Significance of early diagnosis and surgical management in treating Mycobacterium immunogenum-related pyogenic extensor tenosynovitis: a case report.

BACKGROUND: Non-tuberculous mycobacteria (NTM) are environmental organisms that are increasingly contributing to human infections. Mycobacterium immunogenum, a variant of NTM discovered in 2001, is a rapidly growing mycobacterium that exhibits multidrug resistance. Reports of infections caused by this organism, particularly tenosynovitis in the musculoskeletal system, are limited. CASE PRESENTATION: A 71-year-old female with vesicular pemphigus, undergoing immunosuppressive therapy, presented with a progressively enlarging tumour on the dorsum of her right hand, along with erythematous papules that extended across her right forearm. The specimens of skin tissues and blood cultures revealed the presence of M. immunogenum. Magnetic resonance imaging evaluation led to the diagnosis of pyogenic extensor tenosynovitis. A multidrug regimen, comprising amikacin and clarithromycin, was initiated, followed by synovectomy. The patient underwent a course of 180 days of antimicrobial therapy and demonstrated no signs of disease recurrence one year after treatment completion. CONCLUSION: Early diagnosis and surgical intervention are crucial to prevent the adverse prognostic implications of pyogenic extensor tenosynovitis caused by M. immunogenum. Effective management requires precise microbial identification and susceptibility testing, necessitating collaborative engagement with microbiological laboratories.

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli.

Cefmetazole is active against extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum ß-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.

The first case of clade I Candida auris candidemia in a patient with COVID-19 in Japan.

Candida auris is a health hazard because of its antifungal resistance and the potential to cause healthcare-associated outbreaks. To our knowledge, no previous cases of candidemia caused by C. auris have been reported in Japan. Herein, we report the first known case of clade I C. auris candidemia in a Japanese man with coronavirus disease 2019 (COVID-19) infection who was medically evacuated from the Philippines. A 71-year-old Japanese man traveled to Cebu Island in the Philippines 5 months before admission to our hospital. He contracted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Philippines and was admitted to the intensive care unit (ICU) in a local hospital. During his medical evacuation, we implemented precautions given his history of COVID-19 and pneumonia caused by multi-drug-resistant Acinetobacter baumannii complex. His blood culture revealed that C. auris infection was treated with antifungal agents but he did not survive. No evidence of nosocomial transmission was found among other patients in the ICU. This case study determines that accurate detection of C. auris, appropriate antifungal agent selection, precautions, and patient isolation are crucial to prevent nosocomial outbreaks, especially in patients with a history of multidrug-resistant organism (MDRO) colonization or international hospitalization. Medical professionals should recognize the risk of MDROs in international medical evacuation settings, considering the recent resumption of cross-border travel after the COVID-19 pandemic.

Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry.

OBJECTIVES: Pretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). METHODS: Clients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. RESULTS: In total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80-0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14-0.63) were significantly associated with YFV. CONCLUSIONS: Preventive interventions other than YFV should be offered to older adults.

Importance of early diagnosis and surgical treatment of calcified amorphous tumor-related native valve endocarditis caused by Escherichia coli: a case report.

BACKGROUND: Unlike Escherichia coli bacteremia, which is common, E. coli endocarditis is uncommon, particularly in patients with native valve, leading to its delayed diagnosis. CASE PRESENTATION: We present a case of infective endocarditis caused by E. coli in a 78-year-old Japanese man with type 2 diabetes, involving persistent bacteremia and vegetation on the mitral valve (measuring 18 × 4.2 mm in diameter). He presented with recurrent fever after antimicrobial treatment for pyelonephritis. He received antibiotic therapy for 6 weeks and required surgical removal of a calcified amorphous tumor and vegetation with mitral valvuloplasty 7 days after admission. Despite an episode of multiple cerebral infarctions, he recovered fully from the infection. CONCLUSIONS: Follow-up blood cultures should be performed for Gram-negative bacilli bacteremia among patients with unknown focus and an atypical clinical course after treatment. Early diagnosis and aggressive surgical intervention are paramount to achieving good clinical outcomes.

Genomic insights into virulence factors affecting tissue-invasive Klebsiella pneumoniae infection.

BACKGROUND: The key virulence factors responsible for hypervirulent Klebsiella pneumoniae (hvKp) infection remains elusive. METHODS: We analyzed K. pneumoniae isolates collected between 2017 and 2019 and defined hvKp as a pyogenic infection. Classical K. pneumoniae (cKp) involved a non-invasive infection or uncomplicated bacteremia. Isolates belonging to the K. pneumoniae species complex were excluded. RESULTS: We analyzed 112 isolates, including 19 hvKp, 67 cKp, and 26 colonizers, using whole-genome sequencing. Population genomics revealed that the K1-sequence type (ST) 82 (O1v1) clade was distinct from that of the K1-ST23 (O1v2) clone. The virulence gene profiles also differed between K1-ST82 (aerobactin and rmpA) and K1-ST23 (aerobactin, yersiniabactin, salmochelin, colibactin, and rmpA/rmpA2). The K2 genotype was more diverse than that of K1. A neighboring subclade of K1-ST23 (comprising ST29, ST412, ST36, and ST268) showed multidrug resistance and hypervirulence potentials. Logistic-regression analysis revealed that diabetes mellitus was associated with K. pneumoniae infection (odds ratio [OR]: 4.11; 95% confidence interval [CI]: 1.14-14.8). No significant association was found between hvKp diagnosis and clinical characteristics, such as diabetes mellitus or community acquisition. However, the K1 genotype (OR: 9.02; 95% CI: 2.49-32.7; positive-likelihood ratio [LR]: 4.08), rmpA (OR: 8.26; 95% CI: 1.77-38.5; positive LR: 5.83), and aerobactin (OR: 4.59; 95% CI: 1.22-17.2; positive LR: 3.49) were substantial diagnostic predictors of hvKp. CONCLUSIONS: The K1 genotype, rmpA, and aerobactin are prominent predictors of hvKp, suggesting that further pyogenic (metastatic) infection should be examined clinically. These findings may shed light on key hvKp virulence factors.

Impact of an infectious disease physician-led carbapenem postprescription feedback on prescribing behavior in a Japanese tertiary hospital: A before-after study.

INTRODUCTION: There is an insufficient number of infectious disease (ID) physicians in Japan. Hence, we considered a strategy to implement antimicrobial stewardship under these resource-limited settings. METHODS: We compared carbapenem consumption, measured as days of therapy per 100 patient-days, between 24-month baseline and 12-month intervention periods. During the intervention period, an ID physician provided daily advises to prescribers against prolonged carbapenem use (≥14 days). Additionally, we sent all doctors a table containing the weekly point prevalence aggregate of carbapenem use of each department for 7-13 and ≥ 14 days via e-mail. RESULTS: Among the 1241 carbapenem courses during the intervention period, the ID physician provided a total of 96 instances of feedback regarding carbapenem use for ≥14 days, with an acceptance rate of 76%. After the initiation of the intervention, the trend in monthly carbapenem consumption changed (coefficient: -0.62; 95% CI: -1.15 to -0.087, p = 0.024), and its consumption decreased (coefficient: -0.098; 95% CI: -0.16 to -0.039, p = 0.002) without an increase in the consumption of broad-spectrum antimicrobials or in-hospital mortality. Interestingly, the monthly number of carbapenem courses, but not the duration of carbapenem use, significantly decreased (coefficient: -3.02; 95% CI: -4.63 to -1.42, p = 0.001). The carbapenem-related annual estimated savings after the intervention was $83,745, with a 22% cost reduction. CONCLUSIONS: Our ID physician-led daily intervention with weekly feedback regarding long-term carbapenem use was effective in reducing antimicrobial consumption. Such feedback may be useful in changing the prescribing behavior and promoting appropriate antimicrobial usage even in resource-limited settings.

Molecular analysis of virulence factors of hypermucoviscous Klebsiella pneumoniae in a diabetes patient with multifocal intramuscular and musculoskeletal abscesses.

Unusual community-acquired invasive Klebsiella pneumoniae infection has been reported worldwide, particularly in Asia. Recently, several virulence-associated genes of the isolates have been investigated. We report a case of multifocal intramuscular and musculoskeletal abscesses caused by K. pneumoniae in a 61-year-old male diabetes patient. A string test of the K. pneumoniae isolate, which was recovered from abscesses obtained by surgical debridement and drainage, was positive. We used whole-genome sequencing to analyze the virulence-associated gene profile of the isolate. The isolate belonged to the K2 genotype with sequence type 375. The isolate harbored rmpA and rmpA2, which induce serum resistance (hypermucoviscosity). The isolate also carried siderophores, i.e., aerobactin and salmochelin, which are associated with enhanced bacterial growth. The isolate did not harbor K1-unique virulence factors, such as colibactin, microcin, and yersiniabactin. Our K2 strain harbored a combination of virulence plasmid-associated genes-rmpA/A2 and siderophores (aerobactin and salmochelin). Hence, we advocate that essential molecular virulence factors of isolates that cannot be identified by a string test and capsular serotyping alone may exist.

Disseminated nocardiosis with Nocardia brasiliensis bacteremia in a patient with rheumatoid arthritis using tocilizumab.

Here, we present a case of disseminated nocardiosis, involving pneumonia, percutaneous abscess, and bacteremia, in a 67-year-old Japanese woman. She had also been treated for rheumatoid arthritis with prednisolone, methotrexate, and tocilizumab (interleukin-6 receptor inhibitor). Based on the 16S rRNA sequence analysis and a blast search, we identified the isolate as Nocardia brasiliensis. We discontinued methotrexate and tocilizumab on admission, and administered intravenous antimicrobial combination therapy for 6 weeks, followed by oral trimethoprim-sulfamethoxazole for 12 months, in total. Nocardia bacteremia is rare, often difficult to diagnose, and substantially fatal. However, due to our prompt diagnosis within one day of the onset of symptoms, and administration of appropriate treatment based on antimicrobial susceptibilities, this patient succeeded in surviving the infection. Not only microbiologists but also clinicians should be aware of the characteristic bacterial form of Gram/Kinyoun staining for early recognition of nocardiosis.

Molecular epidemiology of ß-lactamase production in penicillin-susceptible Staphylococcus aureus under high-susceptibility conditions.

Little is known about the prevalence of ß-lactamase production in penicillin-susceptible Staphylococcus aureus isolates under high-susceptibility conditions. We analyzed S. aureus isolates with penicillin G minimum inhibitory concentration (MIC) ≤ 0.12 µg/ml that were recovered from in-/outpatients (n = 108) between 2016 and 2017 in Japan. ß-Lactamase production was detected by nitrocefin-based and Clinical and Laboratory Standards Institute penicillin zone edge testing and blaZ PCR. All isolates were categorized as having penicillin G MIC ≤0.03 µg/ml using an automated system; MICs determined based on the microdilution method were 0.016 µg/ml (2%), 0.03 µg/ml (44%), and 0.06 µg/ml (54%). Notably, no isolates harbored the blaZ gene. The results from the nitrocefin-based and zone edge tests were consistent with those obtained by PCR. S. aureus isolates with penicillin G MIC ≤0.03 µg/ml exhibited a low frequency of ß-lactamase production. Thus, screening for ß-lactamase production may be unnecessary for isolates showing such high susceptibility.

[Unexpected Diseases in Two Patients with False-Positive Dengue Immunoglobulin M Antibody Test Results].

In 2014, an outbreak of 162 domestic dengue fever infections occurred in Tokyo, Japan; the first outbreak of its kind in 70 years. Nineteen of these cases were confirmed in our center. Advancements in diagnostic methods have enabled an earlier diagnosis of dengue fever; however, unfamiliarity with the clinical course and characteristics of diagnostic tests for dengue fever can lead to misdiagnosis. We herein describe 2 cases of Japanese patients with false-positive dengue immunoglobulin M antibody test results, who were finally diagnosed as having dermatomyositis and acute hepatitis A infection, respectively.

Case Report: Borderline Lepromatous Leprosy Therapy Complicated by Type 1 Leprosy Reaction and Adverse Reactions with Dapsone and Clofazimine.

Leprosy is a global health issue, causing long-term functional morbidity and stigma. Rapid diagnosis and appropriate treatment are important; however, early diagnosis is often challenging, especially in nonendemic areas. Here, we report a case of borderline lepromatous leprosy accompanied by dapsone-induced (neutropenia, anemia, and methemoglobinemia) and clofazimine-induced (skin discoloration and ichthyosis) side effects and type 1 leprosy reactions during administration of the multidrug therapy. The patient completely recovered without developing any deformities or visual impairment. To ensure early diagnosis and a favorable outcome, clinicians should be aware of the diminished sensation of skin lesions as a key physical finding and manage the drug toxicities and leprosy reactions appropriately in patients on multidrug therapy.

Effectiveness of primary series, first, and second booster vaccination of monovalent mRNA COVID-19 vaccines against symptomatic SARS-CoV-2 infections and severe diseases during the SARS-CoV-2 omicron BA.5 epidemic in Japan: vaccine effectiveness real-time surveillance for SARS-CoV-2 (VERSUS).

BACKGROUND: This study aimed to evaluate VE of primary, first, and second booster ancestral-strain monovalent mRNA COVID-19 vaccination against symptomatic infections and severe diseases in Japan. METHODS: We conducted a test-negative case-control study. We included medically attended episodes and hospitalizations involving individuals aged ≥16 with signs and symptoms from July to November 2022, when Omicron BA.5 was dominant nationwide. To evaluate VE, we calculated adjusted ORs of vaccination among test-positive versus test-negative individuals using a mixed-effects logistic regression. RESULTS: For VE against symptomatic infections among individuals aged 16 to 59, VE of primary vaccination at > 180 days was 26.1% (95% CI: 10.6-38.8%); VE of the first booster was 58.5% (48.4-66.7%) at ≤90 days, decreasing to 41.1% (29.5-50.8%) at 91 to 180 days. For individuals aged ≥60, VE of the first booster was 42.8% (1.7-66.7%) at ≤90 days, dropping to 15.4% (-25.9-43.2%) at 91 to 180 days, and then increasing to 44.0% (16.4-62.5%) after the second booster. For VE against severe diseases, VE of the first and second booster was 77.3% (61.2-86.7%) at ≤90 days and 55.9% (23.4-74.6%) afterward. CONCLUSION: mRNA booster vaccination provided moderate protection against symptomatic infections and high-level protection against severe diseases during the BA.5 epidemic in Japan.

Diagnostic and Therapeutic Challenges in Disseminated Mycobacterium colombiense Infection Caused by Interferon-γ Neutralizing Autoantibodies.

Adult-onset immunodeficiency due to interferon-γ-neutralizing autoantibodies (nIFNγ-autoAbs) can remain underdiagnosed. We present a case of severe Mycobacterium colombiense infection with nIFNγ-autoAbs. To ensure early diagnosis, clinicians should have a high index of suspicion in patients of Asian descent with opportunistic infections and perform QuantiFERON-TB assay for disease screening.

Minocycline-Induced Hyperpigmentation: Importance of Early Diagnosis.

A 75-year-old woman on hemodialysis for end-stage renal failure due to polycystic kidney disease developed dark spots on her limbs. She had been treated for extended spectrum beta-lactamase-producing Escherichia coli bacteremia by a rectovaginal fistula and was on long-term oral minocycline (cumulative dose 45 g). Physical examination revealed dark patches on her forearms and lower legs but no trunk hyperpigmentation or visual impairment. Blood tests were normal. Skin biopsy confirmed minocycline-induced hyperpigmentation. Minocycline-induced pigmentation is categorized into types I-IV, each with unique clinical and histopathological features. Types I and II are reversible upon discontinuing minocycline, whereas types III and IV are permanent. The patient was diagnosed with type II pigmentation, generally occurring with a cumulative dose exceeding 70-100 g; however, her lower dose (45 g) led to pigmentation, possibly influenced by her vitamin D deficiency. Clinicians should evaluate the antimicrobial indication and treatment period, considering not only the benefits but also the side effects and antimicrobial resistance. If minocycline is used, attention should be paid to minocycline-induced hyperpigmentation, and this possibility should be communicated to patients to enable early detection.

Preparation and isolation of mono-Nb substituted Keggin-type phosphomolybdic acid and its application as an oxidation catalyst for isobutylaldehyde and Wacker-type oxidation.

The potassium and proton mixed salt of mono-Nb substituted Keggin-type phosphomolybdate, KH3[PMo11NbO40], was isolated in a pure form by reacting Keggin-type phosphomolybdic acid (H3[PMo12O40]) and potassium hexaniobate (K8Nb6O19) in water, followed by freeze-drying. The all protonic form, H4[PMo11NbO40], was isolated via proton exchange with H-resin and subsequent freeze-drying. The most crucial factor to isolate KH3[PMo11NbO40] and H4[PMo11NbO40] in pure forms is the evaporation of water using the freeze-drying method. Using a similar procedure, the potassium salt of the di-Nb substituted compound K5[PMo10Nb2O40] was isolated. H4[PMo11NbO40] exhibited high catalytic activity for oxidizing isobutylaldehyde to methacrolein and moderate catalytic activity for the Wacker-type oxidation of allyl phenyl ether when combined with Pd(OAc)2.

Diagnostic accuracy of quick SOFA score and inflammatory biomarkers for predicting community-onset bacteremia.

The potential use of quick SOFA (qSOFA) score and inflammatory biomarkers as bacteremia predictors is unelucidated. Herein the aim of this study was to evaluate the diagnostic accuracy of the qSOFA score and biomarkers for predicting community-onset bacteremia. We enrolled adult outpatients with blood culture samples drawn between 2018 and 2020. Contamination, intensive care unit admission, and hemodialysis were excluded. We performed a case-control study, and analyzed 115 patients (58 with bacteremia and 57 without bacteremia). The positive likelihood ratio (LR) for bacteremia was 2.46 (95% confidence interval [CI] 0.76-9.05) for a qSOFA score ≥ 2, and 4.07 (95% CI 1.92-9.58) for tachypnea (≥ 22/min). The highest performing biomarkers were procalcitonin (area under the curve [AUC] 0.80; 95% CI 0.72-0.88), followed by presepsin (AUC 0.69; 95% CI 0.60-0.79), and C-reactive protein (AUC 0.60; 95% CI 0.49-0.70). The estimated optimal cut-off value of procalcitonin was 0.377 ng/mL, with a sensitivity of 74.1%, a specificity of 73.7%, and a positive LR of 2.82. Presepsin was 407 pg/mL, with a sensitivity of 60.3%, a specificity of 75.4%, and a positive LR of 2.46. Procalcitonin was found to be a modestly useful biomarker for predicting non-severe community-onset bacteremia. Tachypnea (≥ 22/min) itself, rather than the qSOFA score, can be a diagnostic predictor. These predictors may aid decision-making regarding the collection of blood culture samples in the emergency department and outpatient clinics.