scholarly journals Candida auris Isolates of the Southern Asian and South African Lineages Exhibit Different Phenotypic and Antifungal Susceptibility Profiles In Vitro

2019 ◽  
Vol 57 (5) ◽  
Author(s):  
Adrien Szekely ◽  
Andrew M. Borman ◽  
Elizabeth M. Johnson

ABSTRACT Candida auris is a serious nosocomial health risk, with widespread outbreaks occurring in hospitals worldwide. Sequence analyses of outbreak isolates revealed that C. auris has simultaneously emerged as four distinct continentally restricted clonal lineages. We previously reported multiple independent introductions of C. auris isolates from at least three of these lineages (the Southern Asia, South African, and Japanese/Korean lineages) into hospitals across the United Kingdom and that isolates circulating in the United Kingdom displayed two different cell phenotypes which correlated with differences in virulence in Galleria mellonella wax moths. Here, we compared the phenotypic characteristics and antifungal susceptibilities of isolates representative of the three geographic clades circulating in the United Kingdom. Isolates of the South African and Japanese/Korean lineages, but not those of the Southern Asian lineage, grew well on media containing actidione. However, unlike Southern Asian lineage isolates, they were unable to produce even rudimentary pseudohyphae in culture. Importantly, although all isolates were fluconazole resistant in vitro, fluconazole and voriconazole exhibited significantly higher MICs against isolates of the South African lineage than against isolates of the Southern Asian lineage. A similar trend was seen with minimum fungicidal concentrations (MFCs), with higher MFCs of the triazole antifungal agents being seen for the South African lineage isolates. Finally, the formation of large cellular aggregates was seen only with isolates of the South African and Japanese/Korean lineages, which correlates with the reduced virulence observed previously in Galleria wax moths inoculated with such isolates. Intriguingly, aggregation could be reversibly induced in isolates of the Southern Asian lineage by exposure to triazole and echinocandin antifungals but not by exposure to amphotericin B or flucytosine.

2020 ◽  
pp. 1-24
Author(s):  
Rehana Cassim

Abstract Section 162 of the South African Companies Act 71 of 2008 empowers courts to declare directors delinquent and hence to disqualify them from office. This article compares the judicial disqualification of directors under this section with the equivalent provisions in the United Kingdom, Australia and the United States of America, which have all influenced the South African act. The article compares the classes of persons who have locus standi to apply to court to disqualify a director from holding office, as well as the grounds for the judicial disqualification of a director, the duration of the disqualification, the application of a prescription period and the discretion conferred on courts to disqualify directors from office. It contends that, in empowering courts to disqualify directors from holding office, section 162 of the South African Companies Act goes too far in certain respects.


Author(s):  
Jacolien Barnard

The implementation of the Consumer Protection Act 68 of 2008 (CPA) has great implications for the South African common law of sale. In this contribution the influence of the CPA on the seller’s common law duty to warrant the buyer against eviction is investigated. Upon evaluation of the relevant provisions of the CPA, the legal position in the United Kingdom – specifically the provisions of the Sales of Goods Act of 1979 – is investigated.


Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 990
Author(s):  
Zoltán Papp ◽  
Andrew M. Borman ◽  
Lajos Forgács ◽  
Renátó Kovács ◽  
Zoltán Tóth ◽  
...  

Candida auris is an emerging multiresistant yeast against which amphotericin B (AMB) is still the first therapeutic choice in certain clinical situations (i.e., meningitis, endophthalmitis, and urinary tract infections). As data about the in vitro killing activity of AMB against C. auris clades are lacking, we determined MICs, minimum fungicidal concentrations (MFCs), and killing activity of AMB against 22 isolates representing the 4 major C. auris clades (South Asian n = 6; East Asian n = 4; South African n = 6, and South American n = 6). MIC values were ≤1 mg/L regardless of clades; MFC ranges were, 1–4 mg/L, 2–4 mg/L, 2 mg/L, and 2–8 mg/L for South Asian, East Asian, South African, and South American clades, respectively. AMB showed concentration-, clade-, and isolate-dependent killing activity. AMB was fungicidal at 1 mg/L against two of six, two of four, three of six, and one of six isolates from the South Asian, East Asian, South African, and South American clades, respectively. Widefield fluorescence microscopy showed cell number decreases at 1 mg/L AMB in cases of the South Asian, East Asian, and South African clades. These data draw attention to the weak killing activity of AMB against C. auris regardless of clades, even when MICs are low (≤1 mg/L). Thus, AMB efficacy is unpredictable in treatment of invasive C. auris infections.


1974 ◽  
Vol 21 (01) ◽  
pp. 58-69
Author(s):  
P. W. Barke

1.1. It is over 17 years since the paper ‘The Actuary in South Africa’ (1) was discussed. In South Africa as elsewhere great changes have taken place and it was felt appropriate to bring the position up to date. Nevertheless those interested are recommended to refer to the 1957 paper and not least to Mr R. G. Mallett's introduction to the discussion. Since the decision was taken to write this paper, Mr Spedding's paper ‘The Actuary in Australia’ (2) has been presented and to facilitate comparison, I have followed the general outline of that paper.1.2. The South African currency is Rands and cents (100 cents equals one Rand). Since South Africa did not follow the United Kingdom devaluation of 1967 the parity was R. 12 equals £7 sterling but South Africa devalued at the end of 1971 and then R. 2 was almost the same as £1. At the time of writing the pound is roughly equivalent to 1·5 Rand.


2019 ◽  
Vol 63 (8) ◽  
Author(s):  
Andrew M. Borman ◽  
Julian Muller ◽  
Jo Walsh-Quantick ◽  
Adrien Szekely ◽  
Zoe Patterson ◽  
...  

ABSTRACTThe triazole drug fluconazole remains one of the most commonly prescribed antifungal drugs, both for prophylaxis in high-risk patients and also as a second-line treatment option for invasiveCandidainfections. Established susceptibility profiles and clinical interpretive breakpoints are available for fluconazole withCandida albicans,Candida glabrata,Candida tropicalis, andCandida parapsilosis, which account for the majority of infections due to pathogenic yeast species. However, less common species for which only limited susceptibility data are available are increasingly reported in high-risk patients and from breakthrough infections. The UK National Mycology Reference Laboratory performs routine antifungal susceptibility testing of clinical isolates of pathogenic yeast submitted from across the United Kingdom. Between 2002 and 2016, ∼32,000 isolates were referred, encompassing 94 different yeast species. Here, we present fluconazole antifungal susceptibility data generated using a CLSI methodology over this 15-year period for 82 species (2,004 isolates) of less common yeast and yeast-like fungi, and amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and anidulafungin, with members of theNakaseomycesclade (C. glabrata,Candida nivariensis, andCandida bracarensis). At least 22 different teleomorph genera, comprising 45 species, exhibited high MICs when tested with fluconazole (>20% of isolates with MICs higher than the clinical breakpoint [≥8 mg/liter] proposed forC. albicans). Since several of these species have been reported anecdotally from breakthrough infections and therapeutic failures in patients receiving fluconazole, the current study underscores the importance of rapid and accurate yeast identification and may aid clinicians dealing with infections with rarer yeasts to decide whether fluconazole would be appropriate.


2021 ◽  
Vol 9 (4) ◽  
pp. 863
Author(s):  
Renátó Kovács ◽  
Zoltán Tóth ◽  
Jeffrey B. Locke ◽  
Lajos Forgács ◽  
Gábor Kardos ◽  
...  

Candida auris is an emerging and frequently multidrug-resistant pathogen against which the echinocandins are the preferred therapeutic option. We compared killing activities of anidulafungin, caspofungin, micafungin, and rezafungin against 13 isolates representing four C. auris clades (South Asian n = 3; East Asian n = 3; South African n = 3; South American n = 4, of which two were of environmental origin). Minimum inhibitory concentration MICs and killing kinetics in RPMI-1640 and RPMI-1640 plus 50% serum (50% serum) were determined. The four echinocandins were never fungicidal and induced large aggregates in RPMI-1640 and, less markedly, in 50% serum. Colony forming unit CFU decreases were found more consistently in 50% serum than in RPMI-1640. Isolates from the East Asian clade were killed at ≥1–≥ 4 mg/L with all echinocandins regardless of media. Anidulafungin and micafungin produced killing at peak drug serum concentration (8 mg/L) against environmental but not clinical isolates from the South American and the South African clades. Micafungin at ≥8 mg/L but not anidulafungin produced CFU decreases against the South Asian clade as well. In 50% serum, rezafungin at ≥1–≥ 8 mg/L produced killing against all four clades. The next generation echinocandin, rezafungin, showed the same or better activity at clinically attainable trough concentration regardless of media, compared with anidulafungin, caspofungin, and micafungin against all four tested C. auris clades.


2018 ◽  
Vol 62 (6) ◽  
Author(s):  
Milena Kordalewska ◽  
Annie Lee ◽  
Steven Park ◽  
Indira Berrio ◽  
Anuradha Chowdhary ◽  
...  

ABSTRACT Candida auris has simultaneously emerged on five continents as a fungal pathogen causing nosocomial outbreaks. The challenges in the treatment of C. auris infections are the variable antifungal susceptibility profiles among clinical isolates and the development of resistance to single or multiple classes of available antifungal drugs. Here, the in vitro susceptibility to echinocandin antifungal drugs was determined and FKS1 sequencing was performed on 106 C. auris clinical isolates. Four isolates were identified to be resistant to all tested echinocandins (MIC ≥ 4 mg/liter) and harbored an S639F mutation in FKS1 hot spot region 1. All remaining isolates were FKS1 wild type (WT) and echinocandin susceptible, with micafungin being the most potent echinocandin (MIC 50 = 0.125 mg/liter). Antifungal susceptibility testing with caspofungin was challenging due to the fact that all FKS1 WT isolates exhibited an Eagle effect (also known as the paradoxical growth effect), which occurred at various intensities. To assess whether the Eagle effect resulted in pharmacodynamic resistance, 8 representative isolates were evaluated for their in vivo drug response in a murine model of invasive candidiasis. All isolates were susceptible to caspofungin at a human therapeutic dose, except for those harboring the S639F mutation. The data suggest that only isolates carrying mutations in FKS1 are echinocandin resistant and that routine in vitro testing of C. auris isolates for susceptibility to caspofungin by the broth microdilution method should be viewed cautiously or avoided.


Author(s):  
Rehana Cassim

Director tenure attracts attention worldwide and is increasingly being recognised as a crucial element in assessing an external (independent non-executive) director’s independence. Director tenure has recently come under the spotlight in South Africa. Shareholder activists are expressing disapproval of lengthy tenures of directors serving on boards of listed public companies and exerting pressure on long-serving directors to resign from office. This article examines whether the South African corporate governance principles regulating director tenure are adequate or in need of revision. The article examines further the corporate governance practices in leading jurisdictions such as the United Kingdom, Malaysia, Singapore, Hong Kong, and India that have recently revised their corporate governance practices. It then makes recommendations for enhancing the South African corporate governance approach to director tenure. It also calls on directors to collaborate with shareholders and independent external experts to examine their approach to director tenure and, if circumstances allow, revise the company’s memorandum of incorporation to limit directors’ tenure or provide for a staggered rotation of directors on the board.


2017 ◽  
Vol 13 (2) ◽  
pp. 20-31
Author(s):  
Anthony O. Nwafor

The concept of corporate rescue lays emphasis on corporate sustainability than liquidation. This trend in corporate legislation which featured in the United Kingdom Insolvency Act of 1986, Australian Corporations Act 2001, Indian Sick Industrial Companies (Special Provisions) Act of 1985 (as replaced by Companies Act, 2013 and supplanted by the Insolvency and Bankruptcy Code, 2016) has been adopted in the South African Companies Act of 2008. The goal(s) of corporate rescue in some of these jurisdictions are not clearly defined. The paper examines, through a comparative analysis, the relevant statutory provisions in the United Kingdom, India, Australia and South Africa and the attendant judicial interpretations of those provisions with a view to discovering the goal(s) of corporate rescue in those jurisdictions. It is argued that while under the United Kingdom and Australian statutory provisions, the administrator could pursue alternative goals of either rescuing the company or achieving better results for the creditors; the South African and Indian statutory provisions do not provide such alternatives. The seeming ancillary purpose of crafting a fair deal for the stakeholders under the South African Companies Act’s provision is not sustainable if the company as an entity cannot be rescued.


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