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AG Seifert
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AG Seifert

Group Leader: Prof. Dr. Harald Seifert
Phone: +49 221 478 32008 [Email protection active, please enable JavaScript.]

Selected recent publications (Acinetobacter baumannii)
Selected recent publications (Staphylococcus aureus)


Dr. Paul G. Higgins (-32011/32231/32212 [Email protection active, please enable JavaScript.] )
Jennifer Nowak (-32231 [Email protection active, please enable JavaScript.] )
Danuta Stefanik (-32212 [Email protection active, please enable JavaScript.] )
Priv.-Doz. Dr. Hilmar Wisplinghoff (-32212 [Email protection active, please enable JavaScript.] )
Esther Zander (-32231 [Email protection active, please enable JavaScript.])

Research Topic:
Acinetobacter baumannii and Staphylococcus aureus

Acinetobacter baumannii
Acinetobacter baumannii is a serious and emerging nosocomial pathogen. The organism is characterised by its innate and acquired antimicrobial resistance, a propensity to cause outbreaks, an ability to survive desiccation (unlike most other gram-negatives) and its survival on inanimate materials. These characteristics mean that once established in a hospital, A. baumannii is difficult to eradicate. A. baumannii is often grouped together with the closely-related Acinetobacter genomic species 3 and 13TU. They are collectively termed the Acinetobacter baumannii group.
Our interest in the Acinetobacter baumannii group is centred on identification and speciation, epidemiology, antimicrobial susceptibility and resistance mechanisms.

(i) For the investigation of Acinetobacter baumannii group epidemicity we evaluated and further developed molecular methods such as pulsed-field gel electrophoresis (PFGE) where we have helped establish a short PFGE protocol, multi locus sequence typing (MLST) where we were involved in establishing the A. baumannii MLST scheme, and more recently, the Diversilab semi-automated rep-PCR typing scheme.

(ii) Our investigation into resistance mechanisms has included fluoroquinolone- and carbapenem-resistance, the distribution of carbapenem-hydrolysing enzymes, identification of novel oxacillinases and the worldwide epidemiology of multi-drug resistant A. baumannii.

(iii) We are also involved in the testing of novel antimicrobial compounds such as tigecycline, finafloxacin and most recently BAL 30072 to determine their anti-Acinetobacter potential.

As part of the BMBF-funded Forschergruppe "Klinische Infectiologie" we are currently involved in a study investigating the expression of A. baumannii efflux pumps and outer membrane proteins under different physiological conditions, and the role of the two-component regulatory system AdeRS in expression of the AdeABC efflux pump system.

Other ongoing projects include the molecular epidemiology of Acinetobacter species isolated from German Hospitals and the molecular epidemiology of Acinetobacter baumannii group bloodstream isolates in the United States.

Selected recent publications (2005-date):
Marti S, Rodriguez-Baño J, Catel-Ferreira M, Jouenne T, Vila J, Seifert H, De E. Biofilm formation at the solid-liquid and air-liquid interfaces by Acinetobacter species. .BMC Res Notes. 2011;4:5.

Higgins PG, Lehmann M, Wisplinghoff H, Seifert H. gyrB multiplex PCR to differentiate between Acinetobacter calcoaceticus and Acinetobacter genomic species 3. J Clin Microbiol. 2010; 48:4592-4.

Higgins PG, Schneiders T, Hamprecht A, Seifert H. In Vivo Selection of a missense mutation in adeR and conversion of the novel blaOXA-164 into blaOXA-58 in carbapenem-resistant Acinetobacter baumannii isolated from a hospitalized patient. Antimicrob Agents Chemother 2010; 54:5021-7.

Figueiredo S, Poirel L, Seifert H, Mugnier P, Benhamou D, Nordmann P. OXA-134, a Naturally-Occurring Carbapenem-Hydrolyzing Class D Beta-Lactamase from Acinetobacter lwoffii. Antimicrob Agents Chemother 2010; 54:5372-5.

Hawser SP, Hackel M, Person MB, Higgins PG, Seifert H, Dowzicky M. In vitro activity of tigecycline against carbapenemase-producing Acinetobacter baumannii. Int J Antimicrob Agents 2010; 36(3):289-90.

Pankuch GA, Seifert H, Appelbaum PC. Activity of doripenem with and without levofloxacin, amikacin, and colistin against Pseudomonas aeruginosa and Acinetobacter baumannii. Diagn Microbiol Infect Dis 2010; 67: 191-197.

Eveillard M, Soltner C, Kempf M, Saint-André JP, Lemarié C, Randrianarivelo C, Seifert H, Wolff M, Joly-Guillou ML. The virulence variability of different Acinetobacter baumannii strains in experimental pneumonia. J Infect 2010; 60: 154-61.

Higgins PG, Stubbings W, Wisplinghoff H, Seifert H. Activity of the investigational fluoroquinolone finafloxacin against ciprofloxacin-sensitive and -resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2010; 54:1613-1615.

Higgins PG, Lehmann M, Seifert H. Inclusion of OXA-143 primers in a multiplex polymerase chain reaction (PCR) for genes encoding prevalent OXA carbapenemasesin Acinetobacter spp. Int J Antimicrob Agents 2010; 35:305.

Higgins PG, Dammhayn C, Hackel M, Seifert H. Global spread of carbapenem-resistant Acinetobacter baumannii. J Antimicrob Chemother 2010; 65:233-238.

Higgins PG, Poirel L, Lehmann M, Nordmann P, Seifert H. OXA-143, a novel carbapenem-hydrolyzing class D beta-lactamase in Acinetobacter baumannii. Antimicrob Agents Chemother 2009; 53:5035-8.

Kohlenberg A, Brümmer S, Higgins PG, Sohr D, Piening BC, de Grahl C, Halle E, Rüden H, Seifert H. Outbreak of carbapenem-resistant Acinetobacter baumannii carrying the carbapenemase OXA-23 in a German university medical centre. J Med Microbiol 2009; 58:1499-507.

Stoeva T, Higgins PG, Savov E, Markovska R, Mitov I, Seifert H. Nosocomial spread of OXA-23 and OXA-58 beta-lactamase-producing Acinetobacter baumannii in a Bulgarian hospital. J Antimicrob Chemother 2009; 63:618-20.

Peleg AY, Seifert H, Paterson DL. Acinetobacter baumannii: Emergence of a successful pathogen. Clin Microbiol Rev 2008; 21: 538-582.

Stoeva T, Higgins PG, Bojkova K, Seifert H. Clonal spread of carbapenem-resistant OXA-23-positive Acinetobacter baumannii in a Bulgarian university hospital. Clin Microbiol Infect 2008; 14:723-7.

Wisplinghoff H, Hippler C, Bartual SG, Haefs C, Stefanik D, Higgins PG, Seifert H. Molecular epidemiology of clinical Acinetobacter baumannii and Acinetobacter genomic species 13TU isolates using a multilocus sequencing typing scheme. Clin Microbiol Infect 2008; 14:708-15.

Pankuch GA, Lin G, Seifert H, Appelbaum PC. Activity of meropenem with and without ciprofloxacian and colistin against Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrob Agents Chemother 2008; 52:333-336.

Higgins PG, Wisplinghoff H, Krut O, Seifert H. A PCR-based method to differentiate between Acinetobacter baumannii and Acinetobacter genomic species 13TU. Clin Microbiol Infect 2007; 13:1199-201.

Dijkshoorn L, Nemec A, Seifert H. An increasing threat in hospitals: multidrug-resistant Acinetobacter baumannii. Nat Rev Microbiol 2007;5:939-951.

Wisplinghoff H, Schmitt R, Wöhrmann A, Stefanik D, Seifert H. Resistance to disinfectants in epidemiologically defined clinical isolates of Acinetobacter baumannii. J Hosp Infect 2007; 66: 174-181.

Pannek S, Higgins PG, Steinke P, Jonas D, Akova M, Bohnert JA, Seifert H, Kern WV. Multidrug efflux inhibition in Acinetobacter baumannii: comparison between 1-(1-naphthylmethyl)-piperazine and phenyl-arginine-beta-naphthylamide. J Antimicrob Chemother 2006; 57:970-4.

Seifert H, Stefanik D, Wisplinghoff H. Comparative in vitro activities of tigecycline and 11 other antimicrobial agents against 215 epidemiologically defined multidrug-resistant Acinetobacter baumannii isolates. J Antimicrob Chemother 2006; 58:1099-1100.

Staphylococcus aureus
In recent years bloodstream infections caused by Staphylococcus aureus have increased considerably and are a major cause of morbidity and mortality worldwide. S. aureus is responsible for about 20% of all catheter-associated bloodstream infections and for about 30% of endocarditis cases. In-hospital mortality of S. aureus bacteremia (SAB) is in the range of 20 to 30%. Furthermore, the emergence of methicillin-resistant S. aureus (MRSA) infections has substantially limited therapeutic options. The clinical course of SAB is very variable. Some patients do not show any overt signs of disease whereas other patients suffer from serious complications that may result from dissemination and metastatic infection of distant organs.

To better understand and predict the clinical course of SAB, we are conducting a prospective observational cohort study on patients with SAB at two university hospitals, Freiburg and Köln (INSTINCT – invasive Staphylococcus aureus infection cohort). In this study quality indicators (such as early removal of intravascular catheters, follow-up blood cultures, transesophageal echocardiography, ensuring adequate antimicrobial treatment) are developed to monitor and improve the management of patient with SAB. Of particular interest is the impact of an early proactive, quality indicator-based management on late complications and survival in patients with SAB. This study is part of the BMBF-funded Forschergruppe "Klinische Infektiologie".

We have been involved in a DG SANCO (Directorate General for Public Health and Consumer Protection)-funded multicenter study (BURDEN) to investigate the burden of resistance at the European level in patients with methicillin-susceptible or -resistant S. aureus bloodstream infections in different hospitals in 14 European countries.

Another multicenter pilot study (preSABATO – S. aureus bacteremia antibiotic treatment options) is coordinated by our group. This pilot study is funded by the German research foundation (DFG) and examines the feasibility of conducting large multicenter trials on antibiotic treatment schemes.

Our interest in S. aureus apart from clinical studies is centred on the molecular epidemiology and antimicrobial susceptibility of methicillin-resistant S. aureus (MRSA). We are currently conducting a study to investigate the possible occurrence of a vancomycin MIC creep among MRSA bloodstream isolates isolated between 1984 and 2010. Also, the possible impact of elevated vancomycin MICs on outcome in patients with SAB from our INSTICT cohort is currently under study.

Selected recent publications (2005-date):
de Kraker ME, Wolkewitz M, Davey PG, Grundmann H; on behalf of the BURDEN study group. The clinical impact of antimicrobial resistance in European hospitals: excess mortality and length of hospital stay related to methicillin resistant Staphylococcus aureus bloodstream infections. Antimicrob Agents Chemother. 2011; Jan 10 [Epub ahead of print]

Kaasch A, Fowler VG, Rieg S, Peyerl-Hoffmann G, Birkholz H, Hellmich M, Kern WV, Seifert H. A simple criteria set can guide echocardiography in nosocomial Staphylococcus aureus bacteremia. Clin Infect Dis. 2011 (in press)

Ammerlaan H, Seifert H, Harbarth S, Brun-Buisson C, Torres A, Antonelli M, Kluytmans J, Bonten M. Adequacy of antimicrobial treatment and outcome of Staphylococcus aureus bacteremia in 9 Western European countries. Clin Infect Dis 2009; 49:997-1005.

Naber CK, Baddour LM, Giamarellos-Bourboulis EJ, Gould IM, Herrmann M, Hoen B, Karchmer AW, Kobayashi Y, Kozlov RS, Lew D, Miró JM, Moellering RC Jr, Moreillon P, Peters G, Rubinstein E, Seifert H, Corey GR. Clinical Consensus Conference: survey on gram-positive bloodstream infections with a focus on Staphylococcus aureus. Clin Infect Dis 2009; 48 Suppl 4:S260-70.

Higgins PG, Rosato AE, Seifert H, Archer GL, Wisplinghoff H. Differential expression of ccrA in methicillin-resistant Staphylococcus aureus strains carrying staphylococcal cassette chromosome mec type II and IVa elements. Antimicrob Agents Chemother 2009; 53:4556-8.

Rieg S, Peyerl-Hoffmann G, de With K, Theilacker C, Wagner D, Hübner J, Dettenkofer M, Kaasch A, Seifert H, Schneider C, Kern WV. Mortality of Staphylococcus aureus bacteremia and infectious diseases specialist consultation - a study of 521patients in germany. J Infect 2009; 59:232-239.

Seifert H, Wisplinghoff H, Kaasch A, Achilles K, Langhorst A, Peyerl-Hoffmann G, Woehrmann A, Fatkenheuer G, Salzberger B, Kern WV. Epidemiologie, Verlauf und Prognose der Staphylococcus aureus Bakteriämie - Erste Ergebnisse der INSTINCT Kohorte. Dtsch Med Wochenschr 2008; 133:340-5.

Kalka-Moll WM, Lee JC, Fabri M, Seifert H. Intrafamilial outbreak of subcutaneous abscesses caused by PVL-positive methicillin-sensitive Staphylococcus aureus. J Infect 2008; 57:278-281.

Wisplinghoff H, Ewertz B, Wisplinghoff S, Stefanik D, Plum G, Perdreau-Remington F, Seifert H. Molecular evolution of Methicillin-resistant Staphylococcus aureus in the Cologne metropolitan area from 1984 to 1998. J Clin Microbiol 2005; 43: 5445-5451.

Seifert H, Oltmanns D, Becker K, Wisplinghoff H, von Eiff C. Recurrent pacemaker-related infection caused by small-colony variants (SCVs) of Staphylococcus lugdunensis. Emerg Infect Dis 2005; 11:1283-1286.

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