ANTIBIOTICS SMART USE (ASU) การใช้ยาต้านจุลชีพอย่างชาญฉลาด Pornpan Koomanachai Division of Infectious diseases and Tropical Medicine Department of Medicine, Faculty of Medicine Siriraj Hospital .

A major threat to public health ปัญหาหลักทางสาธารณสุข ASU Inappropriate use of antibiotics การใช้ยาอย่างไม่เหมาะสม Increasing antimicrobial resistance เชื้อก่อโรคดื้อยาเพิ่มสูง Reduces the effectiveness of antimicrobial treatment ประสิทธิผลในการรักษาลดลง Increased morbidity, mortality, and health care expenditure เพิ่มอัตราตาย ความพิการ และค่าใช้จ่าย A major threat to public health ปัญหาหลักทางสาธารณสุข

ASU Antibiotics Commonly used in ambulatory care facility (ใช้บ่อย) Antibiotics can be purchased without prescriptions (ซื้อเองได้) A systematic review and meta-analysis Antibiotic prescribing in primary care Prescribing an antibiotic in primary care for a respiratory or urinary infection develop bacterial resistance to that antibiotic Costelloe C et al.BMJ 2010;340:c2096

ASU URI and acute diarrhea: common self-limiting (การติดเชื้อทางเดินหายใจส่วนต้นและท้องร่วง เฉียบพลัน) The prevalence of group A streptococci (GAS) in adults with sore throat attending Siriraj Hospital 7.9% to 11.4% No compelling data on antibiotic treatment of patients with URI other than GAS are beneficial Asawapokee N et al. J Infect Dis Antimicrob Agents 1984; 3: 141-5 Treebupachatsakul P et al. J Med Assoc Thai 2006;89(8):1178-86

ASU In healthy individuals with acute diarrhea almost always self-limited; หายได้เอง!!!! Standard guidelines การใช้ยาต้านจุลชีพต้องมีข้อบ่งชี้สำคัญ คือ empiric antibiotic therapy is recommended only for invasive or inflammatory diarrhea especially in special hosts with immunocompromised conditions non-inflammatory diarrhea with moderate or severe dehydration such as cholera

สำนักงานคณะกรรมการอาหารและยา สถาบันวิจัยระบบสาธารณสุข ASU สำนักงานคณะกรรมการอาหารและยา สถาบันวิจัยระบบสาธารณสุข องค์การอนามัยโลก

ASU 1. เป้าหมาย คือ ลดการใช้ยาปฏิชีวนะอย่างพร่ำเพรื่อใน 3 โรคที่พบบ่อย - โรคติดเชื้อทางเดินหายใจส่วนบน - โรคท้องร่วงเฉียบพลัน - แผลเลือดออก 2. ASU เป็นโครงการที่หวังผลให้เกิดการเปลี่ยนแปลงทางพฤติกรรม 3. ASU เหมาะกับสถานพยาบาลที่การสั่งใช้ยาปฏิชีวนะมากเกินจำเป็นมีสาเหตุมาจาก - ความรู้หรือความเชื่อที่คาดเคลื่อนของบุคลากรทาง การแพทย์ - แรงกดดันหรือความคาดหวังของผู้ป่วย 4. ASU ตั้งอยู่บนแนวคิดที่ว่าการเปลี่ยนพฤติกรรมเริ่มจากความรู้ แต่ความรู้อย่างเดียวไม่เพียงพอในการเปลี่ยนพฤติกรรม

PRINCIPLE OF ANTIBIOTIC USED Common Inappropriate Use of Antibiotics CHOOSING ANTIBIOTIC THERAPY BASED SOLELY ON SPECTRUM เลือกใช้ยาโดยดูแต่ความสามารถในการครอบคลุมเชื้อ PROLONGED USE OF IV ANTIBIOTICS ใช้ยาฉีดเป็นเวลานาน USE OF COMBINATION THERAPY TO PREVENT ATB RESISTANCE ใช้ยามากกว่า 1 ขนานเพราะเชื่อว่าจะป้องกันการดื้อยา OVERRELIANCE ON MICROBIOLOGY RESULTS เลือกใช้ยาตามผลเพาะเชื้อเพียงอย่างเดียว USE OF ATB FOR PERSISTENT FEVERS ใช้ยาต้านจุลชีพเพราะไข้ไม่ลดลง INADEQUATE SURGICAL THERAPY AND LACK OF NON-ATB THERAPY OF INFECTION ขาดการรักษาร่วมอื่นๆที่สำคัญ PROLONGED ATB THERAPY OR PROPHYLAXIS ใช้ยานานเกินความจำเป็น

CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective in-vitro, unable to reach the site of infection Urinary tract infections; same pathogens but! drugs for catheter-associated bacteriuria and cystitis differ from those used for pyelonephritis, prostatitis, or epididymitis Fluoroqyuinolones: high concentration in the prostate **moxifloxacin; not achieve significant urinary concentration removed for cure, since microbes causing infections associated with prosthetic joints, shunts, and intravenous lines produce which usually require surgical drainage for cure

CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective;in-vitro, unable to reach the site of infection Chronic infections - decrease vascular permeability chronic pyelonephritis, chronic prostatitis, chronic osteomyelitis Implanted foreign materials biofilm- slime/glycocalyx on plastic/metal surfaces removed for cure, since microbes causing infections associated with prosthetic joints, shunts, and intravenous lines produce which usually require surgical drainage for cure

CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective;in-vitro, unable to reach the site of infection Special barrier or abscesses ocular, fluid, CSF, abscess cavity, prostate, bone aminoglycosides; less active in the low-oxygen, low- pH, and high-protein environment of abscesses ** drainage of abscesses to enhance antimicrobial efficacy removed for cure, since microbes causing infections associated with prosthetic joints, shunts, and intravenous lines produce which usually require surgical drainage for cure

CHOOSING ATB BASED SOLELY ON SPECTRUM Antibiotic tissue penetration ระดับยาในตำแหน่งที่มีการติดเชื้อ ATB effective;in-vitro, unable to reach the site of infection Poor Tissue Concentration of ATB Tigecycline Urinary tract (Lung, Blood) Daptomycin Lung 1st- and 2nd-gen ceph. blood-brain barrier Macrolides blood-brain barrier removed for cure, since microbes causing infections associated with prosthetic joints, shunts, and intravenous lines produce which usually require surgical drainage for cure

CHOOSING ATB BASED SOLELY ON SPECTRUM Bectericidal vs Bacteriostatic therapy การออกฤทธิ์ของยาในการยับยั้งการติดเชื้อ Bactericidal agents cause death and disruption of the bacteria Disruption of cell wall ß-lactams cell membrane daptomycin Bacterial DNA fluoroquinolones Bacteriostatic agents inhibit bacterial replication without killing the organis inhibiting protein synthesis sulfonamides tetracyclines macrolides The distinction is not absolute, and some agents that are bactericidal against certain organisms may only be bacteriostatic *Bactericidal agents are in the serious infections to achieve rapid cure such as endocarditis and meningitis

PROLONGED USE OF IV ANTIBIOTICS IV-to-PO switch therapy เปลี่ยนยาฉีดเป็นยารับประทาน Barrier for intravenous-to-oral (IV-to-PO) นิสัยไม่ดีเก่าๆแก้ยาก!!!! “ Physicians are creatures of habit, and old habits die hard”… Burke A. Cunha, MD (Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501, USA) IV therapy: first used for serious systemic infections Many infections susceptible to IV ATB IV therapy: the preferred mode of ATB administration

Why! Oral antibiotic therapy Advantages (ข้อดี) Disadvantages (ข้อด้อย) Lower ATB acquisition cost No IV ATB administration costs Rapid gastrointestinal absorption (<1 h) even in critically ill patients Eliminates IV-line infections Decreased length of hospital stay Earlier discharge Should not be used in those with impaired gastrointestinal absorption Patient in shock, begin therapy intravenously Increased ecological hazard (oral agent with poor bioavailability potentiate colonization) Cunha BA. Antibiotic essentials. 5th edition. 2006 Cunha BA. Drugs Today 2001;37:311–9 Quintiliani R, Nightingale CH. Infect Dis Clin Practice 1994;3(Suppl):161–7

Cost-effectiveness! IV-to-Oral Switch therapy The study of cost-effectiveness Cost saving/reduction Tuscon, AZ, USA, 2007 by Patanwala AE. from $11,479 to $8923 per a treatment course Switzerland, 2003 von Gunten V. 44 to 92 Euros per a treatment course Buffalo, NY, USA, 2002 by Paladino JA. from $6,145 to $5,265 per a treatment group Hartford, CT, USA, 1993 by Nightingale CH. $150,000 - $250,000 per year Vancouver, 1994 by Jewesson P. $C 21,5 00 per year Netherland, 1992 by Janknegt NG 67,160 per patient per day Annual Surgical site of infection CAP

When! Oral antibiotic therapy Oral absorption in the critically ill - Oral ATBwith good/excellent bioavailability rapidly/well absorbed achieve blood/target tissue levels **except septic shock - Per oral  per nasogastric tube or per percutaneous enteroscopic gastroscopy tube

Requirements of an oral ATB Antibiotic Factors ปัจจัยด้านยาต้านจุลชีพ Host Factors ปัจจัยด้านผู้ป่วย high degree of activity against presumed/known pathogens high bioavailability low resistance potential well tolerated with a good safety profile patient able to sufficiently absorb an oral antibiotic avoid in patients with impaired gastrointestinal absorption

Duke University Medical Centre Criteria ตัวอย่าง Absent of infectious indications requiring parenteral ATB febrile neutropenia significantly immunocompromised meningitis osteomyelitis endocarditis septic shock disseminated viral infections such as HSV Sequential ATB therapy page 602 * Modified from Lelekis and Gould. J Hosp Infect 2001; 48: 249 J Infect 1998; 37(suppl 1):3-9

Duke University Medical Centre Criteria Absent of infectious indications requiring parenteral ATB Infection is not presently serious or life-threatening Improved of signs or symptoms of infection Afebrile or has consistent improvement in fever > 24 hrs WBC count is normalizing Normal gastrointestinal absorption of drugs and the patient is able to receive enteral therapy Sequential ATB therapy page 602 * Modified from Lelekis and Gould. J Hosp Infect 2001; 48: 249 J Infect 1998; 37(suppl 1):3-9

What are types of IV-to-oral switch? Stream-lining: converting from broad-spectrum ATB to single agent with narrow spectrum Sequential: converting IV to oral agents with same chemical Switch: converting IV to oral agents with identical potency Step-down: converting IV to oral agents with reduced Use antibiotics with similar spectrum Sequential therapy is the best option Step down therapy is not recommended unless necessary Use antibiotics with good oral bioavailability (>50%) Consider PK/PD of both IV/oral regimens ศาสตราจารย์แพทย์หญิงนลินี อัศวโภคี

Bioavailability of oral antibiotics > 95% 90-95% 80-89% < 80% Cephalexin Clindamycin Amoxicillin Amoxycillin/ Clavulanic acid Cotrimoxazole Doxycycline Ampicillin/ Sulbactam Clarithromycin Levofloxacin Ofloxacin Ciprofloxacin Dicloxacillin Linezolid Tetracycline Cefditoren pivoxil Metronidazole Cefixime Ceftibuten Cefuroxime axetil Cefpodoxime proxitil Keflex Meiact Cefspan Cedax Zinacef Vantin

USE OF COMBINATION THERAPY? Monotherapy; preferred over combination therapy -> reduces the risk of; drug interactions medication errors missed doses and side effects usually less expensive than combination therapy Combination Therapy drug synergy extended spectrum . Since drug synergy is difficult to assess and the possibility of antagonism always exists, antibiotics should be combined for synergy only if synergy is likely based on experience or actual testing. Combination therapy is not effective in preventing antibiotic resistance, except in very few situations. Antibiotic

Combination Therapy: Synergy β-lactams and aminoglycosides exhibits synergism for treatment of endocarditis caused by; Enterococcus spp. A viridans group streptococci Staphylococcus aureus Penicllin and clindamycin: clinical synergism for treatment of S. pyogenes infection

Combination vs Monotherapy BL vs BL+aminoglycoside Retrospectively analyzing a series of bacteremia combination therapy was an independent protective factor in - shock (OR, 0.6; 95% CI, 0.4 - 0.9) - neutropenia (OR, 0.5; 95% CI, 0.3 - 0.9) Antimicrob Agents Chemother 2010;54(9):3590-6 A meta-analytic/meta-regression study No overall mortality/clinical response benefit with combination The presence of shock/critical illness, the more severely ill group -> increased efficacy in combination Increased risk of death in low- risk patients whom exposed to combination therapy Crit Care Med.2010;38(8):1651-64

Combination vs Monotherapy A propensity-matched analysis multicenter, cohort study Monotherapy vs beta-lactams in combination with aminoglycosides, fluoroquinolones, or macrolides/clindamycin Early combination antibiotic therapy is associated with decreased mortality in septic shock Antimicrob Agents Chemother 2010;54(9):3590-6 A systematic review and meta-analysis of randomised trials BL vs BL+AMG combination No advantage to combination among pts with GN (1835 pts) or P. aeruginosa infections (426 pts) No difference in the rate of development of resistance Nephrotoxicity: significantly more common with combination BMJ 2004;328(7441):668 Combination therapy was also associated with significant reductions in intensive care unit (437 of 1223 [35.7%] vs. 352 of 1223 [28.8%]; odds ratio, 0.75; 95% confidence interval, 0.63-0.92; p = .0006) and hospital mortality (584 of 1223 [47.8%] vs. 457 of 1223 [37.4%]; odds ratio, 0.69; 95% confidence interval, 0.59-0.81; p < .0001). The use of combination therapy was associated with increased ventilator (median and [interquartile range], 10 [0-25] vs. 17 [0-26]; p = .008) and pressor/inotrope-free days (median and [interquartile range], 23 [0-28] vs. 25 [0-28]; p = .007) up to 30 days.

Combination vs monotherapy PRO ข้อมูลสนับสนุน CON ข้อมูลคัดค้าน Synergistic effect – in vitro Good outcome in severely ill (Septic shock, neutropenia) Higher rate of microbiological cure Higher rates of resistance isolates Higher rates of side effects Lack of the power to showed the consistent of good outcome No top level of grading evidence CID 2011;53 (Suppl 2):S33 ICAAC 2011, Chicago & IDSA 2011 Sa n Francisco, USA

COMBINATION THERAPY TO PREVENT ATB RESISTANCE Antibiotic combinations that prevent resistance Anti-pseudomonal penicillin + aminoglycoside Rifampin + other TB drugs (INH, ethambutol, pyrazinamide) (3) 5-flucytosine + amphotericin B (4) Anti-retroviral drugs in HIV/AIDS therapy . Since drug synergy is difficult to assess and the possibility of antagonism always exists, antibiotics should be combined for synergy only if synergy is likely based on experience or actual testing. Combination therapy is not effective in preventing antibiotic resistance, except in very few situations. Antibiotic

Commonly used antibiotic combinations that do not prevent resistance COMBINATION THERAPY TO PREVENT ATB RESISTANCE Commonly used antibiotic combinations that do not prevent resistance ยาที่นิยมใช้ให้หลายขนาน แต่ในความเป็นจริงไม่ได้ป้องกันเชื้อดื้อยา TMP-SMX Ceftazidime in combination with any other ATB Ciprofloxacin in combination with any other ATB (4) Imipenem in combination with any other ATB (5) Most other ATB combinations . Since drug synergy is difficult to assess and the possibility of antagonism always exists, antibiotics should be combined for synergy only if synergy is likely based on experience or actual testing. Combination therapy is not effective in preventing antibiotic resistance, except in very few situations. Antibiotic

OVERRELIANCE ON MICROBIOLOGY RESULTS In vitro data do not differentiate between colonizers and pathogens determine whether the organism is a pathogen or a colonizer colonization should not be treated In vitro data do not necessarily translate into in vivo efficacy "sensitive" or "resistant" to a given antibiotic in-vitro do not necessarily reflect in-vivo activity

OVERRELIANCE ON MICROBIOLOGY RESULTS In vitro susceptibility testing is dependent on the microbe, methodology, and ATB concentration; assumes the isolate was recovered from blood, and is being exposed to serum concentrations Usually higher ATB concentrations than in serum: bladder, urine Lower ATB concentrations than in serum: CSF, ocular In vitro data may be misleading for non-bloodstream infections In-vitro susceptibility testing by the microbiology laboratory assumes the isolate was recovered from blood, and is being exposed to serum concentrations of an antibiotic given in the usual dose. For example, a Klebsiella pneumoniae isolate obtained from the CSF may be reported as "sensitive" to cefazolin even though cefazolin does not penetrate the CSF. Likewise, E. coli and Klebsiella urinary isolates are often reported as "resistant" to ampicillin/sulbactam despite in-vivo efficacy, due to high antibiotic concentrations in the urinary tract. Because microbial susceptibility is concentration-dependent, antibiotics should be prescribed at the usual recommended doses. Attempts to lower cost by reducing dosage may decrease antibiotic efficacy (e.g., cefoxitin 2 gm IV inhibits ~ 85% of B. fragilis isolates, whereas 1 gm IV inhibits only ~ 20% of strains).In-vitro susceptibility testing by the microbiology laboratory assumes the isolate was recovered from blood, and is being exposed to serum concentrations of an antibiotic given in the usual dose. Since some body sites (e.g., bladder, urine) contain higher antibiotic concentrations than found in serum, and other body sites (e.g., CSF) contain lower antibiotic concentrations than found in serum, in-vitro data may be misleading for non-bloodstream infections. For example, a Klebsiella pneumoniae isolate obtained from the CSF may be reported as "sensitive" to cefazolin even though cefazolin does not penetrate the CSF. Likewise, E. coli and Klebsiella urinary isolates are often reported as "resistant" to ampicillin/sulbactam despite in-vivo efficacy, due to high antibiotic concentrations in the urinary tract. Because microbial susceptibility is concentration-dependent, antibiotics should be prescribed at the usual recommended doses. Attempts to lower cost by reducing dosage may decrease antibiotic efficacy (e.g., cefoxitin 2 gm IV inhibits ~ 85% of B. fragilis isolates, whereas 1 gm IV inhibits only ~ 20% of strains).In-vitro susceptibility testing by the microbiology laboratory assumes the isolate was recovered from blood, and is being exposed to serum concentrations of an antibiotic given in the usual dose. Since some body sites (e.g., bladder, urine) contain higher antibiotic concentrations than found in serum, and other body sites (e.g., CSF) contain lower antibiotic concentrations than found in serum, in-vitro data may be misleading for non-bloodstream infections. For example, a Klebsiella pneumoniae isolate obtained from the CSF may be reported as "sensitive" to cefazolin even though cefazolin does not penetrate the CSF. Likewise, E. coli and Klebsiella urinary isolates are often reported as "resistant" to ampicillin/sulbactam despite in-vivo efficacy, due to high antibiotic concentrations in the urinary tract. Because microbial susceptibility is concentration-dependent, antibiotics should be prescribed at the usual recommended doses. Attempts to lower cost by reducing dosage may decrease antibiotic efficacy (e.g., cefoxitin 2 gm IV inhibits ~ 85% of B. fragilis isolates, whereas 1 gm IV inhibits only ~ 20% of strains).

USE OF ANTIBIOTICS FOR PERSISTENT FEVER The most common error in the management of persistent fevers Changing/adding additional antibiotics instead of determining the cause ปรับยาไม่มีการวินิจฉัย More important to reassess the patient Causes of prolonged fevers include Non-infectious medical disorders (e.g., SLE) Drug fever In-vitro susceptibility but inactive in-vivo

USE OF ANTIBIOTICS FOR PERSISTENT FEVER Inadequate spectrum Inadequate ATB blood and tissue levels Undrained abscess, Foreign body-related infection Special barrier CSF Organ hypoperfusion diminished blood supply - chronic osteomyelitis in diabetics) ATB inactivation, ATB antagonism) Fungal superinfection Treating colonization ATB-unresponsive infectious diseases; viral infections Undiagnosed causes of leukocytosis Low-grade fevers should not be treated with prolonged courses of ATB

NON-ATB THERAPY OF INFECTION Operative drainage or débridement Get rid of the high organism burden (abscesses) Corticosteroid: conjunction with ATB therapy Bacterial meningitis Tuberculous meningitis Pneumocystis pneumonia in AIDS Temporary discontinuation or dose reduction of immunosuppressive agents CMV disease in organ transplant recipients or patients with rheumatologic disorders Probiotics -Sx: abscess which the penetration and activity of antimicrobial agents are often inadequate. -Probiotics (such as Lactobacillus and Saccharomyces species) are occasionally used in the management of colitis caused by Clostridium difficile, with the hope of restoring the normal flora that has been altered by antimicrobial administration. 49. Kaul R, McGeer A, Norrby-Teglund A, et al; The Canadian Streptococcal Study Group. Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome—a comparative observational study. Clin Infect Dis. 1999;28(4):800-807. Lancet Infect Dis 2004;4(3):139-143 N Engl J Med 2004;351(17):1741-1751 N Engl J Med 1990;323(21):1444-1450 Anaerobe 2009;15(6):274-280

PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB therapy Prolonged courses of ATB therapy Potential for adverse reactions Problems with adherence Selection of ATB-resistant organisms High cost

PROLONGED ATB THERAPY OR PROPHYLAXIS Potential for adverse reactions Direct Allergy Toxicity Drug-drug interaction Therapeutic failure Indirect Effects on commensal flora Human Clostridium difficile infection Animal Increased chance of infection with drug-resistant pathogens Effects on environmental flora

PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB therapy Examples of optimal duration, shorter but effective course Uncomplicated UTI in women 3 days Community-acquired pneumonia 5 days Ventilator-associated pneumonia 8 days ** not sufficient for the treatment of infections due to P. aeruginosa or in immunocompromised patients Endocarditis, osteomyelitis, 4-6 weeks and intra-abdominal abscesses Cochrane Database Syst Rev 2005;(2):CD004682 Clin Infect Dis. 2003;37(6):752-760 JAMA. 2003;290(19):2588-2598

PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB prophylaxis Presurgical ATB prophylaxis To reduce the incidence of postoperative surgical site infections The ATB should cover the most likely organisms and be present in the tissues At the initial incision Clin Infect Dis. 2004;38(12):1706-1715

PROLONGED ATB THERAPY OR PROPHYLAXIS Duration of ATB prophylaxis Presurgical ATB prophylaxis Adequate serum concentrations during the procedure A single dose of a cephalosporin (such as cefazolin) within 1 hour before the initial incision Avoiding unnecessary broad-spectrum ATB Duration; should not exceed 24 hours Clin Infect Dis. 2004;38(12):1706-1715

Case Study 48-year-old man Fever 8 wks Left cervical lymphadenopathy 8 wks Nausea, vomiting, and hiccup 8 wks Weight loss 5kg/6wks Chronic hepatitis C infection 3 yrs Hepatomegaly with jaundice Anemia

Differential diagnosis Lymphoma TB/Nontuberculous mycobacterium (NTM) Infectious mononucleosis (EBV) Solid tumor: CA nasopharynx, CAesophagus, Hepatoma *HIV (Opportunistic infection or lymphoma) Histoplasmosis CMV Cat scratch disease Hepatitis C

Case Study 58-year-old man Necessary Investigations were performed Blood smear H/C for bacteria, mycobacteria, fungus LN biopsy BM aspiration and biopsy CT; Nasopharyx, thorax, abdomen He was treated with ceftriaxone 2g iv, OD for 3 days. Fever was still high and LFT (hepatocellula rinjury) was worsening with anemia, thrombocytopenia, leucopenia. The ATB was changed to meropenem at day-3 of ceftriaxone. No appropriate provisional diagnosis Use ATB to treat prolonged fever Changed ATB without reassessment the patient

Case Study Bone marrow and LN: Lymphoma with hemophagocytis Treatment - IVIg, Dexamethasone IV -> clinical improved Chemotherapy The patient developed febrile neutropenia. Septic work up was performed and meropenem was prescribed for 5 days and the fever was decreasing while neutrophil was increasing from 150 to 820. Sputum culture grew A. baumannii on day-5 of meropenem then colistin was prescribed, continued meropenem. Use ATB based on culture result to treat colonization Changed ATB without reassessment the patient ATB as a risk of adverse effect; renal toxicity without any benefit ATB cost, IV administration cost but no “cost effectiveness

Case Study The patient still has low grade fever after 7 days of colistin, neutrophil was increasing from 150 to 1,020. Cr rising from 1.2 -> 3.2, sputum C/S grew A. baumannii but resist to colistin. Clinical is similar to previously but this time, no ATB was prescribed. Increasing adverse effect; renal toxicity without any benefit

Messages What is the damage of inappropriate ATB? Morbidity & mortality Adverse effects High cost-ineffectivesness Emergence of resistant How to get appropriate ATB? An accurate diagnosis The need for ATB, which ATB and timing of ATB Rx Using the narrowest spectrum and shortest duration of Rx Switching to oral agents ASAP Dosing regimens of different agents Host characteristics Non-ATB interventions

Pornpan Koomanachai, MD Thank you Pornpan Koomanachai, MD