Optimizing Antibiotics Dr Samir Sahu

Time to Antimicrobial Therapy KHL

Time to Antimicrobial Therapy O hrs – hrs – hrs – hrs – hrs – hrs – hrs – hrs – hrs – hrs – 4 >36 hrs – 29

Appropriate Antibiotics Appropriate therapy mean the first antibiotic that is actually prescribed and given to the patient. If the organism causing the infection is susceptible to it based on in vitro testing, it is an appropriate agent. If it is not susceptible, it is an inappropriate agent.

Severe Sepsis – 5/2006-6/2008 Total cases – 369 Culture positive – 167 Appropriate –Total – 112(67%) Survival-61/112(55%), Mortality- 51/112(45%) Inappropriate – Total – 55(33%), Survival - 27/55(49%), Mortality - 28/55(51%)

Empiric Antibiotic Therapy

Inappropriate Antibiotic Therapy

Klebsiella Pseudomonas MRSA Enterococci Acinetobacter

Epidemiology of Severe Sepsis KHL Year Total Mortality 2004 – 62 (28) – 45% 2005 – 87 (50) – 57.47% 2006 – 149 (89) – 59.73% 2007 – 142 (73) – 51.4% 2008 – 51 (21) – 41%

Epidemiology of Severe Sepsis & Septic Shock

Severe Sepsis/Septic Shock 2004 – 9/24(37.5%)19/36(52%) 2005 – 8/23(34.7%)41/60(68%) 2006 – 16/50(32%)72/95(75%) 2007 – 16/54(29.6%)55/86(64%)

Severe Sepsis/Septic Shock - Mortality

How Antibiograms Can Assist in Choice of Therapy Type of TherapyDescriptionUse of Antibiograms ProphylaxisAntibiotics used to prevent infection Selection of antibiotic EmpiricOrganism is unknown but syndrome is known Selection of antibiotic or combinations of antibiotics Pathogen-directedOrganism is known but susceptibility is unknown Selection of antibiotic Susceptibility-guidedOrganism is known and susceptibility is known Cumulative antibiogram not useful

How Antibiograms Can Assist in Choice of Therapy In an individual institution or a unit within that institution, cumulative antibiotic susceptibility reports on multiple patients ("antibiograms") can be constructed in order to aid with appropriate antibiotic choice. The provision of cumulative antibiotic susceptibility reports (antibiograms) is particularly helpful for choosing empiric and pathogen-directed treatment regimens. The provision of antibiotic susceptibility reports on individual patients is clearly of use to ensure that antimicrobial treatment was adequate for the organism causing the infection. It also assists in antibiotic "streamlining" -- the process by which excessively broad-spectrum empiric antibiotic therapy can be switched to narrower spectrum therapy aimed only at the implicated pathogen(s).

National and International Data on the Extent of Antibiotic Resistance It allows for a comparison of local data with national data to determine whether the extent of resistance is better or worse than national averages. It provides the ability to presage future trends in antibiotic resistance: If resistance is rising for a particular pathogen at a national level, it may be only a matter of time before resistance rates rise locally.

Antibiogram Unit specific - antibiogram for a particular ICU helps create a clinical guideline for antibiotic selection in that unit. An antibiogram-based guideline does not have an unlimited duration of utility. It is prudent to update antibiograms and antibiogram-based antibiotic guidelines on a regular basis. A yearly review should be regarded as a bare minimum.

suneeta / uti Urine Cultures : Organisms isolated GRAM +VE Staph. A Enterococci GRAM -VE E. Coli Pseudomonas Klebsiella Enterobact Acinetobacter Proteus

"How can clinicians obtain antibiograms that are meaningful to their patients?“ An antibiogram for community-acquired E coli isolates from women with uncomplicated urinary tract infection is more likely to be useful in guiding therapy for an individual patient with uncomplicated urinary tract infection than is a hospital antibiogram for E coli.

How to identify patients at risk for Gram negative MDR The risk stratification is based on 3 factors: 1) Contact w/ Health Care System 2) Prior or not antibiotic use 3) Patient Characteristics Risk Stratification Patients type 1Patients type 2Patients type 3 1)No contact with health care system 2)No prior antibiotic treatment 3)Patient young with few co- morbid conditions 1)Contact with health care system (e.g. recent hospital admission, nursing home, dialysis) without invasive procedure 2)Recent antibiotic therapy 3)Patient old with multiple co- morbidities. ( > 60 years) 1)Long hospitalization and or invasive procedures 2)Recent & multiple antibiotic therapies 3)Patient characteristics: cystic fibrosis, structural lung disease, advanced AIDS, neutropenia, other severe immunodeficiency. No risk of infection due to MDRRisk for infections due to MDR (ESBLs AmpC ) however Pseudomonas sp. / AB may not suspected Risk factor for mono- or poly- microbial infections, suspected risk of infection due to Pseudomonas or Acinetobacter

suneeta / uti Urine Cultures : ICU II(Jun-Dec 2007) Organisms isolated GRAM +VE Staph. A (7) Enterococci(13) GRAM -VE E. Coli (15) Pseudomonas(7) Klebsiella(3) Enterobact er(3)

Urine Isolates ICU II – Jun-Dec 2007 UTI with catheter(complicated) suneeta / uti

E.coli-ICU II(Jun-Dec 2007) suneeta / uti

Urine - E.Coli Sensitivity ICU II (Jun-Dec 2007) ICUKHL CA – 20%55% NT – 60%82% OF – 6.5%55%(Gat) Im – 81%99% PT – 30%99% Cef/S89% NFT95% Such an antibiogram can be posted in ICU or be part of a guidelines booklet for an institution or unit.

Enterococci – ICU II(Jun-Dec 2007) suneeta / uti

UTI due to Enterococci Patients with prior antibiotic use & catheterized outside Antibiotics to be used as Empiric choice are Ofloxacin(84%), Vancomycin(92%), Teicoplanin(100%)

Recommendation for UTI The most common community acquired UTI is due to E.coli In the OPD setting(uncomplicated UTI) the antibiotics which can be used are NFT, Netlimycin (PT, IM, Cef/S) In the ICU setting(complicated UTI) the antibiotic of choice will be Imipenem + Teicoplanin to cover Enterococci & Staph

Unit-Specific Antibiogram In ICUs unit-specific antibiograms help optimization of empiric antibiotic prescribing In patients with prolonged ICU stay (arbitrarily defined as ICU length of stay exceeding 14 days), empiric therapy may better be individualized on the basis of avoidance of antibiotics that the patient has previously received. A second principle is avoidance of antibiotics to which colonizing organisms are known to be resistant.

Dialysis Catheter tips

Dialysis Catheter – Staph aureas

ESBLs Resistance of K pneumoniae or E coli to third- generation cephalosporins is actually defined as nonsusceptibility to either aztreonam or third-generation cephalosporins, and is a surrogate marker for the production of extended-spectrum beta lactamases (ESBLs)

Local Susceptibility Data Resistance Gm-ve - KHL Amik L/G PipT Imi/Mer 03/ 04/ 05 03/04/05 03/04/5 03/04/05 E.coli: 45/0-10/10 10/10/40 6/5 /.7 2/5 /.2 Kleb.: 40/8-35/17 10/10/30 3/5/0 3/5/ 0 Pseudo 45/ /10 1/5 10/5 Enterob: 35/5-10 /10 /5 /5 Severe Sepsis : Meropenem/Imipenem>Piptaz> >Amikacin

E.coli- KHL

Avoidance of Unnecessary Admn. De-escalation De-escalate (narrow the spectrum) once organism & susceptibility is known. - minimizes development of resistant pathogens - contains cost - prevents superinfection (candida) - only done 1/3 rd of times(22%) – increased to 70% by education Antibiotic regimen should be re-assessed after hours. Grade E

De-escalation Decreasing the number and/or spectrum of antibiotics, possibly based on culture and sensitivity results Shortening the duration of therapy in patients with uncomplicated infections who are demonstrating signs of clinical improvement Discontinuing antibiotics in patients who have a noninfectious etiology identified for the patient's signs and symptoms

De-escalation Formal Protocols and Guidelines. Antibiotic practice guidelines or protocols have emerged as a potentially effective means of both avoiding unnecessary antibiotic administration and increasing the effectiveness of prescribed antibiotics Several recently published guidelines for the antibiotic management of nosocomial pneumonia and severe sepsis recommend the discontinuation of empiric antibiotic therapy after hours if cultures are negative or the signs of infection have resolved.

Pk/Pd The duration of time (T) that the serum drug concentration remains above the minimum inhibitory concentration (MIC) of the antibiotic (T > MIC) enhances bacterial eradication with beta lactams, carbapenems, monobactams, glycopeptides, and oxazolidinones. Frequent dosing, prolonged infusion times, or continuous infusions can increase the T > MIC and improve clinical and microbiological cure rates. In order to maximize the bactericidal effects of aminoglycosides, clinicians must optimize the maximum drug concentration (Cmax) to the MIC ratio. A Cmax:MIC ratio of ≥ 10:1 with once-daily aminoglycoside dosing (5-7 mg/kg) has been associated with preventing the emergence of resistant organisms, improving clinical response to treatment, and avoiding toxicity. The 24-hour area under the antibiotic concentration curve to the MIC ratio (AUIC) is correlated with fluoroquinolone efficacy and prevention of resistance development. An AUIC value of > 100 has been associated with a significant reduction in the risk for resistance development while on therapy. As a general rule, clinicians should use the greatest approved dose of an antibiotic employed for a potentially life-threatening infection in order to optimize tissue concentrations of the drug and killing of pathogens.

Empiric Antibiotic Selection Appropriate empiric antibiotic selections can be made if the likely pathogens (and their susceptibility profiles) at any particular infection site are known. Cumulative antibiotic susceptibility reports on multiple patients (antibiograms) or national susceptibility data can be useful in guiding empiric antibiotic therapy. Additionally, empiric antibiotic selection should be individualized by taking into account recent antibiotic use and known bacterial colonization status. For example, specific antibiotics should not be used if they have been administered to the patient. Additionally, if a patient is known to have been colonized with highly resistant organisms, the antibiotic choice should be modified to reflect this.

Treatment Algorithm Patients Type 1Patients Type 2Patients Type 3 Treatment Algorithm Suggestions / Recommendations Send a culture before starting antibiotic Approach Infections suspected due to susceptible pathogens Infections suspected due to ESBLs but not Pseudomonas. De-Escalation Ertapenem ( Group 1 Carbapenem) Imipenem / Meropenem ( Which ever shows higher susceptibility) Ampicllin / Amoxicillin or Amoxiclav Cephalaxin or Cefuroxime After culture report: A. De-Escalate to other antibiotic due to non ESBL infections. B. Continue for infections due to ESBLs. C. Escalate to Anti- Pseudomonal AB eg Imipenem. After the culture report: A. De-Escalate to other antibiotic due to non ESBL infections. B. De-escalate to Ertapenem for infectiond due to ESBLs. C. Continue for infections due to non-fermenters.

Sepsis/Septic Shock Usual organism – aerobic Gm –ve, Staph IMP/MER or PIP-TZ + TEI/VAN The Sanford Guide to Antimicrobial Therapy 2008

Surgical Prophylaxis Single dose 1-2 hr before incision Surgery > 3 hrs additional doses intraoperatively not extending 24 hrs

Summary Antimicrobial resistance is a common variable influencing antibiotic prescription decisions and clinical outcomes. Clinicians must be able to balance the need to provide appropriate antimicrobial treatment to patients while minimizing the further development of resistance. The practice of antimicrobial de-escalation should be employed to accomplish this difficult but important balance.

Summary The hospital or unit antibiogram (that is, the cumulative antibiotic susceptibility report) and national surveillance data are key guides to the selection of antibiotics for empiric antimicrobial therapy. Antibiotic choice must be individualized, and patients with serious or life-threatening infections should receive initial broad-spectrum therapy that is subsequently narrowed when pathogen identity and susceptibility results become available allowing pathogen-directed therapy. Appropriate Antibiotic should be given within 1 hr of admission

Antibiotic Audit