing bacteraemia

41. Tunnelled CVC-related blood stream infection Uncomplicated infection Gram-negative bacilli Candida spp. Remove CCV & treat from 10 –14 days For CVC salvage use systemic & antimicrobial lock therapy for 14 days If no response, remove CVC & treat with systemic antibiotics for 10 – 14 days Remove CVC & treat with antifungal therapy for 14 days after last positive culture

42. Strategies for prevention Quality assurance and continuing education Standardisation of aseptic care Staff training in CVC insertion & maintenance Specialised “IV teams” Appropriate staffing levels Audit: site of catheter insertion choice of catheter material hand hygiene aseptic technique catheter site dressing regimens

43. Attributable mortality Attributable mortality in ICU studies remains unclear Ranges from no increase in mortality in studies that controlled for severity of illness 35% attributable mortality in prospective studies that did not use this control Estimated 12 – 25% mortality for each infection when all hospital units assessed

44. Microorganisms involved Coagulase negative staphylococci e.g. S. epidermidis S. aureus Aerobic GNBs e.g. E. coli, Klebsiella spp., Enterobacter spp., Pseudomonas spp., Acinetobacter spp. Candida spp. e.g. C. albicans

45. Catheter Related Blood stream infection (CRBSI) Strict definition Requires a peripheral and central blood culture to be taken together for every episode Expressed as a rate using catheter days as denominator A catheter day is a day when a patient has one or more catheters in place Rates usually low as criteria are very strict and specific

46. BSI considered to be associated with a central line if the line was in during the 48 h period before the development of the BSI. If the time interval >48 h, there should be compelling evidence that the infection is related to the central line. (compelling evidence used is clinical signs as CRBSI and no other apparent source of sepsis) Guidelines for prevention of Intra-vascular Catheter Related infections MMWR August 9,2002/Vol.51/No.RR-10 Catheter- Associated Blood stream infection (CABSI) Definition

47. Catheter Associated Blood stream infection (CABSI) Less strict definition Expressed as a rate using catheter days as denominator Rates usually higher than CRBSI as definition is less specific