Sechenov University Department of Hospital Therapy №2 Lecture topic: Diagnosis of infection and the current concept of sepsis Sergey Yakovlev, Professor Diagnosis of infection and the current concept of sepsis The agenda of the lecture 1. Characteristics of and types of infection 2. Clinical signs and symptoms of infection 3. Concept and diagnosis of sepsis 4. Principles of intensive therapy and rational use of antimicrobial agents in sepsis 5.Diagnosis and antibacterial treatment of infectious endocarditis Definition of Infection • Infection is a clinical and microbiological phenomenon characterized by an inflammatory response of the macroorganism to the presence of microbes in non-sterile tissues or by the invasion of sterile tissues by microorganisms [R. Bone, 1992] • The term "Infection" was introduced into medicine by an Venetian doctor, scientist, astronomer and poet Girolamo Fracastoro (1478—1553) Verona, Veneto Types of infection • Primary infection • Secondary infection – Relapse (the same localization, the same pathogen) – Superinfection (any localization, other pathogen) • Opportunistic infection (immunocompromised host, low-virulent causative microbes that are not pathogenic to a healthy person) – e.g. Pneumocystis jirovecii, Aspergillus spp., Mycobacterium avium intracellulare, Toxoplasma gondii, Cytomegalovirus Classification of infection depending on the conditions of occurrence • Сommunity-acquired infection • Health-care associated infection (HCAI) – Nosocomial (hospital-acquired) infection – Infections in long- term care facilities – Infections in patients receiving hemodialysis – Infections in patients in day hospitals clinics – Previous use of antibiotics or treatment of wounds at home HCAI = risk factor for antibiotic resistance Nosocomial (hospital-acquired) infection • Infection that developed in a patient 48 hours or more after hospitalization – there were no signs of infection upon admission – the patient was not in the incubation period • Infection that occurred after discharge from the hospital, directly related to the hospital stay and treatment – within 1 month – for joint implantation and cardiac devices – within 1 year Community-acquired vs. Hospital-acquired Infection • Community-acquired infections – Regional similarity in etiology and sensitivity of pathogens to antibiotics – Predictable resistance – predicted effectiveness of antibiotics • Hospital- acquired infections – Differences in the etiological structure of infections and the sensitivity of pathogens to antibiotics between hospitals and treatment departments within the hospital – The possibility of rapid selection of resistant microbes in the treatment process – The effectiveness of antibiotics is less predictable and varies • Recommendations for antibacterial therapy are possible only according to local microbiological data The most important forms of community-acquired and hospital-acquired infections Community-acquired infections Hospital-acquired infections • Pneumonia – CAP • Nosocomial pneumoniae, VAP • Acute exacerbation of chronic • Skin and soft tissue infections bronchitis – decubitus ulcer, pressure sore, ulcers, • Pyelonephritis infectious wounds • Surgical site infection • Acute cystitis • Implant-associated infection • Peritonitis • Tertially peritonitis • Skin and soft tissue infections – erysipelas, cellulitis, impetigo, • Catheter-associates UTI pyomyositis, fasciitis • Bloodstream infection • Meningitis • Antibiotic-associates C.difficile • Infectious endocarditis diarrheae and colitis • Sepsis • Sepsis Stages of the infectious process 1. Adhesion of the microbe to the host epithelium 2. Penetration into the internal environment ─ Active – invasion – obligate pathogens ─ Caused by a violation of the host's barrier functions – conditional pathogens 3. Proliferation in internal environments ─ The production of exotoxins ─ Production of cytotoxic factors ─ Induction of an inflammatory response ─ Induction of apoptosis Factors of human anti-infective protection • Mechanical (intact skin, mucous membranes, villi, lysozyme) + Respiratory tract: mucociliary transport + GI tract: acid pH of the stomach, antibacterial properties of bile, pancreatic enzymes • Colonization resistance (normal skin and throat microflora, gastrointestinal tract) • Nonspecific host immune response – Cytokine production (interleukin-1, 10, TNF), fever – Increased vascular permeability – Phagocytic cells (white blood cells, macrophages) • Specific host immune response – The complement system – Immunoglobulins – Lysozyme, opsonins 2. Clinical signs and symptoms of infection Clinical signs and symptoms of infection (1) • General symptoms – Fever – Chills, rigors – Weakness, malaise – Sweating, night sweats – Decreased appetite, nausea – Myalgias, arthralgias – Changes in mental status (headache, confusion, drowsiness, unconsciousness, lethargy) – Lymphadenopathy – Splenomegaly – Systemic inflammatory response syndrome - SIRS Systemic inflammatory response syndrome - SIRS • Systemic response manifested by two or more of the following: – Temperature >38° C or <36° C – Respiratory rate >20 breath/min or CO2 <32 mm Hg – Heart rate >90 bpm – WBC >12x109/L or <4x109/L, or presence of >10% immature neutrophils (“bands”) Clinical signs and symptoms of infection (2) • Local symptoms – rubor, tumor, calor, dolor • Cornelius Celsus (≈25 BC) – skin lesions: erythema, paresthesia, hyperesthesia, rash, herpes labialis – respiratory tract: runny nose, common cold, cough, sputum production, tachypnea, dyspnea, chest congestion and pain – urinary tract: dysuria, flank pain, frequency, urgency – intra-abdominal: vomiting, diarrhea, abdominal pain, flatulence – CNS: stiff neck, headache, photophobia, stupor, coma Clinical signs and symptoms of infection (3) • Laboratory abnormalities – Common • Leukocytosis • Neutrophilia • A shift in the leukocyte formula to the left, the appearance of young forms of neutrophils (myelocytes, metamyelocytes) • Lymphopenia • Hyperglycemia • Proteinuria • The increase in fibrinogen – Less common • Leukopenia • Thrombocytopenia • Anemia • Lactic acidosis • Azotemia Clinical signs and symptoms of infection (3) • Biochemical markers of bacterial infection – C-reactive protein • >24 mg/L • high sensitivity, low specificity – Procalcitonin • >0.5 ng/ml • high specificity, moderate sensitivity – Presepsin • >500 pg/ml • high specificity, moderate-high sensitivity Features of the infection in elderly patients • Symptoms of infection may be mild or even absent – In the elderly, 20% of cases of infection have no fever • The infection can debut with General brain symptoms (impaired consciousness, behavior changes, refusal to eat), hypotension, acute urinary retention, gastrointestinal disorders, or manifest as a decompensation of chronic diseases • In the elderly, it is always necessary to exclude infection in the case of developing conditions such as impaired consciousness, inappropriate behavior, falls Natural course of infection Localized infection (Primary locus) Curing Systemic inflammatory response syndrome (SIRS) Curing Bacteremia No bacteremia Curing Sepsis exitus letalis Curing Septic shock exitus letalis The mortality rate in case of infection 50 45 40 35 30 25 20 15 Risk of Mortality, % Risk of Mortality, 10 5 0 Local infection SIRS Sepsis Septic shock Reasons for death in infection 1. Multiple organ failure 2. Acute circulatory failure (septic shock) 3. Acute coronary syndrome – myocardial infarction, fatal arrhythmias 4. Stroke 5. Thrombohemorrhagic complications – hemorrhage – thrombosis, pulmonary embolism 6. Decompensation of background diseases – diabetes mellitus, cirrhosis of the liver , chronic kidney disease, chronic heart failure, COPD, alcoholic visceropathy 3. Concept and diagnosis of sepsis What is sepsis? Give the most accurate definition A. Sepsis is an infection with bacteremia B. Sepsis is an infection with the formayion of purulent metastatic foci in the organs (septicopyemia) C. Sepsis is a severe infection with a high risk of death D. Sepsis is an organ dysfunction caused by an infection with or without bacteremia E. Sepsis is an acute circulatory failure with inadequate tissue perfusion What is sepsis? Give the most accurate definition A. Sepsis is an infection with bacteremia B. Sepsis is an infection with the formayion of purulent metastatic foci in the organs (septicopyemia) C. Sepsis is a severe infection with a high risk of death D. Sepsis is an organ dysfunction caused by an infection with or without bacteremia E. Sepsis is an acute circulatory failure with inadequate tissue perfusion Changes in the concept of sepsis Sepsis - 1,2 vs. Sepsis - 3 Sepsis-1 & Sepsis-2 Sepsis-3 • Dates of acceptance: 1991 & 2002 • Date of acceptance: 2016 • Sepsis = SIRS + documented • Sepsis = MODS induced by infection infection • Severe sepsis = sepsis + MODS* • Septic shock: sepsis induced • Septic shock: refractory hypotension plus hypoperfusion hypotension (average BP < 65 abnormalities mm Hg, despite catecholamine infusion, and impaired tissue perfusion with lactate level > 2 * Multiple organ dysfunction syndrome mmol/l, despite adequate volume replacement Current concept of Sepsis-3 Intensive Care Med 2016 DOI 10.1007/s00134-017-4683-6 Definitions • Bacteremia – Presence of viable bacteria/fungi in the blood as evidenced by a positive blood culture; may have no accompanying symptoms. Bacteremia can be one of the following: • Transient (e.g. surgical procedures, including dental extraction; urinary catheters) • Intermittent