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Bacterial culture remains the gold standard for the diagnosis of legionellosis. However, past reports indicate that most physicians use the urinary antigen test (UAT) alone. Combining it with other tests is important, especially in patients with negative UAT results. The aim of this study was to investigate the current situation of legionellosis diagnostics and clarify the issues that need to be addressed. Between March 1, 2021 and April 30, 2021, a questionnaire survey was conducted in an anonymous manner among physicians working in Japan. Questionnaires were generated on a website and asked questions in a multiple-choice format. Valid responses were received from 309 physicians during the study period. Most (92.9%) physicians reported using UAT as the initial test for patients suspected of having legionellosis, and <10% reported using other tests (e.g., culture, nucleic acid amplification test [NAAT], Gimenez staining, and serum antibody titer measurement [ATM]). When the initial test result was negative, 63% of physicians reported not conducting additional tests. Even when they chose to run additional tests, at most 27.8%, 23.6%, 12.3%, and 10.4% of all physicians used NAAT, culture, Gimenez staining, and serum ATM, respectively. The major reasons for not using tests other than UAT were "unavailability in the medical facility," "long turn-around time," and "difficult to collect sputum." The present survey revealed that most physicians in Japan used UAT alone for diagnosing legionellosis. Eliminating barriers to creating a reasonable environment and edification of physicians are needed to improve the current situation. [ABSTRACT FROM AUTHOR]

Although rapid antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is convenient, some articles have demonstrated their low sensitivity indicating false-negative results should always be considered. Here, we raise the issue of false-positive on rapid antigen tests for SARS-CoV-2 with the first case of acute HIV infection who repeatedly positive for the rapid antigen test. A 39-year-old man was admitted to our hospital complaining of high-grade fever, dry cough, general fatigue, and anorexia. The rapid antigen test performed on a nasopharyngeal swab sample was positive, therefore the patient was separated in an isolated room apart from the COVID-19 ward while awaiting the confirmatory RT-PCR result. However, the RT-PCR for SARS-CoV-2 performed on nasopharyngeal swabs was repeatedly negative (three times), while the antigen test was repeatedly positive (three times in total). This patient was eventually diagnosed with acute human immunodeficiency virus (HIV) infection based on a high titer of HIV-RNA and absence of plasma HIV-1/2 antibodies. Physicians should consider the possibility of false-positive results in addition to false-negative results when using a rapid antigen test for SARS-CoV-2, and keep in mind that nucleic acid amplification tests are needed to confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Neisseria meningitidis often causes meningitis and meningococcemia; however, meningococcal pneumonia is quite rare. Herein, we report a case of non-invasive meningococcal pneumonia initially misdiagnosed as pneumonia due to Moraxella catarrhalis on the basis of a Gram stain in a 43-year-old woman with asthma, type 2 diabetes mellitus, and schizophrenia. She visited our hospital following a 3-day history of fever, productive cough, and shortness of breath. Since her sputum smear revealed Gram-negative diplococcus and the chest radiograph showed infiltration in the lower right lung field, her initial diagnosis was pneumonia caused by M. catarrhalis . However, the next day, the sputum culture colonies were unlike those of M. catarrhalis , and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed the pathogen to be N. meningitidis . As a result, we administered the appropriate treatment and ensured adequate infection prevention and control measures including, droplet precautions and prophylaxis provided to close contacts. Secondary infection did not occur. Although meningococcal pneumonia is not common, physicians should consider N. meningitidis when Gram-negative diplococci are observed in respiratory specimens, as N. meningitidis cannot be distinguished from M. catarrhalis with Gram staining alone. Moreover, it is also important to monitor the appearance of the pathogenic colonies and to closely coordinate with laboratory technicians to determine appropriate treatments. In this article, we review the previous case reports of meningococcal pneumonia reported in 1984–2015 in Japan, summarizing the clinical characteristics and comparing previous reviews of the literature. [ABSTRACT FROM AUTHOR]

We report a case of fatal pneumonia and viremia due to human parainfluenza virus type 1 (HPIV-1) in a 65-year-old male patient with adult T-cell leukemia–lymphoma (ATL) treated with mogamulizumab, a brand-new therapeutic agent for ATL. To our knowledge, this is the first report describing viremia due to HPIV-1. After administering mogamulizumab, lymphocyte count in the blood was drastically decreased and the patient suffered from complicated infections including gram-negative bacterial sepsis, cytomegalovirus antigenemia and aspergillosis. Although these infections were successfully controlled by broad spectrum antimicrobial therapy, patchy ground-grass opacities in the both lungs were gradually worsened. He finally died due to acute respiratory failure. Since findings of the chest CT was consistent with typical patterns of viral pneumonia, we screened major respiratory viruses in the peripheral blood with multiplex PCR, and it turned out that RNA of HPIV-1 was positive. Although ATL cells were not detected in the autopsied lungs and a variety of other tissues, cytoplasmic inclusion bodies, which are commonly observed in RNA viral infection, were abundantly observed in the autopsied lung tissue. These findings suggest that mogamulizumab accomplished complete remission of ATL, while the chemotherapy-induced prolonged lymphopenia caused fatal pneumonia and viremia due to HPIV-1. As it has been well recognized that community respiratory viruses including HPIV-1 often cause fatal pneumonia in patients with leukemia, but also there is no specific treatment for HPIV-1, we have to enforce standard precautions especially when we treat leukemic patients with intensively immunosuppressive agents such as mogamulizumab. [ABSTRACT FROM AUTHOR]

This prospective study was performed to evaluate and compare the performance of the multiplex PCR Seeplex ® assays and Anyplex™ II assays. From May 2014 until April 2016, a total of 247 respiratory samples were collected in Okinawa, Japan. Multiple respiratory pathogens were detected in 37% of patients with positive results. The most prevalent pathogens were influenza A virus and respiratory syncytial virus B. Despite minor differences in capabilities, both the Seeplex ® assays and Anyplex™ II assays can be easily implemented in diagnostic or research laboratories to optimize the detection and management of respiratory pathogen induced diseases. [ABSTRACT FROM AUTHOR]

Abstract: This work describes the nature and strength of the immune response induced by various Toll-like receptor ligands and their ability to act as vaccine adjuvants. It reviews the various ligands capable of triggering individual TLRs, and then focuses on the efficacy and safety of those agents for which clinical results are available. [Copyright &y& Elsevier]

Abstract: CD1d-restricted NKT cells are reported to play a critical role in the host defense to pulmonary infection with Pseudomonas aeruginosa. However, the contribution of a major subset expressing a Vα14-Jα18 gene segment remains unclear. In the present study, we re-evaluated the role of NKT cells in the neutrophilic inflammatory responses and host defense to this infection using mice genetically lacking Jα18 or CD1d (Jα18KO or CD1dKO mice). These mice cleared the bacteria in lungs at a comparable level to wild-type (WT) mice. There was no significant difference in the local neutrophilic responses, as shown by neutrophil counts and synthesis of MIP-2 and TNF-α, in either KO mice from those in WT mice. Administration of α-galactosylceramide, a specific activator of Vα14+ NKT cells, failed to promote the bacterial clearance and neutrophilic responses, although the same treatment increased the synthesis of IFN-γ, suggesting the involvement of this cytokine downstream of NKT cells. In agreement against this notion, these responses were not further enhanced by administration of recombinant IFN-γ in the infected Jα18KO mice. Our data indicate that NKT cells play a limited role in the development of neutrophilic inflammatory responses and host defense to pulmonary infection with P. aeruginosa. [Copyright &y& Elsevier]

Background Etiological epidemiology and diagnosis are important issues for CAP and NHCAP. Despite the availability of effective therapies, significant morbidity and mortality ensues. Methods We retrospectively analyzed the etiology of 200 pneumonia patients at the University of the Ryukyus Hospital. Patients were categorized into CAP (n = 97) or NHCAP (n = 103), according to the Japanese Respiratory Society guidelines. Diagnoses were made using clinical tests including, Gram stain, bacterial culture, serum and urinary tests. Results Pathogens were detected in 71% of patients, and identified as the source of infection in 52% (104/200). The majority of patients suffered from Streptococcus pneumoniae (32/200), Haemophilus influenzae (22/200), and Moraxella catarrhalis (16/200). Gram stain guided pathogen-oriented therapy decisions for 38 of 96 patients with unknown pathogens. Atypical pathogens were only diagnosed in CAP patients (n = 5). Severity of pneumonia was related to male sex ( p = 0.006), and preexisting conditions, such as chronic heart failure ( p < 0.001) and COPD ( p < 0.001). Risk factors associated with increased length of stay included chronic heart failure, chronic renal failure, other pulmonary diseases and diabetes. Mortality for NHCAP patients was associated with lung cancer and bronchiectasis. CAP patients were more frequently admitted during winter months, while NHCAP patients were admitted during all other seasons. Seasonal patterns for individual pathogens could not be determined. Conclusion Gram staining remains useful to guiding diagnostics. Pathogens affecting CAP and NHCAP patients were not significantly different; as such, attention should be focused on the management of underlying conditions. Clinical outcomes were not affected by guideline discordant therapy. [ABSTRACT FROM AUTHOR]

Previously, Veillonella species had been considered as nonpathogenic and rarely caused serious infections. We report a case of 25-year-old man with osteomyelitis caused by Veillonella species. He was admitted to the hospital due to an open fracture to the left radial bone caused by industrial washing machine accident, and emergency surgery was performed. However, wound infections occurred one week after the operation. Although Acinetobacter baumannii and Serratia marcescens were cultured from the pus, obligate anaerobic bacteria were not detected at that point. Debridement was repeated and antibiotics were changed according to the result of bacterial culture and drug sensitivity. Despite this, the infection was poorly controlled. On the 5th debridement, granulomatous bone tissues on pseudarthrosis were found for the first time at the infection site. Although no bacteria was detected with aerobic culture, anaerobic incubation revealed Gram-negative cocci which was later identified as Veillonella species by 16S rRNA gene sequence analysis. His condition improved without any additional debridement after adding effective antibiotics against Veillonella species. It is well known that prolonged infection with aerobes consumes oxygen in the infection site and leads the environment to more favorable conditions for anaerobic bacteria, thus we speculated that prolonged infection with bacteria such as S. marcescens induced the favorable environment for Veillonella species. Physicians should realize the importance of anaerobic culture method in routine practice, especially in complicated cases such as the present case. In this article, we reviewed case reports of Veillonella infection and summarized the clinical features of this organism. [ABSTRACT FROM AUTHOR]

Here we report six cases of daptomycin (DAP)-induced eosinophilic pneumonia (DIEP) encountered at two medical centers and present a review of 43 DIEP patients from 26 studies to compare the clinical characteristics and radiographic findings of acute and chronic eosinophilic pneumonia (AEP; CEP). Four of the six patients did not exhibit respiratory symptoms, and one patient with only fever was misdiagnosed with DAP-induced fever. According to our literature review and the present findings, male sex and old age were dominant risk factors for DIEP. Fever and fine crackles were the most common clinical manifestations. The DAP dose and duration of administration were not significant risk factors for DIEP, and we also could not find any association between allergic predisposition and DIEP. Among the reviewed patients, 51.8% did not show more than 25% eosinophils in bronchoalveolar lavage, which is a criterion for the diagnosis of drug-induced eosinophilic pneumonia. Chest images of all patients showed CEP patterns such as multiple reticulonodular infiltrates in the subpleural region and diffuse bilateral pulmonary infiltrates with ground-glass opacities. However, 66.7% of patients also exhibited pleural effusion, a feature specific to AEP. All patients showed prompt recovery after DAP withdrawal. Our results suggest that clinicians should consider DIEP as a differential diagnosis when patients receiving DAP therapy, particularly men and elderly patients, present with fever, even in the absence of respiratory symptoms. Furthermore, they should be aware that the occurrence of DIEP is independent of the DAP dose and administration duration, and allergic reaction. [ABSTRACT FROM AUTHOR]

Background and objective In recent years, Streptococcus anginosus group (SAG) bacteria are becoming increasingly recognized as important pneumonia-causing pathogens. Although several small studies have been reported, the features of SAG pneumonia remain unclear, because the identification of SAG from sputum cultures is not routinely performed in most microbiology laboratories. The aim of this study was to elucidate the clinical characteristics of SAG pneumonia. Patient and methods This was a retrospective case-control study utilizing data obtained in our hospital between September 2009 and June 2016. We investigated 31 patients with SAG pneumonia (PWP), and also assessed the difference between the 31 PWP and 37 patients without pneumonia (PWOP) in whose sputum SAG was detected. Results Seventy-one percent of the patients were men and the median age was 78 years in the PWP. Univariate analysis indicated that the PWP were significantly more often a bed-ridden ( p < 0.01) with comorbid aspiration than were the PWOP ( p < 0.05). Among the PWP, nursing and healthcare-associated pneumonia (NHCAP) was the more common type of pneumonia (54.8%). S. anginosus was detected significantly more frequently in sputum cultures of PWP than PWOP ( p < 0.01), and multiple pathogens were detected more frequently in PWP ( p < 0.01). Streptococcus constellatus was the most frequently detected pathogen in patients with a single bacterial infection. Empyema was observed only in patients with multiple bacteria. Conclusions SAG should be recognized as important causative pathogens of pneumonia, particularly among elderly patients with underlying disease associated with aspiration. NHCAP was the more common type of SAG pneumonia in this study. [ABSTRACT FROM AUTHOR]

Among the Citrobacter genus, the most commonly isolated bacteria from human specimens are Citrobacter freundii and Citrobacter koseri , and previous cases of infection due to Citrobacter braakii have been rarely reported. We present a case of bacteremia due to C. braakii in a 38-year-old woman with cervical cancer. She was admitted to our hospital with complaints of a fever, chills, and nausea. Blood culture results showed gram-negative bacilli identified as C. braakii via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, although biochemical testing findings were suggestive of C. freundii . Since a rare pathogen was detected in the present case and the results of additional biochemical studies were suggestive of both C. braakii and Citrobacter farmeri , genetic analysis was conducted. Finally, the gram-negative bacilli were confirmed as C. braakii , a member of the C. freundii complex since 1993, by 16S ribosomal RNA gene sequencing analysis. The gastrointestinal tract was considered the portal of entry, because the patient had a rectal fistula and other cultures such as urine and vaginal discharge incubated species other than C. braakii . The patient recovered after receiving treatment with ciprofloxacin for 14 days. The epidemiology and clinical characteristics of C. braakii infection are still unknown because of the limitations in accurate identification by using currently available commercial biochemical testing and previously, only 6 cases of C. braakii infection have been reported. Physicians should focus on this species, because it causes community-acquired infections, although further studies are needed to clarify the clinical characteristics of C. braakii infections. [ABSTRACT FROM AUTHOR]

Abstract: Previously, we demonstrated that Vα14+ NKT cells and IFN-γ are important upstream components in neutrophil-mediated host defense against infection with Streptococcus pneumoniae. In the present study, we extended these findings by elucidating the role of IFN-γ in this Vα14+ NKT cell-promoted process. Administration of recombinant IFN-γ to Jα18KO mice prolonged the shortened survival, promoted the attenuated clearance of bacteria and improved the reduced accumulation of neutrophils and synthesis of MIP-2 and TNF-α in the lungs, in comparison to wild-type (WT) mice. In addition, intravenous transfer of liver mononuclear cells (LMNC) from WT mice into Jα18KO mice resulted in complete recovery of the depleted responses listed above, whereas such effects were not detected when LMNC were obtained from IFN-γKO or Jα18KO mice. Activation of Vα14+ NKT cells by α-galactosylceramide (α-GalCer) significantly enhanced the clearance of bacteria, accumulation of neutrophils and synthesis of MIP-2 and TNF-α in the infected lungs; this effect was significantly inhibited by a neutralizing anti-IFN-γ antibody. Finally, in a flow cytometric analysis, TNF-α synthesis was detected largely by CD11bbright+ cells in the infected lungs. Our results demonstrated that IFN-γ plays an important role in the neutrophil-mediated host protective responses against pneumococcal infection promoted by Vα14+ NKT cells. [Copyright &y& Elsevier]

Abstract: The present study was designed to elucidate the role of Vγ4+ γδ T cells, a major subset of pulmonary γδ T cells, in host defense against infection with Streptococcus pneumoniae. The proportion and number of whole γδ T cells, identified as CD3+ and TCR-δ+ cells, and Vγ4+ γδ T cells, identified as CD3+ and TCR-Vγ4+ cells, increased in the lungs at 3, 6 and 12h post-infection. Survival of infected mice and lung bacterial clearance were severely impaired in TCR-Vγ4−/− mice compared with control wild-type (WT) mice. The impaired host protection in TCR-Vγ4−/− mice correlated well with attenuated recruitment of neutrophils in lungs. MIP-2 and TNF-α synthesis in the infected tissues was significantly reduced in TCR-Vγ4−/− mice compared with WT mice. Similar results were noted in the synthesis of TNF-α, but not clearly of MIP-2, by lung leukocytes stimulated with live bacteria. Our results demonstrate that Vγ4+ γδ T cells play an important role in the neutrophil-mediated host defense against S. pneumoniae infection by promoting the synthesis of TNF-α and possibly of MIP-2 in the lungs. [Copyright &y& Elsevier]

Abstract: Interleukin (IL)-12 is a critical cytokine in the T helper (Th)1 response and host defense against intracellular microorganisms, while its role in host resistance to extracellular bacteria remains elusive. In the present study, we elucidated the role of IL-12 in the early-phase host defense against acute pulmonary infection with Streptococcus pneumoniae, a typical extracellular bacterium, using IL-12p40 gene-disrupted (IL-12p40KO) mice. IL-12p40KO mice were highly susceptible to S. pneumoniae infection, as indicated by the shortened survival time, which was completely restored by the replacement therapy with recombinant (r) IL-12, and increased bacterial counts in the lung. In these mice, recruitment of neutrophils in the lung was significantly attenuated when compared to that in wild-type (WT) mice, which correlated well with the reduced production of macrophage inflammatory protein (MIP-2) and tumor necrosis factor (TNF)-α in the infected tissues at the early phase of infection. In vitro synthesis of both cytokines by S. pneumoniae-stimulated lung leukocytes was significantly lower in IL-12p40KO mice than in WT mice, and addition of rIL-12 or interferon (IFN)-γ restored the reduced production of MIP-2 and TNF-α in IL-12p40KO mice. Neutralizing anti-IFN-γ monoclonal antibody (mAb) significantly decreased the effect of rIL-12. Anti-IFN-γ mAb shortened the survival time of infected mice and reduced the recruitment of neutrophils and production of MIP-2 and TNF-α in the lungs. Our results indicated that IL-12p40 plays a critical role in the early-phase host defense against S. pneumoniae infection by promoting the recruitment of neutrophils to the infected tissues. [Copyright &y& Elsevier]

Interferon (IFN)-γ plays an essential role in host defense against infection with Mycobacterium tuberculosis, and its synthesis is critically regulated by interleukin (IL)-12, IL-18 and the recently identified IL-23. The present study was designed to determine the roles of these cytokines in IFN-γ-mediated host defenses against M. tuberculosis. For this purpose, we compared host protective responses in IL-12p40 and IL-18 double-knockout (DKO) mice (which lacked both IL-12/IL-18 and also IL-23) and IFN-γ gene-disrupted (GKO) mice. DKO mice were more resistant to the infection than GKO mice, as indicated by their extended survival and reduced live colony numbers in spleen, liver and lung. IFN-γ was detected by ELISA in liver and lung homogenates, but not in spleen and serum, and in all organs by RT-PCR in DKO mice at comparable or reduced levels to those in wild-type mice. IFN-γ production was reduced by depletion of CD4+ T cells, but not of natural killer (NK), NKT, γδT and dendritic cells. Neutralization of IFN-γ or TNF-α by specific monoclonal antibodies (mAbs) significantly shortened the survival time of the infected DKO mice. Furthermore, anti-TNF-α mAb partially attenuated IFN-γ synthesis in the liver of these mice. Finally, the expression level of inducible nitric oxide synthase (iNOS) mRNA in the spleen, liver and lung was considerable in DKO mice but only marginal or undetected in GKO mice. Our results indicate the presence of IL-12-, IL-18- and IL-23-independent host protective responses against mycobacterial infection mediated by IFN-γ, which was secreted from helper T cells. [Copyright &y& Elsevier]