Treatment Guidelines for Antimicrobial Use in Common

Syndromes

Based on ICMR Guidelines, New Delhi, India(2017)

Dr SD Sanyal

Principles of Initial Empirical Antimicrobial Therapy in Patients

with Severe Sepsis and Septic Shock in The Intensive Care Units

Definitions

• SIRS:- Two or more of the following variables:

i. Fever > 38°C (100.4°F) or hypothermia < 36°C (96.8°F) ii. Tachypnea (>20 breaths/min) or PaCO2 < 32 mmHg iii. HR >90 beats/min iv. WBC > 12,000/<4000 cells/mm3, 10% immature band forms

Definitions

• Sepsis : Systemic inflammatory response syndrome that occurs due to a “known or suspected” pathogen (bacteria, viruses, fungi or parasites)

Definitions• Severe sepsis:

- Sepsis plus evidence of organ dysfunction or tissue hypoperfusion as follows:

i. Altered mental status.

ii. Hypoxemia, with PaO2/FIO2 <250

iii.Thrombocytopenia < 100,000/cmm

iv. Bilirubin >2mg/dl

v. INR >1.5 or aPTT> 60 seconds.

vi. Urinary output of 0.5 ml/kg for at least 2 hours or Serum creatinine >2mg/dl despite fluid resuscitation.

Definitionsvii. Tissue hypoperfusion as suspected by mottled skin, capillary refilling time ≥ 2 seconds or lactate >4 mmol/l

viii. Hypotension : Systolic blood pressure (SBP) ≤90 mmHg or mean arterial pressure ≤70 mm Hg

• Sepsis induced hypotension: SBP<90mmHg or MAP<70mmHg or SBP fall > 40 mm Hg

• Septic shock:

- Sepsis induced hypotension that persists despite adequate fluid resuscitation, requiring vasopressors to maintain the blood pressure.

Common Pathogens

• Gram negative:-Pseudomonas aeruginosa -E. coli -Klebsiella pneumoniae -Acinetobacter spp

Common Pathogens

• Gram Positive: - Methicillin resistant Staphylococcus aureus (MRSA) - Entercoccus faecium - Vancomycin resistant enterocccci

• Fungi:- Candida spp

Susceptible Individuals

• Antimicrobial therapy in preceding 90 days • Current hospitalization of 5 days or more • High frequency of community or hospital

antibiotic resistance • Immunosuppressive disease or therapy

Susceptible Individuals

• Presence of multiple risk factors for Health Care Associated Infections:- Hospitalization for ≥2 days in preceeding 90 days- Residence in nursing home or long term care facility -Home infusion therapy-Chronic dialysis within 90 days -Family member with MDR pathogen

Patterns of Antimicrobial Resistance

S.aureus and Enterococci

Enterobacteriacae

P. aeruginosa & A.baumanii

Candida species

Principles of Emperical Therapy

• Form probable diagnosis• Obtain cultures• Source control• Broad spectrum cover• Antibiotics within the first hour• Early Antifungal cover• Antivirals

Choice of AMA• The suspected site of infection

• The clinical syndrome

• The setting in which the infection developed (i.e., home, nursing home, or hospital)

• Medical history

• Epidemiology, susceptibility patterns of bacteria in the hospital and ICU, local microbial-susceptibility patterns, resistance potential

Choice of AMA• Prior antibiotic therapy(previous 3 months)

• Immunological competence of patient

• Severity of underlying illness

• Microbes that previously have been documented to colonize or infect the patient

• Pharmacokinetics of the chosen antimicrobial agent

• Drug allergies / toxicities

• Cost

De-escalation

• As soon as the causative organism is identified on culture

• Choose an agent which is CHEAP and COST EFFECTIVE

• Daily reassessment to perform de-escalation and prevent resistance, reduce costs and avoid super-infections

• Use of LOW PROCALCITONIN levels

RecomendationsClinical condition

Common pathogens

Emperical AMA

Alternate AMA Comments

Urosepsis E. coli, Pseudomonas spp, Enterococcus spp.,Klebsiella spp., Proteus spp., AnaerobesCandidia spp

BL-BLI or

Meropenem or Imipenem-cilastatin.

Fluconazole if Candida

Colistin with Meropenam

In pyelonephritiswith sepsis,Echiocandinsmay beconsidered ifCandida speciesare likely to be resistant to Fluconazole

RecommendationsClinical condition

Common pathogens

Emperical AMA

Alternate AMA Comments

Intra-abdominal Sepsis

E. coli, Pseudomonas spp, Enterococcus spp.,Klebsiella spp., Acinetobacter spp,Proteus spp.,Candidia spp

BL-BLI or

Meropenem or Imipenem-cilastatin.

Colistin with Meropenam

Source controlvitalVancomycin orTeicoplanin ifEnterococcusspp isolated

Fluconazole orEchinocandins if Candida spp isolatedEchinocandins if prior h/o Azole exposure or Fluconazole resistance is suspected

RecommendationsClinical condition

Common pathogens

Emperical AMA

Alternate AMA Comments

Catheter related blood stream infections

Gram –negative pathogens Ecoli Klebsiella spp Enterobacter spp P aeruginosa Gram-positive pathogens CONS S aureus, MRSA

Fungi Candida spp

Carbapenem, or BL-BLI, with or without an aminoglycoside Vancomycin in settings of high MRSA prevalence; Echinocandin or fluconazole if fungal infection suspected

Add colistin for Gram-negative cover where carbapenem resistance rates are high

Where MRSA isolates have vancomycin MI 2 mg/mL, daptomycin, should be used

Cause Undetermined

Surgical Site Infections

Classification of Surgical Wounds• Class I/Clean:

-Uninfected, operative wound with no inflammmation and Resp/GI/Genital/Urinary tract is not entered

• Class II/Clean contaminated:- Resp/GI/Genital/Urinary tract is entered under controlled conditions without unusual contamination

• Class III/Contaminated:- Open fresh accidental wounds. Operations with major break in sterile technique with gross spillage from GIT

• Class IV/ Dirty-infected:- Old traumatic wounds with retained devitalized tissue and those that involve existing clinical infections and perforated viscera

Superficial Incisional SSI - Within 30 days of surgery and infection involves only skin or SC tissue of the incision+ 1 of the following: 1. Purulent drainage, with or without laboratory confirmation, from the superficial incision 2. Organisms isolated from an aseptically obtained culture of fluid or tissue from the superficial incision 3. At least one of the following signs or symptoms of infection:- pain or tenderness- localized swelling, redness, heat - superficial incision is deliberately opened by surgeon, unless incision is culture-negative4. Diagnosis of superficial incisional SSI by the surgeon or attending physician

Superficial Incisional SSI

• Following conditions not to be reported as SSI:- Stitch abscess- Infection of an episiotomy or newborn circumcision site - Infected burn wound- Incisional SSI that extends into the fascial and muscle layers (see deep incisional SSI)

Deep Incisional SSI - Within 30 days without implant or within 1 year with implant

- Infection is likely due to surgery and involves fascial and muscle layers) + 1 of the following:

1. Purulent drainage from the deep incision but not from the organ/space component of the surgical site

2. Spontaneous dehiscence/deliberate opening by a surgeon when the patient has at least 1 of the following : - Fever (>38ºC)- Localized pain or tenderness, unless site is culture-negative- An abscess or infection of the deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic examination.- Diagnosis of a deep incisional SSI by a surgeon or attending physician.

Deep Incisional SSI

• Notes: i. Report infection that involves both superficial and deep incision sites as deep incisional SSI ii. Report an organ/space SSI that drains through the incision as a deep incisional SSI

Organ space SSI• Within 30 days after the operation if no implant is left in place or within

1 year if implant is in place

• Appears to be related to the operation and infection involves any part of the anatomy (e.g., organs or spaces), other than the incision, which was opened or manipulated during an operation and + 1 of the following:

-Purulent drainage from a drain- Organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/space. - An abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation, or by histopathologic or radiologic examination.

-Diagnosis of an organ/space SSI by a surgeon or attending physician.

Operations and Likely Surgical Site Infection (SSI) Pathogens

Operations and Likely Surgical Site Infection (SSI) Pathogens

Resistance patterns of S.aureus

Resistance patterns of Enterobacteriacae

Resistance patterns of Pseudomonas

Peri-operative Prophylaxis• Choice of AMA:

- Dictated by the most common pathogen encountered- Skin pathogens are usual targets: 1st Generation Cephalosporins- H/o allergy to penicillins: Vancomycin/Clindamycin

• Timing of administration:- Before skin incision- All agents 30-60 mins prior- Vancomycin and Flouroquinolones 120mins prior

Peri-operative Prophylaxis• Route of administration:

- Intravenous• Dosage:

- Same as therapy• Duration:

- No longer than 24hrs- Single dose as effective as multiple doses- Multiple doses assoc with a higher risk of Resistance & Colitis

• Re-dosing:- If duration of surgery exceeds 2 x half lives- Blood loss > 1500ml or Haemodilution> 15ml/kg

Pathogen specific AMA therapy

AMA Guidelines for SSI’s

AMA Guidelines for Skin & Soft tissue infections

AMA Guidelines for Skin & Soft tissue infections

Dosages of AMA’s active against MDR organisms

Thank You