Inability to work following COVID-19 vaccination-a relevant aspect for future booster vaccinations.

OBJECTIVES: COVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections. However, vaccine-related inability to work among healthcare workers (HCWs) could overstrain healthcare systems. STUDY DESIGN: The study presented was conducted as part of the prospective CoVacSer cohort study. METHODS: This study examined sick leave and intake of pro re nata medication after the first, second, and third COVID-19 vaccination in HCWs. Data were collected by using an electronic questionnaire. RESULTS: Among 1704 HCWs enrolled, 595 (34.9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273, the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third. CONCLUSION: In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to postvaccination inability to work, which could negatively impact the already strained healthcare system and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.

A new species concept for the clinically relevant Mucor circinelloides complex.

Mucor species are common soil fungi but also known as agents of human infections (mucormycosis) and used in food production and biotechnology. Mucor circinelloides is the Mucor species that is most frequently isolated from clinical sources. The taxonomy of Mucor circinelloides and its close relatives (Mucor circinelloides complex - MCC) is still based on morphology and mating behaviour. The aim of the present study was a revised taxonomy of the MCC using a polyphasic approach. Using a set of 100 strains molecular phylogenetic analysis of five markers (ITS, rpb1, tsr1, mcm7, and cfs, introduced here) were performed, combined with phenotypic studies, mating tests and the determination of the maximum growth temperatures. The multi-locus analyses revealed 16 phylogenetic species of which 14 showed distinct phenotypical traits and were recognised as discrete species. Five of these species are introduced as novel taxa: M. amethystinus sp. nov., M. atramentarius sp. nov., M. variicolumellatus sp. nov., M. pseudocircinelloides sp. nov., and M. pseudolusitanicus sp. nov. The former formae of M. circinelloides represent one or two separate species. In the MCC, the simple presence of well-shaped zygospores only indicates a close relation of both strains, but not necessarily conspecificity. Seven species of the MCC have been implemented in human infection: M. circinelloides, M. griseocyanus, M. janssenii, M. lusitanicus, M. ramosissimus, M. variicolumellatus, and M. velutinosus.

Caspofungin infusion solutions (50 mg/100 mL): chemical stability and antifungal activity against Candida spp.

BACKGROUND: Ready to use caspofungin infusion bags are centrally prepared in the Hospital Pharmacy, University Hospital of Heidelberg, for economic reasons and possibly occurring problems with drug shortages. The aim of this study was a quality control of the in-house preparation of caspofungin infusion bags and the preparation process. Caspofungin concentration with regard to chemical stability and antifungal activity of caspofungin preparations were defined as quality parameters. METHODS: Three caspofungin infusion bags (50 mg in 100 mL 0.9% sodium chloride) were examined every seven days for a total of four weeks. Chemical stability of caspofungin solutions was analyzed using a validated high performance liquid chromatography (HPLC) method. Antifungal activity was assessed by microdilution tests according to the EUCAST protocol. Additionally, concentration and sterility were determined in returned caspofungin infusion bags. RESULTS: The amount of caspofungin in the infusion solutions still exceeded 90% after four weeks (2-8 °C). Antifungal activity was consistent over 28 days with a MIC ≤2 mg/L for different Candida spp. In returned infusion bags, caspofungin concentration was found to be ≥90% in 12 out of 13 bags and sterility was given in all preparations. CONCLUSION: These results show that chemical stability of caspofungin infusion solutions (50 mg/100 mL) can be guaranteed for four weeks at 2-8 °C and are confirmed by corresponding results regarding sterility and antifungal activity.

Endophthalmitis as primary clinical manifestation of fatal fusariosis in an allogeneic stem cell recipient.

The occurrence of infections due to previously rare opportunistic pathogens is increasing despite the use of novel treatment strategies for immunocompromised patients. Here, we report the case of a patient presenting with fever, muscle pain, and bilateral endophthalmitis after allogeneic hematopoietic stem cell transplantation. Fusarium solani was isolated from peripheral blood samples and identified as the cause of gradual bilateral vision loss, despite appropriate antifungal prophylaxis, and therapy including vitrectomy and intraocular instillation of antifungal agents. The patient became comatose; basal meningitis involving both optic nerves was suspected based on magnetic resonance tomography. The patient died 8 days later due to septic multi-organ failure. Autopsy revealed that both kidneys, but no other organs, were infiltrated by Fusarium. No fungus was found in cerebral tissues or cerebrospinal fluid. Our case demonstrates some of the typical clinical features of systemic fusariosis and its potentially fatal outcome. The clinical observations reported here may help clinicians caring for immunocompromised patients to accelerate diagnosis and initiate treatment early at the onset of this fatal complication, and highlight the urgent need for interdisciplinary management of invasive fusariosis.

[The German keratomycosis registry : Initial results of a multicenter survey]. / Das Deutsche Pilz-Keratitis-Register : Erste Ergebnisse einer multizentrischen Erhebung.

BACKGROUND AND PURPOSE: Mycotic keratitis is a serious but relatively rare disease. No targeted data collection in Germany existed until the foundation of the German Pilz-Keratitis Register in 2015. PATIENTS AND METHODS: The inclusion of retrospective and prospective patients was carried out. INCLUSION CRITERIA: diagnosis confirmed by the polymerase chain reaction (PCR), culture, histology or confocal microscopy (IVCM). Collected parameters: date of symptom onset, date and method of diagnosis, risk factors, visual acuity and findings at admission and at follow-up, conservative and surgical treatment. RESULTS: By January 2018, a total of 102 eyes from the years 2000-2017 were reported from 16 centers (64.3% female, mean age 52 years, range 18-95 years). The initial diagnosis was made correctly in only 20.6% of cases. The mean time to correct diagnosis was 31.7 ±â€¯46.9 (0-296) days. The diagnosis was confirmed in cultures in 74.5%, histologically in 30.4%, by PCR in 38.2% and IVCM in 27.4%. Fungal species identified were: 36.7% Fusarium spp., 35.8% Candida spp., 6.4% Aspergillus spp. and 21.1% other. The most important risk factor was the use of contact lenses. The most commonly used antifungal agent was voriconazole (64.7%) followed by amphotericin B (37.2%). Penetrating keratoplasty was performed in 65.7% of the cases and 8.8% of the affected eyes had to be enucleated. The visual acuity of the entire study population increased from the initial 0.16 ±â€¯0.25 (0.001-1.0) decimal to 0.28 ±â€¯0.34 (0-1.0) decimal. CONCLUSION: The correct diagnosis of fungal keratitis is often significantly delayed. The treatment can be very difficult and keratoplasty is often necessary. In order to gain a better understanding of this disease, to recognize previously unknown risk factors and, if necessary, a change in the spectrum of pathogens and to identify approaches to treatment optimization, the fungal keratitis registry will be continued.

[Tintelnotia destructans: new enemy at the gates]. / Tintelnotia destructans: Ein neuer Feind vor dem Tore.

Tintelnotia destructans is a fungal species described for the first time in 2016, which can cause infections of the nails and of the cornea. We describe the second known case worldwide of Tintelnotia destructans-associated keratitis and its therapy. A good sensitivity for amphotericin B and voriconazole was demonstrated in the resistogram for the first time and the successful clinical course was confirmed. The present case study also shows the importance of intensive diagnostics in atypical microbial keratitis.

Dominant active alleles of RIM101 (PRR2) bypass the pH restriction on filamentation of Candida albicans.

Morphological development of the fungal pathogen Candida albicans is profoundly affected by ambient pH. Acidic pH restricts growth to the yeast form, whereas neutral pH permits development of the filamentous form. Superimposed on the pH restriction is a temperature requirement of approximately 37 degrees C for filamentation. The role of pH in development was investigated by selecting revertants of phr2Delta mutants that had gained the ability to grow at acid pH. The extragenic suppressors in two independent revertants were identified as nonsense mutations in the pH response regulator RIM101 (PRR2) that resulted in a carboxy-terminal truncation of the open reading frame. These dominant active alleles conferred the ability to filament at acidic pH, to express PHR1, an alkaline-expressed gene, at acidic pH, and to repress the acid-expressed gene PHR2. It was also observed that both the wild-type and mutant alleles could act as multicopy suppressors of the temperature restriction on filamentation, allowing extensive filamentation at 29 degrees C. The ability of the activated alleles to promote filamentation was dependent upon the developmental regulator EFG1. The results suggest that RIM101 is responsible for the pH dependence of hyphal development.

[3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease in Würzburg 2006]. / 3. Würzburger Workshop zur Epidemiologie, Prävention und Therapie der invasiven Meningokokkenerkrankung 2006.

On October 5th, 2006, the German Reference Centre for Meningococci (NRZM) held the 3rd Workshop on Epidemiology, Prevention and Treatment of Invasive Meningococcal Disease, in collaboration with the German Society for Hygiene and Microbiology (DGHM). Given the recent recommendation of the German Standing Committee on Vaccination (STIKO) for conjugate meningococcal C vaccination of all children in the second year of life, observations from meningococcal C conjugate vaccination campaigns in other European countries were presented and compared to the German situation. Moreover, the newly implemented cluster detection routines employed at the NRZM and their integration into the interactive geographical information system EpiScanGIS were shown. Based on recent experiences from regional outbreaks in Oberallgäu, Sangerhausen, and Greater Aachen, examples for public health intervention were given at the conference. In addition, current developments in the area of meningococcal research, as well as trends in antimicrobial susceptibility were covered. Finally, the latest evidence concerning the clinical management and chemoprophylaxis of this invasive bacterial disease was discussed.

Molecular and phenotypic identification of the yeast pathogen Candida dubliniensis.

Candida dubliniensis is an emerging yeast pathogen generally misclassified as Candida albicans by standard diagnostic procedures. This study examined the efficiency of molecular identification, based on a discriminative PCR test, in a prospective study on the prevalence of C. dubliniensis among 103 oropharyngeal isolates from HIV-infected individuals or transplant recipients, and 30 vaginal isolates. All of the isolates had been classified as C. albicans by standard laboratory procedures. The PCR was evaluated in a blinded fashion against classification achieved by sequencing rDNA. Sequencing results corresponded 100% to the results of the discriminative PCR, indicating the validity of this rapid test. Twenty-one C. dubliniensis isolates were identified, all of them from HIV-infected individuals (prevalence 30%). The internal transcribed spacer regions of the C. dubliniensis isolates were sequenced. Phenotypic features of C. dubliniensis, namely abundant chlamydospore formation, atypical color on CHROMagar, growth defect at 45 degrees C, and colony morphology on Staib agar, were evaluated in a blinded fashion with respect to their discriminative potential, facilitating the design of further epidemiological studies. Carbohydrate assimilation patterns were determined for C. dubliniensis with a novel automated system showing that, in contrast to previous reports, C. dubliniensis is able to utilize D-xylose and trehalose. In evaluating these tests we present a rational approach to identification of the new species and characterization of C. dubliniensis isolates.

No evidence for bradykinin B1 receptors in rat dorsal root ganglion neurons.

Bradykinin receptors are believed to contribute to hyperalgesia under conditions of neuropathic pain. Using calcium imaging we investigated responses to B1 and B2 agonists on isolated rat dorsal root ganglion neurons. No response to the B1 agonist was detected, whereas 12% of neurons responded to the B2 agonist. Northern blot analysis confirmed the lack of B1 receptor expression in dorsal root ganglia, as B1 mRNA was neither detected under normal conditions nor after nerve injury. In the calcium imaging experiments, agonists were applied with an elevated superfusion flow rate to avoid tachyphylaxis to the drug. Normal external solution applied at this flow rate constituted a mechanical stimulus causing a response in some neurons. Thus, in comparable set-ups mechanosensitivity has first to be tested to avoid masking effects.

Effect of the growth medium on the in vitro antifungal activity of micafungin (FK-463) against clinical isolates of Candida dubliniensis.

Micafungin (FK-463), a member of the new candin family of antifungal agents, was highly active against clinical isolates of Candida albicans and Candida dubliniensis. The in vitro activity of micafungin suggested that it was more potent than fluconazole, flucytosine, amphotericin B or voriconazole against C. albicans, and comparable or moderately less effective against C. dubliniensis isolates when high-resolution medium (HR) was used. Lower MICs of micafungin were recorded when RPMI 2% or AM3 2% media were used, indicating an influence of the growth medium on the MIC.

Postmortem isolation of Pseudotaeniolina globosa from a patient with aortic aneurysm.

We describe the isolation of the melanized meristematic fungus Pseudotaeniolina globosa from the aortic wall of a patient who died while undergoing surgery for aortic aneurysm and aortic valve regurgitation as a result of dilated cardiomyopathy. Meristematic fungi related to P. globosa have until now been considered as environmental saprobes found predominantly in ecological niches with low water activity. The isolate was identified by phenotypic analyses and by sequencing of the rDNA internal-transcribed spacer domain. The clinical significance of this isolation remains unclear but isolation of meristematic fungi from clinical specimen should be thoroughly evaluated in terms of their significance in future.

Combined surgical and antifungal treatment of a subcutaneous infection due to Paecilomyces lilacinus.

Paecilomyces lilacinus was the causal agent of a case of subcutaneous infection in a patient with liver cirrhosis. Surgical treatment in combination with systemic amphotericin B therapy led to complete recovery. Retrospectively performed microdilution testing revealed dose dependent in vitro susceptibility of the isolate to voriconazole (MIC = 2 g/ml) and terbinafine (MIC = 1 microg/ml).

Rapid PCR test for discriminating between Candida albicans and Candida dubliniensis isolates using primers derived from the pH-regulated PHR1 and PHR2 genes of C. albicans.

The development of a satisfactory means to reliably distinguish between the two closely related species Candida albicans and Candida dubliniensis in the clinical mycology laboratory has proved difficult because these two species are phenotypically so similar. In this study, we have detected homologues of the pH-regulated C. albicans PHR1 and PHR2 genes in C. dubliniensis. Restriction fragment length polymorphism analysis suggests that there are significant sequence differences between the genes of the two species. In order to exploit this apparent difference, oligonucleotide primers based on the coding sequence of the C. albicans PHR1 structural gene were designed and used in PCR experiments. Use of these primers with C. albicans template DNA from 17 strains yielded a predicted 1.6-kb product, while C. dubliniensis template DNA from 19 strains yielded no product. We therefore propose that PCR using these primers is a rapid and reliable means of distinguishing the two germ tube- and chlamydospore-producing species C. albicans and C. dubliniensis.

Molecular responses to changes in the environmental pH are conserved between the fungal pathogens Candida dubliniensis and Candida albicans.

In this work we cloned CdPHR1 and CdPHR2 from the human fungal pathogen Candida dubliniensis. The two genes are homologues to the pH-regulated genes PHR1 and PHR2 from Candida albicans. The pH-dependent pattern of expression of CdPHR1 and CdPHR2 was conserved in C. dubliniensis. CdPHR1 could be shown to be functionally equivalent to PHR1. The pH-regulated mode of expression was maintained when CdPHR1 was integrated in C. albicans. This indicates a fundamentally similar mode of expressional regulation in the two species. CdPHR1 was furthermore capable of reversing the aberrant phenotype of a Saccharomyces cerevisiae GAS1 deletion mutant. In this species, however, expression of CdPHR1 was no longer under control of the external pH. Expression of CdPHR1 was not detected when it was introduced into Aspergillus nidulans. In conclusion, C. dubliniensis and C. albicans respond to changes in the environmental pH with a change in cell shape and differential gene expression.