Antimicrobial susceptibility of bacterial isolates from patients presenting with ear, nose and throat (ENT) infections in the German community healthcare setting.

Empiric initial antibiotic therapy of bacterial infections is based primarily upon the susceptibility of the most common causative pathogens. The purpose of this study was to provide susceptibility data on six bacterial species known to cause ear, nose and throat (ENT) infections. A total of 1066 isolates collected during a nationwide laboratory-based surveillance study were analysed. All Streptococcus pyogenes isolates were penicillin (PEN)-susceptible, indicating that natural penicillins can still be recommended as the first-line treatment for group A streptococcal tonsillopharyngitis. Of the S. pneumoniae isolates, 92.9% were PEN-susceptible and of the Haemophilus influenzae isolates, 89.7% were amoxicillin-susceptible, retaining aminopenicillins as the first-line treatment for acute otitis media (AOM) and acute rhinosinusitis (ARS), in case antibiotic therapy is considered. In contrast, cefuroxime axetil seems less likely to be suitable for the treatment of AOM or ARS, as all Moraxella catarrhalis and >99% of the H. influenzae isolates were categorised as intermediate or resistant. The susceptibility rates of Pseudomonas aeruginosa were 97-100% for the drugs tested, except for the fluoroquinolones (87.6%). Overall, bacterial isolates from outpatients presenting with ENT infections showed low frequencies of resistance in Germany. However, given the emergence of multidrug resistance to standard antibiotics in Escherichia coli and other pathogens, inappropriate use of broad-spectrum antibiotics for the treatment of ENT infections has to be avoided.

Comparative in vitro activity of oral antimicrobial agents against Enterobacteriaceae from patients with community-acquired urinary tract infections in three European countries.

Enterobacteriaceae causing community-acquired urinary tract infections were examined in selected outpatient clinics and hospitals in Belgium, Germany and Spain using EUCAST breakpoints for susceptibility. A total of 1190 isolates were collected. Escherichia coli isolates were resistant to amoxicillin-clavulanic acid (28.1%), ciprofloxacin (23.4%) and trimethoprim-sulfamethoxazole (21.4%) compared with fosfomycin and nitrofurantoin (each, <1.5%). Ceftibuten (MIC50/90 0.25/0.5 mg/L) and ceftriaxone activity (MIC50/90 ≤0.25 mg/L) was comparable. Ceftibuten (MIC90 ≤0.25 mg/L) was also active against Proteus mirabilis and Klebsiella spp. Extended-spectrum ß-lactamase phenotypes were 7.1% for E. coli, 5.6% for Klebsiella pneumoniae and 0.4% for P. mirabilis. Resistance was common among men and elderly women.

Molecular epidemiology of Acinetobacter baumannii and Acinetobacter nosocomialis in Germany over a 5-year period (2005-2009).

To investigate the species distribution within the Acinetobacter calcoaceticus-Acinetobacter baumannii complex and the molecular epidemiology of A. baumannii and Acinetobacter nosocomialis, 376 Acinetobacter isolates were collected prospectively from hospitalized patients at 15 medical centres in Germany during three surveillance studies conducted over a 5-year period. Species identification was performed by molecular methods. Imipenem minimum inhibitory concentrations (MIC) were determined by broth microdilution. The prevalence of the most common carbapenemase-encoding genes was investigated by oxacillinase (OXA) -multiplex polymerase chain reaction (PCR). The molecular epidemiology was investigated by repetitive sequence-based PCR (rep-PCR; DiversiLab™). Acinetobacter pittii was the most prevalent Acinetobacter species (n = 193), followed by A. baumannii (n = 140), A. calcoaceticus (n = 10) and A. nosocomialis (n = 8). The majority of A. baumannii was represented by sporadic isolates (n = 70, 50%) that showed unique rep-PCR patterns, 25 isolates (18%) clustered with one or two other isolates, and only 45 isolates (32%) belonged to one of the previously described international clonal lineages. The most prevalent clonal lineage was international clone (IC) 2 (n = 34) and IC 1 (n = 6). According to CLSI, 25 A. baumannii isolates were non-susceptible to imipenem (MIC ≥ 8 mg/L), all of which produced an OXA-58-like or OXA-23-like carbapenemase. The rate of imipenem susceptibility among A. baumannii isolates decreased from 96% in 2005 to 76% in 2009. All other Acinetobacter isolates were susceptible to imipenem. The population structure of carbapenem-susceptible A. baumannii in Germany is highly diverse. Imipenem non-susceptibility was strongly associated with the clonal lineages IC 2 and IC 1. These data underscore the high clonality of carbapenem-resistant A. baumannii isolates.

Comparative activity of pradofloxacin and marbofloxacin against coagulase-positive staphylococci in a pharmacokinetic-pharmacodynamic model based on canine pharmacokinetics.

Pradofloxacin (PRA), a novel veterinary 8-cyano-fluoroquinolone (FQ), is active against Staphylococcus pseudintermedius, the primary cause of canine pyoderma. An in vitro pharmacokinetic-pharmacodynamic model was used to compare the activities of PRA and marbofloxacin (MAR) against three clinical isolates of S. pseudintermedius and reference strain Staphylococcus aureus ATCC 6538. Experiments were performed involving populations of 10(10) CFU corresponding to an inoculum density of approximately 5 × 10(7) CFU/mL. The time course of free drug concentrations in canine serum was modelled, resulting from once daily standard oral dosing of 3 mg of PRA/kg and 2 mg of MAR/kg. In addition, experimentally high doses of 6 mg of PRA/kg and 16 mg of MAR/kg were tested against the least susceptible strain. Viable counts were monitored over 24 h. At concentrations associated with standard doses, PRA caused a faster and more sustained killing than MAR of all strains. The ratios of free drug under the concentration-time curve for 24 h over MIC and the maximum concentration of free drug over MIC were at least 90 and 26, and 8.5 and 2.1 for PRA and MAR, respectively. At experimentally high doses, PRA was superior to MAR in terms of immediate killing. Subpopulations with reduced susceptibility to either FQ did not emerge. We conclude that PRA is likely to be an efficacious therapy of canine staphylococcal infections.

Resistance trends and in vitro activity of tigecycline and 17 other antimicrobial agents against Gram-positive and Gram-negative organisms, including multidrug-resistant pathogens, in Germany.

To document the development of resistance to tigecycline in comparison with 17 other antimicrobials, the susceptibilities of 2,741 isolates comprising 16 bacterial species recovered from hospitalised patients in 15 German centres in 2009 were assessed. The results were compared with those of previous trials (German Tigecycline Evaluation Surveillance Trial, G-TEST I and II, performed in 2005 and 2007, respectively) conducted prior to and shortly after the introduction of tigecycline in Germany. Moreover, the in vitro activities of tigecycline against the subset of multidrug-resistant (MDR) pathogens recovered within all three sampling periods (n = 4,988) were evaluated in comparison to the corresponding non-MDR isolates. All susceptibility tests were performed by broth microdilution. Between 2005 and 2009, tigecycline retained its high activity against Gram-positive and Gram-negative organisms, including MDR pathogens. By contrast, an in part marked increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for many Enterobacteriaceae and for non-fermenting Gram-negative bacteria. Against a background of a steadily increasing number of multiresistant pathogens, the activity of tigecycline remained unaltered. With the exception of Acinetobacter isolates with decreased susceptibility to carbapenems, tigecycline's activity profile was not notably affected by organisms resistant to other drug classes and, thus, holds promise as an important therapeutic agent, particularly for situations in which MDR organisms are suspected.

Reference scales for the characterization of cationic electrophiles and neutral nucleophiles.

Twenty-three diarylcarbenium ions and 38 pi-systems (arenes, alkenes, allyl silanes and stannanes, silyl enol ethers, silyl ketene acetals, and enamines) have been defined as basis sets for establishing general reactivity scales for electrophiles and nucleophiles. The rate constants of 209 combinations of these benzhydrylium ions and pi-nucleophiles, 85 of which are first presented in this article, have been subjected to a correlation analysis to determine the electrophilicity parameters E and the nucleophilicity parameters N and s as defined by the equation log k(20 degrees C) = s(N + E) (Mayr, H.; Patz, M. Angew. Chem., Int. Ed. Engl. 1994, 33, 938-957). Though the reactivity scales thus obtained cover more than 16 orders of magnitude, the individual rate constants are reproduced with a standard deviation of a factor of 1.19 (Table 1). It is shown that the reactivity parameters thus derived from the reactions of diarylcarbenium ions with pi-nucleophiles (Figure 3) are also suitable for characterizing the nucleophilic reactivities of alkynes, metal-pi-complexes, and hydride donors (Table 2) and for characterizing the electrophilic reactivities of heterosubstituted and metal-coordinated carbenium ions (Table 3). The reactivity parameters in Figure 3 are, therefore, recommended for the characterization of any new electrophiles and nucleophiles in the reactivity range covered. The linear correlation between the electrophilicity parameters E of benzhydryl cations and the corresponding substituent constants sigma(+) provides Hammett sigma(+) constants for 10 substituents from -1.19 to -2.11, i.e., in a range with only very few previous entries.

Immune responses in hepatitis C virus infection.

Infection with the hepatitis C virus (HCV) commonly causes persistent disease, which may lead to cirrhosis and hepatocellular carcinoma. The pathogenesis of HCV infection is not well understood. It is most likely that both viral and host factors contribute to HCV persistence. This review focuses on the host's immune response to HCV in an attempt to present the current knowledge and concepts of the interactions between the virus and the host during HCV infection. Expansion of B lymphocytes and antibody production to virtually any HCV protein can be detected in most infected patients. However, observations in HCV-infected humans as well as experimental infections in chimpanzees suggest that natural HCV infection does not induce protective immunity, and reinfection can readily be demonstrated after inoculation with homologous or independent strains in HCV-seroconverted animals. Nevertheless, the immune system may gain partial control over HCV even in patients with chronic infection, as HCV infection in severely immunocompromised patients runs a particular cholestatic course which may rapidly lead to death from liver failure. Cytotoxic CD8+ T lymphocyte responses to HCV proteins have been characterized in peripheral blood and liver tissue and were found to be remarkably polyclonal and multispecific. Epitopes were identified on all of the putative HCV proteins, although only few major histocompatibility complex molecules were considered restriction elements. Immunoregulation may be particularly important in HCV infection. The HCV core and NS4 proteins appear to be most immunogenic for peripheral blood lymphocytes, and NS4 specific CD4+ lymphocytes are preferentially compartmentalized to the liver. However, there is an inverse relationship between CD4+ lymphocyte responses and antibody levels in infected patients. Furthermore, a strong cellular response to the HCV core protein apparently favors a benign course of infection. This unusual T-B cell relationship may be the consequence of an altered cytokine release during HCV infection. Alternatively, this virus may have found devices that can disturb immunoregulation in infected patients. A better understanding of these immunological mechanisms induced by HCV infection should make it possible to develop more effective strategies for the prevention and treatment of this insidious disease.

[Directions of an ethic in genetic engineering: evaluation of an ethic for biotechnology]. / Leitlinien einer Ethik der Gentechnik. Vorüberlegungen zu einer Ethik der Biotechnologie.

A fundamentalistic point of view is for the evaluation of genetic engineering inadequate. Using ethics to evaluate the consequences is not valid for gene transfers across species as a morally relevant criterion but is rather the assessment of toxic, pathogenic, and ecological effects of transgenic organisms. A criterion for human genetics is not the inviolability of the human embryo, but social and human tolerance and the consent of the affected.

[The relationship of analytic to biological variance--consequences for diagnosis and for the choice of laboratory tests]. / Das Verhältnis von analytischer zu biologischer Varianz--Konsequenzen für die Diagnostik und für die Auswahl von Labortests.

The paper deals with the formal dependence of diagnostic efficiency of clinical laboratory methods from analytic error. The parameters of frequency distribution and the estimation of variance of the analytical error are taken into account. This dependence is constructed basing on an universal model for solving classification tasks using error-contaminated data. The diagnostic efficiency is calculated as a function of the variance of analytical error. A comparison of calculated efficiencies with data gained in a special experiment showed a good agreement.