Infection and Chemotherapy最新文献

Background: We aimed to identify the genes of 35 pathogens, including viruses, bacteria, and protozoa that cause waterborne infectious diseases, and to assess the feasibility of a wastewater-based surveillance system.

Materials and methods: Wastewater was aseptically sampled once a month from 2 sites. A total of 1 L of wastewater from each site underwent 0.2 µm filtration to generate the sample A. Subsequently, 200 ul of the filtered water was ultra-filtered and concentrated to generate the sample B, which was mixed with sample A in a 1:1 ratio. We performed a Filmarray^® Gastrointestinal (GI) panel (BioFire Diagnnostics', Salt Lake City, UT, USA) test to simultaneously detect 13 enterobacteria, 5 enterovirus, and 4 protozoa. RNA was extracted to assess 18 types of viruses.

Results: Severe acute respiratory syndrome coronavirus 2 adenovirus, bocavirus, and rhinovirus was detected at both site. Norovirus GI/GII was continuously detected at both sites. Moreover, adenovirus, group A rotaviruses, and hepatitis A virus were frequently detected; however, hepatitis E virus was absent at either site. Campylobacter, enteroaggregative Escherichia coli, enterotoxigenic E. coli, Shiga toxin-producing E. coli, and Clostridioides difficile toxin A/B were detected at both sites. Giardia lamblia was also detected in both sites.

Conclusion: We analyze multiple infectious disease pathogens under sample surveillance with incidence. Further in-depth studies on wastewater-based surveillance will be feasible and important.

Background: Pyrazinamide (PZA) is often used as an add-on agent in the treatment of multidrug-resistant tuberculosis, regardless of phenotypic drug susceptibility testing (pDST) results. However, evaluating the effectiveness of PZA is challenging because of its low pH activity, which can result in unreliable pDST results. This study aimed to investigate the genomic characteristics associated with PZA resistance that can be used to develop genotypic DST.

Materials and methods: A publicly available whole genome sequencing (WGS) dataset of 10,725 Mycobacterium tuberculosis complex genomes (3,326 phenotypically PZA-resistant and 7,399 phenotypically PZA-susceptible isolates) were analyzed.

Results: In total, 2,934 pncA non-silent mutations were identified in 2,880 isolates (26.9%). Detected mutations were found throughout the entire coding region of pncA in a scattered pattern, of which the most frequent mutation was p.Q10P (n = 278), followed by p.H57D (n = 167) and c.-11A>G (n = 122). The sensitivity and specificity of the group 1 or 2 mutations reported by the World Health Organization (WHO) mutational catalogue were 73.0% and 98.9%, respectively. We further identified 18 novel pncA mutations that were significantly associated with phenotypically PZA-resistant. In addition to these mutations, we identified 102 large deletions in the pncA gene, and all but two isolates were phenotypically resistant to PZA isolates. Notably, pncA deletions were mutually exclusive to pncA mutations, and more than half of the isolates with pncA large deletions belonged to the East Asian lineage (67.6%). The sensitivity, specificity, positive predictive value, and negative predictive value of the pooled variants (group 1 or 2 mutations, novel resistance-associated mutations, and large deletions of the pncA gene) were 79.0%, 98.9%, 97.0%, and 91.3%, respectively. The area under the curve (AUC) value for the pooled variants was significantly higher than the AUC value for the group 1 or 2 mutations (P <0.001), indicating that the pooled variants have a better discriminative ability for predicting PZA resistance.

Conclusion: Using WGS, we found that the pncA mutations are scattered without specific mutational hotspots, and large deletions associated with PZA resistance are more common in the East Asian lineage of M. tuberculosis isolates. Our data also demonstrated the reliability of group 1 or 2 mutations presented in the WHO mutation catalogue and the need for further investigation on group 3 mutations, contributing to the evaluation of the current knowledge base on mutations associated with the PZA-resistant M. tuberculosis complex.

In patients recovering from coronavirus disease 2019 (COVID-19) pneumonia, respiratory symptoms and radiographic pneumonic infiltrate occasionally persist for many weeks even after viral clearance; thereby, making it difficult to decide on an appropriate treatment. Here, we describe a 46-year-old woman with COVID-19 pneumonia who had persistent radiographic pneumonic infiltration and respiratory symptoms for almost 4 weeks after illness onset, despite viral clearance, and was subsequently diagnosed with secondary organizing pneumonia (SOP) using video-assisted thoracoscopic (VATS) wedge lung biopsy. Intravenous methylprednisolone was administered at an initial dose of 50 mg/day (1 mg/kg) for 7 days and was tapered to a dose of prednisolone 30 mg/day following improvement in the patient's respiratory symptoms and chest radiographic findings. The patient was discharged from the hospital 14 days after the initiation of corticosteroid treatment. The dose of prednisolone was tapered monthly to 20, 15, 10, and 5 mg/day, respectively, at the outpatient clinic for a total duration of 6 months; nearly resolved pneumonic infiltrations were observed in a follow-up computed tomography scan approximately 2 months after she was admitted. To the best of our knowledge, this is the first case report of a COVID-19 associated SOP that was pathologically confirmed through VATS wedge lung biopsy in Korea. SOP should be considered in the differential diagnosis of patients with COVID-19 pneumonia with persistent respiratory symptoms and radiographic pneumonic infiltrations during the recovery phase to avoid the redundant use of antimicrobial or antiviral agents. Furthermore, histological confirmation is essential for the definitive diagnosis of SOP to avoid unnecessarily prolonged corticosteroid treatment.

Outer membrane vesicles (OMVs) are spherical bilayered nanoparticles derived from the outer layer of Gram-negative bacteria. Bacteria communicate with nearby bacteria, their environment, and the cells of their host by secreting OMVs, which are essential for their survival. OMVs also play a critical role in bacterial pathogenesis since they are loaded with virulence factors, toxins, and enzymes. OMVs may modulate the immune response of the host by initiating inflammation through cytokine production and activating the innate immune response. OMVs also contribute to the resistance of bacteria to antibiotics by carrying antibiotic-degrading enzymes and acting as natural protection barriers. Concerns have also been raised regarding OMVs mediating the transfer of antibiotic resistance. Due to their advantageous properties, OMVs are attractive platforms for vaccine discovery and drug delivery research. In this review, we discuss the fundamental structure and biogenesis mechanisms of OMVs as well as their multifaceted roles in bacterial infection pathogenesis and host immune responses. We also discuss application examples of OMVs.

Background: Determination of the release from isolation for coronavirus disease 2019 (COVID-19) in immunocompromised patients who need additional hospitalization for treatment of non-COVID-19 related disease is important to prevent nosocomial transmission. However, there is insufficient evidence for an extended isolation period.

Materials and methods: In September 2021, when the Delta variant was dominant, a nosocomial outbreak of COVID-19 occurred in the nephrology ward of a tertiary hospital in Gwangju, Korea. We conducted epidemiological investigations and whole-genome sequencing (WGS) of this virus.

Results: A man who underwent kidney transplantation was admitted to our hospital for the treatment of acute kidney injury. He was diagnosed with asymptomatic COVID-19 infection during a pre-admission screening test on September 1, 2021 and underwent isolation. After 10 days of isolation in the COVID-19-designated ward, he was transferred to the general nephrology ward. He underwent steroid pulse therapy (September 17 to September 23, >60 mg/day prednisolone) due to acute T-cell rejection. On September 28, 2021, the first patient with COVID-19 was identified in the nephrology ward, and a rapid-response team was activated to identify additional patients with COVID-19 and prevent the spread of COVID-19. Epidemiological investigations revealed that 12 patients, two caregivers, and three healthcare workers from the nephrology ward were diagnosed with COVID-19. The WGS of specimens from 14 nosocomial outbreak samples and released an index patient exhibited the same Delta variant originating from the B.1.617.2 lineage. This hospital-acquired COVID-19 outbreak in the nephrology ward resulted in two (11.7%) deaths in patients who underwent kidney transplantation.

Conclusion: We demonstrated that an immunocompromised patient can cause a nosocomial outbreak due to the prolonged shedding of infectious viruses. Prolonged isolation in patients under active immunosuppressive therapy may be necessary to prevent transmission, especially in the hospital setting.

Although invasive fungal diseases are relatively less common than superficial diseases, there has been an overall increase in their incidence. Here, I review the epidemiology, diagnosis, and treatment of invasive mold diseases (IMDs) such as aspergillosis, mucormycosis, hyalohyphomycosis, and phaeohyphomycosis. Histopathologic demonstration of tissue invasion by hyphae or recovery of mold by the culture of a specimen obtained by a sterile procedure provides definitive evidence of IMD. If IMD cannot be confirmed through invasive procedures, IMD can be diagnosed through clinical criteria such as the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Instituteof Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definitions. For initial primary therapy of invasive aspergillosis, voriconazole or isavuconazole is recommended and lipid formulations of amphotericin B are useful primary alternatives. Echinocandins are representative antifungal agents for salvage therapy. Treatment of invasive mucormycosis involves a combination of urgent surgical debridement of involved tissues and antifungal therapy. Lipid formulations of amphotericin B are the drug of choice for initial therapy. Isavuconazole or posaconazole can be used as salvage or step-down therapy. IMDs other than aspergillosis and mucormycosis include hyalohyphomycosis and phaeohyphomycosis, for which there is no standard therapy and the treatment depends on the clinical disease and status of the patient.

Multisystem inflammatory syndrome in adults (MIS-A) is a rare sequelae after coronavirus disease 2019 (COVID-19) that is characterized by fever as well as cardiovascular and gastrointestinal disorders. We present the case of an 80-year-old Korean woman with MIS-A who experienced febrile sensations, dyspnea, and whole body pain for 7 weeks after being diagnosed with COVID-19. Initial evaluation revealed heart failure, left pleurisy, and sensory neuropathy, but no evidence of infectious diseases was found. Her symptoms improved quickly after starting systemic glucocorticoid therapy, and inflammatory marker levels decreased. When treating patients with fever after COVID-19, it is critical to suspect MIS-A as one of the differential diagnoses for timely diagnosis and treatment.