The objective of this pharmacokinetic (PK)/pharmacodynamic (PD) analysis was to evaluate the efficacy of different dosing regimens of ceftazidime/avibactam (CZA) for the treatment of pulmonary infections by extensively drug-resistant (XDR) Pseudomonas aeruginosa using optimized two-step administration therapy (OTAT) and traditional infusion (TI). We used Monte Carlo simulations (MCS) to integrate PK parameters with PD parameters to assess the adequacy of CZA dosing in critically ill patients with XDR P. aeruginosa pulmonary infections. Dosing models were as follows: 2.5 g q8h, 2.5 g q6h, 4 g q8h, 4 g q6h, 1.25 g q8h, 1.25 g q6h, and 0.94 g q12h. MCS showed that the cumulative fraction of response of all dosing regimens of OTAT was higher than 90%. The probability of target attainment of all dosing regimens of OTAT at MICs (minimal inhibitory concentrations) between 16 mg/L and 32 mg/L was higher than that of TI. Based on these models, PK/PD goals were met with OTAT regimens, even with high MICs (>16 mg/L) compared to traditional infusion (TI) intervals. Thus, this study indicates that OTAT with sufficient PK exposure could improve the efficacy of CZA in critically ill patients with XDR P. aeruginosa pulmonary infections.

In this study, Aeromonas spp. were re-identified, and the clinical aspects associated with Aeromonas bacteremia, as well as drug resistance and virulence genes, were elucidated. A total of 188 isolates were classified into 7 Aeromonas spp. using housekeeping gene sequencing, which was the standard to assess the accuracy of the VITEK MALDI-TOF system and the VITEK2 Compact system. The VITEK MS system and housekeeping gene sequencing had a 39.89% clear coincidence rate, whereas the VITEK2 Compact system and the standard had a 2.13% coincidence rate. Aeromonas bacteremia was associated with septic shock, hematologic malignancy, and post-hepatitic cirrhosis. Hematological malignancy, hypoproteinemia, systemic steroid use, central venous catheterization, and virulence genes act and ast were linked to poor outcomes. Aeromonas bacteremia had a 37.5% mortality rate; however, differences in mortality rates among Aeromonas spp. were observed. According to the broth microdilution method, over 90% of isolates were sensitive to most antimicrobials, except ceftriaxone (83.33%) and imipenem (83.33%). Polymerase chain reaction and DNA sequencing verified the presence of drug resistance genes; bla_CphA was detected in 3 isolates, while bla_NDM-1 was found in one isolate. In summary, common methods for identifying Aeromonas spp. are ineffective. Immunocompromised patients have a higher risk of infection and mortality. Furthermore, carbapenem resistance is a serious problem.

Salmonella foodborne disease outbreaks have markedly decreased in recent years, and different Salmonella serovars have been isolated. To clarify the characteristics of Salmonella strains causing annual epidemics and to estimate the source, we conducted a serotyping test on 1,132 human-derived Salmonella isolates in the 1990s and 2010s, and 1,061 food-derived Salmonella isolates in the 2010s in Tokyo. The serovars commonly isolated from human feces in the 1990s and after 2012 were S. Enteritidis, S. Typhimurium, S. Infantis, S. Thompson, and S. Agona. The new main serovars isolated after 2012 were S. Schwarzengrund, S. Enterica serovar 4:i:-, and S. Chester. In contrast, the main serovars detected from foods after 2012 were S. Infantis, S. Schwarzengrund, S. Agona, S. Manhattan, S. Typhimurium, and S. enterica serovar UT: r:1,5. S. Schwarzengrund has recently been frequently isolated. These strains were mainly isolated from chicken meat and offal. It was suggested that the same serovars of human-derived isolates were also isolated from foods, especially chicken meat and offal, and that these were recently an important causative food of Salmonellosis.

We investigated the epidemiological findings regarding the route of coronavirus disease 2019 (COVID-19) and infection prevention and control (IPC) measures among returnees in the emergency evacuation from Wuhan, China to Japan during the COVID-19 outbreak in 2020. A total of 12 of the 14 returnees (median age [range]: 49.5 years [29–65 years]; 9 men [75%]) had confirmed COVID-19. The proportion of returnees with COVID-19 was 12/566 (2.1%) in Flights 1–3 and 2/263 (0.8%) in Flights 4 and 5. Six patients were asymptomatic on admission, while 3 patients developed symptoms thereafter. None of the participants reported a specific history of contact with animals, going to seafood markets, or visiting medical facilities. Two patients were in contact with an individual who was confirmed or suspected of having COVID-19. Most patients resided in hotels in the center of Wuhan City, taking taxis and trains for commute. Patients relatively adhered to IPC measures such as wearing a mask and hand hygiene. However, emphasis on IPC measures such as universal masking and more rigorous avoidance of exposure risk might have been necessary to prevent infection. In addition, forced social distancing due to lockdown might have contributed to the lower infection rates in Flights 4 and 5, compared to Flights 1–3.

Common Human Coronaviruses (HCoVs), such as NL63, HKU1, 229E, and OC43, induce respiratory tract infections worldwide. Epidemiological studies of HCoVs are of paramount importance because the disease burden and trajectory (in years) have not been well addressed in adults. Here, we aimed to describe the burden of HCoVs in a hospital setting over five years before the coronavirus disease 2019 pandemic. This was a retrospective study of patients (>18 years) between January 1, 2015, and January 1, 2020, whose respiratory specimens were tested by multiplex real-time polymerase chain reaction. In total, 7,861 respiratory samples (4,540 patients) were included, 38% of which tested positive for any respiratory virus. Of these, 212 (12.2%) samples were positive for HCoVs, and their co-infection with other respiratory viruses was 30.6%. Rhinovirus (27.6%) was the most common co-infection among all three HCoVs. The overall prevalence of HCoVs tended to be the highest in the winter (40.9%). Patients aged ≥60 years had the highest prevalence of overall HCoVs (39.7%). Given the duration and large sample size, this study from Turkey is one of the largest to date among adults in the literature. These epidemiological data and molecular surveillance of HCoVs have important implications for the control and prevention of respiratory infections.

A catch-up campaign for measles and rubella (MR) vaccinations was conducted among third-year high school (MR-4) students between 2008 and 2012 as part of governmental policy. We examined three analytical methodologies to assess the vaccination policies. We measured the antibody titers of the first-year students involved and not involved in the catch-up campaign and analyzed the levels of antibody titers after two-or-more-dose vaccination using conventional regression analysis, the individual’s birth year using proxy exposure analysis, and the birth fiscal year using two-stage least square (2SLS) regression as instrumental variables. Of the 379 students invited to participate in the study, 220 (58.0%) vaccinated against measles and 213 (56.2%) vaccinated against rubella were included in the analysis. Conventional regression analysis revealed that two-or-more-dose vaccination produced 0.27 (95% confidence interval [CI], 0.04–0.49) greater log-antibody titers for measles. Proxy exposure analysis of the birth year revealed that two-or-more-dose vaccination produced 0.40 (95% CI, 0.18–0.63) greater log-scale antibody titers against measles. According to the two-stage least squares regression analysis, two-or-more-dose vaccination produced 0.72 (95% CI, 0.31–1.13) greater log-scale antibody titers against measles. All three analyses showed similar trends, but no findings were reported for rubella. These results were consistent across the three analytical methodologies used to assess the vaccination policies.

The control of drug-resistant tuberculosis (TB) is a major challenge. The frequency and mutation characteristics indicate the efficiency of molecular tests for the rapid detection of TB drug resistance. This study examined the existence of katG and inhA mutations for isoniazid (INH) resistance and rpoB mutations for rifampicin (RFP) resistance. In total, 178 drug-resistant Mycobacterium tuberculosis (MTB) isolates were analyzed. Mutations in katG encoding and inhA regulatory regions were detected in 136/168 (81.0%) and 29/168 (17.3%), respectively, with the most prominent mutation of Ser315Thr substitution in katG in 126/168 (75.0%), and -15 C to T substitution in the regulatory region of the inhA (26/168; 15.5%). Two distinct katG mutations (Tyr337Cys, 1003InsG) were identified. Of 125 RFP-resistant isolates, 118 (94.4%) carried mutations affecting the 81-bp RFP resistance-determining region, with the most commonly affected codons 450, 445, and 435 identified in 74 (59.2%), 26 (20.8%), and 12 (9.6%) isolates, respectively. Genetic mutations were highly associated with phenotypic INH and RFP resistance, and the majority shared similarities with those reported in previous studies in Thailand and other Asian countries. These data are useful for guiding the use and improvement of molecular tests for TB drug resistance.

This study was aimed at investigating differences in antibody titers indicative of the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between those who had experienced symptoms of coronavirus disease 2019 (COVID-19) and those who had not. We used data from a cross-sectional survey conducted at the National Cancer Center, Japan, of 434 individuals with no previous COVID-19 infection. The participants self-reported symptoms from the start of 2020. A generalized linear model was used to compare the mean SARS-CoV-2-specific IgG nucleocapsid protein (N-IgG) titer with estimated confidence intervals according to the onset of symptoms indicative of COVID-19. We observed a tendency toward an association between higher mean N-IgG titers and occurrence of high fever within the past 8 months (P = 0.053). The mean N-IgG titer was higher in those with prior symptoms (P = 0.03) and those with over three symptoms (P < 0.01) than in those without symptoms. The mean N-IgG titer was higher in those with symptoms and those with more symptoms that might indicate COVID-19 relative to those without symptoms, suggesting that transient but contained SARS-CoV-2 infection had occurred.

Mosquitoes are important arthropod vectors of arboviruses. The family Phenuiviridae includes several medically important arboviruses, such as the Rift Valley fever phlebovirus and Toscana phlebovirus. Recent comprehensive genetic analyses have identified many novel mosquito-specific viruses that are phylogenetically related to Phenuiviridae. We collected mosquitoes from Hokkaido in northern Japan, and conducted reverse transcription polymerase chain reactions (RT-PCRs) targeting the RNA-dependent RNA polymerase (RdRp) gene of Phenuiviridae. A total of 285 pools, comprising 3,082 mosquitoes from 2 genera and 8 species, were collected. Partial RdRp sequences were detected in 97 pools, which allowed us to classify the viruses into 3 clusters provisionally designated as Etutanne virus (ETTV) 1, 2, and 3. The virus most closely related to ETTVs is Narangue virus (family Phenuiviridae, genus Mobuvirus), which was detected in Mansonia mosquitoes; the nucleotide and amino acid sequences of the Narangue virus are 58.4–66.2% and 64.7–86.7% similar, respectively, to those of ETTVs. PCR and RT-PCR using DNA and RNase digestion methods showed that the ETTVs are RNA viruses that do not form non-retroviral integrated RNA virus sequences in the mosquito genome.

To evaluate the profile of ophthalmological manifestations of patients with chikungunya accompanied by the ophthalmology service at a reference center in the northeast region of Brazil. This retrospective study included the medical records of patients of the Leiria de Andrade Foundation (FLA) who presented ocular manifestations and had a history of prior Chikungunya virus (CHIKV) involvement. The data were collected between August 2018 and March 2019. A total of 230 patients participated in this study, 71.7% were female, and 46.1% were between 61 and 80 years old. Regarding previous pathological history, 71 patients (30%) had comorbidities, and 86 (37%) reported previous ophthalmologic pathology. The most common eye complaint was low visual acuity (LVA). Of the participants, 137 (59.6%) presented ophthalmologic manifestations after CHIKV infection, with cataracts being the most evident. Regarding medication, 85 participants used corticosteroids. The participants were predominantly female, aged between 61 and 80 years, and had previous comorbidities. LVA was the most reported complaint by patients, and cataracts were the main ophthalmological pathology presented.

We report the first pediatric patient infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Japan. The patient was a one-year-old boy who resided in Japan. He went abroad with his parents from November 12, 2021 to November 28, 2021 and had no known contact with coronavirus disease (COVID-19) patients there. Upon arrival at the Narita International Airport on November 28, 2021, his father tested positive for SARS-CoV-2 via a quantitative antigen test. Because the boy and his mother tested negative for SARS-CoV-2, they quarantined together at a hotel separately from his father. On December 4, 2021, the boy tested positive by reverse-transcription polymerase chain reaction (RT-PCR) for SARS-CoV-2, without symptoms, and was hospitalized with his mother; he and his father were both found to be infected with the SARS-CoV-2 Omicron variant. The boy was not vaccinated against COVID-19. RT-PCR results were negative starting on December 20, 2021. The incubation period and required period for negative conversion of SARS-CoV-2 RNA of the Omicron variant case were similar to those of the cases of conventional strains. We should carefully consider the potential of the SARS-CoV-2 Omicron variant to spread widely among unvaccinated children.

Since February 2021, healthcare workers in Japan have been preferentially vaccinated with a messenger RNA vaccine (BNT162b2; Pfizer/BioNTech) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While many studies have confirmed that this vaccine is highly effective in reducing hospitalization and deaths from coronavirus disease 2019 (COVID-19), antibody titers tend to decline at 3 months after vaccination, leading to a risk of breakthrough infections. Thus, information is needed to support the decision regarding the 3rd vaccination. In this study, we investigated the transition of anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) IgG and neutralizing antibody titers in 37 vaccinated Japanese healthcare workers. Samples were collected 6 times starting before vaccination until 6 months after the second vaccination. The levels of anti-SARS-CoV-2 RBD IgG peaked 1 week after the 2nd vaccination, then declined over time and decreased to < 10% at 6 months after the 2nd vaccination. Additionally, approximately one-third of the healthcare workers were seronegative for the Omicron variant 6 months after the 2nd vaccination. Workers with low anti-SARS-CoV-2 RBD IgG levels also had low neutralizing antibody titers. These data support booster dose administration for healthcare workers, especially those with low anti-SARS-CoV-2 RBD IgG levels.

Legionella pneumophila, the primary causative agent of Legionnaires’ disease, is classified into at least 15 serogroups (SGs). Before genotyping, serotyping is first performed to limit the sources of L. pneumophila infections that caused an outbreak. In addition to conventional assays using monoclonal or polyclonal antisera, serotyping using multiplex polymerase chain reaction (M-PCR) was recently developed for L. pneumophila. In this study, we applied the M-PCR system to 41 strains that remained to be SGUT (untypable) by slide agglutination tests among the 220 L. pneumophila strains isolated from bath water in Kobe City during 2016–2020, to determine SG-genotypes (SGg) by PCR amplification of the specific target gene of the SGs. Among the 41 SGUT strains, SGg4/10/14 was the most predominant (24/41, 58.5%), followed by SGg1 (7/41, 17.1%). Seven strains, except for the strains determined as SGg1, were identified as belonging to a single SGg by M-PCR serotyping (SGg5 [3/41, 7.3%], SGg8 [3/41, 7.3%], and SGg7 [1/41, 2.4%]). Furthermore, we found that the seven strains identified as SGg1 harbored particular genotypes. In conclusion, the M-PCR serotyping assay will be helpful for investigating the distribution of L. pneumophila in environmental and clinical settings.

We present a case study of a 6-day-old male infant who was referred to our hospital for fever, jaundice, and poor suckling, and was diagnosed with meningitis due to Edwardsiella tarda. We were able to detect E. tarda DNA after performing broad-range polymerase chain reaction targeting the bacterial 16S rRNA gene followed by a Basic Local Alignment Search Tool analysis of the DNA extracted from the cerebrospinal fluid. Furthermore, Japanese literature review showed that E. tarda caused perinatal invasive infections in mothers and infants and that the risk of fetal meningitis might be related to the food preference of Japanese people for raw fish. It is crucial to disseminate the information that pregnant women should refrain from eating high-risk raw fish, including freshwater fish.

The most common routes of transmission of coronavirus disease 2019 are droplet and contact infections. During dental treatment, several instruments and procedures used generate droplets of saliva and blood, such as during the extraction of an impacted third molar (M3). Surgical masks are often used during tooth extraction. However, the surface structures of surgical masks against droplets are not fully understood. Therefore, we analyzed the droplets that adhered to the surgical masks during impacted M3 extraction using electron microscopy. The surgical mask was divided into three layers and observed using electron microscopy. The outer and inner layers had a similar mesh-like structure, whereas the middle layer had a denser three-dimensional structure. Droplets ranging from 20–100 µm in size, generated during the extraction, adhered to the fibers of the outer layer of the mask. Fewer droplets adhered to the middle layer than to the outer layer. Droplets did not reach the inner layer. In conclusion, we suggest that a surgical mask can prevent droplet infection when performing impacted M3 extraction. This study is expected to contribute to the study of infection control strategies during dental treatments in the future.

During the COVID-19 pandemic in 2021, Japan experienced an outbreak of respiratory syncytial virus (RSV) infection. A total of 51 RSV cases were detected in infant specimens, including 38 rhinorrhea and 13 nasopharyngeal swabs, collected at the Tokyo Metropolitan Institute of Public Health. Of the 51 cases, 12 were RSV-A and 39 were RSV-B. The G protein gene sequence of RSV-A belonged to the ON1 genotype, whereas RSV-B belonged to the BA9 genotype; thus, different types of RSV were detected during the same period, suggesting that the unusual 2021 RSV season was not due to a single strain or genotype. Of all RSV-positive cases, the proportion of patients aged ≥2 years was 56.8% in 2021, higher than the 31.2% reported in the past 5 years. This indicates that infants aged <1 year who were originally susceptible to RSV infection were less likely to be infected with RSV because of the COVID-19 control measures. The 2021 epidemic peaked in the 28th week, 9 weeks earlier than the average from 2016 to 2020. Therefore, it seems necessary to accumulate and analyze further data, such as factors that led to the outbreak and the characteristics of the detected viruses in 2021.