Inhibitory effects of vaginal Lactobacilli on Candida albicans growth, hyphal formation, biofilm development, and epithelial cell adhesion.

Introduction: Antifungal agents are not always efficient in resolving vulvovaginal candidiasis (VVC), a common genital infection caused by the overgrowth of Candida spp., including Candida albicans, or in preventing recurrent infections. Although lactobacilli (which are dominant microorganisms constituting healthy human vaginal microbiota) are important barriers against VVC, the Lactobacillus metabolite concentration needed to suppress VVC is unknown. Methods: We quantitatively evaluated Lactobacillus metabolite concentrations to determine their effect on Candida spp., including 27 vaginal strains of Lactobacillus crispatus, L. jensenii, L. gasseri, Lacticaseibacillus rhamnosus, and Limosilactobacillus vaginalis, with inhibitory abilities against biofilms of C. albicans clinical isolates. Results: Lactobacillus culture supernatants suppressed viable fungi by approximately 24%-92% relative to preformed C. albicans biofilms; however, their suppression differed among strains and not species. A moderate negative correlation was found between Lactobacillus lactate production and biofilm formation, but no correlation was observed between hydrogen peroxide production and biofilm formation. Both lactate and hydrogen peroxide were required to suppress C. albicans planktonic cell growth. Lactobacillus strains that significantly inhibited biofilm formation in culture supernatant also inhibited C. albicans adhesion to epithelial cells in an actual live bacterial adhesion competition test. Discussion: Healthy human microflora and their metabolites may play important roles in the development of new antifungal agent against C. albicans-induced VVC.

Predicting the aggravation of coronavirus disease-19 pneumonia using chest computed tomography scans.

Presently, coronavirus disease-19 (COVID-19) is spreading worldwide without an effective treatment method. For COVID-19, which is often asymptomatic, it is essential to adopt a method that does not cause aggravation, as well as a method to prevent infection. Whether aggravation can be predicted by analyzing the extent of lung damage on chest computed tomography (CT) scans was examined. The extent of lung damage on pre-intubation chest CT scans of 277 patients with COVID-19 was assessed. It was observed that aggravation occurred when the CT scan showed extensive damage associated with ground-glass opacification and/or consolidation (p < 0.0001). The extent of lung damage was similar across the upper, middle, and lower fields. Furthermore, upon comparing the extent of lung damage based on the number of days after onset, a significant difference was found between the severe pneumonia group (SPG) with intubation or those who died and non-severe pneumonia group (NSPG) ≥3 days after onset, with aggravation observed when ≥14.5% of the lungs exhibited damage at 3-5 days (sensitivity: 88.2%, specificity: 72.4%) and when ≥20.1% of the lungs exhibited damage at 6-8 days (sensitivity: 88.2%, specificity: 69.4%). Patients with aggravation suddenly developed hypoxemia after 7 days from the onset; however, chest CT scans obtained in the paucisymptomatic phase without hypoxemia indicated that subsequent aggravation could be predicted based on the degree of lung damage. Furthermore, in subjects aged ≥65 years, a significant difference between the SPG and NSPG was observed in the extent of lung damage early beginning from 3 days after onset, and it was found that the degree of lung damage could serve as a predictor of aggravation. Therefore, to predict and improve prognosis through rapid and appropriate management, evaluating patients with factors indicating poor prognosis using chest CT is essential.

Alleviation of hand-skin roughness after use of alcohol-based hand rub with inhibitory effects on Staphylococcus aureus-producing δ-toxin.

INTRODUCTION: Staphylococcus aureus colonizes rough regions of the skin of the hand. Healing of S. aureus-mediated wounds is promoted by the application of RNA III inhibiting peptide, which inhibits the production of S. aureus virulence factors, including δ-toxin. Herein, we investigated the level of hand-skin roughness in healthcare professionals after they used an alcohol-based hand rub containing polyoxyethylene lauryl ether (formulation E), which inhibits S. aureus δ-toxin production. METHODS: The inhibition rate of S. aureus δ-toxin production by hand rubs, including formulation E, was calculated by quantifying S. aureus δ-toxin concentration in culture medium using high-performance liquid chromatography. Healthcare professionals used formulations E or S (reference alcohol-based hand rub) for 4 weeks. The surface evaluation of the scaliness (SEsc) value was used as an indicator of hand skin roughness. The ΔSEsc value was calculated by subtracting the SEsc value before using the alcohol-based hand rub from the SEsc value 4 weeks after use. RESULTS: The inhibition rates of S. aureus δ-toxin production by formulations E and S were 43% and 10%, respectively. Formulation E significantly reduced ΔSEsc. The difference in ΔSEsc values after using formulations E and S was significant. CONCLUSIONS: The inhibitory effect on S. aureus δ-toxin production was higher with formulation E than with formulation S. Compared to formulations S, formulation E was effective at reducing scaliness and alleviating hand-skin roughness. Furthermore, the inhibitory effect of formulation E on S. aureus δ-toxin production could be associated with a reduction in scaliness and alleviation of hand-skin roughness.

Investigation of the incidence of immunisation stress-related response following COVID-19 vaccination in healthcare workers.

INTRODUCTION: Safe vaccination worldwide is critical to end the coronavirus disease 2019 (COVID-19) pandemic. We aimed to evaluate adverse reactions to vaccination using a web-based questionnaire and examine the risk factors for the occurrence of immunisation stress-related response (ISRR). METHODS: We conducted a questionnaire survey using Google Form® among the employees of St. Marianna University Hospital who had received the COVID-19 vaccine between April 2021 and May 2021, 1 week after the first and second vaccinations. We developed and used a questionnaire to identify individuals with ISRR according to the World Health Organization diagnostic criteria. A generalised linear mixed model was constructed with ISRR onset as the dependent variable, subjects as the random factor, and each parameter as a fixed factor. A multivariate model was constructed using the forced imputation method with factors that were significant in the univariate analysis. RESULTS: We enrolled 2,073 and 1,856 respondents in the first and second questionnaire surveys, respectively. Fifty-five and 33 ISRR cases were identified in the first and second vaccinations, respectively. In the univariate analysis, strong pre-vaccination anxiety (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.30-4.12, p = 0·004) and history of allergy (OR, 1.6; 95% CI, 1.14-2.24, p = 0·007) were significant risk factors. Multivariate analysis also showed that strong pre-vaccination anxiety (OR, 2.1; 95% CI, 1.15-3.80, p = 0.016) and history of allergy (OR, 1.5; 95% CI, 1.09-2.15, p = 0.014) were significant risk factors. CONCLUSIONS: Confirmation of allergy prior to vaccination and subsequent action are essential for addressing ISRR.

Back to normal; serological testing for COVID-19 diagnosis unveils missed infections.

BACKGROUND: The gold standard for coronavirus disease (COVID-19) diagnosis has been the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA by nucleic acid amplification testing (NAAT). On the other hand, serological testing for COVID-19 may offer advantages in detecting possibly overlooked infections by NAAT. METHODS: To evaluate seroconversion of NAAT-negative pneumonia patients, immunoglobulin M (IgM) and IgG targeting the spike protein of SARS-CoV-2 were semiquantified by an immunofluorescence assay. Seroconversion was confirmed by another serological method, targeting the nucleocapsid protein. RESULTS: Eight suspected but unconfirmed COVID-19 pneumonia patients (median age, 39 years; range, 21-55) were included. The median period between symptom onset and NAAT sample collection was 6 days (2-27 days). None of them had tested positive for SARS-CoV-2 by NAAT. In contrast, all eight patients revealed seropositivity with the two serological methods, indicating actual seroconversion against SARS-CoV-2. The median period between onset and blood sampling was 26.5 days (7-51 days). CONCLUSION: Eight patients with COVID-19 pneumonia, initially tested negative for SARS-CoV-2 by NAAT, were finally confirmed of the diagnosis by serological testing. To cover the whole spectrum of this heterogenous infectious disease, serology testing should be implemented to the multitiered diagnostic algorithm for COVID-19.

The peripheral lymphocyte count as a predictor of severe COVID-19 and the effect of treatment with ciclesonide.

We investigated whether reduced lymphocyte count, could predict the development of severe COVID-19. We also examined whether ciclesonide could prevent the development of severe COVID-19 among patients with the predictors. This was a retrospective cohort study. Of the 30 included patients, 12, 14, and 4 were allocated to severe pneumonia, non-severe pneumonia, and non-pneumonia groups, respectively. The group of the low level of lymphocyte counts of the sixth day after onset was significantly intubated approximately three days later. The incidence of the severe pneumoniae requiring intubation are significantly lower in the patients treated with ciclesonide than without it (11.18 % vs 83.33 %, p = 0.0033). The lymphocyte count after ciclesonide treatment in the non-severe pneumonia group was significantly higher (p = 0. 0156) than before. The lymphocyte count could be used to identify patients that may develop severe COVID-19. Treatment with ciclesonide may prevent the development of severe COVID-19.

Eculizumab for Severe Thrombotic Microangiopathy Secondary to Surgical Invasive Stress and Bleeding.

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare condition caused by an excessive activation of the complement pathway based on genetic or acquired dysfunctions in complement regulation, leading to thrombotic microangiopathy (TMA). A complement-amplifying condition (CAC) can trigger aHUS occurrence along with complement abnormality. We herein report a case of severe TMA after laparoscopic myomectomy in a healthy woman. This case was eventually diagnosed as complement-mediated TMA secondary to surgical invasive stress as a CAC, with no definitive diagnosis of aHUS despite a genetic test. The patient fully recovered after several eculizumab administrations.

The effect of gut microbiota and probiotic organisms on the properties of extended spectrum beta-lactamase producing and carbapenem resistant Enterobacteriaceae including growth, beta-lactamase activity and gene transmissibility.

The gut microbiota may play a pivotal role in controlling the antimicrobial resistant (AMR) organisms although the evidences are limited. We investigated the effects of gut microbiota on the growth of AMR organisms, ß-lactamases activity and transmissibility of antimicrobial resistant properties of the extended spectrum ß-lactamase (ESBL)-producing Escherichia coli and carbapenem-resistant Enterobacteriaceae. CTX-M-15-positive, ESBL-producing E. coli and carbapenem resistant Enterobacteriaceae, Bacteroides fragilis, Bifidobacterium longum, Clostridium butyricum, Clostridioides difficile, Clostridium perfringens, Enterococcus faecium, Lactobacillus plantarum and probiotic strain of C. butyricum MIYAIRI 588 were used in this study. The growth of AMR organisms was suppressed by the supernatant of C. butyricum, C. difficile, C. perfringens, E. faecium and L. plantarum in a dose dependent manner but not by that of B. fragilis and B. longum. The ß-lactamase activity produced by E. coli was reduced by the presence of culture supernatant of certain gut microbiota during stationary phase of E. coli. Importantly, C. butyricum MIYAIRI 588 culture supernatant suppressed the transcription of blaCTX-M gene during growth phase of E. coli. The conjugation assay showed the reduction of transmissibility of antibiotic resistant gene by gut microbiota. These findings suggest that certain gut microbiota affect the antibiotic resistant activities of AMR organisms. Further studies are needed to identify the specific mechanism(s) of these actions between AMR organisms and gut microbiota.

Thoracic Aortic Graft Infection due to Candida Albicans with Multiple Embolism in the Left-side Vessels of the Body.

A 79-year-old Japanese man who had undergone thoracic aortic replacement 10 years prior presented with a 3-day history of sore throat. He was initially diagnosed with pharyngitis; however, multiple emboli in the vessels of the left side of the body were recognized. He was diagnosed with thoracic aortic graft infection caused by Candida albicans, with multiple embolisms. Anti-fungal therapy was initiated, but surgical removal of the graft was not performed because of the high risk associated with the operation, and he eventually died. Inappropriate use of antibiotics might have led to a severe fungal infection. As such, the inappropriate use of antimicrobial agents should be avoided.

Factors predicting the cause and prognosis of central line-associated bloodstream infections.

The increased use of indwelling catheters has led to an increased number of deaths due to central line-associated bloodstream infection (CLABSI). Improving CLABSI outcomes requires the identification of clinical characteristics affecting drug selection and factors associated with poor prognosis. The medical records of inpatients admitted to St. Marianna University School of Medicine between April 1, 2010 and March 31, 2013 were evaluated for the results of catheter tip cultures. The clinical characteristics of these cases and the characteristics of the pathogens involved were investigated to identify prognostic factors. Of the 1629 catheter cultures investigated, 183 were CLABSIs. Among them, 105 were caused by gram-positive bacteria, 43 by gram-negative bacteria, and 35 by fungi. Gram-negative CLABSIs were more common in cases with prior colonization by gram-negative bacteria and post-surgical cases. Fungal CLASBIs were more common in the cases with prior colonization by fungi, high-calorie infusion enforcement, broad-spectrum antibiotic treatment, and post-surgical cases. Death was significantly more likely in cases with findings of inflammation at the catheter insertion site and in those with abnormal body temperature, tachycardia, or abnormal white blood cell count. Thus, when treating CLABSI in post-surgical cases and in cases with prior colonization by gram-negative bacteria, therapy should include anti-pseudomonal agents. Considering the factors predicting poor prognostic identified in this study, clinicians must check the vital signs and catheter insertion site in patients with indwelling catheters.

[A case of Streptococcus gallolyticus subsp. gallolyticus infective endocarditis with colon adenoma].

An 80-year-old Japanese man had a fall presented with a 3-week history of right lumbago exacerbated by body movement as well as a 1-week history of anomalous behavior and appetite loss. He visited our hospital complaining of difficulty in standing up. He had a history of mitral prolapse due to an unknown rupture of the chordae tendineae 3 years earlier, which resulted in moderate mitral valve regurgitation and atrial fibrillation. Upon visiting the hospital, he had petechial hemorrhage and jaundice of the conjunctiva, a systolic murmur (Levine II/VI) at the apex and 4th interspace of the left sternal border, and a positive right straight leg raising test result. Moderate bilirubinemia and disseminated intravascular coagulation which were considered to have been produced secondarily were observed. Infective endocarditis was suspected, and 3 sets of blood culture were extracted. The patient was admitted on the same day. Blood cultures were positive for Streptococcus gallolyticus subsp. gallolyticus (6/6) on the following day. Transesophagela echocardiography was carried out on the same day, and vegetation with a diameter of 4mm was observed in the anterior mitral leaflet; the patient was subsequently diagnosed as having infective endocarditis. Colonic endoscopy was performed after hospitalization. Twelve colonic adenomata were found, and endoscopic mucosal resection was performed on one polyp. The bacterium found in the culture was classified as Streptococcus bovis type I, which causes infective endocarditis and bacteremia. Furthermore, this bacteria is a relatively rare causative organism of infective endocarditis. Tolerance to macrolide and tetracycline are reported in the literature. Moreover, the cell wall of this bacterium may have low pathogenicity as well as cause chronic inflammation in the large intestine mucous membrane, colonic polyps, and colorectal cancer. Several colonic adenomata and a partial shift to a malignant pathology were observed in this case. When this bacterium is detected, searching for a pathological change in the large intestine is believed to be indispensable.

[A case of MRSA infection in multiple artificial joints successfully treated with conservative medical treatment].

We report herein on a case with multiple MRSA prosthetic arthritis and osteomyelitis successfully treated medically. Our patient was a 64-year-old Japanese woman with a previous medical history of malignant rheumatoid arthritis and multiple surgical interventions with an atlantoaxial fixation in 2003, artificial joint replacement of both knee joints in 2006, and of the right hip joint in September, 2007. She was initially hospitalized due to MRSA arthritis in the right hip in October, 2007. Thereafter, multiple joint infections occurred sequentially in the right knee joint in January 2008 and the left hip joint in June 2008. More recently, the patient was re-admitted in January 2009 due to cervical osteomyelitis with MRSA infection. The patient had been treated with a combination of vancomycin and rifampin for 17 weeks and followed by sulfamethoxazole/trimetoprim in the out-patient setting up to the present. Although the complete resolution of multiple deep MRSA infections with prosthetic arthritis and osteomyelitis is not expected without removing the infectious sources, our patient was successfully treated with chronic antibiotic suppressive therapy. Therefore, we report on our case with a literature review.

[A case of acute septic osteomyelitis onset due to Streptococcus dysgalactiae subsp. equisimilis in an elderly diabetic patient].

Group C streptococci are increasingly causing invasive infections such as that we report here. A 70-year-old man being treated for diabetes and seen at the emergency room for neck pain and fever was hospitalized for possible sepsis. His temperature was 39.8 degrees C, regular pulse 101 bpm, and pain reinforced in flexing and cervical rotation. Streptococcus dysgalactiae subsp. equisimilis (SDSE) was cultured from blood. Neck pain gradually decreased with of 2 million units PCG 6 times/day. Magnetic resonance imaging (MRI) of the cervical spine showed high-intensity areas in fat-suppression imaging at C7, Thl and intervertebral disks plus enhancement around the vertebral body, yielding a diagnosis of cervicothoracic vertebral osteomyelitis. Antimicrobial intravenous therapy continuede 6 weeks. The man was discharged after 45 days without relapse.