COVID-19 vaccine effectiveness against severe COVID-19 requiring oxygen therapy, invasive mechanical ventilation, and death in Japan: A multicenter case-control study (MOTIVATE study).

INTRODUCTION: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation. METHODS: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients. RESULTS: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes. CONCLUSION: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron.

A Case of Uncomplicated Bacteremia Caused by Capnocytophaga canimorsus in an Immunocompetent Patient.

This report describes uncomplicated bacteremia caused by Capnocytophaga canimorsus in an immunocompetent woman who presented with rigor and fever. She was hemodynamically stable. Two blood samples were immediately cultured because rigor indicated bacteremia. Although her symptoms were relieved, Gram-negative rods grew from blood cultures. She noted that she had been bitten by her dog before the first examination. The bacterium was confirmed as C. canimorsus by gene analysis. Infection with C. canimorsus can be fatal when accompanied by sepsis in elderly or immunocompromised patients. However, this case was considered rare as the patient was 41 years old and immunocompetent.

Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan.

BACKGROUND: Repeated emergence of variants with immune escape capacity and waning immunity from vaccination are major concerns for COVID-19. We examined whether the surge in Omicron subvariant BA.5 cases was due to immune escape or waning immunity through vaccine effectiveness (VE) evaluation. METHODS: A test-negative case-control study was conducted in 16 clinics/hospitals during the BA.1/BA.2-dominant and BA.5-dominant periods. VE against symptomatic infection was estimated after adjusting for age, sex, comorbidity, occupation, testing frequency, prior infection, close contact history, clinic/hospital, week, and preventive measures. Absolute VE (aVE) was calculated for 2/3/4 doses, compared to the unvaccinated. Relative VE (rVE) was calculated, comparing 3 vs 2 and 4 vs 3 doses. RESULTS: 13,025 individuals were tested during the BA.1/BA.2-dominant and BA.5-dominant periods with similar baseline characteristics. For BA.1/BA.2, aVE was 52 % (95 %CI:34-66) 14 days-3 months post-dose 2, 42 % (29-52) > 6 months post-dose 2, 71 % (64-77) 14 days-3 months post-dose 3, and 68 % (52-79) 3-6 months post-dose 3. rVE was 49 % (38-57) 14 days-3 months post-dose 3 and 45 % (18-63) 3-6 months post-dose 3. For BA.5, aVE was 56 % (27-73) 3-6 months post-dose 2, 32 % (12-47) > 6 months post-dose 2, 70 % (61-78) 14 days-3 months post-dose 3, 59 % (48-68) 3-6 months post-dose 3, 50 % (29-64) > 6 months post-dose 3, and 74 % (61-83) ≥ 14 days post-dose 4. rVE was 56 % (45-65) 14 days-3 months post-dose 3, 39 % (27-48) 3-6 months post-dose 3, 25 % (-2-45) > 6 months post-dose 3, and 30 % (-6-54) ≥ 14 days post-dose 4. CONCLUSIONS: Booster doses initially provided high protection against BA.5 at a level similar to that against BA.1/BA.2. However, the protection seemed shorter-lasting against BA.5, which likely contributed to the surge. Furthermore, rVE post-dose 4 was low even among recent vaccinees. These results support the introduction of variant-containing vaccines and emphasize the need for vaccines with longer duration of protection.

Phenotypic and Genotypic Traits of Pasteurella multocida subsp. septica Isolates From the Wounds of Two Patients Due to Dog or Cat Biting, 2023.

We describe the phenotypic and genotypic traits of Pasteurella multocida subsp. septica isolates from the dog/cat bite wounds of two patients in 2023. A 79-year-old man with diabetes mellitus and cerebral infarction who was bitten by a dog on his left hand developed deep inflammation under the tendon between his left fourth and fifth fingers. The patient's condition was resolved with antimicrobial treatment and surgical intervention. Another patient, a healthy 49-year-old woman who was bitten by a cat on her left hand, developed superficial inflammation of the left thumb and index finger. The patient's condition improved with antimicrobial treatment without surgical intervention. The isolates from the two patients had similar biochemical properties, and the antimicrobial susceptibility data for both isolates indicated erythromycin resistance. Genotypic analyses revealed clade 2 on the dendrogram of repetitive sequence-based fingerprinting, capsule serogroup cap genotype A, and hsf-1-nanH-pmHAS (virulence-associated genes). Our observations show that the two isolates have similar phenotypic and genotypic traits, regardless of differences in patient background, biting pets, wound inflammation, or the necessity of surgical intervention.

Effectiveness of BA.1- and BA.4/BA. 5-Containing Bivalent COVID-19 mRNA Vaccines Against Symptomatic SARS-CoV-2 Infection During the BA.5-Dominant Period in Japan.

In this multicenter, prospective, test-negative, case-control study in Japan, the effectiveness of both BA.1-containing and BA.4/BA.5-containing bivalent coronavirus disease 2019 mRNA vaccines against symptomatic infection during the BA.5-dominant period was high compared with no vaccination (65% and 76%) and moderate compared with monovalent vaccines administered over half a year earlier (46% combined).

A case of Bacillus subtilis var. natto bacteremia caused by ingestion of natto during COVID-19 treatment in a maintenance hemodialysis patient with multiple myeloma.

A 70-year-old woman, who started on hemodialysis 7 months before for end-stage renal disease due to diabetic nephropathy and was diagnosed with symptomatic multiple myeloma 1 month before, was admitted to our hospital with critical coronavirus disease 2019 and treated with long-term immunosuppressive therapy such as steroids and tocilizumab. During treatment, Bacillus subtilis was detected in the blood cultures. We could not exclude the association of natto (fermented soybeans) with B. subtilis var. natto, which the patient had been eating every day from 8 days after admission. She was prohibited from eating natto and treated with vancomycin. Later, B. subtilis detected in the blood culture was identified as B. subtilis var. natto, which was identical with those contained in the natto that the patient consumed daily using a next-generation sequencer. Gut dysbiosis due to old age, malignant tumor, diabetes mellitus, end-stage renal disease, and intestinal inflammation caused by severe acute respiratory syndrome coronavirus 2 increased intestinal permeability and the risk of bacterial translocation, causing B. subtilis var. natto bacteremia. Therefore, careful consideration might be given to the intake of fermented foods containing live bacteria in patients with severe immunocompromised conditions.

A Case of Asymptomatic Pulmonary Nocardia cyriacigeorgica Infection With Mild Diabetes Mellitus.

Nocardiosis is a relatively rare opportunistic infection, ranging from localized to systemic diseases, commonly occurring in immunocompromised patients with high mortality rates. We present a case of a 61-year-old man who received medical treatment for type 2 diabetes mellitus and underwent a physical examination that showed abnormal chest shadows on radiography. Chest computed tomography revealed bronchiectasis and infiltration in the left lower lobe. Nocardia spp. was detected in the bronchial washes, and he was started on sulfamethoxazole-trimethoprim under the diagnosis of pulmonary nocardiosis. 16S ribosomal RNA gene sequencing analysis identified the species as Nocardia cyriacigeorgica. His pulmonary lesions successfully improved after treatment for six months. Pulmonary nocardiosis often presents with symptoms such as hemoptysis and blood-tinged sputum, and bronchiectasis has been identified as an underlying condition. Even in hosts without underlying immunocompromising conditions, Nocardia spp. can be a causative microorganism of pulmonary infections, and it should be considered in the differential diagnoses.

Nafamostat Mesylate Monotherapy in Patients with Moderate COVID-19: a Single-Center, Retrospective Study.

Coronavirus disease (COVID-19) has spread dramatically worldwide. Nafamostat mesylate inhibits intracellular entry of the novel severe acute respiratory syndrome coronavirus 2 and is believed to have therapeutic potential for treating patients with COVID-19. In this study, patients with moderate COVID-19 who were admitted to our hospital were retrospectively analyzed. Thirty-one patients received monotherapy with nafamostat mesylate, and 33 patients were treated conservatively. Nafamostat mesylate was administered with continuous intravenous infusion for an average of 4.5 days. Compared with the conservative treatment, nafamostat mesylate did not improve outcomes or laboratory data 5 days after admission. In addition, no significant differences in laboratory data 5 days after admission and outcomes in high-risk patients were observed. The incidence of hyperkalemia was significantly higher in the nafamostat mesylate group; however, none of the patients required additional treatment. In conclusion, monotherapy with nafamostat mesylate did not improve clinical outcomes in patients with moderate COVID-19. This study did not examine the therapeutic potential of combining nafamostat mesylate with other antiviral agents, and further investigation is required. Because of the high incidence of hyperkalemia, regular laboratory monitoring is required during the use of nafamostat mesylate.

Comparison between Invasive and Non-Invasive Streptococcus agalactiae Isolates from Human Adults, Based on Virulence Gene Profiles, Capsular Genotypes, Sequence Types, and Antimicrobial Resistance Patterns.

This study assessed whether invasive group B Streptococcus (GBS) isolates were similar to non-invasive isolates from adult patients. Invasive and non-invasive GBS isolates were collected from three hospitals and two laboratory centers between January 2015 and October 2019. The isolates were identified by 16S rRNA amplicon sequencing and amplification of the GBS-specific dltS gene. The virulence gene profiles, capsular genotypes, sequence types (STs)/clonal complexes (CCs), and antimicrobial resistance (AMR) phenotypes/genotypes were determined for the 72 invasive and 50 non-invasive isolates that were comparatively analyzed. We observed a significantly decreased rate of rib detection in the invasive isolates compared to that in the non-invasive isolates (77.8% vs. 92.0%, P < 0.05). Additionally, we found significant differences in the prevalence of CC1 (23.6% vs. 46.0%, P < 0.05) and CC26 (12.5% vs. 2.0%, P < 0.05) between invasive and non-invasive populations. However, there were no significant differences in the comparative data of the virulence gene profiles, capsular genotypes, other STs/CCs, and AMR phenotypes/genotypes between the two populations. These findings suggest that both invasive and non-invasive isolates share similar features in terms of virulence gene profile, capsular genotype, ST/CC, and AMR genotype/phenotype (except for the rates of rib detection and CC1/CC26 prevalence).

Breakthrough and persistent bacteremia due to serotype K1 Klebsiella pneumoniae in an immunocompetent patient.

Herein, we report a case of breakthrough and persistent bacteremia due to serotype K1 Klebsiella pneumoniae in an immunocompetent 53- year-old man. He was diagnosed with pyogenic spondylitis owing to back pain and based on magnetic resonance imaging findings. On admission, several imaging studies were taken to search for other abscesses and infective endocarditis; however, there were no significant findings. Additionally, blood cultures were negative. Upon treatment with intravenous ampicillin/sulbactam, the patient's symptoms improved. However, eleven days after admission, the patient experienced a fever and worsening back pain. Blood cultures were taken again, and K. pneumoniae was detected, which showed sensitivity to ampicillin/sulbactam. Fourteen days after admission, K. pneumoniae was detected again, suggesting breakthrough and persistent bacteremia with K. pneumoniae. The source of the K. pneumoniae infection was unknown. The antimicrobial regimen was changed to a combination of ceftriaxone and gentamicin. Sixty days after admission, the patient was discharged without any sequelae. The isolated K. pneumoniae strains were found to carry rmpA and were confirmed as serotype K1; thus, detected hypervirulent K. pneumoniae (HvKP). HvKP is an increasingly recognized pathotype of K. pneumoniae characterized clinically by its ability to cause organ- or life-threatening infections in healthy persons. To the best of our knowledge, our case is the first report of spondylitis due to confirmed HvKP. Moreover, HvKP caused breakthrough and persistent bacteremia on an immunocompetent patient.

Repetitive cellulitis caused by Streptococcus agalactiae isolates with different genotypic and phenotypic features in a patient having upper extremity with lymphedema after mastectomy and axillary lymph node dissection.

Previously reported cases of recurrent cellulitis/erysipelas affecting chronically lymphedematous skin regions have been demonstrated to be due to Streptococcus agalactiae isolates with closely related genetic background which may be suggestive of relapse rather than reinfection. Herein, we report the occurrence of three episodes of repetitive cellulitis caused by S. agalactiae strains with different genotypic and phenotypic characteristics, including different antimicrobial susceptibility patterns (tetracycline, macrolide/lincosamide, and fluoroquinolone classes), in the left upper extremity of a patient with lymphedema, following left mastectomy and axillary lymph node dissection. The genotypic and phenotypic characteristics of the three isolates were confirmed based on the random amplified polymorphic DNA patterns, DNA profiles of virulence factors (bca-rib-bac-lmb-cylE), data on biofilm formation and cell invasion, antimicrobial susceptibility testing results, antimicrobial resistance (AMR) genotypes, and amino acid mutations associated with AMR. These results revealed that reinfection with S. agalactiae, rather than recurrence, occurred during the three episodes. In conclusion, microbiologic studies such as blood cultures or tissue cultures are certainly helpful in the management of recurrent infections or invasive infections such as bacteremia in order to better target antimicrobial therapy, regardless of the data previously presented.

Draft Genome Sequence of Streptococcus canis Clinical Strain TA4, Harboring the M-Like Protein Gene and Isolated in Japan from a Patient with Bacteremia.

Streptococcus canis is an animal-origin ß-hemolytic bacterium that can cause severe infections in animals and occasionally infects humans. Here, we report a draft genome sequence of an S. canis strain harboring the M-like protein gene. This strain was isolated from a patient with bacteremia (reported by Taniyama et al. [D. Taniyama, Y. Abe, T. Sakai, T. Kikuchi, and T. Takahashi, IDCases 7:48-52, 2017, https://doi.org/10.1016/j.idcr.2017.01.002]). The draft genome comprises 2,129,080 bp in 60 contigs.

Pleural empyema and streptococcal toxic shock syndrome due to Streptococcus pyogenes in a healthy Spanish traveler in Japan.

Group A Streptococcus (GAS, Streptococcus pyogenes) causes invasive infections including streptococcal toxic shock syndrome (STSS) and local infections. To our knowledge, this is the first report of a case of an invasive GAS infection with pneumonia and pleural empyema (PE) followed by STSS (disseminated intravascular coagulation [DIC] and acute renal insufficiency) in a healthy male adult. He received combined supportive therapies of PE drainage, anti-DIC agent, hemodialysis, and antimicrobials and eventually made a clinical recovery. GAS isolated from PE was found to have emm1/speA genes, suggestive of a pathogenic strain. Clinicians should be aware of the possibility of this disease entity (pneumonia, PE, and STSS) in healthy male adults as well as children and adult women.

Draft Genome Sequence of Clinical Strain TANI1 of Streptococcus suis Serotype 5 Isolated from a Bacteremia Patient in Japan.

Streptococcus suis is a swine pathogen that causes severe economic damage to the porcine industry. It occasionally evokes zoonotic infection in humans. Here, we report a draft genome sequence of a S. suis serotype 5 strain isolated from a bacteremia patient that was reported by Taniyama et al. (D. Taniyama, M. Sakurai, T. Sakai, T. Kikuchi, and T. Takahashi, IDCases 6:36-38, 2016, https://doi.org/10.1016/j.idcr.2016.09.011).

Human case of bacteremia caused by Streptococcus canis sequence type 9 harboring the scm gene.

Streptococcus canis (Sc) is a zoonotic pathogen that is transferred mainly from companion animals to humans. One of the major virulence factors in Sc is the M-like protein encoded by the scm gene, which is involved in anti-phagocytic activities, as well as the recruitment of plasminogen to the bacterial surface in cooperation with enolase, and the consequent enhancement of bacterial transmigration and survival. This is the first reported human case of uncomplicated bacteremia following a dog bite, caused by Streptococcus canis harboring the scm gene. The similarity of the 16S rRNA from the infecting species to that of the Sc type strain, as well as the amplification of the species-specific cfg gene, encoding a co-hemolysin, was used to confirm the species identity. Furthermore, the isolate was confirmed as sequence type 9. The partial scm gene sequence harbored by the isolate was closely related to those of other two Sc strains. While this isolate did not possess the erm(A), erm(B), or mef(A), macrolide/lincosamide resistance genes, it was not susceptible to azithromycin: its susceptibility was intermediate. Even though human Sc bacteremia is rare, clinicians should be aware of this microorganism, as well as Pasteurella sp., Prevotella sp., and Capnocytophaga sp., when examining and treating patients with fever who maintain close contact with companion animals.

Human case of bacteremia due to Streptococcus suis serotype 5 in Japan: The first report and literature review.

Streptococcus suis is a zoonotic pathogen that can be transferred from pigs to humans. The serotypes 2 and 14 are prevalent among patients with S. suis infections, while other serotypes (i.e., 1, 4, 5, 16, and 24) have been detected in rare human cases. To the best of our knowledge, the present patient handling with raw pork is the first human case of uncomplicated bacteremia due to S. suis serotype 5 in Japan. We confirmed the new sequence type 752 of this isolate. Virulence-associated gene profiling was performed; both sly (encoding the hemolysin suilysin) and mrp (encoding a muramidase-released protein) were detected without amplification of epf (encoding the extracellular factor). Our polymerase chain reaction-based results indicated that this isolate possessed both tet(O), the tetracycline-resistance determinant, and erm(B), the macrolide/lincosamide-resistance determinant. In addition, we provide the review of literature concerning clinical and microbiological features of four human cases of infection due to S. suis serotype 5. Clinicians should be aware of this microorganism when examining and treating patients with fever, who are handling raw pork or having close contact with infected pigs even if they are immunocompetent.