SEPTICEMIA, SEPSIS, SEPTICEMIA, SEPSIS, SEPTIC SHOCKSEPTIC SHOCK
DefinitionDefinition
An expert consensus conference of the An expert consensus conference of the American College of Chest Physicians and American College of Chest Physicians and the Society of Critical Care coined the the Society of Critical Care coined the phrase systemic inflammatory response phrase systemic inflammatory response syndrome (SIRS) to describe a clinical syndrome (SIRS) to describe a clinical syndrome believed to be the result of an syndrome believed to be the result of an overly activated inflammatory response. overly activated inflammatory response.
This new definition recognized the important This new definition recognized the important role that endogenous mediators of systemic role that endogenous mediators of systemic inflammation play in sepsis, which was no inflammation play in sepsis, which was no longer regarded as being caused by longer regarded as being caused by microbial pathogenicity factors alone .microbial pathogenicity factors alone .
SepticemiaSepticemia is a dramatic clinical syndrome, is a dramatic clinical syndrome, which result fromwhich result from acute invasion of the acute invasion of the bloodstream by certain microorganism or their bloodstream by certain microorganism or their toxic products. toxic products.
Fever, chills, tachycardia, tachypnea and altered Fever, chills, tachycardia, tachypnea and altered mentation are common acute manifestations of mentation are common acute manifestations of septicemia. septicemia.
BacteremiaBacteremia: is the presence of vivid bacteria in : is the presence of vivid bacteria in bloodstream confirmed by the blood culture with bloodstream confirmed by the blood culture with the isolation of a pathogen.the isolation of a pathogen.
Systemic inflammatory response Systemic inflammatory response syndrome (SIRSsyndrome (SIRS): contains two or ): contains two or more of the following conditions:more of the following conditions:
fever, over the 38oC or hypothermia less than fever, over the 38oC or hypothermia less than 36oC;36oC;
tachypneea more than 20 breaths/min;tachypneea more than 20 breaths/min; tachycardia more than 90 beats/min.;tachycardia more than 90 beats/min.; leucocytosis more than 12000/mmc;leucocytosis more than 12000/mmc; leucopenia less than 4000/mmc or more than 10 leucopenia less than 4000/mmc or more than 10
percents immaturepercents immature forms. forms.
SepsisSepsis means: SIRS plus a means: SIRS plus a documented infection documented infection
Severe sepsisSevere sepsis Septic shockSeptic shock
Multiple organ dysfunction Multiple organ dysfunction syndrome (MODSsyndrome (MODS) )
Respiratory: PaO2<80 mmHg, PaCO2>50mmHg, Respiratory: PaO2<80 mmHg, PaCO2>50mmHg, respiratory rate<5/min, or >50/min;respiratory rate<5/min, or >50/min;
Renal system: increased serum creatinine, Renal system: increased serum creatinine, oliguria (<480ml/24h);oliguria (<480ml/24h);
Cardiovascular system: hypotension, heart Cardiovascular system: hypotension, heart rate<55/min, ph<7.25;rate<55/min, ph<7.25;
Hepatic system: serum bilirubin>60mg/l, Hepatic system: serum bilirubin>60mg/l, TP<15%;TP<15%;
Gastrointestinal system: bleedings, pancreatitis, Gastrointestinal system: bleedings, pancreatitis, ileus, perforation;ileus, perforation;
CNS: Glasgow coma score <6;CNS: Glasgow coma score <6; Hematologic system: platelet count<20000/mmc, Hematologic system: platelet count<20000/mmc,
leucocytes<1000/mmc, hematocrit<20%.leucocytes<1000/mmc, hematocrit<20%.
EtiologyEtiology
Multiple components of the microbial Multiple components of the microbial structure may initiate the systemic structure may initiate the systemic inflammatory response.inflammatory response.
Gram positive:Gram positive: Streptococcus pneumoniaeStreptococcus pneumoniae Staphylococcus aureus/epidermidisStaphylococcus aureus/epidermidis Streptococcus pyogenesStreptococcus pyogenes ClostridiumClostridium
Gram negative:Gram negative: Neisseria meningitidisNeisseria meningitidis Gram negative bacilli: E. coli, Salmonella, Gram negative bacilli: E. coli, Salmonella,
Klebsiella, Pseudomonas, Yersinia pestis, Vibrio Klebsiella, Pseudomonas, Yersinia pestis, Vibrio vulnificansvulnificans, , Aeromonas speciesAeromonas species
Rickettsia rickettsiiRickettsia rickettsii Capnocytophaga canimorsusCapnocytophaga canimorsus Erlichia speciesErlichia species Bartonella speciesBartonella species Dengue virusesDengue viruses Viruses - causes of the hantavirus Viruses - causes of the hantavirus
pulmonary syndromepulmonary syndrome Plasmodium falciparumPlasmodium falciparum Babesia microtiBabesia microti Anaerobes: peptococcus, microaerofili Anaerobes: peptococcus, microaerofili
streptococci, Actimomyces israelii.streptococci, Actimomyces israelii.
EpidemiologyEpidemiology
Predisposing factorsPredisposing factors include: include:
diabetes mellitus,diabetes mellitus, cirrhosis, cirrhosis, alcoholism, alcoholism, leukemia, lymphoma or disseminated carcinoma, leukemia, lymphoma or disseminated carcinoma, cytotoxic chemotherapy and immunosuppresive cytotoxic chemotherapy and immunosuppresive
drugs which cause neutropenia,drugs which cause neutropenia, total parenteral nutrition,total parenteral nutrition, a variety of surgical procedures and infections a variety of surgical procedures and infections
arising from the urinary, biliary or gastrointestinal arising from the urinary, biliary or gastrointestinal tracts.tracts.
Pathogenesis and pathologyPathogenesis and pathology
Most of the bacteria causing Most of the bacteria causing gram-negative sepsisgram-negative sepsis are are normal commensals in the gastrointestinal tract. From normal commensals in the gastrointestinal tract. From there they may spread to contiguous structures (as in there they may spread to contiguous structures (as in peritonitis after appendiceal perforation), or they may peritonitis after appendiceal perforation), or they may migrate from the perineum into the urethra or bladder.migrate from the perineum into the urethra or bladder.
Gram-negative bacteremia follows infection in a primary Gram-negative bacteremia follows infection in a primary forms, usually the:forms, usually the:
genitourinary tract, genitourinary tract, biliary tree, biliary tree, gastrointestinal tract or gastrointestinal tract or lungs and lungs and less commonly, the skin, bones and joints.less commonly, the skin, bones and joints. Metastatic abscessMetastatic abscess formation may complicate bacteremia. formation may complicate bacteremia.
The involved target organs are:The involved target organs are:
lungs: pulmonary-edema, hemorrhage and hyaline lungs: pulmonary-edema, hemorrhage and hyaline membrane formation, abscesses, bronchopneumoniamembrane formation, abscesses, bronchopneumonia
kidney: tubular or cortical necrosis,kidney: tubular or cortical necrosis, myocardium: patchy necrosis, superficial ulceration or even myocardium: patchy necrosis, superficial ulceration or even
hemorrhage necrosis hemorrhage necrosis gastrointestinal tract, superficial ulceration or even gastrointestinal tract, superficial ulceration or even
hemorrhage necrosis hemorrhage necrosis capillaries in many tissues: leukocyte-platelet or fibrin capillaries in many tissues: leukocyte-platelet or fibrin
thrombus formationthrombus formation brain /meninges: abscesses, meningitisbrain /meninges: abscesses, meningitis
PathophysiologyPathophysiology
Table 1:Table 1: Virulence factors of Staphylococcus aureus and their Virulence factors of Staphylococcus aureus and their proposed pathogenic mechanismproposed pathogenic mechanism
VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS AND THEIR PROPOSED VIRULENCE FACTORS OF STAPHYLOCOCCUS AUREUS AND THEIR PROPOSED PATHOGENIC MECHANISMPATHOGENIC MECHANISM ` `
Twart host defensesTwart host defensesMicrocapsuleMicrocapsuleProtein AProtein ACoagulaseCoagulaseFatty acid-metabolizing enzymeFatty acid-metabolizing enzymeLeukocidin and/or gama-toxinLeukocidin and/or gama-toxinInvade tissueProteasesInvade tissueProteasesNucleasesLipasesNucleasesLipasesHyaluronate lyaseHyaluronate lyaseStaphylokinaseElicit sepsis syndromeStaphylokinaseElicit sepsis syndromeToxic shock syndrome toxinToxic shock syndrome toxinEnterotoxinsEnterotoxinsCytolytic toxins (alpha, beta, gama and delta)Induce specific toxinosisCytolytic toxins (alpha, beta, gama and delta)Induce specific toxinosisToxic shock syndrome toxinToxic shock syndrome toxinEnterotoxinExfoliative toxinEnterotoxinExfoliative toxinAttach to endothelial cells and basement membraneAttach to endothelial cells and basement membraneBinding proteins for fibrinogen, fibronectin, laminin, collagen, vitronectin and Binding proteins for fibrinogen, fibronectin, laminin, collagen, vitronectin and thrombospondinthrombospondin
Clinical manifestationsClinical manifestations
Clinical manifestations are related to the following Clinical manifestations are related to the following elements:elements:
I.Portal of entryI.Portal of entry Skin: erysipelas, staphylococcal skin infection, Skin: erysipelas, staphylococcal skin infection,
trauma, burns;trauma, burns; Respiratory tract infectionsRespiratory tract infections Gastrointestinal tract lesions: stomatitis, Gastrointestinal tract lesions: stomatitis,
gingivitis, teeth extraction, enterocolitis;gingivitis, teeth extraction, enterocolitis; Genito-urinary tract infectionsGenito-urinary tract infections
II.Lymphangitis and primary sites of infectionII.Lymphangitis and primary sites of infectionIII.Positive blood culturesIII.Positive blood cultures: hematogenous : hematogenous
dissemination is manifested with fever, chills, dissemination is manifested with fever, chills, headache;headache;
IV.Metastatic foci of infectionIV.Metastatic foci of infection::
Cardiovascular system: infective endocarditis, myocarditis, pericarditisCardiovascular system: infective endocarditis, myocarditis, pericarditis
Central nervous system: brain abscess, epidural abscess, purulent Central nervous system: brain abscess, epidural abscess, purulent meningitis (confusion, obtundation, coma);meningitis (confusion, obtundation, coma);
Respiratory system: bronchopneumonia, pleural effusion (acute Respiratory system: bronchopneumonia, pleural effusion (acute respiratory distress syndrome, tachypnea, hypocapnea);respiratory distress syndrome, tachypnea, hypocapnea);
Gastrointestinal: liver and spleen abscess, impaired gastrointestinal Gastrointestinal: liver and spleen abscess, impaired gastrointestinal motility, sterss related mucosal disease, hyperbilirubinemia, elevation of motility, sterss related mucosal disease, hyperbilirubinemia, elevation of liver enzymes.liver enzymes.
Renal system: renal abscess, nephritisRenal system: renal abscess, nephritis
Bone and joint involvement: osteitis, osteomyelitis, spondylodiscitis, Bone and joint involvement: osteitis, osteomyelitis, spondylodiscitis, arthritisarthritis
Cutaneous manifestations: cellulitis, flegmons, diffuse erythroderma Cutaneous manifestations: cellulitis, flegmons, diffuse erythroderma (caused by gram-positive organisms and by the action of pyrogenic or (caused by gram-positive organisms and by the action of pyrogenic or erythrogenic toxins); colorful skin lesions such as ecthyma gangrenosum erythrogenic toxins); colorful skin lesions such as ecthyma gangrenosum (associated with P. aeruginosa septicemia), colorful vezicular or bullous (associated with P. aeruginosa septicemia), colorful vezicular or bullous lesions, cellulitis, petechial lesions (may appear in gram negative lesions, cellulitis, petechial lesions (may appear in gram negative septicemia)septicemia)
Toxic shock syndrome Toxic shock syndrome
Clinical manifestationsClinical manifestations
1. Hemodynamic changes:1. Hemodynamic changes:2. Dermatologic findings:2. Dermatologic findings:3. Severe myalgias, muscle tenderness, 3. Severe myalgias, muscle tenderness,
weaknessweakness4. Diarrhea, nausea, vomiting]4. Diarrhea, nausea, vomiting]5. Encephalopathy5. Encephalopathy6. Respiratory distress syndrome6. Respiratory distress syndrome7. Acute renal failure7. Acute renal failure8. Hepatic necrosis8. Hepatic necrosis9. Disseminated intravascular coagulation.9. Disseminated intravascular coagulation.
Table 4: Table 4: Streptococcal Toxic Shock SyndromeStreptococcal Toxic Shock SyndromeStreptococcal Toxic Shock Streptococcal Toxic Shock Syndrome – definitionSyndrome – definition
An acute, febrile illness that begins with a mild An acute, febrile illness that begins with a mild viral-like prodrome or minor soft-tissue infection viral-like prodrome or minor soft-tissue infection and may progress to shock, multiorgan failure and and may progress to shock, multiorgan failure and death death
Symptoms Symptoms Early symptoms are vague:Early symptoms are vague:Viral-like prodromeViral-like prodromeSevere pain and erythema of an extremitySevere pain and erythema of an extremityMental confusion Mental confusion
SignsSigns Hypotension, systolicHypotension, systolicFever > 38 degreeFever > 38 degreeSoft-tissue swellingSoft-tissue swellingTendernessTendernessRespiratory failure, rales, cyanosis, tachypneea Respiratory failure, rales, cyanosis, tachypneea
Laboratory featuresLaboratory features Hematologic:Hematologic:Marked left shiftMarked left shiftDecline in hematocritDecline in hematocritThrombocytopeniaThrombocytopeniaRenal azotemia (2,5 x normal on admission) and Renal azotemia (2,5 x normal on admission) and hematuriahematuriaHypocalcemiaHypocalcemiaHypoalbuminemiaHypoalbuminemiaCreatine phosphokinase elevationCreatine phosphokinase elevationPulmonary abnormalities:Pulmonary abnormalities:-Pulmonary infiltrate on chest x-ray-Pulmonary infiltrate on chest x-ray-Hypoxia -Hypoxia
Table 5. Laboratory investigations in sepsisTable 5. Laboratory investigations in sepsis
Complete blood countComplete blood countBlood chemistryBlood chemistryUrinalysisUrinalysisChest radiographyChest radiographyErythrocyte sedimentation Erythrocyte sedimentation raterateBlood cultures (3 or more Blood cultures (3 or more separate specimens)separate specimens)Cultures from other biologic Cultures from other biologic fluids (pus, pleural effusion, fluids (pus, pleural effusion, joint effusion, catheter, etc)joint effusion, catheter, etc)
Antinuclear antibodiesAntinuclear antibodiesRheumatoid factorRheumatoid factorComputed tomography of Computed tomography of abdomen, pelvis, other sitesabdomen, pelvis, other sitesRadionuclide scansVenous Radionuclide scansVenous duplex imaging of lower limbsduplex imaging of lower limbsEchocardiographyEchocardiography
Differential diagnosisDifferential diagnosis
Infectious diseasesInfectious diseases
Bacterial infectionsBacterial infections Rickettsial infections Rickettsial infections Viral infections:, Viral infections:, Parasitic infections:Parasitic infections: Fungal infections:Fungal infections:
Non-infectious diseasesNon-infectious diseases
Neoplastic diseases:;Neoplastic diseases:; Autoimmune diseases: Autoimmune diseases: Hypersensitivity;Hypersensitivity; Granulomatous diseases: Granulomatous diseases: Other: CNS hemorrhage, CNS degenerative diseases, Other: CNS hemorrhage, CNS degenerative diseases,
familial Mediteranean fever, cholangitis.familial Mediteranean fever, cholangitis.
TreatmentTreatment
A. Initial therapy for the sepsis syndromeA. Initial therapy for the sepsis syndrome
Community-acquired infectionsCommunity-acquired infections
Suspected staphyloccocal etiology: oxacillin+aminoglycosideSuspected staphyloccocal etiology: oxacillin+aminoglycosideSuspected genito-urinary source: a third generation cephalosporin Suspected genito-urinary source: a third generation cephalosporin
(3GC); a quinolone; ticarcillin/piperacillin with/without an (3GC); a quinolone; ticarcillin/piperacillin with/without an aminoglycoside;aminoglycoside;
Non-urinary tract source: 3GC or ampicillin/ticarcillin/piperacillin – Non-urinary tract source: 3GC or ampicillin/ticarcillin/piperacillin – beta lactamase-inhibitor (BLI)beta lactamase-inhibitor (BLI)
Hospital-acquired infections:Hospital-acquired infections:
Non-neutropenic patients: 3GC with/without metronidazole, cefepime, Non-neutropenic patients: 3GC with/without metronidazole, cefepime, a beta lactam drug-BLI/imipenem with/without an aminoglycosidea beta lactam drug-BLI/imipenem with/without an aminoglycoside
Neutropenic patients: ceftazidime + an aminoglycoside; ticarcillin-Neutropenic patients: ceftazidime + an aminoglycoside; ticarcillin-clavulanat/piperacillin-tazobactam + an aminoglycoside; clavulanat/piperacillin-tazobactam + an aminoglycoside; imipenem/meropenem + an aminoglycoside.imipenem/meropenem + an aminoglycoside.
Tabel 6Tabel 6..First intention treatment and alternative First intention treatment and alternative therapy for infective endocarditis on native valvetherapy for infective endocarditis on native valve
EtiologyEtiology First intention treatmentFirst intention treatment Alternative Alternative S.aureus meti-S.aureus meti-SS.aureus meti-RS.viridans, S. SS.aureus meti-RS.viridans, S.
bovis- bovis- sensitive to Pen. sensitive to Pen. G(CMI<o,1microg/ml)G(CMI<o,1microg/ml)
S.viridans, S.bovisS.viridans, S.bovis with CMI with CMI PenG:0,1-0,5microg/mlPenG:0,1-0,5microg/ml..
S viridans, S.bovisS viridans, S.bovis (CMI(CMI PenG>1),PenG>1),
enterococi enterococi sensitive to sensitive to ampi/Pen G, vanco, ampi/Pen G, vanco, gentagenta
EnterocociEnterococi (CMI Pen G (CMI Pen G >16ng/ml)>16ng/ml)
EnterocociEnterococi pen/ampi R, high pen/ampi R, high resistance to genta, resistance to genta, vanco-Rvanco-R
Difteroizi Difteroizi sensitive to genta sensitive to genta (MIC<4/ml)(MIC<4/ml)Difteroizi Difteroizi resistent to genta resistent to genta (>4/ml)(>4/ml)
gram-negative cocobacili gram-negative cocobacili from the group from the group HACEK*HACEK*
BartonellaCandidaBartonellaCandidaEI on valvular prothesis EI on valvular prothesis
with negative with negative bloodculturesbloodcultures
(oxaciline 8g/d iv, every 4h)x4-6wks (oxaciline 8g/d iv, every 4h)x4-6wks +gentax3-5days+gentax3-5days
(Vanco 2g/d iv, every 12h)x4-6wks (Vanco 2g/d iv, every 12h)x4-6wks Pen.G 12-18milU/d, iv, cont/4hx2 Pen.G 12-18milU/d, iv, cont/4hx2
wks + genta 3mg/kg/d x2wks wks + genta 3mg/kg/d x2wks oror
Pen G x4wks orPen G x4wks orCeftriaxone 4g/d x4wksCeftriaxone 4g/d x4wksPen G 18mil U/d x4wks+genta Pen G 18mil U/d x4wks+genta
3mg/kg/d x 2wks,3mg/kg/d x 2wks,Pen G 18milU/24h, 4-6spt+genta 4-Pen G 18milU/24h, 4-6spt+genta 4-
6wks, or (AMP12g/zi iv cont or 6wks, or (AMP12g/zi iv cont or every 4h+genta)x4-6wksevery 4h+genta)x4-6wks
Vanco+gentax4-6wksVanco+gentax4-6wksQuinupristin/dalfopristin or linezolid Quinupristin/dalfopristin or linezolid
1200mg/zi iv1200mg/zi ivPenG+gentax6wksPenG+gentax6wksVancox6wksVancox6wksCeftriaxone 2-3g iv or cefotaxime Ceftriaxone 2-3g iv or cefotaxime
3g ivx6wks3g ivx6wksFluoroquinolone or RIF or macrolideFluoroquinolone or RIF or macrolideAmfotericine B+/-an azol Amfotericine B+/-an azol
(fluconazole)(fluconazole)Vanco+RIF+gentax6wks Vanco+RIF+gentax6wks
1. Cefazolin 6g ivx4-1. Cefazolin 6g ivx4-6weeks+genta3mg/k6weeks+genta3mg/kgx3-5d, OR 2. Vanco gx3-5d, OR 2. Vanco 4-6wks4-6wks3. (Ceftriaxone + 3. (Ceftriaxone + genta)x2wksgenta)x2wks4. vanco 30mg/kgc/d 4. vanco 30mg/kgc/d until la 2g/dx4wksuntil la 2g/dx4wks
5. (vanco+genta) x4-5. (vanco+genta) x4-6wks6wks
7.Vancox6wks7.Vancox6wksAmpi 12g/d+(strepto Ampi 12g/d+(strepto 15mg/kg-1g/d or 15mg/kg-1g/d or genta)x6wksgenta)x6wks
Table 7. Infective endocarditis on prosthetic Table 7. Infective endocarditis on prosthetic valvevalve
Etiology Etiology First intention First intention treatmenttreatment
AlternativeAlternative
S. epidermidisS. epidermidisS.aureus meti-RS.aureus meti-RS.aureus meti-SS.aureus meti-S
EI on valvular prothesis EI on valvular prothesis with negative with negative bloodculturesbloodculturesFor the other etiologyFor the other etiology
(Vanco 2g/d iv, every (Vanco 2g/d iv, every 12h+RIF 900mg/d, 12h+RIF 900mg/d, every 8h)x6wks every 8h)x6wks +genta* 240mg/d +genta* 240mg/d every 8 hx2wksevery 8 hx2wks“ “ ““ “ “ (oxaciline 8g/d iv, (oxaciline 8g/d iv, every 4h+RIF)x6wks every 4h+RIF)x6wks +gentax2wks+gentax2wksVanco+RIF+gentax6wkVanco+RIF+gentax6wkssAs for the native valve As for the native valve endocarditis. endocarditis.
Vanco+FluoroquinoloneVanco+Fluoroquinolone+RIF+RIF
“ “ ““ “ “
B. Adjunctive measures in the treatment B. Adjunctive measures in the treatment of sepsis syndromeof sepsis syndrome
Maintenance of adequate tissue perfusion with Maintenance of adequate tissue perfusion with volume replacement: normal saline solution, fresh volume replacement: normal saline solution, fresh frozen plasma, albumin, dextran, crystaloid frozen plasma, albumin, dextran, crystaloid solutions.solutions.
Sympatomimetic amines: dopamine, dobutamineSympatomimetic amines: dopamine, dobutamine
Corticosteroids for gram-negative rod septicemia-is Corticosteroids for gram-negative rod septicemia-is controversed.controversed.
Diuretics for the early oliguric phases of schock.Diuretics for the early oliguric phases of schock.
