Optimizing Antibiotics

Dr Samir Sahu

Time to Antimicrobial TherapyKHL

0 hrs 1-2 hrs

2-3 hrs

3-4 hrs

4-5 hrs

5-6 hrs

6-9 hrs

9-12 hrs

12-24 hrs

24-36 hrs

>36 hrs

0

5

10

15

20

25

30

35

No

Time to Antimicrobial Therapy

• O hrs – 24• 1-2 hrs – 15• 2-3 hrs – 10• 3-4 hrs – 9• 4-5 hrs – 10• 5-6 hrs – 3• 6-9 hrs – 7• 9-12 hrs – 2• 12-24 hrs – 13• 24-36 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

Total Appropriate Inappropiate0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

MortalitySurvival

Empiric Antibiotic Therapy

Total Appropriate Inappropriate0

20

40

60

80

100

120

140

160

180

TotalSurvivalMortality

Inappropriate Antibiotic Therapy

E.coli

Pseudomonas

Klebsiella

Enterobac

ter

Acineto

bacter

MSS

AM

RSA

Enteroco

cci0

5

10

15

20

25

30

35

40

InappropriateAppropriate

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

2004 2005 2006 20070

20

40

60

80

100

120

140

160

survivalmortality

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

2004 2005 2006 20070

20

40

60

80

100

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140

160

180

SepsisSeptic ShockSevere Sepsis

How Antibiograms Can Assist in Choice of Therapy

Type of Therapy Description Use of AntibiogramsProphylaxis Antibiotics used to

prevent infectionSelection of antibiotic

Empiric Organism is unknown but syndrome is known

Selection of antibiotic or combinations of antibiotics

Pathogen-directed Organism is known but susceptibility is unknown

Selection of antibiotic

Susceptibility-guided Organism 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 2005-08 24

Urine Cultures :2005-2007 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 System2) Prior or not antibiotic use3) Patient Characteristics

Risk Stratification

Patients type 1 Patients type 2 Patients type 3

1)No contact with health care system2)No prior antibiotic treatment3)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 therapy3)Patient old with multiple co-morbidities. ( > 60 years)

1)Long hospitalization and or invasive procedures2)Recent & multiple antibiotic therapies3)Patient characteristics: cystic fibrosis, structural lung disease, advanced AIDS, neutropenia, other severe immunodeficiency.

No risk of infection due to MDR Risk 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 2005-08 27

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)

suneeta / uti 2005-08 28

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

E.coli Psedo Enterococci MSSA MRSA0

2

4

6

8

10

12

14

16

Urine isolates

Series 1

suneeta / uti 2005-08 29

E.coli-ICU II(Jun-Dec 2007)

CA NT OF Im PT0

2

4

6

8

10

12

14

16

ResSen

Urine - E.Coli Sensitivity ICU II (Jun-Dec 2007)

ICU KHL• CA – 20% 55%• NT – 60% 82%• OF – 6.5% 55%(Gat)• Im – 81% 99%• PT – 30% 99%• Cef/S 89%• NFT 95%• Such an antibiogram can be posted in ICU or be part of

a guidelines booklet for an institution or unit.

suneeta / uti 2005-08 31

Enterococci – ICU II(Jun-Dec 2007)

AS OF VA TE0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

ResSen

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 2007-08

Category 10

2

4

6

8

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12

14

16

MRSAMSSAEnterococciKlebsiellaPseudoAcineto

Dialysis Catheter – Staph aureas

Staph aureas0

5

10

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25

30

OxacilinOfloxacinVancoTeico

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 DataResistance 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 45/5-28 10/10 1/5 10/5• Enterob: 35/5-10 /10 /5 /5

Severe Sepsis :

Meropenem/Imipenem>Piptaz> >Amikacin

E.coli- KHL

Amikacin CA Gatifloxacin Cef+sul PIPTaz Imipenem0

20

40

60

80

100

120

20032004200520062007

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 1/3rd of times(22%) – increased to 70% by education

• Antibiotic regimen should be re-assessed after 48-72hours.

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 48-72 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 AlgorithmPatients Type 1 Patients Type 2 Patients Type 3

Treatment Algorithm

Suggestions / RecommendationsSend a culture before starting antibiotic

Send a culture before starting antibiotic

Send a culture before starting antibiotic

Approach

Infections suspected due to susceptible pathogens

Infections suspected due to ESBLs but not Pseudomonas.

De-Escalation

De-Escalation 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

Ceftriaxo

ne

Ceftazidim

e

Cef/Sul

Ofloxacin

Amikacin

Im+M

ero

Piptazo

0

1000

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8000

2006-072007-08