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. ACCP/SCCM Consensus Definitions
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
Hypotension despite fluid resuscitation
Multiple Organ Dysfunction Syndrome (MODS)
Altered organ function in an acutely ill patient
Homeostasis cannot be maintained without intervention
The American College of Chest Physicians (ACCP) and Society of Critical Care Medicine (SCCM) held a consensus conference in August 1991 to agree on a set of definitions that could be applied to patients with sepsis and organ dysfunction. The consensus panel also recommended the use of severity scoring methods to characterize the disease and develop a comprehensive model for the syndrome.
This slide provides a brief definition of the various components of the sepsis syndrome. Notably, this is a non-linear process rather than a continuum and the presence of organ dysfunction identifies a population with a significant risk of mortality.
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Bone RC et al. Chest. 1992;101:

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
The systemic inflammatory response syndrome (SIRS) is a clinical response arising from a nonspecific insult manifested by two or more of the following:
Fever or hypothermia
Tachycardia
Tachypnea
Leukocytosis, leukopenia, or a left-shift (increase in immature neutrophilic leukocytes in the blood)
Recent evidence indicates that hemostatic changes play a significant role in many SIRS-linked disorders.
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Opal SM, Thijs L, Cavaillon JM, et al. Relationships between coagulation and inflammatory processes. Crit Care Med. 2000; 28:S81-2.
Adapted from: Bone RC et al. Chest. 1992;101:
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
Severe sepsis is sepsis plus signs and symptoms of acute organ dysfunction, hypoperfusion, or hypotension. Hypoperfusion and perfusion abnormalities may include, but are not limited to, lactic acidosis, oliguria, or an acute alteration in mental status.
As shown on the next slide, organ dysfunction may involve any of the following alone or in combination:
Cardiovascular system
Kidney
Respiratory system
Liver
Hematologic (blood, coagulation)
Central nervous system
Presence of an otherwise unexplained metabolic acidosis
Bone RC, Balk RA, Cerra FB, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Chest. 1992;101:
Adapted from: Bone RC et al. Chest. 1992;101:

6. Infection Sepsis Severe Sepsis Septic Shock
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. 2. Organ Localization of infection
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

9. 3. Tissue Localization of Infection
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

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

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

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

13. 4. Suspected Microbiology of Infection
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)

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

16. 4. Suspected Microbiology of Infection
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

17. Empiric Treatment: Intra-abdominal Infection
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

18. Introduction Fever 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 Parameters Goals
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 Evaluation Definition 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 Evaluation Normal 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 Evaluation Variation 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 Evaluation Non-infectious Causes of Fever can be Life-threatening
Adrenal insufficiency
Thyroid storm
Malignant hyperthermia
Heat stroke

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

26. Initiating Fever Evaluation Temperature 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 Evaluation Clinical 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 Evaluation Obtaining Blood Cultures Skin 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 Evaluation Obtaining Blood Cultures Blood 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 Evaluation Obtaining Blood Cultures Number 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 Evaluation CXR & 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 Evaluation Urinalysis 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 Evaluation Stool 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 Use Optimal 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 Insertion Incidence of Catheter Colonization: Kemp and associates
Femoral line: 36%
Internal jugular: 17%
Subclavian: 5%

41. Type of the Device Risk 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 Infections Definitions Colonized 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 Infections Definitions Catheter-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 Infections Definitions Infusate-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 Infections Definitions Local 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
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 & Fever Diagnostic 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:

51. Diagnostic Strategy based on Clinical Evaluation only
Autopsy Results
Andrews et al, chest 1981;80:

54. Chastre et al. Evaluation of bronchoscopic techniques for the
diagnosis of nosocomial pneumonia. Am J Respir Crit Care
Med 1995; 152:

55. Diagnostic Strategy based on Invasive Evaluation
Bronchoalveolar Lavage

58. Chastre et al. Evaluation of bronchoscopic techniques for the
diagnosis of nosocomial pneumonia. Am J Respir Crit Care
Med 1995; 152:

60. Diagnostic Strategy based on Invasive Evaluation Protected Brush Specimen

61. Diagnostic Strategy based on Invasive Evaluation Protected Brush Specimen Drawbacks: False Negative Results
Bronchoscopy performed at an early stage of infection with bacterial burden below the concentration necessary to reach diagnostic significance
Specimens obtained from unaffected segments
Specimens incorrectly processed
Specimens obtained after initiation of a new antimicrobial therapy

62. Quantitative Cultures of Nonbronchoscopic Distal
Intermediate Strategy Based on Quantitative Culture of Nonbronchoscopic Samples
Quantitative Cultures of Nonbronchoscopic Distal
Protected Specimen
Represents a good alternative in patients with very unstable conditions and in patients for whom it is not possible to delay the initiation of antimicrobial treatment while awaiting bronchoscopy
Diagnosis can be missed, especially in the case of upper lobes or left lung infection

63. Jourdain et al. Role of quantitative cultures of Endotracheal aspirates for the diagnosis of nosocomial pneumonia. Am J Resp Crit Care Med 1995; 152:
68% VS 84%

64. Intermediate Strategy Based on Quantitative Culture of Nonbronchoscopic Samples
Quantitative Cultures of Endotracheal aspirates

65. Diarrhea & Fever in ICU Diarrhea is caused by enteral feeding or drugs
The only common enteric cause of fever in the ICU is Clostridium difficile
C. difficile accounts for about 25% of all cases of antibiotic-related diarrhea

66. Pseudomembraneous Colitis

67. Methylene Blue Stain

68. Cytotoxin Effect on Baby Hamster kidney Cells

72. UTI & Fever in ICU
The presence of pyuria can help establish the importance of urinary bacteria
Leukocyte esterase dipstick test is easy and simple
Gram stain of a centrifuged urine sediment may provide clues to the type of microorganisms present

73. Other Causes of Fever in ICU Respiratory
Tracheobronchitis
Empyema
Lung abscess
Sinusitis

74. Other Causes of Fever in ICU Wound & Soft Tissue
Wound infection
Decubitus ulcers
Cellulitis
Deep-seated abscess: sub-diaphragmatic

75. Other Causes of Fever in ICU Gastrointestinal
Ischemic colitis
Acalculous cholecystitis
Cholangitis
Transfusion-related hepatitis: CMV, hepatitis C, and hepatitis B
Intraabdominal abscess
Diverticulitis

76. Other Causes of Fever in ICU Prosthetic Devices
Cardiac valve/pacemaker
Joint replacement prosthesis
Peritoneal dialysis catheter
CNS intraventricular shunt

77. Non-Infectious Source of Fever in ICU Drugs
Antibiotics: B-lactam agents
Anti-epileptic drugs: phenytoin
Antiarrythmics: quinidine and procainamide
Antihypertensive: methyldopa

78. Non-Infectious Source of Fever in ICU Post-operative
Up till 72 hours postoperative
Atelectasis
Post-pericardiotomy syndrome

79. Non-Infectious Source of Fever in ICU Vascular Conditions
Deep venous thrombophlebitis
Pulmonary embolism and infarction
Bowel ischemia
Hemorrhage into CNS, retroperitonium, joint, lung, and adrenals
Myocardial infarction and Dressler’s syndrome

80. Non-Infectious Source of Fever in ICU Inflammatory Conditions
Reaction to blood products
Proliferative phase of ARDS
Infusion of interleukin-2, granulocyte macrophage colony stimulating factor, and granulocyte colony stimulating factor
Postpericardiotomy syndrome
Pancreatitis
Vasculitis

81. Non-Infectious Source of Fever in ICU Metabolic Conditions
Heat stroke
Malignant hyperthermia
Neuroleptic malignant syndrome
Adrenal insufficiency
Alcohol withdrawal
Seizures
Hyperthyroidism

82. Non-Infectious Source of Fever in ICU Neoplasms
Lymphoma
Renal cell carcinoma
Hepatoma
Malignant metastatic to the liver
Colon carcinoma