Approach of Infected patient in Critical Care Unit

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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

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1. What Sepsis Syndrome are we Dealing with?

• Infection
• Sepsis
• Severe sepsis
• Septic shock
• Multi-organ system failure

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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
• Sepsis
• Hypotension despite fluid resuscitation
• Multiple Organ Dysfunction Syndrome (MODS)
• Altered organ function in an acutely ill patient
• Homeostasis cannot be maintained without
  intervention

Bone RC et al. Chest. 19921011644-55.
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SIRS More Than Just a Systemic Inflammatory
Response

• SIRS A clinical response arising from a
  nonspecific insult manifested by ?2 of the
  following
• Temperature ?38C or ?36C
• HR ?90 beats/min
• Respirations ?20/min
• WBC count ?12,000/mL or ?4,000/mL or gt10
  immature neutrophils
• Recent evidence indicates that hemostatic changes
  are also involved

Adapted from Bone RC et al. Chest.
19921011644-55. Opal SM et al. Crit Care Med.
200028S81-2.
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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.
19921011644-55.
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Sepsis Syndromes
Infection Sepsis Severe
Sepsis Septic Shock
Microbiological Phenomenon
Infection SIRS
Sepsis End-Organ Damage
Severe Sepsis Refractory Hypotension
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Sepsis Parameters

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

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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

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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

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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

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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

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4. Suspected Microbiology of Infection

• Intra-abdominal infection
• E. coli
• Klebsiella
• B. fragilis
• Enterococcus
• Candida

• Urinary tract infection
• E. coli
• Proteus
• Enterococcus

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4. Suspected Microbiology of Infection

• Meningitis lt1 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)

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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

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5. Empiric Treatment

• Appropriate coverage
• Adequate dose MIC, MBC
• Appropriate route

• Absorption
• Penetration
• Tissue level
• Cellular level

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4. Suspected Microbiology of Infection

• Meningitis lt1 month
• Group B strep 49
• E. Coli 18
• Listeria 7
• Gram neg. 10
• AmpicillinCefotaxime

• Meningitis 1 mo-50 yrs
• S. pneumoniae
• Meningococci
• H. flu (very rare)
• VancomycinCeftriaxone or cefotaxime

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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

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IntroductionFever Work-Up

• Automatic set order
• Repeated several times within 24 hours
• Time consuming
• Costly
• Disruptive and patients discomfort
• Considerable blood loss
• Unneeded radiation

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Practice ParametersGoals

• Rational consumption of resources
• Efficient evaluation

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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

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Initiating Fever EvaluationDefinition of Fever

• Arbitrary core temperature gt38.0C, or two
  consecutive elevation of gt 38.3C
• The lower the temperature that is used to define
  fever, the more sensitive and less specific the
  indicator is for detecting an infectious etiology

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Initiating Fever Evaluation Normal Body
Temperature

• Normal body temperature is 37.0C
• Varies by 0.5C to 1C according to circadian
  rhythm and menstrual cycle
• Exercise can increase temperature by 2C to 3C

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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

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Initiating Fever Evaluation Non-infectious
Causes of Fever can be Life-threatening

• Adrenal insufficiency
• Thyroid storm
• Malignant hyperthermia
• Heat stroke

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Initiating Fever Evaluation Infected Patient but
Afebrile

• Elderly
• Open abdominal wounds
• Large burns
• Extracorporeal membrane oxygenation
• Patients taking anti-inflammatory or anti-pyretic
  drugs

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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

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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

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Bacterial Synergistic Gangrene
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Anaerobic Cellulitis
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Initiating Fever Evaluation Obtaining 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

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Initiating Fever Evaluation Obtaining 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

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Initiating Fever Evaluation Obtaining 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)

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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

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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

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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

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Infectious Causes of Fever

• Catheter-related Infections
• ICU acquired Pneumonia
• Urinary Tract Infection
• Pseudomembraneous colitis
• Wound Infection
• Sinusitis
• Acaculous cholecystitis

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Vascular Devices fever

• Localized infection
• Exit site infection
• Tunnel infection
• Systemic infection
• Allergic reaction

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Relative Risks of CR-BSI

• Duration of catheter in place
• Anatomic site of insertion
• Type of the device
• Catheter composition
• A-Line, Central line, Hickmans catheter
• Regular vs antibiotic-impregnated catheter
• Patient population
• Techniques used in insertion and maintenance
• Frequency of manipulation

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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

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Anatomic Site of InsertionIncidence of Catheter
Colonization Kemp and associates

• Femoral line 36
• Internal jugular 17
• Subclavian 5

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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

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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

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Catheter Related InfectionsDefinitionsCatheter-R
elated 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

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Catheter Related InfectionsDefinitionsInfusate-R
elated Bloodstream Infection

• Isolation of the same organism from the infusate
  and from separate percutaneous peripheral blood
  culture
• No other identifiable source of infection

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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

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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.

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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

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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

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Diagnostic Strategy based on Clinical Evaluation
only
Andrews et al, chest 198180254-258
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Diagnostic Strategy based on Clinical Evaluation
only
Autopsy Results
Andrews et al, chest 198180254-258
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Chastre et al. Evaluation of bronchoscopic
techniques for the diagnosis of nosocomial
pneumonia. Am J Respir Crit Care Med 1995
152231-240
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Diagnostic Strategy based on Invasive Evaluation
Bronchoalveolar Lavage

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Chastre et al. Evaluation of bronchoscopic
techniques for the diagnosis of nosocomial
pneumonia. Am J Respir Crit Care Med 1995
152231-240
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Diagnostic Strategy based on Invasive
EvaluationProtected Brush Specimen
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Diagnostic Strategy based on Invasive Evaluation
Protected Brush SpecimenDrawbacks 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

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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

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Jourdain et al. Role of quantitative cultures of
Endotracheal aspirates for the diagnosis of
nosocomial pneumonia. Am J Resp Crit Care Med
1995 152241-246
68 VS 84
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Intermediate Strategy Based on Quantitative
Culture of Nonbronchoscopic Samples
Quantitative Cultures of Endotracheal aspirates
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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

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Pseudomembraneous Colitis
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Methylene Blue Stain
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Cytotoxin Effect on Baby Hamster kidney Cells
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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

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Other Causes of Fever in ICURespiratory

• Tracheobronchitis
• Empyema
• Lung abscess
• Sinusitis

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Other Causes of Fever in ICUWound Soft Tissue

• Wound infection
• Decubitus ulcers
• Cellulitis
• Deep-seated abscess sub-diaphragmatic

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Other Causes of Fever in ICUGastrointestinal

• Ischemic colitis
• Acalculous cholecystitis
• Cholangitis
• Transfusion-related hepatitis CMV, hepatitis C,
  and hepatitis B
• Intraabdominal abscess
• Diverticulitis

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Other Causes of Fever in ICUProsthetic Devices

• Cardiac valve/pacemaker
• Joint replacement prosthesis
• Peritoneal dialysis catheter
• CNS intraventricular shunt

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Non-Infectious Source of Fever in ICUDrugs

• Antibiotics B-lactam agents
• Anti-epileptic drugs phenytoin
• Antiarrythmics quinidine and procainamide
• Antihypertensive methyldopa

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Non-Infectious Source of Fever in
ICUPost-operative

• Up till 72 hours postoperative
• Atelectasis
• Post-pericardiotomy syndrome

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Non-Infectious Source of Fever in ICUVascular
Conditions

• Deep venous thrombophlebitis
• Pulmonary embolism and infarction
• Bowel ischemia
• Hemorrhage into CNS, retroperitonium, joint,
  lung, and adrenals
• Myocardial infarction and Dresslers syndrome

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Non-Infectious Source of Fever in
ICUInflammatory 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

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Non-Infectious Source of Fever in ICUMetabolic
Conditions

• Heat stroke
• Malignant hyperthermia
• Neuroleptic malignant syndrome
• Adrenal insufficiency
• Alcohol withdrawal
• Seizures
• Hyperthyroidism

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Non-Infectious Source of Fever in ICUNeoplasms

• Lymphoma
• Renal cell carcinoma
• Hepatoma
• Malignant metastatic to the liver
• Colon carcinoma