1. INFECTION AND INFECTIOUS PROCESS
DR. N. RAMESH NAIR
MATHA HOSPITAL

2. SURVIVING SEPSIS CAMPAIGN
GUIDELINES PUBLISHED IN CRITICAL CARE MEDICINE 2013

3. INFECTION
Infection is a pathologic process caused by invasion of normal sterile tissue, or fluid or body cavity by pathogenic microorganism
SEPSIS is systemic response to infection
SEVERE SEPSIS is complicated by organ dysfunction
SEPTIC SHOCK is a state of acute circulatory failure

4. Ineraction between host and microrganism
Predominently pro inflammatory SIRS
Mixed antagonistic response MARS
Predominently anti inflammatory CARS

5. HOST DEFENCE Defense against infection skin and mm
If this is breached immune response falls into INNATE and ADAPTVIE IMMUNE system

6. Innate Defense
High speed on the the scene reaction to foreign material
COMPLIMENT PATHWAYS . Activated compliment produces membrane attack (MAC) which punches holes in the surface of foreign organism
PHAGOCYTES Macrophages and Neutrophils
NATURAL KILLER CELLS (NK) are in the same family of Lymphocytes

7. ADAPTIVE DEFENCE
B Lymphocytes producing Ab IgM first Ab very effective in activating compliment and viral neutralizing
IgG 75% of Ab in blood
IgA most abundant in the body
IgE role in defense against parasites
T Cells
Cytotoxic T Lymphocytes
Helper T cell

8. Common Pathogens infecting humans
Bacteria
Viruses
Fungi
Parasites Protozoa, helminths

9. BODY RESPONSE TO INFECTION
Can be predominently inflammatory SIRS ( Systemic inflammatory response )
Can be predominently anti inflammatory CARS ( Compensatory anti inflammatory syndrome )
Can be mixed MARS ( Mixed antagonistic response syndrome )

10. SIRS
GENERAL VARIABLES INFLAMMATORY VARIABLES HEMODYNAMIC VARIABLES ORGAN DYSFUNCTION VARIABLES TISSUE PERFUSION VARIABLES

11. GENERAL VARIABLES Fever (> 38.30 C)
Hypothermia (core temperature< 36 0 C)
Heart rate >90/min
Tachypnoea
Altered mental status
Significant edema or positive fluid balance (>20 mL/kg over 24 hr)
Hyperglycemia (plasma glucose > 140 mg/dl in the absence of diabetes

12. INFLAMMATORY VARIABLES
Leukocytosis (WBC count >12,000/cmm)
Leucopenia (WBC count <4000/comm.)
Normal WBC count with greater than 10% immature forms.
Plasma C-reactive protein more than two so above the normal value.
Plasma Procalcitonin more than twice above the normal value.

13. HEMODYNAMIC VARIABLES
Arterial hypotension (SBP<90 mm Hg, MAP<70 mmHg, or an SBP decrease>40mm Hg in adults from base line
MAP is DBP + 1/3rd PP

14. ORGAN DYSFUNCTION VARIABLES
Arterial hypoxemia (Pa00/ Fio0 <300)
Acute oliguria (urine output <0.5mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation)
Creatinine increase> 0.5mg/dL
Coagulation abnormalities (INR>1.5 or aPTT>60 s)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count <100,000 µL -1 )
Hyperbilirubinemia (plasma total bilirubin > 4 mg /dL

15. TISSUE PERFUSION VARIABLES
Hyperlactatemia (> 1 mmol/L)
Decreased capilary refill

16. SEVERE SEPSIS Sepsis – induced hypotension
Lactate above upper limits laboratory normal.
Urine output < 0.5 mL/kg/hr for more than 2 hrs despite adequate fluid resuscitation.
Acute lung injury with Pa00/ Fio0 <250 in the absence of pneumonia as infection source
Acute lung injury with Pa00/ Fio0 <200 in the presence of pneumonia as infection source
Creatinine >2.0 mg/dL
Bilirubin > 2 mg/dL
Platelet count <100,000 µL
Coagulopathy (international normalized ratio > 1.5)

17. Treatment To be completed in 3 hours
Measure lactate level
Obtain blood cultures prior to administration of antibiotics
Administer broad spectrum antibiotics
Administer 30ml/ kgm Crystalloid for hypotension or lactate > 4mmol

18. Treatment To be completed with in 6 hours
Give vasopressors for hypotension that does not respond to initial fluid resuscitation to maintain MAP > 65mm Hg
In the event of persistent hypotension despite volume resuscitation measure CVP and \Central venous oxygen saturation
Target CVP > 8mm Hg, Scvo2 >70% and lactate normal

19. INITIAL RESUSCITATION
Goals during the first 6 hrs of resuscitation.
Central venous pressure 8 – 12 mm Hg.
Mean arterial pressure (MAP)> 65 mm Hg
Urine output > 0.5 mL/kg/hr
Central venous (superior vena cava) or mixed venous oxygen saturation 70% or 65%, respectively .
In patients with elevated lactate levels targeting resuscitation to normalize lactate

20. Screening for Sepsis and Performance Improvement
Routine screening of potentially infected seriously ill patients for severe sepsis to allow earlier implementation of therapy
Hospital–based performance improvement efforts in severe sepsis

21. DIAGNOSIS
Cultures as clinically appropriate before antimicrobial therapy if no significant delay (> 45 mins) in the start of antimicrobial
. At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device.
Use of the 1,3 beta-D-glucan assay , mannan and anti-mannan antibody assays , if available and invasive
candidiasis is in the differential diagnosis of cause of infection.
Imaging studies performed promptly to confirm a potential source of infection (UG).

22. ANTIMICROBIAL THERAPY
Administration of effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock as the goal of therapy.
Initial empiric anti-infective therapy of one or more drugs that have activity against all likely pathogens (bacterial and/or fungal or viral) and that penetrate in adequate concentrations into tissues presumed to be the source of sepsis
Antimicrobial regimen should be reassessed daily for potential de escalation
Use of low procalcitonin levels or similar biomarkers to assist the clinician in the discontinuation of empiric antibiotics in patients who initially appeared septic, but have no subsequent evidence of infection

23. Combination empirical therapy for neutropenic patients with severe sepsis and for patients with difficult-to-treat, multidrugresistant bacterial pathogens such as Acinetobacter and Pseudomonas spp.
For patients with severe infections associated with respiratory failure and septic shock, combination therapy with an extended spectrum beta-lactam and either an aminoglycoside or a fluoroquinolone is for P. aeruginosa bacteremia
A combination of beta-lactam and macrolide for patients with septic shock from bacteremic Streptococcus pneumoniae infections (grade 2B).

24. INITIAL RESUSCITATION AND INFECTION ISSUES
Empiric combination therapy should not be administered for more than 3–5 days. De-escalation to the most appropriate single therapy should be performed as soon as the susceptibility profile is known .
Duration of therapy typically 7–10 days; longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection, bacteremia with S. aureus; some fungal and viral infections or immunologic deficiencies, including neutropenia
Antiviral therapy initiated as early as possible in patients with severe sepsis or septic shock of viral origin .
Antimicrobial agents should not be used in patients with severe inflammatory states determined to be of noninfectious cause .

25. SOURCE CONTROL
A specific anatomical diagnosis of infection requiring consideration for emergent source control be sought and diagnosed or excluded as rapidly as possible, and intervention be undertaken for source control within the first 12 hr after the diagnosis is made, if feasible .
When infected peripancreatic necrosis is identified as a potential source of infection, definitive intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred .
When source control in a severely septic patient is required, the effective intervention associated with the least physiologic insult should be used (eg, percutaneous rather than surgical drainage of an abscess) .
If intravascular access devices are a possible source of severe sepsis or septic shock, they should be removed promptly after other vascular access has been established .

26. INFECTION PREVENTION
Selective oral decontamination and selective digestive decontamination should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia; This infection control measure can then be instituted in health care settings and regions where this methodology is found to be effective
Oral chlorhexidine gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator-associated pneumonia in ICU patients with severe sepsis

27. Haemodynamic support and Adjunctive therapy
Fluid Therapy for Severe Sepsis
Crystalloids as initial fluid 30 ml/kgm as minimum
A portion of this can be albumin
More rapid fuid adminisrtion and greater amount needed in some pts

28. vasopressors Nor epinephrine as first choice
Dopamine as an alternative only
in selected pts with low risk of tachyarrhythmia or absolute bradycardia
All pts on vasopressors have an arterial catheter if available
INOTROPIC THERAPY
Dobutamine infusion up to 20 microgm/kg/mt in presence of myocardial dysfunction or signs of hypo perfusion despite adequate IV volume and adequate MAP

29. CORTICOSTEROIDS
If adequate fluid and vasopressor cannot achieve haemodynamic stability HYDROCORTISONE 200mg/ day as continous infusion
Corticosteroids not given in absence of shock
Do not use ACTH stimulation test

30. Blood products
In the absence of myocardial ischemia or actvie bleeding RBC transfusion only if HB below 7 gm . TARGET 7 to 9 gm
Do not use erythropoitin
Do not use FFP to correct lab clotting abnormality in the absence of bleeding or planned invasive procedures
Platlets prophylaxis if <10000/cm in the absence of bleeding. If pt has risk of bleeding < Higher counts > for active bleeding, surgery, invasive procedure

31. Do not use IV IG in adult pts with severe sepsis and septic shock
MECHANICAL VENTILATION for sepsis induced ARDS
SEDATION continous or intrmittent sedation be minimized in mechanically ventilated pts.
A short course of NMBA of not greater than 48 hrs with early sepsis induced ARDS and PaO2/ FiO2 <150

32. GLUCOSE CONTROL
Protocol approach when 2 cosecutive readings above 180 mgm
Target upper blood glucose < 180 mgm
RENAL REPLACEMENT THERAPY for ARF
BICARBONATE THERAPY Do not use when hypo perfusion induced lactic acidosis with PH >7.15
DVT PROOHYLAXIS LMWH S/C twice daily. If RF use drug with low renal metabolism.
Graduated compression stockings in pts with C/I to heparin

33. NUTRITION
Oral feeding as tolerated rather than complete IV glucose with in first 48 hrs
Low dose feeding up to 500 cals per day and advance only as tolerated
Use IV glucose and enteral nutrition rather than TPN
STRESS ULCER PROPHYLAXIS PPI

34. SETTING GOALS OF CARE
Discuss goals of care and prognosis with patients and families

35. CAREFUL INFECTION CONTROL PRACTICES
Hand washing
Expert nursing care
Catheter care
Barrier precautions
Airway Management
Elevation of the head of bed
Sub glotic suctioning

36. Infections Acquired by HCW from PTS
Viral GE
Meningococcal Meningitis
Mycobacterium TB
Influenza
Chickenpox
Viral haemorrhagic fever
Pertrussis
Diphtheria
During SARS epidemic of to 60% of HCW got infected with

37. Significant Innnoculation of Bloodthrough hollow bore needle
RISKS
HB 30% if HBEAg + and 3% if HBEAb +
HC 3% if HCV+
HIV 0.3% if donor is HIV +

38. Risk Assessment Extent and depth of injury Size and type of needle
Visible contamination of blood
Site
Source pts HB, HC, and HIV status
Stage of illness if HIV +
Hepatitis B vaccine status/Ab of recipient
Pregnancy

39. HCV No immediate intervention HCV RNA tested at 6 and 12 weeks by PCR
Anti HCV tested at 12 and 24 weeks
If signs of infection refer to experts for HCV chemotherapy

40. HBV HBV status of person exposed
1 dose or less of HBV vaccine- Accelerated course of HBV vaccine at 0, 1 ,2 months . Also give HBIG
2 doses or more- 1 dose of vaccine followed by 2nd dose 1 month later
Anti HBS > 10 micromols/ml – one booster dose of vaccine
Anti HBS < 10 mmol/ml – HBIg and booster dose of vaccine

41. PEP of HCW for accidental exposure to HIV
Needle stick 0.3 %, mucous membrane exposure 0.09%
Wash with soap and water, spash water to nose, eyes, mouth, skin
Report to authority
Blood from pt and HCW send for HIV, HB, HC
INITATION OF PEP
Do base line HIV ELISA
Steat PEP in first 24 hrs preferably with in 2 hrs

42. Basic PEP Prophylaxis
Zidovudine 300mgm BD + Lamivudine 150 mgm BD
A third drug ca be added in case of high risk exposure expanded HIV Post exposure prophylaxis
Indinavir 800mgm 8th hrly on empty stomach
PEP continued for4 weeks
HIV ELISA at 6 weeks, 12 weeks and 6 months
Reduces chances of person becoming positive by 80%

43. Duration of Antibiotic Therapy for Immunocopetent patients
URINARY TRACT INFECTION
Uncomplicated cystitis 3 days
Pyelonephritis to 14 days
Asymtomatic bacteriuria of pregnancy 3 to 7 days
PHARYNGITIS
Group A Streptococcus days
COMMUNITY ACQUIRED PNEUMONIA
CAP 7days
HAP 7 to 14 days

44. INFECTIOUS DIARRHOEA
Cl. Difficile 10 days
Salmonella 7 to 14 days
Shigella 3 to 5 days
Campylobacter 5 days
Giardia 10 days
SKIN AND SOFT TISSUE INFECTION
Impetigo 7 to 10 days
Cellulitis 7 to 14 days

45. BONE AND JOINT INFECTION
Acute septic arthritis 3 weeks
Acute haematogenous osteomyelitis 3 weeks
Chronic osteomyelitis weeks
INTRAVASCULAR CATHETER INDUCED INFECTION
Coagulase negative Staph 5 to 7days
S.aureus 14 days
Gram negative bacilli 10 t0 14 days
Candida days

46. MENINGITIS
Meningococcal 7 days
H. influenza days
S. pneumonia to 14 days
Group B Streptococcus to 21 days
Gram negative bacilli days
Listeria > 21 days

47. INFECTIVE ENDOCARDITIS
Viridans sstrptococci & S. bovis. (Native) 2 to 4 weeks
S,pneumonia & Group A,B,C,E,G streptococci 4 weeks
S.aureus ( native valve) 6 weeks
S.aureus ( prosthetic valve) > 6 weeks
Enterococci ( native or prosthetic ) 4 to 6 weeks
HACEK 4 weeks
Culture Negative 4 to 6 weeks

48. ADULT IMMUNIZATION
Disease prevention is the most cost effective option to protect and promote health of populations and immunization is the key to achieve the same
Hillman Alan L , Schwartz J , et al American college of Physicians. Annals Internal Med Health 1993; 0003:4819

49. Cholera Vaccine ORAL CHOLERA VACCINE Dukoral
Administered as 2 separate doses, 1 to 6 weeks apart for those above 6 years
Confers 85% - 90% protection for 6 months among all age groups

50. Hepatitis A Virus Havrix® (GlaxoSmithKline) Recommendations:
Universal immunization not recommended as yet
Costly vaccine
Adults at risk and adults who are negative for anti-HAV antibodies are likely to benefit most

51. Vaccination schedule for hepatitis A virus
2 doses 0 and 6 months

52. Post-exposure prophylaxis
TWO doses Six months apart
In healthy persons [1 and 40 years], a single dose hepatitis A vaccine is preferred to anti-HAV immunoglobulin
In persons over 40 years, the manifestations of hepatitis A are more severe
Administration of anti-HAV immunoglobulin (0.02 ml/
kg, intramuscularly) as soon as possible, within two weeks
following exposure is preferred
If the anti-HAV immunoglobulin is not available, the vaccine can be used

53. Hepatitis B Virus
Administered at 0, 1, and 6 months as an IM injection in the deltoid using a mm needle (Level A)
Protection (defined as anti-HBs antibody titer of 10 mIU/ml or higher) following the first, second and third doses of the vaccine has been observed to be 20% to 30%;75% to 80%; and 90% to 95% respectively
Recommendations:
Indicated for all unvaccinated adults at risk for HBV infection

54. Hepatitis B - Post-exposure screening
Required only for patients with ESRD ; CLD ; HIV infection ) sex partners of HBsAg positive person); infants born to HBsAg-positive women , certain health care workers at high risk
Performed 1 to 2 months after administration of the last dose of the vaccine series
The anti-HBs titre should be maintained above 10 mIU/ml in all groups except in CKD patients on dialysis in whom a titre of over 100 mIU/ml is desired

55. Booster doses Not indicated in persons with normal immune status
For CKD patients, assess the need for booster doses by annual anti-HBs antibody titre testing
When anti-HBs levels decline to <10 mIU/ ml, annual anti-HBs testing and booster doses should be con sidered for persons with an ongoing risk for exposure (<100 mIU/ml in patients on dialysis)

56. Influenza Virus
Trivalent inactivated influenza vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available
TIV administered by an annual, single intramuscular dose of 0.5 ml.
The LAIV administered by the intranasal use and is approved for use in adults aged up to 50 years

57. Influenza vaccine - Recommendations
In the developed countries recommended to people at high risk for influenza-related complications, such as the elderly (age > 65 years); and COPD patients

58. Measles, Mumps And Rubella
MMR live attenuated vaccine available as 0.5 ml
Administered subcutaneously into the upper arm
Recommendations:
all adults (except those who have history of suffering from all the three disease / received two doses of MMR
For adult immunization, two doses of the vaccine are
Recommended

59. Meningococcal Meningitis
Recommendations:
Routine vaccination of all adults not recommended
Can be used during an outbreak;
a single dose of bivalent vaccine is recommended days before

60. API Guidelines on Pneumococcal Vaccine
Not routinely recommended
People with splenectomy
API guidelines. Expert group of the Association of Physicians of India on Adult Immunization in India. JAPI. 2009;57:345-55

61. Rabies vaccine - Recommendations
Post-exposure treatment:
No need to wait for laboratory confirmation of diagnosis to start treatment
Immediately post exposure, wound care started, the degree of exposure classified and the post-exposure treatment started
The animal observed for 10 days
Post-exposure vaccination can be discontinued if the animal is healthy after 10 days
0,3,7,14,28 and 90th days

62. Rabies: Passive immunization
Carried out with human rabies immunoglobulin (HRIG) (20 IU/kg body weight; up to a maximum of 1500 IU) or equine rabies immunoglobulin (ERIG) (40 IU/kg body weight; maximum of 3000 IU)
ERIG must be given only after administering the test dose
Immunoglobulin infiltrated as much as possible into and around the wounds; remaining if any, should be given intramuscularly at a site away from the vaccine site

63. Rabies: Management of re-exposure
On re-exposure following a full course of either pre-or postexposure vaccination, 2 booster doses administered
intramuscularly or intradermally on days 0 and 3 irrespective of category of exposure or time elapsed since previous vaccination
Rabies immunoglobulin is not indicated

64. Rabies: Special situations
Rabies vaccines and rabies immunoglobulin are safe during pregnancy, lactation and in immuno-compromised states including HIV infection and AIDS
The post-exposure prophylaxis remains the same on exposure to a vaccinated animal

65. Typhoid Fever Vaccines available are: (ii) live oral Ty21a vaccine;
(iii) Injectable Vi polysaccharide vaccine; and .
Limited data are available on the Vi-rEPA vaccine
Live oral Ty21a vaccine is an orally administered live attenuated Ty2 strain of Salmonella typhi

66. Typhoid vaccine - Recommendations
Either Ty21a or Vi vaccine may be used as both have comparable efficacy (51% vs 55% at 3 years) and both are safe
Between the capsule and liquid formulations of Ty21a, liquid formulation is recommended
Three doses of Ty21a capsules/sachets (liquid formulation) administered on alternate days
This series should be repeated once in every 3 years as a booster dose.

67. Typhoid vaccine - Recommendations
The capsule formulation should be taken orally with plain, cold or lukewarm water
Following the administration of the vaccine, food should be taken only after one hour
The Vi vaccine is given as a single subcutaneous or intramuscular dose of 0.5 ml. A booster is recommended
once in every 3 years

68. Varicella Virus
Varilrix (GlaxoSmithKline) 2 doses , 2nd dose 4 to 6 weeks after 1st dose
Varicella zoster immune globulin (VZIG):
Can prevent varicella in nonimmune, healthy individuals if administered within 72 hours of exposure
Lowers attack rates among immunocompromized persons if administered no later than 96 hours of exposure
Recommended dose is 125 units/10 kg of body weight, up to a maximum of 625 units

69. Varicella vaccine - Special situations
Two doses of varicella vaccine are strongly recommended in adults at increased risk for exposure of varicella such as health care personnel etc.
Postpartum women who do not have evidence of varicella immunity be given the first dose of vaccine before discharge from the health care facility and second dose 4–8 weeks later
Women should be counseled to avoid conception
for 1 month after each dose of varicella vaccine
All HIV-infected persons with CD4 <200 cells/μL should
receive two doses

70. Varicella vaccine - Special situations
During outbreaks two-dose vaccination schedule is recommended
Post-exposure prophylaxis recommended for unvaccinated persons without other evidence of immunity against varicella; preferably within 3 – 5 days of exposure to varicella rash
Contraindications:
History of a serious reaction (e.g., anaphylaxis) after a previous dose
Women who are pregnant or may become pregnant within 1 month

71. Varicella vaccine - Contraindications
Patients with malignant conditions, including blood dyscrasias, leukemia, lymphomas of any type
Persons receiving high-dose systemic immuno suppressive therapy including oral corticosteroids
HIV-seropositive adult or adolescent with CD4+T-lymphocytes count <200 cells/μL
Recommendations for varicella zoster immune globulin:
Immunocompromised patients for passive immunization
Pregnant women

72. THANKS