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Edit Comment Close Premium member Presentation Transcript Slide 1: INHALATIONAL ANTIBIOTICS IN ICU Ubaidur Rahaman Senior Resident Dept of CCM, SGPGIMS, Lucknow,India INHALATIONAL ANTIBIOTICS IN ICU WHY NEW ROUTE: INHALATIONAL ANTIBIOTICS IN ICU WHY NEW ROUTE Respiratory tract as a conduit for therapeutic drug delivery not a new concept inhaled aerosols, smoke, and steam for pleasure, and spiritual enlightment . INHALATIONAL ANTIBIOTICS IN ICU WHY NEW ROUTE: INHALATIONAL ANTIBIOTICS IN ICU WHY NEW ROUTE COLONIZATION OROPHARHYNGEAL TRACHEOBRONCHEAL Tracheobronchitis Pneumonea PROPHYLAXIS TREATMENTSlide 4: poor penetration into lung parenchyma –higher therapeutic dose Adverse effects- AGS- ototoxicity and nephrotoxicity Polymyxins - nephrotoxicity, neuromuscular blockade, and neurotoxicity Higher dose delivery to distal airways and lung parenchyma- lower therapeutic dose Lower risk of systemic side effects INHALATIONAL ANTIBIOTICS IN ICU WHY NEW ROUTE Inhaled therapy Systemic AntibioticsSlide 5: Lung distribution and pharmacokinetics of nebulized tobramycin -Le Conte P, Am rev resp dis1993, 147:1279-82 INHALATIONAL ANTIBIOTICS IN ICU IS IT EFFECTIVE Concentration of gentamycin in bronchial secretion after intramuscular and endobronchial administration- Klastersky J, J clin pharmacol, 1975, 15, 518-24 Gentamycin 2mg/kg concentration achieved- endobronchial secretion serum I.M. route <2ug/ml >6ug/ml Endobronchial route >400ug/ml <1ug/ml Mean lung tissue conc. 5.5ug/ml after 4 hours ; 3-61ug/ml after 12 hours Inhaled amikacin achieves high epithelial lining fluid concentration in Gram neg pneumonea in intubated an mechanically ventilated patients. Luyt CE, Jacob A, Am J Respir Crit Care Med 2007; 175:A 328 INHALATIONAL ANTIBIOTICS IN ICU IS IT EFFECTIVE: INHALATIONAL ANTIBIOTICS IN ICU IS IT EFFECTIVE dose delivered to lung was 21.9% of neb charge sputum conc- peak- 1005-5839 ug/ml, trough- 234-520 ug/ml serum conc- undetectable in all (except one who was in renal failure-8.7 ug/ml of amikacin) weekly culture revealed eradication of pseudomonas, serratia mersescence, enterobactor aerogenes EFFICACY IN CRITICALLY ILL PATIENT TO BE DETERMINED Aerosolized antibiotic in mechanically ventilated patients: delivery and response. Lucy B. Palmer, Gerald C. Smaldone, crit care med; 1998; 26:1:31-39 Aerosolized amikacin and gentamycin for 14-21 days in 9 cycles in mechanically venilated stable patients colonized with G neg organism producing purulent secrection INHALATIONAL ANTIBIOTICS IN ICU PAST: INHALATIONAL ANTIBIOTICS IN ICU PAST Documented efficacy in cystic fibrosis Data are scarce in critically ill patients on mechanical ventilation since 1950 - earlier trial ended in increased incidence of infection and adverse effects ( Aerosol Polymyxin and Pneumonia in Seriously Ill Patients T. W. Feeley, G. C. du Moulin,, N Engl J Med 1975; 293:471-475)Slide 8: Falagas ME, Siempos II, Bliziotis IA, Michalopoulos: Administration of antibiotics via the respiratory tract for the prevention of ICU-acquired pneumonia: a meta-analysis of comparative trials. Crit Care 2006; 10:R123. 1950 – 2005:Meta-analysis of 5 RCTs (414 pts) ICU-acquired pneumonia was statistically less common in the cohorts receiving aerosolized antibiotic prophylaxis. No difference in mortality Could not evaluate effect on resistance of bacteria INHALATIONAL ANTIBIOTICS IN ICU PREVENTION OF COLONIZATION AND NOSOCOMIAL PNEUMONEA INHALATIONAL ANTIBIOTICS IN ICU TREATMENT OF TRACHEOBRONCHITIS: INHALATIONAL ANTIBIOTICS IN ICU TREATMENT OF TRACHEOBRONCHITIS Palmer LB, Smaldone GC, Chen JJ, et al. Aerosolized antibiotics and ventilator-associated tracheobronchitis in the ICU Crit Care Med 2008; 36:2008–2013. reduced clinical signs of respiratory infection, pulmonary infection score, progression to VAP, Reduced bacterial resistance, reduced use of systemic antibiotics, and earlier discontinuation of mechanical ventilation. Based on Gram stain of the tracheal aspirate, patients received aerosolized vancomycin or gentamycin for 14 days versus placebo.Slide 10: Ioannidou E, Siempos II, Falagas ME. Administration of antibiotics via the respiratory tract for the treatment of patients with nosocomial pneumonia : a meta-analysis. J Antimicrob Chemother 2007; 60:1216–1226. INHALATIONAL ANTIBIOTICS IN ICU TREATMENT OF NOSOCOMIAL PNEUMONEA No difference was demonstrated for mortality, emergence of resistance, or adverse event. META ANYLYSIS OF 5 TRIALS Statistically higher success rate for the treatment of nosocomial pneumonia if receiving inhaled or endotracheally instilled antibiotics in the 176 patients.Slide 11: Falgas ME, Agrafiotis M, Athanassa Z, et al Administration of antibiotic through respiratory tract as monotherapy for pneumonea Exper Rev Antiinf Ther 2008;6:447-452 INHALATIONAL ANTIBIOTICS IN ICU MONOTHERAPY OF NOSOCOMIAL PNEUMONEA TREATING PATIENT WITH VAP WITH AEROSOLIZED ANTIBIOTIC ALONE IS PREMATURE This therapy might be considered when systemic access is not available, refused by the patient or concern regarding bioavailability to lung or systemic toxicitySlide 12: Lesho E . Role of inhaled anibacterial in hospital aquired and ventilator associated pneumonea . Expert Rev Anti Infect Ther 2005;3(3):445-451 INHALATIONAL ANTIBIOTICS IN ICU RECOMMENDATION FOR PREVENTION OF NOSOCOMIAL PNEUMONEA Hagerman JK, Hancock KE, Klepser ME. Aerosolized antibiotics: a critical appraisal of their use. Expert Opin Drug Deliv 2006;3(1)71-78 There are limited data available to support the routine use of this modality Despite optimized delivery systems…inhaled antibiotics can still not be recommended for preventing VAP Recent evidence base reviews have interpreted supporting data as week Universally recommended against routinely using for VAP prophylaxix untill stronger data are availableSlide 13: NO RECOMMENDATION ABOUT ANTIBIOTIC INDICATION ,SELECTION, DOSE, FREQUENCY, DURATION INHALATIONAL ANTIBIOTICS IN ICU RECOMMENDATION FOR TREATMENT OF NOSOCOMIAL PNEUMONEA MULTIPLE CONSENSUS GROUP RECOMMEND AGAINST USING IN ESTABLISHED VAP ESPECIALLY AS MONOTHERAPY ( Neil R MacIntyre, Bruce K Rubin MEngr, Should Aerosolized antibiotic be administered to prevent or treat VAP in patient who do not have cysic fibrosis? Respir Care, April 2007;52;4:416-20 ) CAN BE RECOMMENDED TO TREAT MDR VAP – COLISTIN AND AGS (C.E. Luyt, Alain Combes, Ania Nieszkowska, JL Trouillet, Aerosolized antibiotics to treat VAP . Curr Opin infect dis ;2009;22:154-158) Legal concern- airway as a route of Antiobiotic delivery not approved by USFDA (EVEN FOR TOBRAMYCIN FOR WHICH SPECIFIC PREPARATION TOBI IS AVAILABLE)Slide 14: IT IS VERY POSSIBLE THAT AEROSOLIZED ANTIBIOTIC MAY BECOME A MAINSTAY IN PREVENTING VAP IN FUTURE Neil R MacIntyre, Bruce K Rubin MEngr, Should Aerosolized antibiotic be administered to prevent or treat VAP in patient who do not have cysic fibrosis? Respir Care , April 2007;52;4:416-20 ) INHALATIONAL ANTIBIOTICS IN ICUSlide 15: INHALATIONAL ANTIBIOTICS IN ICU PROBLEMS BRONCHOSPSM Pretreatment with albuterol 2.5 mg SYSTEMIC TOXICITY AND INTRODUCTION OF NEW INFECTION PATIENT RELATED DEVICE RELATED DRUG RELATED DRUG DELIVERY VENTILATOR RELATED CIRCUIT RELATED EMERGENCE OF RESISTANCESlide 16: INHALATIONAL ANTIBIOTICS IN ICU PROBLEMS- DRUG DELIVERY PATIENT RELATED: Airway obstruction Dynamic hyperinflation PVA VENTILATOR RELATED: MODE- spontaneous, volume control Vt- higher >500, small Vd RR- lower Ti- longer flow waveform- square waveform better than descending ramp triggering- flow triggering –loss of drug DEVICE RELATED: Type of nebulizer- Jet/ ultrasonic Flow – 6-8 lt Position in circuit- around 35-45 cm from Y connector or ETT Continuous/ intermittent operation duration of nebulization CIRCUIT RELATED: ETT- Inhaled gas humidity Inhaled gas density/ viscocity DRUG RELATED: Dose Particle size- 1-5 micron Volume- 4-5 ml( neb charge)Slide 17: SPECIFIC DOSING OF DRUGS: Amikacin- 400 mg q8-12h Gentamycin- 80 mg q8h Tobramycin ( TOBI)- 300 mg q 12h colistin- 150 mg ( 2 mu) q 8-12h Vancomycin- 125 mg q8h EACH DOSE SHOULD BE DILUTED TO A TOTAL VOLUME OF 4 ml INHALATIONAL ANTIBIOTICS IN ICU Aerosolized antibiotic therapy in ICU- guidelines prepared by Surgical Education, Orlando Regional Medical Centre. Approved 05-05-2009Slide 18: Thankyou You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.