Effects of additive corticosteroid therapy on 90-day survival in patients with community-onset pneumonia.

INTRODUCTION: Systemic corticosteroid therapy is occasionally used as an additive therapy, especially for patients with severe pneumonia. However, its recommendation for use in patients with pneumonia varies worldwide, and its efficacy is unclear. METHODS: Adult Japanese patients hospitalized with community-onset pneumonia between January and December 2012 were analyzed using the Diagnostic Procedure Combination database. The patients were classified into mild-to-moderate and severe groups using the A-DROP (age, dehydration, respiration, orientation, and blood pressure) system. The 90-day survival rate was evaluated between the presence or absence of corticosteroid treatment using the Kaplan-Meier method in the overall, mild-to-moderate and severe groups, respectively. The patients' clinical characteristics were adjusted between the two groups using the inverse probability of treatment weighting method. RESULTS: Among 123,811, 110,534 patients were classified as mild-to-moderate grade (corticosteroid group: 8,465, non-corticosteroid group: 102,069) and 13,277 patients were classified as severe grade (corticosteroid group: 1,338, non-corticosteroid group: 11,939). The 90-day survival rate was higher in the non-corticosteroid group than in the corticosteroid group in patients with pneumonia of overall grade (weighted hazard ratio [HR]: 1.36; P < 0.001) and those with mild-to-moderate grade (weighted HR: 1.46; P < 0.001). However, there were no significant differences in the outcomes between the two groups in those with severe grade (weighted HR: 1.08; P = 0.38). CONCLUSIONS: Additive systemic corticosteroid therapy may be related to poor 90-day prognosis in patients with mild-to-moderate grade community-onset pneumonia, although it may not be positively associated with its prognosis in those with severe grade.

Clinical factors influencing the performance of bacterial multiplex polymerase chain reaction in patients with community-onset pneumonia.

The etiologic diagnostic yield of community-onset pneumonia (COP) using conventional methods is low. Bacterial multiplex polymerase chain reaction (mPCR) has been shown to be more sensitive than conventional methods. This study assessed the clinical factors influencing bacterial mPCR results in patients with COP. Patients with COP admitted to a tertiary care hospital between November 2015 and April 2016 were retrospectively assessed. Conventional methods included culture-based methods and serology for Mycoplasma pneumoniae. Bacterial mPCR that could identify Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, and Legionella pneumophilia was performed. Bacterial mPCR was performed in a total of 342 patients with COP in the study. Bacterial mPCR alone provided etiology in 99 patients. The total etiologic diagnosis rates improved from 22.2 to 51.1% when bacterial mPCR was added to conventional methods. Additional diagnostic benefits of bacterial mPCR were more prominent in the prior antibiotic non-exposure group (77.8% vs 63.5%, P = 0.015) and in the low-risk group with low CURB 65 score (62.6% vs 44.9%, P = 0.005). Patients who required ICU care, those with healthcare-associated pneumonia (HCAP), and patients with any underlying diseases were not associated with the additional pathogen detection rates using bacterial mPCR. By supplementing conventional diagnostic methods with bacterial mPCR-based methods, the overall pathogen detection rates improved in patients with COP. Moreover, the additional diagnostic usefulness of bacterial mPCR was significantly higher in patients without prior antibiotic exposure and in the mild-to-moderate-risk group with lower CURB 65 score.

1g versus 2 g daily intravenous ceftriaxone in the treatment of community onset pneumonia - a propensity score analysis of data from a Japanese multicenter registry.

BACKGROUND: Community-onset pneumonia (COP) is a combined concept of community acquired pneumonia and the previous classification of healthcare-associated pneumonia. Although ceftriaxone (CRO) is one of the treatment choices for COP, it is unclear whether 1 or 2 g CRO daily has better efficacy. We compared the effectiveness of 1 g with 2 g of CRO for COP treatment. We hypothesized that 1 g CRO would show non-inferiority over 2 g CRO. METHODS: This study was an analysis of prospectively registered data of the patients with COP from four Japanese hospitals (the Adult Pneumonia Study Group-Japan: APSG-J). We included subjects who were initially treated solely with 1 or 2 g of CRO. The propensity score was estimated from the 33 pre-treatment variables, including age, sex, weight, pre-existing comorbidities, prescribed drugs, risk factors for aspiration pneumonia, vital signs, laboratory data, and a finding from chest xrays. The primary endpoint was the cure rate, for which a non-inferiority analysis was performed with a margin of 0.05. In addition, we performed three sensitivity analyses; using data limited to the group in which CRO solely was used until the completion of treatment, using data limited to inpatient cases, and performing a generalized linear mixed-effect logistic regression analysis to assess the primary outcome after adjusting for random hospital effects. RESULTS: Of the 3817 adult subjects with pneumonia who were registered in the APSG-J study, 290 and 216 were initially treated solely with 1 or 2 g of CRO, respectively. Propensity score matching was used to extract 175 subjects in each group. The cure rate was 94.6 and 93.1% in the 1 and 2 g CRO groups, respectively (risk difference 1.5%; 95% confidence interval - 3.1 to 6.0; p = 0.009 for non-inferiority). The results of the sensitivity analyses were consistent with the primary result. CONCLUSIONS: The propensity score-matched analysis of multicenter cohort data from Japan revealed that the cure rate for COP patients treated with 1 g daily CRO was non-inferior to that of patients treated with 2 g daily CRO.

Extended-spectrum antibiotics for community-acquired pneumonia with a low risk for drug-resistant pathogens.

OBJECTIVES: The potential hazards of extended-spectrum antibiotic therapy for patients with community-acquired pneumonia (CAP) with low risk for drug-resistant pathogens (DRPs) remain unclear; however, risk assessment for DRPs is essential to determine the initial antibiotics to be administered. The study objective was to assess the effect of unnecessary extended-spectrum therapy on the mortality of such patients. METHODS: A post hoc analysis was conducted after a prospective multicenter observational study for CAP. Multivariable logistic regression analysis was performed to assess the effect of extended-spectrum therapy on 30-day mortality. Three sensitivity analyses, including propensity score analysis to confirm the robustness of findings, were also performed. RESULTS: Among 750 patients with CAP, 416 with CAP with a low risk for DRPs were analyzed; of these, 257 underwent standard therapy and 159 underwent extended-spectrum therapy. The 30-day mortality was 3.9% and 13.8% in the standard and extended-spectrum therapy groups, respectively. Primary analysis revealed that extended-spectrum therapy was associated with increased 30-day mortality compared with standard therapy (adjusted odds ratio 2.82; 95% confidence interval 1.20-6.66). The results of the sensitivity analyses were consistent with those of the primary analysis. CONCLUSION: Physicians should assess the risk for DRPs when determining the empirical antibiotic therapy and should refrain from administering unnecessary extended-spectrum antibiotics for patients with CAP with a low risk for DRPs.

Risk factors for community-onset pneumonia caused by drug-resistant pathogens: A prospective cohort study.

INTRODUCTION: There is no consensual definition of risk factors for drug resistant pathogens (DRP) in community-onset pneumonia (COP). Healthcare-associated pneumonia criteria have been abandoned because they were found to have weak discriminative power. Our aim was to identify risk factors for DRP in COP. METHODS: Prospective cohort study, conducted over a two years' period, in a community-based hospital, including all adult patients with COP criteria. Univariate and multivariate logistic regression modeling were performed to understand the association of risk factors (demographic, clinical and epidemiological) with COP by a DRP (PES: Pseudomonas aeruginosa, extended-spectrum ß-lactamase producing Enterobacteriaceae, Methicillin-resistant Staphylococcus aureus; and other non-fermenting gram-negative bacteria, namely Acinetobacter baumannii). RESULTS: A total of 660 cases of COP were included, with a mean (±SD) age of 74±15 years and 58.9% of males. Microbiological documentation was possible in 32.6% of the cases. There were 197 cases selected for further analysis, of which 37 were cases of PES. The multivariate logistic regression model retained antibiotic use in the previous 90 days (adjusted OR=4.411, 95%CI [1.745-11.148]) and being bed-ridden (adjusted OR=5.492, 95%CI [2.121-14.222]), adjusted for Charlson's Index, CURB 65 and provenience from a long-term care facility. The area under the ROC curve for this model was 0.832, 95%CI [0.756-0.908], higher than the application of the HCAP criteria (AUROC = 0.676, 95%CI [0.582-0.770]). CONCLUSION: In this study, antibiotic use in the previous 90 days and being bed-ridden were independently associated with COP caused by DRP, after adjustment for Charlson's Index, CURB 65 and provenience from a long-term care facility.

Are third-generation cephalosporins associated with a better prognosis than amoxicillin-clavulanate in patients hospitalized in the medical ward for community-onset pneumonia?

OBJECTIVES: We aimed to assess whether treatment with ceftriaxone/cefotaxime is associated with lower in-hospital mortality than amoxicillin-clavulanate in pati0ents hospitalized in medical wards for community-onset pneumonia. METHODS: We conducted a retrospective and multicentre study of patients hospitalized in French medical wards for community-onset pneumonia between 2002 and 2015. Treatments with ceftriaxone/cefotaxime or amoxicillin-clavulanate were defined by their start in the emergency department for a duration of 5 days or more with no other ß-lactam. A logistic regression analysis was performed on the overall population, and a propensity score analysis was restricted to patients treated with either ceftriaxone/cefotaxime or amoxicillin-clavulanate. RESULTS: 1698 patients (median age, 80 y) were included, of which 716 and 198 were treated with amoxicillin-clavulanate and ceftriaxone/cefotaxime, respectively. In-hospital mortality was 10% (9-12%). In multivariate analysis, factors associated with in-hospital mortality were treatment with ceftriaxone/cefotaxime (aOR 2.9; (1.4-5.7)), pneumonia severity index class 4 or 5 (aOR 7.8 (4.3-15.7)), do-not-resuscitate order (aOR 8.7 (5.2-14.6)) and fluid therapy (aOR 6.3 (2.5-15.1)). The propensity score analysis was performed on 178 patients treated with ceftriaxone/cefotaxime matched with 178 patients treated with amoxicillin-clavulanate; no significant association between treatment with ceftriaxone/cefotaxime and in-hospital mortality was found (OR 1.5 (0.7-3.0)). CONCLUSION: In the largest study aiming to compare amoxicillin-clavulanate and ceftriaxone/cefotaxime in community-onset pneumonia, ceftriaxone/cefotaxime was not associated with lower in-hospital mortality than amoxicillin-clavulanate. Our results suggest that ceftriaxone/cefotaxime should not be preferred over amoxicillin-clavulanate for patients hospitalized in medical wards with community-onset pneumonia.

Risk Factors for Community-Onset Pneumonia Caused by Levofloxacin-Nonsusceptible Streptococcus pneumoniae.

BACKGROUND: Fluoroquinolones are antibiotics commonly used in the treatment of infections caused by Streptococcus pneumoniae. However, rates of fluoroquinolone resistance are increasing with their frequent use. We designed this study to verify current fluoroquinolone resistance rates and risk factors for community-onset pneumococcal pneumonia. METHODS: A retrospective case-control study was conducted in a tertiary referral hospital. The study population comprised patients admitted for pneumococcal pneumonia between January 2011 and May 2017. The case group included community-onset pneumonia caused by levofloxacin-nonsusceptible S. pneumoniae. The control group consisted of two patients with levofloxacin-susceptible S. pneumoniae who were admitted around the same time as each case. RESULTS: A total of 198 pneumococcal pneumonia cases were identified during the study period. Twenty-five levofloxacin-resistant S. pneumoniae cases and 3 levofloxacin-intermediate S. pneumoniae cases were included in the case group (nonsusceptibility rate = 14.1%). Multivariate analysis showed that healthcare-associated factors (odds ratio [OR] 4.78, 95% confidence interval [CI] 1.39-16.43, p = 0.013), bronchopulmonary disease (OR 3.79, 95% CI 1.07-13.40, p = 0.039), cerebrovascular disease (OR 6.08, 95% CI 1.24-29.75, p = 0.026), and exposure to fluoroquinolones within the previous 3 months (OR 5.89, 95% CI 1.21-28.68, p = 0.028) were associated with nonsusceptibility to levofloxacin. CONCLUSION: Independent risk factors for levofloxacin-nonsusceptible pneumococcal pneumonia were recent hospitalization, bronchopulmonary disease, cerebrovascular disease, and prior antibiotic use within 3 months. Careful selection of empirical antibiotics is thus needed in at-risk patients. Similarly, efforts to prevent the interpersonal spread of drug-resistant pathogens in long-term care facilities and to restrict unnecessary fluoroquinolone prescriptions are important.

Frequency of detection of Chlamydophila pneumoniae using bronchoalveolar lavage fluid in patients with community-onset pneumonia.

BACKGROUND: Chlamydophila pneumoniae is a causative pathogen of lower respiratory tract infection, which generally infects healthy, young people. However, it is often difficult to evaluate acute C. pneumoniae infection using upper respiratory tract specimens and/or sputum samples due to its persistent infection or colonization. The interpretation of frequency of detection of C. pneumoniae seems to be insufficient in community-onset pneumonia. The aim of this study was to evaluate the presence of C. pneumoniae using bronchoalveolar lavage fluid (BALF) samples. METHODS: BALF samples from 147 patients with pneumonia were retrospectively evaluated using C. pneumoniae-specific polymerase chain reaction (PCR) primers. RESULTS: None of the samples had positive PCR results for C. pneumoniae using two different sets of specific primers. Single and paired serological analyses were performed in 54 (36.7%) and 37 (25.2%) patients, respectively. These analyses revealed that 1 of 37 (2.7%) patients had a presumptive acute infection with C. pneumoniae, 8 of the 54 (14.8%) patients were suspected of having a C. pneumoniae infection, and 7 of the 37 (18.9%) patients were suspected of having past C. pneumoniae infection. In addition, cultivation and/or 16S rRNA gene sequencing detected Haemophilus influenzae in the presumptive case using the serological method. CONCLUSIONS: The results of the present study revealed that C. pneumoniae might be a minor causative agent of community-onset pneumonia according to an evaluation of specimens obtained from the lower respiratory tract.