Sepsis from a microbiological perspective Veronika Holá Institute for Microbiology Faculty of Medicine, Masaryk University  and St. Anne´s Faculty Hospital in Brno TZKM, spring 2021 Sepsis • Definition od sepsis • Septic haemodynamic • Presence of infection • SIRS • Systemic Inflammatory Response Syndrome (SIRS) • Sepsis = SIRS + infection • Severe sepsis = sepssis + signs of organ dysfunction • Septic shock = severe sepsis + haemodynamic changes Response of the macroorganism Infection, SIRS, sepsis Bone, R., Balk, R., Cerra, F., Dellinger, R., Fein, A., Knaus, W., Schein, R., et al. (1992). Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest, 101(6), 1644–1655. Sepsis • Cytokine storm • Systemic Inflammatory Response Syndrome (SIRS) • Reaction of immune system to microbial products  • SIRS include – 1) Body temperature <36 °C or >38 °C  – 2) Heart rate greater than 90 beats per minute – 3) Tachypnea (high respiratory rate), >20 breaths per minute  or arterial partial pressure of carbon dioxide <4.3 kPa (32 mmHg) – 4) White blood cell count <4000 cells/mm³ (4 x 109 cells/L) or >12,000  cells/mm³ (12 x 109 cells/L) or the presence of >10% immature neutrophils (band forms) ‐ "left‐shift" • The septic patients meet criteria for SIRS • Clinical symptoms – Temperature – Respiratory rate – Pulse rate – Nausea – Confusion – Blood pressure – Urine secretion • + Laboratory markers – Number of leukocytes – Haemocoagulation – Respiratory‐metabolical acidosis – Organ dysfunction – Inflammatory markers Bedside dg. of sepsis SIRS criteria x SOFA score x qSOFA score • SOFA score ‐ Sequential organ failure assessment  score • Based on six different scores – Respiratory, cardiovascular, hepatic, coagulation, renal and  neurological systems • qSOFA ‐ simplified – Low blood pressure (SBP ≤ 100 mmHg) – High respiratory rate (≥ 22 breaths/min) – Altered mentation (GCS < 15) Sepsis vs. microbaemia Bacteriaemia  !!! Starting sepsis  Interaction with immunity system  Cytokines  endothelium of capillars + inflammation  Systemic Inflammatory Response Syndrome (SIRS) + Compensatory Anti‐inflammatory Response Syndrome (CARS) Sepsis vs. microbaemia • Sepsis x bacteraemia and bacteraemia x sepsis • Blood normally sterile  • Not necessarily present in developed sepsis  • High risk of multi‐organ failure • Sepsis ‐ mortality • Septic shock The phases of the development of  the generalized infection  Recovery Lethal result Chronic sepsis 1. 2. 3. 4. 5. Syndrome of the systemic  inflammatory answer Purulent resorptive fever Local inflectional focus SepticopyemiaSepticemia • Microbial process • Necessary conditions • Most bacteria – only in attenuated patient Pathogenesis of sepsis http://faculty.washington.edu/alexbert/MEDEX/ • Clinical symptoms • Pathological physiology – Local x generalized inflammation • Laboratory markers www.nzma.org.nz • Developes mostly from localised infection • Necessary conditions – Large population of microbes – Stimulation of cytokins release – Dissemination • Most bacteria – only in attenuated patient Pathogenesis of sepsis I. 13 • Pathogenesis of damage – „hot shoc“  – „cold shoc“ • Respiratory problems • Accute renal failure Pathogenesis of sepsis II. 14 • Icterus • Hemorragic necroses • Involvement of mental functions • Metabolic acidosis • Increased level of stress hormons (cortisol) • Mailfunction of O2 metabolism Pathogenesis of sepsis III. 15 • Lungs • Kidneys • Heart • Livers • Intestine • Brain • Adrenals • Pancreas (B‐cells) • Coagulation system (DIC) • Leukocytes (PMNs) Organ dysfunction in sepsis Therapy of sepsis • Intensive • Complex • ATB treatment not satisfactory • Need of shock treatment • Event. surgical intervention Spectrum of etiological agents of sepses • Autumn semester microbiological lectures – Wound sepsis – Fulminant sepsis – Urosepsis – Intraabdominal sepsis – Nosocomial sepsis – Sepsis puerperalis – Newborn sepsis – Blood stream infections • Catheter‐related BSI & sepsis • Catheter sepsis • Trombophlebitis • Central sepsis – Endarteritis and (trombo‐)phlebitis – Endocarditis • Accute endocarditis • Subaccute and chronic endocarditis  sepsis lenta  • „Culture‐negative“ endocarditis BSI related sepsis • Rapidity • Sensitivity • Specifity  • Correct sampling technique Microbiological dg. of sepsis Haemoculture sampling • Patient with suspiction of bacterial infection – CRP > 60 mg/l – Fever in anamnesis – (Inserted catheters) • Aseptic sampling • 2‐3 haemoculture bottles • 30‐60 min. intervals • Before ATB treatment • If treated, sample prior to next ATB dose Haemoculture sampling • Skin disinfection – 0,5% chlorhexidine in 70% alcohol – Polyvinylpyrolidon w. 10% of iodine – Iodine tincture – 70% alcohol • Change of needle • Disinfection of bottle end‐seal Bruker Daltonics textbookofbacteriology.net PCR – quantification Broad range PCR  assay FISH (Fluorescent in situ hybridisation) etc. ID  (60 min) www.aquilantscientific.ie Culture (up to 7 days) „Genetics“(cca 37 hod.) Sequenace PCR identification Typing (MLAST, PFGE…) etc. ID     (hrs‐days) Rapidity + sensitivity + specifity ID     (hrs‐days) Haemoculture examination Haemoculture examination • Positivity • Length of culture – HACEK  – Fungaemia • TTD  • No of anaerobic BSI very low • Serology • Biochemistry • MALDI from sample Other possibilitieas of sepsis diagnostic Chance of ATBs to affect infectious process Focal infections MODS multiple organ dysfunction syndrome Sepsis Septic shock Bacteriaemia & fungaemia ATB M O R T A L I T Y ATB ATB Treatment of the sepsis • Control the infection – Elimination of CA  – Finding the focus and surgical intervention – Removal of cause of septic state • Symptomatic therapy – Breething support  – Adjustment of haemodynamic – Support for failing organs – Continuous veno‐venous hemodiafiltration – In DIC (disseminated intravascular coagulation)