Dr. Shaiful Azam Sazzad. MD Student (Thesis Part) Critical Care Medicine Dhaka Medical College

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Dr. Shaiful Azam Sazzad MD Student (Thesis Part) Critical Care Medicine Dhaka Medical College

INTRODUCTION ICU acquired infection account for substantial morbidity, mortality and expense. Infection and Sepsis are leading cause of death ICU about 40%. Account for 40% of all ICU expenditure.

EPIDEMIOLOGY The Most important infection in the ICU are : Sepsis without an obvious focus Catheter related blood Stream infection (CRBSI) Ventilator associated Pneumonia (VAP) Catheter associated Urinary tract infection (CAUTI). Wound infection Intra abdominal sepsis

PREVALENCE A one day point prevalence of infection analysis in different ICU in 17 European countries, the prevalence rate of ICU infection was 20.6%. They are: 1. Pneumonia 46.9% 2. Infection of lower respiratory tract 17.8% 3. Urinary tract infection 17.6%

MICROBIOLOGY : Causative Pathogen : Staphylococcus Aureus 30.1% Pseudomonas aeruginosa 28.7% Coagulase Negative staphylococci 19.1% Entero Cocci 11.7% Streptococcus pyogenes Coliforms E.coli Klebsiella Proteus Acintobacter

MICROBIOLOGY : Source of infection : Primary (outside of hospital) Nosocomial (Hospital Acquired) Exogenous-from Environment of ICU Endogenous-by normal microbial flora

MICROBIOLOGY : Cause of infection : ICU is an environment where significant cross infection can occur Immune compromised host-due to organ failure, invasive procedures, malnutrition and Immune supressive drug may cause infection by more benign organism. Broad spectrum antibiotic change microbial ecology by selectively killing organism, thus original flora replace by other organism.

MICROBIOLOGY : Drug Resistance: Permanent threat to antimicrobial therapy in ICU Cause: Failure of hospital hygiene Pressure on selective use of antibiotic Mobile genetic elements that encode bacterial resistance Most drug resistance occur by genetical either by chromosome or by Plasmid mediated doing up regulation of genetical materials and acquiring Genes that code for antibiotic resistance. 6 more common MDR pathogen (ESKAPE) E- Enterococes Facium A.-Acintobactur S- S. Aurus P- Pseuodomonas Aeruginosa K- Klebsielln pneumonia E- Enterobacter

CLINICAL PRESENTATION : Fever is a dilemma in ICU infection : Fevers is most important presentation of infection. Fever is significant when body temp 38.3 0 C (100 0 F). But 50% of ICU patient with fever have no apparent infection, is a sign of systemic inflammation. If fever documented perform focused diagnostic test and procedures according to the Fever Assessment Guidelines.

ANTI MICROBIAL THERAPY Principles of antimicrobial therapy in intensive care unit. Categorization of infection, isolation of organism and specific anti microbial therapy is advised. But without delay. Consider other diseases and organ function Consider the microbial spectrum activity and toxic effect. Avoid broad spectrum antibiotic that will alter normal microbiological environment. Use monotherapy where possible sepsis and no organism identified. Empirical treatment for 72 hours and monitor clinical improvement in patient where no organism isolated. If no improvement within 72 hours than combination therapy can be start. Specific therapy should be guided by culture and discontinue if culture is sterile.

ANTI MICROBIAL THERAPY Chose of Antimicrobial therapy on the basis of three criteria. Flora friendliness. Low resistance potential. Anti-inflammation propensity.

ANTI MICROBIAL THERAPY Groups of Antibiotic that s are mostly chosen in ICU B- Lactam- Penicilin, Cephalosporins, Monabactam, Carbapenem Macrolid, clindamycin, Linezolid Polymyxins- Colistin. Glycopeptide- Vancomycin, Teicoplanin Polyenes- Amphotericin B.

ANTI MICROBIAL THERAPY Empiric Antibiotic use in Critically ill Patients 1. Empric antibiotic choices based on syndromic approach 2. Early initiation of antibiotic therapy 3. Risk assessment for MDR- pathogen, ( long time ventilation, prior use of antibiotic) 4. Combination therapy advocated then monotherapy when MDR resistant suspect

ANTI MICROBIAL THERAPY Sepsis / Septic shock without an obvious focus : Where the source may not be apparent Diagnosis : Based on clinical criteria, there is limitation in identification and isolation of offending organism. Sepsis : The systemic response to infection Presence sign of SIRS : temperature >39 0 C or <35 0 C WBC count 12 10 9 /L Heart Rate >90 beat/min Respiratory Rate > 20/min Severe Sepsis: Sepsis with evidence of organ failure due to DIC and coagulation profile abnormality. Septic shock: Sepsis + Hypotension + Altered Coagulation Profile organ failure.

ANTI MICROBIAL THERAPY Cont. Treatment: Sepsis / Septic shock without an obvious focus : Empirical Therapy for severe sepsis with no obvious focus Clinical condition Antimicrobial regimens Immunocompetent Piperacillinadult Tazobactam/Meropenem/Cefepime ±Vancomycin Neutropenia Piperacillin- (<500) Tazobactam/Meropenem/Cefepime +Aminoglycoside±Vancomycin IV drug user Vancomycin MS KRISNA SARIN, M VADIVELAN, CHANAVEERAPPA BAMMIGATTI. Indian Journal of clinical practice. Vol-23, No-10 March, 2013.

ANTI MICROBIAL THERAPY Cont. Treatment: Sepsis/Septic shock without an obvious focus : Empirical coverage for maethicillin-resistant staphylococcus aureus (MRSA) with vancomycin is required in the following situations. Patients with indwelling vascular cheaters If patients has received quinolone prophylaxis If the institution has a high incidence of MRSA infections. If there is a high prevalence of MRSA isolates in the community.

ANTI MICROBIAL THERAPY Cont. Combination Therapy usually chosen for suspected pseudomonas infection in Sepsis/Septic shock without an obvious focus : Neutropanic fever Severe sepsis & septic shock Presence of serious infection like pneumonia, endocarditis, meningitis Combination therapy : Ceftazidim or Piperacillin-tazo boctam or meropenmun with an aminoglycosides.

ANTI MICROBIAL THERAPY Sepsis with an identified focus : Ventilator Associated Pneumonia (VAP) Diagnosis : A new infiltrate in chest x-ray with two of following : Fever Leucocytosis Detoriation of SpO 2 /PaO 2 Purulent tracheal secretion Two type : Early VAP-within 5 days of hospital admission. Late VAP after 5 days of hospital admission.

ANTI MICROBIAL THERAPY Cont. Treatment : Emperical Therapy recommendated with a single agent in early VAP : Ceftriaxone Levofloxacin/ Moxifloxacin Ampicillin + salvactam Combination Therapy in late VAP where suspected MDR pathogen : (The drugs are used) Ceftazidim / Cefepime Imepenam /Meropenam Piperacillin - Tazobactum + Aminoglysides/ Fluroqunolone + vencomycin / Linuzolid

ANTI MICROBIAL THERAPY Sepsis with an identified focus : Catheter related blood stream infection (CRBSI) Diagnosis : Depends on blood culture Same organism from catheter tip and blood culture. Treatment : Combination Therapy : 4 th Generation Cephalosporin / Carbapenam + Vancomycin An Amnioglycoside is added if pseudomonas suspected. Catheter must be removed in severe sepsis.

ANTI MICROBIAL THERAPY Sepsis with an identified focus : Catheter Associated UTI (CAUTI) Diagnosis : Bacteriuria >10 3 coloney forming unit. Symptom compatible with UTI. Often by Polymicrobial or MDR pathogen. Treatment : According to Urine culture Catheter has to be replaced when. It has been more then 2 weeks.

ANTI MICROBIAL THERAPY Anti biotic therapy depending on the site of infection Site of infection Bacteria Suggested treatment UTI Intra-abdominal sepsis Pneumonia CRBSI E. coli P. aeruginosa Enterococcus species Staphylococcus species E. coli P. aeruginosa Enterococcus species Bacteroides species Enterobacter P. aeruginosa S. aureus S. pneumoniae H. influenzae Enterobacter P. aeruginosa S. aureus Ceftriaxone or Ceftazidime Aminoglycoside Ertapenem Piperacillin- Tazobactam Third - or fourth generation cephalosporin (Active against P. aeruginosa) + Metronidazole B-Lactam Aminoglycoside Vencomycin If MDR pathogen 3 rd generation cephalosporin ± mocrolid Vancomycin +B-Lactam with activity against P. aeruginosa MS KRISNA SARIN, M VADIVELAN, CHANAVEERAPPA BAMMIGATTI. Indian Journal of clinical practice. Vol-23, No-10 March, 2013.

ANTI MICROBIAL THERAPY Treatment option for resistant Gram-positive bacteria Drug Activity against MRSA Activity against resistant S. pneunomia Activity against Vancomycin resistant enterococci Vancomycin Yes Yes No Linezolid Yes No Yes Tigecycline Yes Yes Yes MS KRISNA SARIN, M VADIVELAN, CHANAVEERAPPA BAMMIGATTI. Indian Journal of clinical practice. Vol-23, No-10 March, 2013.

ANTI MICROBIAL THERAPY Treatment option for resistant Gram-negative bacteria Organism Emperical therapy : Monomicrobial infection Polymicrobial infection First line therapy Carbapenem Tigecycline (not in UTIs) ± Antipsedomonal agent Carbapenem+Vancomycin Second line therapy Piperacillin-Tazobactam Colistin Piperacillin- Tazobactam + Vancomycin Directed therapy : ESBL producing Enterobacteriacease Tigecycline (not in UTIs) ± Antipseudomonal agent Carbapenam Piperacillin-Tazobactam Colistin + Vancomycin Tigecyclinne (not in UTIs) Fluoroquinolone Colistin Carbapenemase producing Tigecycline Fosfomycin Enterobacteriaceae Colistin MDR P. aeruginosa Meropenem Colistin MS KRISNA SARIN, M VADIVELAN, CHANAVEERAPPA BAMMIGATTI. Indian Journal of clinical practice. Vol-23, No-10 March, 2013.

ANTI MICROBIAL THERAPY Optimization of Antibiotic Therapy (To prevent drug resistance and ensure good response) Establish Antibiotic Guideline/Protocol. Schedule change in antibiotic. Combining Antibiotic therapy. Antibiotic rotation/class cycling. Area specific antimicrobial therapy. Antimicrobial de escalation.

ANTIBIOTIC POLICIES Why does an ICU need a Antibiotic Policy Every ICU should have a well structured guidelines on the use of Antimicrobial Agent to guarantee that patient requiring intensive care receive appropriate antimicrobials for a relevant period to prevent and treat infections. To prevent rate of infection and cross infection in ICU. To prevent drug resistance. For cost effectiveness of patient.

ANTIBIOTIC POLICIES Criteria of antibiotic guideline for ICU The main feature of an antibiotic policy in the ICU is the use of a minimum of well-established antimicrobial agents that are associated with a minimum of side effects, but also allow the control of the ICU infections. Antibiotic guideline vary between ICUs This variation is based on local cause of infection, resistance pattern, availability of drugs, cost and patient factor.

ANTIBIOTIC POLICIES How to make an Antibiotic Guidelines for ICU These guidelines should meet the therapeutic needs of consultant allow collaborations of intensivist, Microbiologist, clinical Pharmacist & statisticians. Microbiologist- to perform daily surveillance of pathogen in ICU and to update antibiogram. Clinical Pharmacist- to monitor doses, efficacy, toxicity and to control drug expenditure. Statistician- for audit, research, antimicrobial guidelines aid educational program. Intensivist- to monitor drug response by clinically and by other parameter

CONCLUSION Prevention of infection in the best way to control infection specially strict aseptic procedure to introduce central venous catheter, suction and cleaning airway, oral cavity and maintain aseptic procedure to introduce ET tube, catheter are mandatory.