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antimicrobial resistance

1. ANTIBIOTIC RESISTANCE & ANTIMICROBIAL STEWARSHIP DR MEGHANA B S ASSISTANT PROFESSOR DEPARTMENT OF GENERAL MEDICINE ESIC & PGIMSR

2. COMPETENCIES:

3. AMR DEVELOPMENT RESISTANCE TO ANTIMICROBIAL AGENT BY MICROORGANISM INTRINSIC RESISTANCE Inherently present in nature. Aminogycosides - anerobes Vancomycin - Gram negative Colistin - Burkholderia, Proteus

4. Acquired resistance Initially sensitive to antibiotic later acquire genes to develop resistance to particular organism ANTIBIOTIC PRESSURE SELECTION OF RESISTANT ISOLATES MULTIPLICATION OF RESISTANT STRAINS SPREAD IN THE ENVIRONMENT DUE TO POOR INFECTION CONTROL PRACTICE Therapeutic challenge

5. Poor infection control practices

6. CAUSES OF ANTIBIOTIC RESISTANCE CRISIS Misuse and Overuse of antibiotic Inappropriate prescription Extensive agriculture use of antibiotics Availability of fewer newer antibiotics

7. Misuse and Overuse of Antibiotics DIARRHOEA URTI SORETHROAT DENGUE , CHIKUNGUNYA, MALARIA ASYMPTOMATIC BACTERIURIA OVERLAPPING SPECTRA double gram negative coverage REDUNCTANT ANTIBIOTIC -meropenam and metronidazole INEFFECTIVE ANTIBIOTIC Cloxacillin -MRSA INFERIOR ANTIBIOTIC

8. ANTIMICROBIA L S T EWARDSHIP Definition The right antibiotic for the right patient at the right time with the right dose the right route the least harm to the patient and future patient

9. Antimicrobial stewardship consists of systematic measurement and coordinated interventions designed to promote the optimal use of antimicrobial agents, including their choice, dosing, route, and duration of administration . This applies not only to antibacterial agents, but antifungals , antivirals, and antiretrovirals as well. The primary goal of antimicrobial stewardship is to optimize clinical outcomes while minimizing unintended consequences of antimicrobial use. Additional benefits include improving susceptibility rates to targeted antimicrobials and optimizing resource utilization

10. PRINCIPLES OF OPTIMAL ANTIMICROBIALUSE INITIATING EMPIRIC ANTIBIOTIC THERAPY — Initiation of empiric antibacterial therapy consists of the following: ● Choosing the optimal antimicrobial regimen (after obtaining culture[s] from relevant sites), taking into consideration: The severity and trajectory of illness The likely pathogens and their anatomic source (with consideration of source control), based on information from Gram stain and other rapid tests as appropriate The likelihood of drug resistance (eg, known colonization with resistant pathogens, recent antimicrobial use, exposure to health care facilities, local resistance patterns) Host factors, including those that may preclude use of a particular antimicrobial class (eg, allergy), increase the risk of toxicity (eg, marginal or unstable renal function), or influence spectrum of coverage (eg, immunocompromise) Determining the appropriate dosing and route of administration (eg, intravenous in the critically ill) Initiating antimicrobial therapy as promptly as possible

11. We suggest prescribing 2 antipseudomonal antibiotics from different classes for the empiric treatment of suspected VAP only in patients with any of the following: a risk factor for antimicrobial resistance (Table 2), patients in units where >10% of gram-negative isolates are resistant to an agent being considered for monotherapy, and patients in an ICU where local antimicrobial susceptibility rates are not available

12. we often use empiric antibiotics in the following circumstances: ●Severe disease (fever, more than six stools per day, volume depletion warranting hospitalization) ●Features suggestive of invasive bacterial infection, such as bloody or mucoid stools (except in cases of nonsevere disease when fever is low or absent) ●Host factors that increase the risk for complications, including age >70 years old and comorbidities such as cardiac disease and immunocompromising conditions

13. Tailoring antimicrobial therapy ("antimicrobial time-out") In patients receiving empiric antimicrobial therapy, the regimen should be re-evaluated on a continuing basis as the clinical status evolves and microbiology results become available (often after 48 to 72 hours). At this point, an "antimicrobial time-out" should be performed, in which microbiology results are reviewed and antimicrobial therapy is adjusted from empiric to definitive antimicrobial therapy. The spectrum of coverage may be narrowed or broadened as appropriate, the dose may be adjusted as needed, and unnecessary components of the regimen should be eliminated. If it is apparent that the patient's clinical status is not the result of bacterial infection, antimicrobials may be discontinued altogether. During the antimicrobial time-out, the indication and duration of antimicrobial therapy should be estimated and stated in the medical record.

14. Tran sition from i ntra v enous to oral therapy Stewardship programs can develop a protocol defining the appropriate patients for this intervention, taking into account the indication for therapy, the suitability of the oral agent's coverage and bioavailability, the patient's clinical stability, and the patient's ability to tolerate oral or enteral medications.

15. Using the shortest effective duration of therapy A critical element in the safe use of antimicrobials lies in restricting their administration to the minimum duration required for maximum efficacy . The appropriate durations of therapy are well studied for a number of infectious disease syndromes, such as pneumonia, Staphylococcus aureus infection, candidemia, and complicated intra-abdominal infections

16. The use of serum procalcitonin measurements has been demonstrated to provide the clinician with confidence to discontinue therapy in critically ill patients with suspected bacterial pneumonia or undifferentiated sepsis

17. Experts suggest that daily reviews of antibiotic selection , until a definitive diagnosis and treatment duration are established, can optimize treatment. Provider-led reviews of antibiotics can focus on four key questions : Does this patient have an infection that will respond to antibiotics ? Have proper cultures and diagnostic tests been performed ? Can antibiotics be stopped or improved by narrowing the spectrum (also referred to as “de-escalation”) or changing from intravenous to oral ? How long should the patient receive the antibiotic(s), considering both the hospital stay and any post-discharge therapy ?

18. Pharmacokinetic monitoring Optimal antimicrobial dosing and administration necessitate adherence to relevant pharmacokinetic (PK)/pharmacodynamics principles. Individual PK monitoring and adjustment programs should be implemented for patients receiving aminoglycosides or vancomycin

19. TIGECYCLINE LINEZOLID MAXIMUM ONCE DAILY DOSING TO HIT PROPER CONCENTRATION CONSTANT LEVELS OF ANTIBIOTICS BD/TID Choose drug with longest half life

20. For concentration-dependent antibiotics, a high initial dose is essential for maximum bactericidal effect, and for aminoglycosides, a high initial dose has been associated with a lower mortality. However, R enal function plays no role in the calculation of the LD. For time-dependent antibiotics, where the critical factor is time above the MIC, the initial dose may not be crucial for pharmacokinetic effect; however, a large initial dose is often chosen to ensure good tissue penetration.

21. The V olume of distribution of hydrophilic agents (which disperse mainly in water) will be altered by changes in the permeability of the microvascular endothelium and consequent alterations in extracellular body water; a well-recognized phenomenon in the pathophysiology of sepsis. This will result in a larger predicted V and thus a larger required LD. In contrast, lipophilic agents have a greater affinity for adipose tissue, therefore an obese patient may require a higher than predicted dose of a lipophilic antibiotic to achieve the targeted plasma concentration.

22. STEWARDSHIP PROGRAM INTERVENTIONS AMS TEAM ID PHYSICIAN, INFECTION CONTROL SPECIALIST CLINICAL MICROBIOLOGIST CLINICAL PHARMACIST STEWARDSHIP NURSES

23. ANTIMICROBIAL STEWARD Infectious disease physician Clinical microbiologists Medicine consultant

24. Framing antimicrobial policy pocket handbook. prepared by AMS team. Compliant to the standard national and international antibiotic guideline and local antibiogram pattern.

25. UTI - E. COLI, STAPHYLOCOCCUS SAPROPHYTICUS, KLEBSIELLA PNEUMONIA CIPROFLOXACIN 500 MG BD 5 DAYS

26. E. COLI, STAPHYLOCOCCUS SAPROPHYTICUS, KLEBSIELLA PNEUMONIA, PROTEUS MIRABILIS AMIKACIN 1 GM OD GENTAMYCIN 7MG/KG/DAY OD 14 DAYS CEFOPERAZONE SULBACTAM 3 GM IV 12 TH HOURLY ERTAPENAM 1GM IV OD

27. E COLI, KLEBSIELLA PNEUMONIA,PROTEUS MIRABILIS, PSEUDOMONAS AEROGINOSA, ENTEROCCUS SPECIES PIPERACILLIN TAZOBACTAM 4.5GM IV 6 TH HOURLY OR AMIKACIN 1 GM IV OD OR CEFOPERAZONE SULBACTAM 3 GM IV 12 HOURLY Alternatives- Imipenam, Meropenam

28. Not to routinely add anaerobic coverage for suspected aspiration pneumonia unless lung abscess or empyema is suspected Patients who aspirate gastric contents are considered to have aspiration pneumonitis. Many of these patients have resolution of symptoms within 24 to 48 hours and require only supportive treatment, without antibiotics

29. s. pnuemonia, haemophilus influenza, M. catarrhalis Ceftriaxone 1 gm iv bd Levofloxacin 500 mg od 5-7 days Alternatives- Azithromycin 500 mg od 5 days Piperacillin tazobactam 4.5 gm iv tid

30. Pseudomonas aeroginosa,K. pneumonia ESBL,Acinetobacter specis Meropenam 1g iv tid Alternative - Colistin iv 5 MU LOADING DOSE 2 MU iv 8 hourly

31. Lung abscess, Empyema S pneumonia, Ecoli, klebsiella, Pseudomonas aeroginosa, S. aureus , anaerobes Piperacillin - Tazobactam 4.5 gm iv 6th hourly or Cefoperazone sulbactam 3 gm iv 12 hourly ADD Clindamycin 600-900 mg IV 8 hourly 3-4 weeks

32. Gastroenteritis

33. GE WITH SEVERE DEHYDRATION Ecoli, Salmonella, Cl difficle Ciprofloxacin 500 mg IV BD + Metronidazole 500 mg tid IV 5DAYS

34. Bacillary Dysentry Shigella sp, Campylobacter, non typhoidal salmonellosis Ceftriaxone 2 gm iv od 5 dAYS or Oral cefixime 5 dyas For Camylobacter doc- Azithromycin Shiga toxin producing E.coli- Antibiotics not recommended due to HUS

35. Hospital acquired Diarrhoea C.difficle Metronidazole 400 mg oral tds 5days severe disease- Vancomycin 250 mg oral 6 hourly

36. Acute bacterial meningitis S pneumonia,H influenza, Neisseria meningitidis Ceftrixone 2 gm iv 12 th hourly Cefotaxime 2 gm iv 4 -6 th hourly - 10-14 days No need to add VANCOMYCIN as primary agent as ceftriaxon eresistant pneumococcus is not coomon in india Listeria is also rare in India so Ampicillin also not indicated

37. STEWARDSHIP PROGRAM INTERVENTIONS Antimicrobial oversight — Antimicrobial oversight is the foundation of any stewardship program and should include one or both of the following strategies Prospective audit and feedback (PAF) Preauthorization

38. Prospective audit and feedback (PAF) I n programs that utilize PAF, trained staff (typically stewardship pharmacists or infectious disease physicians) review antimicrobial orders and provide verbal or written recommendations to prescribers regarding optimization of antimicrobial use. The intervention does not delay the first dose of antimicrobial therapy, and acceptance of recommendations is voluntary. With this approach, prescriber autonomy in clinical decision-making is preserved .

39. Thrice-weekly audit and feedback programs in community hospitals have been associated with reduced antimicrobial utilization and cost savings. Once-weekly programs targeting asymptomatic bacteriuria in long-term care facility residents also reduced antimicrobial use

40. Preauthorization In programs that utilize preauthorization, approval is required (by an infectious disease physician or pharmacist) before certain antimicrobial agents may be administered

41. Facility-specific clinical protocols — Antimicrobial stewardship programs should develop facility-specific clinical practice guidelines and pathways for common infections based on local epidemiology, susceptibility patterns, and drug availability or preference. Infectious disease syndromes include community-acquired pneumonia, urinary tract infections, skin and soft tissue infections, fever, and neutropenia.

42. clinical guidelines developed by national institutions are comprehensive, but their recommendations may be difficult to apply to individual patients. Institution-specific protocols can streamline information most relevant to daily practice into an easy-to-use format. Within these protocols, stewardship programs can highlight appropriate empiric therapy, reinforce de-escalation of antimicrobials based upon clinical and microbiologic data, encourage a switch from intravenous to oral therapy, and recommend an appropriate duration of therapy.

43. Engaging staff — The presence of engaged infectious disease physicians is critical. Nurses are important but underutilized members of the antimicrobial stewardship team . Nurses can assist in intravenous to oral transitions, prompting "antibiotic timeouts" and optimizing the collection of specimens for microbiologic culture to avoid contamination , which may lead to suboptimal antibiotic use.

44. Reducing the incidence of C. difficile infection Antimicrobial stewardship programs should implement interventions that reduce the incidence of C. difficile infection (CDI), in collaboration with infection control programs . In general, CDI is a "two-hit" disease: it requires the acquisition of C. difficile and alteration of the intestinal microbiome, most often by exposure to antimicrobials. stewardship programs target the reduction of exposure to certain antimicrobials suggested to increase risk of CDI (such as fluoroquinolones, clindamycin, and cephalosporins).

45. THE MICROBIOLOGY LABORATORY AND STEWARDSHIP The clinical microbiology laboratory has an integral role in promoting appropriate antimicrobial use. The microbiology laboratory compiles antibiogram information at intervals (often annually) and makes decisions regarding implementation of rapid diagnostic tests in addition to ongoing communication with clinicians and infection control practitioners

46. Antibiogram — An antibiogram is a summary of antimicrobial susceptibility data for bacterial isolates recovered by a microbiology laboratory over a defined period of time (usually one year). Antibiograms may be used by clinicians to guide choice of empiric antimicrobial therapy and by stewardship programs to develop facility-specific clinical protocols and monitor resistance trends.

47. STEWARDSHIP PROGRAM METRICS Measuring antimicrobial use and cost savings — Antimicrobial use may be estimated in days of therapy (DOT) or defined daily dose (DDD); use of DOT is preferred DOT is an aggregate sum of days for which any amount of a specific antimicrobial agent is administered to a particular patient (numerator) divided by a standardized denominator. DOT refers to the number of days a patient receives an antimicrobial, regardless of the dose administered. Cost cannot be calculated easily based on DOT because dose is not included.

48. DDD aggregates the total number of grams of each antimicrobial administered during a period of time divided by a standard DDD designated by the World Health Organization (WHO). DDD underestimates the antimicrobial exposure in patients with renal failure and does not account for weight-based dosing, making this metric inappropriate for pediatric populations.

49. Outcome measures — Outcome measures in patients treated with antimicrobials for infectious disease syndromes include the following : ●Hospital and intensive care unit length of stay ●Readmission rates ●Number of patients with infection due to multidrug-resistant organisms ●Mortality due to infection ●C. difficile infection rates (hospital acquired versus all) ●Emergence of antimicrobial resistance over time

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