Antibiotic stewardship

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Antibiotic stewardship:

Antibiotic stewardship Dr Bikram Gupta MD Anaesthesia PDCC in Critical Care

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“The fact that the antibiotic prescribing fraternity has not yet accepted stewardship of the emerging problem of XDR Gram-negative bacilli has given rise to an ethical dilemma both in South Africa and internationally. To delay the imminent end of the antibiotic era, it may well be time now to challenge the right of doctors to prescribe whichever antibiotic they wish, including the dosage and duration ” Brink et al, South African Med J2008;98: 586-592

What is antibiotic stewardship :

What is antibiotic stewardship Stewardship is an ethic that embodies responsible planning and management of resources. The concept of stewardship has been applied in diverse realms, including with respect to environment, economics, health, property, information, and religion, and is linked to the concept of sustainability . The term continues to be used in many specific ways, but it is also used in a more general way to refer to a responsibility to take care of something belonging to someone else.

Antibiotic stewardship : definition:

Antibiotic stewardship : definition A system of informatics, data collection, personnel, and policy/procedures which promotes the optimal selection, dosing, and duration of therapy with antimicrobial agents throughout the course of their use. An effective antimicrobial stewardship program will limit inappropriate and excessive antimicrobial use, but more importantly, will improve and optimize therapy and clinical outcomes for the individual infected patient.

Consequences of Inappropriate Rx: Collateral Damage :

Consequences of Inappropriate Rx: Collateral Damage Excessive use Inappropriate drug administration Suboptimal dosing Collateral damage Selection of drug-resistant organisms Infection with MDR pathogens Super-infection with fungal pathogens Clostridium difficile infection

Goals of antibiotic stewardship:

Goals of antibiotic stewardship Prevent or slow the emergence of antimicrobial resistance Optimize selection, dose, and duration of treatment Reduce adverse drug events including secondary infection(eg. Clostridium difficile antibiotic associated diarrhea) Reduce morbidity and mortality Reduce length of stay Reduce health care expenditure

Strategies for Antimicrobial Stewardship:

Strategies for Antimicrobial Stewardship Antimicrobial Stewardship Prospective audit of antimicrobial use with intervention and feedback Education Guidelines and clinical pathways Formulary restriction and pre- authorisation Antimicrobial cycling Combination therapy Antimicrobial order forms Parenteral to oral conversion Dose optimisation Streamlining or de-escalation

Steps for Antimicrobial Stewardship:

Steps for Antimicrobial Stewardship Step 1- formulate a plan for antibiotic selection Step 2- send appropriate cultures Step 3- start antibiotics early Step 4 – choose empirical antibiotics appropriately Step 5 – stratify the risk of infection with drug resistant organisms Step 6 – follow pharmacokinetics and Pharmacodynamics principles while prescribing antibiotics Step 7 – assess the patient daily and de-escalate antibiotics once culture results are obtained Step 8 – consider the combination of antibiotics in specific situations Step 9 – decide on duration of antibiotic therapy Step 10 – implement antibiotic stewardship program

Step 1- Formulate a plan for antibiotic selection :

Step 1- Formulate a plan for antibiotic selection Antibiotics in the ICU are given – Either empirically for presumed infection with culture report pending Prophylactically mainly perioperative Definitively when infection is documented with positive culture results. Reason for antibiotic selection should be clearly documented in the antibiotic order form, which should be audited periodically for correctness. Appropriate antibiotics should be chosen depending on local epidemiology and resistance pattern.

Step 2: send appropriate culture:

Step 2: send appropriate culture This should ideally be done prior to starting antibiotics. Blood, urine, sputum, and endotracheal secretion should be promptly transported to the microbiology laboratory and expeditiously processed.

Step 3 :Start antibiotics early :

Step 3 :Start antibiotics early Delays in effective antimicrobial coverage :- Detrimental impact on patient morbidity and mortality An increased risk of sepsis Higher costs Increased ventilator days for patients with ventilator-associated pneumonia (VAP)

Step 3 :Start antibiotics early :

Step 3 :Start antibiotics early Every hour delay in starting effective antibiotics from the onset of septic shock increases the risk of death from sepsis by 6-10%. Antibiotics should be started within 1 hour of recognition of septic shock as “time is issue”.

Step 4:choose empirical antibiotics appropriately:

Step 4:choose empirical antibiotics appropriately Empirical antibiotics should be chosen carefully as initial wrong choice increases mortality, even if antibiotic is changed appropriately after culture results are obtained. Any empiric antibiotic regimen should be reassessed and tailored as soon as culture and sensitivity results become available. This practice serves to reduce costs, decrease the incidence of super infection and minimize the development of antimicrobial resistance.

Empirical antimicrobial therapy:

Empirical antimicrobial therapy Several factors must be considered when selecting empirical antimicrobial therapy: Patient-specific factors Presumed source of infection (i.e., blood, sputum, urine, intra-abdominal) Presence of co-morbid conditions (i.e., recent surgery or trauma, chronic illness) Previous antibiotic administration history Microbiological factors Identification of the most likely pathogens and their unit-specific susceptibility patterns Pharmacologic factors Potential drug toxicity (i.e. aminoglycosides) Bioavailability Distribution to the site of infection

Empirical Antibiotic Selection:

Empirical Antibiotic Selection **Antibiotics should be tailored when susceptibilities become available** Organism Antibiotic Alternative Gram-positive organisms Staphylococci aureus Cefazolin or Vancomycin Linezolid Coagulase -negative staphylococci Vancomycin Linezolid S. pneumoniae Ceftriaxone Moxifloxacin Enterococcus faecalis Ampicillin +/- Gentamicin Vancomycin +/- Gentamicin Enterococcus faecium Linezolid Quinupristin / dalfopristin

Empiric Antibiotic Selection:

Empiric Antibiotic Selection **Antibiotics should be tailored when susceptibilities become available** Organism Antibiotic Alternative Gram-Negative organisms Serratia * Piperacillin / tazobactam / Gentamicin β- lactam / Ciprofloxacin or Ciprofloxacin / Aminoglycoside Pseudomonas aeruginosa * Piperacillin / tazobactam / Tobramycin Acinetobacter* Cefepime / Gentamicin Citrobacter * Cefepime / Gentamicin Enterobacter * Piperacillin / tazobactam / Gentamicin The “SPACE” pneumonic can be used to remember gram-negative organisms that should be double-covered until susceptibility results are available.

Empiric Antibiotic Selection:

Empiric Antibiotic Selection Gram-negative organisms Organism Antibiotic Alternative E. coli (non-ESBL isolate) Cefazolin Gentamicin Klebsiella (non-ESBL isolate) Cefazolin Gentamicin or Quinolone Haemophilus influenzae Azithromycin Cefuroxime E. coli or Klebsiella (ESBL producer) Meropenem Stenotrophomonas maltophilia Trimethoprim / sulfamethoxazole Ticarcillin / clavulanic acid

CDC RECOMMENDATIONS FOR PRUDENT VANCOMYCIN USE:

CDC RECOMMENDATIONS FOR PRUDENT VANCOMYCIN USE SITUATIONS IN WHICH THE USE OF VANCOMYCIN IS APPROPRIATE OR ACCEPTABLE For treatment of serious infections caused by beta- lactam -resistant gram-positive microorganisms. For treatment of infections caused by gram-positive microorganisms in patients who have serious allergies to beta- lactam antimicrobials. When antibiotic-associated colitis fails to respond to metronidazole therapy or is severe and potentially life-threatening. Prophylaxis, as recommended by the American Heart Association, for endocarditis following certain procedures in patients at high risk for endocarditis . Prophylaxis for major surgical procedures involving implantation of prosthetic materials or devices at institutions that have a high rate of infections caused by MRSA or MRSE.

SITUATIONS IN WHICH THE USE OF VANCOMYCIN SHOULD BE DISCOURAGED:

SITUATIONS IN WHICH THE USE OF VANCOMYCIN SHOULD BE DISCOURAGED Routine surgical prophylaxis other than in a patient who has a life-threatening allergy to betalactam antibiotics. Empiric antimicrobial therapy for a febrile neutropenic patient. Treatment in response to a single blood culture positive for coagulase-negative staphylococcus, if other blood cultures taken during the same time frame are negative.

SITUATIONS IN WHICH THE USE OF VANCOMYCIN SHOULD BE DISCOURAGED:

SITUATIONS IN WHICH THE USE OF VANCOMYCIN SHOULD BE DISCOURAGED Systemic or local prophylaxis for infection or colonization of indwelling central or peripheral intravascular catheters. Selective decontamination of the digestive tract. Eradication of MRSA colonization. Primary treatment of antibiotic-associated colitis. Routine prophylaxis for patients on CAPD or HD. Use of vancomycin solution for topical application or irrigation.

Step 5: Stratify the risk of infection with drug-resistant organisms :

Step 5: Stratify the risk of infection with drug-resistant organisms The patient should be assessed for risk of infection with multidrug-resistant bacteria. If one or more risk factors are present ,antibiotic choice should be broadened to cover these organisms.

Risk factor for drug-resistant bacteria:

Risk factor for drug-resistant bacteria Antimicrobial therapy in preceding 90 days Current hospitalization of 5 days or more High frequency of antibiotic resistance in the community or in the specific hospital unit Immunosuppressive disease and/or therapy Hospitalization for 2 days or more in preceding 90 days Residence in the nursing home or extended care facility

Risk factor for drug-resistant bacteria:

Risk factor for drug-resistant bacteria Chronic dialysis within 30 days Home infusion therapy(including antibiotic) Home wound care Having a family member with a recent history of infection with multidrug resistant pathogen.

Step 6: follow pharmacokinetic and pharmacodynamic principles while prescribing antibiotics:

Step 6: follow pharmacokinetic and pharmacodynamic principles while prescribing antibiotics Give adequate intravenous dose Give antibiotics that penetrate in adequate concentration into the presumed source of sepsis. Time dependant antibiotics like ß- lactams (maximum bacterial inhibition depends on time above minimum inhibitory concentration) should be given as a continuous infusion.

The Interrelationship of Hydrophilicity and Lipophilicity of Antibiotic Molecules on Pharmacokinetic Characteristics:

The Interrelationship of Hydrophilicity and Lipophilicity of Antibiotic Molecules on Pharmacokinetic Characteristics Hydrophilic compound -Low V d - Predom . renal clearance - Low intracellular penetration V d increased CL inceased or decreased (renal) Beta lactam Aminoglycosides Glycopeptides Linezolid colistin Lipophilic compound -High V d - Predom , hepatic clearance - High intracellular penetration V d largely unchanged CL increased or decreased (hepatic) Fluoroquinolones Macrolides Lincosamides tigecycline General Pk Altered ICU Pk Examples

Pharmacodynamics goals:

Pharmacodynamics goals Parameter Goal Antimicrobial drug classes Time above MIC >50-60 % of the dosing interval All ß lactams Macrolides Linezolid Peak conc.: MIC ratio ≥ 10:1 Aminoglycoside v s gram – ve organism Area under curve (AUC) :MIC ratio ≥ 30-50:1 ≥ 125:1 Fluoroquinolones v s Gram + ve organism Fluoroquinolones v s Gram - ve organism

Step 6: follow pharmacokinetic and pharmacodynamic principles while prescribing antibiotics:

Step 6: follow pharmacokinetic and pharmacodynamic principles while prescribing antibiotics Dose dependent antibiotics like aminoglycosides (maximum bacterial inhibition depends on peak antibiotic concentration) should be given as once-daily bolus dose. Adjust the dose of antibiotics depending on renal and hepatic dysfunction.

Step 7:Assess the patient daily and de-escalate antibiotics once culture results obtained:

Step 7:Assess the patient daily and de-escalate antibiotics once culture results obtained Clinical response should be assessed frequently ,and if the patient is responding favorably, antibiotics should be de-escalated to a narrower spectrum ,and unnecessary antibiotics should be stopped if culture results permit. Decisions to continue, narrow or stop antimicrobial therapy must be made on the basis of clinician judgment and laboratory information like decrease in leukocytosis, decreasing C reactive protein, and a low procalcitonin level.

Step 8: consider combination of antibiotics in specific situations :

Step 8: consider combination of antibiotics in specific situations The combination of antibiotics (two appropriate antibiotics against the same organism)is indicated in difficult to treat multidrug resistant pathogens like Acinetobacter and Pseudomonas sp. Combination is also indicated for neutropenic patients with severe sepsis and selected patients with severe Pseudomonas infection with respiratory failure and shock. Similarly, a combination of beta- lactam and macrolide is recommended for pneumococcal bacteremia .

Step 9:decide on duration of antibiotic therapy :

Step 9:decide on duration of antibiotic therapy Duration of therapy should typically be 7-10 days. Longer courses may be appropriate in patients who have a slow clinical response, undrainable foci of infection ,or immunologic deficiencies including neutropenia. If culture result is negative and there is a favorable clinical response ,most antibiotics can be stopped in 5 days. In Pseudomonas and Acinetobacter infection, severe sepsis should be treated for 2 weeks.

Step 10: Implement antibiotic stewardship program:

Step 10: Implement antibiotic stewardship program Constitute an antibiotic stewardship team along with the microbiologist ,infection control nurse, infectious disease consultant and clinical pharmacist. Educating ICU staff the principles of antibiotic stewardship is of prime importance. Proper utilization of local antibiogram should be done. Utilize optimally the information obtained from the microbiology laboratory. Work in close collaboration with microbiologist and other physicians involved in antibiotic prescribing.

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Thank you

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