Rational Usage of Antibioticsdr. Rizky Perdana,SpPD,KPTI,FINASIMDivision of Tropical and Infectious DiseasesDepartment of Internal MedicineFaculty of Medicine University of SriwijayaMoh. Hoesin HospitalPrudential Use of Antibiotic in Adult

Apa itu Prudential Use of Antibiotic in Adult ???Untuk memahami nya, mari kita simak kasus-kasus pada slide berikut iniSilahkan baca baik-baik

Facta di Klinik

Curhat pasien tentang antibiotika"Kira kira 2 bulan yang lalu saya sakit tenggorokan. Lalu saya ke dokter umum diberi antibiotik Fixef 100 untuk 4 hari (8 biji). Setelah abis, tenggorok masih sakit saya ke dokter umum yang lain lagi dan mendapat volequin untuk 5 hari dan ternyata tidak juga hilang, masih saja terasa sakit terutama menelan. Saya kembali ke dokter umum pertama, dan mendapat Mezatrin selama 3 hari. Lagi2 juga masih sakit setelah Mezatrinnya abis. Saya pindahke dokter lain dan diberi Capsinat 500 untuk 5 hari (15 biji). Setelah obat itu abis ternyata masih aja sakit lagi

Akhirnya saya ke THT. Kali ini obatnya Claneksi 500 (15 biji) untuk 5 hari, setelah abis lagi-lagi masih sakit dikit, ditambah lagi Claneksi 500 (15 biji) untuk 5 hari lagi. Terus sakitnya sudah banyak berkurang saya kembali lagi dan dokter THT melihat masih ada merah dikit terus ditambah lagi Claneksi 500 (10 biji). Selain antibiotik ada juga obat2 anti alergi dan anti radang. Bersamaan dengan habisnya obat itu saya harus menjalani laparoskopi diagnostik untuk kandungan. Terus dokter kandungan memberi Claneksi 500 lagi 15 biji lagi. Waktu itu tenggorokan saya juga luka akibat selang bius sehingga sakit buat nelan. Jadi total saya menghabiskan Claneksi 500 sebanyak 55 biji dalam waktu sekitar 20 hari.

Tetapi setelah obat habis beberapa hari kemudian sakitnya muncul lagi Dok..

Malah setelah 2 minggu saya minum obat itu kok malah merasakan sering sakit perut bagian bawah dan saya pun sering mengalami diare. Saat ini saya tidak hanya mengalami sakit tenggorok yang tidak kunjung reda, malah sakit saya bertambah lagi seperti perut saya sering kram dan diare. Apakah ini efek samping obat antibiotik yang saya minum itu? dan apakah saya sudah kebal dengan antibiotik? Bolehkah minum antibiotik jangka panjang seperti saya itu? Saya takut pergi ke dokter lagi untuk sakit perut dan diare yang saya alami karena pasti mendapat antibiotika lagi. Mohon sarannya dok. Terima kasih

A worldwide problem1Associated with increased morbidity, mortality, and hospital costs1Occurs in both hospitals and the community2Antibiotic Resistance1: R. A. Kulkarni et al. Indian J Surg. 2005: Volume 67(6): 308-315.2 Ben-David D, Rubenstein E. Curr Opin Infect Dis 2002;15:151-156.

Policy & Advocacy of IDSA; July 2004 BAD BUGS, NO DRUGS As Antibiotic Discovery Stagnates A Public Health Crisis BrewsCurrent Problems of Bacterial Resistance

Perl TM. Gram Negative Bacterial Resistance in Healthcare: The Brave New World HealthcareNative Organisms

Antimicrobial Resistance: Key Prevention StrategiesPathogenSusceptible Pathogen

Consideration When Choosingan Antibacterial AgentMicrobiology Mechanism of action Antibacterial spectrumDrugPK Absorption Distribution Metabolism Excretion Optimal dosing regimenConcentrationat infection sitePathogen MICPD Time vs. concentration dependent killing Bactericidal vs. bacteriostatic activity Tissue penetration Persistence of antibacterial effectOutcome Clinical efficacy Bacterial eradication Compliance with dosing regimen Tolerability Rate of resolution Prevention of resistance (Scaglione, 2002)

Rational Antimicrobial Therapy

Factors in Choices of Antibiotics:Drug Interactions

Examples of Antibiotics-Drugs Interactions

Antibiotic Usage in Clinical Practice

Step in Infectious Diseases ManagementMicrobiological specimenMicrobiological result

Empirical Initial AntibioticsDepends on :Presumed site of infectionSuspected or known pathogensGrams stain resultsPreviously have been documented to colonize or infect the patientLocal resistance patternsLimited spectrum of antibiotics availableAllergiesCostHost factor

1. Immunocompetence2. Immunodeficiency / immunocompromized :NeutropeniaIndwelling medical devicesHospitalized patients, esp. ICU patientsNeoplasm Corticosteroid/ Cytotoxic agentBurnDiabetesTraumaDrugs user, AlcoholicElderly, neonatal, pregnancy and purpureumDialysis, implants/ prostheses Who is the Host ?

Factors Involved in Optimal Initial Antibiotic Therapy

Antimicrobial Combination: When we need?Unknown focus of infectionPolymicrobial infection, eg: abscess caused by multiple aerob and anaerob organismsDecrease resistance rate, eg: Tb treatment Decrease dose related toxicityIncrease antimicrobial potency Chambers HF. Antimicrobial agents. 2001

Strategy for Empirical Treatment

Pohan HT, 2005Antibiotic selection based on susceptibility and resistance pattern, immunity status, comorbidity, organ dysfunctionAntibiotic monotherapy or combinationEscalationDe-escalationOutpatientHospitalizedStable conditionSevere/ high riskPatient

Choosing The Right StrategyEscalation: not life threatening infectionDe-escalation:

De-escalation Approach to Antimicrobial UtilizationObtain appropriate microbial sample for culture and special stainFollow up: temp, WBC, CXR, PaO2/FiO2, haemodynamic, organ functionSearch for superinfection, abscess formation, non-infectious caused of feverKollef, Drugs 2003;63 (20): 2157YesNo

Antibiotics in De-escalation:Combining Rapid and Appropriateiv antibiotics as early as possible, within the first hourBroadspectrum active against likely bacterial/fungal pathogens, good penetration into presumed sourceReassess antimicrobial regimens dailyCombination therapy should be considered in Pseudomonas infections, neutropenic patients de-escalateStop antimicrobial therapy if cause is found to be non-infectious

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Crit Care Med 2008; 36(1): 296-327

Kumar A. et.al. Crit Care Med 2006;34:1589-96

De-escalation Approach to Antimicrobial UtilizationObtain appropriate microbial sample for culture and special stainFollow up: temp, WBC, CXR, PaO2/FiO2, haemodynamic, organ functionSearch for superinfection, abscess formation, non-infectious caused of feverKollef, Drugs 2003;63 (20): 2157YesNo

Antimicrobial Treatment based on Microbiological Culture Results Microbiological culture results

Colonization Pathogen

No treat Sensitive Resistant

Treat with Antibiotics Optimized Recommended Combination PKPD Antibiotics

Strategy in Managing MDRTreat pathogen not colonizationBased on local susceptibility dataMonotherapy or combinationOptimalization PK/PDConsidered comorbidities, organ functionPrevent transmission

Control of Antibiotic UsageAvoid antibiotic homogeneityPromote appropriate use of multiple drug classApply formulary control and restrict of specific agent or drug class that resistant Consider antibiotic cycling, rotation or mixed use of antibiotic classesDevelop and promote antibiotic guidelines and protocol based on local data

Antibiotic PolicyClassification of antibiotics Class A : Not restricted Class B : Not restricted, under supervision Class C : RestrictedImplementationEvaluation and surveillanceAuditing

Classification of Antibiotics

Class A Class B Class CAminoglicoside PenicillinCephalosporin gen.I,IIChloramphenicolFucidic acidLincosamideMacrolideNitroimidazolFluoroquinolone gen.I,IITetracylineTMP-SMXFosfomicin Polypeptide Cephalosporine gen IIIFluoroquinolone gen III-IVErtapenemVancomycin

TeicoplaninLinezolideCefepimeCefpiromeCeftazidimePip-TazoCarbapenemTygecicline

Implementation of Antimicrobial Policy in HospitalWARDMild Moderate SevereICU

CommunityHospitalOutpatientClass AClass AInpatient

Class B

Class B/CClass C

Class C

Evaluate the quantity of antibiotic usageRetrospectively from the medical recordFrom medical prescriptionEvaluate the quality of antibiotic usageUsing classification by GyssensEvaluation and Surveillance12

Evaluation category of Antibiotics Usage by GyssensI. Correct UsageII. Incorrect due to:a) Incorrect dose b) Incorrect interval c) Incorrect routeIII. Incorrect due to:a) duration too long b) duration too shortIV. Incorrect due to: Alternative drug that isa) more effective b) less toxic c) cheaper d) more specificV.No IndicationVI.Medical record is insufficient to be evaluated

Evaluation and SurveillanceSurveillance of every inpatient ward, intensive care ward, and surgery room periodically, e.g. monthly surveillance in internal medicine wardReport of surveillance periodically, e.g. report of surveillance in internal medicine ward every 6 months

AuditingPeriodically done by antibiotic team (multi department), commissioned by management of hospitalAudit of medical records, copy of prescriptions Percentage of compliance to antibiotic guideline Reward and punishment

ConclusionsTypes of antibiotic usage: empirical, definite, prophylaxis, pre-emptiveRational antibiotic therapy: rapid, appropriate, cost effectiveThe implementation of antibiotic policy to promote: rational use of antibiotics, cost-effective therapy, prevent collateral damage

ISICM PERDICI Gran Melia Hotel Jakarta,6 Juni 2009 Pkl. 14.35-14.55 WIB**Ref 3, p 151, C2, 1, L1-5

Ref 3, p 153, C1, 2, L1-7

Ref 3, p 151, C2, 1, L3-5Ref 4, p 166, C2, 4, L5-10, 5, L1-3, 5-10

CMK

Ref 1, p 3, C2, Bullets 2, 3Ref 2, p 185, C1, 1, L7-12; p 189, C2, 2, L4-7

Ref 3, p 153, C1, 2, L1-7

Ref 3, p 151, C2, 1, L3-5Ref 4, p 166, C2, 4, L5-10, 5, L1-3, 5-10

Ref 1, p 3, C1, 4, L9-11ReferencesInfectious Diseases Society of America (IDSA). Bad bugs, no drugs: As antibiotic discovery stagnatesA public health crisis brews. Available at http://www.idsociety.org/pa/ISDA_Paper4_final_web.pdf. Accessed July 2005.Cosgrove SE, Kaye KS, Eliopoulous GM et al. Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med 2002;162:185190.Ben-David D, Rubenstein E. Appropriate use of antibiotics for respiratory infections: Review of recent statements. Curr Opin Infect Dis 2002;15:151156.Colodner R, Rock W, Chazan B et al. Risk factors for the development of extended-spectrum beta-lactamase-producing bacteria in nonhospitalized patients. Eur J Clin Microbiol Infect Dis 2004;23:163167.*Once a pathogen produces infection, antimicrobial treatment may be essential. However, antimicrobial use promotes selection of antimicrobial-resistant strains of pathogens.As the prevalence of resistant strains increases in a population, subsequent infections are increasingly likely to be caused by these resistant strains.Fortunately, this cycle of emerging antimicrobial resistance / multi-drug resistance can be interrupted.Preventing infections in the first place will certainly reduce the need for antimicrobial exposure and the emergence and selection of resistant strains.Effective diagnosis and treatment will benefit the patient and decrease the opportunity for development and selection of resistant microbes; this requires rapid accurate diagnosis, identification of the causative pathogen, and determination of its antimicrobial susceptibility. Optimizing antimicrobial use is another key strategy; optimal use will ensure proper patient care and at the same time avoid overuse of broad-spectrum antimicrobials and unnecessary treatment. Finally, preventing transmission of resistant organisms from one person to another is critical to successful prevention efforts.

**Antibiotic policy in hospital should be arrange and implemented in hospital.Antibiotic policy include the rule to use antibiotics for community or hospital infections, which agent should be restricted, cycling and rotate to mixed the used of antibiotic class.Some drugs that used of nosocomial infection and resistant pathogen should be restrictly use and the usage should be controlled and recommended by infectious diseases specialist. Drugs that have resistant and ineffective to most pathogen should not to use untill the drugs become senstive again.

Implementation of antimicrobial policy need the commitment from all the physician in the hospital. Hospital antibiotics committee have an importat role for contolling the implementation of the policy.