Nirmatrelvir Resistance in an Immunocompromised Patient with Persistent Coronavirus Disease 2019.

Although the coronavirus disease 2019 (COVID-19) pandemic is coming to an end, it still poses a threat to the immunocompromised and others with underlying diseases. Especially in cases of persistent COVID-19, new mutations conferring resistance to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) therapies have considerable clinical implications. We present a patient who independently acquired a T21I mutation in the 3CL protease after nirmatrelvir exposure. The T21I mutation in the 3CL protease is one of the most frequent mutations responsible for nirmatrelvir resistance. However, limited reports exist on actual cases of SARS-CoV-2 with T21I and other mutations in the 3CL protease. The patient, a 55 year-old male, had COVID-19 during chemotherapy for multiple myeloma. He was treated with nirmatrelvir early in the course of the disease but relapsed, and SARS-CoV-2 with a T21I mutation in the 3CL protease was detected in nasopharyngeal swab fluid. The patient had temporary respiratory failure but later recovered well. During treatment with remdesivir and dexamethasone, viruses with the T21I mutation in the 3CL protease showed a decreasing trend during disease progression while increasing during improvement. The impact of drug-resistant SARS-CoV-2 on the clinical course, including its severity, remains unknown. Our study is important for examining the clinical impact of nirmatrelvir resistance in COVID-19.

Recurrent Bacillus subtilis Var. Natto Bacteremia and Review of the Literature on Bacillus subtilis: The First Case Report.

BACKGROUND Fermented foods, such as yogurt, are often considered healthy; however, there have been numerous reported cases of bacteremia associated with their consumption. In this report, we present a case of Bacillus subtilis var. natto (B. subtilis var. natto) bacteremia related to the consumption of natto, a traditional Japanese food made from fermented soybeans. We also conducted a literature review on B. subtilis bacteremia. CASE REPORT We report the case of a 41-year-old woman who presented with fever, had a medical history of congenital liver fibrosis, and experienced recurrent B. subtilis var. natto bacteremia along with acute cholangitis. Although she discontinued eating natto, she developed pyogenic thrombophlebitis due to B. subtilis var. natto. We successfully treated her with meropenem and an anti-coagulant. To investigate the management and prognosis of B. subtilis var. natto bacteremia, we conducted a literature review of B. subtilis intra-abdominal infection. We identified 17 papers describing 30 cases of B. subtilis intra-abdominal infection, 4 cases of which were caused by B. subtilis var. natto; the median age of the patients was 71 years (range, 15-96 years), 14 patients (47%) were female, and 3 patients (10%) died. From our findings, our case was the only one of recurrent B. subtilis var. natto infection. Even after patients discontinue eating natto, they should be carefully monitored. CONCLUSIONS Due to advancements in PCR identification techniques, case reports of infections caused by B. subtilis var. natto are increasing.

SARS-CoV-2 RT-PCR as a universal screening on planned admission in asymptomatic patients.

Universal screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on admission is reportedly beneficial in preventing nosocomial infections. However, some issues remain, including low positivity rate, cost, and time required for testing. We describe SARS-CoV-2 reverse transcription polymerase chain reaction (PCR) for universal screening in asymptomatic patients on planned admissions. In total, 14,574 patients were included between October 12, 2020, and June 23, 2022. The PCR-positive rate for the period was 0.44 % (64/14,574). The PCR positivity for the epidemic period by strain was 0.28 % (95 % confidence interval [CI] 0.12-0.56 %), 0.16 % (95 % CI 0.05-0.37 %), 0.21 % (95 % CI 0.09-0.41 %), and 0.9 % (95 % CI 0.65-1.2 %) for the wild-type strain, Alpha, Delta, and Omicron variants, respectively. The proportion of Ct values < 30 was higher in the first half of the epidemic (first vs. second, 29.4 % [95 % CI 16.9-44.8 %] vs. 16.7 % [95 % CI 6.0-28.5 %]), whereas that of Ct values ≥ 35 increased significantly in the second half (first vs. second, 32.4 % [95 % CI 19.3-47.8 %] vs. 70.0 % [95 % CI 53.5-83.4 %]). Of all positives, 50 % (32/64) had a coronavirus disease (COVID-19) history before PCR screening, with a median of 28 days (10-105) from COVID-19 onset or positive to PCR screening. PCR screening may help detect positives with high viral loads early in the epidemic for each mutant strain, with an increasing proportion of positives with low viral loads later in the epidemic. PCR testing may be unnecessary for recently diagnosed cases and patients in whom reinfection is unlikely.

Effect of vaccine program on IgG antibody titers for measles, rubella, varicella, and mumps in young adults in Japan: Survey between 2018 and 2021.

INTRODUCTION: Improved routine immunizations in Japan have led to a reduction in vaccine-preventable diseases. Due to changes in the vaccination program, current young adults received their second vaccination for measles and rubella at different times depending on their birth year, and most of them have not been vaccinated against varicella and mumps. This study investigated the effect of vaccine programs on the immunity of people in Japan. METHODS: Immunoglobulin G antibody (IgG) titers against four viruses were determined by enzyme immunoassay in 795 students at a medical university. Titers for measles and rubella were compared according to the students' birth dates (Group 1: April 2, 1990-April 1, 2000; Group 2: April 2, 2000). RESULTS: The titers of students that satisfied the standard IgG values against measles, rubella, varicella, and mumps were 24.3%, 56.9%, 87.4%, and 47.2%, respectively. Measles and rubella titers were lower in group 2 (estimated mean period from last vaccination, 7.0 years) than group 1 (13.5 years) (p = 0.023 measles, p = 0.037 rubella), indicating attenuation of titers over time. Varicella and mumps antibody prevalence indicated that these infections were endemic, whereas rates of negative titers were higher than those for measles and rubella. CONCLUSIONS: IgG titers against viruses were affected by vaccination programs. Declining titers after vaccination should be monitored when the diseases are almost eliminated and boosting is absent. Antibody testing is meaningful for recommending vaccinations and for surveillance of waning immunity. Continuous improvements of vaccination program should be considered to prevent and eliminate diseases.

Usefulness of a newly developed high-speed polymerase chain reaction analysis system for the diagnosis of Clostridioides difficile infection.

INTRODUCTION: The incidence of Clostridioides difficile infection (CDI) has been continuously increasing and thereby became an important issue worldwide. Appropriate diagnosis, management, and infection control are required for patients with CDI. Enzyme immunoassay (EIA) is a widely used standard diagnostic tool for C. difficile-specific glutamate dehydrogenase (GDH) and C. difficile toxins (toxins A and B). However, the sensitivity of EIA in detecting C. difficile toxins has been reported to be relatively low, resulting in CDI underdiagnosis. Therefore, nucleic acid amplification tests (NAAT) are recently developed for higher sensitivity/specificity test. METHODS: In this study, a total of 279 stool samples submitted for CDI diagnosis were examined using an independently developed new high-speed polymerase chain reaction (PCR) device (PathOC RightGene, Metaboscreen). In parallel, results were compared with those of definitive diagnosis and conventional diagnostic methods (EIA, real-time PCR) to assess the inspection accuracy. RESULTS: PathOC RightGene showed high sensitivity (96.7%) and specificity (96.7%). Regarding the measurement time, C. difficile-specific and C. difficile toxin genes were simultaneously detected in approximately 25 min for one sample (including the preprocessing and measurement time). CONCLUSION: PathOC RightGene has been found to show both excellent sensitivity and rapidity and thus can be used for the reliable and early diagnosis, which are needed for the appropriate management of CDI.

Milian's ear sign: Erysipelas.

A clinical case is presented here of a patient with fever and ear pain. Physical examination revealed "Milian's ear sign", which supports the diagnosis of erysipelas rather than cellulitis. After intravenous antibacterial treatment, the patient recovered.

Synthesis and properties of diazirinyl organo-platinum compounds for manipulations of photoaffinity labeled components.

Synthesis of diazirinyl organo-platinum complexes, which specifically interact with purine base, characterization of photoreactivity and interaction between guanosine 5'-monophosphate (GMP) were examined. The results indicated that the diazirinyl organo-platinum complex was useful for manipulations of photoaffinity labeled components.