Environmental monitoring for filamentous fungal pathogens in hematopoietic cell transplant units.

The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment, and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as hematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions. As a collaborative effort between authors affiliated to the Infection Prevention and Control Working Group and the Fungal Infection Working Group of the International Society of Antimicrobial Chemotherapy (ISAC), we reviewed the English language literature and international guidance to describe the evidence behind the need for environmental monitoring for filamentous fungi as a quality assurance approach with an emphasis on required additional precautions during periods of construction. Many different clinical sampling approaches have been described for air, water, and surface sampling with significant variation in laboratory methodologies between reports. Importantly, there are no agreed-upon thresholds that correlate with an increase in the clinical risk of mould infections. We highlight important areas for future research to assure a safe environment for highly immunocompromized patients.

Mould infections have a high mortality in high-risk patients. Ventilation engineering significantly reduces the risk of acquiring such infections. Environmental sampling for moulds is carried out in many centers in addition to standard precautions. We review the literature on this subject.

Carriage of multidrug-resistant carbapenemase-producing gram-negative bacteria in patients admitted to NHS Greater Glasgow and Clyde hospitals: Implications for treatment.

BACKGROUND: Infections caused by gram-negative carbapenemase-producing organisms (CPO) have become a global phenomenon. Screening of patients for CPO that was carried out at 48-h intervals enables early detection of carriers for infection control purposes and planning therapy. METHODS: We investigated the bacterial flora detected on screening, the enzymes that conferred resistance and the proportion of patients who developed bacteraemia with CPO and their therapy. RESULTS: In all, 27 patients had a positive screen for CPO. A small but significant (7.5%) proportion of patients were not detected on initial screening. Escherichia coli and Klebsiella were predominant. New-Delhi metallo ß-lactamase and oxacillin carbapenemases were the main enzymatic mechanisms of resistance. Four (14.8%) patients developed bacteraemia with CPO (30- and 90-day survival 100% and 75%, respectively). CONCLUSION: A single negative screen does not rule out colonisation. A significant proportion of patients colonised with CPO develop bacteraemia. Vigilance is needed to prevent the nosocomial spread of CPO.

The battle against fungi: lessons in antifungal stewardship from COVID 19 times

The COVID-19 pandemic has highlighted the detrimental effect of secondary pathogens in patients with a primary viral insult. In addition to superinfections with bacterial pathogens, invasive fungal infections were increasingly reported. The diagnosis of pulmonary fungal infections has always been challenging; however, it became even more problematic in the setting of COVID-19, particularly regarding the interpretation of radiological findings and mycology test results in patients with these infections. Moreover, prolonged hospitalization in ICU, coupled with underlying host factors. such as preexisting immunosuppression, use of immunomodulatory agents, and pulmonary compromise, caused additional vulnerability to fungal infections in this patient population. In addition, the heavy workload, redeployment of untrained staff, and inconsistent supply of gloves, gowns, and masks during the COVID-19 outbreak made it harder for healthcare workers to strictly adhere to preventive measures for infection control. Taken together, these factors favored patient-to-patient spread of fungal infections, such as those caused by Candida auris, or environment-to-patient transmission, including nosocomial aspergillosis. As fungal infections were associated with increased morbidity and mortality, empirical treatment was overly used and abused in COVID-19-infected patients, potentially contributing to increased resistance in fungal pathogens. The aim of this paper was to focus on essential elements of antifungal stewardship in COVID-19 for three fungal infections, COVID-19-associated candidemia (CAC), -pulmonary aspergillosis (CAPA), and -mucormycosis (CAM).

Epidemiology, management and outcome of candidaemia in patients with diabetes.

BACKGROUND: Candidaemia is the commonest fungal bloodstream infection in hospitalised patients. Diabetes is one of the risk factors for mortality from candidaemia. METHODS: We compared the epidemiology, clinical characteristics and management of candidaemia in patients with and without diabetes. RESULTS: Over a 10-year period, 200 episodes of Candida bloodstream infection were documented. Patients with diabetes were younger (58.7 vs 65.5 years), less likely to be suffering from cancer (21.8% vs 36%), and had significantly lower 30-day and 90-day crude mortality (17.2% vs 35.6% and 28.4% vs 48.6%, respectively). Candida glabrata was more common in patients with diabetes (39.3% vs 29.7%). Based on European Confederation of Medical Mycology (ECMM) quality indicators, the management of patients with and without diabetes was similar. DISCUSSION: Our study highlights the importance of epidemiological data in relation to candidaemia in patients with diabetes and the growing threat of invasive C. glabrata infection in this subset of patients.

A prospective surveillance study to determine the prevalence of 16S rRNA methyltransferase-producing Gram-negative bacteria in the UK.

OBJECTIVES: To determine the prevalence of 16S rRNA methyltransferase- (16S RMTase-) producing Gram-negative bacteria in patients in the UK and to identify potential risk factors for their acquisition. METHODS: A 6 month prospective surveillance study was conducted from 1 May to 31 October 2016, wherein 14 hospital laboratories submitted Acinetobacter baumannii, Enterobacterales and Pseudomonas aeruginosa isolates that displayed high-level amikacin resistance according to their testing methods, e.g. no zone of inhibition with amikacin discs. Isolates were linked to patient travel history, medical care abroad, and previous antibiotic exposure using a surveillance questionnaire. In the reference laboratory, isolates confirmed to grow on Mueller-Hinton agar supplemented with 256 mg/L amikacin were screened by PCR for 16S RMTase genes armA, rmtA-rmtH and npmA, and carbapenemase genes (blaKPC, blaNDM, blaOXA-48-like and blaVIM). STs and total antibiotic resistance gene complement were determined via WGS. Prevalence was determined using denominators for each bacterial species provided by participating hospital laboratories. RESULTS: Eighty-four isolates (44.7%), among 188 submitted isolates, exhibited high-level amikacin resistance (MIC >256 mg/L), and 79 (94.0%) of these harboured 16S RMTase genes. armA (54.4%, 43/79) was the most common, followed by rmtB (17.7%, 14/79), rmtF (13.9%, 11/79), rmtC (12.7%, 10/79) and armA + rmtF (1.3%, 1/79). The overall period prevalence of 16S RMTase-producing Gram-negative bacteria was 0.1% (79/71 063). Potential risk factors identified through multivariate statistical analysis included being male and polymyxin use. CONCLUSIONS: The UK prevalence of 16S RMTase-producing Gram-negative bacteria is low, but continued surveillance is needed to monitor their spread and inform intervention strategies.

European confederation of medical mycology quality of clinical candidaemia management score: A review of the points based best practice recommendations.

Candidaemia is associated with high mortality. In the last few years, several guidelines have been published on the management of Candida bloodstream infection. However, adherence to the practice guidelines has been suboptimal. In order to facilitate and objectively measure the adherence to good practice recommendations, a scoring criterion was published by the European Confederation of Medical Mycology (ECMM). The ECMM Quality (EQUAL) of Clinical Candidaemia Management is an audit tool that comprises of 10 quality indicators. Each quality indicator is allotted between 1 and 3 points. The maximum achievable score is 22 or 19 in patients with or without a central venous catheter, respectively. This paper reviews each of the 10 quality indicators and provides the context for improving quality within the individual domains. The review also suggests areas that are in need of further clarity or areas which merit attention in the future updates of the EQUAL scoring system so that clinicians are able to derive maximum benefit from the audit tool. The EQUAL scoring tool is an important milestone in the quality improvement aspect of the management of candidaemia and contributes to the various components of clinical governance in the management of Candida infection of the bloodstream.

Refractory Human Cutaneous Protothecosis.

A 67-year-old Scottish woman presented to her general practitioner with a subcentimeter lump between her shoulder blades. The lump was suspected to be an epidermal cyst and was excised. The patient had a history of controlled diabetes. Most summers, she spent a month near a beach resort in Mexico. The lump reappeared after 6 months within the scar area and was re- excised. Both skin excisions were performed in the primary care setting without histologic assessment.

Candidaemia in the elderly: Epidemiology, management and adherence to the European Confederation of Medical Mycology quality indicators.

BACKGROUND: Candidaemia in the elderly has not been extensively investigated. OBJECTIVES: We compared the management of candidaemia in the elderly patients (age ≥65 years) and the very elderly subgroup of patients (age ≥75 years) with those belonging to the younger group (age <65 years) using the European Confederation of Medical Mycology (ECMM) Quality (EQUAL) standard. PATIENTS & METHODS: Over a 10-year period (April 2011-March 2020), patients with candida bloodstream infection were identified. Data pertaining to demographics, clinical risk factors, antifungal treatment, central venous catheter and investigations such as echocardiogram and fundoscopy were obtained from electronic sources and medical case notes. RESULTS: A total of 174 episodes of candidaemia were recorded, comprising of 74 episodes in younger patients and 100 in the elderly, of whom 56 were in the very elderly patients. Of the 177 Candida species recovered, 79 were Candida albicans. EQUAL scores were analysed for 148 patients. The mean score was significantly lower in the elderly (10.4) and the very elderly (9.7) patients compared to the patients in the younger age group (12.19) (P < .01). In particular, this was due to lower blood culture volume drawn (P < .01) and, in the very elderly group, significantly lower scores for the quality indicators pertaining to echocardiogram and fundoscopy (P = .03). The overall mean EQUAL score was 11.16 (median 11; interquartile range 8-14). The 30-day survival was 68% and was similar between all groups. CONCLUSIONS: Areas of improvement were identified in the management of candidaemia in the elderly patients.

A Rare Case of Mixed Infectious Keratitis Caused by Pseudomonas koreensis and Aspergillus fumigatus.

We report the clinical and microbiological features of contact lens-related mixed infectious keratitis caused by a spore-forming filamentous fungus and a rare gram-negative bacterial infection. A 66-year-old Caucasian female presented with right eye (OD) pain after sleeping in her 2-weekly contact lenses for 3 days. On presentation, corrected distance visual acuity was 0.46 LogMAR OD and 0.20 in the left eye. Slit lamp biomicroscopy revealed a 1.9 mm by 1.9 mm area of dense stromal infiltrate with epithelial defect. Corneal scrapes grew Aspergillus fumigatus and Pseudomonas koreensis, and culture-directed microbial therapy with oral and topical voriconazole and topical fortified gentamicin along with regular debridement resulted in slow resolution of the infection, leaving a dense stromal scar in the visual axis requiring penetrating keratoplasty. Mixed infectious keratitis caused by filamentous fungi and gram-negative bacteria is rare. Pseudomonas koreensis infection has not been previously reported as a cause of infectious keratitis in humans. In our experience, these mixed infections require prolonged systemic and topical therapy and the secondary scarring may require surgical intervention for vision rehabilitation.

Antifungal stewardship with an emphasis on candidaemia.

Antimicrobial resistance is a global threat. To counter the growing menace of antibiotic resistance, several stewardship initiatives have been incorporated as part of the overarching strategy of healthcare delivery. In contrast, antifungal stewardship (AFS) has attracted less attention for several reasons, such as limited antifungal resistance and the lesser burden of fungal infections compared with bacterial infections. However, the emergence of resistant fungi, such as multidrug-resistant Candida auris, has provided impetus to AFS programmes. This review summarises existing data on AFS programmes, particularly in relation to invasive candidiasis, both in the empirical setting and in the setting of proven infection.

Management of candidaemia with reference to the European confederation of medical mycology quality indicators.

Background: Candidaemia is associated with high mortality. The European Confederation of Medical Mycology (ECMM) has recently proposed the ECMM Quality of Clinical Candidemia Management (EQUAL) scoring criteria which provide an objective measure of adherence to various good practice recommendations. The maximum score is 22 in patients with a central venous catheter (CVC) and 19 in patients without a CVC. Our objective was to audit the management of patients with candidaemia against the ECMM recommendations. Methods: We interrogated our prospective database against individual ECMM recommendations. The audit period was from April 2011 to February 2019. Data were collected from electronic records and case-notes. Results: A total of 131 patients were audited. The mean (maximum) scores for the individual good practice recommendations were as follows: adequate volume of blood culture 0.98 (3) points, identification of Candida species 3 (3) points, antifungal susceptibility testing 1.98 (2) points, echocardiogram 0.51 (1) point, ophthalmoscopy 0.3 (1) point, initial treatment with echinocandin 1.32 (3) points, step-down therapy 0.74 (2) points, treatment for 14 days following first negative follow-up culture 1.37 (2) points, removal of CVC 1.79 (3 for removal within 24 hours or 2 for removal within 72 hours) points, and daily follow up blood cultures 0 (2) points. The overall mean EQUAL score was 11.04. The mean scores of survivors and non-survivors were 11.21 and 10.54 respectively. Performance of ophthalmoscopic examination was associated with a favourable outcome. Conclusion: The audit highlights the need for improvement in the clinical aspects of management of candidaemia.

WhatsApp, Doc?

Confidentiality underpins the trust between doctors and patients. As far back as the 2nd century BC, the great Indian physician, Charak, had stated: "Nothing that happens in the house of the sick man must be told outside, nor must the patient's condition be told to anyone who might do harm by that knowledge to the patient or to another".

One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers.

BACKGROUND: The aim of this study was to characterise the microbiome of new and recurrent diabetic foot ulcers using 16S amplicon sequencing (16S AS), allowing the identification of a wider range of bacterial species that may be important in the development of chronicity in these debilitating wounds. Twenty patients not receiving antibiotics for the past three months were selected, with swabs taken from each individual for culture and 16S AS. DNA was isolated using a combination of bead beating and kit extraction. Samples were sequenced on the Illumina Hiseq 2500 platform. RESULTS: Conventional laboratory culture showed positive growth from only 55 % of the patients, whereas 16S AS was positive for 75 % of the patients (41 unique genera, representing 82 different operational taxonomic units (OTU's). S. aureus was isolated in 72 % of culture-positive samples, whereas the most commonly detected bacteria in all ulcers were Peptoniphilus spp., Anaerococcus spp. and Corynebacterium spp., with the addition of Staphylococcus spp. in new ulcers. The majority of OTU's residing in both new and recurrent ulcers (over 67 %) were identified as facultative or strict anaerobic Gram-positive organisms. Principal component analysis (PCA) showed no difference in clustering between the two groups (new and recurrent ulcers). CONCLUSIONS: The abundance of anaerobic bacteria has important implications for treatment as it suggests that the microbiome of each ulcer "starts afresh" and that, although diverse, are not distinctly different from one another with respect to new or recurrent ulcers. Therefore, when considering antibiotic therapy the duration of current ulceration may be a more important consideration than a history of healed ulcer.

Primary invasive aspergillosis with disseminated intravascular coagulation as a presenting feature of non-Hodgkin's lymphoma.

Invasive aspergillosis (IA) is a life-threatening infection. IA is usually seen in severely immunocompromised patients. However, IA as a presenting feature of non-Hodgkin's lymphoma is rare. The patient we describe had no signs or symptoms of lymphoma prior to hospital admission. A. fumigatus was isolated from respiratory tract specimens on the day of admission and fungal elements were detected on autopsy. Isolation of Aspergillus in patients with severe sepsis should trigger a search haematological malignancy.