Study of factors related to recurrence within 30 days after pneumonia treatment for community-onset pneumonia

IntroductionIt is not uncommon for patients hospitalized with pneumonia to experience an early relapse. Here, we investigated the factors related to pneumonia recurrence in Japan.PurposeWe aimed to elucidate the factors related to early recurrence after completion of pneumonia treatment.MethodsWe examined 696 patients with community-acquired pneumonia (CAP) and nursing and healthcare-associated pneumonia (NHCAP) who were admitted to our hospital between October 2010 and February 2018, excluding those who died during hospitalization. Logistic regression analysis was used to assess the endpoint of recurrence within 30 days after the end of antibiotic treatment.ResultsNHCAP, chronic lung disease and duration of antibiotic treatment were significant risk factors for recurrence of pneumonia within 30 days after antibiotic discontinuation. Aspiration pneumonia was not be a significant factor in the early recurrence of pneumonia.ConclusionsLong-term use of antimicrobials may be a risk factor in early recurrence of pneumonia.     

Mortality changes for patients with pneumococcal pneumonia from 2012 to 2017 in Japan

IntroductionPneumococcal pneumonia has a high morbidity and mortality in adults, especially those ≥65 years old. In the past decade, pneumococcal vaccination programs have been initiated worldwide, however, few data concerning mortality changes are available in pneumococcal pneumonia patients and there are no reports clarifying these current changes in Japan.MethodsJapanese patients ≥65 years old hospitalized with pneumococcal pneumonia between April 2012 and March 2018 were analyzed using the Diagnostic Procedure Combination database. In-hospital mortality was evaluated, and the odds ratios for this outcome in each fiscal year compared with that in 2012 was analyzed using multivariable logistic regression models.ResultsBetween 2012 and 2017, data of 47,375 pneumococcal pneumonia patients ≥65 years old were extracted. The incidence per 1000 person-years for in-hospital mortality was 60.4 in 2012, 56.8 in 2013, 63.2 in 2014, 56.1 in 2015, 73.0 in 2016, and 67.4 in 2017 and the odds ratios for in-hospital mortality in 2013, 2014, 2015, 2016, and 2017 compared with that in 2012 were 1.00, 1.05, 1.04, 1.06, and 0.98, respectively. There were no significant differences between 2012 and each year from 2013 to 2017. Low BMI; low ADL score; high A-DROP score; comorbid malignancy and heart failure; the coexistence of invasive pneumococcal infection; and the use of invasive mechanical ventilation were independent risk factors for in-hospital mortality.ConclusionsThere were no changes in in-hospital mortality in pneumococcal pneumonia patients between 2012 or each year from 2013 to 2017 and further epidemiological observations are necessary.     

Switching from intravenous to oral antibiotics in hospitalized patients with community-acquired pneumonia: A real-world analysis 2010–2018

The Japanese Respiratory Society 2017 guidelines strongly recommend switching from intravenous (IV) to oral antibiotics in patients with community-acquired pneumonia (CAP), following improvement in clinical symptoms and laboratory findings. Here, we retrospectively investigated the real-world, nationwide treatment and switching patterns for hospitalized patients with CAP in Japan using administrative data from 372 Japanese Diagnosis Procedure Combination hospitals from April 2010 to December 2018. Hospitalizations for CAP (patient age ≥20 years) with an A-DROP classification for CAP severity and IV antibiotics initiated on the admission date were included. Overall, 210,314 hospitalizations (moderate CAP: 61.7%) in 183,607 patients were analyzed. The median (interquartile range [IQR]) age at admission was 79 (70–86) years. Penicillin (51.9%) and cephalosporin (38.9%) were the most common IV antibiotic classes used and the median (IQR) duration of IV use was 8 (6–11) days. Switching to oral antibiotics during a hospitalization occurred in 30.1% (n = 63,311) of patients after a median (IQR) of 7 (5–10) days of IV treatment. The most frequently used oral antibiotic classes after a switch were fluoroquinolone (45.9%) and penicillin (24.8%). The switch rate was higher among hospitalizations with milder CAP, in respiratory medicine ward and in larger hospitals. The overall switch rates did not change over the study period. The findings from this analysis suggest that early switch from IV to oral antibiotics was not widely implemented during the 8 years of the study period. Further observation will be needed to see the potential impact of the guidelines update in 2017 in Japan.     

Comparison of safety between high and low doses of sulbactam/ampicillin: A retrospective observational study in Japanese patients with pneumonia

Although 12 g/day sulbactam/ampicillin (SBT/ABPC) is approved in Japan, differences in the frequency of adverse effects induced by conventional (≤6 g/day) and high (≥9 g/day) doses remain unclear. We performed a retrospective observational study on SBT/ABPC-treated hospitalized adult patients with pneumonia from October 2015 to January 2018 to compare the safety between high and low doses. Patients were divided into high-dose (≥9 g/day, n = 200) and low-dose (≤6 g/day, n = 246) groups. We used logistic regression to determine propensity scores for the high-dose and low-dose groups and compared the incidence of adverse effects after propensity score adjustment (n = 200 in each group). Following propensity score adjustment, the frequency of elevated alanine aminotransferase (ALT) level was still significantly higher in the high-dose group than in the low-dose group (21% versus 11%, p = 0.006). In contrast, the frequencies of elevated alkaline phosphatase, aspartate aminotransferase, and serum creatinine levels and decreased white blood cell and platelet counts, and incidence of anemia, were not. Changes in blood urea nitrogen levels, erythrocyte count, and hematocrit were not significantly different between the two dose groups. There were two cases of rash reported to the Pharmaceuticals and Medical Devices Agency as an adverse effect in the high-dose group. Thirty-day mortality rates were not significantly different after propensity score adjustment. Our analysis suggests that an increase in the ALT grade was more frequent in patients treated with a daily dose of SBT/ABPC of ≥9 g.     

Prevalence of thromboembolic events and status of prophylactic anticoagulant therapy in hospitalized patients with COVID-19 in Japan

IntroductionOne of the most prominent and concerning complications associated with coronavirus disease 2019 (COVID-19) is venous and arterial thromboembolisms. The aim of the present study was to delineate the prevalence of thromboembolic events and the current status of prophylactic anticoagulation therapy in patients with COVID-19 in Japan.MethodsBetween February 1 and August 31, 2020, we performed a dual-center, retrospective cohort study based on data obtained from the medical charts of COVID-19 patients admitted to healthcare facilities in Japan. The primary outcome was any thromboembolic event including pulmonary embolism (PE), deep vein thrombosis (DVT), myocardial infarction, ischemic stroke and other systemic thromboemboli.ResultsDuring the study period, we extracted 628 consecutive patients admitted for COVID-19. Prophylactic anticoagulant therapy was administered in 63 (10%) patients of whom 20 (31.7%) were admitted to the intensive care unit (ICU). Thromboembolic events occurred in 18 (2.9%) patients (14.3% of patients in ICU and 2.2% of patients in the general wards). DVT were detected in 13 (2.1%) patients, PE in 11 (1.8%), and both DVT and PE in 6 (0.96%) patients. An increasing prevalence in thromboembolic events was noted with progressive clinical severity. Overall in-hospital mortality was 4.8%.ConclusionsProphylactic anticoagulation therapy was administered in only 10% of all hospitalized COVID-19 patients. The prevalence of any thromboembolic events was 2.9% in COVID-19 patients with most events occurring in severe and critical patients. Therefore, prophylactic anticoagulation therapy may be warranted in severe and critical patients but in asymptomatic to moderate patients the practice remains controversial.     

Impact of rifampicin on the pharmacokinetics of clarithromycin and 14-hydroxy clarithromycin in patients with multidrug combination therapy for pulmonary Mycobacterium avium complex infection

IntroductionClarithromycin (CAM), ethambutol (EB), and rifampicin (RFP) combination therapy is used to treat pulmonary Mycobacterium avium complex (MAC) infection; however, serum CAM concentration decreases due to RFP-mediated induction of CYP3A activity. Therefore, we investigated the pharmacokinetics of CAM, 14-hydroxy clarithromycin (14-OH CAM), EB, and RFP in patients receiving this three-drug combination therapy.MethodsCAM monotherapy was started, EB was added 2 weeks later, and RFP was added 2 weeks after that. Serum CAM, 14-OH CAM, EB, and RFP concentrations were measured before and at 2, 4, 6, and 12 or 24 h after administration on days 14, 28, and 42, and pharmacokinetic parameters were calculated.ResultsMedian area under the curve (AUC) of CAM decreased by 92.1% from 0 to 12 h after concomitant administration of RFP compared with CAM monotherapy [1.7 (interquartile range [IQR], 1.4–1.8) μg·h/mL vs. 21.5 (IQR, 17.7–32.3) μg·h/mL, respectively]. In contrast, median AUC of 14-OH CAM was not significantly different between concomitant administration of RFP [9.1 (IQR, 7.9–10.9) μg·h/mL] and CAM monotherapy [8.2 (IQR, 6.3–9.3) μg·h/mL]. AUCs of CAM and 14-OH CAM did not change in CAM+EB combination therapy.ConclusionsWhen RFP is combined with CAM in the treatment of pulmonary MAC infection, the blood concentration of CAM significantly decreased and that of the active metabolite 14-OH CAM increased, but not significantly. Our results suggest that combination therapy with CAM and RFP needs to be reconsidered and may require dose modification in the treatment of pulmonary MAC infection.     

Risk factors associated with methicillin-resistant Staphylococcus aureus isolation from serially collected sputum samples of patients hospitalized with pneumonia

IntroductionRisk factors associated with the new detection of methicillin-resistant Staphylococcus aureus (MRSA) during hospitalization remain unclear. This study aimed to identify risk factors associated with MRSA isolation from the sputum of patients admitted with pneumonia, during their hospitalization.MethodsPatients were prospectively enrolled from 2003 to 2012. Sputum samples were collected for bacterial cultures on days 1, 4, 7, 11, and 14 of hospitalization and thereafter. Cases of MRSA first isolated from sputum obtained before day 4 were defined as “carriage on admission.” Cases of MRSA first isolated on day 4 and thereafter, were defined as “new detection after admission.” Statistical analysis was used to investigate the risk factors associated with MRSA isolation.ResultsMRSA was isolated from 167 of 1,008 patients (carriage: 47; new detection: 120). Multivariate analysis revealed that the risk factors for MRSA carriage were activities of daily living (ADL) disability prior to admission (odds ratio [OR], 2.92; 95% confidence interval [CI], 1.37–6.22) and hospitalization within the previous 90 days (OR, 3.75; 95% CI, 1.90–7.41). ADL disability prior to admission (risk ratio [RR], 1.82; 95% CI, 1.17–2.84) and a high pneumonia severity index score upon admission (RR, 2.20; 95% CI, 1.37–3.65) were risk factors for new detection of MRSA.ConclusionsSeveral risk factors were found to be associated with MRSA carriage and/or its new detection, based on the sputum samples from patients admitted with pneumonia. These factors may be indicators for selective surveillance and the early implementation of infection control measures.     

Usefulness of β-lactam and macrolide combination therapy for treating community-acquired pneumonia patients hospitalized in the intensive care unit: Propensity score analysis of a prospective cohort study

IntroductionWhether β-lactam and macrolide combination therapy reduces mortality in severe community-acquired pneumonia (SCAP) patients hospitalized in the intensive care unit (ICU) is controversial. The aim of the present study was to evaluate the usefulness of β-lactam and macrolide combination therapy for SCAP patients hospitalized in the ICU.MethodsA prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized SCAP patients admitted to the ICU within 24 h between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting (IPTW) analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score.ResultsA total of 78 patients were included, with 48 patients in the non-macrolide-containing β-lactam therapy group and 30 patients in the macrolide combination therapy group. β-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P = 0.015) and 14-day mortality (6.7% vs. 31.3%; P = 0.020), but not ICU mortality (10% vs 27.1%, P = 0.08) compared with non-macrolide-containing β-lactam therapy. After adjusting by IPTW, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09–0.96; P = 0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04–0.92; P = 0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08–1.36; P = 0.13).ConclusionsCombination therapy with β-lactam and macrolides significantly improved the prognosis of SCAP patients hospitalized in the ICU compared with a non-macrolide-containing β-lactam regimen.     

Daily practice and prognostic factors for pneumonia caused by methicillin-resistant Staphylococcus aureus in Japan: A multicenter prospective observational cohort study

Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia.This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed.In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31–14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35–7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26–9.92) were risk factors for mortality.In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.     

Effects of low-intensity pulsed ultrasound on pain and functional disability in patients with early-stage lumbar spondylolysis: A randomized controlled trial

BackgroundLow Intensity Pulsed Ultrasound (LIPUS) is beneficial in accelerating fracture recovery, enhancing their capacity to execute tasks of daily life and, as a result, their autonomy.ObjectiveTo compare the outcomes of routine physical therapy and routine physical therapy along with LIPUS in patients with early-stage lumbar spondylolysis.MethodsThirty-four (29 males and 5 females) patients exhibiting symptomatic low back pain for at least four weeks were recruited and randomly divided into control group (CG) and intervention group (IG) group. Randomization was done by using goldfish bowl method and allocation was done by using sealed envelope method. Parallel assignment was done. Numeric Pain Rating Scale (NPRS) was utilized for the measurement of pain and Oswestry Disability Index (ODI) for functional disability. Patients were assessed at baseline, at the end of 12th and 20th week. Interventions were applied by two physical therapists (one male and one female) having more than eight years of clinical experience for 10 weeks on alternate days.ResultsIntervention group reported significant percentage change of 47% at 12th week and 65% at 20th week for pain and 42% at 12th week and 81% at 20th week for functional disability compared with 40% at 12th week and 37% at 20th week for pain and 3% at 12th week and 25% at 20th week follow-up for functional disability from baseline in control group.ConclusionLow-intensity pulsed ultrasound has significantly reduced pain and functional disability in patients with early-stage lumbar spondylolysis by using following parameters; 1.1-MHz oscillation frequency, 1-kHz pulsed frequency, 100-mW/cm² spatial intensity, 2 ms pulse duration, 100Hz pulse repetition rate, 20% pulse duty cycle, and 20-min duration on alternate days.     

The efficacy and safety of sitafloxacin and garenoxacin for the treatment of pneumonia in elderly patients: A randomized,multicenter, open-label trial

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3–10 days. The primary efficacy endpoint was the clinical cure rate at 5–10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6–95.6) and 88.9% (95% confidence interval: 77.4–95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients.     

Characterization of plasma daptomycin in patients with serum highly glycated albumin and obesity

PurposePlasma daptomycin has not been fully characterized in diabetic and obese patients. This study aimed to evaluate the associations of plasma daptomycin with glycation of serum albumin and obesity.MethodsInfectious patients (n = 70) receiving intravenous daptomycin were enrolled. The plasma concentration of total and free daptomycin were determined using liquid chromatograph-tandem mass spectrometer. The associations of the plasma concentrations of daptomycin with clinical factors including serum albumin fractionations and physical status (obese including overweight, body mass index ≥ 25.0) were investigated. Daptomycin doses were adjusted using total body-weight.ResultsThe serum albumin level was positively and negatively correlated with the plasma concentration of total daptomycin and its free fraction proportion, respectively. The serum non-glycated albumin was negatively correlated with the free fraction proportion. The dose-normalized plasma concentration of total daptomycin was higher in the obese patients than in non-obese patients when the body-weight was corrected with total and adjusted values. For the dose adjustment with lean body-weight, no difference was observed in the dose-normalized plasma concentration of total daptomycin between the physical statuses. For each body-weight correction method, physical status did not affect the dose-normalized plasma concentration of free daptomycin.ConclusionThe glycation of serum albumin and obesity did not associate with dose-normalized plasma free daptomycin. In obese patients, daptomycin dosage adjustment with total body-weight and adjusted body-weight may lead to an apparent excessive exposure resulting in overdosage compared to lean body-weight.     

Factors associated with acid-fast bacillus isolation in patients with noncystic fibrosis bronchiectasis: A cross-sectional study

IntroductionAcid-fast bacillus (AFB) is a major pathogen that causes noncystic fibrosis bronchiectasis requiring multidrug chemotherapy. Bronchoscopic bronchial wash is performed to determine the causative pathogens of bronchiectasis; but, predictive factors for AFB isolation have not been fully elucidated. This study aimed to determine the factors associated with AFB isolation from bronchial wash samples.MethodsThis was a single-center, cross-sectional study. Patients undergoing bronchoscopic bronchial wash for bronchiectasis were included, whereas those who did not undergo high-resolution computed tomography (HRCT); had acute pneumonia, interstitial lung disease, and a positive polymerase chain reaction result but a negative culture result for AFB; or in whom a guide sheath was used for suspected lung cancer were excluded. Binomial logistic regression was used to analyze the factors associated with a positive culture for AFB.ResultsOf the 96 included cases, AFB isolation was observed in the bronchial wash fluid of 26 patients (27%). No smoking history, a positive result for antiglycopeptidolipid (GPL)-core IgA antibody, and the presence of tree-in-bud appearance, multiple granular and nodular images on HRCT were more commonly observed in patients with AFB isolation than in those without. In the multivariate analysis, the tree-in-bud appearance (odds ratio, 4.223; 95% CI, 1.046–17.052) and anti-GPL core IgA antibody (odds ratio, 9.443; 95% CI, 2.206–40.421) were significantly associated with AFB isolation.ConclusionsThe tree-in-bud appearance on HRCT is likely to predict AFB isolation independent of anti-GPL core IgA antibody results. Bronchoscopic bronchial wash should be recommended for bronchiectasis with multiple granulomas on HRCT.     

Factors associated with cytomegalovirus antigenemia in patients with rheumatic disease: A retrospective study

IntroductionThis study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases.MethodsA single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed.ResultsA total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360–49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781–0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21–44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days.ConclusionsThe daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important.     

Factors significantly associated with COVID-19 severity in symptomatic patients: A retrospective single-center study

IntroductionThe severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020.MethodsAll patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients’ records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software.ResultsData from 61 patients (16 Pt–CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt–CSI were significantly older and had hypertension or diabetes than Pt-MMI (P < 0.001, 0.014 and < 0.001, respectively). Serum albumin levels were significantly lower in Pt–CSI than in Pt-MMI (P < 0.001), whereas the neutrophil-to-lymphocyte ratio and C-reactive protein level were significantly higher in Pt–CSI than in Pt-MMI (P < 0.001 and P < 0.001, respectively). In the CT images of 60 patients, bilateral lung lesions were more frequently observed in Pt–CSI than in Pt-MMI (P = 0.013). Among the 16 Pt–CSI, 15 received antiviral therapy, 12 received tocilizumab, five underwent methylprednisolone treatment, six received mechanical ventilation, and one died.ConclusionsThe illness severity of Japanese COVID-Pts was associated with older age, hypertension and/or diabetes, low serum albumin, high neutrophil-to-lymphocyte ratio, and C-reactive protein.     

Efficacy of early administration of liposomal amphotericin B in patients with septic shock: A nationwide observational study

IntroductionLiposomal amphotericin B (L-AMB), a broad spectrum anti-fungicidal drug, is often administered to treat invasive fungal infections (IFIs). However, the most suitable time to initiate treatment in septic shock patients with IFI is unknown.MethodsPatients with septic shock treated with L-AMB were identified from the Japanese Diagnosis Procedure Combination national database and were stratified according to L-AMB treatment initiation either at septic shock onset (early L-AMB group) or after the onset (delayed L-AMB group) to determine their survival rates following septic shock onset and the shock cessation period.ResultsWe identified 141 patients administered L-AMB on the day of or after septic shock onset: 60 patients received early treatment, whereas 81 patients received delayed treatment. Survival rates after septic shock onset were higher in the early L-AMB group than in the delayed L-AMB group (4 weeks: 68.4% vs 57.9%, P = 0.197; 6 weeks: 62.2% vs 44.5%, P = 0.061; 12 weeks: 43.4% vs 35.0%, P = 0.168, respectively). The septic shock cessation period was shorter in the early L-AMB group than in the delayed L-AMB group (7.0 ± 7.0 days vs 16.5 ± 15.4 days, P < 0.001), with a significant difference confirmed after adjusting for confounding factors with propensity score matching (7.1 ± 7.2 days vs 16.7 ± 14.0 days, P = 0.001).ConclusionEarly L-AMB administration at septic shock onset may be associated with early shock cessation.     

Systemic corticosteroid as an adjunctive treatment for lower respiratory tract infection in children with severe motor and intellectual disabilities

IntroductionChildren with severe motor and intellectual disabilities (SMID) are susceptible to severe lower respiratory tract infection (LTRI). As SMID patients are prone to develop recurrent wheezing and are often diagnosed with bronchial asthma, they frequently receive systemic corticosteroids as an adjunctive treatment for LRTIs. However, the efficacy of corticosteroid therapy for LTRIs in SMID children is unclear. We investigated whether or not corticosteroid therapy was associated with better clinical outcomes for SMID children with LRTIs.MethodsOur retrospective study enrolled 217 SMID children 1–15 years old hospitalized for LTRIs. We compared the clinical characteristics and outcomes between patients with and without corticosteroid therapy.ResultsOf the 217 patients, 29 (13.3%) received corticosteroid therapy. The proportion of patients with a history of bronchial asthma was higher and LRTI was more severe in patients with corticosteroid therapy than in those without the therapy. The length of hospital stay (LOHS) was significantly longer in patients with corticosteroid therapy (median 13 days) than in those without corticosteroid therapy (median 9 days) (P = 0.02). The same tendency was shown for the LOHS in patients with severe or moderate LRTI, although not to a significant extent.ConclusionSystemic corticosteroid therapy was not associated with better clinical outcomes in SMID children with LRTIs, even if the patients suffer from severe LRTIs. Corticosteroids should be used cautiously for LRTIs in SMID children because bronchial asthma is likely to be overdiagnosed in these children.     

Steroid pulse therapy for severe fever with thrombocytopenia syndrome patients may not improve prognosis: Retrospective analysis with overlap weighting using a national inpatient database

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease caused by the SFTS virus. Effective treatment for SFTS has not been established, but steroid pulse therapy is often used. This study aimed to verify whether steroid pulse therapy for SFTS improves prognosis or not.MethodsData of SFTS patients were obtained from the Japanese Diagnosis Procedure Combination Database from April 2013 to March 2021. Patients treated with steroid pulse therapy were compared with untreated patients, using overlap weighting and traditional multivariable regression analysis to evaluate the impact of steroid pulse therapy on prognosis.Results412 SFTS patients were included in this study, and 66 (16%) underwent steroid pulse therapy within 3 days of admission and were allocated to the steroid pulse therapy group. After overlap weighting, patients in the steroid pulse therapy group had a significantly higher in-hospital mortality rate than patients in the control group (31.1% vs. 20.5%; difference: +10.6%; 95% confidence interval: +2.2% to +19.0%). There were no statistically significant differences in hospitalization cost and length of hospital stay between the two groups. The results of the sensitivity analysis using traditional multivariable regression were similar to those of the main analysis.ConclusionIn the analysis of SFTS patients using the Japanese Diagnosis Procedure Combination inpatient data, steroid pulse therapy did not improve patient prognosis. The evidence does not support the universal use of steroid pulse therapy in patients with severe SFTS.     

Critically ill patients with COVID-19 in Tokyo,Japan: A single-center case series

IntroductionWe reported, in our previous study, a patient with coronavirus disease 2019 (COVID-19) who was successfully treated with extracorporeal membrane oxygenation. Data on clinical courses and outcomes of critically ill patients with COVID-19 in Japan are limited in the literature. This study aimed to describe the clinical courses and outcomes of critically ill patients with COVID-19 in Tokyo, Japan.MethodsThis is a single-center case series study. Patients with COVID-19 treated with mechanical ventilation (MV) were reviewed retrospectively. Data on baseline characteristics, in-hospital treatment, and outcomes were collected.ResultsBetween February 2, 2020, and June 30, 2020, 14 critically ill patients with COVID-19 were treated with MV. Most patients were male and had comorbidities, especially hypertension or diabetes; 35.7% were overweight and 21.4% were obese. The majority of the patients had dyspnea on admission. The median duration of MV was 10.5 days, and the 28-day mortality rate was 35.7%. In the four patients with COVID-19 who died, the cause of death was respiratory failure.ConclusionsAs in previous reports from other countries, the mortality rate of patients with COVID-19 requiring intensive care remains high in Tokyo. Further study on the appropriate timing of MV initiation and specific treatments for critically ill patients with COVID-19 is needed.     

Body Mass Index and 90-Day Mortality Among 35,406 Danish Patients Hospitalized for Infection

ObjectiveTo examine the association between body mass index (BMI) and mortality after hospitalization for infection because obesity is associated with increased energy reserves that may protect against death from severe infections.Patients and MethodsOf 76,044 patients admitted with a primary infection diagnosis from January 1, 2011, to September 30, 2015, in Central Denmark, we examined a subgroup of 35,406 patients with a known BMI. We compared the 90-day death risk among patients with underweight, overweight, or obesity with a reference cohort of normal-weight patients. We also examined the impact of comorbid conditions, including cancer, tobacco smoking, and recent weight changes, on the associations and adjusted for other potential confounding factors.ResultsThe 90-day mortality after hospital admission was 9.8% (3479 of 35,406) for any infection, 10.5% (466 of 4425) for urinary tract infection, 17.3% (1536 of 8855) for pneumonia, 24.9% (986 of 3964) for sepsis, and 6.2% (114 of 1831) for skin infection. The 90-day adjusted hazard ratio (aHR) for death was substantially increased in patients with underweight (aHR, 1.75; 95% CI, 1.58 to 1.94) compared with normal-weight patients. In contrast, mortality aHRs were decreased in patients with overweight (aHR, 0.64; 95% CI; 0.58 to 0.69) and obesity (aHR, 0.55; 95% CI; 0.49 to 0.62). Mortality reductions with overweight and obesity were consistent for all major infection types and remained robust independent of recent weight changes, smoking status, or comorbid conditions. Mortality was highest in patients without an apparent reason for their underweight (smoking/known disease), suggesting a role of undiagnosed comorbid conditions.ConclusionWe found evidence that higher BMI (overweight and obesity) is associated with improved survival following acute hospitalization for infection, whereas underweight increases the risk for death.