Approach of Infected patient in Critical Care Unit

1. Approach of Infected patient in Critical Care Unit Mazen Kherallah, MD, FCCP Consultant, Infectious Disease & Critical Care Chairman, Critical Care Department King Faisal Specialist Hospital & Research Center

2. 1. What Sepsis Syndrome are we Dealing with? • Infection • Sepsis • Severe sepsis • Septic shock • Multi-organ system failure

3. Infection Inflammatory response to microorganisms, or Invasion of normally sterile tissues Systemic Inflammatory Response Syndrome (SIRS) Systemic response to a variety of processes Sepsis Infection plus 2 SIRS criteria Severe Sepsis Sepsis Organ dysfunction Septic shock Sepsis Hypotension despite fluid resuscitation Multiple Organ Dysfunction Syndrome (MODS) Altered organ function in an acutely ill patient Homeostasis cannot be maintained without intervention ACCP/SCCM Consensus Definitions Bone RC et al. Chest. 1992;101:1644-55.

4. SIRS: More Than Just a Systemic Inflammatory Response • SIRS: A clinical response arising from a nonspecific insult manifested by 2 of the following: • Temperature 38°C or 36°C • HR 90 beats/min • Respirations 20/min • WBC count 12,000/mL or 4,000/mL or >10% immature neutrophils • Recent evidence indicates that hemostatic changes are also involved Adapted from: Bone RC et al. Chest. 1992;101:1644-55. Opal SM et al. Crit Care Med. 2000;28:S81-2.

5. Severe Sepsis: Acute Organ Dysfunction and Disordered Hemostasis • Severe Sepsis: Sepsis with signs of organ dysfunction in 1 of the following systems: • Cardiovascular • Renal • Respiratory • Hepatic • Hemostasis • CNS • Unexplained metabolic acidosis Adapted from: Bone RC et al. Chest. 1992;101:1644-55.

6. Sepsis Syndromes Infection Sepsis Severe Sepsis Septic Shock Microbiological Phenomenon Infection + SIRS Sepsis + End-Organ Damage Severe Sepsis + Refractory Hypotension

7. Sepsis Parameters: • Leukocytosis with left shift • Bandemia • Toxic granulation • Elevated sed. Rate • C- reactive protein • Acute phase reactant: fibrinogen, haptoglobin,.. • IL1, IL6, IL8

8. Skin Soft tissue CNS Upper airway Lower airway Head and neck Mediastinal GI Liver Biliary tract Intra-abdominal Bones and joints Urinary tract Genital tract Blood stream infection Systemic 2. Organ Localization of infection

9. Skin and soft tissue: Superficial epidermal layers (impetigo) Deeper epidermal layers (Icthyma) Superficial subcutaneous: Erysipelas Deeper subcut.: cellulitis Folliculitis Hydradenitis Fascia: Fasciitis Fat: panuculitis Lower respiratory tract: Alveolar: consolidative pneumonia Interstitial: atypical pneumonia Pleural: empyema 3. Tissue Localization of Infection

10. Host factors Immunosuppression Age Gender Previous antibiotics Co-morbidity: SSD DM CGD Environmental Community: contacts Travel Animals Hospital: Location Nursing homes 4. Suspected Microbiology of Infection

11. Community acquired pneumonia: Lobar pneumonia Streptococcus Pn. H. flu Moraxella catarrhalis Staphylococcal Klebsiella Community acquired pneumonia: interstitial: Mycoplasma Pn. Legionella Viral 4. Suspected Microbiology of Infection

12. Intra-abdominal infection E. coli Klebsiella B. fragilis Enterococcus Candida Urinary tract infection E. coli Proteus Enterococcus 4. Suspected Microbiology of Infection

13. Meningitis: <1 month: Group B strep 49% E. Coli 18% Listeria 7% Gram neg. 10% Meningitis: 1 mo-50 yrs: S. pneumoniae Meningococci H. flu (very rare) 4. Suspected Microbiology of Infection

14. 5. Surgical Indication: • Foreign body: central line infection • Prosthesis: PVE, Prosthetic infection • Sequestration: chronic osteomyelitis • Gangrene: wet gangrene • Obstructed normal draining procedure: cholecystitis • No penetration for antibiotics: empyema, abscess

15. Appropriate coverage Adequate dose: MIC, MBC Appropriate route Absorption Penetration Tissue level Cellular level 5. Empiric Treatment

16. Meningitis: <1 month: Group B strep 49% E. Coli 18% Listeria 7% Gram neg. 10% Ampicillin+Cefotaxime Meningitis: 1 mo-50 yrs: S. pneumoniae Meningococci H. flu (very rare) Vancomycin+Ceftriaxone or cefotaxime 4. Suspected Microbiology of Infection

17. E. coli, Klebsiella Amp/sulbactam Piperacillin/tazobactam Ticarcillin/clavaulinate Aztreonam Imipenem Cefazolin Cefuroxime Ceftriaxone Ciprofloxacin B. Fragilis Amp/sulbactam Piperacillin/tazobactam Ticarcillin/clavaulinate Imipenem Cefoxitin Clindamycin Metronidazole Chloramphonicole Empiric Treatment: Intra-abdominal Infection

18. IntroductionFever Work-Up • Automatic set order • Repeated several times within 24 hours • Time consuming • Costly • Disruptive and patient’s discomfort • Considerable blood loss • Unneeded radiation

19. Practice ParametersGoals • Rational consumption of resources • Efficient evaluation

20. The Search for the Underlying Cause of Fever? • What temperature should elicit an evaluation? • When are blood cultures warranted • When should intravascular catheters be cultured or removed • When are cultures of respiratory secretions, urine, stool, or CSF warranted • When are radiological studies warranted

21. Initiating Fever EvaluationDefinition of Fever • Arbitrary: core temperature >38.0°C, or two consecutive elevation of > 38.3°C • The lower the temperature that is used to define fever, the more sensitive and less specific the indicator is for detecting an infectious etiology

22. Initiating Fever EvaluationNormal Body Temperature • Normal body temperature is 37.0°C • Varies by 0.5°C to 1°C according to circadian rhythm and menstrual cycle • Exercise can increase temperature by 2°C to 3°C

23. Initiating Fever EvaluationVariation of Temperature in ICU • Specialized mattresses • Hot lights • Air conditioning • Cardiopulmonary bypass • Peritoneal lavage • Dialysis and continuous hemofiltration • Drugs altering thermoregulatory mechanisms

24. Initiating Fever EvaluationNon-infectious Causes of Fever can be Life-threatening • Adrenal insufficiency • Thyroid storm • Malignant hyperthermia • Heat stroke

25. Initiating Fever EvaluationInfected Patient but Afebrile • Elderly • Open abdominal wounds • Large burns • Extracorporeal membrane oxygenation • Patients taking anti-inflammatory or anti-pyretic drugs

26. Initiating Fever EvaluationTemperature Measurement • Most accurately measured using intravascular or bladder thermistor • Mouth, rectal or external auditory measurements using electronic probes is acceptable in appropriate patients • Axillary measurements should not be used

27. Initiating Fever EvaluationClinical Evaluation • A new onset of temperature to or above 38.3C is reasonable trigger for a clinical assessment but not necessarily a laboratory or radiological evaluation • Clinical assessment may reveal a purulent wound or phlebitic leg, then diagnosis and therapy for that infectious process should commence

28. Bacterial Synergistic Gangrene

29. Anaerobic Cellulitis

30. Initiating Fever EvaluationObtaining Blood CulturesSkin Preperation • The site of venipunture should be cleaned with either 10% povidone iodine or 1-2% tincture of iodine. If the patient is allergic to iodine alcohol 70% swabs should be used • The access to intravascular device and to the stopper on the culture bottle should be cleaned with 70% alcohol • Iodophors must be allowed to dry to provide maximal antiseptic activity

31. Initiating Fever EvaluationObtaining Blood CulturesBlood Volume • One blood culture is defined as a sample of blood drawn at a single time at a single site • One milliliter of blood is needed per five milliliter of media • 5 ml of blood is injected into each of two or three bottles for routine blood culture • 10-15 ml per one set of blood cultre

32. Initiating Fever EvaluationObtaining Blood CulturesNumber of Cultures & Sites • Two cultures 10 minutes apart after the onset of fever. Culture should not be repeated till 24 hours passed • Each culture should be drawn by separate venipuncture • One culture can be obtained from the most recently inserted catheter in case venipuncture is difficult (the second B/C from a venipuncture site)

33. Initiating Fever EvaluationCXR & Sputum • Chest x-ray in an erect sitting position during deep inspiration • The absence of infiltrates, masses or effusion does not exclude pneumonia, abscess or empyema • Respiratory secretion obtained by suctioned or expectorated sputum is adequate for initial evaluation

34. Initiating Fever EvaluationUrinalysis and Urine Culture • Obtain urine for culture and for determination of the presence of pyuria • Patients who have Foley catheter in place should have urine collected from the urine port of the catheter and not from the drainage bag • Urine should be transported to the laboratory rapidly to avoid bacterial multiplication, otherwise should be refrigerated

35. Initiating Fever EvaluationStool Examination • Mandatory when more than 2 stools per day conform to the container in which they are placed in a patient at risk for C-difficile • Stool should be sent for WBC or lactoferrin latex agglutination test • Stool should be sent for c-diff assay for at least 2 times in 24 hours • Stool should not be sent for other enteric pathogens unless the patient is HIV or present to the hospital with diarrhea

36. Infectious Causes of Fever • Catheter-related Infections • ICU acquired Pneumonia • Urinary Tract Infection • Pseudomembraneous colitis • Wound Infection • Sinusitis • Acaculous cholecystitis

37. Vascular Devices & fever • Localized infection • Exit site infection • Tunnel infection • Systemic infection • Allergic reaction

38. Relative Risks of CR-BSI • Duration of catheter in place • Anatomic site of insertion • Type of the device: • Catheter composition • A-Line, Central line, Hickman’s catheter • Regular vs antibiotic-impregnated catheter • Patient population • Techniques used in insertion and maintenance • Frequency of manipulation

39. Duration of Catheter UseOptimal Time for Catheter Removal? • The incidence of CR-BSI is directly proportional to the length of time the catheter is used • The risk that any catheter may cause CR-BSI is low if the catheter is removed within 3 days • The optimal time for catheter removal is unknown

40. Anatomic Site of InsertionIncidence of Catheter Colonization: Kemp and associates • Femoral line: 36% • Internal jugular: 17% • Subclavian: 5%

41. Type of the DeviceRisk of CR-BSI • Short-term noncuffed central venous catheters: 5-10 cases per 1000 catheter days • Peripheral IV catheter: less than 0.2 cases per 1000 catheter days • Permanent surgically implanted central device: 2 bacteremias per 1000 catheter days

42. Catheter Related InfectionsDefinitionsColonized Catheter • Positive culture from the catheter tip or intracutaneous segment without evidence of systemic infection • Semiquantitative culture of 15 or more CFU is used to consider culture as positive • Values of less than 15 CFU are regarded as negative culture, contaminant, or insignificant infection requiring no therapy

43. Catheter Related InfectionsDefinitionsCatheter-Related Bloodstream Infection • A positive catheter culture 15 CFU with concomitant positive blood culture • A quantitative blood culture drawn from the catheter shows marked step-up in concentration of organisms (ten-fold or greater) as compared with peripherally drawn quantitative blood culture • No other identifiable source of infection

44. Catheter Related InfectionsDefinitionsInfusate-Related Bloodstream Infection • Isolation of the same organism from the infusate and from separate percutaneous peripheral blood culture • No other identifiable source of infection

45. Catheter Related InfectionsDefinitionsLocal Catheter-Related Infection • Growth of 15 or more CFU from a catheter specimen by semiquantitative culture • Local signs of inflammation: erythema, swelling, tenderness, purulent material • Negative peripheral blood culture

46. When the Catheter Should be Removed in a Febrile Patient?No other identifiable Source • For stable patients with fever, there is no necessity to remove or change all indwelling catheters unless CR-BSI or Local infection is documented • If patients are in shock, manifest peripheral embolization, DIC or ARDS, removal of all intravascular catheters and reinsertion at new sites is indicated.

47. Pulmonary Infections & FeverDiagnostic Strategies • Empirical strategy based only on clinical evaluation • Invasive strategy based on fiberoptic bronchoscopy and quantitative cultures of distal uncontaminated pulmonary secretions • Intermediate strategy based on quantitative culture of nonbronchoscopic sample

48. Diagnostic Strategy based on Clinical Evaluation only • Fever, cough, sputum production, new pulmonary infiltrate and elevated leukocyte count. • May not be present in the hospitalized patients with nosocomial pneumonia • May be present but may not be caused by pneumonia: CHF, ARDS, atelectasis

50. Diagnostic Strategy based on Clinical Evaluation only Andrews et al, chest 1981;80:254-258