The definition of the heterogeneous group of coagulase-negative staphylococci (CoNS) is still based on diagnostic procedures that fulfill the clinical need to differentiate between Staphylococcus aureus and those staphylococci classified historically as being less or nonpathogenic. Due to patient- and procedure-related changes, CoNS now represent one of the major nosocomial pathogens, with S. epidermidis and S. haemolyticus being the most significant species. They account substantially for foreign body-related infections and infections in preterm newborns. While S. saprophyticus has been associated with acute urethritis, S. lugdunensis has a unique status, in some aspects resembling S. aureus in causing infectious endocarditis. In addition to CoNS found as food-associated saprophytes, many other CoNS species colonize the skin and mucous membranes of humans and animals and are less frequently involved in clinically manifested infections. This blurred gradation in terms of pathogenicity is reflected by species- and strain-specific virulence factors and the development of different host-defending strategies. Clearly, CoNS possess fewer virulence properties than S. aureus, with a respectively different disease spectrum. In this regard, host susceptibility is much more important. Therapeutically, CoNS are challenging due to the large proportion of methicillin-resistant strains and increasing numbers of isolates with less susceptibility to glycopeptides.

Coagulase-Negative Staphylococci

Campylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni, there is increasing recognition of the clinical importance of emerging Campylobacter species, including Campylobacter concisus and Campylobacter ureolyticus. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of Campylobacter infection.

Global Epidemiology of Campylobacter Infection

The incidence of fungal infections has increased significantly, so contributing to morbidity and mortality. This is caused by an increase in antimicrobial resistance and the restricted number of antifungal drugs, which retain many side effects. Candida species are major human fungal pathogens that cause both mucosal and deep tissue infections. Recent evidence suggests that the majority of infections produced by this pathogen are associated with biofilm growth. Biofilms are biological communities with a high degree of organization, in which micro-organisms form structured, coordinated and functional communities. These biological communities are embedded in a self-created extracellular matrix. Biofilm production is also associated with a high level of antimicrobial resistance of the associated organisms. The ability of Candida species to form drug-resistant biofilms is an important factor in their contribution to human disease. The study of plants as an alternative to other forms of drug discovery has attracted great attention because, according to the World Health Organization, these would be the best sources for obtaining a wide variety of drugs and could benefit a large population. Furthermore, silver nanoparticles, antibodies and photodynamic inactivation have also been used with good results. This article presents a brief review of the literature regarding the epidemiology of Candida species, as well as their pathogenicity and ability to form biofilms, the antifungal activity of natural products and other therapeutic options.

Candida species: current epidemiology, pathogenicity, biofilm formation, natural antifungal products and new therapeutic options

The incidence of invasive mycoses is increasing, especially among patients who are immunocompromised or hospitalized with serious underlying diseases. Such infections may be broken into two broad categories: opportunistic and endemic. The most important agents of the opportunistic mycoses are Candida spp., Cryptococcus neoformans, Pneumocystis jirovecii, and Aspergillus spp. (although the list of potential pathogens is ever expanding); while the most commonly encountered endemic mycoses are due to Histoplasma capsulatum, Coccidioides immitis/posadasii, and Blastomyces dermatitidis. This review discusses the epidemiologic profiles of these invasive mycoses in North America, as well as risk factors for infection, and the pathogens' antifungal susceptibility.

Epidemiology of Invasive Mycoses in North America

Trichoderma is a genus of common filamentous fungi that display a remarkable range of lifestyles and interactions with other fungi, animals and plants. Because of their ability to antagonize plant-pathogenic fungi and to stimulate plant growth and defence responses, some Trichoderma strains are used for biological control of plant diseases. In this Review, we discuss recent advances in molecular ecology and genomics which indicate that the interactions of Trichoderma spp. with animals and plants may have evolved as a result of saprotrophy on fungal biomass (mycotrophy) and various forms of parasitism on other fungi (mycoparasitism), combined with broad environmental opportunism.

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Trichoderma : the genomics of opportunistic success

Candida albicans are the most common fungi associated with biofilm-related infections. Biofilms are defined as microbial communities encased in a matrix of extracellular polymeric substances. The most important feature of biofilm growth is the high resistance to antimicrobial agents that can be up to 1000-fold greater than that of planktonic cells. This review discusses the factors affecting antifungal resistance as well as activity of mono- and combination therapy of different antifungal classes and antifungal activity in vitro and in vivo against C. albicans biofilms.

Antifungal susceptibility of Candida albicans in biofilms

Methods: Ten C. albicans bloodstream isolates used in this study were collected from intensive care patients admitted to the Vienna University Hospital between 2006 and 2007. Chequerboard tests were employed to determine the efficacy of the antifungal combinations amphotericin B/caspofungin and amphotericin B/ posaconazole against both planktonic cells and biofilms. C. albicans biofilms were prepared using the static microtitre plate model. The activity of antifungal combination therapy was determined by visual reading for planktonic cells and using the XTT assay for biofilms. Results: For Candida biofilms the median MIC was 4 mg/L for amphotericin B and caspofungin, and .256 mg/L for posaconazole. The combination amphotericin B/posaconazole yielded synergism [fractional inhibitory concentration index (FICI) ,0.26], whereas amphotericin B/caspofungin yielded indifferent interaction only (FICI 0.75‐1.25) against all isolates when grown in biofilms. Under planktonic conditions, synergism was demonstrable for the combination amphotericin B/caspofungin against 4 of the 10 isolates, whereas the combination of caspofungin/posaconazole was indifferent against all tested isolates. Conclusions: We showed that MICs for planktonic and biofilm forms of C. albicans were much lower when treated with an antifungal combination than when treated with single agents. The combination of amphotericin B/posaconazole yielded synergism against Candida biofilms, whereas amphotericin B/caspofungin yielded indifferent interaction.

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In vitro activity of antifungal combinations against Candida albicans biofilms

Objectives: Akacid plus® is a new member of the polymeric guanidine family of disinfectants. It was especially developed to enhance the antimicrobial activity of this class with significantly less toxicity. The in vitro activity of Akacid plus® compared with chlorhexidine digluconate and mupirocin was tested against a total of 369 recent clinical isolates. Methods: The organisms tested by CLSI reference methods included the following: Staphylococcus aureus (98), Staphylococcus epidermidis (9), Bacillus spp. (2), Enterococcus faecalis (32), Klebsiella spp. (45), Enterobacter spp. (20), Escherichia coli (65), Salmonella spp. (6), Shigella spp. (2), Yersinia enterocolitica (1), Acinetobacterspp. (4), Proteus spp. (7), Pseudomonas aeruginosa (59), Stenotrophomonas maltophilia (4), Candida spp. (10) and Aspergillus spp. (7). In vitro selection of resistance to Akacid plus® was carried out on 24 strains. Toxicological analyses were also performed. Results: All tested agents were more effective against Staphylococcus spp. and Bacillus spp. than against E. faecalis and Gram-negative bacteria. The MIC 90 s of chlorhexidine and mupirocin showed a 4-fold and 32-fold increase for methicillin-resistant S. aureus in comparison with methicillin-susceptible strains, while MIC values of Akacid plus® were similar for antibiotic-susceptible and multiresistant strains. Bactericidal action of Akacid plus® was observed at 1-2x MIC. The in vitro selection of resistance test showed no increase in MIC values of Akacid plus® for any isolate after 30 passages. In addition, Akacid plus® showed low oral and dermal toxicity. Conclusions: These preliminary results demonstrate the broad antimicrobial properties of Akacid plus®, which makes it a promising tool for topical application in the prophylaxis and treatment of bacterial and fungal infections.

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Antimicrobial and toxicological profile of the new biocide Akacid plus.

Summary
Invasive fungal infections cause significant morbidity and mortality in immunocompromised patients. Azoles, and fluconazole in particular, are very active against Candida albicans, and are used widely because of their good tolerability. However, the increasing use of azole antifungals for the treatment of mucosal and systemic Candida infections has resulted in the selection and/or emergence of resistant Candida strains. The main mechanisms of azole resistance among Candida species are the development of bypass pathways, alterations in the ERG 11 gene encoding the azole target enzyme, and the up-regulation of genes encoding efflux pumps. A better understanding of the mechanisms and clinical impact of antifungal resistance is essential to prompt and efficient treatment of patients with invasive mycoses and to improve the outcome of such infections.

Azole-resistant Candida spp. – emerging pathogens?

The aim of this study was to examine the antifungal activity of amphotericin B, caspofungin and posaconazole on Candida albicans biofilms in the intermediate and mature development phases. Candida albicans biofilms, previously grown for either 24, 48 or 72 h in 96-well microtitre plates, were treated for 48 h with amphotericin B, caspofungin or posaconazole in increasing concentrations according to the respective minimal inhibitory concentration (MIC) determined for planktonic cells (1-128 x MIC). The biofilms were quantified using the mean optical density (OD) determined by XTT assay. Antifungal activities were expressed as percentage of reduction in OD of drug-treated biofilms compared to untreated biofilms. To test the fungicidal activity of antifungal agents, the unfixed biofilms were scraped off and seeded to Sabouraud agar. Caspofungin and amphotericin B showed higher activity against C. albicans biofilm grown for 24 h and 72 h (>or=50% reduction of OD) than biofilms grown for 48 h, whereas posaconazole showed similar, but reduced activity against all phases of C. albicans biofilm (<or=50% reduction of OD). Caspofungin at 1-4 x MIC achieved the greatest decrease in the biofilm OD grown for 24, 48 and 72 h, whereas amphotericin B showed dose-dependent activity. However, all tested antifungals failed to reach fungicidal activity in all biofilm development phases.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1439-0507.2009.01690.x

Christina Kratzer

Papers

Antifungal susceptibility of Candida albicans in biofilms

In vitro activity of antifungal combinations against Candida albicans biofilms

Antimicrobial and toxicological profile of the new biocide Akacid plus.

Azole-resistant Candida spp. – emerging pathogens?

Antifungal activity of amphotericin B, caspofungin and posaconazole on Candida albicans biofilms in intermediate and mature development phases