1. Septicaemia MBBS Batch 17 Dr.P.K.Rajesh

2. Case 0 60 year old with increased pulse, heart and respiratory rates. Low blood pressure, low urine output Febrile WBC count low (not this could be high too) Blood culture-No organisms isolated

3. OBJECTIVES Define bacteraemia, septicaemia, toxaemia. Explain the aetiopathogenesis of septicaemia. Discuss the complications of septicaemia leading to MODS. Describe the laboratory diagnosis of the microorganisms causing septicaemia

4. LEARNING OUTCOMES At the end of this lecture the students should be able to 1.define bacteraemia, septicaemia, toxaemia. 2.identify the risk factors that favour development of septicaemia. 3.describe the events that can lead to sepsis and septicaemia. 4.list common organisms causing septicaemia. 5.recognize and state the complications of septicaemia. 6. describe the laboratory protocol used to diagnose the causative agents of septicaemia.

5. Blood stream infections (BSI) Bacteraemia depicts presence of bacteria in blood. Sepsis is a clinical term used to describe a patient who has symptomatic bacteraemia, with or without organ dysfunction. Sustained bacteraemia, in contrast to transient bacteraemia, may result in a sustained febrile response that may be associated with an organ dysfunction. Septicaemia refers to the active multiplication of bacteria/microorganisms in the bloodstream that results in an overwhelming infection.

6. Bacteria causing tissue damage Direct damage of the target tissue Indirect damage by over activation of immune system

7. Tissue damage due to infection- a general scheme

8. Pathophysiology The pathophysiology of sepsis is complex and results from the effects of circulating bacterial products, mediated by cytokine release, occurring as a result of sustained bacteraemia. Cytokines released in response to endotoxins or otherwise, are responsible for the clinically observable effects of the bacteraemia on the host. Impaired pulmonary, hepatic, or renal function may result from excessive cytokine release during the septic process.

9. Pathogenesis to complications Pathogenesis of septic shock is a spectrum of conditions that may or may not be accompanied by the presence of bacteria in the bloodstream Precipitating agents e.g. endotoxin Toxic shock syndrome toxin (S. aureus) erythrogenic toxin (group A streptococcus) Cell wall of Gram-positive bacteria Activation of complement Monocytes Cytokines (e.g. TNF, IL-1) Neutrophils Adhesins Endothelial INJURY Capillary leak Fever Disseminated, intravascular, coagulation Shock Multiple organ failure

10. Septic shock Serious medical condition caused by decreased tissue perfusion and oxygen delivery (peripheral vasodilatation and pooling of blood) as a result of infection and sepsis The microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome (formerly known as multiple organ failure) and death.

11. CAUSES Septicaemia usually arises as a result of localised infection in the body. The primary site of infection may occur in the: Respiratory system Skin/IV cannula The gastrointestinal system Genitourinary system. Bacteria usually spill over from the primary infection site into the blood and are carried throughout the body thereby spreading infection to various systems of the body.

12. Common organisms involved/source of infection Staphylococcus aureus- Skin/IV catheters Streptococcus pneumoniae- LRTI Neisseria meningitidis-(pre)meningitis E.coli- UTI/Indwelling bladder catheters Klebsiella pneumoniae- RTI/VAP VAP-Ventilator associated pneumoniae Salmonella typhi- typhoid fever-toxaemia

13. Notes on sources of infection Sepsis or septic shock may be associated with the direct introduction of microbes into the blood stream via intravenous infusion (eg, IV line, other device-associated infections). There may be perforations or rupture of an intra-abdominal or pelvic structure. Bacteremia from bacteruria (urosepsis) may complicate cystitis in compromised hosts. Intrarenal infection (pyelonephritis), renal abscess (intrarenal or extrarenal), acute prostatitis, or prostatic abscess may cause urosepsis in immunocompetent hosts. In addition, sepsis may be caused by overwhelming pneumococcal infection in patients with impaired/absent splenic function. Meningococcemia from a respiratory source also may result in sepsis with or without associated meningitis.

14. Microbial Triggers ● Gram-negative bacteria : lipopolysaccharide ● Gram-positive bacteria: – Lipoteichoic acid/cell wall muramyl peptides – Superantigens Toxins ● Staphylococcal Toxic Shock Syndrome Toxin,TSST ● Streptococcal pyrogenic exotoxin, SPE

15. Activity of endotoxin

16. Lab Studies- INTERPRETATION I.Blood cultures-refer to the endocarditis lecture o Blood culture isolates might suggest the underlying disease process. o Bacteroides fragilis suggests a colonic or pelvic source whereas Klebsiella species or enterococci suggest a gallbladder or urinary tract source more frequently than an intra-abdominal source. II. Cultures from suspected source of infection Urine, respiratory specimen, IV cannula, wounds etc

17. Imaging Studies Chest radiograph Ultrasound CT scan or MRI Gallium or indium scan

18. Mortality/Morbidity Approximately 30% of patients die directly or indirectly from BSI Underlying diseases (e.g. malignancy) or accompanying life-threatening conditions (e.g. multiple severe trauma) also contribute to an unfavourable outcome Mortality rates are –Very high even with prompt therapy. –Gram positive 10 – 20% –Gram negative 25 – 40% –Septic shock 40 – 90%

19. Mortality Factors associated with a high mortality rate include: –extremes of age (i.e. very young [premature neonate] or the elderly [>75 years]) –white cell count (i.e. 30 x 10 9 /L) –polymicrobial infection (e.g. E. coli and S. aureus from pneumonia with BSI) –significant or severe underlying disease (e.g. diabetic ketoacidosis) –inappropriate or inadequate initial antibiotics

20. Aetiology of clinically significant bacteraemia (bloodstream infection) Organism Escherichia coli Staphylococcus aureus Streptococcus pneumoniae Klebsiella spp. Pseudomonas aeruginosa ‘Viridans’ streptococci Coagulase-negative staphylococci Miscellaneous Hospital (HA) or community (CA) acquired HA = CA HA > CA, 2:1 CA > HA, 10:1 HA > CA, 3:1 HA > CA, 10:1 CA > HA, 3:1 HA > CA, 20:1 Varies with organism Incidence (% of total cases) 29 19 13 7 5 4 19

21. Take home 35% of septic shock cases derive from urinary tract infections, 15% from the respiratory tract, 15% from skin catheters (such as IVs); over 30% of all cases are idiopathic in origin.