Metarhizium anisopliae infection of an adult wētāpunga (Deinacrida heteracantha)

Antifungal therapy in 'bone marrow failure'.

Clinical Utility of Routine Use of Fungal Blood Cultures

Case presentation: This case report details a 37-year-old immunocompetent woman from Barretos, SP, previously controlled for hypertension, who presented with refractory right hip pain, fever, right flank pain, confusion, disorganized speech, fluctuating episodes of myoclonus, migrainous headache, occasional unexplained laughter, and a single visual hallucination. Hospitalized on May 3, 2024, at Santa Casa de Barretos, initial treatment targeted urinary tract infection with ceftriaxone. Neurological evaluation revealed intentional tremor worse on the right, frontal release signs, recent anterograde amnesia, and anomia. Diagnostic hypotheses included encephalitis associated with pyelonephritis/sepsis, prompting cerebrospinal fluid (CSF) puncture, cranial CT, and MRI. Empirical treatment with acyclovir, ceftriaxone (CNS dose), and dexamethasone was initiated but showed no clinical improvement. CSF analysis revealed hyperproteinorrachia, hypoglycorrhachia, and lymphocytic pleocytosis, suggestive of fungal encephalitis despite negative fungal serologies and culture. Infectious disease consultation advised repeat CSF sampling, broadening the investigation to include acid-fast bacilli, MTB-RIF (molecular tuberculosis rapid test), viral panel, fungal culture, and escalated antibiotic therapy (ampicillin and amikacin), alongside continued acyclovir for 21 days. Persistent clinical decline led to a repeat MRI showing findings indicative of fungal encephalitis, confirmed by positive urine culture for kluyveromyces marxianus. Empirical treatment with amphotericin B for CNS was commenced, resulting in significant improvement in consciousness level and CSF parameters after one week. Discharge planning included fluconazole therapy with scheduled serial imaging and CSF exams to guide future medication discontinuation. Ongoing CSF fungal culture is pending. Fungal CNS infections, including fungal encephalitis, are particularly challenging due to their dependence on host immune status and the virulence of the fungal strain involved. These infections often lead to substantial morbidity in immunocompromised individuals and can result in severe, potentially fatal neurological outcomes. This case highlights the unusual occurrence and diagnostic hurdles of fungal encephalitis in immunocompetent patients, originating from a primary urinary tract infection. The timely initiation of empirical antifungal therapy with amphotericin B, despite initial negative cultures, played a critical role in achieving clinical improvement. Given the intricate diagnostic and therapeutic landscape, further investigation into the diverse etiologies of encephalitis, including fungal infections in immunocompetent individuals, is crucial for optimizing patient outcomes.

53-Year-Old Man With a Swollen Finger

Intensive cytotoxic chemotherapy for people with cancer can cause severe and prolonged cytopenia, especially neutropenia, a critical condition that is potentially life-threatening. When manifested by fever and neutropenia, it is called febrile neutropenia (FN).Invasive fungal disease (IFD) is one of the serious aetiologies of chemotherapy-induced FN. In pre-emptive therapy, physicians only initiate antifungal therapy when an invasive fungal infection is detected by a diagnostic test. Compared to empirical antifungal therapy, pre-emptive therapy may reduce the use of antifungal agents and associated adverse effects, but may increase mortality. The benefits and harms associated with the two treatment strategies have yet to be determined. OBJECTIVES: To assess the relative efficacy, safety, and impact on antifungal agent use of pre-emptive versus empirical antifungal therapy in people with cancer who have febrile neutropenia. We searched CENTRAL, MEDLINE Ovid, Embase Ovid, and ClinicalTrials.gov to October 2021. We included randomised controlled trials (RCTs) that compared pre-emptive antifungal therapy with empirical antifungal therapy for people with cancer. We identified 2257 records from the databases and handsearching. After removing duplicates, screening titles and abstracts, and reviewing full-text reports, we included seven studies in the review. We evaluated the effects on all-cause mortality, mortality ascribed to fungal infection, proportion of antifungal agent use (other than prophylactic use), duration of antifungal use (days), invasive fungal infection detection, and adverse effects for the comparison of pre-emptive versus empirical antifungal therapy. We presented the overall certainty of the evidence for each outcome according to the GRADE approach. This review includes 1480 participants from seven randomised controlled trials. Included studies only enroled participants at high risk of FN (e.g. people with haematological malignancy); none of them included participants at low risk (e.g. people with solid tumours). Low-certainty evidence suggests there may be little to no difference between pre-emptive and empirical antifungal treatment for all-cause mortality (risk ratio (RR) 0.97, 95% confidence interval (CI) 0.72 to 1.30; absolute effect, reduced by 3/1000); and for mortality ascribed to fungal infection (RR 0.92, 95% CI 0.45 to 1.89; absolute effect, reduced by 2/1000). Pre-emptive therapy may decrease the proportion of antifungal agent used more than empirical therapy (other than prophylactic use; RR 0.71, 95% CI 0.47 to 1.05; absolute effect, reduced by 125/1000; very low-certainty evidence). Pre-emptive therapy may reduce the duration of antifungal use more than empirical treatment (mean difference (MD) -3.52 days, 95% CI -6.99 to -0.06, very low-certainty evidence). Pre-emptive therapy may increase invasive fungal infection detection compared to empirical treatment (RR 1.70, 95% CI 0.71 to 4.05; absolute effect, increased by 43/1000; very low-certainty evidence). Although we were unable to pool adverse events in a meta-analysis, there seemed to be no apparent difference in the frequency or severity of adverse events between groups. Due to the nature of the intervention, none of the seven RCTs could blind participants and personnel related to performance bias. We identified considerable clinical and statistical heterogeneity, which reduced the certainty of the evidence for each outcome. However, the two mortality outcomes had less statistical heterogeneity than other outcomes. For people with cancer who are at high-risk of febrile neutropenia, pre-emptive antifungal therapy may reduce the duration and rate of use of antifungal agents compared to empirical therapy, without increasing over-all and IFD-related mortality; but the evidence regarding invasive fungal infection detection and adverse events was inconsistent and uncertain.

BackgroundBlood culture techniques have improved to the point where they are considered sensitive enough for detection of Candida. Expert guidelines clarifying the utility of use of dedicated fungal isolator cultures are lacking, and we wondered what utility, if any, they add for the diagnosis of candidemia.MethodsAll patients with cultures between March 2016-February 2020 positive for Candida were examined via manual chart review, noting time to positivity and time of initiation of antifungal therapy.ResultsWe focused on cases of candidemia where a fungal culture was ordered and turned positive (59 out of the total 181 cases of candidemia). We eliminated an additional 10 cases where fungal cultures were sent while already on antifungal therapy or in patients already known to be fungemic, given our interest in de novo diagnoses. Another case was removed due to lack of clinical details, as the patient was discharged prior to culture results and managed at a different medical facility.There were 14 cases with discordant growth (fungal culture positive, bacterial culture negative). One patient passed away prior to culture results, but in the remaining 13 cases, the fungal culture changed clinical management, in most cases by prompting initiation of antifungal therapy.The remaining 36 cases involved with concordant growth between bacterial and fungal cultures. In 11 of those cases, the fungal culture isolated yeast 12 or more hours faster than its paired bacterial culture (average 40.7 +/- 26.6 hours). In 7 of these cases, the fungal culture changed management – in the remaining cases, the patient was already on empiric therapy.Among all cultures sent in patients not receiving antifungals that isolated Candida, the overall time to positivity for fungal cultures was 37.2 +/- 13 hours, while bacterial cultures took 54 +/- 26.4 hours.Fungal Culture ResultsConclusionFungal cultures changed management in 20/59 cases of candidemia (34%) either by making the diagnosis faster than a bacterial culture or making it outright. Given the morbidity and mortality associated with candidemia, rapid diagnosis is critically important. More specific guidelines optimizing how to best utilize fungal cultures to help standardize practice among clinicians will be critical going forward.DisclosuresOmai Garner, PhD, D(ABMM), Beckman Coulter (Scientific Research Study Investigator)

Empiric Antifungal Therapy with Amphotericin B in the Era of Fluconazole Prophylaxis: a Cohort Study in Adults with Acute Myeloid Leukemia Treated within An Institutional Antifungal Policy.

Study DesignRetrospective study.PurposeTo identify the rate of positive acid-fast bacillus (AFB) and fungal cultures during spine debridement, determine whether these infections are more common in certain spine segments, identify comorbidities associated with these infections, and determine whether the universal performance of fungal and AFB cultures during spine debridement is cost effective.Overview of LiteratureSpine infections are associated with significant morbidity and costs. Spine fungal and AFB infections are rare, but their incidence has not been well documented. As such, guidance regarding sample procurement for AFB and fungal cultures is lacking.MethodsA retrospective review of medical record data from patients undergoing spine irrigation and debridement (I&D) at the University of Missouri over a 10-year period was performed.ResultsFor patients undergoing spine I&D, there was a 4% incidence of fungal infection and 0.49% rate of AFB infection. Steroid use was associated with a higher likelihood (odds ratio, 5.62; 95% confidence interval, 1.33–23.75) of positive fungal or AFB cultures. Although not significant, patients undergoing multiple I&D procedures had higher rates of positive fungal cultures during each subsequent I&D. Over a 10-year period, if fungal cultures are obtained for each patient, it would cost our healthcare system $12,151.58. This is compared to an average cost of $177,297.64 per missed fungal infection requiring subsequent treatment.ConclusionsSpine fungal infections occur infrequently at a rate of 4%. Physicians should strongly consider obtaining samples for fungal cultures in patients undergoing spine I&D, especially those using steroids and those undergoing multiple I&Ds. Our AFB culture rates mirror the false positive rates seen in previous orthopedic literature. It is unlikely to be cost effective to send for AFB cultures in areas with low endemic rates of AFB.

Background Early antifungal therapy of invasive aspergillosis (IA) has been shown to be associated with improved outcome. Given the difficulty to establish the diagnosis of IA based on conventional methods, early initiation of empiric antifungal therapy has been used in patients with clinically suspected IA. Diagnostic-driven approach (DDA) relies on using novel diagnostic methods (e.g., early galactomannan testing). In this current study, we compared the outcomes of hematological malignancy (HM) patients with IA who were treated with Voriconazole using the DDA (DDA-Vori) vs. empiric therapy with a non-Voriconazole containing regimen (EMP-non-Vori) or empiric therapy with Voriconazole (EMP-Vori).Methods We retrospectively reviewed the medical records of 604 HM patients with documented, proven or probable IA (according to EORTC/MSG criteria) diagnosed between July, 1993 and February, 2016 at our center. We included 346 patients with underlying host factors, a suggestive CT findings of IA, and positive biopsy, fungal culture or galactomannan indicative of IA, and who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all causing mortality and IA attributable mortality.ResultsThe patients’ median age was 54 years and 59% were males. By multivariate analysis, factors that were predictive of a favorable response included: localized/sinus IA vs. disseminated/pulmonary IA (P < 0.0001), not receiving WBC transfusion (P < 0.01), and DDA-VORI vs. EMP-non-Vori (P < 0.0001). On the other hand, predictors of mortality within 6 weeks of initiation of IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (P < 0.01), not having stem-cell transplant within 1 year prior of IA (P = 0.01) and EMP-non-Vori vs. DDA-Vori (P < 0.001).Conclusion DDA-Vori is associated with a better outcome (response and survival) when compared with EMP-non-Vori and equivalent outcome to EMP-Vori. The superior to equivalent outcome associated with the DDA approach could also reduce unnecessary costs and adverse events associated with widespread use of empiric therapy.DisclosuresI. Raad, Merck: Grant Investigator, Research grant. Allergan: Grant Investigator, Research grant. Infective Technologies, LLC: Co-Inventor of the Nitroglycerin-Citrate-Ethanol catheter lock solution technology which is owned by the University of Texas MD Anderson Cancer Center (UTMDACC) and has been licensed by Novel Anti-Infective Technologies, LLC in which Dr. Raad is a s and Shareholder, Licensing agreement or royalty

ABSTRACTCritically ill patients are at risk for fungal infections, but there is a paucity of data regarding the clinical utility of dedicated fungal blood cultures to detect such infections. A retrospective review was conducted of patients admitted to the surgical and burn intensive care units at Parkland Memorial Hospital between 1 January 2013 and 31 December 2017 for whom blood cultures (aerobic, anaerobic, and/or fungal cultures) were sent. A total of 1,094 aerobic and anaerobic blood culture sets and 523 fungal blood cultures were sent. Of the aerobic and anaerobic culture sets, 42/1,094 (3.8%) were positive for fungal growth. All fungal species cultured were Candida. Of the fungal blood cultures, 4/523 (0.76%) were positive for growth. Fungal species isolated included Candida albicans, Aspergillus fumigatus, and Histoplasma capsulatum. All 4 patients with positive fungal blood cultures were on empirical antifungal therapy prior to results, and the antifungal regimen was changed for 1 patient based on culture data. The average duration to final fungal culture result was 46 days, while the time to preliminary results varied dramatically. Two of the four patients died prior to fungal culture results, thereby rendering the culture data inconsequential in patient care decisions. This study demonstrates that regular aerobic and anaerobic blood cultures sets are sufficient in detecting the most common causes of fungemia and that results from fungal cultures rarely impact treatment management decisions in patients in surgical and burn intensive care units. There is little clinical utility to routine fungal cultures in this patient population.IMPORTANCE This study demonstrates that regular aerobic and anaerobic blood culture sets are sufficient in detecting the most common causes of fungemia, and thus, sending fungal blood cultures for patients in surgical and burn intensive care units is not a good use of resources.

Many bacterial infections can cause multisystem or metastatic infection, commonly through haematogenous spread, with preferred sites or tropism depending upon specific organism. For example, Staphylococcus aureus is a well-recognized cause of infective endocarditis, joint infection, and vertebral osteomyelitis. Klebsiella pneumoniae can cause endogenous endophthalmitis in association with a pyogenic liver abscess, a syndrome well described in East Asia. Streptococcus pneumoniae typically causes lower respiratory tract infections or bacterial meningitis. The combination of meningitis, pneumonia, and endocarditis is called ‘Austrian syndrome’ and is strongly associated with hyposplenism or alcohol abuse. Other examples of bacteria that disseminate and cause multisystem infection are covered elsewhere. C. albicans or non-albicans species in the blood can metastasize to the eye (causing chorioretinitis or endophthalmitis) or to the heart (causing infective endocarditis). The primary sites of infection are commonly the GI tract or intravascular catheters, and high-risk groups include patients who have recently undergone abdominal surgery, received multiple courses of intravenous antibiotics, and are receiving total parenteral nutrition. Empirical treatment is with either IV liposomal amphotericin or an echinocandin before stepping down to an oral azole, commonly fluconazole at a dose of 400mg od. Because of the risk of metastatic spread, minimum duration is normally two weeks after the first negative blood culture. Cryptococcosis is caused by one of two species: Cryptococcus neoformans or Cryptococcus gattii. Unlike C. neoformans, C. gattii can cause infection in immunocompetent people. The clinical syndrome, Cryptococcosis, is an opportunistic infection for AIDS, but other conditions that predispose to infection are lymphoma, sarcoidosis, liver cirrhosis, and corticosteroids. Following inhalation, cryptococci can disseminate to the cerebrospinal fluid (CSF) and cause meningitis. Occasionally, Cryptococcoma—umbilicated papules on the skin— can occur. Symptoms are often subacute and include fever and dry cough. Following dissemination to the CSF, headache and confusion can occur. Diagnosis is based upon detection of capsular antigen by latex particle agglutination or culture, typically from blood or CSF. For meningitis, treatment consists of three phases. The induction phase is two weeks of IV liposomal amphotericin and flucytosine, followed by consolidation with eight weeks of oral fluconazole 800mg once daily, then finally secondary prophylaxis, 200mg orally once daily.

Statistical Correlations Between Quantifiable Disease Variables and Prognosis in Hematological Malignancy Patients Treated with Itraconazole as An Empirical Antifungal Therapy: A Prospective Multicenter Observational Study in Korea

Cost-effectiveness analysis of micafungin versus fluconazole for prophylaxis of invasive fungal infections in patients undergoing hematopoietic stem cell transplantation in Korea

Culture positivity among donor corneas: a single eye bank series

Invasive fungal infection is a major cause of morbidity and mortality in patients with febrile neutropenia unresponsive to antibacterial treatment. Empirical antifungal therapy with amphotericin B has been the standard of care for these patients; however, there remains a need for less toxic alternative drugs. We conducted a prospective study to evaluate the efficacy and safety of micafungin (MCFG), a novel antifungal agent of the echinocandin class, in an empirical therapy setting for patients with febrile neutropenia. A total of 31 patients with acute leukemia who developed febrile neutropenia were enrolled in the study. Among them, 18 patients fulfilling the protocol-defined criteria, including 10 with persistent fever and 8 with recurrent fever, received MCFG empirically. Underlying diseases consisted of acute myeloid leukemia (n=15) and acute lymphoblastic leukemia (n=3). The median duration of neutropenia and drug administration was 22 and 9.5 days, respectively. Treatment success, defined as defervescence during the neutropenic period, absence of breakthrough fungal infections, and requiring no replacement of antifungal drugs, was achieved in 14 patients (78%). None of the patients required discontinuation or dose reduction due to adverse events except for one patient with severe hypokalemia. Although the studied patients were limited in number, our results indicate that MCFG is an encouraging agent for empirical antifungal therapy in patients with febrile neutropenia, and deserves further investigation in large-scale studies.