Clinical characteristics and risk factors for mortality in patients with community-acquired staphylococcal pneumonia.

Staphylococcus aureus (S. aureus) is increasing in prevalence as a causative pathogen of community-acquired pneumonia (CAP). However, reports on the clinical features and mortality risk factors for S. aureus CAP are limited. We therefore aimed to identify the clinical characteristics and risk factors for mortality in these patients. We performed a post hoc and multivariate analysis of a multicenter prospective observational study that included adult hospitalized patients with S. aureus CAP. To elucidate the features of S. aureus CAP, we comparatively analyzed pneumococcal CAP (PCAP). We analyzed 196 patients with S. aureus CAP and 198 patients with PCAP. S. aureus CAP had a 30-day mortality of 16% (31/196) and a higher frequency of factors such as advanced age, comorbidities, poor functional ability, altered mental status, hypoalbuminemia, hyponatremia/hypernatremia, acidemia, and hypoxemia. In the multivariate analysis, the significant risk factors for mortality in S. aureus CAP were PaO2/FiO2 ≤250 [adjusted odds ratio (AOR), 3.29; 95% confidence interval (CI), 1.20-9.04] and albumin <3.0 g/dL (AOR, 2.41; 95% CI, 1.01-5.83). Non-ambulatory status tended to increase the risk (AOR, 2.40; 95% CI, 0.93-6.17). Methicillin resistance was not associated with mortality. In PCAP, hypoalbuminemia and non-ambulatory status affected mortality but hypoxemia did not. In conclusion, patients with S. aureus CAP have distinct clinical features, and their mortality risk factors can include hypoxemia and hypoalbuminemia. Physicians should recognize that the factors influencing mortality might differ somewhat among causative pathogens, and appropriate management should be performed after obtaining information on the causative pathogen.

Effects of lymphocyte and neutrophil counts and their time courses on mortality in patients with postoperative pneumonia.

The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC < 500 cells/µL) at diagnosis was associated with worse 90-day survival in both types of pneumonia. In POP patients, neutrophilia (ANC > 7500 cells/µL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia.

Risk factors for antibiotic resistance in hospital-acquired and ventilator-associated pneumonia.

INTRODUCTION: Understanding risk factors for antibiotic resistance (AR) in patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is important to select appropriate initial antibiotics and reduce broad-spectrum antibiotic overuse. However, available evidence is limited. We aimed to identify risk factors for AR in those patients. METHODS: This prospective observational study was conducted at a tertiary-care hospital. Pathogens with AR were defined as those resistant to ampicillin-sulbactam or ceftriaxone. Risk factors for AR in patients with HAP and VAP were assessed using penalized logistic regression analysis. RESULTS: In total, 557 patients with HAP and VAP were enrolled. Pathogens were isolated from 315 patients, with AR identified in 68.3% (215/315). Among antibiotic-resistant pathogens (ARPs), Pseudomonas aeruginosa was isolated most frequently, followed by methicillin-resistant Staphylococcus aureus (MRSA). Significant risk factors for AR were chronic renal diseases (adjusted odds ratio: 2.82, 95% confidence interval: 1.79-7.83), history of ARP infection/colonization within the past 1 year (2.80, 1.90-7.02), bedridden state (1.84, 1.28-3.91), tube feeding (1.58, 1.09-2.98), and peripheral or central venous catheterization (1.57, 1.06-2.96). Additionally, a risk factor for ARPs that should be treated with anti-MRSA antibiotics was prior MRSA infection/colonization history. Those for ARPs requiring dual antipseudomonal antibiotics included prior non-MRSA ARP or MRSA infection/colonization history and bedridden state. CONCLUSIONS: The five factors we highlighted can be important criteria for identifying patients at risk of AR. Physicians should consider these potential risk factors when selecting antibiotics for initial empirical therapy in patients with HAP and VAP.

A prediction rule for severe adverse events in all inpatients with community-acquired pneumonia: a multicenter observational study.

BACKGROUND: Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP. METHODS: Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study. RESULTS: The ALL-COP SCORE rule included albumin (< 2 g/dL, 2 points; 2-3 g/dL, 1 point), white blood cell (< 4000 cells/µL, 3 points), chronic lung disease (1 point), confusion (2 points), PaO2/FIO2 ratio (< 200 mmHg, 3 points; 200-300 mmHg, 1 point), potassium (≥ 5.0 mEq/L, 2 points), arterial pH (< 7.35, 2 points), systolic blood pressure (< 90 mmHg, 2 points), PaCO2 (> 45 mmHg, 2 points), HCO3- (< 20 mmol/L, 1 point), respiratory rate (≥ 30 breaths/min, 1 point), pleural effusion (1 point), and extent of chest radiographical infiltration in unilateral lung (> 2/3, 2 points; 1/2-2/3, 1 point). Patients with 4-5, 6-7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity. CONCLUSIONS: ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points. TRIAL REGISTRATION: This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.

Effects of isomaltulose ingestion on postexercise hydration state and heat loss responses in young men.

NEW FINDINGS: What is the central question of this study? What are the effects of isomaltulose, an ingredient in carbohydrate-electrolyte beverages to maintain glycaemia and attenuate the risk of dehydration during exercise heat stress, on postexercise rehydration and physiological heat loss responses? What is the main finding and its importance? Consumption of a 6.5% isomaltulose-electrolyte beverage following exercise heat stress restored hydration following a 2 h recovery as compared to a 2% solution or water only. While the 6.5% isomaltulose-electrolytes increased plasma volume and plasma osmolality, which are known to modulate postexercise heat loss, sweating and cutaneous vascular responses did not differ between conditions. Consequently, ingestion beverages containing 6.5% isomaltulose-electrolytes enhanced postexercise rehydration without affecting heat loss responses. ABSTRACT: Isomaltulose is a disaccharide carbohydrate widely used during exercise to maintain glycaemia and hydration. We investigated the effects of ingesting a beverage containing isomaltulose and electrolytes on postexercise hydration state and physiological heat loss responses. In a randomized, single-blind cross-over design, 10 young healthy men were hypohydrated by performing up to three 30 min successive moderate-intensity (50% heart rate reserve) bouts of cycling, each separated by 10 min, while wearing a water-perfusion suit heated to 45°C. The protocol continued until a 2% reduction in body mass was achieved. Thereafter, participants performed a final 15 min moderate-intensity exercise bout followed by a 2 h recovery. Following cessation of exercise, participants ingested a beverage consisting of (i) water only (Water), (ii) 2% isomaltulose (CHO-2%), or (iii) 6.5% isomaltulose (CHO-6.5%) equal to the volume of 2% body mass loss within the first 30 min of the recovery. Changes in plasma volume (ΔPV) after fluid ingestion were greater for CHO-6.5% compared with CHO-2% (120 min postexercise) and Water (90 and 120 min) (all P ≤ 0.040). Plasma osmolality remained elevated with CHO-6.5% compared with consumption of the other beverages at 30 and 90 min postexercise (all P ≤ 0.050). Urine output tended to be reduced with CHO-6.5% compared to other fluid conditions (main effect, P = 0.069). Rectal and mean skin temperatures, chest sweat rate and cutaneous perfusion did not differ between conditions (all P > 0.05). In conclusion, compared with CHO-2% and Water, consuming a beverage consisting of CHO-6.5% and electrolytes during recovery under heat stress enhances PV recovery without modulating physiological heat loss responses.

BK virus-associated viruria and viremia in a patient with lymphangioleiomyomatosis after lung re-transplantation: A case report and review of the literature on BK virus infection post-lung transplantation.

The BK virus (BKV) is a member of the polyomaviridae family of DNA viruses. BKV reactivates under a highly immunosuppressed state and causes renal dysfunction. In renal transplant patients, BKV infection leads to tubular impairment and loss of transplanted kidney grafts. However, few studies have reported on the relationship between BKV and lung transplantation. Adjustment of the dosage of immunosuppressants is needed in some cases, but the treatment method has not been established. Here, we report a case of BKV-associated viruria and viremia in a patient with lymphangioleiomyomatosis (LAM) after lung re-transplantation. A 44-year-old female refractory LAM patient who had undergone lung re-transplantation 3 months earlier was diagnosed with BKV-associated viruria and viremia. Urine cytology indicated decoy cells and the urine and serum polymerase chain reaction test was positive for BKV. As scheduled after re-transplantation surgery, immunosuppressive drugs were progressively reduced. This patient was considered to have experienced spontaneous BKV-associated viremia and viruria. Review of the literature suggested that 17%-42% of BKV-associated viruria cases have been reported after lung transplantation, but cases of BKV-associated nephropathy are rarely reported. Based on the present case, doctors involved in lung transplantation should monitor patients for BKV infection. Decoy cell monitoring by urine cytology is a useful screening method in the follow-up observation after lung transplantation. Early-stage interventions may prevent BKV-associated nephropathy even in patients who have developed BKV viremia, and sirolimus can be administered to patients with histories of BKV infection if they are carefully monitored.

A Hypothesis-Generating Study of the Combination of Aspirin plus Macrolides in Patients with Severe Community-Acquired Pneumonia.

While the inflammatory response to severe pneumonia is paramount in limiting and resolving the infection, excessive inflammation can lead to deleterious effects. We theorized that patients with severe community-acquired pneumonia (CAP) who were treated with macrolides and aspirin would receive benefit beyond that of conventional antibiotic therapy. An observational study was conducted with patients with severe CAP. All patients were admitted to 5 teaching hospitals (in Italy, the United States, Japan, and China), and data were gathered from their electronic medical records. Severe pneumonia was defined according to Infectious Diseases Society of America/American Thoracic Society criteria. Patients were divided into 4 groups, i.e., (i) the aspirin-only group (ASG), (ii) the macrolide-only group (MG), (iii) the aspirin plus macrolide group (ASMG), or (iv) the neither aspirin nor macrolide group (NASMG). Survival rates for the 4 groups were evaluated after adjustment for confounders and after weighting by propensity score. A total of 1,295 patients were included in the analysis. There were 237 patients (18.3%) in the ASG, 294 (22.7%) in the MG, 148 (11.4%) in the ASMG, and 616 (47.6%) in the NASMG. The mortality rate at 30 days was 15.5% in the ASMG, compared to 28.2% in the NASMG, 23.8% in the MG, and 21.1% in the ASG. After propensity score analysis, receipt of aspirin plus macrolide (hazard ratio, 0.71 [95% confidence interval, 0.58 to 0.88]; P = 0.002) was associated with a higher 30-day survival rate. This is a hypothesis-generating study in which data suggest that the combination of aspirin plus a macrolide improves 30-day survival rates for patients with severe CAP. Further randomized studies will need to be undertaken to confirm this phenomenon.

Validation of the prediction rules identifying drug-resistant pathogens in community-onset pneumonia.

BACKGROUND: Appropriate initial antibiotic treatment and avoiding administration of unnecessary broad-spectrum antibiotics are important for the treatment of pneumonia. To achieve this, assessment of risk for drug-resistant pathogens (DRPs) at diagnosis is essential. PURPOSE: The aim of this study was to validate a predictive rule for DRPs that we previously proposed (the community-acquired pneumonia drug-resistant pathogen [CAP-DRP] rule), comparing several other predictive methods. PATIENTS AND METHODS: A prospective observational study was conducted in hospitalized patients with community-onset pneumonia at four institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP-DRPs. RESULTS: CAP-DRPs were identified in 73 (10.1%) of 721 patients analyzed. The CAP-DRP rule differentiated low vs high risk of CAP-DRP at the threshold of ≥3 points or 2 points plus any of methicillin-resistant Staphylococcus aureus specific factors with a sensitivity of 0.45, specificity of 0.87, positive predictive value of 0.47, negative predictive value of 0.87, and accuracy of 0.79. Its discrimination performance, area under the receiver operating characteristic curve, was 0.73 (95% confidence interval 0.66-0.79). Specificity of the CAP-DRP rule against CAP-DRPs was the highest among the six predictive rules tested. CONCLUSION: The performance of the predictive rules and criteria for CAP-DRPs was limited. However, the CAP-DRP rule yielded high specificity and could specify patients who should be treated with non-broad-spectrum antibiotics, eg, a non-pseudomonal ß-lactam plus a macrolide, more precisely.

Mortality in patients with community-onset pneumonia at low risk of drug-resistant pathogens: Impact of ß-lactam plus macrolide combination therapy.

BACKGROUND AND OBJECTIVE: Drug-resistant pathogen (DRP) risk stratification is important for choosing a treatment strategy for community-onset pneumonia. Evidence for benefits of non-antipseudomonal ß-lactam plus macrolide combination therapy (BLM) on mortality is limited in patients at low DRP risk. Risk factors for mortality remain to be clarified. METHODS: Post hoc analysis using a prospective multicentre study cohort of community-onset pneumonia was performed to assess 30-day differences in mortality between non-antipseudomonal ß-lactam monotherapy (BL) and BLM groups. Logistic regression analysis was performed to assess the therapeutic effect and risk factors for mortality in patients at low DRP risk. RESULTS: In total, 594 patients with community-onset pneumonia at low DRP risk (369 BL and 225 BLM) were analysed. The 30-day mortality in BL and BLM was 13.8% and 1.8%, respectively (P < 0.001). Multivariate analysis showed that BLM reduced the 30-day mortality (adjusted odds ratio: 0.28, 95% CI: 0.09-0.87) compared with BL. Independent prognostic factors for 30-day mortality included arterial partial pressure of carbon dioxide (PaCO2 ) > 50 mm Hg, white blood cell count < 4000/mm3 , non-ambulatory status, albumin < 3.0 g/dL, haematocrit < 30%, age ≥ 80 years, respiratory rate > 25/min and body temperature < 36°C. CONCLUSION: In patients with community-onset pneumonia at low DRP risk, BLM treatment reduced 30-day mortality compared with BL. Independent risk factors for mortality are potential confounding factors when assessing antibiotic effects in randomized clinical trials.

Risk factors for 30-day mortality in patients with pneumonia who receive appropriate initial antibiotics: an observational cohort study.

BACKGROUND: Appropriate initial antibiotics are essential for the treatment of infectious diseases. However, some patients with pneumonia might develop adverse outcomes, despite receiving appropriate initial antibiotics. We aimed to clarify the risk factors for 30-day mortality in patients who received appropriate initial antibiotics and to identify potential candidates who would benefit from adjunctive therapy. METHODS: From March 15, to Dec 22, 2010, we did a prospective, observational study at ten medical institutions in hospitalised patients (aged ≥20 years) with pneumonia. We did a multivariable logistic regression analysis to calculate odds ratios (ORs) and 95% CI to assess the risk factors for 30-day mortality. This study was registered with the University Medical Information Network in Japan, number UMIN000003306. FINDINGS: The 30-day mortality was 11% (61 of 579 patients) in the appropriate initial antibiotic treatment group and 17% (29 of 168) in the inappropriate initial antibiotic treatment group. Albumin concentration of less than 30 mg/L (adjusted OR 3·39, 95% CI 1·83-6·28), non-ambulatory status (3·34, 1·84-6·05), pH of less than 7·35 (3·13, 1·52-6·42), respiration rate of at least 30 breaths per min (2·33, 1·28-4·24), and blood urea nitrogen of at least 7·14 mmol/L (2·20, 1·13-4·30) were independent risk factors in patients given appropriate initial antibiotic treatment. The 30-day mortality was 1% (one of 126 patients), 1% (two of 168), 17% (23 of 137), 22% (20 of 89), and 44% (14 of 32) for patients with no, one, two, three, and four or five risk factors, respectively. INTERPRETATION: Patients with two or more risk factors were at a higher risk of death during the 30 days assessed than were individuals with no or one risk factor, despite appropriate initial antibiotic treatment. Therefore, adjunctive therapy might be important for improving outcomes in patients with two or more risk factors. FUNDING: Central Japan Lung Study Group.

Risk factors for drug-resistant pathogens in community-acquired and healthcare-associated pneumonia.

RATIONALE: Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia. OBJECTIVES: To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patients with CAP and HCAP. METHODS: A prospective observational study was conducted in hospitalized patients with pneumonia at 10 institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant pathogens (CAP-DRPs). MEASUREMENTS AND MAIN RESULTS: In total, 1,413 patients (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11), previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid-suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95% CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the combined patients with CAP and HCAP. The area under the receiver operating characteristic curve for counting the number of risk factors was 0.79 (95% CI, 0.74-0.84). CONCLUSIONS: The clinical profile of HCAP was different from that of CAP. However, physicians can predict drug resistance in patients with either CAP or HCAP by taking account of the cumulative number of the risk factors. Clinical trial registered with https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000004001&language=E ; number UMIN000003306.

[A case of secondary pulmonary malignant lymphoma with multiple pulmonary nodules and spiculation].

A 72-year-old man presented to our hospital with fatigue and anemia. Chest CT showed multiple nodular shadows. We first suspected lung cancer and multiple metastatic lesions because some nodules had spiculation. However, PET-CT revealed the small intestine, thyroid and rib as well as these nodules to be positive for FDG uptake, suggesting malignant lymphoma and lung involvement. For diagnosis, lung biopsy by video-assisted thoracic surgery (VATS) was performed. Pathologic examination of the lung biopsy specimen showed diffuse large B-cell lymphoma. We diagnosed secondary pulmonary malignant lymphoma.

[A case of severe asthma responsive to omalizumab treatment despite a low serum IgE level and lack of sensitized allergens].

A 49-year-old female patient suffering from severe intractable asthma uncontrolled even with high-dose inhaled glucocorticosteroids (fluticasone 1000 µg/day+ciclesonide 800 µg/day), salmeterol inhaler (100 µg/day) and oral betamethasone (1 mg/day) was admitted to our hospital because of severe asthma attack. The total serum IgE level was low at 9 (IU/mL). Though perennial allergens was also negative, administration of 150 mg omalizumab was started in August 2009 with the patient's consent, resulting in noticeable improvements in asthma symptoms and the peak expiratory flow (PEF) were achieved. Due to her weight gain and general malaise, the drug was discontinued after the second administration, resulting in worsening of asthma symptoms. Omalizumab therapy was restarted in January 2010 and marked improvements in asthma symptoms and PEF were noted. The effects continued for approximately three weeks after administration. After the sixth administration, the dose of oral betamethasone successfully reduced to 0.5 mg/day. When comparing the six-month pre- and post-omalizumab therapy period, asthma-related events such as unscheduled hospital visits were also reduced, and the dose of oral betamethasone could also be reduced to 64% of the pre-therapy period after the omalizumab treatment. This case strongly suggests the therapeutic effect of omalizumab in the treatment of severe intractable asthma with low serum IgE level without identifiable allergens.