NEW ANTIBIOTICS 2014

• SAMIR EL ANSARY

Critical Care Antibiotics

Sepsis MortalityDelay of antibiotic treatment

• In-hospital mortality was 29.7%

• Statistically significant increase in the probability of death associated with the number of hours of delay for first antibiotic administration.

• Adjusted hospital mortality increased steadily after 1 hour of time to antibiotic administration.

• Results were similar in patients with severe sepsis and septic shock, regardless of the number of organ failure

Severe infections:risk factors for increased mortality

• Delay of antibiotic therapy

– But early therapy influences accuracy of the diagnosis

• Inadequate antibiotic therapy

– But broad-spectrum antibiotic therapy increases antibiotic consumption

• Increase of MDR pathogens

New Antibiotics

• Gram positive Infection

New Oxazolidinones

•Tedizolid

Pleuromutilines

New Antibiotics

• Gram positive Infection– New Oxazolidinones

• Tedizolid

– Pleuromutilines

• Gram negative Infection– ESBL/KPC Activity

• New beta-lactam inhibitors

• Pseudomonas activity– Ceftobiprole

– Ceftolozan/Tazobactam

– β-Hairpin Peptidomimetika (PEM)

New Antibiotics

• Gram positive Infection

– New Oxazolidinones

• Tedizolid

– Pleuromutilines

• Gram negative Infection

– ESBL/KPC Activity

• New beta-lactam inhibitors

• Pseudomonas activity

– Ceftobiprole

– Ceftolozan/Tazobactam

– β-Hairpin Peptidomimetika (PEM)

New AntibioticsThe Pipeline

Gram negative Infection

ESBL/KPC Activity

New beta-lactam inhibitors

Pseudomonas activity

Ceftobiprole

Ceftolozan/Tazobactam

β-Hairpin Peptidomimetika (PEM)

MRSA infectionsTreatment different for different sites of infection

• Pneumonia

– Linezold

• Sepsis

– Pneumogenic Sepsis

• Linezolid + Vancomycin

– Sepsis of unknown origin

• Vancomycin or daptomycin

• Joint/Valve infection

– Daptomycin

• CNS Infection

– Ceftarolin

Ceftaroline fosamil: Administered as a Prodrug

NS

O

S

N

N +

O O

NHN

S N

NH

N

O

P

HO

O

HO

S

C H3

O

NS S

N

N +

O O

N H

N

S N

NH2

N

O

S

C H3

O

O

Prodrug: Ceftaroline fosamil

Active metabolite: Ceftaroline

Plasma phospatase

Rapid biotransformation in plasma

Bactericidal activity

mod. nach Zhanel et al, Drugs 2009, 69 (7): 809-31

ESBL Treatment

• Carbapenems, Carbapenems, Carbapenems …..

Hot Topics in Pneumogenic Sepsis and ARDS

• (Pneumogenic) Sepsis

– General considerations

– Treatment

– New Antibiotics

– Immunomodulators

• ARDS

– Ventilation strategies

– Immunomodulators

Humoral immune response:

anti-bacterial modes of action

100-fold higher phagocytosis-promoting activity compared to IgG10

IgM exhibits:

1000-fold higher affinity towards C1q (first protein in the classical complement pathway) than IgG11

neutralization of antibiotic-induced endotoxin release12

1. Increase of bacterial phagocytosis

2. Induction of bacterial lysis due to specific activation of complement on bacterial surfaces

3. Neutralisation of toxins

IgM immunoglobulins for infection - Why?

Molnar Z, Nierhaus A, Esen F. Annual Update in ICEM 2013; 145-52

• MRSA NP remains an important healthcare burden

• Linezolid demonstrated statistically superior clinical efficacy versus vancomycin in the treatment of MRSA NP in the ZEPHyR study1

• Overall, linezolid demonstrated an acceptable safety and tolerability profile for the treatment of proven MRSA nosocomial pneumonia1

• Linezolid was associated with lower rates of pneumonia-related rehospitalisation versus vancomycin in a US retrospective study 2

Conclusions

SAMIR EL ANSARYICU PROFESSOR

AIN SHAMSCAIRO

elansarysamir@yahoo.com

GOOD LUCK