Antifungal Usage Research Articles

The Effects of COVID-19 on Antifungal Prescribing in the UK—Lessons to Learn

Fungal infections are increasingly prevalent; however, antifungal stewardship attracts little funding or attention. Previous studies have shown that knowledge of guidelines and scientific evidence regarding antifungals is poor, leading to prescribing based on personal experiences and the inherent biases this entails. We carried out a retrospective study of inpatient antifungal usage at two major hospitals. We assessed the longitudinal trends in antifungal usage and the effect of COVID-19 on antifungal prescription, alongside levels of empirical and diagnostically targeted antifungal usage. Our results showed that the longitudinal patterns of total systemic antifungal usage within the trusts were similar to national prescribing trends; however, the composition of antifungals varied considerably, even when looking exclusively at the more homogenous group of COVID-19 patients. We showed a high level of empirical antifungal use in COVID-19 patients, with neither trust adhering to international recommendations and instead appearing to follow prior prescribing habits. This study highlights the significant challenges to optimise antifungal use with prescribing behaviour largely dictated by habit, a lack of adherence to guidelines, and high rates of empirical non-diagnostic-based prescribing. Further research and resources are required to understand the impact of antifungal stewardship on improving antifungal prescribing behaviours in this setting and the effects on outcome.

Antifungal resistance profile and genetic relatedness of moulds from rural groundwater sources

Antifungal resistance remains a significant public health threat, yet poorly investigated. This study for the first time investigated the antifungal profile of moulds isolated from groundwaters in a rural community of Osun State, Southwest Nigeria. Groundwater samples were collected during dry and rainy seasons, and processed for mould isolation using standard methods. The isolates were presumptively identified and screened for in vitro susceptibility using 4 antifungals conventionally employed in clinical cases. Multiple antifungal resistance phenotypes and indices were equally evaluated. Representative of each putatively identified species were confirmed using molecular techniques. A total of 29 and 27 moulds were obtained during the dry and rainy seasons, respectively. Genus Aspergillus was the most prevalent (30.4%). Of the 56 isolates subjected to antifungal susceptibility testing, 55(98%) were resistant to fluconazole, followed by flucytosine 49(88%), ketoconazole 45(80%) and amphotericin B 31(55%). Exactly 46 isolates were multidrug-resistant, 23(50%) each, to 3 and 4 drugs, respectively. The multiple antifungal resistance index (MARI) evaluated was 1 in all the samples A-Q, except C (0.75), transcending the threshold limit of 0.2, indicating the isolates to be of high antifungal usage origin. The molecularly identified species had 99–100% similarity with reference strains from GenBank and evolutionary relationship of taxa revealed 10 distinct clades. The outcome of this study reveals a rise in the frequency of antifungal resistance in moulds towards standard drugs, thus, advocating for adequate investigations targeted at monitoring antifungal resistance in groundwater milieus.

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

Antifungal Drug Usage in European Neonatal Units: A Multicenter Weekly Point Prevalence Study.

Data on antifungal prescribing in neonatal patients are limited to either single-center or single-country studies or to 1-day recording. Therefore, we assessed antifungal longitudinal usage in neonatal units (NUs) within Europe. CALYPSO, a prospective weekly point prevalence study on antifungal drug usage in NUs in 18 hospitals (8 European countries), was conducted in 2020 during a 12-week period. All patients receiving systemic antifungals were included. Ward demographics were collected at the beginning; ward and patient data including indication, risk factors and antifungal regimen were weekly collected prospectively. Among 27 participating NUs, 15 (56%) practiced antifungal prophylaxis for neonates with birth weight <1000 g or <1500 g and additional risk factors. In total, 174 patients received antifungals with a median frequency per week of 10.5% ranging from 6.9% to 12.6%. Indication for antifungal prescribing was prophylaxis in 135/174 (78%) courses and treatment in 22% [39 courses (69% empirical, 10% preemptive, 21% targeted)]. Fluconazole was the most frequent systemic agent used both for prophylaxis (133/135) and treatment (15/39, 39%). Among neonates receiving prophylaxis, the most common risk factors were prematurity (119/135, 88%), mechanical ventilation (109/135, 81%) and central vascular catheters (89/135, 66%). However, gestational age <28 weeks was only recorded in 55/135 (41%) courses and birth weight <1000 g in 48/135 (35%). Most common reason for empirical treatment was late-onset sepsis; all 8 targeted courses were prescribed for invasive candidiasis. Antifungal usage in European NUs is driven by prophylaxis and empirical treatment with fluconazole being the most prescribed agent for both indications.

Fungal Infections, Treatment and Antifungal Resistance: The Sub-Saharan African Context.

Fungal pathogens cause a wide range of infections in humans, from superficial to disfiguring, allergic syndromes, and life-threatening invasive infections, affecting over a billion individuals globally. With an estimated 1.5 million deaths annually attributable to them, fungal pathogens are a major cause of mortality in humans, especially people with underlying immunosuppression. The continuous increase in the population of individuals at risk of fungal infections in sub-Saharan Africa, such as HIV patients, tuberculosis patients, intensive care patients, patients with haematological malignancies, transplant (haematopoietic stem cell and organ) recipients and the growing global threat of multidrug-resistant fungal strains, raise the need for an appreciation of the region's perspective on antifungal usage and resistance. In addition, the unavailability of recently introduced novel antifungal drugs in sub-Saharan Africa further calls for regular evaluation of resistance to antifungal agents in these settings. This is critical for ensuring appropriate and optimal use of the limited available arsenal to minimise antifungal resistance. This review, therefore, elaborates on the multifaceted nature of fungal resistance to the available antifungal drugs on the market and further provides insights into the prevalence of fungal infections and the use of antifungal agents in sub-Saharan Africa.

A quasi-experimental analysis comparing antimicrobial usage on COVID-19 and non-COVID-19 wards.

To describe antimicrobial usage (AMU) trends before and during the coronavirus disease 2019 (COVID-19) pandemic, between COVID-19 and non-COVID-19 wards, and if there was any association with a COVID-19 order set. Quasi-experimental retrospective interrupted time series analysis of AMU rates with a contemporaneous comparison of COVID-19 versus non-COVID-19 control wards. Analysis using incidence rate ratios (IRR) was conducted using a Poisson regression generalized linear model. Five COVID-19 and 4 comparable non-COVID-19 wards and 6 intensive care units (ICUs) at 4 hospitals during pandemic waves 1-4. All inpatients receiving systemic antimicrobials. The COVID-19 checkbox antimicrobial order set was implemented in March 2020, to be used only if considered clinically indicated with modification in August 2021. The primary outcome was a change in AMU rates (defined daily dose per 100 patient days per month) comparing pre- versus peri-pandemic periods and COVID-19 versus control non-COVID-19 wards. Secondary outcomes included antifungal usage rate in ICUs and assessing AMUs following implementation and modification of a COVID-19 order set. Significantly greater rates of AMU (IRR[95%CI]) were observed on COVID-19 wards versus non-COVID-19 wards during waves 1-4 for all systemic antimicrobials (1.76[1.71-1.81], 1.10[1.07-1.13], 1.48[1.43-1.53], and 1.06[1.03-1.09]); for azithromycin (11.76[9.80-14.23], 10.96[9.49-12.74], 12.41[10.73-14.45], and 4.88[4.31-5.55]); and for ceftriaxone (2.39[2.16-2.65], 3.64[3.29-4.03], 2.94[2.67-3.23], and 1.62[1.49-1.76]). We observed significantly increased AMU rates of all systemic agents during the first 4 waves of the pandemic and on COVID-19 wards compared with control wards for azithromycin and ceftriaxone. These agents saw a twofold reduction following order-set removal, suggesting that the clinical decision-support tool order set, as utilized, had influenced prescribing behavior.

Stewardship-Guided T2Candida Testing Shortens Time to Antifungal Treatment and Reduces Antifungal Usage Among Medical Intensive Care Unit Patients With Septic Shock.

Diagnosis of invasive candidiasis (IC) is limited by insensitivity and slow turnaround of cultures. Our objectives were to define the performance of T2Candida, a nonculture test, under guidance of a diagnostic stewardship program, and evaluate impact on time to antifungal initiation and antifungal utilization. This was a retrospective study of adult medical intensive care unit (MICU) patients with septic shock for whom T2Candida testing was performed from March 2017 to March 2020. Patients with positive T2Candida results during this period were compared to MICU patients who did not undergo T2Candida testing but had septic shock and blood cultures positive for Candida from January 2016 through March 2020. Overall, 155 T2Candida tests from 143 patients were included. Nine percent of T2Candida tests were positive compared to 4.5% of blood cultures. Sensitivity, specificity, positive predictive value, and negative predictive value of T2Candida for proven and probable IC were 78%, 95%, 50%, and 99%, respectively. Patients who tested positive for T2Candida (n = 14) were diagnosed earlier and initiated on antifungal therapy sooner than patients with IC (n = 14) diagnosed by blood culture alone (median, 5.6 vs 60 hours; P < .0001). Median antifungal days of therapy/1000 patient-days were 23.3/month preimplementation and 15/month postimplementation (P = .007). Following a negative T2Candida result, empiric antifungals were either not administered in 58% or discontinued within 72 hours in 96% of patients. Diagnostic stewardship guided T2Candida testing resulted in reduced time to IC diagnosis, faster initiation of antifungal therapy, and lower antifungal usage among MICU patients with septic shock.

Risk factors for progression to bacteremia among patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia in the Intensive Care Unit

Antibiotic-resistant Acinetobacter baumannii (A. baumannii) is a common cause of hospital-acquired infections. This study aimed to identify independent factors associated with progression from nosocomial pneumonia to bacteremia in patients infected with carbapenem-resistant A. baumannii (CR-AB). From 2019 to 2021, we conducted a retrospective anaylsis of the medical records of 159 nosocomial CR-AB pneumonia patients in our Intensive Care Unit (ICU). We employed both univariate and multivariable logistic regression models to identify factors associated with the progression of nosocomial CR-AB pneumonia to bacteremia. Among the 159 patients with nosocomial CR-AB pneumonia, 40 experienced progression to bacteremia and 38 died within 28 days following diagnosis. Patients who developed bacteremia had a significantly higher 28-day mortality rate compared to those without bloodstream infection (47.50% vs. 15.97%). Multivariable logistic regression revealed that higher levels of C-Reactive protein (CRP) (OR = 1.01) and the use of continuous veno-venous hemofiltration (CVVH) treatment (OR = 2.93) were independently associated with an elevated risk of developing bacteremia. Among patients who developed bloodstream infection, those who died within 28 days exhibited significantly higher level of interleukin-6 (IL-6), a greater frequency of antifungal drugs usage, and a longer duration of machanical ventilation compared to survivors. Furthermore, the use of antifungal drugs was the only factor that associated with 28-day mortality (OR = 4.70). In ICU patients with central venous catheters who have CR-AB pneumonia and are on mechanical ventilation, higher CRP levels and CVVH treatment are risk factors for developing bacteremia. Among patients with bacteremia, the use of antifungal drugs is associated with 28-day mortality.

A retrospective investigation of Candida spp. and its antifungal susceptibility profile in cancer patients at a South Indian tertiary care hospital

Among the most frequently recognized pathogenic fungi, . from Clinical samples plays a vital role. In recent decades, poor antifungal therapy usage critically in immunocompromised patients has led to antifungal drug resistance among . Hence, expeditious and dependable species identification is crucial for the effective implantation of treatment strategies and the management of diseases. The purpose of the study was to look at the presence of in various Clinical samples taken from cancer patients who are being treated at a tertiary care hospital in South India. The primary objective of this investigation is to ascertain the susceptibility patterns shown by antifungal drugs. This retrospective investigation was undertaken between January 2022 to April 2023. The isolates were subjected to antifungal susceptibility (AFST) by both Conventional (disc diffusion assay) and Automated methods (VITEK-2 compact - AST YSO1). The susceptibility pattern was recorded against antifungal agents like Fluconazole (FLU), Voriconazole (VOR), Amphotericin B (AMB), and Caspofungin. . was identified by conventional method (Chrome ID) as per standard laboratory protocols and by an automated method using MALDI – TOF. Among 215 samples received from cancer patients suggestive of Candidiasis, albicans (64.6%) was the predominant isolate, and the lowest one was (2.25%). Male patients had a higher prevalence of (55.8%). Similarly, the prevalence was higher in patients over 60, with male patients having an incidence of 38.3% and female patients having 23%. By disk diffusion assay and showed 100% sensitivity to all antifungals used in this study. We conclude that the disc diffusion assay is a more cost-effective, user-friendly, and effective screening test than the VITEK 2, and it has the potential to be used as a workable method for Antifungal susceptibility test. The use of Chrome ID for identification of . is cost-effective and reliable. However, MALDI TOF has the advantage of rapidity, providing correct findings promptly. The timely delivery of diagnostic reports facilitates early diagnosis of patients. Therefore, it is recommended in this research to use MALDI TOF for the identification of . and the disc diffusion technique for antifungal susceptibility testing (AFST).

The Relationship Between GLIM Criteria and Recovery Times in the Leukemia Treatment Process

Fatma YILMAZ1, Merih Reis ARAS1, Hacer Berna AFACAN OZTURK1, Umit Yavuz MALKAN2, Ayse Arslan KAPUCI3, Ahmet Kursad GUNES1, Murat ALBAYRAK1 1Ankara Etlik State Hospital, Department of Hematology, Ankara 2Hacettepe University Faculty of Medicine, Department of Hematology, Ankara 3Hacettepe University Faculty of Medicine, Department of Hematology, Ankara Keywords: GLIM criteria, Leukemias, Malnutrition, Recovery time Malnutrition is an important point in patients with hematological malignancies, especially in patients with leukemia who have the potential to enter into prolonged neutropenia. There is no generally accepted approach algorithm with a common consensus in determining the risk of malnutrition. The GLIM criteria, developed by a common consensus of major global nutrition societies (Global Leadership Initiative on Malnutrition), are one of the most frequently used approaches recently. Method A total of 50 patients with a diagnosis of leukemia (AML, ALL) were included in the study. NRS-2002 and then GLIM criteria were used to determine the nutritional status of the patients. The study parameters were evaluated by dividing the patients into two groups as malnourished and non-malnourished. Comparing the malnourished group to the non-malnourished group; while platelet, albumin, and prealbumin values and anthropometric measurements were found to be statistically significantly low, infection incidence rate, fever duration and rate, the need for multiple and longer courses of antibiotics and antifungal usage rate were found to be statistically significantly high (p&lt; 0.005). Adequate nutritional level of the patient does not affect the neutrophil and platelet recovery time, but infection incidence rate and rate of fever within the same period of neutropenia statistically significantly reduces the need for antibiotics and antifungals. In patients with a diagnosis of leukemia who have long hospital stays, it is important to ensure adequate calorie intake with regular dietitian follow-up, to obtain a balanced calorie intake from macronutrients, and to add micronutrient support.

Antifungal Stewardship Programs in Children: Challenges and Opportunities.

Antifungal Stewardship Programs in Children: Challenges and Opportunities.

Current Trends in Antifungal Prophylaxis for High-Risk Neonates in Neonatal Intensive Care Units in India: A Nationwide Survey.

Background Prophylactic antifungals are often used in high-risk babies in neonatal intensive care units (NICUs) to reduce invasive fungal infections (IFIs). However, existing guidelines regarding prophylactic antifungal usage do not clearly define the high-risk population. This study aimed to assess the practices related to prophylactic antifungal use in NICUs in India. Methods For this cross-sectional study, an online structured questionnaire was completed by neonatologists who worked in level 3 NICUs in 12 states in India during the period June 2022 to August 2022. Results Data from 151 NICUs were analyzed. 71.7% of respondents were from private hospitals, and 28.3% were from government hospitals. Nearly one-fourth of the units (28.5%) used antifungal prophylaxis in all extremely low birth weight (ELBW) babies, while another one-fourth (25.8%) used a case-based approach. The remaining NICUs (45.7%) did not use prophylactic antifungals. Among the users, the preferred antifungal was fluconazole; 3 mg/kg and 6 mg/kg were the dosage regimens used. The commonly used interval for administering fluconazole was 72 hours (69.2% of units). The intravenous route was the preferred route of administration (84.1%). Factors that influenced the non-users were the low incidence of fungal infections in their NICUs and concern about the development of resistance. It was noted that the users felt strongly about the need for further recommendations from pediatric societies and more studies on the efficacy of antifungals. Conclusion There is considerable variation in the use of prophylactic antifungals across NICUs in India. Among the users, uniformity in the choice of antifungal and interval of administration was observed. Further recommendations from pediatric societies, including the definitions of neonates at-risk of fungal infections, are required to ensure consistency in practice and help clinicians decide whether or not to use prophylactic antifungals.

Unusual infections and diabetes: dangerous fungi

Unusual infections and diabetes: dangerous fungi

348. Cell-free plasma next-generation sequencing assists in the evaluation of invasive mold infection in patients with COVID-19: a case series

Abstract Background Distinguishing COVID-19 Associated Pulmonary Aspergillosis (CAPA) and invasive mold infections (IMIs) from other causes of secondary pneumonia in COVID-19 can be challenging. 1,3-β-D-Glucan and galactomannan are commonly utilized biomarkers for the workup of IMIs but are limited by a lack of specificity and sensitivity respectively. Cell-free plasma next-generation sequencing (cfNGS) is a promising non-invasive approach that can provide direct detection of pathogens in patient's serum. This study explored its potential role in the evaluation of secondary pneumonia in patients with COVID-19. Methods We performed a retrospective single-center observational study from March 2020 to December 2021 at Virginia Commonwealth University Medical Center, a 811-bed tertiary care center, to evaluate patients with laboratory confirmed SARS-CoV-2 virus infection who underwent cfNGS for the evaluation of CAPA. CfNGS (Karius, Inc., Redwood City, CA) was performed at the discretion of the clinical provider and we evaluated the test indication, patient history, clinical impact, correlation with serum biomarkers, and 30 day all-cause mortality. Results Thirteen patients were evaluated and none had Aspergillus species detected. One patient had Pneumocystis jirovecii on cfNGS. There was a 76.9% (10/13) concordance rate with patients’ serum fungal biomarkers. CfNGS also detected concomitant organisms in 53.8% (7/13) of our cohort. These data assisted in changes of clinical management for 84.6% (11/13) of patients and lead to the change in antifungal usage in 69.2% (9/13). Conclusion In this study, both negative and positive cfNGS test results assisted in important clinical decision making. cfNGS may have a role in the evaluation of CAPA or other IMIs in patients with COVID-19. Disclosures Megan M. Morales, MD, Karius: Paid speaker.

Immunomodulatory drug fingolimod (FTY720) restricts the growth of opportunistic yeast Candida albicans in vitro and in a mouse candidiasis model.

Fingolimod (FTY720) is a drug derived from the fungicidal compound myriocin. As it was unclear whether FTY720 has antifungal effects as well, we aimed to characterize its effect on Candida albicans in vitro and in a mouse candidiasis model. First, antifungal susceptibility testing was performed in vitro. Then, a randomized, six-arm, parallel, open-label trial was conducted on 48 mice receiving oral FTY720 (0.3 mg/kg/day), intraperitoneal C. albicans inoculation, or placebo with different combinations and chorological patterns. The outcome measures of the trial included serum concentrations of interleukin-10 and interferon-gamma, absolute lymphocyte counts, and fungal burden values in the mice's livers, kidneys, and vaginas. Broth microdilution assay revealed FTY720's minimum inhibitory concentration (MIC99) to be 0.25 mg/mL for C. albicans. The infected mice treated with FTY720 showed lower fungal burden values than the ones not treated with FTY720 (p<0.05). As expected, the mice treated with FTY720 showed a less-inflammatory immune profile compared to the ones not treated with FTY720. We hypothesize that FTY720 synergizes the host's innate immune functions by inducing the production of reactive oxygen species. Further studies are warranted to unveil the mechanistic explanations of our observations and clarify further aspects of repurposing FTY720 for clinical antifungal usage.

P078 Baseline antifungal usage patterns and knowledge regarding management of invasive fungal infections as a part of a multidisciplinary antifungal stewardship (AFS) program

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM ObjectivesTo establish a baseline of antifungal usage patterns (indication, duration, toxicity, and cost) and physician's knowledge of management of invasive fungal infections, as a basis for implementation of a multidisciplinary antifungal stewardship (AFS) program at a tertiary care center.MethodsData including clinical history, investigations, and antifungal therapy was collected by chart review and bedside rounds from 100 patients with laboratory-confirmed invasive fungal infections (IFIs). Requirement and adequacy of antifungal therapy were assessed in comparison with IDSA and EORTC/MSG guidelines and scored at discharge/death using the Valerio system. This system assigns points to six parameters: indication, optimal selection of antifungal agent, dosage according to individual characteristics, loading and maintenance dose, therapy adjustment after microbiological results, route of administration, and length of therapy. The maximum score (10) indicates appropriate therapy. Any score of ˂ 10 is classified as inappropriate.ResultsOut of 100 patients who met the criteria for IFI, 85 patients had a single IFI, 45 (52.9%) of whom received appropriate antifungal therapy, 17 (20%) received other than the recommended antifungal therapy and 23 (27.1%) received no antifungals. A total of 15 patients had dual IFIs, 10 (66.7%) of whom received other than the recommended antifungal therapy for one or both infections, 1 (6.7%) was treated appropriately for one infection but left untreated for the other, 2 (13.4%) patients were untreated for both infections and 2 (13.4%) were appropriately treated for both infections. The most common types of inappropriate antifungal use were inappropriate antifungal for organism (16 incidents), inadequate dosage (11 incidents), inappropriate antifungal for site (6 incidents), inadequate duration (6 incidents), and failure to adjust antifungal therapy based on microbiological test results (6 incidents). Common reasons observed for inappropriate antifungal use were delay in starting antifungal therapy or in ordering appropriate tests for establishing diagnosis, uncertainty in distinguishing fungal pathogens from colonisers, lack of rigorous antifungal charting, unavailability of first-line drug, and attempts to use a single antifungal to cover dual IFIs.ConclusionsThere are several inadequacies in Valerio scoring system, i.e., no weightage given to timely initiation of treatment, no deductions for delay in starting treatment once reports have been received, or for use of unnecessary antifungals in addition to recommended ones. Antifungals are often chosen by organism only while ignoring site-specific action and penetration of the drug. There is no comprehensive system for recording antifungal use, making it difficult to ascertain cumulative antifungal use over time. Direct association could not be made between inappropriate antifungal use and outcome as most patients had multiple comorbidities apart from fungal infection. Where fungal infection occurs along with TB, fungi are often considered commensals and left untreated. Many immunocompetent patients with IFIs are ‘unclassifiable’, ie, cannot be categorized under existing guidelines. Even for ‘classifiable’ patients, there is considerable subjectivity in antifungal treatment guidelines. There is a need for a standardized algorithm-based treatment at institutional level for these groups of patients.

Evaluation of efficacy and safety of adjuvant Ayurvedic therapy in patients with severe post-covid mucor-mycosis at a Government tertiary care hospital – A Case-Control study

BackgroundIn the wake of the unprecedented Mucormycosis epidemic following the delta variant run second wave of SARS COV-2, the Government of Telangana decided to utilize Ayurveda for its adjuvant immune-boosting role. Based on clinical assessment of patients, Mucor mycosis was identified as Vataja vidradhi and treatment was planned. ObjectiveTo assess the safety and efficacy of Ayurvedic regime as an adjuvant therapy in post covid mucor mycosis patients at Gandhi Hospital, the largest Government tertiary care center in Telangana. MethodsIn this prospective case control study, 77 patients with positive or probable post covid mucor mycosis were included. The varunadi kwatha regimen could be given in very few patients precluding its meaningful analysis. 65 patients received Pancha Tikta Ghrita Guggulu [PTGG] regimen. These patients were assigned into 2 groups; Intervention [A] group n = 36, who used PTGG for a mean duration of 34.1 days and Control [B] group [drop outs] n = 29 who used PTGG for a mean duration of 2.1 days. Objective parameters like biochemical changes and parameters like disease progression, recurrence, mortality rate, subjective and objective wellbeing, readmission, repeat surgeries, and persistence of symptoms were assessed before and after treatment. Statistical analysis was done using Mann Whitney, chi square and ANOVA test. ResultsThe Intervention group mortality rate was ZERO where as it was 13.8% in control group. The statistical analysis showed significant improvement in all clinical parameters tested. ConclusionPTGG based regimen as adjuvant seemed to help across the entire spectrum of Mucormycosis. It was safe and tolerated very well with concomitant antifungal usage and in pre and post-operative patients, thus validating the host factor modification approach of Ayurveda and an integrative usage.

Predictive factors in treatment response of malignant external otitis.

To evaluate the prevalence and impact of various predictive factors including diabetes control in malignant external otitis (MEO) treatment response. In a cross-sectional study on MEO patients, we defined treatment response with three indices; ESR level decrease, hospitalization period, and systemic antifungal drug usage. The impact of diabetes control and other predictive factors on these indices have been evaluated. Overall, 164 patients with a mean age of 67.8 ± 9.7years were included. Cranial nerve involvement was present in 56 patients. Nine patients had immunodeficiency. 19.5% of cases had leukocytosis. Diabetes mellitus was present in 156 patients, suffering for an average of 13.9 ± 8.6years. The overall mean hemoglobin A1C (HbA1c) level was 8.3% (4.4-12.8%), and the mean fasting blood sugar was 146.4mg/dl (63-292mg/dl). 29.3% of patients had good diabetes control before admission (HbA1c < 7%), 54.9% had poor control (7% < HbA1c < 10%) and 15.9% had very poor glycemic control (HbA1c > 10%). The predictive role for the following factors were not statistically significant: age, gender, comorbidities, diabetes, diabetes management method used before and during hospitalization, diabetes duration, leukocytosis, immunodeficiency, fasting blood sugar level, HbA1c level, glycemic control index, and insulin amount. However, CRP level with a mean value of 34.3mg/L showed a significant correlation with ESR decrease, hospitalization period, and antifungal drug usage. CRP level could be used as a predictor for the hospitalization period, the need for systemic antifungal and ESR level decrease. It would be helpful to check the CRP level at the time of diagnosis to predict the hospitalization period and the necessity of systemic antifungal management to adjust the treatment strategy.

A 4-Year Prospective Study on Anti-fungal and Reserved Antimicrobial Drugs under Antimicrobial Stewardship Program

Introduction: In 2018 and 2021, CIMS hospital conducted an audit to analyse the quality of antifungal use. We conducted a follow-up audit after four years of the antifungal stewardship programme (AFS) to evaluate the program’s long-term effects. We assessed antifungal usage in Medical &amp; surgical Patients receiving systemic antifungals using a preset score. Antibiotics and its classes designated as antimicrobial reserved products are intended to be used only in the treatment of confirmed or suspected infections caused by multidrug-resistant organisms. Materials and Methods: The research was conducted in a medical &amp; surgical unit at tertiary care hospital during a four-year period. The sensitivity pattern was identified after the laboratory data were processed. Some of the newer AMs were labelled as “Reserve,” requiring the completion of an authorization form prior to prescription. Results: Patients treated with antimicrobial drugs in medical and ICU wards were assessed. The results of both the audits revealed that there was a decrease in the irrational cases of both reserved antimicrobial and antifungal cases in successive years. The year 2020 showed fewer irrational cases of antifungals. Conclusion: With time the use of correct dosage regimen, proper route of administration and proper handling of patients has led to decrease in the irrational cases of antimicrobials.

On Fruits and Fungi: A Risk of Antifungal Usage in Food Storage and Distribution in Driving Drug Resistance in Candida auris.

ABSTRACTThe continuous emergence of antifungal drug resistance is a mounting concern for the treatment of fungal infections worldwide. While many pathogenic fungi exhibit some level of antifungal drug resistance, the identification of Candida auris has brought this phenomenon to the fore in recent years. C. auris exhibits resistance to all antifungal drugs used for treatment, and it does so at a very high rate, with more than 90% of isolates being resistant to at least one drug and roughly 4% being panresistant. However, the environmental factors driving this exceptionally high antifungal drug resistance remain unidentified. The presence of C. auris on stored apples that are treated with antifungals during storage suggests a possible route to selection of drug-resistant C. auris isolates that may have contributed to the evolution of this deadly pathogen. This study further suggests that the adage “an apple a day keeps the doctor away” may need to be revisited in light of the discovery of C. auris on the surface of apples.