Johannes Hübner

Mortality of S. aureus bacteremia and infectious diseases specialist consultation – A study of 521 patients in Germany

OBJECTIVES To evaluate the relationship between mortality of bloodstream infection due to Staphylococcus aureus and infectious diseases specialist consultation and other factors potentially associated with outcomes. METHODS A 6-year cohort study was conducted at a 1600-bed university hospital. Consecutive adult patients with S. aureus bacteremia were assessed using a standardised data collection and review form. A new infectious diseases service increased its consultations for S. aureus bacteremia from 33% of cases in 2002 to >80% in 2007. Infectious disease consultation and other factors potentially associated with in-hospital mortality were analysed by multivariate logistic regression. RESULTS A total of 521 patients were studied. All-cause in-hospital mortality was 22%, 90-day mortality was 32%. Factors significantly associated with in-hospital mortality in multivariate analysis were ICU admission (OR 5.8, CI 3.5-9.7), MRSA (OR 2.6, CI 1.4-4.9), age >/=60 years (OR 2.4, CI 1.4-4.2), a diagnosis of endocarditis (OR 2.8, CI 1.4-5.7), a non-fatal underlying disease/comorbidity according to the McCabe classification (OR 0.2, CI 0.1-0.4), and infectious disease specialist consultation (OR 0.6, CI 0.4-1.0). CONCLUSIONS These data suggest that outcome of S. aureus bacteremia may be improved by an expert consultation service.

Lipoproteins Are Critical TLR2 Activating Toxins in Group B Streptococcal Sepsis

Group B streptococcus (GBS) is the most important cause of neonatal sepsis, which is mediated in part by TLR2. However, GBS components that potently induce cytokines via TLR2 are largely unknown. We found that GBS strains of the same serotype differ in released factors that activate TLR2. Several lines of genetic and biochemical evidence indicated that lipoteichoic acid (LTA), the most widely studied TLR2 agonist in Gram-positive bacteria, was not essential for TLR2 activation. We thus examined the role of GBS lipoproteins in this process by inactivating two genes essential for bacterial lipoprotein (BLP) maturation: the prolipoprotein diacylglyceryl transferase gene (lgt) and the lipoprotein signal peptidase gene (lsp). We found that Lgt modification of the N-terminal sequence called lipobox was not critical for Lsp cleavage of BLPs. In the absence of lgt and lsp, lipoprotein signal peptides were processed by the type I signal peptidase. Importantly, both the Δlgt and the Δlsp mutant were impaired in TLR2 activation. In contrast to released factors, fixed Δlgt and Δlsp GBS cells exhibited normal inflammatory activity indicating that extracellular toxins and cell wall components activate phagocytes through independent pathways. In addition, the Δlgt mutant exhibited increased lethality in a model of neonatal GBS sepsis. Notably, LTA comprised little, if any, inflammatory potency when extracted from Δlgt GBS. In conclusion, mature BLPs, and not LTA, are the major TLR2 activating factors from GBS and significantly contribute to GBS sepsis.

Communicable Diseases Prioritized for Surveillance and Epidemiological Research: Results of a Standardized Prioritization Procedure in Germany, 2011

Introduction To establish strategic priorities for the German national public health institute (RKI) and guide the institutes mid-term strategic decisions, we prioritized infectious pathogens in accordance with their importance for national surveillance and epidemiological research. Methods We used the Delphi process with internal (RKI) and external experts and a metric-consensus approach to score pathogens according to ten three-tiered criteria. Additional experts were invited to weight each criterion, leading to the calculation of a median weight by which each score was multiplied. We ranked the pathogens according to the total weighted score and divided them into four priority groups. Results 127 pathogens were scored. Eighty-six experts participated in the weighting; “Case fatality rate” was rated as the most important criterion. Twenty-six pathogens were ranked in the highest priority group; among those were pathogens with internationally recognised importance (e.g., Human Immunodeficiency Virus, Mycobacterium tuberculosis, Influenza virus, Hepatitis C virus, Neisseria meningitides), pathogens frequently causing large outbreaks (e.g., Campylobacter spp.), and nosocomial pathogens associated with antimicrobial resistance. Other pathogens in the highest priority group included Helicobacter pylori, Respiratory Syncytial Virus, Varicella zoster virus and Hantavirus. Discussion While several pathogens from the highest priority group already have a high profile in national and international health policy documents, high scores for other pathogens (e.g., Helicobacter pylori, Respiratory syncytial virus or Hantavirus) indicate a possible under-recognised importance within the current German public health framework. A process to strengthen respective surveillance systems and research has been started. The prioritization methodology has worked well; its modular structure makes it potentially useful for other settings.

CXCL13 may improve diagnosis in early neuroborreliosis with atypical laboratory findings.

BackgroundCurrent guidelines regarding Lyme neuroborreliosis [LNB] require the presence of intrathecal Borrelia burgdorferi-specific antibody production for the definite diagnosis of LNB. However, about 20% of early stage infections present without an elevated antibody index. Moreover, intrathecal B. burgdorferi specific antibody synthesis may persist long after successful therapy of LNB. Recently published data indicate that CXCL13 seems to be a promising diagnostic tool for early stage LNB. In addition, CXCL13 might be suitable for treatment monitoring.Case presentationWe report on a 39-year-old male patient from southern Germany, who has been suffering from subfebrile body temperatures and meningeal headache for six weeks. On the second day after hospital admission he developed peripheral palsy of the VII. cranial nerve. Cerebrospinal fluid (CSF) analysis showed granulocytic pleocytosis, elevated total protein and blood-CSF barrier dysfunction. Differential diagnostics for granulocytic pleocytosis were unremarkable. Only a second lumbar puncture, on day 6 after admission, revealed a lymphocytic pleocytosis. Serologic testing pointed to clear intrathecal Borrelia specific IgG antibody production. Interestingly, no anti-OspC antibodies were detectable. DNA of the rare Borrelia garinii OspA-type 7 could be amplified from the first CSF sample. The monitoring of CXCL13 in all CSF samples documented a fast decrease from 5000 pg/ml to 450 pg/ml after appropriate antibiotic treatment.ConclusionCXCL13 is a novel biomarker with high sensitivity and specificity for acute LNB. Our data show, that CXCL13 might be helpful in unclear cases and support the presumption that it might be a valuable tool for treatment monitoring. Anti-OspC antibody negativity is a rare observation, given the need of OspC for infection of the human hosts. Most likely this is due to a lack of sensitivity of OspC immunoblots that are unable to detect rare OspC variants.

Cross infections due to coagulase-negative staphylococci in high-risk patients.

Until recently, infections due to coagulase-negative staphylococci (CNS) have been regarded as endogenous in origin. However, there are now increasingly reports in the literature on the endemic occurrence of distinct strains of CNS. Several outbreaks due to CNS are reported in cardiac surgery or in neonates. The latter seem to be high risk populations in regard to CNS infections because of certain risk factors (i.e. degree of immunosupression, routine use of central venous catheters and parenteral lipids as well as broad spectrum antibiotic therapy). On the other hand, these newborn babies have no physiological skin flora and are therefore easily colonized by multiresistent bacteria. The persistence of certain well-defined Staphylococcus epidermidis (SE) strains in neonatal intensive care units have been demonstrated over periods as long as a decade. Specific putative virulence factors (i.e. slime production and polysaccharide/adhesin PS/A) were more common in endemic strains as compared to single isolates. Pulsed-field gel electrophoresis (PFGE) proves to be a powerful tool in the study of the epidemiology of CNS while other modern typing techniques (ribotyping, plasmid typing) were also used in the literature to investigate outbreaks of CNS infections.

Combination effect of SCE-2787 and cefepime with aminoglycosides on nosocomial gram-negative bacteria

SummaryThein vitro activity of cefepime and SCE-2787, two new parenteral cephalosporins, and the combination effect with tobramycin and gentamicin against nosocomial gram-negative rods was studied using checker-board agar dilution technique. Cefepime showed excellentin-vitro activity againstKlebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens andProteus vulgaris (MIC90 0.03–0.125 mg/l) and good to moderate activity againstAcinetobacter anitratus, Pseudomonas aeruginosa andPseudomonas cepacia (MIC90 4–16 mg/l). SCE-2787 had an excellent activity againstCitrobacter spp. (MIC90 0.125 mg/l) and a very good activity againstA. anitratus, P. aeruginosa andP. vulgaris (MIC90 1–2 mg/l).Pseudomonas maltophilia was not inhibited at therapeutically achievable concentrations (MIC90 64 mg/l). On average, 14–28% of the strains were inhibited by synergistic SCE-2787 aminoglycoside-combinations, whereas only 8.6% were inhibited by a synergistic effect of the combination with cefepime and gentamicin. No antagonism occurred with any of the combinations.ZusammenfassungMittels der Checker-board-Agar-Dilutionstechnik wurden Cefepime und SCE-2787, zwei neue parenterale Cephalosporine sowie die Kombinationswirkung dieser Substanzen mit den Aminoglykosiden Tobramycin und Gentamicin gegen klinisch wichtige gramnegative Erreger untersucht. Cefepim zeigte eine ausgezeichneteIn-vitro-Wirksamkeit gegenüberKlebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens andProteus vulgaris, wobei die MHK90-Werte zwischen 0,03 und 0,125 mg/l lagen; eine gute bis mäßige Aktivität zeigte die Substanz gegenAcinetobacter anitratus, Pseudomonas aeruginosa undPseudomonas cepacia (MHK90-Werte zwischen 4 und 16 mg/l). SCE-2787 wies eine ausgezeichnete Aktivität gegenCitrobacter spp. (MHK90 0,125 mg/l) und eine sehr gute Aktivität gegenA. anitratus, P. aeruginosa undP. vulgaris auf (MHK90-Werte 1–2 mg/l),Pseudomonas maltophilia wurde allerdings von therapeutisch erreichbaren Konzentrationen nicht gehemmt (MHK90 64 mg/l). Bei 14–28% der Stämme wurde ein synergistischer Effekt der SCE-2787-Aminoglycosid-Kombination und in 8,6% der Stämme eine synergistische Wirkung der Cefepim-Gentamicin-Kombination beobachtet. Eine antagonistische Wirkung konnte bei keiner der untersuchten Kombinationen festgestellt werden.