Investigation of predictors for in-hospital death or long-term hospitalization in community-acquired pneumonia with risk factors for aspiration.

Background: It is known that the mortality of pneumonia in patients with risk factors for aspiration is worse than that in those without these risk factors. However, it is still unknown which risk factors for aspiration predict prognosis. Therefore, we aimed to determine which risk factors for aspiration are associated with death or prolonged hospitalization. Methods: We prospectively followed patients with community-acquired pneumonia at a single hospital providing acute to chronic care in Japan until they died or were discharged. Patients at any risk of aspiration were included. The associations between pneumonia severity, individual risk factors for aspiration, and in-hospital death or prolonged hospitalization were investigated. Overall survival was estimated by the Kaplan - Meier method, and the factors associated with in-hospital death or prolonged hospitalization were investigated by multivariate analysis using factors selected by a stepwise method. Results: In total, 765 patients with pneumonia and risk factors for aspiration were recruited. One hundred and ten patients deceased, and 259 patients were hospitalized over 27 days. In-hospital death increased as the number of risk factors for aspiration increased. In the multivariate analysis, male, impaired consciousness, acidemia, elevated blood urea nitrogen, and bedridden status before the onset of pneumonia were associated with in-hospital death (odds ratio [OR]: 2.5, 2.5, 3.6, 3.1, and 2.6; 95% confidence interval [CI]: 1.6-4.1, 1.4-4.2, 1.6-8.0, 1.9-5.0, and 1.6-4.2 respectively). In the Cox regression analysis, these factors were also associated with in-hospital death. None of the vital signs at admission were associated. Tachycardia, elevated blood urea nitrogen, hyponatremia, and bedridden status were associated with hospitalization for >27 days (OR: 4.1, 2.3, 4.3, and 2.9; 95% CI: 1.3-12.9, 1.5-3.4, 2.0-9.4, and 2.0-4.0, respectively). Conclusions: Blood sampling findings and bedridden status are useful for predicting in-hospital mortality and long-term hospitalization in patients with pneumonia and any risk factor for aspiration.

Protein C activity as a potential prognostic factor for nursing home-acquired pneumonia.

INTRODUCTION: Despite the poor prognosis for nursing home acquired pneumonia (NHAP), a useful prognostic factor is lacking. We evaluated protein C (PC) activity as a predictor of in-hospital death in patients with NHAP and community-acquired pneumonia (CAP). METHODS: This prospective, observational study included all patients hospitalized with pneumonia between July 2007 and December 2012 in a single hospital. We measured PC activity at admission and investigated whether it was different between survivors and non-survivors. We also examined whether PC activity < 55% was a predictor for in-hospital death of pneumonia by logistic regression analysis with CURB-65 items (confusion, blood urea >20 mg/dL, respiratory rate >30/min, and blood pressure <90/60 mmHg, age >65). When it was a useful prognostic factor for pneumonia, we combined PC activity with the existing prognostic scores, the pneumonia severity index (PSI) and CURB-65, and analyzed its additional effect by comparing the areas under the receiver operating characteristic curves (AUCs) of the modified and original scores. RESULTS: Participants comprised 75 NHAP and 315 CAP patients. PC activity was lower among non-survivors than among survivors in NHAP and all-pneumonia (CAP+NHAP). PC activity <55% was a useful prognostic predictor for NHAP (Odds ratio 7.39 (95% CI; 1.59-34.38), and when PSI or CURB-65 was combined with PC activity, the AUC improved (from 0.712 to 0.820 for PSI, and 0.657 to 0.734 for CURB-65). CONCLUSIONS: PC activity was useful for predicting in-hospital death of pneumonia, especially in NHAP, and became more useful when combined with the PSI or CURB-65.

Hypercalcemia Associated with the Ectopic Expression of 25-hydroxyvitamin D3-1α-hydroxylase in Diffuse Large B-cell Lymphoma.

An 82-year-old man was transferred to our hospital due to impaired consciousness. His albumin-corrected calcium level was 14.2 mg/dL, intact parathyroid hormone (PTH) and PTH-related protein levels were reduced, and his 1,25-dihydroxyvitamin D [1,25 (OH) 2VitD] level was elevated at 71.5 pg/mL. Computed tomography revealed masses on the bilateral ribs. The mass on the rib was biopsied and diagnosed as diffuse large B-cell lymphoma (DLBCL). Immunostaining of the biopsy sample with the anti-CYP27B1 antibody revealed the ectopic expression of 1α-hydroxylase in the lesion. We herein report a rare case of hypercalcemia induced by the overproduction of 1,25 (OH) 2VitD in DLBCL ectopically expressing 1α-hydroxylase.

The association of high Vancomycin trough concentration with acute kidney injury during combination therapy of Piperacillin/Tazobactam and Vancomycin.

BACKGROUND: Co-administration of Piperacillin/Tazobactam (PIPC/TAZ) and Vancomycin (VCM) as an antibiotic therapy for severe infectious diseases increases the risk of nephrotoxicity. We retrospectively investigated the utility of monitoring VCM trough concentration in early stage of developing acute kidney injury (AKI) on this combination therapy. METHODS: We enrolled all infectious disease patients who were managed with concurrent PIPC/TAZ and VCM. The record of dosage and the administration interval of each antibiotic and its clinical parameters, as well as the VCM trough concentrations, blood culture for bacteria, and serum creatinine values, were collected. VCM trough concentration was measured during the initial 48-72 h of VCM administration. Nephrotoxicity was evaluated as the degree of AKI. RESULTS: A total of 47 patients fulfilling the criteria were registered, and AKI developed in 10 patients. There was no statistical difference between the AKI and non-AKI groups with regard to age, height, weight, basal creatinine level, body surface area, body mass index, PIPC/TAZ dose, VCM dose, gender, artificial management, and death within around 30 days. The VCM trough level was increased significantly in the AKI group (mean [standard deviation {SD}]: 25.9 [7.8] µg/mL) compared to that in the non-AKI group (mean [SD]: 15.7 [6.9] µg/mL) (p = 0.003). During the clinical course, renal function returned to normal levels in three out of four AKI stage 2 patients, whereas only partial recovery was achieved in all AKI stage 3 patients. CONCLUSIONS: A high VCM trough concentration may have an influence on the occurrence of AKI during combination therapy of PIPC/TAZ and VCM. Careful monitoring of VCM trough concentration will be required to prevent AKI progression.

Development and validation of a new scoring system for prognostic prediction of community-acquired pneumonia in older adults.

The discriminative power of CURB-65 for mortality in community-acquired pneumonia (CAP) is suspected to decrease with age. However, a useful prognostic prediction model for older patients with CAP has not been established. This study aimed to develop and validate a new scoring system for predicting mortality in older patients with CAP. We recruited two prospective cohorts including patients aged ≥ 65 years and hospitalized with CAP. In the derivation (n = 872) and validation cohorts (n = 1,158), the average age was 82.0 and 80.6 years and the 30-day mortality rate was 7.6% (n = 66) and 7.4% (n = 86), respectively. A new scoring system was developed based on factors associated with 30-day mortality, identified by multivariate analysis in the derivation cohort. This scoring system named CHUBA comprised five variables: confusion, hypoxemia (SpO2 ≤ 90% or PaO2 ≤ 60 mmHg), blood urea nitrogen ≥ 30 mg/dL, bedridden state, and serum albumin level ≤ 3.0 g/dL. With regard to 30-day mortality, the area under the receiver operating characteristic curve for CURB-65 and CHUBA was 0.672 (95% confidence interval, 0.607-0.732) and 0.809 (95% confidence interval, 0.751-0.856; P < 0.001), respectively. The effectiveness of CHUBA was statistically confirmed in the external validation cohort. In conclusion, a simpler novel scoring system, CHUBA, was established for predicting mortality in older patients with CAP.

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

INTRODUCTION: Risk 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. METHODS: Patients 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. RESULTS: MRSA 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. CONCLUSIONS: Several 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.

Comparison of ceftriaxone plus macrolide and ampicillin/sulbactam plus macrolide in treatment for patients with community-acquired pneumonia without risk factors for aspiration: an open-label, quasi-randomized, controlled trial.

BACKGROUND: Ceftriaxone (CTRX) and ampicillin/sulbactam (ABPC/SBT) are recommended by various guidelines as the first-line antibiotics for community-acquired pneumonia (CAP). However, which of these antibiotics is more effective for treating non-aspiration CAP remains unclear. METHODS: This study was a prospective, single-center, open-label, quasi-randomized controlled trial. Patients with adult CAP without risk for aspiration were allocated to either a CTRX or ABPC/SBT group based on the date of hospital admission. Macrolide was added to patients in each group. The primary outcome was the clinical response in the validated per-protocol (VPP) population at end of treatment (EOT). The secondary outcomes were clinical response during treatment and at end of study (EOS) in the VPP population, and mortality rate at day 30 in the modified intention-to-treat (MITT) population. RESULTS: Of 696 screened patients, 433 patients were excluded and 263 patients were allocated to receive either of the treatments. Males comprised 54% of patients and mean age and PSI were 62.1 ± 19.8 years and 69.3 ± 30.0, respectively, with 124 patients allocated to the CTRX group and 138 patients allocated to the ABPC/SBT group. The clinical effectiveness rate for the VPP population at EOT was 90% in the CTRX and 96% in the ABPC/SBT group (p = 0.072, 95% confidence interval [CI] of risk difference [RD]: - 12.6-0.8%). No significant difference in effectiveness at day 4 was observed between the CTRX and ABPC/SBT groups (p = 0.079, 95%CI of RD: - 12.1-0.4%), but at day 7, ABPC/SBT was significantly more effective than CTRX in the VPP population (p = 0.047, 95%CI of RD: - 13.3--0.4%). No significant difference in late response at EOS was seen between CTRX and ABPC/SBT groups: cure (89 [86%] and 102 [94%]), relapse (5 [5%] and 1 [1%]) and failure (10 [10%] and 5 [5%]; p = 0.053). Deaths within 30 days in MITT population was higher in CTRX group (4 [3%]) than in ABPC/SBT group (0 [0%]) (p = 0.048, 95%CI of RD: 0.1-6.3%). CONCLUSION: No significant difference in effectiveness was found between ABPC/SBT and CTRX at EOT. However, ABPC/SBT might be more effective in the early phase of treatment. TRIAL REGISTRATION: UMIN-CTR, UMIN000037464. Registered 25 July 2019 - Retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042262.

Cefepime vs. meropenem for moderate-to-severe pneumonia in patients at risk for aspiration: An open-label, randomized study.

BACKGROUND: Treatment of aspiration pneumonia is an important problem due to aging of populations worldwide. However, the effectiveness of cefepime in aspiration pneumonia has not yet been evaluated. AIM: To compare the clinical efficacy and safety of cefepime and meropenem in patients with moderate-to-severe aspiration pneumonia. METHODS: In this open-label, randomized study, either cefepime 1 g or meropenem 0.5 g was administered intravenously every 8 h to patients with moderate-to-severe community-acquired or nursing-home acquired pneumonia at risk for aspiration for an average of 10.5 days. The primary outcome was the clinical response rate at the end of treatment (EOT) in the validated per-protocol (VPP)-population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in the VPP-population, and survival at day 30 in the modified intention-to-treat (MITT)-population. RESULTS: There was no difference between the groups in the primary or secondary outcomes or safety. Significant improvement was observed in each group on day 4. CONCLUSION: Cefepime is as effective and safe as meropenem in the treatment of moderate-to-severe aspiration pneumonia. CLINICAL TRIALS IDENTIFIER: UMIN000001349.

Epidemic Myalgia Associated with Human Parechovirus Type 3 Infection.

A 42-year-old man was hospitalized due to a fever, orchiodynia, and extremely severe myalgia predominantly in the extremities, which made it difficult for him to stand or walk. He had a history of contact with his son who had acute upper respiratory infection. Based on the characteristic clinical symptoms and detection of the partial sequence of human parechovirus type 3 (HPeV3) in throat swabs as well as stool and serum samples, he was diagnosed with epidemic myalgia associated with HPeV3 infection. Because HPeV3 infection is widespread among children in Japan, HPeV3-associated myalgia should be considered when adult patients manifest such distinguishing clinical characteristics.

A case of pulmonary tuberculosis diagnosed in a patient with manifestations of haemophagocytic lymphohistiocytosis.

An 80-year-old woman was admitted with continuous fever, hepatic dysfunction and cytopaenia. The presence of hepatosplenomegaly, hyperferritinaemia, hypofibrinogenaemia and phagocytosis by macrophages in the bone marrow was consistent with a diagnosis of haemophagocytic lymphohistiocytosis (HLH). We suspected that HLH was induced by pre-existing tuberculosis, and antitubercular agents were started. Positive nucleic acid amplification and sputum culture for Mycobacterium tuberculosis resulted in a diagnosis of pulmonary tuberculosis. The patient improved with three months of treatment. In this patient, manifestations of HLH preceded those of pulmonary tuberculosis. A diagnosis of HLH should increase suspicion of disseminated tuberculosis and thus contribute to early detection.

A case of pernicious anemia requiring differential diagnosis of autoimmune hemolytic anemia complication.

An 80-year-old female was admitted to our hospital due to malaise. The initial diagnosis on admission was pernicious anemia (PA), Hashimoto thyroiditis and autoimmune atrophic gastritis. Autoimmune hemolytic anemia was suspected because direct antiglobulin test (DAT) was positive. Treatment with vitamin B12 improved anemia, with the disappearance of hemolysis. In some cases, PA patients with positive DAT may have hemolysis without the involvement of the autoimmune mechanism. Therefore, it is important to carefully assess PA patients with hemolysis and positive DAT for the prevention of unnecessary administration of steroid therapy.

Tazobactam/piperacillin for moderate-to-severe pneumonia in patients with risk for aspiration: comparison with imipenem/cilastatin.

BACKGROUND: Treatment of aspiration pneumonia is becoming an important issue due to aging of populations worldwide. Effectiveness of tazobactam/piperacillin (TAZ/PIPC) in aspiration pneumonia is not clear. PURPOSE: To compare clinical efficacy between TAZ/PIPC (1:4 compound) and imipenem/cilastatin (IPM/CS) in patients with moderate-to-severe aspiration pneumonia. PATIENTS AND METHODS: In this open-label, randomized study either TAZ/PIPC 5 g or IPM/CS 1 g was intravenously administered every 12 h to patients with moderate-to-severe community-acquired aspiration pneumonia or nursing home-acquired pneumonia with risk for aspiration pneumonia for average 11 days. The primary outcome was clinical response rate at the end of treatment (EOT) in validated per-protocol (VPP) population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in VPP population, and survival at day 30 in modified intention-to-treat (MITT) population. RESULTS: There was no difference between the groups in primary or secondary outcome. However, significantly faster improvement as measured by axillary temperature (p < 0.05) and WBC count (p = 0.01) was observed under TAZ/PIPC treatment. In patients with gram-positive bacterial infection, TAZ/PIPC was more effective at EOT in VPP population (p = 0.03). CONCLUSION: TAZ/PIPC is as effective and safe as IPM/CS in the treatment of moderate- to-severe aspiration pneumonia.