Strategies in the Selection of Antibiotic Therapy in the ICU

8/12/2019 Strategies in the Selection of Antibiotic Therapy in the ICU

1/56

Strategies in the Selection of

Antibiotic Therapy in the ICU

Dr. Abdullah Alshimemeri

Consultant Pulmonary and Critical care Medicine,

Associate Professor, College of Medicine, King SaudBin Abdulaziz University for Health Sciences

Riyadh, Saudi Arabia.


2/56

Scope of the Problem

Inadequate Initial

Antibiotic Therapy

Bacterial Resistance


3/56

What Is Initial

Inadequate Therapy?


4/56

Myth There is time to start with one therapy and then

escalate later, if needed.

Fact Inadequate initial antimicrobial therapy increases mortality.

Changing from inadequate to appropriate therapy may notdecrease mortality.

Initially delayed appropriate antibiotic therapy (IDAAT) isinadequate therapy.

Kollef MH et al. Chest 1999;115:462-474.Ibrahim EH et al. Chest 2000;118:146-155.

Iregui M et al. Chest 2002;122:262-268.

Initial Inadequate Therapy InCritically Ill Patients with Serious

Infections


5/56

Defining Initial Inadequate

Therapy

The antibiotic did not cover the infecting

pathogen(s)

The pathogen was resistant to the antibiotic

Dosing was not adequate

Combination therapy was not used, if indicated.

1Kollef MH et al. Chest1999;115:462-474.

2Ibrahim EH et al. Chest2000;118:146-155 .

Initial therapy is considered to be inadequateif:


6/56

Initial Appropriate Therapy

Empiric broad-spectrum therapy initiated at the first suspicion ofserious infection.

Selection of antibiotic to ensure adequate coverage of all likely

pathogens. Factors to consider when defining appropriate therapy:

Microbiologic data

Monotherapy vs. combination therapy

Dose and dosing frequency

Penetration

Timing

Toxicity

Risk of influencing resistance

Prior antibiotic use

Kollef MH et al. Chest1999;115:462-474 .


7/56

Factors in Selecting InitialAppropriate Therapy

Patient features: Choose empiric therapy based on site and

severity of infection, and physician assessment of the likelihood

for deterioration and mortality.

Local susceptibility and epidemiology: Choose empiric therapyto cover the likely infecting pathogens based on patterns while

considering prior antibiotic therapy.

Initial antibiotic therapy dosing and duration: Choose initial

empiric therapy that will deliver enough antibiotic to the site ofinfection and be well-tolerated (consider antibiotic penetration).

Combination vs. monotherapy: Initial antibiotic choice should

give broad enough coverage, avoid emergence of resistance, and

have the potential for synergy if necessary.


8/56

Nosocomial Infection

0

5

10

15

20

25

30

35

Percent

UTI Pneumonia Bloodstream

Infection

other

Richards MJ et al, CCM. 1999;27:887-882


9/56

NNISNationa Nosocomial Infections ecnallievruS

0

5

10

15

20

25

30

35

40

Percen

t

BSI Pneumonia

CN staph

Enterococci

S. aureus

P. aeruginosa

Enterobacter

Richards MJ et al, CCM. 1999;27:887-882


10/56


11/56

Inadequate Initial

Antibiotic Therapy

0 10 20 30 40 50 60 70 80

Rello, 1997

Alvarez-lerma,

1996

Luna, 1997

Kollef, 1998

% patients receiving inadequate initial therapy


12/56

Mortality Associated with

Initial Inadequate Therapy

0 20 40 60 80 100

Luna, 1997

Ibrahim, 2000

Kollef, 1998

Kollef, 1999

Rello, 1997

Alvarez-lerma, 1996

%Mortality

Initial Inadequate Therapy Initial Adequate herapy


13/56

Inadequate Antimicrobial

Therapy

2000 consecutive MICU/SICU patients

655 (25.8%) with infections

169 (8.5%) with inadequate therapy

Kollef MH, et al chest. February 1999;115(2):462-474


14/56

Cohort of Infected Patients

and Inadequate Therapy

Risk factor Adjusted Odds

Prior ABs 3.39

BSI 1.88

APACHE II 1.04

Decreasing age 1.01

1.0b1



15/56

Most Common

Pathogens

Inadequate therapy (n=169)

P. aeruginosa: 53

MRSA: 45

VRE: 13

Adequate therapy (n=486)

Escherchia coli: 76

MSSA: 88



16/56

Clinical Outcomes

Variable Inadequate

Rx (n=169)

Adequate Rx

(n=486)

Organfailure

2.51.5 1.91.4

Hospital

LOS (days)22.825.7 2025.8

APACHE II 10.210.2 7.18.5

Decreasing

age11.110.6 7.69.2

1.0b1



17/56

Hospital Mortality of

Infected Patients

0

10

20

30

40

50

60

Hospital

Mortality (%)

All Causes ID related

Inadequate therapy Adequate therapy


P


18/56

Reduce Inappropriate Initial

Antimicrobial Therapy

Guidelines

Broad spectrum and combination antibiotics

ID consultation

Automated antibiotic consultant

More selective and sensitive diagnostic

methods


19/56

Clinical Guidelines for the Treatment

of Ventilator Associated Pneumonia

Prospective study: 50 patients were evaluated in

the before group and 52 in the after group

Administration ofvancomycin/imipenem/ciprofloxacin within 12

hours of clinical diagnosis

Antibiotic modification after24-48 hrs Seven-day course of therapy (>7 days if

symptoms and signs are persisted)

Ibrahim EH et al. Crit Care Med, 2001;29: 1109-1115


20/56

Ibrahim EH et al. Cri t Care Med, 2001;29: 1109-1115

05

10

15

20

25

30

35

Percent

Befor After

Incidence of

Inadequate Antibiotic

Therapy

Clinical Guidelines for the Treatment

of Ventilator Associated Pneumonia


21/56

Automated Antibiotic

Consultant

0

10

2030

40

50

60

7080

90

100

AAC MDs

Inade

quatetherapy%

Inadequate Abx

EvansArch Int Med

1994


22/56

ID Consultation

0

1020

30

40

50

60

70

80

%

ID Other MDs

Frequency of

Inadequate Intitial

Therapy

Byl B. Clin I nf Dis; 1989


23/56

Emergent Bacterial

Resistance

Bacterial Resistance


24/56

Impact of Antibiotic Restriction on

Resistance

Neurosurgical ICU in London

0

10

20

30

40

50

60

Total infections Infections due to Klebseilla aerogenes

1968 1969 1970

All antibiotics stopped

Price. Lancet. 1970


25/56

Decrease in Hospital-acquired ICU

Infection Rates, NNIS, 1990-1999

Type of ICU CR-BSI (%) VAP (%) CR-UTI (%)

Medical 44 56 46

Surgical 31 38 30

Pediatric 32 26 59


26/56

Possible Explanation for

Decrease in Infection Rate

Efforts to prevent infections: new research

findings, prevention guidelines

True decrease secondary to adhesion to

infection control policies


27/56

Emerging Pathogens

Methicillin-resistant Staphylococcus aureus(MRSA)

Methicillin-resistant Staphylococcus epidermitis

(MRSE) Vancomycin-resistant enterococci (VRE)

Vancomycin-intermediate Staphylococcus aureus(VISA)

Extended-spectrum beta-lactamase (ESBL)-producing gram-negative organisms

Multidrug-resistantAcinetobacter spp.


28/56

Antibacterial Resistance in

Nosocomial InfectionsGram-Negative Pathogens

P. AeruginosaResistance to imipenem

0

5

10

15

20

25

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Rate%

P. AeruginosaResistance to quinolones

0

5

10

15

20

25

30

35

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Rate%

Klebsiella pneumoniaeResistance to third-generation cephalosporins

0

2

4

6

8

10

12

14

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

Rate% ICU

Non-ICU

Fridkin and Gaynes. Clin Chest Med. 1999:20:302-315


29/56

Antibacterial Resistance in

Nosocomial InfectionsGram-Positive Pathogens

MRSA

0

10

20

30

40

50

60

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Rate%

Methicillin-resistant Coagulase-

negative Staphylococcus

0

10

20

30

4050

60

70

80

90

100

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Rate%

Vancomycin-resistant enterococci

0

5

10

15

20

25

30

35

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

Rate% ICU

Non-ICU

Fridkin and Gaynes. Clin Chest Med. 1999:20:302-315


30/56

Methicillin Resistant

Staphylococci by setting

010

20

30

40

5060

70

80

90

ICU Non-ICU Outpatient

%

resistan

t

S.aureus Coagulase-negative Staphylococci

Fridkin. Clin I nfect Dis.1999


31/56

Vancomycin-resistant

Staphylococcus aureus

June 2202- First case of VRSA isolated from aswab obtained from a catheter exit site

The isolate was resistant to: Oxacillin (MIC >16 g/ml)

Vancomycin (MIC >128 g/ml)

The isolate contained: The oxacillin-resistant gene mecA The vanA vancomycin resistant gene from

enterococci

CDC MMWR. 2002;51:565-567


32/56

Epidemiology of VRE

Present in all 50 states in the United States

Number of isolated continues to grow

Recognized in Europe, Japan, Central and

South America

Resistance to alternate antibiotic therapy

continues to be a problem


33/56

Risk Factors for VRE

Prior broad spectrum antibiotics (especially

cephalosporins and vancomycin)

Prolonged hospitalization Immunocompromised host

Neutropenia

Admission to an intensive care unit

Renal failure requiring dialysis

Noskin. J Lab Clin M ed. 1997


34/56

Antibiotics and Colonization

with VRE

Antimicrobial Odds Ration P

Penicillins 2.2 0.10

2nd

and 3rd

Cephalosporins

9.4


35/56

Use of Vancomycin in US

and Rate of VRE

0

20

40

60

80

100

120

84 85 86 87 88 89 90 91 92 93 94 95 96 97

Kilo

gram

ofvanco(X100)

purchased

02

4

6

8

10

1214

16

18

20

%

VRE

Usage of Vancomycin Rate of VRE

Kirsl et al. Historical usage of vancomycin. Antimicrob Agent Chemo1998

National Nosocomial Infection Surveillance System (CDC)

l b


36/56

Enterococcal Resistance by

Species

0

10

20

30

40

50

60

70

80

90

E. faecium E. fecalis

Ampicillin resistant

Vancomycin resistant

Jones. Diagn. Microbiol I nfect Dis. 1998


37/56

Outcome of Enterococcus

faecium Bacteremia

Outcome Measure VSE

(n=32)

VRE

(n=21)

P

Mortality 13 (41) 16 (76) 0.009

Directly related 3 (9) 8 (38) 0.01

Indirectly related 6 (19) 5 (24) 0.24

Unrelated 4 (13) 3 (14) 0.31

Survival 19 (59) 5 (24) 0.009

Total hospital costs $56,507 $83,897 0.04

Stosor. Arch I ntern Med. 1998

E t d d S t


38/56

Extended Spectrum -

lactamases

ESBLs ESBL inactivates oxyamino beta-lactams and fourth-

generation cephalosporins (to some extent) andaztreonam

Large plasmids encoding multiple antibioticresistance determinants including aminoglycosidemodifying enzymes

Strains producing ESBL are typically sensitive to

cephamycins and carbapenems Common ESBL-producers: K. pneumoniae, and less

common other Enterobactericae


39/56

Emergence of Carbapenem-

resistantAcinetobacter spp.

Frequent use of aminoglycosides,fluroquinolones, ureidopenicillins and thirdgeneration cephalosporins

Reported from South America, Europe, FarEast, Middle East, and United States

Numerous outbreaks (some strainssusceptible only to polymyxin B)

High mortality rates Endemic in some hospitals


40/56

Endemic Carbapenem-Resistant

Acinetobacter spp. In Brooklyn,

New York

15 hospitals

November 1997, all aerobic bacteria collected

Acinetobacter spp. (233) accounted for 10% of the gram negativebacilli

Carbapenem resistance ranged from 0-100%

10% of isolated were susceptible only to polymyxin

Risk factors

Use of third generation cephalosporins plus aztreonam

Environment and healthcare worker hands contamination

documented

PFGE (pulsed-field gel electrophoresis ) documented inter- andintra-hospital spread

VM Manikal et al. CID. 2000


41/56

Antimicrobial Susceptibility of 233

Acinetobacter spp., 15 Hospital,

Brooklyn, New York

VM Manikal et al. CID. 2000

Efforts to Decrease the Rate of


42/56


Emergent Antimicrobial

Resistance

CDC guidelines and barrier

precautions

Antibiotic restriction

Selective bowel decontamination

Rotation antibiotics

Short antibiotic course


43/56

Antimicrobial Utilization and

Resistance

Interdisciplinary team in Indianapolis tocontrol resistant organisms

Interventions:

Reduce third generation cephalosporin use

Reduce imipenem use

Encourage use of ampicillin/sulbactam and

piperacillin/tazobactam Enhance compliance with infection control

Education regarding antimicrobial resistance

A i i bi l U ili i d


44/56

Antimicrobial Utilization and

Resistance

Rate of Resistance (%)Bacteria 1994 1998

VRE 16 6

E. cloacae 61 28

E. Aerogenes 63 11

Acinetobacter

17 9MRSA 34 23

Piperacillin/tazobactam resistant

Smith. Pharmacotherapy1999


45/56

Impact of a Rotating Empiric Antibiotic

Schedule on Infectious Mortality in an

Intensive Care Unit

0

510

15

20

25

30

35

No rotation Rotation

VAP Mortality%

Raymond DP. Crit Care Med 01-Jun-2001, 29(6);1101-8

Sh C A ibi i


46/56

Short Course Antibiotic

Therapy

Hospital Acquired Pneumonia

Clinical Pulmonary Infection Score (CPIS)

6

Antibiotics

10-21 days

Ciprofloxacin

3 days

Antibiotics

10-21 days

6 treat

as pneumonia

Reevaluate CPIS at 3 days

Singh N, et al. Am J Resp Crit Care Med. 2000;162:505-511

Sh t C A tibi ti


47/56

Short Course Antibiotic

Therapy

Hospital Acquired Pneumonia

0

510

15

20

2530

35

40

Percent

Short Standard

Superinfection Rate

Singh N, et al. Am J Resp Crit Care Med. 2000;162:505-511


48/56

In Conclusion:

d l


49/56

Reduce Inappropriate Initial

Antimicrobial Therapy

Guidelines and goal directed protocols

Broad spectrum and combination

antibiotics

ID consultation

Automated antibiotic consultant! More selective and sensitive diagnostic

methods



50/56

Efforts to Decrease the Rate ofEmergent Antimicrobial

Resistance CDC guidelines and barrier precautions

Antibiotic restriction and appropriate utilization:

Decrease cephalosporin use Increase extended-spectrum penicillin/beta-

lactamase inhibitor use

Limit carbapenem and vancomycin use to

desired therapy

Rotation antibiotics

Short course antibiotic course: HAP


51/56

ConclusionWise Use of Antimicrobial

Decrease cephalosporin use

Increase extended-spectrumpenicillin/beta-lactamase inhibitor use

Limit carbapenem and vancomycin use to

desired therapy


52/56

Importance of Timing of Antibiotic

Administration

107 patients with VAP in a medical ICU

All patients received an antibiotic shown to be active

in vitro against the bacteria

33 patients received treatment that was delayed for 24

hours (28.6 5.8 hours) (classified as receiving IDAAT)

74 patients received treatment timely within 24 hours

(12.5 4.2 hours)

Risk factors for hospital mortalityIregui et al. Chest 2002;122:262268

IDAAT

31%

Timely


53/56

Appropriate Early Antibiotic Therapy

Reduces Mortality Rates In Patients With

Suspected VAP

Iregui et al. Chest 2002;122:262268

Mortality (%)

Hospital mortality Mortality attributedto VAP

0

60

80

20

40

p


54/56

Summary

Initial inadequate therapy:

Inadequate initial empiric therapy leads to increased mortalityin patients with serious infection.

Initial appropriate therapy:

Means starting with a broad-spectrum antibiotic and then focusingbased on clinical and microbiological data. Broad-spectrumantibiotics should not be held in reserve.

Should be based on patient stratification, and local epidemiologyand susceptibility patterns.

Includes use of appropriate drug, dose, and duration.


55/56

An Art in Medicine

Balance

An Evidence-Based Problem:

Mortality with

Inadequate Therapy

A Theoretical Dilemma:

Concern of Resistance with

Broad-Spectrum Therapy


56/56

THANK YOU

Strategies in the Selection of Antibiotic Therapy in the ICU

Documents

Transcript of Strategies in the Selection of Antibiotic Therapy in the ICU