Riina Rautemaa-Richardson

The global problem of antifungal resistance: prevalence, mechanisms, and management

All serious fungal infections need appropriate antifungal therapy for successful patient outcome. Only a few classes of antifungal drugs are available, so the emergence of resistance to single drug classes and now multidrug resistance greatly hampers patient management. Azole resistance among Candida and Aspergillus species is one of the greatest challenges to clinical success, followed by echinocandin and multidrug resistance among some Candida species, especially Candida glabrata. The spread of agriculturally derived azole-resistant Aspergillus fumigatus and emerging threats such as multidrug resistant Candida auris are also alarming. The molecular mechanisms that cause drug resistance are naturally occurring in less susceptible species and are acquired in strains of susceptible organisms. Drug resistance mechanisms include altered drug-target interactions, reduced cellular drug concentrations mediated by drug efflux transporters, and permeability barriers associated with biofilms. Although C auris is inherently multidrug resistant, other strains typically develop resistance through stepwise selection of multiple drug-resistance mechanisms. Cellular stress induced by drug treatment promotes adaptation, which contributes to breakthrough resistance. Drug exposure also drives the emergence of resistance. An effective antifungal stewardship programme is essential to control drug resistance, and should incorporate rapid fungal diagnostics, therapeutic drug monitoring, and clinical intervention teams. The development of better diagnostic tools and strategies that allow targeted use of antifungals is essential to preserve drug effectiveness.

Biofilm-Forming Capability of Highly Virulent, Multidrug-Resistant Candida auris

The emerging multidrug-resistant yeast pathogen Candida auris has attracted considerable attention as a source of healthcare–associated infections. We report that this highly virulent yeast has the capacity to form antifungal resistant biofilms sensitive to the disinfectant chlorhexidine in vitro.

Effect of pH on In Vitro Susceptibility of Candida glabrata and Candida albicans to 11 Antifungal Agents and Implications for Clinical Use

ABSTRACT The treatment of vulvovaginal candidiasis (VVC) due to Candida glabrata is challenging, with limited therapeutic options. Unexplained disappointing clinical efficacy has been reported with systemic and topical azole antifungal agents in spite of in vitro susceptibility. Given that the vaginal pH of patients with VVC is unchanged at 4 to 4.5, we studied the effect of pH on the in vitro activity of 11 antifungal agents against 40 C. glabrata isolates and compared activity against 15 fluconazole-sensitive and 10 reduced-fluconazole-susceptibility C. albicans strains. In vitro susceptibility to flucytosine, fluconazole, voriconazole, posaconazole, itraconazole, ketoconazole, clotrimazole, miconazole, ciclopirox olamine, amphotericin B, and caspofungin was determined using the CLSI method for yeast susceptibility testing. Test media were buffered to pHs of 7, 6, 5, and 4. Under conditions of reduced pH, C. glabrata isolates remained susceptible to caspofungin and flucytosine; however, there was a dramatic increase in the MIC90 for amphotericin B and every azole drug tested. Although susceptible to other azole drugs tested at pH 7, C. albicans strains with reduced fluconazole susceptibility also demonstrated reduced susceptibility to amphotericin B and all azoles at pH 4. In contrast, fluconazole-sensitive C. albicans isolates remained susceptible at low pH to azoles, in keeping with clinical observations. In selecting agents for treatment of recurrent C. glabrata vaginitis, clinicians should recognize the limitations of in vitro susceptibility testing utilizing pH 7.0.

Predictors of mortality in chronic pulmonary aspergillosis

Chronic pulmonary aspergillosis (CPA) is a chronic progressive infection that destroys lung tissue in non-immunocompromised patients. Contemporary series suggest 50–85% 5-year mortality, with few prognostic factors identified. A cohort of 387 CPA patients referred to the UKs National Aspergillosis Centre from 1992 to June 2012 was studied until June 2015. The impact of objective and subjective variables including age, sex, previous pulmonary conditions, dyspnoea score, quality of life, serum albumin and C-reactive protein and radiological appearances were assessed using Kaplan–Meier curves, log rank tests and Cox proportional hazards modelling. In samples of patients, retrospective review of time from likely onset of CPA to referral and cause of death were also investigated. Survival was 86%, 62% and 47% at 1, 5 and 10u2005years, respectively. Increased mortality was associated with nontuberculous mycobacterial infection (hazard ratio 2.07, 95% CI 1.22–3.52; p<0.001) and chronic obstructive pulmonary disease (1.57, 1.05–2.36; p=0.029) as well as higher age (1.053, 1.03–1.07 per year; p<0.001), lower albumin (0.92, 0.87–0.96 per g·L−1), lower activity (1.021, 1.01–1.03 per point increase in St Georges Respiratory Questionnaire activity domain; p<0.001) and having one, and especially, bilateral aspergillomas (p<0.001). Several factors impact on mortality of CPA, and can be evaluated as tools to assess CPA prognosis. This article describes the worlds largest experience of chronic pulmonary aspergillosis and its outcome http://ow.ly/pG9X305Yw8L

Management of severe acute dental infections

#### The bottom linennAcute dental infection typically occurs when bacteria invade the dental pulp (nerve) and spread to tissues surrounding the tooth. Radiological signs of tooth associated infection in the supporting bone are extremely common, affecting 0.5-13.9% (mean 5.4%) of all teeth in a large systematic analysis of cross sectional studies.1 In addition to localised disease, dental infections can spread regionally and haematogenously, causing serious disseminated infections, especially in patients who are medically compromised.2 3 General medical practitioners and those working in emergency departments are frequently asked to treat patients presenting with dental problems but often have little or no training in this area.4 The purpose of this review is to help general practitioners and non-specialists with the initial diagnosis and management of acute dental infections.nn#### Sources and selection criteriannWe searched Medline 1950-2013 for the keywords “dental abscess”, “odontogenic infection”, “endodontic abscess”, “periapical abscess and microbiology”, and “clinical trials”. Embase was also searched, including the Cochrane database …

Quality control for diagnostic oral microbiology laboratories in European countries

Abstract Participation in diagnostic microbiology internal and external quality control (QC) processes is good laboratory practice and an essential component of a quality management system. However, no QC scheme for diagnostic oral microbiology existed until 2009 when the Clinical Oral Microbiology (COMB) Network was created. At the European Oral Microbiology Workshop in 2008, 12 laboratories processing clinical oral microbiological samples were identified. All these were recruited to participate into the study and six laboratories from six European countries completed both the online survey and the first QC round. Three additional laboratories participated in the second round. Based on the survey, European oral microbiology laboratories process a significant (mean per laboratory 4,135) number of diagnostic samples from the oral cavity annually. A majority of the laboratories did not participate in any internal or external QC programme and nearly half of the laboratories did not have standard operating procedures for the tests they performed. In both QC rounds, there was a large variation in the results, interpretation and reporting of antibiotic susceptibility testing among the laboratories. In conclusion, the results of this study demonstrate the need for harmonisation of laboratory processing methods and interpretation of results for oral microbiology specimens. The QC rounds highlighted the value of external QC in evaluating the efficacy and safety of processes, materials and methods used in the laboratory. The use of standardised methods is also a prerequisite for multi-centre epidemiological studies that can provide important information on emerging microbes and trends in anti-microbial susceptibility for empirical prescribing in oro-facial infections.

Global burden of recurrent vulvovaginal candidiasis: a systematic review

Recurrent vulvovaginal candidiasis is a debilitating, long-term condition that can severely affect the quality of life of affected women. No estimates of the global prevalence or lifetime incidence of this disease have been reported. For this systematic review, we searched PubMed, Embase, and Web of Science databases for population-based studies published between 1985 and 2016 that reported on the prevalence of recurrent vulvovaginal candidiasis, defined as four or more episodes of the infection every year. We identified 489 unique articles, of which eight were included, consisting of 17u2008365 patients from 11 countries. We generated estimates of annual global prevalence, estimated lifetime incidence and economic loss due to recurrent vulvovaginal candidiasis, and predicted the number of women at risk to 2030. Worldwide, recurrent vulvovaginal candidiasis affects about 138 million women annually (range 103-172 million), with a global annual prevalence of 3871 per 100u2008000 women; 372 million women are affected by recurrent vulvovaginal candidiasis over their lifetime. The 25-34 year age group has the highest prevalence (9%). By 2030, the population of women with recurrent vulvovaginal candidiasis each year is estimated to increase to almost 158 million, resulting in 20u2008240u2008664 extra cases with current trends using base case estimates in parallel with an estimated growth in females from 3·34 billion to 4·181 billion. In high-income countries, the economic burden from lost productivity could be up to US

Volatile organic compound detection as a potential means of diagnosing cutaneous wound infections

14·39 billion annually. The high prevalence, substantial morbidity, and economic losses of recurrent vulvovaginal candidiasis require better solutions and improved quality of care for affected women.

Cutaneous wound biofilm and the potential for electrical stimulation in management of the microbiome

Chronic cutaneous wound infections and surgical site infections (SSIs) present a huge burden on the healthcare system and can lead to increased morbidity and mortality. Current diagnostic methods of identifying and confirming infection involve culture‐based and molecular methods. Both techniques are time‐consuming and delays commonly lead to untargeted empirical treatment. An ideal diagnostic method would be noninvasive and highly sensitive and detect pathogenic organisms with a high degree of accuracy to allow targeted treatment. Volatile organic compounds (VOCs) are a diverse group of carbon‐based molecules produced and released by humans and microorganisms. VOC detection has the potential in aiding cutaneous wound infection diagnostics using noninvasive and time‐efficient methods. This review provides a comprehensive update on VOCs produced and emitted by bacteria commonly associated with chronic wounds and SSIs. VOC sampling has the advantage of being painless, time‐efficient, noninvasive, and reproducible. VOCs emitted by these organisms are diverse. In vitro studies have identified potential signature volatile profiles, which can be used in detecting these microorganisms. Combining these profiles with volatile profiles emitted from acute, chronic and surgical wounds in vivo could potentially allow identification of bacterial‐specific VOCs. VOC detection has the potential for a relatively inexpensive, portable, noninvasive, and reliable clinical diagnostic tool, which could be used in detecting cutaneous wound infections and guiding their optimal management.

EQUAL Candida Score: An ECMM score derived from current guidelines to measure QUAlity of Clinical Candidaemia Management

Infection contributes significantly to delayed cutaneous wound healing, which impacts patient care. External application of electrical stimulation (ES) has beneficial effects on wound repair and regeneration. The majority of studies to date have explored ES in relation to planktonic microorganisms, yet evidence indicates that bacteria in chronic wounds reside as antibiotic-resistant polymicrobial biofilms, which contribute to impairing wound healing. Culture-independent sequencing techniques have revolutionized our understanding of the skin microbiome and allowed a more accurate determination of microbial taxa and their relative abundance in wounds allowing a greater understanding of the host-microbial interface. Future studies combining the fields of ES, biofilm and microbiome research are necessary to fully elucidate the use of ES in the management of wound infection.