Questioning the 14-day dogma in candidemia treatment duration.

The growing threat of antimicrobial resistance (AMR) is a global concern. With AMR directly causing 1.27 million deaths in 2019 and projections of up to 10 million annual deaths by 2050, optimising infectious disease treatments is imperative. Prudent antimicrobial use, including treatment duration, can mitigate AMR emergence. This is particularly critical in candidemia, a severe condition with a 45% crude mortality rate, as the 14-day minimum treatment period has not been challenged in randomised comparison. A comprehensive literature search was conducted in August 2023, revealing seven original articles and two case series discussing treatment durations of less than 14 days for candidemia. No interventional trials or prospective observational studies assessing shorter durations were found. Historical studies showed varying candidemia treatment durations, questioning the current 14-day minimum recommendation. Recent research observed no significant survival differences between patients receiving shorter or longer treatment, emphasising the need for evidence-based guidance. Treatment duration reduction post-blood culture clearance could decrease exposure to antifungal drugs, limiting selection pressure, especially in the context of emerging multiresistant Candida species. Candidemia's complexity, emerging resistance and potential for shorter in-hospital stays underscore the urgency of refining treatment strategies. Evidence-driven candidemia treatment durations are imperative to balance efficacy with resistance prevention and ensure the longevity of antifungal therapies. Further research and clinical trials are needed to establish evidence-based guidelines for candidemia treatment duration.

Attributable mortality of candidemia after introduction of echinocandins.

OBJECTIVES: Candidemia is among the most frequent nosocomial bloodstream infections. Landmark case-control studies on amphotericin B and fluconazole estimated attributable mortality rates of 38% and 49%, respectively. After introduction of echinocandins, these may have decreased. METHODS: In a case-control design, 100 consecutive, hospitalised patients with candidemia were enrolled at the University Hospital of Cologne, Germany between 2014 and 2017. Controls were patients without candidemia matched for age, sex, year and duration of hospitalisation, main admission diagnosis and Patient Clinical Complexity Level (PCCL). Main data captured were risk factors for candidemia, attributable mortality rates and diagnostic and therapeutic adherence according to the EQUAL Candida score. RESULTS: Overall mortality rates for cases and controls were 43% and 17% (P < .001), respectively; day 30 mortality rates were 38% and 11% (P = .03), accounting for an attributable mortality of 26% and 27%. Guideline adherence was higher in surviving vs non-surviving patients: while survivors reached a median of 17 (IQR: 16-19) points, non-surviving cases reached a median 16 (IQR: 14-18) points out of 22 maximum achievable points (P = .028). Risk factors for candidemia were more frequent in cases compared to control patients, especially chronic pulmonary disease (25% vs 16%; P = n.s.), chronic liver disease (21% vs 6%; P = .002), stay on intensive care unit (70% vs 64%; P = n.s.), respiratory failure (56% vs 50%; P = n.s.) and central venous catheter (97% vs 35%; P < .001). CONCLUSIONS: Attributable mortality of nosocomial candidemia is still substantial but has decreased compared to previous studies with similar design.

Risk factors and mortality in invasive Rasamsonia spp. infection: Analysis of cases in the FungiScope® registry and from the literature.

BACKGROUND: The new Rasamsonia spp. complex can develop invasive infection in immunosuppression or chronic pulmonary disease. It has potential to be misidentified as other genera due to morphological similarities. Nowadays, there is a gap of knowledge on this fungi. OBJECTIVES: To provide knowledge base of risk factors and therapeutic decisions in invasive Rasamsonia spp. complex infection. PATIENTS/METHODS: Cases of invasive infection due to Rasamsonia spp. (formerly Geosmithia/Penicillium spp.) from FungiScope® registry and all reported cases from a literature were included. RESULTS: We identified 23 invasive infections due to Rasamsonia spp., six (26.1%) in the FungiScope® registry. Main risk factors were chronic granulomatous disease (n = 12, 52.2%), immunosuppressive treatment (n = 10, 43.5%), haematopoietic stem cell transplantation (n = 7, 30.4%), graft-versus-host disease and major surgery (n = 4, 17.4%, each). Predominantly affected organs were the lungs (n = 21, 91.3%), disease disseminated in seven cases (30.4%). Fungal misidentification occurred in 47.8% (n = 11), and sequencing was used in 69.6% of the patients (n = 16) to diagnose. Breakthrough infection occurred in 13 patients (56.5%). All patients received antifungal treatment, mostly posaconazole (n = 11), caspofungin (n = 10) or voriconazole (n = 9). Combination therapy was administered in 13 patients (56.5%). Susceptibility testing showed high minimum inhibitory concentrations for azoles and amphotericin B, but not for echinocandins. No preferable treatment influencing favourable outcome was identified. Overall mortality was 39% (n = 9). CONCLUSION: Rasamsonia spp. are emerging fungi causing life-threatening infections, especially in immunocompromised and critically ill patients. Mortality is high. Treatment is challenging and clinicians dealing with this patient population should become aware of this infection constituting a medical emergency.

Rare mould infections caused by Mucorales, Lomentospora prolificans and Fusarium, in San Diego, CA: the role of antifungal combination therapy.

Non-Aspergillus invasive mould infections (IMIs) are associated with devastating morbidity and mortality rates and are increasingly diagnosed in immunocompromised hosts. The aim of this study was to describe the epidemiology and outcomes of non-Aspergillus IMIs at a university hospital in San Diego, California, USA. A retrospective chart review of the medical records of all patients with cultures growing non-Aspergillus moulds at the microbiology laboratory in the Center for Academic Laboratory Medicine, Department of Pathology, University of California, San Diego (UCSD) Health between mid-2014 and mid-2017 (3-year period) was performed. A total of 23 cases of non-Aspergillus IMI were identified, including 10 cases of mucormycosis, 8 cases of lomentosporiosis and 5 cases of fusariosis. Antifungal susceptibility testing was performed for 14 isolates, and 10/11 Fusarium and Lomentospora isolates had minimum inhibitory concentrations (MICs) of >16 µg/mL for voriconazole and/or posaconazole. Overall 180-day mortality was significantly lower among those who received combination antifungal therapy than among those who received single-agent therapy [3/13 (23%) vs. 9/10 (90%); P = 0.003]. In conclusion, Lomentospora prolificans (35% of non-Aspergillus IMIs) and Fusarium spp. (22%) accounted for high proportions of non-Aspergillus IMIs during the study period. Non-Aspergillus IMIs were detected in patients with various underlying diseases and were associated with high mortality rates, which was significantly lower in those who received antifungal combination therapy.

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

Candida species frequently cause blood stream infections and are reported to be the third to tenth most commonly isolated pathogens. Guidelines and standardised treatment algorithms provided by professional organisations aim to facilitate decision-making regarding diagnosis, management and treatment of candidaemia. In routine clinical practise, however, it may be challenging to comply with these guidelines. The reasons include lack of familiarity or feasibility to adherence, but also their length and complexity. There is no tool to measure guideline adherence currently. To provide such a tool, we reviewed the current guidelines provided by the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) and by the Infectious Diseases Society of America (IDSA), and selected the strongest recommendations for management quality as the bases for our scoring tool. Factors incorporated were diagnostic (blood cultures, echocardiography, ophthalmoscopy, species identification) and follow-up procedures (repeat blood cultures until negative result) as well as key treatment parameters (echinocandin treatment, step down to fluconazole depending on susceptibility result, CVC removal). The EQUAL Candida Score weighs and aggregates factors recommended for the ideal management of candidaemia and provides a tool for antifungal stewardship as well as for measuring guideline adherence.

Bone and joint infections by Mucorales, Scedosporium, Fusarium and even rarer fungi.

Mucorales, Scedosporium and Fusarium species are rarely considered as cause for bone and joint infections. However, these moulds are emerging as important fungal pathogens in immunocompromised and immunocompetent patients. Typical pre-disposing host conditions are immunosuppression and diabetes. Most common causative pathogens are Mucorales followed by Scedosporium and Fusarium. Acremonium and Phialemonium species are rare but some case reports exist. MRI is the gold standard imaging technique. Tissue specimens obtained as aspirates, imaging guided biopsy or open surgery need mycological and histopathological work-up for genus and species identification. Multimodal treatment strategies combine surgical debridement, drainage of joints or abscesses, removal of infected prosthetic joints and systemic antifungals. The treatment of mucormycosis is polyene based and may be combined with either posaconazole or - in rare cases - caspofungin. As Scedosporium species are intrinsically resistant to polyenes and azoles show absence of in vitro activity, voriconazole plus synergistic treatment regimens become the therapeutic standard. In fusariosis, fungal susceptibility is virtually impossible to predict, so that combination treatment of voriconazole and lipid-based amphotericin B should be the first-line strategy while susceptibility results are pending. In the absence of randomized controlled trials, infections due to the above moulds should be registered, e.g. in the registries of the European Confederation of Medical Mycology (ECMM).