Need for less tight glucose control in early pregnancy after embryogenesis due to high risk of maternal hypoglycaemia in women with pre-existing diabetes can be compensated by good control in late pregnancy.

AIM: Poor glucose control is associated with adverse outcomes in pregnancies with pre-existing diabetes. However, strict glucose control increases the risk of severe hypoglycaemia, particularly in the first trimester. Therefore, we aimed to investigate whether less tight glucose control in the first trimester determines adverse outcomes or can be compensated for by good control in late pregnancy. METHODS: Retrospective data were collected from 517 singleton pregnancies complicated by pre-existing diabetes delivering between 2010 and 2017. Three hundred and thirty-six pregnancies fulfilled the inclusion criteria of having available HbA1c values either pre-conception or in the first trimester (65% type 1 diabetes, 35% type 2 diabetes). RESULTS: Higher HbA1c values in the first trimester were associated with increasing rates of large for gestational age (LGA) neonates, preterm delivery or neonatal intensive care unit admissions. Multiple regression analysis demonstrated third trimester HbA1c , type 1 diabetes, multiparity and excess weight gain, but not first trimester HbA1c , to be independently predictive for LGA. Pre-eclampsia and third trimester HbA1c increased the risk for preterm delivery. If HbA1c was ≤ 42 mmol/mol (6.0%) in the third trimester, rates of adverse outcomes were not significantly higher even if HbA1c targets of ≤ 48 mmol/mol (6.5%) had not been met in the first trimester. Good first trimester glucose control did not modify the rates of adverse outcomes if HbA1c was > 42 mmol/mol (6.0%) in the third trimester. CONCLUSIONS: Less tight glycaemic control, for example due to high frequency of severe hypoglycaemia in the first trimester, does not lead to increased adverse neonatal events if followed by tight control in the third trimester. Besides glycaemic control, excess weight gain is a modifiable predictor of adverse outcome.

Higher rates of large-for-gestational-age newborns mediated by excess maternal weight gain in pregnancies with Type 1 diabetes and use of continuous subcutaneous insulin infusion vs multiple dose insulin injection.

AIMS: To compare glycaemic control, maternal and neonatal outcomes in pregnancies with Type 1 diabetes, managed either by continuous subcutaneous insulin infusion, multiple daily insulin injection or switch from multiple daily insulin injection (MDI) to continuous subcutaneous insulin infusion (CSII) in early pregnancy. RESEARCH DESIGN AND METHODS: Data from 339 singleton pregnancies were retrospectively reviewed. HbA1c values were measured preconception and in each trimester. In a secondary analysis, use of CSII pre-pregnancy was compared with initiation of CSII during pregnancy. RESULTS: MDI was used in 140 pregnancies (41.3%) and CSII was used in 199 (58.7%), including 34 pregnancies (10.0%) during which the women switched to CSII. In pregnancies during which CSII was used duration of diabetes [median (interquartile range) 16.0 (8.0-23.0) years vs 11.0 (5.5-17.5) years; P<0.001] was longer, and the Institute of Medicine recommendations for appropriate weight gain were exceeded more often (64.8% vs. 50.8%; P=0.01). CSII use and pre-pregnancy BMI were independent predictors of excess weight gain. There was no difference in glucose control, but CSII was associated with higher birth weight [median (interquartile range) 3720 (3365-4100) g vs 3360 (3365-4100) g; P<0.001] and higher large-for-gestational-age (LGA) rate (44.7% vs. 33.6%; P=0.04) than MDI. HbA1c concentration in the third trimester and excess weight gain were predictive of LGA infants [odds ratio 2.33 (95% CI 1.54-3.51); P<0.001 and 1.89 (95% CI 1.02-3.51); P=0.04]. In pregnancies where CSII therapy was initiated in the first trimester and in those with pre-pregnancy use, similar glucose control and outcome was achieved. CONCLUSIONS: There was no advantage of CSII with respect to glycaemic control and neonatal outcomes. The rate of LGA neonates was higher in the CSII group, possibly mediated by excess maternal weight gain, which was more frequent than in women treated with MDI.

[CF Lung Disease - a German S3 Guideline: Module 2: Diagnostics and Treatment in Chronic Infection with Pseudomonas aeruginosa]. / S3-Leitlinie: Lungenerkrankung bei Mukoviszidose ­ Modul 2: Diagnostik und Therapie bei der chronischen Infektion mit Pseudomonas aeruginosa.

Cystic Fibrosis (CF) is the most common autosomal-recessive genetic disease affecting approximately 8000 people in Germany. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the epithelial lining fluid which leads to chronic inflammation of the airways. Recurrent infections of the airways as well as pulmonary exacerbations aggravate chronic inflammation, lead to pulmonary fibrosis and tissue destruction up to global respiratory insufficiency, which is responsible for the mortality in over 90 % of patients. The main aim of pulmonary treatment in CF is to reduce pulmonary inflammation and chronic infection. Pseudomonas aeruginosa (Pa) is the most relevant pathogen in the course of CF lung disease. Colonization and chronic infection are leading to additional loss of pulmonary function. There are many possibilities to treat Pa-infection. This is a S3-clinical guideline which implements a definition for chronic Pa-infection and demonstrates evidence-based diagnostic methods and medical treatment for Pa-infection in order to give guidance for individual treatment options.

Prevalence and characterization of azole-resistant Aspergillus fumigatus in patients with cystic fibrosis: a prospective multicentre study in Germany.

Objectives: Aspergillus fumigatus is the most prevalent filamentous fungus in the respiratory tract of patients with cystic fibrosis (CF). The aim of this prospective multicentre study was to investigate the prevalence of azole-resistant A. fumigatus (ARAF) in respiratory secretions from CF patients across Germany and to characterize ARAF isolates by phenotypic and molecular methods. Methods: Twelve tertiary care centres from Germany participated in the study. In total, 2888 A. fumigatus isolates from 961 CF patients were screened for ARAF by using azole-containing agar plates. Antifungal susceptibility testing of isolates was performed by broth microdilution according to EUCAST guidelines. Analysis of mutations mediating resistance was performed using PCR and sequencing of the cyp51A gene. Furthermore, genotyping by microsatellite PCR was performed. Results: Of a total of 2888 A. fumigatus isolates, 101 isolates from 51 CF patients were found to be azole resistant (prevalence per patient 5.3%). The Essen centre had the highest prevalence (9.1%) followed by Munich (7.8%), Münster (6.0%) and Hannover (5.2%). Most ARAF isolates (n = 89) carried the TR34/L98H mutation followed by eight G54E/R, one TR46/Y121F/T289A and one F219S mutation. In two isolates no mutation was found. Genotyping results showed no major clustering. Forty-five percent of CF patients with ARAF had previously received azole therapy. Conclusions: This is the first multicentre study analysing the prevalence of ARAF isolates in German CF patients. Because of a resistance rate of up to 9%, susceptibility testing of A. fumigatus isolates from CF patients receiving antifungal treatment should be part of standard diagnostic work-up.

[Necrotizing funisitis : Histopathological indicator of occult congenital syphilis]. / Nekrotisierende Funikulitis : Histopathologischer Indikator für eine okkulte konnatale Syphilis.

Congenital syphilis is a rare disease in central Europe. Placental changes may be non-specific but a typical finding is necrotizing funisitis of the umbilical cord. In a case report we describe how the histopathological incidental finding of B lymphocyte-rich, necrotizing funisitis led to the diagnosis of a previously unknown Treponema pallidum infection in parents and their newborn child. The pathological suspicion of congenital syphilis, although rare, has implications for the clinical management (serological evaluation of parents and child as well as the social environment, evaluation of viral coinfection and treatment decision) and is a notifiable disease.

Fungal epidemiology and diversity in cystic fibrosis patients over a 5-year period in a national reference center.

The knowledge on prevalence rates of yeasts and moulds in patients with cystic fibrosis (CF) in Germany is scarce. The aim of this report is to give an overview of the diversity and epidemiology of fungal species in CF patients. Over a 5-year period, all fungal isolates cultured from microbiological specimen from CF patients were recorded. Beside standard bacteriological culture media two fungal media were used for cultivation. Species were identified by microscopy, biochemical profiling, MALDI-TOF analysis or DNA sequencing methods. In sum, 25,975 clinical samples from CF patients were analyzed. About 75% of CF patients were colonized by yeasts, mainly Candida albicans (38%) and Candida dubliniensis (12%). In 35% of the patients Aspergillus spp. (Aspergillus fumigatus: 29%) were detected, followed by Exophiala dermatitidis and Scedosporium/Lomentospora complex isolates (4% each). Data for other fungal species are shown. Over a 5-year period, the epidemiology of fungal species detected in CF patients was relatively constant. Clinical microbiology laboratories should carefully monitor samples from CF patients for newly occurring fungal pathogens.

Prevalence of Scedosporium species and Lomentospora prolificans in patients with cystic fibrosis in a multicenter trial by use of a selective medium.

OBJECTIVE: Detection of hyphomycetes of the Scedosporium apiospermum complex and Lomentospora prolificans (Sac-Lp) is not yet standardized. Prevalence rates in patients with cystic fibrosis (CF) and the resistance pattern of these pathogens in Germany are unknown. METHODS: In a one-year prospective study 11 laboratories used a selective medium for isolation of Sac-Lp, examining >11,600 respiratory samples from 2346 patients with CF. Isolates were identified by molecular methods and tested for susceptibility to antifungal drugs. RESULTS: The prevalence of Sac-Lp in patients with CF in Germany varied from 0.0 to 10.5% (mean: 3.1%) among the clinical centres. The benefit of the selective medium SceSel(+) compared to standard media for fungi was documented for >5000 samples. High antifungal resistance was detected in the S. apiospermum complex, and the multiresistance of L. prolificans was confirmed. CONCLUSION: Microbiology laboratories should be aware of these resistant species in patients with CF and consider using a selective medium.

Validation of a novel real-time PCR for detecting Rasamsonia argillacea species complex in respiratory secretions from cystic fibrosis patients.

Members of the recently introduced fungal genus Rasamsonia (formerly included in the Geosmithia genus) have been described as emerging pathogens in immunosuppressed hosts or patients with cystic fibrosis (CF). Rasamsonia species have often been misidentified as Penicillium or Paecilomyces because of similar morphological characteristics. We validated a commercially available real-time PCR assay (Primerdesign™, UK) for accurate detection of species from the Rasamsonia argillacea complex. First, we tested this assay with a collection of 74 reference strains and clinical isolates and then compared the PCR with cultures of 234 respiratory samples from 152 patients with CF from two University Hospitals in Germany and France. The assay reliably detected the three main species within the Rasamsonia argillacea species complex (R. argillacea, R. piperina, R. aegroticola), which are typically encountered in CF patients. The limit of DNA detection was between 0.01 and 1 pg/µL. Analysis of the DNA extracts from respiratory specimens of CF patients revealed that four out of the 153 patients studied (2.6%) were colonized with R. argillacea species complex. Two species from the R. argillacea complex grew in the parallel cultures from the same patients. In one patient the PCR was positive 5 months before culture. The real-time PCR assay is a sensitive and specific method for detecting the three most important species of the R. argillacea species complex encountered in the CF context. Detection of these emerging pathogens in respiratory secretions from CF patients by this novel assay may increase our understanding of the occurrence and epidemiology of the R. argillacea species complex.

Multilocus sequence typing of Scedosporium apiospermum and Pseudallescheria boydii isolates from cystic fibrosis patients.

BACKGROUND: Scedosporium and Pseudallescheria species are the second most common lung-colonising fungi in cystic fibrosis (CF) patients. For epidemiological reasons it is important to trace sources of infection, routes of transmission and to determine whether these fungi are transient or permanent colonisers of the respiratory tract. Molecular typing methods like multilocus sequence typing (MLST) help provide this data. METHODS: Clinical isolates of the P. boydii complex (including S. apiospermum and P. boydii) from CF patients in different regions of Germany were studied using MLST. Five gene loci, ACT, CAL, RPB2, BT2 and SOD2, were analysed. RESULTS: The S. apiospermum isolates from 34 patients were assigned to 32 sequence types (STs), and the P. boydii isolates from 14 patients to 8 STs. The results revealed that patients can be colonised by individual strains for years. CONCLUSIONS: The MLST scheme developed for S. apiospermum and P. boydii is a highly effective tool for epidemiologic studies worldwide. The MLST data are accessible at http://mlst.mycologylab.org/.

In vitro activity of colistin as single agent and in combination with antifungals against filamentous fungi occurring in patients with cystic fibrosis.

Because published reports indicate that the antibiotic colistin (COL) has antifungal properties, this study investigated the antifungal in vitro activity of COL as single agent and in combination with the antifungal compounds voriconazole (VRC), caspofungin (CAS) and amphotericin B (AMB) against Scedosporium/Pseudallescheria spp., Exophiala dermatitidis and Geosmithia argillacea. In total, susceptibility was determined for 77 Scedosporium/Pseudallescheria spp., 82 E. dermatitidis and 17 G. argillacea isolates. The minimal inhibitory concentrations (MICs) of COL and the antifungals as single compound and in combination were determined with MIC test strips. Drug interactions were detected by crossing the MIC test strips at a 90º angle. The fractional inhibitory concentration index was used to categorise the drugs' interaction. The MIC50 value of COL was 12 µg ml(-1) for S. prolificans, 16 µg ml(-1) for P. apiosperma, 16 µg ml(-1) for P. boydii, 12 µg ml(-1) for E. dermatiditis and 6 µg ml(-1) for G. argillacea. VRC was the most active drug in combination without any antagonism with the exception of few P. boydii isolates. COL as single agent and in most combinations with antifungals exhibits in vitro antifungal activity against filamentous ascomycetes occurring in cystic fibrosis patients and may offer a novel therapeutic option, especially for multidrug-resistant S. prolificans.

A resonant photoemission applied to cerium oxide based nanocrystals.

Cerium 4f level occupation determines the properties of cerium oxide based catalysts in a significant way. The Ce 4f level of nanosized cerium oxide particles was investigated with the use of resonant photoelectron spectroscopy in the Ce 4d-4f photoabsorption region. A strong interaction of ceria with different additives, e.g. Pd and Sn, led to a partial Ce4+-->Ce3+ transition that was observed as a significant resonance enhancement of 4f photoemission intensity. Increases of the CO oxidation catalytic activity were observed simultaneously. The ratio of resonance enhancement of Ce photoemission intensity DCe(3+)/DCe(4+) was used to monitor Ce(3+) and Ce(4+) state occupation. The relative parameter DCe(3+)/DCe(4+) was found to be particularly useful in the case of photoemission studies of nanopowder ceria catalysts.

[Multiple abscesses in immunocompetent patients caused by Panton-Valentine leukocidin positive Staphylococcus aureus]. / Multiple Abszesse bei immunkompetenten Patienten durch Panton-Valentin-Leukozidin-positiven Staphylococcus aureus.

We report cases of immunocompetent patients showing multiple abscesses by a Panton-Valentine leukocidin (PVL) positive Staphylococcus aureus. PVL is considered to be an important virulence factor. The most common manifestations by this pathogen are recurrent or multiple abscesses of the skin. Seldom necrotizing pneumonia with high mortality occurs. Even methicillin-resistant PVL positive isolates have been identified in Germany. Only appropriate infection control measures in combination with antimicrobial therapy resulted in successful eradication of this pathogen. Dermatologists should be informed about this specific type of infection and about the appropriate infection control measures.

LightCycler-based differentiation of Mycobacterium abscessus and Mycobacterium chelonae.

In this study we introduce a rapid procedure to identify Mycobacterium abscessus (types I and II) and M. chelonae using LightCycler-based analysis of the hsp65 gene. Results from 36 clinical strains were compared with hsp65 gene restriction analysis and biochemical profiles of bacilli. As all three methods yielded identical results for each isolate, this procedure offers an excellent alternative to previously established nucleic acid amplification-based techniques for the diagnosis of mycobacterial diseases.

Rapid testing for nitrate reductase activity of Mycobacterium tuberculosis grown in an automated culture system.

In order to reduce the time to detection of nitrate reductase activity, which is arguably the most widely used phenotypic trait to differentiate between Mycobacterium tuberculosis, Mycobacterium bovis and Mycobacterium bovis BCG, the following study was conducted using cultures grown in an automated system. Automated culture systems, which are typically based on liquid medium, have greatly reduced the time-to-recovery of mycobacteria. Yet subsequent testing of isolates for nitrate reductase activity may take several weeks, because culture on solid media is required. Presented here is a procedure to obtain a final result within 24 h for nitrate reductase activity of cultures grown in an automated culture system. Using this procedure, Mycobacterium tuberculosis was rapidly differentiated from Mycobacterium bovis and Mycobacterium bovis BCG.

Instability and site-specific excision of integration-proficient mycobacteriophage L5 plasmids: development of stably maintained integrative vectors.

Integrative vectors expressing foreign genes are used as tools for the development of recombinant vaccines in mycobacteria since it is assumed that these vectors are stably maintained even without antibiotic selection. We here demonstrate that integration-proficient vectors are lost from the mycobacterial genome in high frequency. Loss of integrated vectors occurred in recA+ and in recA-strains, indicating a RecA-independent mechanism. Loss of the integrated vector was prevented when integrase gene function was carried on a separate plasmid that is unable to replicate in mycobacteria, indicating that excision is a function of integrase. By providing attP in cis and integrase function in trans, vectors integrating at the attB site are stably maintained, even when carrying genes that deleteriously affect the host.

[The Fitz-Hugh-Curtis syndrome in a 15-year-old girl]. / Fitzuv-Hughuv-Curtisuv syndrom u 15leté dívky.

The authors describe the development of the disease in a 15-year-old girl hospitalized on account of temperatures and vague pain in the right hypogastrium. Within a short time the pain shifted to the right epigastrium, became more intensive (with deterioration during inspiration) and concurrently the patient developed marked muscular tension in the whole right upper abdominal quadrant. The condition was associated with leucocytosis and a high red cell sedimentation rate. Marked tenderness and muscular tension persisted for cca 48 hours, afterwards, following symptomatic treatment, relatively rapid regression of the complaints and clinical picture occurred. Auxiliary examinations did not reveal any marked pathological changes of the abdominal and thoracic organs. Only during the post-acute phase of the disease gonococcal infection of the sex organs was revealed and adequate treatment was started. The authors evaluated the disease as gonococcal perihepatitis, known in the literature as Fitz-Hugh-Curtis syndrome.