Atopic dermatitis shows significant cutaneous comorbidity: results from large-scale investigations in the working population.

BACKGROUND: Atopic dermatitis (AD) is one of the most common chronic inflammatory diseases of the skin. Rare large-scale data have been published on the prevalence of concomitant dermatoses. OBJECTIVE: To analyse the prevalence and cutaneous comorbidity of AD in Germany. METHODS: A cross-sectional study on voluntary whole-body skin checks by trained dermatologists in over 400 companies throughout Germany reflecting the adult working population was conducted. Prevalence ratios (PR) were calculated to compare dermatological comorbidity in employees with and without current AD. A logistic regression analysis controlling for age, sex and skin type revealed odds ratios (OR) of the occurrence of skin diseases in AD. RESULTS: A total of N = 118 939 people were examined between 2006 and 2017 (43.2% female, mean age 43.2 ± 10.7 years, min. age 16 years, max. age 70 years). AD (point prevalence) was identified in 1.45% (men: 1.50%, women 1.39%) and decreased significantly with age. Self-reported lifetime prevalence of AD was 4.95% (men: 3.72%, women: 6.55%). The following skin diseases were significantly more frequent in people with current AD: Contact dermatitis (PR: 3.38), hand eczema (PR: 4.62), exsiccation dermatosis (PR: 2.19), folliculitis (PR: 1.95) and port-wine stains (PR: 1.49). Among those, folliculitis was the most frequent (prevalence in AD 16.42%). Controlled for age, sex and skin type, AD was significantly associated with - among others - hand eczema (OR: 3.96; 95% CI: 2.95-5.32), contact dermatitis (OR: 2.97; 95% CI: 1.50-5.88) and exsiccation dermatosis (OR: 1.78; 95% CI: 1.30-2.44). Psoriasis was significantly less frequent in people with AD (OR: 0.61; 95% CI: 0.39-0.94). CONCLUSION: In summary, cutaneous comorbidity is frequent and of great importance in people with AD, suggesting the need for comprehensive, dermatologically guided diagnostics in AD.

Epidemiology and dermatological comorbidity of seborrhoeic dermatitis: population-based study in 161 269 employees.

BACKGROUND: Seborrhoeic dermatitis is a common but epidemiologically poorly researched chronic skin disease. OBJECTIVES: To characterize the prevalence and dermatological comorbidity of seborrhoeic dermatitis in Germany. METHODS: In the course of voluntary company skin checks, full-body examinations were carried out in more than 500 companies by experienced dermatologists and documented electronically. RESULTS: In total, 161 269 participants were included (men 55·5%, mean age 43·2 ± 10·9 years). Seborrhoeic dermatitis was identified in 3·2% (men 4·6%, women 1·4%). A significant difference was found between age groups (2·0% in < 35; 3·6% in 35-64; 4·4% ≥ 65 years). The most frequent concomitant skin conditions were: folliculitis [17·0%, 95% confidence interval (CI) 15·9-18·1], onychomycosis (9·1%, 95% CI 8·3-10·0), tinea pedis (7·1%, 95% CI 6·3-7·8), rosacea (4·1%, 95% CI 3·6-4·7), acne (4·0%, 95% CI 3·4-4·5) and psoriasis (2·7%, 95% CI 2·3-3·2). Regression analysis revealed the following relative dermatological comorbidities when controlling for age and sex: folliculitis [odds ratio (OR) 2·1, 95% CI 2·0-2·3], contact dermatitis (OR 1·8, 95% CI 1·1-2·8), intertriginous dermatitis (OR 1·8, 95% CI 1·4-2·2), rosacea (OR 1·6, 95% CI 1·4-1·8), acne (OR 1·4, 95% CI 1·2-1·7), pyoderma (OR 1·4, 95% CI 1·1-1·8), tinea corporis (OR 1·4, 95% CI 1·0-2·0), pityriasis versicolor (OR 1·3, 95% CI 1·0-1·7) and psoriasis (OR 1·2, 95% CI 1·0-1·5). CONCLUSIONS: Seborrhoeic dermatitis is a common disease, which is more prevalent in men and older people, and it has an increased rate of dermatological comorbidity. However, absolute differences in the prevalence of comorbidities are small and negligible. Nevertheless, the findings underline the need for integrated, complete dermatological diagnostics and therapy.

Pneumococcal vaccination: what have we learnt so far and what can we expect in the future?

Individuals <2 years and ≥ 50 years of age, as well as those with other specific risk factors, are especially vulnerable to invasive pneumococcal disease (IPD). Conjugate vaccines have been developed against encapsulated bacteria such as Streptococcus pneumoniae to provide improved immune responses. The 7-valent pneumococcal conjugate vaccine (PCV7) has significantly reduced the burden of vaccine-type pneumococcal diseases in children, including invasive disease and pneumonia and acute otitis media. There have also been significant declines in antimicrobial resistance in 7-valent vaccine serotypes and carriage of S. pneumoniae in the post-PCV7 era. Two to three years after the introduction of PCV13, there is emerging, global evidence of a reduced burden of pneumococcal diseases in children, including declines in IPD (UK and Germany) and nasopharyngeal carriage of PCV13 serotypes (Portugal and France). The functional immunogenicity of PCV13 in individuals ≥ 50 years of age has been demonstrated in clinical trials in comparison with the 23-valent pneumococcal polysaccharide vaccine and for children and adults 6 to 49 years of age. Between 2011 and 2013, PCV13 received market authorisation by the European Medicines Agency (EMA) for these additional age groups and is now available in Europe for the prevention of pneumococcal disease in all age groups.

Penicillin susceptibility breakpoints for Streptococcus pneumoniae and their effect on susceptibility categorisation in Germany (1997-2013).

Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. From July 1, 1997, to June 30, 2013, data on penicillin susceptibility were available for 20,437 isolates. 2,790 of these isolates (13.7 %) originate from patients with meningitis and 17,647 isolates (86.3 %) are from non-meningitis cases. A slight decline in isolates susceptible at 0.06 and 0.12 µg/ml can be noticed over the years. Overall, 89.1 % of the isolates had minimum inhibitory concentrations (MICs) of ≤0.015 µg/ml. In 2012/2013, the first three isolates of Streptococcus pneumoniae with MICs of 8 µg/ml were found. The application of different guidelines with other MIC breakpoints for the interpretation of penicillin resistance leads to differences in susceptibility categorisation. According to the pre-2008 Clinical and Laboratory Standards Institute (CLSI) interpretive criteria, 5.3 % of isolates overall were intermediate and 1.4 % were resistant to penicillin. Application of the 2008-2014 CLSI interpretive criteria resulted in 7.6 % resistance among meningitis cases and 0.5 % intermediate resistance in non-meningitis cases. Referring to the 2009-2014 European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints, 7.6 % of the isolates in the meningitis group were resistant to penicillin. In the non-meningitis group, 6.1 % of the isolates were intermediate and 0.5 % were resistant. These differences should be kept in mind when surveillance studies on pneumococcal penicillin resistance are compared.

Serotype distribution in pneumococcal acute otitis media with ruptured tympanic membrane or sepsis in Germany.

This retrospective analysis examined the pneumococcal serotype distribution of acute otitis media in Germany from 1995 to 2007. Data from the German National Reference Centre for Streptococci included 512 cases of pneumococcal otitis media in children and adults. Infections were mainly seen in children aged <5 years, who represented 67.0% of all reported cases. Most isolates (86.7%) were from spontaneous ruptures of the tympanum; 11.1% of the isolates were from otogenic sepsis or meningitis. Serotype 19F was the leading serotype (21.5%); serotype 3 (13.9%) was also often encountered. In children aged <5 years, the 7-valent, 10-valent, and 13-valent pneumococcal conjugate vaccines covered 54.3%, 60.2%, and 84.6% of the serotypes, respectively. Reduced penicillin susceptibility (minimum inhibitory concentration >or=0.1 mg/l) was seen in 11.0% of strains; 22.4% of strains were resistant to macrolides. Although based on a very limited selection of acute otitis media isolates, this analysis provides an estimate of the pneumococcal serotypes responsible for otitis media in Germany and underscores the need for future prospective studies.

Risk factor analysis for pneumococcal meningitis in adults with invasive pneumococcal infection.

Pneumococcal meningitis is a subgroup of invasive pneumococcal disease with a case-fatality rate of up to 30% and long-term sequelae in more than 50% of cases in adults in developed countries. We aimed to determine risk factors for this particular form of pneumococcal disease. We conducted a prospective population-based laboratory study of invasive pneumococcal disease in adults in North-Rhine-Westphalia, Germany from February 2001 to August 2006. All isolates underwent serotyping and susceptibility testing at the National Reference Centre for Streptococci in Aachen, Germany. Data were analysed using multiple linear regression. A total of 1043 isolates from bacteraemia and 131 isolates from meningitis were included into the study. Serotype 23F and being female were independent risk factors for pneumococcal meningitis. Being 60 years and serotype 1 were associated with a reduced odds ratio. Season, penicillin and macrolide resistance were not statistically associated with CNS involvement.

Epidemiology of invasive Streptococcus pyogenes infections in Germany, 1996-2002: results from a voluntary laboratory surveillance system.

A nationwide voluntary laboratory-based surveillance study of invasive Streptococcus pyogenes (group A streptococcus; GAS) infections was conducted in Germany between 1996 and 2002. Demographical and clinical information concerning the patients was obtained from the medical files. Multiple logistic regression analysis was used to determine risk-factors for fatal outcome. Invasive isolates were obtained from 475 patients, with 251 (52.8%) of the isolates cultured from blood. The most frequent emm types were emm1 (36.4%), emm28 (8.8%) and emm3 (8%). The speA, speC and ssa genes were present at variable frequencies in different emm types. The highest frequencies of speA and speC were found in emm1 (speA, 93.6%) and emm4 (speC, 94.7%), respectively. The estimated annual incidence of invasive GAS disease for 1997-2002 was 0.1 cases/100 000 individuals. This apparently low incidence rate might be explained by the voluntary nature of the surveillance system, resulting in relatively few cases being referred to the laboratory. Complete clinical information was available for 165 cases. The overall case fatality rate was 40.6%, and was highest (65.2%) in the group aged 60-69 years. Shock, an age of >or=30 years and adult respiratory distress syndrome were predictors of a fatal outcome in a multiple logistic regression analysis. Overall, 6.7% of the cases were considered to be nosocomial, and nine cases of puerperal sepsis were observed. The study underscores the importance of invasive S. pyogenes disease in Germany.

Molecular epidemiology of penicillin-non-susceptible Streptococcus pneumoniae isolates from children with invasive pneumococcal disease in Germany.

A population-based nationwide surveillance of antibiotic resistance associated with invasive pneumococcal disease (IPD) in children and adolescents (aged<16 years) was performed in Germany between 1997 and 2004. In total, 1517 isolates were collected, of which 5.1% and 1.1% were intermediately- or fully-resistant, respectively, to penicillin G. During the 8-year study period, an increase in resistance to both penicillin G and erythromycin A was observed, and the frequency of isolates exhibiting reduced susceptibility to penicillin G or erythromycin A increased from 1.4% and 11.1%, respectively, in 1997, to 8.7% and 29.0%, respectively, in 2004. Among the penicillin non-susceptible pneumococcal isolates, serotypes 14 (24.5% of isolates), 23F (16.0%) and 6B (16.0%) were found most frequently. Multilocus sequence typing of 58 (62%) penicillin G non-susceptible isolates revealed that sequence type (ST) 156 (Spain9V-3 clone) and its single-locus variant ST 557 were widespread in Germany. Moreover, 17 new penicillin G non-susceptible STs were defined for the first time. The study illustrated the genetic heterogeneity of antibiotic-resistant pneumococcal isolates in Germany.

Invasive pneumococcal disease in adults in North-Rhine Westphalia, Germany, 2001-2003.

A population-based survey of invasive pneumococcal disease (IPD) was conducted among adults in North-Rhine Westphalia, Germany. The study included 202 of the 386 hospitals in the region, together with the 27 microbiological laboratories that submitted reports of IPD in these hospitals to the National Reference Centre for Streptococci. The reports of 16 laboratories were comprehensively reviewed. Most (95.8%) IPD isolates were susceptible to penicillin G, but 14.5% were resistant to clarithromycin. Serotypes 14 (15.6%), 3 (9.3%), 4 (7.1%) and 7F (7.9%) were the most common. The serotype coverage of the 23-valent pneumococcal polysaccharide vaccine was 80.8%. During 2001-2003, the annual incidence of IPD, after correcting for laboratory and hospital under-reporting, was 16.2/100 000 in individuals aged >or= 65 years. In three university hospitals, blood cultures were obtained for only 37% of patients with community-acquired pneumonia, and fewer than one-third of such cultures were obtained in one hospital before antibiotics were prescribed, suggesting that the true incidence of IPD was closer to 50/100 000.

Increasing antimicrobial resistance in gram-negative bacilli isolated from patients in intensive care units.

BACKGROUND: We investigated gram-negative bacilli from patients in intensive care units to determine whether antimicrobial resistance was increasing. METHODS: Minimal inhibitory concentrations were determined by broth microdilution on 334 gram-negative bacilli collected in 1990, 1995, and 1998. RESULTS: During the 3 study years, the types of gram-negative bacilli encountered in our intensive care units changed with proportional increases of Pseudomonas sp and decreases of inducible enterics. Dramatic increases in resistance for ceftazidime, cefotaxime, and piperacillin were paralleled between respiratory-tract isolates and inducible enterics. By 1998, ticarcillin was more active than piperacillin against most isolates except Escherichia coli and Klebsiella sp, and most isolates became more resistant to gentamicin and tobramycin. CONCLUSIONS: Continuous changes in the types of gram-negative bacilli and antimicrobial resistance complicate empirical selection of antimicrobials in the intensive care units. These complications will place more emphasis on communication and strategy formations among health care workers (nurses, physicians, laboratorians, and pharmacists) in an effort to treat infections in a timely and effective manner.

Streptococcus mitis with unusually high level resistance to beta-lactam antibiotics.

Penicillin-resistant oral streptococci constitute the genetic reservoir for beta-lactam resistance in S. pneumoniae. Here we report the isolation of clinical strains of S. mitis with unusually high MIC values for beta-lactam antibiotics; resistance to benzylpenicillin was 64 microg/ml and to cefotaxime 128 microg/ml. Among the beta-lactam compounds tested, only the carbapenems imipenem and meropenem showed MICs below 32 microg/ml. Both S. mitis strains were resistant to tetracycline and were highly resistant to aminoglycosides. Pulse field mapping of chromosomal DNA revealed identical patterns in both strains, indicating clonal identity of the two isolates. Using chromosomal S. mitis DNA, the laboratory strain S. pneumoniae R6 could be transformed in four successive steps to cefotaxime and benzylpenicillin resistance of 64 microg/ml. The results exemplify the importance of commensal streptococci for the development of cefotaxime resistance in S. pneumoniae.

Macrolide resistance in Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany.

Macrolide-resistance was assessed in 216 consecutive Streptococcus pyogenes isolates from throat infections in the region of Aachen, Germany. Seventeen isolates were resistant to erythromycin: 12 isolates revealed a macrolide (M) phenotype and harbored mefA, and five strains expressed an inducible macrolide-lincosamide-streptogramin B (MLSB) phenotype of which four strains harbored ermA(TR) and one strain contained ermB(AM). Telithromycin (HMR 3647) and quinupristin/dalfopristin remained active particularly against the ermA(TR)-containing S. pyogenes isolates studied. Random amplified polymorphic DNA analysis identified multiple clones among erythromycin-resistant strains, but did not discriminate beyond the emm-type. mefA was present in three isolates either with emm2, emm12, or emm75, and in nine isolates with emm4. All four strains with ermA(TR) contained emm77, and the single strain with ermB(AM) harbored emm1. Despite the relative low rate of macrolide-resistance, these data suggest that at least three different macrolide-resistance determinants are prevalent in Germany and that mefA has spread rapidly into multiple clones of S. pyogenes.

The cell wall-associated serine protease PrtA: a highly conserved virulence factor of Streptococcus pneumoniae.

The surface-associated subtilisin-like serine protease PrtA was identified by screening a genomic expression library from Streptococcus pneumoniae using a convalescent-phase serum. In Western blot analysis two forms of PrtA were detected in whole cell lysate and a truncated form only in culture supernatant suggesting that PrtA is produced as a precursor protein, translocated to the cell surface, truncated, and released into the surroundings. A 5' fragment of the gene was found highly conserved among 78 pneumococcal isolates of clinical relevance. Immunogenicity of PrtA, limited genetic variation, and the involvement in pneumococcal virulence demonstrated in in vivo experiments might identify PrtA as a promising candidate for a protein based vaccine.

Global distribution of Streptococcus pneumoniae serotypes isolated from paediatric patients during 1999-2000 and the in vitro efficacy of telithromycin and comparators.

Few data exist on the distribution of Streptococcus pneumoniae serotypes in many countries and in non-invasive disease overall. Here, data are presented from 772 paediatric isolates from children with community-acquired respiratory tract infections isolated from the PROTEKT global surveillance study during 1999-2000. Overall, 60.0 % of isolates were covered by the 7-valent pneumococcal vaccine formulation (PCV7), with greater coverage in the USA compared with Europe (69.6 vs 55.5 %, P = 0.014). Geographically dispersed clones of serogroups 3, 11 and 15 accounted for most of the isolates outside PCV7 coverage. Overall, macrolide, penicillin and cotrimoxazole non-susceptibility rates were high; however, all isolates were susceptible to telithromycin. Although only 7.4 % of isolates were resistant to amoxycillin/clavulanate, a higher prevalence of resistance was found in isolates from the USA and South Korea. This study shows the feasibility and importance of serotyping antibiotic surveillance study isolates and the potential of telithromycin as an important option for empiric therapy.

Penicillin-resistant Streptococcus pneumoniae in Germany: genetic relationship to clones from other European countries.

Penicillin-resistant Streptococcus pneumoniae strains isolated in different parts of Germany between 1982 and 1992 were compared with penicillin-resistant isolates, mainly of serogroups 6, 9, 14, 19 and 23, from other European countries. The main clones were recognised by their serotypes, antibiotic resistance patterns and penicillin-binding protein properties, and this typing was confirmed by multi-locus enzyme electrophoresis for a sample of 43 selected isolates. Eleven of the 14 resistant German isolates could be assigned to five genotypes isolated also in other countries. These included representatives of two distinct serotype 23F lineages predominant in Spain and France; a cluster of three serotype 6B isolates identical to clones in Spain, France, Finland and Hungary; and a serotype 9V clone of a type prevalent in Spain and now also in France. Serotype 19A clones of the type found in Hungary were not collected in Germany. The data suggest that two 23F lineages, represented by seven isolates from different locations, have become disseminated in Germany. Several resistant types found in the former West Germany resembled those found elsewhere in Western Europe whereas those from East Germany were distinct or, in one case, resembled a clone from Hungary. These data may reflect pre-unification travel patterns.

High-level fluoroquinolone resistance in a clinical Streptoccoccus pyogenes isolate in Germany.

An isolate of Streptococcus pyogenes isolated from a 63-year-old woman with a serious wound infection was found to be highly resistant to fluoroquinolones (levofloxacin MIC > or = 32 mg/L). DNA amplification and sequencing revealed a serine-81 to phenylalanine substitution in gyrA and three substitutions in parC: serine-79 to phenylalanine, aspartic acid-91 to asparagine, and serine-140 to proline. To our knowledge, this is the first report from a European country of a clinical isolate of S. pyogenes with high-level fluoroquinolone resistance.

Delayed thrombosis of synthetic microvascular bypass grafts.

A 3-mm-diameter synthetic polytetrafluoroethylene (PTFE) cervical carotid bypass graft 20 cm in length was implanted in 30 dogs for the evaluation of blood flow, tissue response, and patency at intervals of 1 to 120 days. Although 4 of 5 grafts removed after 5 to 8 days were patent (80%), long term patency was observed in only 1 graft (10%). Aspirin treatment did not influence patency. Scanning electron microscopy demonstrated the lack of a neoendothelial layer upon the luminal surfaces of patent grafts, which were covered with a fibrin-blood cell lining. Subintimal fibrosis resulted in stenosis at sites of anastomosis in thrombosed grafts. The graft length, its small caliber, and a 40% decrease in blood flow after implantation may have contributed to thrombosis of the bypass graft in this model. Synthetic PTFE microvascular grafts may not be suitable for clinical use in extracranial-intracranial arterial bypass surgery.

Antibacterial resistance among children with community-acquired respiratory tract infections (PROTEKT 1999-2000).

OBJECTIVE: To determine the susceptibility of bacterial respiratory tract pathogens, isolated from children (0-12 years) as part of the global PROTEKT surveillance study (1999-2000), to a range of antibacterials, including the ketolide telithromycin. METHODS: Minimum inhibitory concentrations of the antibacterials studied were determined at a central laboratory using the NCCLS microdilution broth method. Macrolide resistance mechanisms were detected by PCR. RESULTS: Of 779 Streptococcus pneumoniae isolates worldwide, 43% were non-susceptible to penicillin (18% intermediate; 25% resistant) and 37% were resistant to erythromycin, with considerable intercountry variation. Eighteen per cent of 653 Haemophilus influenzae and >90% of 316 Moraxella catarrhalis isolates produced beta-lactamase. Of 640 Streptococcus pyogenes isolates, 10% were resistant to erythromycin, with considerable intercountry variation. All S. pneumoniae and 99.8% of H. influenzae isolates were susceptible to telithromycin using breakpoints proposed to the NCCLS (

Increased titers of antibodies against streptococcal M12 and M19 proteins in patients with Tourette's syndrome.

It has been suggested that a post-streptococcal autoimmune process may be involved in the pathogenesis of a subgroup of children with tics and obsessive-compulsive symptoms (PANDAS). Elevated antibody titers against streptococcal antigens have also been described in adult patients suffering from Tourette's syndrome (TS). In order to characterise further streptococcal antigens, we focussed on M proteins. M proteins are a major virulence factor of group A streptococci and known to evoke an immunologic cross-reaction with diverse epitopes of human tissue including brain tissue. Therefore, antibodies against M proteins may play a role in the pathophysiology of at least a subgroup of TS patients. Antibodies against M proteins were studied in 25 adult patients suffering from TS and 25 healthy controls after careful medical examination. The antibody titers against the peptides M1, M4, M6, M12 and M19 were estimated by ELISA. Our results show increased titers of antibodies against the streptococcal M12 and M19 proteins in TS patients as compared with controls, while antibody titers against M1, M4 and M6 did not differ between the TS and control groups. Elevated serum titers of antibodies against M12 and M19 proteins support the view that a streptococcus-induced autoimmune process may be involved in TS. The finding of a possible autoimmune origin of TS has implications for both pathophysiology and future therapeutic strategies.