Job No: 11925

Date of Preparation: February 2003

SERIOUS INFECTIONSTHE ROLE OF

The single strike

Job No: 11925

Date of Preparation: February 2003

Job No: 11925

Date of Preparation: February 2003

The golden age of antibiotics began during World War II when penicillin became

widely available

Job No: 11925

Date of Preparation: February 2003

‘Inappropriate’ antibacterial use(wrong choice, dose or duration)

Use of an agent with sub-optimal properties

has the potential:

1) For clinical failure and

2) To select and maintain bacteria that are

resistant to a wide range of antibacterials

Craig. Clin Infect Dis 1998; 26:1–12

Garau et al. ICMAS, Seville, Spain 2000 [poster 7.09]

Dagan et al. Pediatr Infect Dis J 2000; 19:95–101

Dagan et al. J Antimicrob Chemother 2001; 47:129–140

Job No: 11925

Date of Preparation: February 2003

“The most effective strategy against antimicrobial

resistance is to get the job done right first time – to

unequivocally destroy microbes – thereby defeating

resistance before it starts.”

WHO press release, June 2000: Drug resistance threatens to reverse medical progress

Job No: 11925

Date of Preparation: February 2003

50

40

30

20

10

0

Pneumonia Lower

respiratory

tract

Urinary

tract

Bloodstream

46.9%

17.8% 17.6%

12%

Infe

cti

on t

ype (

%)

n = 2064

INCIDENCE OFICU-ACQUIRED INFECTIONS

• EPIC study: Most common ICU-acquired infections

Vincent J-L et al. JAMA 1995; 274: 639-644.

Job No: 11925

Date of Preparation: February 2003

Vincent J-L et al. JAMA 1995; 274: 639-644.

Edbrooke DL et al. Crit Care Med 1999; 27: 1760-1767.

UK study

ICU patients with sepsis*: 50-60% mortality

ICU patients without sepsis*: 29% mortality

*defined as severe sepsis and early septic shock

MORTALITY

EPIC study

ICU acquired pneumonia: 31% mortality

Job No: 11925

Date of Preparation: February 2003

DiGiovine B et al. Am J Respir Crit Care Med 1999; 160: 976-981. Vincent J-L et al. JAMA 1995; 274: 639-644. Edbrooke DL et al. Crit Care Med 1999; 27: 1760-1767.

SUMMARY OF COMPLICATIONS OF ICU INFECTION

• Increased duration of stay

• Increased cost of care

• Increased risk of mortality

Job No: 11925

Date of Preparation: February 2003

Job No: 11925

Date of Preparation: February 2003Vincent J-L et al. JAMA 1995: 274: 639-644.

50

40

30

20

10

0

Path

ogens

(%)

Enterobacteriaceae Staph. aureus P. aeruginosa Coagulase-

negative

staphylococci

34.4%

30.1%28.7%

19.1%

Fungi

17.1%

MOST COMMON PATHOGENS IN ICU

EPIC study

Job No: 11925

Date of Preparation: February 2003Adapted from BNF 44, 2002; pp258-259.

EMPIRICAL ANTIBIOTIC THERAPY

• Spectrum of activity covers prevalent organisms

• Local sensitivities are high with suspected bacteria

• Low toxicity

• Low side effect profile

• Cost-effectiveness

Desirable features

Job No: 11925

Date of Preparation: February 2003

Organism

S. aureus (n=73)

Streptococcus spp. (n=15)

E. coli (n=48)

Klebsiella spp. (n=23)

Enterobacter spp. (n=22)

S. marcescens (n=16)

P. aeruginosa (n=50)

MEM

97.3

100

100

100

100

100

94.0

CTX

86.3

100

93.8

78.3

68.2

37.5

2.0

TAZ

89.0

100

89.6

69.6

59.1

31.3

76.0

CIP

83.6

26.7

97.9

82.6

100

75.0

90.0

CAZ

12.3

100

97.9

82.6

63.6

68.8

54.0

> 90% Susceptibility 70-90% Susceptibility <70% Susceptibility

Masterton RG. Meropenem susceptibility of bacterial isolates from the UK. Part of the MYSTIC antimicrobial surveillance programme 1997-1999. Presented at ECCMID, May 28th-31st 2000,Stockholm, Sweden

MEM=meropenem, CAZ=ceftazidime, CTX=cefotaxime, TAZ=piperacillin + tazobactam, CIP=ciprofloxacin

Gram-positive

bacteria

Enterobacteriaceae

and other

Gram-negative

bacteria

SUSCEPTIBILITY (%) OF STRAINS FROM ICUs (UK)

Job No: 11925

Date of Preparation: February 2003

Organism

BC

Non-BC

E. coli BC

Non-BC

P. aeruginosa BC

Non-BC

MEM

97.6

96.9

100

99.9

80.8

79.2

TAZ

95.3

94.5

94.1

92.1

82.5

84.2

CIP

90.3

85.9

75.2

84.1

69.4

64.4

GM

95.5

94.3

94.2

88.4

73.2

60.4

CAZ

73.9

68.7

96.7

94.0

70.6

70.5

> 90% Susceptibility 70-90% Susceptibility <70% Susceptibility

S. aureus

(MSSA)

SUSCEPTIBILITY (%) OF THE THREE MOST COMMONLY ISOLATED ORGANISMS (EUROPE)

Goossens H, Turner P and the MYSTIC Advisory Board (Europe). Comparison of the antimicrobial susceptibility of organisms isolated from blood cultures and other sources: data from the MYSTIC programme in Europe. Poster presented at ECCMID, April 24-27, 2002, Milan, Italy.

BC: blood culture MSSA: methicillin-sensitive S. aureus

MEM=meropenem, CAZ=ceftazidime, TAZ=piperacillin + tazobactam, CIP=ciprofloxacin, GM=gentamicin

Job No: 11925

Date of Preparation: February 2003

BC: blood culture

MEM=meropenem, TAZ=piperacillin + tazobactam, CIP=ciprofloxacin, GM=gentamicin

Organism

E. coli BC

Non-BC

K. pneumoniae BC

Non-BC

> 90% Susceptibility 70-90% Susceptibility <70% Susceptibility

MEM

100

99.4

100

100

TAZ

88.5

80.1

51.8

56.7

CIP

69.2

65.4

77.8

64.6

GM

89.5

60.2

41.2

38.1

No. ESBL-producing

strains/no. isolates

tested (%)

26/492 (5.3%)

156/1967 (7.9%)

54/200 (27%)

195/1088 (17.9%)

Goossens H, Turner P and the MYSTIC Advisory Board (Europe). Comparison of the antimicrobial susceptibility of organisms isolated from blood cultures and other sources: data from the MYSTIC programme in Europe. Poster presented at ECCMID, April 24-27, 2002, Milan, Italy.

SUSCEPTIBILITY (%) OF ESBL-PRODUCINGSTRAINS (EUROPE)

Job No: 11925

Date of Preparation: February 2003

MERONEM RESULTS

Babini GS, Livermore DM. J Antimicrob Chemother 2000; 45: 183-189.

BACTERIAL RESISTANCEKLEBSIELLA SPP – ESBL PRODUCERS

• 99% very susceptible to Meronem (mode MIC 0.03 mg/L)

• Only three strains had decreased susceptibility to Meronem (MICs 2-4 mg/L)

• All three strains were unable to hydrolyse Meronem

Job No: 11925

Date of Preparation: February 2003

Clinical efficacy

Job No: 11925

Date of Preparation: February 2003Mouton YJ et al. J Antimicrob Chemother 1995; 36 (suppl A): 145-156.

Community-acquired LRTIs

Meronem

(n=45)

Ceftazidime/amikacin

(n=44)

100

p=0.072 (ns)90

80

70

60

50

40

30

20

10

0

93%

79%

% patients

with

clinical

response*

*cured or improved at end of treatment

CLINICAL RESPONSE

Job No: 11925

Date of Preparation: February 2003Verwaest C et al. Clin Microbiol Infect 2000; 6: 294-301.

% patients

with

clinical

response*

0

10

20

30

40

50

60

70

80

90

Overall

Meronem imipenem/cilastatin

LRTIs Intra-abdominal Sepsis

100

77%

68% 68% 69%

95.5%

77%

100%

40%

p=0.185 (ns)n = 178

*cured or improved

CLINICAL RESPONSEMeronem vs imipenem/cilastatin

Job No: 11925

Date of Preparation: February 2003Norrby SR, Gildon KM. Scand J Infect Dis 1999; 31: 3-10.

“This new analysis supports the previous findings that

meropenem has a favourable and acceptable safety profile”

*events occurring in at least 1% of Meronem treatment

exposures

SAFETY PROFILE OF MERONEMA review of 4872 patients

Meronem-related adverse events*

Diarrhoea 2.3%

Rash 1.4%

Nausea/vomiting 1.4%

Injection site inflammation 1.1%

Job No: 11925

Date of Preparation: February 2003

Job No: 11925

Date of Preparation: February 2003

A Confident Start

Job No: 11925

Date of Preparation: February 2003

Job No: 11925

Date of Preparation: February 2003

The future is in your hands

Thank You