ROLE OF ANTIBIOTICS IN SEPTIC SHOCK

-------------------------------- ------------ ---- REVATHI P , L.RADHAKRISHNAN MANICKAVASAGAM S, THIRUMALAIKOLUNDUSUBRAMANIAN P DEPARTMENT OF PHARMACOLOGY, CHENNAI MEDICAL COLLEGE HOSPITAL & RESEARCH CENTRE (SRM GROUP), IRUNGALUR, TIRUCHIRAPALLI-621 005. Correspondence:<reva1923@yahoo.com>

INTRODUCTION
Septic shock is a medical condition as a result of severe infection and sepsis, though the microbe may be systemic or localized to a particular site. It can cause multiple organ dysfunction syndrome (formerly known as multiple organ failure) and death. Its most common victims are children, immunocompromised individuals, and the elderly, as their immune systems cannot deal with the infection as effectively as those of healthy adults.

SPECTRUM

Parasite

Virus

Infection
Fungus

Severe Sepsis
shock

Sepsis

SIRS
Severe SIRS Trauma

Bacteria
BSI

Burns

COMMON SOURCES OF SEPSIS

Respiratory35% Urinary tract35% Intra Abdominal10% Unknown10% Meningitis/septic arthritis/10% skin/vascular access devices

The distribution of infectious agents in sepsis

the most updated studies show the following incidences

Gram-positive bacteria 40 52.1% Gram-negative bacteria 37.6 38%; fungi 4.6 17%. The rate of mixed infections varies between 4.7 and 18%, and the incidence of infections due to Pseudomonas(14%), Acinetobacter(4%) and Methicillin-resistant Staphylococcus aureus(17%) species. Among (rarely) viruses & fungal infections, the leading cause is Candida sp .

PATHOPHYSIOLOGY:

Most cases of septic shock (approximately 70%) are caused by endotoxin-producing Gram-negative bacilli Endotoxins -bacterial membrane lipopolysaccharides (LPS) consisting of a toxic fatty acid (lipid A) core common to all Gram-negative bacteria, and a complex polysaccharide coat (including O antigen) unique for each species. Analogous molecules in the walls of Gram-positive bacteria and fungi can also elicit septic shock.

PATHOPHYSIOLOGY

Pathogenic features of the microorganism Patients immune response to these features Failure of the immune system to control an initially localised infection Exaggerated immune and inflammatory response Cellular dysfunction Vasodilatation and leaky capillaries Distributive shock Myocardial depression Bone marrow suppression Activation of clotting cascade DIC Organ dysfunction MODS Death

PATHOPHYSIOLOGY

Signs and Symptoms are most common in patients with severe sepsis Tachypnea 99% Tachycardia 97% Fever > 38C 70% Chills Hypothermia < 36C13% Metabolic acidosis38% Acute oliguria54% Acute encephalopathy35%.

LABORATORY INVESTIGATIONS
Serum Lactate, an important indicator of tissue perfusion, should be measured even if there are no signs of hypotension.

Appropriate cultures 1,3 -d-glucan assay (grade 2B), mannan and anti-mannan antibody assays (grade 2C) when invasive candidiasis is in the differential diagnosis of infection. Imaging studies- to confirm a potential source of infection Blood culture- Obtaining at least two sets of blood cultures (both aerobic and anaerobic bottles) before antimicrobial therapy, Culture-such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of infection Gram stain- respiratory tract Rapid influenza antigen testing Biomarkers (PCT, CRP) X-ray, Imaging studies-MRI, CT

Screening for Sepsis and Performance Improvement

ANTIMICROBIAL THERAPY

The administration of effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock should be the goal of therapy.

CHOOSING ANTIBIOTICS IN SEPSIS:

There is no, single, best regimen Consider the site of the infection Consider which organisms most often cause infection at that site Choose antibiotic(s) with the appropriate spectrum After obtaining cultures(At least one blood draw should be
percutaneous and one should be through each vascular assist device that has been in place longer than 48 hours & sites as indicated ),

give antibiotics quickly and empirically at appropriate dose Antibiotics should be started during the first hour of sepsis treatment, right after the sampling of cultures

ANTIBIOTIC MANAGEMENT OF SEVERE SEPSIS ANDSEPTICSHOCK

Is patient immuno compromised? HIV positive Neutrophenia Chronic corticosteroids Malnutrition Receiving chemotheraphy If no: Consider like bacterial infection based on clinical presentation If yes: Consider obtaining consultation with infectious disease expert Patient may need antimicrobial theraphy directed to oppurtunistic pathogens in addition to bacterial pathogens

RISK FACTOR FOR HEALTHCARE ASSOCIATED INFECTION PRESENT Recent hospitalization,Residence in nursing home, Regular visit to hospital clinic and dialysis Home infusion OR wound therapy
If yes: Consider nosocomial bacterial pathogen that are potentially antibiotic resistance:,MRSA, Pseudomonas aeruginosa, Acinetobacter species, Klebsiella pneumoniae E.Coli

If no: Consider community based bacterial pathogen that are antibiotic sensitive, Streptococcus pneumoniae, Escherichia coli, Legiolella pneumophila

Modified /Combined and or narrow anti biotic regimen based on the organism identified and susceptibility testing

Apparent source of sepsis

Empirical antibiotic regimen

Penicillin allergic not immediate hypersensitivity

Penicillin allergicimmediate hypersensitivity (anaphylasis)

Sereve specis,no obvious sources of infection and the patient is immunocompetent

Flucloxacillin 2mgIV 6th hrly + Gentamicin 7mg /kg for 1 day(maxi-640 mg)

Cephazolin 2g IV,8-hourly plus gentamicin 7mg/kg,for 1dose(max 640 mg)

ADD ceftriaxone 2g IV,12-hourly

Vancomycin 1to1.5g IV 12hourly plus gentamicin 7mg/kg IV,for 1dose(max 640mg)

ADD moxifloxacin 400mg IV daily

Meningococcal or pneumoccocal infection suspected If toxin mediated shock present or likely

ADD benzyl penicillin 1.8g IV,4-hourly ADD lincomycin 600mg IV,8hourly OR clindamycin 900mg IV,8hourly

ADD lincomycin 600mg IV,8hourly OR clindamycin 900mg IV,8hourly

ADD lincomycin 600mg IV,8hourly OR clindamycin 900mg IV,8hourly

febrile neutropaenic (neutrophils <1.0)

Piperacilin 4g &tazobactam 500mg IV,8hourly plus gentamicn 7mg/kg IV,for 1dose(max 640 mg) ADD vancomycin
1to 1.5g IV,12hourly

Cefepime 2g IV,8hourly +gentamicin 7mg/kg IVfor 1dose (max 640 mg)

Vancomycin 1to 1.5g IV,12 hourly +gentamicin 7mg/kg IV, for 1dose (max 640 mg)

If in shock,known MRSA colonised or clinical evidence for vascular catheter related infection

ADD vancomycin 1 to 1.5g IV,12hourly Ceftriaxone 1g IV, daily + azithromycin 500mg IV, daily Moxifloxacin 400mg IV,daily +azithromycin 500mg IV, daily

Severe pneumonia(com munity acquired)

Ceftriaxone 1g IV, daily + azithromycin 500mg IV, daily

Urinary tract infection

Ampicillin 2g IV, 6-houriy + gentamicn 7mg/kg IV for 1 dose (max 640 mg)

Ceftriaxone 1g IV, Seek ID/MICRO daily + advice gentamicin 7mg/kg IV, for 1 dose (max 640 mg)

 The antimicrobial regimen should be reassessed daily for potential de-escalation to prevent the development of resistance, to reduce toxicity, and to reduce costs Consider combination therapy for neutropenic patients and those with Pseudomonas infections. Stop antimicrobial therapy immediately if the condition is determined to be a non-infectious cause.

INFECTION PREVENTION
selective oral decontamination (SOD) and selective digestive decontamination (SDD) should be introduced and investigated as a method to reduce the incidence of ventilator-associated pneumonia (VAP); oral chlorhexidine gluconate (CHG) be used as a form of oropharyngeal decontamination toreduce the risk of VAP in ICU patients with severe sepsis Nursing considerations-hand washing, expert nursing care, catheter care, barrier precautions, airway management, elevation of the head of the bed, subglottic suctioning

SELECT SINGLE AGENT OR COMBINATION THERAPY

Ceftriaxone or Ampicillin or Ertapenen plus or macrolide

 Broad spectrum cephalosporin(cefepime) or Carbapenem(imipenem) or Beta lactem inhibitor(piperacilil) or Amino glycoside(gentamycin ,amikacil) plus MRSA directed agent(vancomycin)

ANTIBIOTICS THERAPY
For immunocompetent patient: Ceftriazone 2 gm daily+ meropenem 1 gm 8hourly + cefepime 2gm 12 hourly.if allergic to beta lactams beta ciprofloxcin 500 mg 12hourly+ clindamycin 600 mg 8hourly For neutropenic patient:meropenem 1gm 8hourly + cefepnine 2gm 8hourly For IV drug users:vancomycin 15mg/kg 12hourly+ gentamycin 5-7mg/kg 24hourly

 For AIDS patients: Cefepime 2 gm 8hourly+tobramycin 5-7mg/kg 24hourly If allergy to betalactems,ciproflaxin 500mg 12hourly+vancomycin 15 mg/kg 12hourly+tobramycin 5-7mg/kg/day

On microbes Nor do I doubt if the most formidable armies ever heere upon earth is a sort of soldiers who for their smallness are not visible Sir William Petty, 1640