Guideline: Vulvovaginal candidosis (AWMF 015/072, level S2k).

Approximately 70-75% of women will have vulvovaginal candidosis (VVC) at least once in their lifetime. In premenopausal, pregnant, asymptomatic and healthy women and women with acute VVC, Candida albicans is the predominant species. The diagnosis of VVC should be based on clinical symptoms and microscopic detection of pseudohyphae. Symptoms alone do not allow reliable differentiation of the causes of vaginitis. In recurrent or complicated cases, diagnostics should involve fungal culture with species identification. Serological determination of antibody titres has no role in VVC. Before the induction of therapy, VVC should always be medically confirmed. Acute VVC can be treated with local imidazoles, polyenes or ciclopirox olamine, using vaginal tablets, ovules or creams. Triazoles can also be prescribed orally, together with antifungal creams, for the treatment of the vulva. Commonly available antimycotics are generally well tolerated, and the different regimens show similarly good results. Antiseptics are potentially effective but act against the physiological vaginal flora. Neither a woman with asymptomatic colonisation nor an asymptomatic sexual partner should be treated. Women with chronic recurrent Candida albicans vulvovaginitis should undergo dose-reducing maintenance therapy with oral triazoles. Unnecessary antimycotic therapies should always be avoided, and non-albicans vaginitis should be treated with alternative antifungal agents. In the last 6 weeks of pregnancy, women should receive antifungal treatment to reduce the risk of vertical transmission, oral thrush and diaper dermatitis of the newborn. Local treatment is preferred during pregnancy.

Nitroxoline: an option for the treatment of urinary tract infection with multi-resistant uropathogenic bacteria.

The number of multi-resistant uropathogens is increasing. A multi-morbid patient developed a symptomatic urinary tract infection with two multi-resistant bacteria, namely Klebsiella pneumoniae and Proteus mirabilis. Nitroxoline was the only drug active against both uropathogens. Obviously, nitroxoline can be an option for the therapy of a urinary tract infection with multi-resistant uropathogens.

[Infections after bite wounds : For example rat bite fever due to Streptobacillus moniliformis]. / Infektionen nach Bissverletzungen : Zum Beispiel Rattenbissfieber durch Streptobacillus moniliformis.

Rat bite fever due to Streptobacillus moniliformis induces typical but not pathognomonic clinical signs, such as local purulent wound infection followed by maculopapular exanthema, myalgia as well as purulent joint infections. Severe complications, such as osteomyelitis and endocarditis are possible. it seems that this infection is rarely diagnosed but this infection could be much more common because the final diagnostic proof is difficult to achieve. Firstly, the culture of these bacteria is critical because the bacteria are fastidious and secondly the exact differentiation of the isolates is hardly possible by standard laboratory methods. Modern techniques such as mass spectroscopy (MALDI-TOF) and molecular biology allow a precise clarification. Surgical cleansing of infection sites in combination with a rational antibiotic therapy, for example with beta-lactam antibiotics, are generally able to cure the infection if treatment is started early enough. In addition, vaccinations, for example against tetanus and rabies have to be considered in this situation as for all other bite wound infections.

[Fungi in the gut - the gut mycobiome]. / Pilze im Darm ­ das Mykobiom des Darms.

Many different fungi, including yeasts and molds, can be found in the intestinal tract of humans constituting the gut mycobiome. In case the bacterial flora is altered, the fungal flora may react inversely. By a so-called fungal diet, however, the composition of the mycobiome can hardly be influenced. Whereas some fungi are only transiently present in the gut after oral uptake, others, such as Candida, Saccharomyces, Rhodotorula, Trichosporon, Geotrichum, amongst others, are members of the residential, autochthonous gut flora. Some of these fungi exert beneficial effects, for example by synthesizing useful materials. Rhodotorula can produce fatty acids and carotenoids. Others are able to metabolize toxic compounds, for example mycotoxins as well as procarcinogenic items in food. Toxins, as well as pathogenic bacteria, can be bound to mannans on the surface of fungi und can consequently be exported. Some fungi are said to exert probiotic activities. Certain fungal constituents, such as glucans, may even stimulate the immune system. On the other hand, some fungi cannot only colonize the gut asymptomatically but can also be noxious under certain conditions when, for example, the bacterial flora is disturbed. By means of their virulence factors, they can damage the gut epithelium and even penetrate into the Mukosa inducing inflammation, They can also aggravate chronic inflammatory processes. Fungi play a role in the development of obesity. Lastly, fungi in the gut represent a reservoir from which they may spread to other sites when the conditions are favorable.

Estimated burden of fungal infections in Germany.

In the late 1980's, the incidence of invasive fungal diseases (IFDs) in Germany was estimated with 36.000 IFDs per year. The current number of fungal infections (FI) occurring each year in Germany is still not known. In the actual analysis, data on incidence of fungal infections in various patients groups at risk for FI were calculated and mostly estimated from various (mostly national) resources. According to the very heterogenous data resources robust data or statistics could not be obtained but preliminary estimations could be made and compared with data from other areas in the world using a deterministic model that has consistently been applied in many countries by the LIFE program ( www.LIFE-worldwide.org). In 2012, of the 80.52 million population (adults 64.47 million; 41.14 million female, 39.38 million male), 20% are children (0-14 years) and 16% of population are ≥65 years old. Using local data and literature estimates of the incidence or prevalence of fungal infections, about 9.6 million (12%) people in Germany suffer from a fungal infection each year. These figures are dominated (95%) by fungal skin disease and recurrent vulvo-vaginal candidosis. In general, considerable uncertainty surrounds the total numbers because IFDs do not belong to the list of reportable infectious diseases in Germany and most patients were not hospitalised because of the IFD but a distinct underlying disease.

Fusarium spp.: infections and intoxications.

The genus Fusarium, member of the Hypocreaceae family, comprises over 500 spp. with an ever-evolving taxonomy. These fungi, some highly pathogenic, primarily affect various plants, including major crops like maize, rice, cereals, and potatoes, leading to significant agricultural losses and contributing to human undernutrition in certain regions. Additionally, Fusarium spp. produce harmful mycotoxins like trichothecenes, fumonisins, zearalenones, etc., posing health risks to animals and humans. These toxins generally transferred to food items can cause diverse issues, including organ failure, cancer, and hormonal disturbances, with effects sometimes appearing years after exposure. The fungi's vast genetic repertoire enables them to produce a range of virulence factors, leading to infections in both animals and humans, particularly in immunocompromised individuals. Fusarium spp. can cause systemic infections and local infections like keratitis. Due to limited antifungal effectiveness and biofilm formation, these infections are often challenging to treat with poor outcomes.

Canibacter oris - a fairly unknown pathogenic agent of bite wound infections.

Here, we report on the second case of bite wound infection by Canibacter oris. This bacterium belongs to the family of Microbacteriaceae in the order of Microbacterales in the class of Actinobacteria, which are prevalent in the oral flora. Possibly this bacterium has been overlooked until now, because it cannot be recognized by conventional differentiation methods. MALDI-TOF as well as PCR are able to identify this pathogen.

Antifungal activity of nitroxoline against Candida auris isolates.

OBJECTIVES: To investigate the in vitro activity of nitroxoline against a molecularly characterized collection of clinical Candida auris isolates. METHODS: Thirty-five clinical isolates of C. auris from diverse sources representing all five different C. auris clades were included in the study. Nitroxoline activity was assessed using broth microdilution. Additionally, susceptibility testing by disc diffusion was assessed on RPMI-1640 and Müller-Hinton agar plates. Minimal inhibitory concentrations of the antifungals fluconazole, voriconazole, amphotericin B and anidulafungin were determined. RESULTS: Nitroxoline MICs ranged from 0.125 to 1 mg/L (MIC50/90 0.25/0.5 mg/L). Compared with amphotericin B (MIC >1 mg/L in 4/35 isolates), anidulafungin (MIC >0.06 mg/L in 26/35 isolates) and fluconazole (MIC >4 mg/L in 31/35 isolates), in vitro activity of nitroxoline was high. Isolates belonging to clade I had marginally lower nitroxoline MICs (range 0.125-0.5 mg/L, mean MIC 0.375 mg/L) compared with clade III (range 0.5-1 mg/L, mean MIC 0.7 mg/L; p = 0.0094). The correlation of MIC and inhibition zones by disc diffusion was good when using RPMI-agar for disc diffusion, with a Pearson's correlation coefficient of -0.74 (95% CI -0.86 to -0.54). CONCLUSIONS: Nitroxoline has excellent in vitro activity against C. auris isolates, with MICs of 0.125-1 mg/L (for comparison, the EUCAST breakpoint for uncomplicated urinary tract infection with Escherichia coli is ≤ 16 mg/L). It is an approved, well-tolerated antimicrobial that achieves high urinary concentrations after oral administration and could be a useful treatment option in C. auris candiduria.

Compared with Cotrimoxazole Nitroxoline Seems to Be a Better Option for the Treatment and Prophylaxis of Urinary Tract Infections Caused by Multidrug-Resistant Uropathogens: An In Vitro Study.

The resistance of uropathogens to various antibiotics is increasing, but nitroxoline remains active in vitro against some relevant multidrug resistant uropathogenic bacteria. E. coli strains, which are among the most common uropathogens, are unanimously susceptible. Thus, nitroxoline is an option for the therapy of urinary tract infections caused by multiresistant bacteria. Since nitroxoline is active against bacteria in biofilms, it will also be effective in patients with indwelling catheters or foreign bodies in the urinary tract. Cotrimoxazole, on the other hand, which, in principle, can also act on bacteria in biofilms, is frequently inactive against multiresistant uropathogens. Based on phenotypic resistance data from a large number of urine isolates, structural characterisation of an MDR plasmid of a recent ST131 uropathogenic E. coli isolate, and publicly available genomic data of resistant enterobacteria, we show that nitroxoline could be used instead of cotrimoxazole for intervention against MDR uropathogens. Particularly in uropathogenic E. coli, but also in other enterobacterial uropathogens, the frequent parallel resistance to different antibiotics due to the accumulation of multiple antibiotic resistance determinants on mobile genetic elements argues for greater consideration of nitroxoline in the treatment of uncomplicated urinary tract infections.

Vulvovaginal Candidosis (Excluding Mucocutaneous Candidosis): Guideline of the German (DGGG), Austrian (OEGGG) and Swiss (SGGG) Society of Gynecology and Obstetrics (S2k-Level, AWMF Registry Number 015/072, September 2020).

Aim The aim of this official guideline, published and coordinated by the German (DGGG), Austrian (OEGGG) and Swiss (SGGG) Societies of Gynecology and Obstetrics in collaboration with the DMykG, DDG and AGII societies, was to provide consensus-based recommendations obtained by evaluating the relevant literature for the diagnosis, treatment and management of women with vulvovaginal candidosis. Methods This S2k guideline represents the structured consensus of a representative panel of experts with a range of different professional backgrounds commissioned by the Guideline Committee of the above-mentioned societies. Recommendations This guideline gives recommendations for the diagnosis, management, counseling, prophylaxis and screening of vulvovaginal candidosis.

Malignant Keratitis Caused by a Highly-Resistant Strain of Fusarium Tonkinense from the Fusarium Solani Complex.

Fusarium spp. are moulds ubiquitously distributed in nature and only occasionally pathogenic for humans. Species of the Fusarium solani complex are the predominant keratitis-inducing pathogens, because they are endowed with proper virulence factors. These fungi can adhere to the cornea creating a biofilm and, with the help of enzymes and cytotoxins, penetrate the cornea. Whereas an intact cornea is hardly able to be invaded by Fusarium spp. in spite of appropriate virulence factors, these opportunistic fungi may profit from predisposing conditions, for example mechanical injuries. This can lead to a progressive course of corneal infection and may finally affect the whole eye up to the need for enucleation. Here, we present and discuss the clinical, microbiological and histopathological aspects of a particular case due to Fusarium tonkinense of the Fusarium solani complex with severe consequences in a patient without any obvious predisposing factors. A broad portfolio of antifungal agents was applied, both topically and systemically as well as two penetrating keratoplasties were performed. The exact determination of the etiologic agent of the fungal infection proved likewise to be very challenging.

Large listeriosis outbreak linked to cheese made from pasteurized milk, Germany, 2006-2007.

A commercial cheese (acid curd) made from pasteurized milk caused a large listeriosis outbreak in Germany from October 2006 through February 2007. The Listeria monocytogenes outbreak strain was identified in humans and in cheese samples from a patient's home and from the production plant. During the outbreak period, 189 patients were affected, which was 97% above the mean case number for the respective time period of the years 2002 to 2005. Of patients with available detailed information on cheese consumption (n=47), 70% reported to have consumed the incriminated cheese product. Recent European food safety alerts due to Listeria-contaminated cheeses more often concerned products made from pasteurized or heat-treated milk than from raw milk. The findings should be considered in prevention guidelines addressing vulnerable populations.

The Medical Relevance of Fusarium spp.

The most important medical relevance of Fusarium spp. is based on their phytopathogenic property, contributing to hunger and undernutrition in the world. A few Fusarium spp., such as F. oxysporum and F. solani, are opportunistic pathogens and can induce local infections, i.e., of nails, skin, eye, and nasal sinuses, as well as occasionally, severe, systemic infections, especially in immunocompromised patients. These clinical diseases are rather difficult to cure by antimycotics, whereby the azoles, such as voriconazole, and liposomal amphotericin B give relatively the best results. There are at least two sources of infection, namely the environment and the gut mycobiome of a patient. A marked impact on human health has the ability of some Fusarium spp. to produce several mycotoxins, for example, the highly active trichothecenes. These mycotoxins may act either as pathogenicity factors, which means that they damage the host and hamper its defense, or as virulence factors, enhancing the aggressiveness of the fungi. Acute intoxications are rare, but chronic exposition by food items is a definite health risk, although in an individual case, it remains difficult to describe the role of mycotoxins for inducing disease. Mycotoxins taken up either by food or produced in the gut may possibly induce an imbalance of the intestinal microbiome. A particular aspect is the utilization of F. venetatum to produce cholesterol-free, protein-rich food items.

Diagnostic yield of blood cultures from antibiotic-naïve and antibiotically treated patients with haematological malignancies and high-risk neutropenia.

In patients with prolonged episodes of neutropenia, infections are associated with significant mortality. The exact diagnostic yield of blood cultures in this high-risk population is still unclear. To assess the yield of blood cultures, the spectrum of pathogenic organisms and the influence of blood culture results on the therapeutic management, we retrospectively evaluated the results from 2520 blood cultures obtained from 126 consecutive patients with high-risk neutropenia. Bacterial pathogens were detected in 219 blood culture samples (8.7%) of which 172 were Gram-positive and 47 were Gram-negative bacteria. Fungal pathogens were found in 13 blood cultures. A higher rate of Gram-positive pathogens and of fungi was found in patients with central venous catheters. Pathogens were detected in 14.3% of blood cultures obtained before the institution of antibiotic treatment and in 7% of blood cultures obtained under antibiotic treatment. Treatment was modified in 116/232 (50%) of positive blood culture findings. In patients with high-risk neutropenia, blood cultures are a valid diagnostic tool, both in antibiotic-naïve patients and in patients receiving antibiotic treatment, and provide important information for clinical decision making. The epidemiological data obtained are helpful for selecting empirical antibiotic treatment regimens.

Is there a serious risk of resistance development to azoles among fungi due to the widespread use and long-term application of azole antifungals in medicine?

It is well known that development of antibiotic resistance in bacteria is not a matter of if but of when. Recently, azoles have been recommended for long-term prophylaxis of invasive fungal infections; hence, it could be argued that fungi also will become resistant to these agents. However, fungi are different from bacteria in several critical points. Bacteria display several resistance mechanisms: alteration of the target, limited access to the target and modification/inactivation of the antibacterial compound. In fungi some mechanisms of resistance to azoles are also known; with azoles for example, alterations of the 14alpha-demethylase target, as well as efflux pumps. It has been observed that these phenotypes develop in yeast populations either due to mutations or to selection processes. However, enzymes which destroy azoles are not found. Furthermore, a horizontal transfer of genes coding resistance traits does not occur in fungi, which means that an explosive expansion of resistances is unlikely to occur, especially in moulds. Indeed, in epidemiologic studies on human and environmental isolates there is convincing evidence that azole resistance is quite uncommon.

Rhodotorula spp. in the gut - foe or friend?

Rhodotorula spp. belong to the basidiomyceteous fungi. They are widespread in the environment. Transmission to humans occur mainly through air and food. Intestinal colonization is rather common, but an overgrowth is normally suppressed, since their optimal growth temperature is exceeded in the body. A massive presence in the gut indicates a disturbance of the balance of the microbial flora due to different causes. One particular reason will be the treatment with azoles because this will create an advantage for these azole resistant fungi. First of all, the finding of increased numbers of Rhodotorula in stool specimen is not alarming. In contrast, the colonized human will profit from such a situation since these fungi produce a lot of useful nutrients such as proteins, lipids, folate, and carotinoids. Furthermore, a probiotic effect due to regulation of multiplication of pathogenic bacteria and by neutralizing or destroying their toxins can be anticipated. On the other hand, their massive presence may increase the risk of fungemia and ensuing organ infections especially when the host defense system is hampered. Indeed, Rhodotorula spp. range among the emerging fungal pathogens in the compromised host. However, it can be doubted whether all these opportunistic infections reported originate primarily from the gut.

Gliotoxin production by clinical and environmental Aspergillus fumigatus strains.

The mycotoxin gliotoxin is produced by fungi of the genus Aspergillus, including the important human pathogen Aspergillus fumigatus. Gliotoxin exerts a broad spectrum of immunosuppressive effects in vitro and is detectable in the sera of patients suffering from invasive aspergillosis. In order to correlate the pathogenic potential of A. fumigatus with the ability to produce gliotoxin and to investigate the taxonomic distribution of gliotoxin-producing Aspergillus strains among clinical isolates, a total of 158 Aspergillus isolates comprising four different species (A. fumigatus, n=100; A. terreus, n=27; A. niger, n=16; A. flavus, n=15) were collected from different medical centers (some originating from probable cases of aspergillosis) and from environmental samples in Germany and Austria. Remarkably, gliotoxin was detected in most culture filtrates of A. fumigatus of both clinical (98%) and environmental (96%) origin. The toxin was also detected, with decreasing frequency, in culture filtrates of A. niger (56%), A. terreus (37%), and A. flavus (13%). The highest gliotoxin concentrations were detected in A. fumigatus strains of clinical (max. 21.35 microg/ml, mean 5.75 microg/ml) and environmental (max. 26.25 microg/ml, mean 5.27 microg/ml) origin. Gliotoxin productivity of other Aspergillus species was significantly lower. Culture supernatants of A. fumigatus strains lacking gliotoxin production showed a significantly lower cytotoxicity on macrophage-like cells and T-cells in vitro. In contrast, lack of gliotoxin production in the other Aspergillus species tested had no significant influence on the cytotoxic effect of culture supernatant on these immune cells.

Rapid identification and typing of listeria species by matrix-assisted laser desorption ionization-time of flight mass spectrometry.

Listeria monocytogenes is a food-borne pathogen that is the causative agent of human listeriosis, an opportunistic infection that primarily infects pregnant women and immunologically compromised individuals. Rapid, accurate discrimination between Listeria strains is essential for appropriate therapeutic management and timely intervention for infection control. A rapid method involving matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) that shows promise for identification of Listeria species and typing and even allows for differentiation at the level of clonal lineages among pathogenic strains of L. monocytogenes is presented. A total of 146 strains of different Listeria species and serotypes as well as clinical isolates were analyzed. The method was compared with the pulsed-field gel electrophoresis analysis of 48 Listeria strains comprising L. monocytogenes strains isolated from food-borne epidemics and sporadic cases, isolates representing different serotypes, and a number of Listeria strains whose genomes have been completely sequenced. Following a short inactivation/extraction procedure, cell material from a bacterial colony was deposited on a sample target, dried, overlaid with a matrix necessary for the MALDI process, and analyzed by MALDI-TOF MS. This technique examines the chemistry of major proteins, yielding profile spectra consisting of a series of peaks, a characteristic "fingerprint" mainly derived from ribosomal proteins. Specimens can be prepared in a few minutes from plate or liquid cultures, and a spectrum can be obtained within 1 minute. Mass spectra derived from Listeria isolates showed characteristic peaks, conserved at both the species and lineage levels. MALDI-TOF MS fingerprinting may have potential for Listeria identification and subtyping and may improve infection control measures.

Pneumocystis jiroveci pneumonia in a patient with Wegener's granulomatosis treated efficiently with caspofungin.

A patient with Wegener's granulomatosis was on steroids (20 mg prednisolone per day) when he fell ill with an atypical pneumonia caused by Pneumocystis, which was diagnosed by detection of antigen in repeated bronchial lavage specimens. Because other treatment options were contraindicated, he received intravenous caspofungin starting with a loading dose of 70 mg and a maintenance dose of 50 mg daily over 3 weeks thereafter. The patient's complaints subsequently resolved within days after initiation of treatment. Tolerability of the drug was excellent. No relapse occurred during the ongoing 4 years, although immunosuppressive therapy continued.

Listeria infections of the eye.

The bacterium Listeria monocytogenes resides originally in the environment. Infections of the eye have been induced experimentally; for example, in rabbits and guinea pigs. Natural ocular infections occur in various animals; in most instances, they are induced exogenously; for example, by contaminated silage affecting primarily the conjunctiva, cornea, or the anterior chamber. Sporadic infections as well as outbreaks have been described. In humans, besides exogenous infections, endogenous infections also occur, inducing mainly endophthalmitis. Since an exact diagnosis of the causative agent is often delayed, specific therapy starts too late, so that the outcome is often poor. The antibiotics of primary choice would be ampicillin or a quinolone such as moxifloxacin or levofloxacin. The role of fosfomycin for therapy of ocular infections is discussed.