Fever and antibiotics

1. FEVER IN INTENSIVE CARE
UNIT
Dr. Nathan Muluberhan(E M
r e s i d e n t )
August
2017

2. OUTLINE
 DEFINITIONS OF TERMS
 PATHOGENESIS OF FEVER
 SIGNIFICANCE OF FEVER
 FEVER IN ICU
 INFECTIOUS CAUSE
 NON INFECTIOUS CAUSE

3. DEFINITIONS
 F E V E R :
 elevation of body temperature that exceeds the normal daily
variation and occurs in conjunction with an increase in the hypothalamic set point.
 H Y P E R T H E R M I A :
 elevation of body temperature in a setting of unchanged the hypothalamic
thermoregulatory center is
 HYPERPYREXIA:
 an extraordinarily high fever (>41.5ºC)
 P Y R O G E N S :
 is any substance that causes fever

4. PATHOGENESIS

5. TEMPERATURE MEASUREMENT
 Normal body temperature is generally considered to be
37.0°C (98.6°F) with a circadian variation of between 0.5
to 1.0°C.
 The Society of Critical Care Medicine define fever in the
ICU as a temperature >38.3°C (>101°F).

6. SIGNIFICANCE OF FEVER
 Enhance the resistance of animals to infection
 Enhance several parameters of immune
function
 some pathogens such as Streptococcus
pneumoniae are inhibited by febrile
temperatures.
 a To of 38°C shown to increased survival in
patients with SBP

7.  Increase
 cardiac output
 oxygen consumption
 carbon dioxide production
 energy expenditure
 Poor neurologic outcome in patients with stroke and TBI.
 Maternal fever has been suggested to be a cause
 fetal malformations and spontaneous abortions
SIGNIFICANCE OF FEVER CONT…

8. FEVER IN ICU
 Fever complicates up to 70 % of all ICU admissions.
 DIFFERENTIAL:
 Fevers between 38.3ºC (101ºF) and 38.8ºC (101.8ºF) may be
infectious or noninfectious.
 Fevers between 38.9 (102ºF) and 41ºC (105.8ºF) can be
assumed to be infectious.
 Fevers ≥41.1ºC (106ºF) are usually noninfectious.

9. INFECTIOUS CAUSES OF FEVER
 Bacteremia
 VAP
 Intravascular
catheter-related
infection
 Surgical site
infection
 Sinusitis
 Cellulitis
 Cholangitis
 Diverticulitis
 Empyema
 Intra-abdominal
abscess
 Endocarditis
 Myonecrosis
 Necrotizing
fasciitis
 Pseudomembran
oucolitis
 Septic arthritis

10. VENTILATOR-ASSOCIATED PNEUMONIA(VAP)
 Incidence of 10 -25%
 Attributable mortality of 25-50 %
 Risk of 3%/day the first five days, 2%/day during
day 5 to 10 and 1%/day the day after that.

11.  Typically presents with:
 a new or progressive pulmonary infiltrate
 one or more of the following findings:
 fever, purulent tracheobronchial secretions,
leukocytosis,
 increased respiratory rate, decreased tidal
volume, increased minute ventilation, and
decreased oxygenation
VENTILATOR-ASSOCIATED PNEUMONIA
CONT…

12. CATHETER-ASSOCIATED SEPSIS
 is defined as blood stream infection due to an organism
that has colonized a vascular catheter
 Approximately 5% of patients with indwelling vascular
catheters (uncoated) will develop blood stream infection

13.  If catheter sepsis is suspected
 the catheter should be changed to a new site
 Send culture of the catheter tip.
CATHETER-ASSOCIATED SEPSIS
CONT…

14. URINARY TRACT INFECTIONS (UTIS)
 account for between 25 to 50% of all infections
 Defined as:
 the presence of fever >38ºC, SPT, CVAT
 Urine culture with
 >10(5) cfu/mL irrespective of urinalysis
 >10(3) cfu/mL with evidence of pyuria

15.  Bacteriuria should be treated following
 urinary tract manipulation or surgery
 patients with kidney stones & urinary tract
obstruction
 Patient with neutropenia
URINARY TRACT INFECTIONS CONT…

16. CLOSTRIDIA DIFFICILE Colitis
 About 20% of all hospitalized patients become
“infected” with C difficile
 only 1/3 develop diarrhea.
 Use of clindamycin, 3rd generation cephalosporin
and fluoroquinolones is the risk factor
 Other risk factors:
 use of PPI, GI surgery, prolonged ICU stay and tube
feeding

17.  Symptoms usually begins shortly after
antibiotics therapy
 Clinical spectrum includes:
 Colitis, pseudomembranous colitis, fulminant
colitis
 Stool assay for toxin A and B by ELISA
 Further work up: cytotoxic assay,
sigmoidoscopy and CT scan
CLOSTRIDIA DIFFICILE Colitis
CONT…

18.  Stop the offending antibiotics if possible
 Provide adequate fluid and electrolytes
 Don’t use antimotility agents
 If specific rx required use metronidazole
 Strict contact isolation of the patient
CLOSTRIDIA DIFFICILE Colitis
CONT…

19. SINUSITIS
 sinusitis is common following nasal
intubation
 with an incidence of up to 85% after a week of
intubation.
 The maxillary sinus is most commonly
involved

20.  Major criteria: cough & purulent nasal discharge
 Minor criteria: headache or earache, facial or tooth
pain, fever, malodours breath sore throat and
wheezing
 Sinusitis on CT
 total opacification
 the presence of an air fluid level within any of the
paranasal sinuses.
SINUSITIS CONT…

21.  MICROBIOLOGY:
 Pseudomonas (60%)
 Stap. Aureus (33%)
 Treatment
 Remove all nasal tubes
 Drainage (Needle(Maxillary) or surgical (ethmoid and
sphenoid))
 Antibiotics
SINUSITIS CONT…

22. Brain Cerebral infraction/ hemorrhage, SAH
Heart MI, Pericarditis
Pulmonary Aspiration, Atelectasis, PE, ARDS
Abdomen GI bleeding, ischemic bowel, pancreatitis, hepatitis, adrenal
crisis
vascular DVT, Thrombophlebitis
cutaneous Decubitus ulcers
miscellaneou Drug fever, fat embolism, neoplasms, blood transfusion, gout,
NON INFECTIOUS CAUSES OF FEVER

23. DRUG FEVER
 It can occur several days after the initiation of the
drug,
 can produce high fevers (>38.9ºC) without other
signs.
 The true incidence is unknown.
 Cause:
 Stimulation of heat production(eg. Thyroxine)
 Limit of heat dissipation (eg. atropine)
 Alter thermoregultion (eg. antihistamines,

24. ADRENAL CRISIS
 occurs in patients with previously adrenal
insufficiency who are subjected to a serious
infection or other major stress.
 manifestation
 Distributive shock is the predominant
 fever, nausea, vomiting, abdominal pain, fatigue,
lethargy, hypoglycemia, confusion, or coma

25. EMERGENCY TREATMENT
 Adequate fluid resuscitation
 Draw blood for electrolytes, glucose, cortisol and
ACTH
 Glucocorticoid
 Dexamethasone
 Hydrocortisone is preferred with known primary
adrenal insufficiency with potassium >6.0 meq/L.
(because of its mineralocorticoid activity)
ADRENAL CRISIS CONT…

26. ACUTE HEMOLYTIC TRANSFUSION
REACTION
 A medical emergency that results from the
rapid destruction of donor red blood cells by
recipient antibodies.
 Usually due to ABO incompatibility.
 Common clinical manifestations
 fever, chills, distributive shock, disseminated
intravascular coagulation, and acute kidney injury.

27.  Stop the transfusion.
 Maintain the patient's airway, blood pressure, and
heart rate.
 Begin an infusion of normal saline immediately
 Avoid the use of Ringer's lactate solution because its
content of calcium may initiate clotting of any blood
remaining in the intravenous line.
 Avoid dextrose- containing solutions because the dextrose
may hemolyze any of the remaining red cells in the line.
ACUTE HEMOLYTIC TRANSFUSION
REACTION CONT…

28. ACALCULOUS CHOLECYSTITIS
 0.2 to 1.5 % of patients in ICU
 presents with fever, leukocytosis, and vague
abdominal discomfort.
 May progress to gangrene and perforation.
 have a mortality rate as high as 30 to 40 %

29.  ULTRASOUND
 Absence of gallstones or sludge
 Thickening of the gallbladder wall (>5 mm) with pericholecystic
fluid
 A positive Murphy's sign induced by the ultrasound probe
 Failure to visualize the gallbladder
 Frank perforation of the gallbladder with associated abscess
formation
 TREATMENT
 broad spectrum antibiotics
 cholecystectomy with drainage of any associated abscess
ACALCULOUS CHOLECYSTITIS
CONT…

30. ANTIBIOTIC USE IN INTENSIVE
CARE UNIT
Dr. Nathan Muluberhan(E M
r e s i d e n t )
August 2017

31. OBJECTIVES
 principles of antibiotic use
 optimize use of antibiotic
 multidrug resistant bacteria
 To look at the role of novel biomarker
in guiding antibiotic therapy

32. PRINCIPLES OF ANTIBIOTIC
PRESCRIPTION
 Send for appropriate investigations (minimum required
for dx, prognosis and follow up) before initiation of
antibiotics
 Change in antibiotics would be done after sending fresh
culture
 Follow the hospital antibiotics policy. If alternative has
chosen, document the reason
 Check for factors which will affects drug choice and
dose(eg. Renal function, interaction and allergy)
 Check appropriate dose is prescribed

33.  All IV antibiotics may only given for 48-72 hrs without
review
 Once culture result available descalate and if not,
document the reason
 Emperic therapy initation delay for await of micro report
would be life threatining and mortality rate will be
increased
 Antibiotics therapy based on a clinically defined infection
is justified
 Rapid tests such as gram stain can help determine
theraputic choice when emperic therapy is required
PRINCIPLES OF ANTIBIOTIC
PRESCRIPTION

34. STRATEGIES TO OPTIMIZE THE USE
OF ANTIMICROBIALS
1. Use of PK/PD parameters for dose
adjustment
2. De-escalation therapy
3. Antibacterial cycling
4. Pre-emptive therapy

36. YUMC

37. 1. CONCENTRATION DEPENDENT KILLING ACTIVITY
AND MODERATE TO PROLONGED PERSISTENT
EFFECTS
 More rapid killing effect against micro organisms than
low concentrations
 Allows the administrations of high doses with widely
separated frequencies of administration
 Aminoglycosides, Fluoroquinolones, Metronidazole,
Colistin, Rifampicin, Clindamycin

38. CONCENTRATION DEPENDENT CONT…
 AMINOGLYCOSIDES
 Doses of these antimicrobials administered to critically ill patients
are frequently insufficient
Rea RS, et al. Suboptimal aminoglycoside dosing in critically ill patients. Ther
Drug Monit 2008; 30: 674-81
 FLUOROQUINOLONES
 Using a Monte Carlo dosing simulation, doses of 400mg every 8-
12hrs givento 1-2 patients did not reach the necessary killing
concentrations for P.aeruginosa, A.baumannii strains

39. 2. TIME DEPENDENT KILLING ACTIVITY AND
MINIMAL PERSISTENT EFFECTS
 Maintain blood concentrations above MIC for
prolonged time periods
 These drugs should be given by continuous
infusion
 Beta lactams and Linezolid

40. 3. TIME DEPENDENT KILLING ACTIVITY AND
MODERATE TO PROLONGED PERSISTENT EFFECTS
 Glycopeptides (Vancomycin, Teicoplanin)
 The duration of effect is longer and the possibility of
regrowth of micro-organisms during the dosing
interval is more limited
 In humans, AUC/MIC value >350 was an independent
factor associated with clinical success in patients with
S.aureus proven lower respiratory tract infection
 Tetracyclines

41. DE-ESCALATION THERAPY
 Initial administration of broad spectrum empirical
treatment
 To cover pathogens, most frequently related to the
infection
 Rapid adjustment of antibacterial treatment
once the causative pathogen has been identified

42. STARTING ANTIBIOTIC THERAPY

43. DURATION OF ANTIBIOTIC THERAPY
 The optimal duration of antibiotic therapy for
bacteremia is unknown.
 some evidence that would suggest that there
is no significant difference in mortality, clinical
and microbiological cure b/n shorter and long
durations
 i.e. 5 – 7 days versus 8 -21 days in critically ill
patients with bacteremia.

44. ANTIBACTERIAL CYCLING
 The scheduled rotation of one class of
antibacterial
 One or more different classes with comparable
spectra of activity
 Different mechanisms of resistance
 Some weeks and a few months

45. PRE-EMPTIVE THERAPY
 The administration of antimicrobials in certain
patients at very high risk of opportunistic infections
before the onset of clinical signs of infection
 Developed in hematological patients and/or transplant
recipients
 CMV, aspergillosis
 In critical illness patients at high risk of candidemia or
invasive candidiasis

46. CANDIDA SCORE
 A bedside scoring system for preemptive antifungal
treatment in nonneutropenic critically ill patients with
Candida colonization. Crit Care Med 2006; 34: 730-7
 “Candida score” >2.5 accurately selected patients who
would benefit from early antifungal treatment.
Candida score = 0.908* (TPN) + 0.997* (surgery)+ 1.112* (multifocal candida
colonization) + 2.038* (severe sepsis)
1 if present
0 if absent

47. MULTIDRUG RESISTANT
BACTERIA
 Increasing prevalence of multidrug-resistant
pathogens in ICUs
 CDC Report shows from 1999 and 2006/2007
 VRE (from 24.7% to 33.3 % of enterococci isolates)
 MRSA (from 53.5 % to 56.2 % of S. aureus isolates)
 P. aeruginosa resistant to imipenem (from16.4 to
25.3) or fluoroquinolones (from 23.0 to 30.7) from P.
aeruginosa isolates

48. RISK FACTORS
 Older age
 Presence of underlying comorbid conditions
 higher severity of illness indices
 Long hospital courses prior to the ICU admission,
 Receipt of antimicrobial therapy prior to the ICU
admission.
 Presence of indwelling devices
 Recent surgery or other invasive procedure
 Frequent manipulation and contact with healthcare
person

49. PREVENTION OF RESISTANCE IN THE ICU
 Strategies can be separated into two major
categories:
 strategies that attempt to improve the efficacy and
utilization of antimicrobial therapy
 infection control measures

50. INFECTION CONTROL MEASURES
 good hand hygiene compliance
 Active surveillance of patients for
asymptomatic colonization
 Institution surveillance for infections with
multidrug-resistant bacteria
 Daily chlorhexidine bathing

51. NOVEL BIOMARKERS
 PROCALCITONIN
 best studied biomarker for guiding antibiotic treatment
duration in the hospital setting.
 It’s dynamics within 72 hours after onset of sepsis may be
correlated both with appropriateness of the empirical
antibiotic therapy
 integrated in clinical algorithms have been shown to
reduce the duration of antibiotic courses by 25-65% in
hospitalized and more severely ill patients with CAP and
sepsis

52. REFERENCES
 Harrison's Principles of Internal Medicine, 19th ed
 Up-to-date 21.6
 Practice Guidelines for Evaluating New Fever in
Critically Ill Adult Patients. From the National Institutes
of Health, Bethesda, and the Johns Hopkins Hospital and St.
Agnes Hospital
 Annual Update in Intensive Care and Emergency
Medicine 2016

53. Thank You