PubMed 12.02.2017

Stichwort ESBL – E. coli

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Mädchen, 6 Jahre alt

Herkunft „Goldener Halbmond“

perforierte Appendizitis

Enterobakterien in vitro DSP Blutkulturen 2015

Gramnegative Sepsis

Bauch, Harntrakt

Bis vor 5 Jahren

• Amoxicillin / Clav

• Ampicillin / Sulb

• Ciprofloxacin

• Levofloxacin

Jetzt

• Tazonam

• Cephalosporine 3 & 4

• Peneme

All-cause mortality at the end of follow-up for BL/BLIs versus carbapenems

b-Lactam/b-lactamase inhibitors versus carbapenems for the treatment of sepsis:

systematic review and meta-analysis of randomized controlled trials Shachaf Shibe, JAC 2015

Carbapeneme

Substanz Indikation Bemerkung

Ertapenem

Invanz

ESBL

SSTI

IAI

1 x täglich

ambulante i.v. AB Therapie !

Septischer Bauch !

Urosepsis! Imipenem

Meropenem 3 x 1 gr

nosokomial

Meropenem in Vitro DSP 2013-2015 (ca. 2090 Einzelisolate)

Fosfomycin facts

• Gute Penetration in schwer

erreichbare Kompartments

Knochen, Liquor, Lunge, …

• Gute Penetration in

Abszesse

• aktiv bei niedrigem pH

• Synergie mit Laktamen

• keine Organtoxizität

• Elektrolyte !

• therapeutische Breite

12 – 16 – 24 gr / Tag

• Inhalativ, Dauerinfusion

Fosfomycin Indikationen

alt

• DFS

• Pleuraempyem

• Hirnabszess, …

• Osteitis

• komplizierte …

neu z.B.

• Harnwegsinfekte

• urologische Prophylaxe

• chirurgische Prophylaxe

• Empirie bei V.a. MRE

• Monotherapie!

Matthew E. Falagas et al. Clin Infect Dis. 2008;46:1069-1077

Amikacin fosfomycin inhalation solution 300 mg of amikacin 120 mg

of fosfomycin twice daily for 10 days

Nebulized and intravenous colistin in experimental pneumonia

caused by Pseudomonas aeruginosa

Quin Lu

Efficacy of High-dose Nebulized Colistin (3 x 5 MIO !!!) in Ventilator associated

Pneumonia Caused by Multidrug-resistant Pseudomonas aeruginosa and

Acinetobacter baumannii Qin Lu, Anesthesiology 2012

During the subsequent cultures, the last cultures positive for MDRAB in the case

group were at day 8.2 ± 6.4 after the index day, but were at day 21.5 ± 4.5 (p

<0.001) in the control group

Inhal. Dosierung 2 x 2 MIO IE

Tigecyclin & Acinetobacter

• Occurrence of carbapenem-resistant Acinetobacter baumannii clones at multiple hospitals in London and Southeast England. J Clin Microbiol. 2006

• Activity of tigecycline (GAR-936) against Acinetobacter baumannii strains, including those resistant to imipenem. Antimicrob Agents Chemother. 2004

• Successful treatment of septic shock due to pan-resistant Acinetobacter baumannii using combined antimicrobial therapy including tigecycline. Eur J Clin Microbiol Infect Dis. 2006

Pharmacokinetic Considerations regarding Tigecycline for Multidrug-

Resistant (MDR) Klebsiella pneumoniae or MDR Acinetobacter

baumannii Urosepsis

Burke A. Cunha in JOURNAL OF CLINICAL MICROBIOLOGY, 2009

High-dose tigecycline-associated alterations in coagulation

parameters in critically ill patients with severe infections International Journal of Antimicrobial Agents 45 (2015) 84–95

Neue AB ab 2015

• Ceftarolin ZINFORO ®

• Ceftobiprol ZEVTERA ®

• Ceftazidim – Avibactam CEREXA ®

AVYZAC ®

• Ceftolozan – Tazobactam ZERBAXA ®

• Tedizolid SIVEXTRO ®

• Dalbavancin XYDALBA ®

• Oritovancin ORBACTIV ®

Ceftolozan Tazobactam in vitro Februar & März 2016

Pat liegt im DSP von Mrz - Juli

April Mai Juni

Colistin pharmacokinetics

Clinical Microbiology and Infection Volume 18, Issue 1, pages 30-39, 11 OCT 2011

Simulations of steady-state colistin methanesulphonate (CMS) (a) and colistin (b) plasma concentrations vs. time following administration of the same daily dose of CMS with various dosing regimens (9 MIU/24 h (red), 4.5 MIU/12 h (blue), and 3 MIU/8 h (green)), for a typical patient with creatinine clearance set at 60 mL/min, CMS non-renal clearance and colistin clearance equal to 50 mL/min, and CMS and colistin Vss set at 15 L.

Efficacy and safety of high-dose ampicillin/sulbactam vs. colistin as monotherapy for the

treatment of multidrug resistant Acinetobacter baumannii ventilator-associated

pneumonia

Alex P. Betrosian et al Journal of Infection (2008)

COL 3 MIU every 8 h

Amp/Sulb 9 g every 8 h

• In the kill-curve studies

azithromycin and rifampin were rapidly bactericidal

sulbactam was more slowly bactericidal.

Trovafloxacin and doxycycline were bacteriostatic

None of the antimicrobials tested were bactericidal against

all strains tested

• The synergy studies demonstrated that the combinations of

sulbactam with azithromycin, rifampin, doxycycline, or

trovafloxacin were generally additive or indifferent.