Fever and antibiotics

Fever and antibiotics

1. Fever in intensive care unit Dr. Nathan Muluberhan( EM resident ) August 2017

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

3. DEFINITIONS FEVER: elevation of body temperature that exceeds the normal daily variation and occurs in conjunction with an increase in the hypothalamic set point. HYPERTHERMIA: elevation of body temperature in a setting of unchanged the hypothalamic thermoregulatory center is HYPERPYREXIA : an extraordinarily high fever (>41.5ºC ) PYROGENS: 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 T o of 38°C shown to increased survival in patients with SBP

7. I ncrease 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 Meningitis Myonecrosis Necrotizing fasciitis Pseudomembranoucolitis Septic arthritis

10. VENTILATOR-ASSOCIATED PNEUMONIA(VAP) I ncidence 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. T ypically 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, 3 rd generation cephalosporin and fluoroquinolones is the risk factor O ther 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)) A ntibiotics 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 miscellaneous Drug fever, fat embolism, neoplasms, blood transfusion, gout, rejection 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, phenothiazines , antiparkinson drugs)

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 D examethasone 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. U sually 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( EM resident ) 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 Use of PK/PD parameters for dose adjustment De-escalation therapy Antibacterial cycling Pre-emptive therapy

35. YUMC

36. 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

37. 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

38. 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

39. 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

40. 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

41. STARTING ANTIBIOTIC THERAPY

42. 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.

43. 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

44. 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

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

51. REFERENCES Harrison's Principles of Internal Medicine, 19 th 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

52. Thank You