Case Discussion: optimizing Antimicrobial therapy in Real Practice Sang Usayaporn, B.Pharm Prof. Terapong Tantawichien, M.D. Chulalongkorn University Griffith M, Postelnick M, Scheetz M. Expert Rev Anti Infect Ther. 2012;10(1):63-73. Schematic diagram of the antimicrobial stewardship program prospective audit with immediate concurrent feedback To optimize antimicrobial use - Critically Ill patients - Obesity, BW - Immunocompromised hosts - Comorbidities and medications - Site of infection - Renal/Hepatic impairment - Drug allergy - Environment Host -Spectrum of activity -PK/PD -Administration -Stability -ADRs and DIs -Monitoring - Pathogenesis -Antimicrobial susceptibility test -MIC -Mechanism of resistances Pathogens Antimicrobial agents Eur J Clin Microbiol Infect Dis. 2012 ;31(6):947-55.
Diagnosis of community-acquired pneumonia 1. New pulmonary infiltration / 2. Acute onset (duration 2 weeks) / 3. Symptoms and signs of LRI (3 in 5) Fever / Cough ± productive sputum / Dyspnea / Pleuritic chest pain Consolidation or crackles on P.E. / ** This diagnosis criteria does not include patient who discharge hospital within 3 weeks, immunocompromised host and organ transplantation patients http://www.thaichest.org/atat3/pdf/guideline/pneumonia.pdf X CURB-65 @ ER @ Ward Confusion Uremia (>20 mg/dl) Respirator y rate ( 30/min) LowBlood flow (SBP<90or DBP 60mm Hg) Age 65 years X / (BUN =95 mg/dl) X (24/min) / (100/54mmH g) X (24/min) X (151/85mmH g) X (Age 51 years) Prim Care Respir J. 2010 Mar;19(1):21-7. Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72. Most common etiologies IDSA/ATS guideline 2007 THAI Thoracic Society guideline 2001 ICU admitted with risk of P. aeruginosa Recommended empirical antibiotics for community acquired pneumonia Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72. http://www.thaichest.org/atat3/pdf/guideline/pneumonia.pdf Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72.
empirical antimicrobial regimens to treat severe CAP J Antimicrob Chemother 2011; 66 Suppl 3: iii3 iii9 Summary of influenza antiviral treatment recommendations MMWR January 21, 2011 Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72.
Does acute bronchitis need antibiotic treatment? 1.Yes 2.No 3.Not sure Acute Bronchitis Acute bronchitis is a disease characterized by inflammation of the large airways within the lung accompanied by a cough lasting from 1 to 3 weeks. without the presence of pneumonia as confirmed by the absence of an infiltrate on chest radiograph Viral infections account for an estimated 85% to 95%of acute bronchitis cases with bacterial causesbeing more common in patients with chronic health problems. Bacterial pathogens involved are those that cause community-acquired pneumonia such as Mycoplasma pneumonia, Streptococcus pneumonia, Haemophilus influenza, Moraxella catarrhalis, and Bordetella pertussis. J Pharm Pract. 2012 Dec;25(6):586-90. Benefit Antibiotics for acute bronchitis reduction in cough duration (small benefit ) 1 reduction in days feeling ill and a reduction in days with limited activity There was no significant difference in presence of productive cough at follow-up or mean duration of cough. 2 Risk adverse effects resistance cost 1. SmucnyJ, Fahey T, Becker L, et al. Cochrane Database SystRev. 2004;(4):CD000245.10. 2. Smith SM, Fahey T, Smucny J, Becker LA. Cochrane Database Syst Rev. 2010;(4):CD000245.
Acute Bronchitis Therapy Symptomatic treatment A majority of systematic reviews have found no benefit from using antibiotics with the exception of a modest reduction in duration of symptoms. Antimicrobial therapy should be reserved for those cases where a pathogen is isolated or in high-risk patients presenting with symptoms of influenza infection during influenza season. J Pharm Pract. 2012 Dec;25(6):586-90. Does tracheobronchitis need antibiotic treatment? 1. Yes 2.No 3.Not sure
Diagnosis criteria VAP vs VAT Pathogenesis of bacterial L-RTI Oropharynx colonization Bacterial Pathogens Cuff leak/biofilm Bacterial pathogens Number, Type & Virulence Lung defenses Cilia, Humoral, Cellular Tracheal Colonization VARI VAT VAP Clin Chest Med 2011; 32: 547-57 Clin Chest Med 2011; 32: 547-57 The rate of tracheobronchitis that progressed to pneumonia was 29% 1 Tracheobronchitisis a precursor to pneumonia, and that treatment of tracheobronchitis can prevent pneumonia and improve patient outcomes 2 Chest 2009;135;521-528 1. Am J Med. 2013 Jun;126(6)542-549. 2. Nseir S et al. Eur Respir J. 2002;20:1483-1489.
Impact of VAT on clinical outcome In a large cohort of intubated and mechanically ventilated patients Impact of antimicrobial treatment on outcomes in patients with VAT 2 RCTs evaluated the impact of antimicrobial treatment on outcome of VAT patients. 1 2 Reduce duration of mechanical ventilation, ICU stay Prevent VAT patients progress to VAP coexistence of VAP CurrOpinInfect Dis 2009 22:148 153 Eur Respir J 2002; 30:1193 1207 1.Crit Care Med 2008; 36:2008 2013. 2. Crit Care 2008; 12:R62. Treatment: VAT Pros More ventilator free day Reduced the incidence of subsequent VAP Duration of treatment still controversy Cons May not decrease mortality Risk for Multi-drug resistance organism Additional cost ADR lower frequency of subsequent pneumonia and more ventilator-free days Respir Med. 2010 Mar;104(3):325-36. CurrOpinInfect Dis 2009 22:148 153
Retrospective evaluation of data collected during 24 months from patients hospitalized in a tertiary medical center. The analysis included 36 patients. VPA mean +/-SEM plasma concentration decreased from of 50.8 +/-4.5 microg/ml to 9.9 +/- 2.1 microg/ml (P <.001) following meropenem administration. After discontinuation of meropenem, VPA plasma concentrations remained low for 7 days and then gradually increased after 8 to 14 days, reaching values comparable to those before meropeneminitiation. Different daily VPA doses showed a similar pattern of decreased VPA concentrations. In conclusion, the interaction between meropenem and VPA causes a significant decrease in VPA plasma concentration, apparently within 24 hours. As the therapeutic effects of VPA are plasma concentration dependent, the data suggest that these drugs should not be administered concomitantly. J Clin Pharmacol. 2009;49:1363-9 Singh N et al. Am J Respir Crit Care Med. 2000;162:505-11. Antibiotic duration* Ciprofloxacin 3 days Standard 3 days 10 days LOS ICU* 9 days 15 days Antibiotic resistance/ superinfection* 14% 38% Clinical pulmonary infection score (CPIS) Clinical pulmonary infection score (CPIS) < Day 3 CPIS Score >6 Continue ATB Am J Respir Crit Care Med 2000;162: 505 11. Am J Respir Crit Care Med 2005;171:388-416.
oxyhemoglobin dissociation curve The relationship between oxygen saturation and the partial pressure of oxygen inarterial blood O 2 sat 90% = PaO 2 60 mmhg O 2 sat 98% = PaO 2 100 mmhg Delayed resolution of pneumonia Both the clinical and radiographic diagnosis ofpneumoniamay be difficult in the elderly especially if there is co-existing congestive heart failure. Curr Opin Pulm Med. 1996 May;2(3):192-7. Delayed resolution of pneumonia. When is slow healing too slow? Slowly resolving or nonresolvingpneumoniais a clinical challenge, but we believe it can be dealt with in a rational and decisive manner. The following risk factors have been established for delayed radiographic resolution ofpneumoniaand should be considered in patient evaluation: Coexisting medical conditions History of smoking, Advanced age, Multilobarinvolvement, Persistent fever or leukocytosis. Diabetes, chronic obstructive pulmonary disease, renalfailure, and alcohol abuse can impair immune function, which slows normal clearing of infiltrates. Common and uncommon infectious agents, conditions that mimicpneumonia(eg, a neoplasm, congestiveheart failure), and pulmonary complications (eg, abscess) can also result in delayed resolution. Postgrad Med. 1996 Jan;99(1):151-4, 157-8. radiographic improvement often lags behind clinical parameters, especially in the elderly and in individuals with coexisting disease (e.g., chronic obstructive pulmonary disease) Am J Respir Crit Care Med. 2005;171:388-416. Jacquez, John. 1979; Respiratory Physiology. McGraw-Hill. pages 56 175. PediatrNurs. 2004 Jan-Feb;30(1):14-20. Natural resistance of P. aeruginosaand A. baumannii to antibiotics Treatment of Acinetobacter infections Any nosocomial infection due to A.baumannii manda antimicrobial therapy that is based on the sensitivitie of the pathogen. Common treatment options include ceftazidime, cefepime, carbapenems, sulbactam, piperacillin/tazobactam, aminoglycosides, quinolones, polymyxinse and B, minocycline, doxycycline, and tigecycline Itis known that most A. baumanniistrains are resista to several antimicrobial agents such as penicillins, ampicillin, macrolides, second-and third-generation cephalosporins, and chloramphenicol. Arch. Immunol. Ther. Exp., 2006;54:113 20. Expert Opin. Pharmacother. 2010 ;11(5):779-88. Data from the National Antimicrobial Resistance Surveillance Thailand(NARST)
The de-escalation strategy Respir Care 2005;50(7):932 952. Joung et al. Critical Care 2011, 15:R79 How do you handle clinician hesitation to de-escalate antimicrobial therapy in a patient with negative cultures? American Thoracic Society, Infectious Diseases Society of America. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med. 2005;171:388-416. Semin Respir Crit Care Med. 2006 Feb;27(1):45-50.
de-escalate antimicrobial therapy In an attempt to minimize mortality, patients with hospital-acquired pneumonia, including VAP, typically receive as empiric therapy a threedrug regimen that provides coverage against methicillin-resistant Staphylococcus aureus(mrsa) and Pseudomonas aeruginosa(p. aeruginosa). Guidelines of the American Thoracic Society and Infectious Diseases Society of America for managing hospital-acquired, ventilator-associated, and healthcare-associated pneumonia suggest that antimicrobial therapy may be de-escalated by discontinuing coverage for MRSA and P. aeruginosa in patients with clinical improvement who were not receiving antibiotics when cultures were obtained if sputum cultures are negative for these pathogens. How long s the optimal duration of the antimicrobial treatment? 1. 7 days 2. 10 days 3. 14 days 4. 21 days 5. Not known ASHP Advantage E-Newsletter September 2011 JAMA. 2003 Nov 19;290(19):2588-98. Multiresistant pathogens 44% 62.3% P=.04(0.21 to 0.95) JAMA 2003;290:2588-2598
Clinical Infectious Diseases 2011;52(10):1232 1240 Assess clinical stability : 48-72 hr Conceptual framework for ASP interventions that are categorized into interventions made before and after antimicrobial prescription Clinical parameters including the white blood cell count and measures of oxygenation and core temperature have been used in several studies to define the normal pattern of resolution of HAP/VAP. Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72. Am J Respir Crit Care Med. 2005;171:388-416. Curr Infect Dis Rep 2012;14:592 600.
Take home message The Pharmacist's Role in ASPs Noninfectious syndromes that mimic infections Gouty arthritis, Drug fever Optimize antimicrobial usage: Appropriate Choice, Route, Dosage, Duration To improve efficacy, minimize drug-related adverse events, reduce treatment-related costs, and limit the potential for emergence of antimicrobial resistance Practitioners may be more receptive to the stewardship program when suggestions are not only limited to a reduction of antibiotic usage but are also focused on optimal patient care. In this era of accountability and antibiotic resistant `superbugs, there is no room for complacency in the use of antimicrobials and we can no longer afford to shy away from the responsibility of ensuring responsible antimicrobial prescribing. Thank you for your attention