Alex Soriano

Hospital Clínic de Barcelona

MSSA: oxacillin versus other beta-

lactam choices

B-lactam MIC50 (µg/mL)

Cloxacillin

Amoxi-clav

Cefazolin (1st)

Cefuroxime (2nd)

Ceftriaxone (3rd)

Cefepime (4th)

Ceftaroline* (5th)

Imipenem

Minimun inhibitory concentration (MIC) of different ß-

lactams against methicillin-susceptible S. aureus.

EUCAST.org (access 20-2-2012)

MIC90 (µg/mL)

0.25

1

0.5

1

4

2

0.25

0.03

0.5

2

1

2

4

4

0.5

0.06

* Jones R, et al. JAC 2010; 65 (suppl 4): 17-31

2 g/4h

1-2 g/6-8h

1-2 g/8h

Carrizosa J, et al. Treatment of Experimental Staphylococcus

aureus Endocarditis: Comparison of Cephalothin, Cefazolin,

and Methicillin

Antimicrob Agents Chemother 1978; 13: 74-7

Clinical experience with cefazolin in infectious

endocarditis and Staphylococcus aureus

bacteremia

Reference Nº pat.

AACh 1973; 4: 525

JAMA 1977; 237:569

CID 2003; 37: 1194

CID 2005; 41: 127

AACh 2009; 53: 3437

Total endocarditis

Total

Failure (%)

3

2

1

1

12

7

19

1

2

1

1

3

5 (71.4)

8 (41)

Lee S, et al. Is Cefazolin Inferior to Nafcillin for Treatment

of Methicillin-Susceptible S. aureus Bacteremia?

Antimicrob Agents Chemother 2011; 55: 5122-6

N=138

Shuford JA, et al. Lack of association of S. aureus type A ß-

lactamase with cefazolin combined with antimicrobial spacer

placement prosthetic joint infection treatment failure.

Diag Microbiol Infect Dis 2006; 54: 189-192

Zeller V, et al. Continuous Cefazolin Infusion To Treat Bone

and Joint Infections: Clinical Efficacy, Feasibility, Safety, and

Serum and Bone Concentrations

Antimicrob Agents Chemother 2009; 53: 883-7

Success rate:

82/88 (93%)

Staphylococcus aureus (PSSA)

PBP 1 2 3 4

Penicillin

peptidoglucan

Staphylococcus aureus (PSSA)

PBP 1 2 3 4

Penicillin

PBP 1 2 3 4

peptidoglucan

DN

A

ß-lactamase

PBP 1 2 3 4

peptidoglucan

DN

A

ß-lactamase

PBP 1 2 3 4

DN

A

ß-lactamase

3 4

DN

A

ß-lactamase

methicillin

cephalosp.

penicillin

ß-lactams stable to the hydrolisis

of ß-lactamase:

3 4

DN

A

ß-lactamase

•Bla type A

•Bla type B

•Bla type C

•Bla type D

OXA

-

-

-

-

CFZ

++

-

-

+

PEN

++++

++++

++++

++++

CLV

-

-

++

+

TZB

-

-

++

+

Nannini EC, et al. Inoculum Effect with Cefazolin among

Clinical Isolates of MSSA: Frequency and Possible Cause of

Cefazolin Treatment Failure

Antimicrob Agents Chemother 2009; 53: 3437-41

Type of ß-lactamase

(n=98)

cefazolin

MIC (µg/mL)

std. inoculum

A Bla producers (n=25)

B Bla producers (n=15)

C Bla producers (n=45)

Bla-negative strains (n=13)

1.3

0.9

0.9

0.6

Std inoculum= 5x105 CFU/mL

S. aureus producing ß-lactamases

MIC

(µ

g/m

L)

104 105 106 107 108

CFU/mL

Nannini EC, et al. Inoculum Effect with Cefazolin among

Clinical Isolates of MSSA: Frequency and Possible Cause of

Cefazolin Treatment Failure

Antimicrob Agents Chemother 2009; 53: 3437-41

Type of ß-lactamase

(n=98)

cefazolin

MIC (µg/mL)

std. inoculum

A Bla producers (n=25)

B Bla producers (n=15)

C Bla producers (n=45)

Bla-negative strains (n=13)

1.3

0.9

0.9

0.6

11.2

2.8

5.6

1

cefazolin

MIC (µg/mL)

high inoculum

Std inoculum= 5x105 CFU/mL

High inoculum= 5x107 CFU/mL

Nannini EC, et al. Inoculum Effect with Cefazolin among

Clinical Isolates of MSSA: Frequency and Possible Cause of

Cefazolin Treatment Failure

Antimicrob Agents Chemother 2009; 53: 3437-41

Low inoculum= 5x104 CFU/mL

Std inoculum= 5x105 CFU/mL

Intermediate inoculum= 5x106 CFU/mL

High inoculum= 5x107 CFU/mL

MIC

(µ

g/m

L)

104 105 106 107 108

CFU/mL

S. aureus producing ß-lactamases

•Pneumonia

•Endocarditis

•Abscess (not

drained)

•FBI (not

removed)

Lee S, et al. Is Cefazolin Inferior to Nafcillin for Treatment

of Methicillin-Susceptible S. aureus Bacteremia?

Antimicrob Agents Chemother 2011; 55: 5122-6

Cefazolin (n=49)

4 PN and 1 IE

Nafcillin (n=89)

11 PN and 12 IE

Zeller V, et al. Continuous Cefazolin Infusion To Treat Bone

and Joint Infections: Clinical Efficacy, Feasibility, Safety, and

Serum and Bone Concentrations

Antimicrob Agents Chemother 2009; 53: 883-7

Success rate:

82/88 (93%)

Time (h)

Cef

azol

in o

ncen

trat

ion

0 24

Loading dose: 0.5-1 g

Maintaining dose: 60-80 mg/kg (2-6 g/24h)

Zeller V, et al. Continuous Cefazolin Infusion To Treat Bone

and Joint Infections: Clinical Efficacy, Feasibility, Safety, and

Serum and Bone Concentrations

Antimicrob Agents Chemother 2009; 53: 883-7

• 94% underwent surgery

• 100% a second atb (rifampin,

gentamycin)

1.- Oxa-cloxacillin

2.- Cefazolin if HI-

MIC is low

MSSA: oxacillin versus other beta-lactam choices

• Infectious

endocarditis

• Pneumonia

•Big abscess not

drained

• Foreign-body

infections, when

the implant is not

removed

Guy E. Thwaites and Vanya Gant. Are bloodstream leukocytes

Trojan Horses for the metastasis of Staphylococcus aureus?

Nat Rev Microbiol 2011; 9: 215-22

• Intracellular concentration

• SCV phenotype

diffusion

biofilms

Holmes NE, et al. Antibiotic Choice May Not Explain Poorer

Outcomes in Patients With Staphylococcus aureus Bacteremia

and High Vancomycin Minimum Inhibitory Concentrations.

J Infect Dis 2011; 204: 340-7

• Infectious

endocarditis

• Pneumonia

•Big abscess not

drained

• Foreign-body

infections, when

the implant is not

removed

1.- Oxa-cloxacillin

2.- Cefazolin if HI-

MIC is low

MSSA: oxacillin versus other beta-lactam choices

2nd ATB

• AG

• Rif

• FQ

• Fos

• Dap

• Lin

+

Severity

Vanco MIC

Biofilm

Source

Kumar A, et al. Early combination antibiotic therapy yields

improved survival compared with monotherapy in septic shock: A propensity-matched analysis.

Crit Care Med 2010; 38: 1773-85

ß-lactam +

macrolide

Kumar A, et al. Early combination antibiotic therapy yields

improved survival compared with monotherapy in septic shock: A propensity-matched analysis.

Crit Care Med 2010; 38: 1773-85

Kumar A, et al. Early combination antibiotic therapy yields

improved survival compared with monotherapy in septic shock: A propensity-matched analysis.

Crit Care Med 2010; 38: 1773-85

Monotherapy Combination

Nº deaths/total

HR (95%CI) P