Clinical and Microbiological Characteristics of Bacteremia Caused by Carbapenemase-producing Enterobacterales in Minami Ibaraki Area, Japan.

Although recent propagation of carbapenemase-producing Enterobacterales (CPE) has become a problem worldwide, the picture of CPE infection in Japan has not fully been elucidated. In this study, we examined clinical and microbiological characteristics of invasive CPE infection occurring at 8 hospitals in Minami Ibaraki Area between July 2001 to June 2017. Of 7294 Enterobacterales strains isolated from independent cases of bacteremia and/or meningitis, 10 (0.14%) were CPE (8 Enterobacter cloacae-complex, 1 Escherichia coli, and 1 Edwardsiella tarda）, all of which had the blaIMP-1 gene and susceptible to gentamicin and trimethoprim/sulfamethoxazole. These strains were isolated from 7 adult and 2 infant bacteremia (1 infant patient developed CPE bacteremia twice) after 2007. The most common portal of entry was intravenous catheters. All of the adult patients were recovered, while the infant patients eventually died. Genomic analyses showed that the 8 E. cloacae-complex strains were classified into 5 groups, each of which was exclusively detected in specific facilities at intervals of up to 3 years, suggesting persistent colonization in the facilities. This study showed that invasive CPE infection in the area was rare, caused by IMP-1-type CPE having susceptibility to various antibiotics, and nonfatal among adult patients.

To treat or not to treat: Assessing the role of anti-enterococcal therapy for intra-abdominal infections in patients with cancer.

The clinical significance of enterococci in intra-abdominal infections, particularly those caused by multiple organisms, remains unclear. There are no definitive guidelines regarding the use of empiric therapy with antimicrobial agents targeting enterococci. In this study, we evaluated the impact of the initial antimicrobial therapy administration of anti-enterococcal agents on the treatment of intra-abdominal infections in patients with cancer in whom enterococci were isolated from ascitic fluid cultures. This retrospective study was conducted at Shizuoka Cancer Center between January 1, 2014, and December 31, 2020, on all adult patients with cancer with enterococci in their ascitic fluid cultures. The primary outcome was all-cause mortality, and the secondary outcomes were composite outcomes consisting of three components (mortality, recurrence, and treatment failure) and the risk factors associated with all-cause mortality and composite outcomes. In total, 103 patients were included: 61 received treatment covering enterococci, and 42 did not. The mortality rates did not differ significantly between the treated and untreated groups (treated: 8/61 [13.1%]; untreated: 5/42 [11.9%]; p = 1.00). Additionally, no significant difference was observed between the groups in terms of composite outcomes (treated group: 11/61 [18.0%]; untreated group: 9/42 [21.4%]; p = 0.80). Multivariate analysis showed that performance status (PS2-4; p < 0.0001) was an independent risk factor for mortality. The composite outcome was also significantly higher for PS2-4 (p = 0.007). Anti-enterococcal treatment was not associated with mortality or the composite outcome. In patients with cancer and intra-abdominal infections caused by enterococci, anti-enterococcal therapy was not associated with prognosis, whereas PS2 or higher was associated with prognosis. The results of this study suggest that the initial routine administration of anti-enterococcal agents for intra-abdominal infections may not be essential for all patients with cancer. To substantiate these findings, validation by a prospective randomized trial is warranted.

Distribution of ticks and their possession of spotted fever group Rickettsia in Ibaraki prefecture.

INTRODUCTION: Tick-borne diseases (TBDs) are a growing threat in Japan. However, distribution of ticks and their possession of human pathogens remain poorly understood. METHODS: In the present study, we collected 3477 ticks at 6 remote, woodland sites in Ibaraki prefecture between May 23 and November 4, 2021, and investigated the distribution and the possession of spotted fever group Rickettia (SFGR). RESULTS: The collected ticks included Haemaphysalis flava (78.3 %), Haemaphysalis longicornis (9.0 %), Haemaphysalis hystricis (4.6 %), Ixodes turdus (4.3 %), Amblyomma testudinarium (2.1 %), Haemaphysalis cornigera (0.9 %), Haemaphysalis formosensis (0.9 %), Haemaphysalis megaspinosa (0.2 %), Ixodes ovatus (0.1 %), Ixodes nipponensis (0.09 %), and Ixodes columnae (0.03 %). Of 2160 DNA samples extracted from the ticks, the gltA gene and the 17-kDa antigen gene of SFGR were detected in 67 samples. Among 1682 samples from adult and nymph ticks, the positive rate of SFGR was 2.7 %. Sequence analyses of the partial 17-kDa antigen gene demonstrated that the detected SFGR were classified into 8 groups (G1 to G8). The sequences of G2, G4, G5, G6, and G7 were either identical to or differed by one base pair from those of Rickettsia asiatica, Rickettsia tamurae, Rickettsia monacensis, Rickettsia canadensis, and Rickettsia felis, respectively. CONCLUSION: The present study revealed a diverse tick fauna in Ibaraki prefecture, including detection of species commonly found in southwestern Japan. Although the prevalence of SFGR in ticks was lower than in previous studies, several SFGR causing human infection may be present.

Prospective study of three saliva qualitative antigen testing kits for the detection of SARS-CoV-2 among mainly symptomatic patients in Japan.

INTRODUCTION: Rapid qualitative antigen testing has been widely used for the laboratory diagnosis of COVID-19 with nasopharyngeal samples. Saliva samples have been used as alternative samples, but the analytical performance of those samples for qualitative antigen testing has not been sufficiently evaluated. METHODS: A prospective observational study evaluated the analytical performance of three In Vitro Diagnostics (IVD) approved COVID-19 rapid antigen detection kits for saliva between June 2022 and July 2022 in Japan using real-time reverse transcription polymerase chain reaction (RT-qPCR) as a reference. A nasopharyngeal sample and a saliva sample were simultaneously obtained, and RT-qPCR was performed. RESULTS: In total, saliva samples and nasopharyngeal samples were collected from 471 individuals (RT-qPCR-positive, n = 145) for the analysis. Of these, 96.6% were symptomatic. The median copy numbers were 1.7 × 106 copies/mL for saliva samples and 1.2 × 108 copies/mL for nasopharyngeal samples (p < 0.001). Compared with the reference, the sensitivity and specificity were 44.8% and 99.7% for ImunoAce SARS-CoV-2 Saliva, 57.2% and 99.1% for Espline SARS-CoV-2 N, and 60.0% and 99.1% for QuickChaser Auto SARS-CoV-2, respectively. The sensitivities of all antigen testing kit were 100% for saliva samples with a high viral load (>107 copies/mL), whereas the sensitivities were <70% for high-viral-load nasopharyngeal samples (>107 copies/mL). CONCLUSION: COVID-19 rapid antigen detection kits with saliva showed high specificity, but the sensitivity varied among kits, and were also insufficient for the detection of symptomatic COVID-19 patients.

Analytical performance of the rapid qualitative antigen kit for the detection of SARS-CoV-2 during widespread circulation of the Omicron variant.

INTRODUCTION: Rapid qualitative antigen testing is essential in the clinical management of COVID-19. However, most evaluations of antigen tests have been performed before the emergence of the Omicron variant. METHODS: This prospective observational study evaluated QuickNavi-COVID19 Ag, a rapid antigen detection test between December 2021 and February 2022 in Japan, using real-time reverse transcription (RT)-PCR as a reference. Two nasopharyngeal samples were simultaneously collected for antigen testing and for RT-PCR. Variant analysis of the SARS-CoV-2 genomic sequencing was also performed. RESULTS: In total, nasopharyngeal samples were collected from 1073 participants (417 positive; 919 symptomatic; 154 asymptomatic) for analysis. Compared with those of RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 94.2% (95% CI: 91.6%-96.3%), 99.5% (95% CI: 98.7%-99.9%), 99.2% (95% CI: 97.8%-99.8%), and 96.5% (95% CI: 94.8%-97.7%), respectively. The sensitivity among symptomatic individuals was 94.3% (95% CI: 91.5%-96.4%). Overall, 85.9% of sequences were classified as Omicron sublineage BA.1, 12.4% were Omicron sublineage BA.2, and 1.6% were Delta B.1.617.2. (Delta variant). Most of the samples (87.1%) had Ct values of <25, and the sensitivity was 47.4% for low viral load samples (Ct ≥ 30); a similar trend has been observed in both symptomatic and asymptomatic groups. CONCLUSIONS: The QuickNavi-COVID19 Ag test showed sufficient diagnostic performance for the detection of the SARS-CoV-2 Omicron sublineages BA.1 and BA.2 from nasopharyngeal samples. However, the current study was mainly performed in symptomatic patients and the results are not sufficiently applicable for asymptomatic patients.

Clinical Performance of the cobas Liat SARS-CoV-2 & Influenza A/B Assay in Nasal Samples.

BACKGROUND AND OBJECTIVE: Point-of-care type molecular diagnostic tests have been used for detecting SARS-CoV-2, although their clinical utility with nasal samples has yet to be established. This study evaluated the clinical performance of the cobas Liat SARS-CoV-2 & Influenza A/B (Liat) assay in nasal samples. METHODS: Nasal and nasopharyngeal samples were collected and were tested using the Liat, the cobas 6800 system and the cobas SARS-CoV-2 & Influenza A/B (cobas), and a method developed by National Institute of Infectious Diseases, Japan (NIID). RESULTS: A total of 814 nasal samples were collected. The Liat assay was positive for SARS-CoV-2 in 113 (13.9%). The total, positive, and negative concordance rate between the Liat and cobas/NIID assays were 99.3%/98.4%, 99.1%/100%, and 99.3%/98.2%, respectively. Five samples were positive only using the Liat assay. Their Ct values ranged from 31.9 to 37.2. The Ct values of the Liat assay were significantly lower (p < 0.001) but were correlated (p < 0.001) with those of other molecular assays. In the participants who tested positive for SARS-CoV-2 on the Liat assay using nasopharyngeal samples, 88.2% of their nasal samples also tested positive using the Liat assay. CONCLUSION: The Liat assay showed high concordance with other molecular assays in nasal samples. Some discordance occurred in samples with Ct values > 30 on the Liat assay.

A prospective clinical evaluation of the diagnostic accuracy of the SARS-CoV-2 rapid antigen test using anterior nasal samples.

INTRODUCTION: The diagnostic accuracy of antigen testing of anterior nasal (AN) samples for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has not been evaluated in the Japanese population. This study assessed the diagnostic accuracy of the Roche SARS-CoV-2 rapid antigen test (rapid antigen test) using AN samples. METHODS: Two AN samples and one nasopharyngeal (NP) sample were collected from individuals undergoing screening for SARS-CoV-2 infection. The results of the rapid antigen test and the reverse-transcription polymerase chain reaction (RT-PCR) test using AN samples were compared to those of RT-PCR tests using NP samples. RESULTS: Samples were collected from 800 participants, 95 and 110 of whom tested positive for SARS-CoV-2 on RT-PCR tests of AN and NP samples, respectively. The overall sensitivity/specificity of the AN rapid antigen test and AN RT-PCR were 72.7%/100% and 86.4%/100%, respectively. In symptomatic cases, the sensitivities of the AN rapid antigen test and AN RT-PCR were 84.7% and 94.9%, respectively. In asymptomatic cases, the sensitivities of the AN rapid antigen test and AN RT-PCR were 58.8% and 76.5%, respectively. The sensitivity of the AN rapid antigen test was over 80% in cases with cycle threshold (Ct) values < 25; it significantly decreased with an increase in the Ct values (p < 0.001). CONCLUSION: The rapid antigen test with AN samples had a favorable sensitivity, especially in symptomatic cases or in cases with Ct values < 25. It gave no false-positive results. Compared with AN-RT PCR, the AN rapid antigen test had a modestly lower sensitivity in asymptomatic cases.

A prospective evaluation of diagnostic performance of a combo rapid antigen test QuickNavi-Flu+COVID19 Ag.

INTRODUCTION: Since respiratory sample collection is an uncomfortable experience, simultaneous detection of pathogens with a single swab is preferable. We prospectively evaluated the clinical performance of a newly developed antigen test QuickNavi-Flu+COVID19 Ag (Denka Co., Ltd., Tokyo, Japan) which can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses at the same time with a single testing device. METHODS: We included those who were suspected of contracting coronavirus disease 2019 (COVID-19) and were referred to a PCR center at Ibaraki prefecture in Japan, between August 2, 2021 to September 13, 2021, when the variant carrying L452R spike mutation of SARS-CoV-2 were prevalent. Additional nasopharyngeal samples and anterior nasal samples were obtained for the antigen test and were compared with a reference real-time reverse transcription PCR (RT-PCR) using nasopharyngeal samples. RESULTS: In total, 1510 nasopharyngeal samples and 862 anterior nasal samples were evaluated. During the study period, influenza viruses were not detected by QuickNavi-Flu+COVID19 Ag and reference real-time RT-PCR. For SARS-CoV-2 detection in nasopharyngeal samples, the sensitivity and specificity of the antigen test were 80.9% and 99.8%, respectively. The sensitivity and specificity using anterior nasal samples were 67.8% and 100%, respectively. In symptomatic cases, the sensitivities increased to 88.3% with nasopharyngeal samples and 73.7% with anterior nasal samples. There were three cases of discrepant results between the antigen test and the real-time RT-PCR. All of them were positive with the antigen test but negative with the real-time RT-PCR in SARS-CoV-2 detection. CONCLUSION: A combo kit, QuickNavi-Flu+COVID19 Ag, showed an acceptable sensitivity and sufficient specificity for SARS-CoV-2 detection, especially using nasopharyngeal sample collected from symptomatic patients.

Effectiveness of oral antibiotics for treating pyelonephritis caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: A case series.

BACKGROUND: Recently, the spread of multidrug-resistant bacteria has become a global problem. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae (enterobacteria) is one example. The incidence of urinary tract infections caused by ESBL-producing enterobacteria has been increasing in some Japanese community settings. Currently, there is insufficient evidence on the effectiveness of oral antibiotics used for the treatment of pyelonephritis caused by ESBL-producing enterobacteria. We investigated the effectiveness of oral antibacterial agents against pyelonephritis caused by ESBL-producing Enterobacteriaceae. METHODS: The records of patients who had been treated for pyelonephritis caused by ESBL-producing enterobacteria with oral antibiotics between April 1, 2014, and March 31, 2019, were reviewed retrospectively to assess the effectiveness of oral antibiotic treatment. RESULTS: A total of seven cases were identified, including 1 patient with a positive blood culture and one patient with a Pitt bacteremia score of four points, indicating that the infections were severe. The antibiotics used to treat pyelonephritis were amoxicillin-clavulanic acid (n = 3), minocycline (n = 1), levofloxacin (n = 3), and sulfamethoxazole-trimethoprim with amoxicillin-clavulanic acid (n = 1). None of the patients had recurrence of pyelonephritis in the 60 days following oral antibiotic treatment, and there were no deaths during the 60-day follow-up period. CONCLUSIONS: These antibiotics should be considered for oral treatment of pyelonephritis caused by ESBL-producing enterobacteria. However, as there is insufficient evidence available on the effectiveness of these antibiotics for the management of ESBL-producing enterobacterial infections, further large-scale prospective studies are needed.

Neisseria macacae bacteremia: report of two cases with a literature review.

BACKGROUND: Neisseria macacae was discovered in the oral cavity of monkeys in 1983. In humans, it has been isolated from the upper respiratory tract of neutropenic patients. However, only two cases of N. macacae bacteremia have been reported in a 65-year-old man with infective endocarditis and a 5-month-old child with fever and petechiae. There are no reports of infections in cancer patients. Here, we present two cases of N. macacae bacteremia in cancer patients. CASE PRESENTATION: In the first case, a 42-year-old woman who underwent ovarian cancer surgery presented with duodenal invasion associated with multiple lymph node metastasis. N. macacae was isolated from her blood culture and identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). In the second case, a 69-year-old woman with a long-standing history of esophagogastric junction cancer presented with fever. She had stage IVB cancer with lung, bone, and multiple lymph node metastasis. The last chemotherapy was administered 5 weeks before N. macacae was detected using MALDI-TOF MS and nitrate test negative. In both cases, transthoracic echography showed no vegetation. Antibiotics were administered for 14 and 13 days in the first and second cases, respectively. In both cases, fever alleviated on day 4 of antibiotic administration. Both patients were discharged after their conditions improved. CONCLUSIONS: This, to our knowledge, is the first report of N. macacae bacteremia in cancer patients. Both patients, mucosal damage was observed in the upper gastrointestinal tract. Therefore, exclusion diagnosis suggested that bacteremia invasion was caused by mucosal rupture in both cases. Both cases responded well to treatment with ß-lactam antibiotics and improved after 2 weeks. Modifying the treatment based on the source of the infection may shorten the treatment period. Therefore, further research on N. macacae bacteremia is necessary. Immunocompromised patients such as those with cancer are susceptible to mucosal damage by unusual bacterial species such as N. macacae despite not having contact with monkeys.

Infectious disease specialist consultations in a Japanese cancer center: a retrospective review of 776 cases.

BACKGROUND: Little is known about the impact of infectious disease (ID) consultations on the management of patients with cancer. This study aimed to describe the consultation services provided by ID specialists to all departments in a comprehensive cancer center in Japan. METHODS: We conducted a retrospective review of ID consultations with adult patients at a comprehensive cancer center in Japan from April 2017 to March 2018. RESULTS: During the study period, 776 patients with cancer had an ID consultation. Of these, 414 (53.4%) were hospital inpatients. Reasons for the ID consultation comprised clinical management (n = 481, 62.0%), immunization (n = 272, 35.1%), and infection control (n = 23, 3.0%). Of the 474 ID consultations for diagnostic purposes, the most frequent condition was fever or elevated inflammatory markers of unknown origin (n = 125, 26.4%). The most frequent diagnoses after the diagnostic ID consultation were hepatobiliary infections (n = 97, 22.4%), respiratory infections (n = 89, 20.618.8%), and intra-abdominal infections (n = 71, 16.4%). The commonest reasons for immunization consultations were to prevent seasonal influenza (n = 193, 71.0%) and post-splenectomy vaccination (n = 58, 21.3%). The commonest reasons for infection control consultations were suspected tuberculosis or contact with tuberculosis (n = 11, 47.8%) and herpes zoster infection (shingles) (n = 7, 30.4%). CONCLUSIONS: ID specialists play an important role in the clinical management of patients with cancer. ID physicians who work in cancer centers need to be specialized in treating IDs, diagnosing the causes of fevers of unknown origin, and controlling infection.

Treatable Bedridden Elderly -Recovery from Flexion Contracture after Cortisol Replacement in a Patient with Isolated Adrenocorticotropic Hormone Deficiency.

Isolated adrenocorticotropic hormone deficiency (IAD) is a rare disorder with diverse clinical presentations. A 79-year-old man was bedridden for six months due to flexion contractures of the bilateral hips and knees, along with hyponatremia. He was diagnosed with IAD based on the results of endocrine tests. After one month of corticosteroid replacement, he recovered and was able to stand up by himself. Although flexion contracture is a rare symptom of IAD, steroid replacement therapy may be effective, even for seemingly irreversibly bedridden elderly patients. In bedridden elderly patients with flexion contractures, we should consider and look for any signs of adrenal insufficiency.

Wernicke encephalopathy and pellagra in an alcoholic and malnourished patient.

Deficiency of multiple vitamins can be identified in alcoholic and malnourished patients. We report a patient with Wernicke encephalopathy, a B1 deficiency and pellagra, a niacin deficiency. A 61-year-old Japanese man presented with generalised weakness. He had drunk alcohol heavily for more than a year without eating adequate meals. Physical examination showed disorientation, eye movement impairment, muscle wasting and a rash over the limbs. Multivitamin supplementations improved all the symptoms. Pellagra causes dementia, diarrhoea, or dermatitis, and can mimic non-specific erythaema in alcoholics. The differential diagnosis between pellagra and non-specific erythaema is important because of the treatability of pellagra by niacin supplementation.

The close relationship between heparanase and cyclooxygenase-2 expressions in signet-ring cell carcinoma of the stomach.

Signet-ring cell carcinoma (SRC) of the stomach exhibits diffuse growth and invasion without forming ducts. Destruction of the surrounding basal membrane and angiogenesis appear to be required for SRC to exhibit marked invasion and growth. We recently reported that heparanase (HPA) and cyclooxygenase-2 (COX-2) were strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in SRC of the stomach. We examined HPA and COX-2 expression in 3 cell lines derived from SRC of the stomach and in 50 SRC lesions of stomach by immunohistochemistry (IHC), in situ hybridization, and reverse transcriptase-polymerase chain reaction (RT-PCR). We also examined the relationships among HPA expression, COX-2 expression, and the clinicopathologic features of SRC, mean age, sex, invasion depth, regional lymph node metastasis, lymphatic invasion, and venous blood vessel invasion. Of the 3 cell lines, 2 exhibited both HPA and COX-2 mRNA expression on RT-PCR. Of the 3 cell lines, 1 exhibited only HPA mRNA expression on RT-PCR. Heparanase expression was confirmed in 23 (46%) of 50 tumor samples by IHC. COX-2 expression was confirmed in 25 (50%) of the 50 tumor samples by IHC. In situ hybridization revealed messenger RNA expression in the same area as in that revealed by IHC. A close correlation was noted between HPA and COX-2 expressions (P < .0001). The present study thus elucidated the biologic features of SRC of the stomach related to growth and angiogenesis.