strategicmanagement of cap and hap caused by fluoroquinolone resistant pathogens

Visit Udompanich,MD. Chest Service Chulalongkorn Hospital Bangkok, Thailand STRATEGIC MANAGEMENT OF CAP/HAP CAUSED BY FLUOROQUINOLONE RESISTANT PATHOGENS • non smoker, no any chronic disease – Fever, cough with scant sputum for one day – Difficulty in taking full breath – T. 38.7, BP 120/70 – Rales at RLL • How do you manage this patient? First Case A 42 year old businessman Community Acquired Pneumonia (CAP) • Leading causes of morbidity and mortality due to infections • Incidence (USA) – 1-12 / 1,000/ year in general population – 25-44 / 1,000/ year in > 65 years – Cost > 17,000,000,000 $ / year • Proper management reduces morbidity and cost Fine MJ, et al. Prognosis of CAP; JAMA 1996;275:134-141 Management of CAP • Choosing the “right” antibiotic • Respiratory and supportive care – Oxygen therapy – Clearance of bronchial secretion – Antipyretic, antitussive – Nutritional support • Treatment of complications – Shock – Respiratory failure Bartlett JG, et al. Guidelines for the management of CAP. CID 2000;31:347-82 What is the “right” antibiotic? • The ‘right’ antibiotic for CAP – Active against likely etiologies • What is the most likely etiology? • What is its antibiotic susceptibility ( or resistant) ? – Easy to administer • Oral • Once a day – Good bioavailability (easy for i.v. to p.o. switch) – No or little side effects – Cheap Bartlett JG, et al. Guidelines for the management of CAP. CID 2000;31:347-82 KEY BACTERIAL PATHOGENS IN CAP Reimer and Carroll: Clin Infect Dis 26:742-748, 1998. Marrie: Infect Dis Clin North Am 12:723-740,1998. Bartlett et al: Clin Infect Dis 26:811-838, 1998 6% 16% 10% 7% H. influenzae S. pneumoniae Streptococcus pneumoniae is the primary recognized bacterial cause of community respiratory infections Atypical Pathogens: 23% 1% S. pneumoniae M. catarrhalis H. influenzae Legionella spp. M. pneumoniae C. pneumoniae Others 1 % 16% 40% 20% Etiologies of CAP – Hundreds of organisms can cause CAP • BUT – The majority of CAP are caused by a group of few organisms • S. pneumoniae • H. influenzae • M. pneumoniae • C. pneumoniae • Legionella • Influenza viruses – Account for 80-90 % of CAP – Co infection in 20-30 % (commonly S. pneumoniae and Mycoplasma) Bartlett et al: Clin Infect Dis 26:811-838, 1998 Community Acquired Pneumonia • The likely etiology cannot be accurately predicted from clinical or radiological features. • Extensive investigations usually not cost- effective – In up to 50% of CAP no etiology can be identified – The results always come too late • Most patients can be treated successfully without any knowledge of an infecting microorganism. Bartlett et al: Community-Acquired Pneumonia. NEJM 1995;333:1618-1624 Selection of Antibiotics in CAP • Should be based on – Local bacteriology and sensitivity pattern – Host factors (risks for DR bacteria) • Age • Comorbid conditions • Previous antibiotics used – Severity of CAP • More severe CAP should receive broader coverage IDSA-ATS Consensus Guidelines on CAP; CID 2007:44 (Suppl 2) S27-S72 Drugs Resistant S. pneumoniae is increasing worldwide TRUST 9 * 2005 TRUST 10 * 2006 TRUST 11 * 2007 TRUST 12 * 2008 Antimicrobial agent %R %R %R %R Penicillin 15.6 14.5 13.3 15.7 Azithromycin 28.8 31.9 32.3 33.4 Ciprofloxacin 2.3 1.8 2.2 1.5 Ceftriaxone 0.7 1.0 1.4 1.4 Levofloxacin 0.8 0.6 0.7 0.6 Moxifloxacin 0.5 0.5 0.2 0.2 Data on file, TRUST 9-12. Ortho-McNeil-Janssen Pharmaceuticals, Inc. [...]... 2005;171:388-416 Conclusions • Nosocomial pneumonia: – Leading causes of death due to infection – Increase morbidity, mortality, and cost • Most frequent infecting pathogens: – Gram-negative bacteria (mostly MDR) • P aeruginosa • Enterobacter baumanii • K pneumoniae – MRSA ATS/IDSA Guidelines Am J Respir Crit Care Med 2005;171:388-416 Management of CAP and HAP • Antibiotic alone is not enough • Respiratory Care... Guidelines on CAP; CID 2007:44 (Suppl 2) S27-S72 IDSA/ATS Guidelines: Inpatient Treatment Recommendations for CAP • Non ICU – Fluoroquinolones or – β lactam + macrolides • ICU – β lactam + Macrolides or – β lactam + fluoroquinolones • Suspect Pseudomonas add aminoglycosides • Suspect MRSA add vancomycin or linezolid IDSA-ATS Consensus Guidelines on CAP; CID 2007:44 (Suppl 2) S27-S72 Costs of antibiotic... Klebsiella Spp • Proteus spp • E.coli – More drug resistant bacteria ATS/IDSA Guidelines Am J Respir Crit Care Med 2005;171:388-416 Antibiotic Resistant Bacteria are Even More Common in HAP Infect Control Hosp Epidemiol.2013;34(1);1-14 Risk Factors for MDR Pathogens • Antimicrobial therapy in preceding 90 days • Current hospitalization of > 5 days • High frequency of antibiotic resistance in the community... Antibiotic Therapy for MDR Pathogens ATS/IDSA Guidelines Am J Respir Crit Care Med 2005;171:388-416 General Principles When Considering How to De-Escalate • Identify the organism and know its susceptibilities • Assess and potentially modify initial selection of antibiotics • Make the decision in the context of patient progress on the initial regimen • Individualize the duration of therapy ATS/IDSA Guidelines...Antibiotics Selection for CAP in View of Increasing Drug Resistance • Choices – Single antibiotic • Respiratory fluoroquinolones • β lactam ( not active against Mycoplasma, DRSP) • Macrolides ( DRSP and DR H.flu worrisome) – Combination • β lactam + macrolides ( DRSP a problem) • β lactam + fluoroquinolones ( no more effecive than FQ alone) IDSA-ATS Consensus Guidelines on CAP; CID 2007:44 (Suppl 2)... development of bacterial resistance? • Bacteria resistant to multiple antibiotics are increasing rapidly • New antibiotics are few and do not keep up • We have to use the available antibiotics more wisely CnnD CDC Features Preventing Antibiotic Resistance Nov 2012 Pharmacodynamic Parameters and Outcome Cmax = Peak Cmax/MIC For fluoroquinolones, AUC:MIC predicts microbiologic eradication and clinical... Concentrations Peak plasma levels Mean Levofloxacin Plasma Concentration: Time Profiles • Mean Plasma Concentration (μg/mL) 12 • 10 8 750 mg IV* 6 500 mg IV* 4 • 2 0 0 6 Time (h) 18 12 Levofloxacin is a concentrationdependent killer Increasing dosage by 50% results in 90% higher peak concentration and 115% higher AUC This make it more effective against partially resistant organisms 24 *In healthy volunteers... Infections • A meta analysis of 17 studies – Outcome measured : mortality – Overall odd ratio 0.96 • ( 95% CI 0.70-1.32) – For Pseudomonas 0.50 • ( 95% CI 0.30-0.79) Sefdar N, et al Lancet Infect Dis 2004;4:519-527 Management Strategies Empiric Antibiotic Therapy for HAP HAP Suspected (All Disease Severity) Late Onset (> 5 days) or Risk Factors for Multidrug Resistant (MDR) Pathogens NO Limited Spectrum... Outpatient Treatment Recommendations for CAP • Low risk for MDR – Macrolides or – doxycycline • Increase risk for MDR – Respiratory fluoroquinolones • Levofloxacin or • Moxifloxacin or – Combination • Macrolides + β lactam • Doxycycline + β lactam IDSA-ATS Consensus Guidelines on CAP; CID 2007:44 (Suppl 2) S27-S72 Risk Factors for DRSP in Adult Patients With CAP – Age >65 years – β-lactam therapy within... Critical Issues in the Treatment of Nosocomial Pneumonia • Not all lung infiltrates are pneumonia – Inappropriate antibiotics increase super infection and mortality • Always consider alternative diagnosis – Heart failure – Atelectasis – Pulmonary embolism – Other chronic lung diseases – Etc… Kirtland SH, et al Chest 1997;112:445-457 Antibiotics For HAP • Early onset – – – – Levofloxacin…or Ampicillin/Sulbactam…or . Udompanich,MD. Chest Service Chulalongkorn Hospital Bangkok, Thailand STRATEGIC MANAGEMENT OF CAP/ HAP CAUSED BY FLUOROQUINOLONE RESISTANT PATHOGENS • non smoker, no any chronic disease – Fever, cough. morbidity and cost Fine MJ, et al. Prognosis of CAP; JAMA 1996;275:134-141 Management of CAP • Choosing the “right” antibiotic • Respiratory and supportive care – Oxygen therapy – Clearance of bronchial. pneumoniae Others 1 % 16% 40% 20% Etiologies of CAP – Hundreds of organisms can cause CAP • BUT – The majority of CAP are caused by a group of few organisms • S. pneumoniae • H. influenzae • M. pneumoniae •