Invasive fusariosis in patients with leukaemia in the era of mould-active azoles: increasing incidence, frequent breakthrough infections and lack of improved outcomes.

OBJECTIVES: Historically, patients with leukaemia and invasive fusariosis (IF) have experienced poor outcomes in the setting of persistent immunosuppression. Herein, we retrospectively reviewed the incidence, presentation and outcomes of IF that are scarcely studied in contemporary cohorts of leukaemia patients. METHODS: We identified adult leukaemia patients with proven or probable IF at MD Anderson Cancer Center during 2009-21. Independent risk factors for 42 day mortality after IF diagnosis were determined using a multivariable logistic regression model. Combined with historical data, the annual IF incidence density over the past 23 years was estimated using Poisson regression analysis. RESULTS: Among 140 leukaemia patients with IF (114 proven), 118 patients (84%) had relapsed/refractory leukaemia and 124 (89%) had neutropenia at IF diagnosis. One hundred patients (71%) had pulmonary IF, 88 (63%) had disseminated IF and 48 (34%) had fungaemia. Coinfections were common (55%). Eighty-nine patients (64%) had breakthrough IF to mould-active triazoles. Most patients (84%) received combination antifungal therapy. Neutrophil recovery [adjusted OR (aOR), 0.04; 95% CI, 0.01-0.14; P < 0.0001], pulmonary IF (aOR, 3.28; 95% CI, 1.11-9.70; P = 0.032) and high SOFA score (aOR, 1.91 per 1-point increase; 95% CI, 1.47-2.50; P < 0.0001) were independent predictors of 42 day mortality outcomes. From 1998 to 2021, IF incidence density increased significantly at an annual ratio of 1.03 (95% CI, 1.01-1.06; P = 0.04). CONCLUSIONS: IF is predominantly seen in patients with relapsed/refractory leukaemia and increasingly seen as a breakthrough infection to mould-active triazoles. Despite frequent combination antifungal therapy, high mortality rates have persisted in patients with lasting neutropenia.

Invasive mucorales sinusitis in a young patient with Emberger syndrome and newly diagnosed AML: A case report and literature review of invasive fungal infections in GATA2 deficiency.

Germline pathogenic variants (PVs) in the gene encoding the GATA2 transcription factor can result in profound reductions of monocytes, dendritic cells, natural killer cells and B cells. GATA2 PVs are associated with an increased risk of myeloid malignancies and a predisposition to nontuberculous mycobacterial and human papillomavirus infections. Additionally, invasive fungal infections (IFIs) have been reported in individuals with GATA2 PVs, even in the absence of myeloid malignancies. In this report, we present the case of a 40-year-old man with Emberger syndrome (GATA2 mutation, recently diagnosed acute myeloid leukaemia [AML] and history of lymphedema with hearing loss) who developed Mucorales sinusitis while receiving his first course of remission induction chemotherapy. Additionally, we review the literature on all published cases of proven IFIs in patients with GATA2 PVs. Clinicians should be aware that patients with GATA2 PVs could be vulnerable to opportunistic IFIs, even in the absence of AML and antineoplastic therapy. Furthermore, the distinctly unusual occurrence of mucormycosis during the first course of induction chemotherapy for AML in our patient indicates that patients with germline GATA2 PVs receiving induction chemotherapy for AML might be at high risk for early onset of IFIs due to aggressive, opportunistic moulds.

Probiotic-related Clostridium butyricum bacteremia: a case report and literature review.

We report three cases of Clostridium butyricum bacteremia associated with taking C. butyricum-related probiotics. We performed a literature review and found 11 cases of C. butyricum bacteremia including our cases. Nine cases related to probiotics. We should consider that probiotics may infect clinically unstable patients.

Acute heart failure associated with toxic shock syndrome due to methicillin-susceptible Staphylococcus aureus during the postpartum period: case report and systematic literature review.

BACKGROUND: Toxic shock syndrome (TSS) caused by Staphylococcus aureus in the postpartum period is a rare but life-threatening disease. We present a case of acute heart failure as the initial presentation of TSS due to methicillin-susceptible Staphylococcus aureus (MSSA) and describe its clinical characteristics with a systematic literature review. CASE PRESENTATION: A 34-year-old woman, 8 days after a normal vaginal delivery presented to our hospital with dyspnea and fever. She had jugular venous distension, bilateral leg edema, and erythema. Laboratory examinations revealed elevated NT-pro-BNP level of 3,233 pg/mL. Transthoracic echocardiography showed elevated tricuspid regurgitation peak gradient, with decreased respiratory variability of the inferior vena cava diameter and bilateral pleural effusions. The patient was hospitalized with suspicion of congestive heart failure. MSSA positive for toxic shock syndrome exotoxin-1 was detected in the culture of the perineal incision wound, and we diagnosed TSS caused by MSSA. Intravenous diuretics were administered, along with eventual cefazolin plus clindamycin. After 2 weeks of antimicrobial therapy, the patient showed improvement and was discharged. No recurrence was observed at the 24-month follow-up. CONCLUSION: This is a rare case report of acute heart failure being the initial manifestation of TSS due to MSSA in the postpartum period. Clinicians should consider TSS as a possibility in postpartum patients with acute heart failure. This systematic review provides insights into its clinical features, treatment regimens, and prognosis of TSS by S. aureus in the postpartum period. TSS requires an appropriate, prompt diagnosis, because delayed treatment can be fatal.

Predicting bacteremia caused by Streptococcus anginosus group: A new scoring method.

BACKGROUND: Viridans group streptococci (VGS) are the most common causative organisms of infective endocarditis. Among VGS, the Streptococcus anginosus group (SAG) is often associated with abscess formation, and delayed diagnosis leads to increased morbidity and mortality. This study aims to examine the factors associated with SAG bacteremia and develop a predictive scoring method. METHODS: This single-center retrospective case-control study of patients with VGS bacteremia compared the background and clinical characteristics between the SAG and non-SAG groups. The univariate analysis used the χ2 test and t-test. The multivariate analysis was conducted using logistic regression. RESULTS: Out of 161 patients, 95 had SAG and 66 had non-SAG bacteremia. Age >63 years: 2 points (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.64-7.54); solid tumor: 2 points (OR = 4.44, 95% CI: 1.42-6.77); C-reactive protein >7.61 mg/dL: 3 points (OR = 5.40, 95% CI: 2.49-11.72), and white blood cell count >8550/µL: 2 points (OR = 2.76, 95% CI: 1.29-2.91) were found to be independently associated with SAG bacteremia. After totaling the above variables and adding 1 point for diabetes mellitus, the area under the receiver operating curve was 0.81 (95% CI: 0.74-0.88). The sensitivity and specificity were 51% and 88%, respectively, at a cut-off of 6 points. CONCLUSIONS: In patients with VGS bacteremia, a score of 6 points or higher using this method predicts SAG with high specificity.

SEASON GAP score: A predictor of Clostridioides difficile infection among patients with tube feeding.

INTRODUCTION: Clostridioides difficile infection (CDI) is an important community- and hospital-acquired infection. Patients receiving tube feeding often have diarrhoea, and it is still unclear whether the traditional criteria for submitting samples for Clostridioides difficile (CD) testing as determined by the frequency of the diarrhoea apply to these patients. METHODS: We conducted a retrospective study comparing the clinical features of tube-fed inpatients with suspected CDI, with CDI, and those without CDI admitted between 2004 and 2020. Univariate associations were assessed using the chi-square test, Fisher's exact test, or student's t-test, and multivariate analysis was conducted using logistic regression analysis. RESULTS: Among 805 tube-fed inpatients with and suspected CDI, 163 (20.2%) had CDI and 642 (79.8%) did not. The following seven predictors, independently associated with CDI, were used to develop the SEASON GAP score: male (Sex) (1 point), Emaciation (1 point), days from Admission to testing ≥21 days (2 points), Stool frequency/day ≥5 times (1 point), seasON (summer: 2 points, spring and winter: 1 point), GAstrostomy (2 points), and no prior Proton pump inhibitor use (1 point). In a receiver operating characteristic curve, the area under the curve was 0.77 (95% confidence interval: 0.73-0.80). The optimal cut-off point was 3.5. A score of ≤3 had a sensitivity, specificity, and negative predictive value of 81%, 60%, and 93%, respectively. CONCLUSIONS: The SEASON GAP score is useful in ruling out CDI in patients with tube feeding, thus reducing unnecessary CD testing and antimicrobial use.

Penicillin- and third-generation cephalosporin-resistant strains of Streptococcus pneumoniae meningitis: Case report and literature review.

BACKGROUND: Treatment of patients with penicillin-resistant S. pneumoniae (PRSP) is complicated because of the relatively poor blood-brain barrier penetration of effective antimicrobials. Our case: A previously healthy 70-year-old woman, a traveler from China to Japan, was admitted to our hospital with fever and loss of consciousness. She has no history of pneumococcal vaccination. She was diagnosed with bacterial meningitis due to penicillin-and third-generation cephalosporin-resistant strains of S. pneumoniae. The patient was successfully treated with a combination therapy of vancomycin (VCM) and levofloxacin (LVFX) and recovered without any neurological sequelae. As the treatment of penicillin-and third-generation cephalosporin-resistant strains of S. pneumoniae meningitis remains unclear, we conducted a review of the reported cases of meningitis caused by penicillin- and cephalosporin-resistant S. pneumoniae. METHOD: We performed a search using the keywords "penicillin-resistant Streptococcus pneumoniae," "meningitis," and "pneumococcal meningitis". We searched the electronic databases PubMed, Embase, and Ichushi from their inception to March 2020. Subsequently, two authors independently reviewed the resulting database records, retrieved full texts for eligibility assessment, and extracted data from these cases. RESULT: We identified 18 papers describing thirty-five cases of penicillin- and cephalosporin-resistant S. pneumoniae meningitis including our case. The patient's characteristics were; median age: 50 years, men:50%, 85% of cases received combination regimens of antibiotics: Ceftroriaxone (CTRX) plus VCM (20 cases), CTRX plus VCM plus rifampicin (RFP) (two cases), CTRX plus linezolid (one case), fluoroquinolones (two cases), carbapenems (six cases), Thirty-five percent received steroids. Twenty-four percent of patients died. Twenty-six percent of patients complicated neurological sequalae. CONCLUSION: Combination therapy including VCM plus LVFX could be a treatment option.

Enterococcus hirae bacteremia associated with acute pyelonephritis in a patient with alcoholic cirrhosis: a case report and literature review.

BACKGROUND: Infections caused by Enterococcus hirae are common in animals, with instances of transmission to humans being rare. Further, few cases have been reported in humans because of the difficulty in identifying the bacteria. Herein, we report a case of pyelonephritis caused by E. hirae bacteremia and conduct a literature review on E. hirae bacteremia. CASE PRESENTATION: A 57-year-old male patient with alcoholic cirrhosis and neurogenic bladder presented with fever and chills that had persisted for 3 days. Physical examination revealed tenderness of the right costovertebral angle. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) of the patient's blood and urine samples revealed the presence of E. hirae, and pyelonephritis was diagnosed. The patient was treated successfully with intravenous ampicillin followed by oral linezolid for a total of three weeks. CONCLUSION: The literature review we conducted revealed that E. hirae bacteremia is frequently reported in urinary tract infections, biliary tract infections, and infective endocarditis and is more likely to occur in patients with diabetes, liver cirrhosis, and chronic kidney disease. However, mortality is not common because of the high antimicrobial susceptibility of E. hirae. With the advancements in MALDI-TOF MS, the number of reports of E. hirae infections has also increased, and clinicians need to consider E. hirae as a possible causative pathogen of urinary tract infections in patients with known risk factors.

Campylobacter fetus bacteremia and meningitis in an acute lymphoblastic leukemia patient undergoing maintenance therapy: a case report.

BACKGROUND: Campylobacter fetus is an uncommon Campylobacter species, and its infections mainly cause infective endocarditis, aortic aneurysm, and meningitis rather than enteritis. It is more likely to be detected in blood than Campylobacter jejuni or Campylobacter coli, specifically reported in 53% of patients. In our case, C. fetus was detected in both blood and cerebrospinal fluid (CSF) cultures. CASE PRESENTATION: A 33-year-old woman, who was on maintenance chemotherapy for acute lymphoblastic leukemia (ALL), presented to our clinic with chief complaints of severe headache and nausea. Blood and CSF cultures revealed C. fetus. We administrated meropenem 2 g intravenously (IV) every 8 h for 3 weeks, and she was discharged without neurological sequelae. CONCLUSION: We encountered a case of C. fetus meningitis without gastrointestinal symptoms, neck stiffness or jolt accentuation in a patient with ALL. Undercooked beef was considered the source of C. fetus infection in this case, suggesting that the need for a neutropenic diet and safe food handling be considered.

Use of PCR in the diagnosis of pericardial amebiasis: a case report and systematic review of the literature.

BACKGROUND: Entamoeba histolytica (E. histolytica) is rarely identified as a cause of amebic pericarditis. We report a case of amebic pericarditis complicated by cardiac tamponade, in which the diagnosis was missed initially and was made retrospectively by polymerase chain reaction (PCR) testing of a stored sample of pericardial fluid. Furthermore, we performed a systematic review of the literature on amebic pericarditis. CASE PRESENTATION: A 71-year-old Japanese man who had a history of sexual intercourse with several commercial sex workers 4 months previously, presented to our hospital with left chest pain and cough. He was admitted on suspicion of pericarditis. On hospital day 7, he developed cardiac tamponade requiring urgent pericardiocentesis. The patient's symptoms temporarily improved, but 1 month later, he returned with fever and abdominal pain, and multiple liver lesions were found in the right lobe. Polymerase chain reaction of the aspiration fluid of the liver lesion and pericardial and pleural fluid stored from the previous hospitalization were all positive for E. histolytica. Together with the positive serum antibody for E. histolytica, a diagnosis of amebic pericarditis was made. Notably, the diagnosis was missed initially and was made retrospectively by performing PCR testing. The patient improved with metronidazole 750 mg thrice daily for 14 days, followed by paromomycin 500 mg thrice daily for 10 days. CONCLUSIONS: This case suggests that, although only 122 cases of amebic pericarditis have been reported, clinicians should be aware of E. histolytica as a potential causative pathogen. The polymerase chain reaction method was used to detect E. histolytica in the pericardial effusion and was found to be useful for the diagnosis of amebic pericarditis in addition to the positive results for the serum antibody testing for E. histolytica. Because of the high mortality associated with delayed treatment, prompt diagnosis should be made.

Vagococcus fluvialis as a causative pathogen of bloodstream and decubitus ulcer infection: Case report and systematic review of the literature.

BACKGROUND: Vagococcal infections are uncommon in humans; there are limited studies on the clinical manifestations, the optimal methods for identifications, and antimicrobial susceptibility testing for vagococcal infections. Here, we have reported a case of Vagococcus fluvialis-induced bacteremia and decubitus ulcer and have systematically reviewed other reported Vagococcus infections. CASE PRESENTATION: A 74-year-old man presented to our emergency department with muscle weakness on his left extremities, dysarthria, and altered mental status along with fever for the past 4 days. Physical examination revealed a decubitus ulcer with foul smelling and yellowish exudative pus on his left chest wall and abdomen, forearm, thigh, and lower leg. He was empirically treated with 2.25 mg of piperacillin/tazobactam every 8 hours and 0.5 g of vancomycin every 24 hours intravenously (IV) for his decubitus ulcer. Vagococcus fluvialis was detected in both aerobic and anaerobic blood cultures (upon admission) using the VITEC 2 GP ID card (bioMérieux) and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). We continued the mentioned IV antimicrobial therapies for 4 weeks following which the patient was transferred to a long-term care facility for further rehabilitation. CONCLUSIONS: To our best knowledge, this is the first literature review of Vagococcus infections in humans. Since it is challenging to distinguish Vagococcus from Enterococcus by a conventional method due to the similarity of its biochemical properties to those of Enterococcus, based on our literature review, 16S rRNA sequencing or analysis of bacterial protein profile using MALDI-TOF MS may be useful for the precise identification.

Disseminated nocardiosis due to Nocardia terpenica.

We report the first case of disseminated nocardiosis due to trimethoprim/sulfamethoxazole-resistant Nocardia terpenica successfully treated with meropenem and clarithromycin. The patient travelled to Japan from Australia via Southeast Asia, which led to differential diagnoses of multiple lung nodules including miliary tuberculosis and melioidosis as well as nocardiosis. Because of variety of susceptibility depending on the Nocardia species, clinicians need to confirm the species and investigate its susceptibility.

Essential consultants' skills and attitudes (Willing CONSULT): a cross-sectional survey.

BACKGROUND: Despite multi-professional collaboration via consultation being increasingly important given the variety of disease diagnoses and treatment, the key elements as consultants remain unclear. The study aimed to identify the skills and attitudes that are important for consultants from the residents' perspective so that they can be targeted as priority goals in subsequent educational interventions. METHODS: We conducted our research in two phases: a preliminary survey (May 1 to 14, 2020) and a main survey (June 1 to 14, 2020). As a preliminary survey, first-year postgraduate residents at St. Luke's International Hospital in Tokyo, Japan, were first asked an open-ended question about the types of skills and attitudes that are important for consultants. After eliminating duplicate answers, there were 19 skills and attitudes in total. In the main survey with residents who completed their residency training at our institute, from 2014 to 2018 and current residents (2019-2020), we first asked them about their demographic characteristics (gender, years of postgraduate education, and type of specialty). Then, they answered how important each skill and attitude are for consultants. All 19 items were scored on a seven-point Likert scale that ranged from 0 (completely disagree) to 6 (totally agree). Cronbach's alpha confirmed the internal consistency of the questionnaire items. Principal component analysis and exploratory factor analysis were performed. RESULTS: The survey included 107 individuals (61.1 %, 175 potential participants). The median postgraduate years of education was four (interquartile range: 2-5), and 64.5 % were men (n = 69). Seven key elements for consultants were identified and termed Willing CONSULT. These included (1) willingness (willingness to accept consultation requests), (2) contact (easy access to consultants), (3) needs (consideration of consulters' needs), (4) suggestions and support (providing clear recommendations and suggestions, following up on the patients, and supporting the consulters continuously), (5) urgency (considering the situation's urgency and responding appropriately), (6) learning opportunities (providing teaching points), and (7) text (writing medical records). CONCLUSIONS: We propose Willing CONSULT, which are important skills and attitudes for consultants.

Pacemaker infection and endocarditis due to Parvimonas micra: A case report and systematic review.

Infective endocarditis caused by Parvimonas micra is rare. Its clinical features are presented in this systematic review. We also describe the case of an 82-year-old man with infective endocarditis and pacemaker infection due to P. micra. There are some reports of recurrence during antimicrobial therapy; hence, careful follow-up is necessary.

Infected aortic aneurysm caused by Helicobacter cinaedi: case series and systematic review of the literature.

BACKGROUND: Helicobacter cinaedi is rarely identified as a cause of infected aneurysms; however, the number of reported cases has been increasing over several decades, especially in Japan. We report three cases of aortic aneurysm infected by H. cinaedi that were successfully treated using meropenem plus surgical stent graft replacement or intravascular stenting. Furthermore, we performed a systematic review of the literature regarding aortic aneurysm infected by H. cinaedi. CASE PRESENTATION: We present three rare cases of infected aneurysm caused by H. cinaedi in adults. Blood and tissue cultures and 16S rRNA gene sequencing were used for diagnosis. Two patients underwent urgent surgical stent graft replacement, and the other patient underwent intravascular stenting. All three cases were treated successfully with intravenous meropenem for 4 to 6 weeks. CONCLUSIONS: These cases suggest that although aneurysms infected by H. cinaedi are rare, clinicians should be aware of H. cinaedi as a potential causative pathogen, even in immunocompetent patients. Prolonged incubation periods for blood cultures are necessary for the accurate detection of H. cinaedi.

Aspergillus meningitis in a patient with chronic lymphocytic leukemia.

Central nervous system aspergillosis is relatively rare and difficult to diagnose. Here, we report a case of 90-year-old man with chronic lymphocytic leukemia who presented with a month-long gradually worsening headache followed by 3 days of low-grade fever associated with altered mental status. Aspergillus meningitis diagnosed using Aspergillus galactomannan antigen in the cerebrospinal fluid and treated with voriconazole. Delayed diagnosis and treatment of Aspergillus meningitis is typically associated with high mortality; therefore, it is imperative to include this disease in the differential diagnoses of subacute meningitis.

The mammalian circadian clock protein period counteracts cryptochrome in phosphorylation dynamics of circadian locomotor output cycles kaput (CLOCK).

The circadian transcription factor CLOCK exhibits a circadian oscillation in its phosphorylation levels. Although it remains unclear whether this phosphorylation contributes to circadian rhythm generation, it has been suggested to be involved in transcriptional activity, intracellular localization, and degradative turnover of CLOCK. Here, we obtained direct evidence that CLOCK phosphorylation may be essential for autonomous circadian oscillation in clock gene expression. Importantly, we found that the circadian transcriptional repressors Cryptochrome (CRY) and Period (PER) showed an opposite effect on CLOCK phosphorylation; CRY impaired BMAL1-dependent CLOCK phosphorylation, whereas PER protected the phosphorylation against CRY. Interestingly, unlike PER1 and PER2, PER3 did not exert a protective action, which correlates with the phenotypic differences among mice lacking the Per genes. Further studies on the regulatory mechanism of CLOCK phosphorylation would thus lead to elucidation of the mechanism of CRY-mediated transcriptional repression and an understanding of the true role of PER in the negative feedback system.