Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings. METHODS: A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens. RESULTS: E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure. CONCLUSIONS: The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

Clinical and bacterial features of Group B streptococci with reduced penicillin susceptibility from respiratory specimens: a case-control study.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an invasive pathogen that causes sepsis and meningitis among infants, elderly adults, and immunosuppressed patients. Generally, GBS is susceptible to penicillin; however, GBS with reduced penicillin susceptibility (PRGBS) has been reported. PRGBS are commonly isolated from respiratory specimens, but clinical features of patients with PRGBS remain unclear. In this case-control study, clinical features of patients with PRGBS and bacterial characteristics of these isolates from respiratory specimens were investigated. Patients with GBS at the University of the Ryukyus Hospital between January 2017 and June 2018 were retrospectively investigated. GBS were further classified into penicillin-susceptible GBS (PSGBS) and PRGBS using a drug susceptibility test. Moreover, serotypes, genotypes, and drug resistance genes of PRGBS isolates were determined. In total, 362 GBS were isolated, of which 46 were collected from respiratory specimens, which had the highest rate of PRGBS (24%). Compared to patients with PSGBS, those with PRGBS were more likely to have neuromuscular disease, poor performance status, risk of multidrug-resistant pathogen infection, prior pneumonia history within 1 year, and prior penicillin use within 1 year. Among eight PRGBS isolates, multilocus sequence typing revealed that five isolates were sequence type (ST) 358, two were ST3 and ST10, respectively, and one isolate was ST1404. All PRGBS isolates belonged to the ST1/ST19/ST10 group. This study reveals clinical characteristics of patients with PRGBS from respiratory specimens. Because invasive GBS infection cases are increasing, especially in the elderly, more attention should be paid to this infection.

Correlates of lifetime and past one-year HIV-testing experience among men who have sex with men in Japan.

This study aimed to examine correlates of lifetime and past-year HIV testing among men who have sex with men (MSM) in Japan. A unique, anonymous online self-report survey was conducted in 2015. A total of 776 participants completed the survey and answered questions on sociodemographic information, HIV-testing experience, history of syphilis, experience talking about HIV, recognition of AIDS-related community-based organization (CBO) materials, and sex behaviors. HIV-testing experience and related factors were assessed for two groups: regional cities and Tokyo and Osaka. A Poisson regression analysis revealed that higher lifetime HIV testing was associated with older age, previous syphilis diagnosis, and experience talking about HIV. Moreover, higher HIV testing in the past year was associated with experience talking about HIV with friends and recognition of HIV-related CBO materials. Increased dissemination of HIV-related information provided by CBOs may, therefore, be an effective prevention policy intervention targeted at Japanese MSM to promote regular testing and maintain their interest in HIV issues.

False-positive for SARS-CoV-2 antigen test in a man with acute HIV infection.

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.

Revised hospital antibiotic formulary reduces antimicrobial consumption and promotes a shift towards narrow-spectrum antibiotic usage.

BACKGROUND: In Japan, the national action plan to adress antimicrobial resistance problems aimed to reduce the use of oral cephalosporins, quinolones, and macrolides per day per 1000 inhabitants by 50% from the levelin 2013 by 2020. The aim of this study was to evaluate the effects of a revised antibiotic formulary on in- and out-hospital oral antibiotic prescribing practices at a 600-bed university hospital. METHOD: A retrospective before-and-after comparison study was conducted. All antimicrobial consumption data in the reviewed classes from 1 January 2013 to 31 December 2018, were extracted from the hospital database's electronic medical records. The data were measured in the defined daily dose and antibiotic use density (defined daily dose per 1000 patient-days). RESULTS: The total oral antibiotic use densities for in-hospital prescriptions in 2013 and 2018 were 117.95 and 75.42, respectively, and 239.83 and 193.88, respectively, for out-hospital prescriptions. From 2013 to 2018, antibiotic use densities of second- and third-generation cephalosporins, macrolides and fluoroquinolones for in-hospital prescriptions changed annually by -49.00%, -92.67%, +0.49% and -48.19%, and out-hospital prescriptions of these antibiotics changed by +76.69%, -86.37%, -16.29% and -51.75%, over the same period. Penicillin prescriptions increased by 71.31% for in-hospital and 42.72% for out-hospital prescriptions over this period. CONCLUSIONS: The revised hospital antibiotic formulary reduced total antibiotic consumption and increased the use of narrow-spectrum antibiotics for both in- and out-hospital prescriptions.

Clinical Features of Human Metapneumovirus Pneumonia in Non-Immunocompromised Patients: An Investigation of Three Long-Term Care Facility Outbreaks.

Background: Several studies have reported outbreaks due to human metapneumovirus (hMPV) in long-term care facilities (LTCF) for the elderly. However, most of these reports are epidemiological studies and do not investigate the clinical features of hMPV pneumonia. Methods: Three independent outbreaks of hMPV occurred at separate LTCF for intellectually challenged and elderly residents. A retrospective evaluation of hMPV pneumonia and its clinical and radiological features was conducted using available medical records and data. Results: In 105 hMPV infections, 49% of patients developed pneumonia. The median age of pneumonia cases was significantly higher than non-pneumonia cases (P < .001). Clinical manifestations of hMPV pneumonia included high fever, wheezing in 43%, and respiratory failure in 31% of patients. An elevated number of white blood cells as well as increased levels of C-reactive protein, creatine phosphokinase, and both aspartate and alanine transaminases was also observed among pneumonia cases. Evaluation of chest imaging revealed proximal bronchial wall thickenings radiating outward from the hilum in most patients. Conclusions: The aforementioned characteristics should be considered as representative of hMPV pneumonia. Patients presenting with these features should have laboratory testing performed for prompt diagnosis.

The clinical and phylogenetic investigation for a nosocomial outbreak of respiratory syncytial virus infection in an adult hemato-oncology unit.

Although many reports have already shown RSV outbreaks among hemato-oncology patients, genomic studies detecting similar RSV strains prior to an outbreak in the hospital are rare. In 2014, the University of the Ryukyus hospital hemato-oncology unit experienced, and successfully managed, a respiratory syncytial virus (RSV) nosocomial outbreak. During the outbreak investigation, genotyping and phylogenetic analysis was used to identify a potential source for the outbreak. Nasopharyngeal swabs were tested for RSV using three tests: (1) rapid antigen test (RAT); (2) reverse transcriptase polymerase chain reaction (PCR); or (3) quantitative PCR (RT-qPCR); a positive PCR reaction was considered a confirmed case of RSV. Phylogenetic analysis of the G protein was performed for outbreak and reference samples from non-outbreak periods of the same year. In total, 12 confirmed cases were identified, including 8 hemato-oncology patients. Patient samples were collected weekly, until all confirmed RSV cases returned RSV negative test results. Median time of suspected viral shedding was 16 days (n = 5, range: 8-37 days). Sensitivity and specificity of the RAT compared with RT-qPCR were 30% and 91% (n = 42). Phylogenetic analysis revealed nine genetically identical strains; eight occurring during the outbreak time period and one strain was detected 1 month prior. A genetically similar RSV detected 1 month before is considered one potential source of this outbreak. As such, healthcare providers should always enforce standard precautions, especially in the hemato-oncology unit.

Pulmonary strongyloidiasis: assessment between manifestation and radiological findings in 16 severe strongyloidiasis cases.

BACKGROUND: Strongyloidiasis is a chronic parasitic infection caused by Strongyloides stercoralis. Severe cases such as, hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), can involve pulmonary manifestations. These manifestations frequently aid the diagnosis of strongyloidiasis. Here, we present the pulmonary manifestations and radiological findings of severe strongyloidiasis. METHODS: From January 2004 to December 2014, all patients diagnosed with severe strongyloidiasis at the University of the Ryukyus Hospital or affiliated hospitals in Okinawa, Japan, were included in this retrospective study. All diagnoses were confirmed by the microscopic or histopathological identification of larvae. Severe strongyloidiasis was defined by the presence of any of the following: 1) the identification of S. stercoralis from extra gastrointestinal specimens, 2) sepsis, 3) meningitis, 4) acute respiratory failure, or 5) respiratory tract hemorrhage. Patients were assigned to either HS or DS. Medical records were further reviewed to extract related clinical features and radiological findings. RESULTS: Sixteen severe strongyloidiasis cases were included. Of those, fifteen cases had pulmonary manifestations, eight had acute respiratory distress syndrome (ARDS) (53%), seven had enteric bacterial pneumonia (46%) and five had pulmonary hemorrhage (33%). Acute respiratory failure was a common indicator for pulmonary manifestation (87%). Chest X-ray findings frequently showed diffuse shadows (71%). Additionally, ileum gas was detected for ten of the sixteen cases in the upper abdomen during assessment with chest X-ray. While, chest CT findings frequently showed ground-glass opacity (GGO) in 89% of patients. Interlobular septal thickening was also frequently shown (67%), always accompanying GGO in upper lobes. CONCLUSIONS: In summary, our study described HS/DS cases with pulmonary manifestations including, ARDS, bacterial pneumonia and pulmonary hemorrhage. Chest X-ray findings in HS/DS cases frequently showed diffuse shadows, and the combination of GGO and interlobular septal thickening in chest CT was common in HS/DS, regardless of accompanying pulmonary manifestations. This CT finding suggests alveolar hemorrhage could be used as a potential marker indicating the transition from latent to symptomatic state. Respiratory specimens are especially useful for detecting larvae in cases of HS/DS.

Evaluation of Anyplex™ II RV16 and RB5 real-time RT-PCR compared to Seeplex® RV15 OneStep ACE and PneumoBacter ACE for the simultaneous detection of upper respiratory pathogens.

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.

Etiological analysis and epidemiological comparison among adult CAP and NHCAP patients in Okinawa, Japan.

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.

Correlations between extent of X-ray infiltration and levels of serum C-reactive protein in adult non-severe community-acquired pneumonia.

Pneumonia cases can vary in both severity and chest X-ray findings. Elevated C-reactive protein (CRP) levels may be an indicator of disease severity. We retrospectively evaluated factors correlated with the extent of chest X-ray infiltration both in community-acquired pneumonia (CAP) and a subgroup of cases with pneumococcal pneumonia. In a clinical study that evaluated the efficacy of sitafloxacin, 137 patients with CAP had been previously enrolled. In our study, 75 patients with pneumococcal pneumonia were identified among these 137 CAP patients. The extent of chest X-ray infiltration was scored and correlations with age, sex, body temperature, white blood cell (WBC) count, and CRP levels were analyzed using multivariate analysis with logistic regression. Significant correlations were observed between the extent of chest X-ray infiltration and CRP levels in both CAP and pneumococcal pneumonia. Our data indicates that CRP is a valuable and informative resource that could reflect the severity of pneumonia in cases of both CAP and pneumococcal pneumonia.

The prevalence of airway obstruction among Japanese HIV-positive male patients compared with general population; a case-control study of single center analysis.

BACKGROUND AND OBJECTIVE: Previous studies have suggested that human immunodeficiency virus (HIV) infection and/or the airway colonization of Pneumocystis jirovecii (Pcj) impact on the progression of airway obstruction, such as chronic obstructive pulmonary disease (COPD). This study was aimed to evaluate the relationship between HIV infection, airway colonization of Pcj and airway obstruction in Japanese male patients. METHODS: Case-control study of 49 HIV-positive and 257 HIV-negative men were enrolled in this study. Airway obstruction was determined by spirometry. Cigarette smoking was determined by a self report. Laboratory data were obtained from medical records. Among HIV positive patients, the airway colonization of Pcj was evaluated by induced sputum using the real time polymerase chain reaction method. RESULTS: Forty-eight out of 49 (97.9%) HIV-positive patients received antiretroviral therapy, and their median CD4 cell counts were 491/µL (79-935). The prevalence of airway obstruction as determined by spirometry was 10.2% (5/49) in HIV-positive subjects and 2.4% (5/208) in HIV-negative subjects (p = 0.024). Compared with the control group, HIV-positive patients were significantly younger (median age 44 vs 40, p = 0.019). After adjusting for age, pack-years of smoking, HIV infection was an independent risk factor for airway obstruction (OR; 10.93, 95%CI 1.99-60.1, p = 0.006). None of patient was detected the airway colonization of Pcj. CONCLUSIONS: HIV infection was an independent risk factor for airway obstruction regardless of airway colonization of Pcj. Health-care providers should be aware of the increased likelihood of airway obstruction among HIV-positive patients.

Clinical evaluation of high mobility group box 1 protein in Legionella pneumophila pneumonia.

High mobility group box 1 (HMGB-1) protein is involved in acute lung injury due to various etiologies. We evaluated HMGB-1 levels in sera and bronchoalveolar fluids in patients with pneumonia caused by Legionella pneumophila. Levels of HMGB-1 in the sera of patients with L. pneumophila pneumonia (32 cases) and control subjects (24 cases) were determined. Serum HMGB-1 levels in Legionella pneumonia were similar to those of the control subjects. No significant correlation between HMGB-1 levels and other biomarkers and the outcome of cases was observed. In contrast, HMGB-1 levels, as well as interferon-γ, in bronchoalveolar (BA) fluids from severe L. pneumophila pneumonia (7 cases) were significantly higher than those in the sera of identical patients. HMGB-1 levels in BA fluids were relatively higher in pneumonia cases with ALI than those without ALI. Our findings suggest that intra-pulmonary HMGB-1 may be involved in the pathophysiology of pneumonia caused by L. pneumophila.

Are MMSE and HDS-R neuropsychological tests adequate for screening HIV-associated neurocognitive disorders?

HIV-associated neurocognitive disorders (HAND) are one of major comorbidities in patients with HIV-1 infection. There are currently no standardized tests for screening HAND in such patients. The sensitivity of the cognitive function tests routinely used in clinical practice, such as the Mini-Mental State Examination and the Revised Hasegawa's Dementia Scale, is inadequate to rule out HAND, even in patients with clear abnormal behavior. We report a 41-year-old man with HIV-associated dementia, the most severe form of HAND, in whom the simplified methods did not show abnormal results, and a comprehensive battery of neuropsychological tests which covering several cognitive domains was needed to detect cognitive impairment.

Role of Brevundimonas vesicularis in supporting the growth of Legionella in nutrient-poor environments.

In 1986, we encountered the first case of Legionella micdadei pneumonia in Japan. In the follow-up study to determine the infection route of L. micdadei, we isolated Brevundimonas vesicularis from the shower hose of the patient�s home. This motivated us to explore the symbiosis between B. vesicularis and Legionella in this study. B. vesicularis type strain, B. vesicularis Kobe strain, Legionella pneumophila serogroup 1 type strain, and L. micdadei Kobe strain were used. B. vesicularis was inoculated into 0.01 M phosphate buffer solution containing artificial sand, and varying concentrations of glucose at 0.1%, 0.01%, and 0.001%. Legionella was added to the cultures after ten days of incubation, and Legionella viable counts were monitored over time. After three days of incubation, Legionella counts increased approximately twofold in flasks containing 0.001% glucose, but Legionella counts decreased in both B. vesicularis inoculated and non-inoculated flasks containing higher concentrations of glucose. The counts were significantly higher in flasks inoculated with B. vesicularis than in non-inoculated flasks throughout the experiments. Under the nutrient-poor conditions, the presence of B. vesicularis was found to aid a further increase in Legionella counts. Further research is necessary to understand the symbiotic conditions most supporting the growth of L. micdadei.

Early switch therapy from intravenous sulbactam/ampicillin to oral garenoxacin in patients with community-acquired pneumonia: a multicenter, randomized study in Japan.

The switch from intravenous to oral antibiotic therapy is recommended for treating hospitalized patients with community-acquired pneumonia (CAP). We performed a multicenter, randomized study to assess the benefit of switching from intravenous sulbactam/ampicillin (SBT/ABPC) to oral garenoxacin (GRNX) in patients with CAP. Among adult CAP patients who must be hospitalized for intravenous antibiotic treatment, those with Pneumonia Patient Outcomes Research Team (PORT) scores of II-IV (mild to moderate) were initially treated with intravenous SBT/ABPC (6 g/day) for 3 days. A total of 108 patients who fulfilled the inclusion criteria (improved respiratory symptoms, CRP < 15 mg/dl, adequately improved oral intake, fever ≤ 38 °C for ≥ 12 h), were divided into two groups based on the antibiotic administered, the GRNX (switch to GRNX 400 mg/day) and SBT/ABPC groups (continuous administration of SBT/ABPC), for 4 days. Improvement in clinical symptoms, chest radiographic findings, and clinical effectiveness were evaluated by a central review board. Improvement in clinical symptoms was 96.3 and 90.2% in the GRNX and SBT/ABPC groups, respectively. Improvement in chest radiographic findings was 94.4 and 90.2% and clinical effectiveness was 94.4 and 90.2% in the GRNX and SBT/ABPC groups, respectively. Microbiological efficacy was 90.9 and 69.2% in the GRNX and SBT/ABPC groups, respectively. There were no significant differences between the groups. Converting to GRNX was as effective as continuous SBT/ABPC treatment in mild to moderate CAP patients in whom initial intravenous antibiotic treatment was successful.

[A case of pleural tuberculoma with new pulmonary infiltration during anti-tuberculosis therapy].

A 61-year-old woman who had received treatment for tuberculous pleurisy for 2 months visited our outpatient clinic. Chest computed tomography (CT) showed the presence of a lens-shaped pleural mass with pulmonary infiltration, despite the decreased pleural effusion. Two weeks later, chest CT showed an increase in the size of the mass and expansion of the intrapulmonary shadow. Percutaneous CT-guided lung biopsy was performed, and histopathological examination revealed granulomatous inflammation without caseous necrosis or acid-fast bacilli. Sputum culture was negative for acid-fast bacilli. Anti-tuberculosis medication was continued, and the lesions eventually resolved. These lesions were diagnosed as pleural tuberculomas, and the intrapulmonary infiltration was considered to be due to the paradoxical worsening of the patient's condition.

[Factors associated with HIV testing behavior and intention among men who have sex with men (MSM) in Japan].

OBJECTIVES: This study aimed to explore the factors associated with HIV testing behavior and intention among men who have sex with men (MSM) in Japan. METHODS: A self-administered survey was distributed to gay bar customers in Tokyo, Kanagawa, Osaka, Aichi, Fukuoka, and Okinawa from 2010 to early 2011. A total of 4,572 completed surveys were received by mail. Participants were divided into 3 groups based on HIV testing experience and intention: Group 1 consisted of those who had tested at least once in their lives; Group 2 consisted of those who had never tested but had an intention to test; and Group 3 was made up of those who had never tested and had no intention to test. Associations between groups were assessed using Chi-square goodness-of-fit test and multiple logistic regression. RESULTS: Among the 2,809 respondents reporting anal sex within the previous six months, 131 HIV-positive cases were excluded. Data were thus analyzed from 2,678 MSM; 61% (n=1,633) of participants reported having taken an HIV test at least once in their lives, 20.2% (n=541) reported never having tested but with an intention to test, and 18.8% (n=504) reported never having tested and had no intention to test in the future. Knowledge about HIV and testing, STI history, sexuality, academic background, knowing someone with HIV, and condom use in the past six months all correlated with HIV testing experience when compared between groups 1 and 2. Conversations on HIV/AIDS with friends, lifetime STI history, knowing someone with HIV, conversations on HIV/AIDS with a sexual partner, and older age were all correlated with intention of taking an HIV test when compared between groups 2 and 3. CONCLUSION: Among gay bar customers, those who know someone living with HIV and those who had conversations with friends about HIV/AIDS in the previous six months were more likely to take an HIV test compared to those who had never tested but had an intention to test. Thus, although knowledge about HIV and testing is important, knowing someone with HIV and having conversations about HIV/AIDS with friends are also important. Such factors should be considered in promoting the uptake of voluntary HIV testing among MSM.