Adrian Ceccato

New Sepsis Definition (Sepsis-3) and Community-acquired Pneumonia Mortality. A Validation and Clinical Decision-Making Study

Rationale: The Sepsis‐3 Task Force updated the clinical criteria for sepsis, excluding the need for systemic inflammatory response syndrome (SIRS) criteria. The clinical implications of the proposed flowchart including the quick Sequential (Sepsis‐related) Organ Failure Assessment (qSOFA) and SOFA scores are unknown. Objectives: To perform a clinical decision‐making analysis of Sepsis‐3 in patients with community‐acquired pneumonia. Methods: This was a cohort study including adult patients with community‐acquired pneumonia from two Spanish university hospitals. SIRS, qSOFA, the Confusion, Respiratory Rate and Blood Pressure (CRB) score, modified SOFA (mSOFA), the Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB‐65) score, and Pneumonia Severity Index (PSI) were calculated with data from the emergency department. We used decision‐curve analysis to evaluate the clinical usefulness of each score and the primary outcome was in‐hospital mortality. Measurements and Main Results: Of 6,874 patients, 442 (6.4%) died in‐hospital. SIRS presented the worst discrimination, followed by qSOFA, CRB, mSOFA, CURB‐65, and PSI. Overall, overestimation of in‐hospital mortality and miscalibration was more evident for qSOFA and mSOFA. SIRS had lower net benefit than qSOFA and CRB, significantly increasing the risk of over‐treatment and being comparable with the “treat‐all” strategy. PSI had higher net benefit than mSOFA and CURB‐65 for mortality, whereas mSOFA seemed more applicable when considering mortality/intensive care unit admission. Sepsis‐3 flowchart resulted in better identification of patients at high risk of mortality. Conclusions: qSOFA and CRB outperformed SIRS and presented better clinical usefulness as prompt tools for patients with community‐acquired pneumonia in the emergency department. Among the tools for a comprehensive patient assessment, PSI had the best decision‐aid tool profile.

New aspects in the management of pneumonia

Despite improvements in the management of community-acquired pneumonia (CAP), morbidity and mortality are still high, especially in patients with more severe disease. Early and appropriate antibiotics remain the cornerstone in the treatment of CAP. However, two aspects seem to contribute to a worse outcome: an uncontrolled inflammatory reaction and an inadequate immune response. Adjuvant treatments, such as corticosteroids and intravenous immunoglobulins, have been proposed to counterbalance these effects. The use of corticosteroids in patients with severe CAP and a strong inflammatory reaction can reduce the time to clinical stability, the risk of treatment failure, and the risk of progression to acute respiratory distress syndrome. The administration of intravenous immunoglobulins seems to reinforce the immune response to the infection in particular in patients with inadequate levels of antibodies and when an enriched IgM preparation has been used; however, more studies are needed to determinate their impact on outcome and to define the population that will receive more benefit.

Acute respiratory distress syndrome in mechanically ventilated patients with community-acquired pneumonia

Our aim was to assess the incidence, characteristics, aetiology, risk factors and mortality of acute respiratory distress syndrome (ARDS) in intensive care unit (ICU) patients with community-acquired pneumonia (CAP) using the Berlin definition. We prospectively enrolled consecutive mechanically ventilated adult ICU patients with CAP over 20 years, and compared them with mechanically ventilated patients without ARDS. The main outcome was 30-day mortality. Among 5334 patients hospitalised with CAP, 930 (17%) were admitted to the ICU and 432 required mechanical ventilation; 125 (29%) cases met the Berlin ARDS criteria. ARDS was present in 2% of hospitalised patients and 13% of ICU patients. Based on the baseline arterial oxygen tension/inspiratory oxygen fraction ratio, 60 (48%), 49 (40%) and 15 (12%) patients had mild, moderate and severe ARDS, respectively. Streptococcus pneumoniae was the most frequent pathogen, with no significant differences in aetiology between groups. Higher organ system dysfunction and previous antibiotic use were independent risk factors for ARDS in the multivariate analysis, while previous inhaled corticosteroids were independently associated with a lower risk. The 30-day mortality was similar between patients with and without ARDS (25% versus 30%, p=0.25), confirmed by propensity-adjusted multivariate analysis. ARDS occurs as a complication of CAP in 29% of mechanically ventilated patients, but is not related to the aetiology or mortality. In mechanically ventilated patients with community-acquired pneumonia, ARDS based on the Berlin criteria was not related to aetiology or mortality http://ow.ly/BDMm30izoCN

Invasive Disease vs Urinary Antigen-Confirmed Pneumococcal Community-Acquired Pneumonia

BACKGROUND: The burden of pneumococcal disease is measured only through patients with invasive pneumococcal disease. The urinary antigen test (UAT) for pneumococcus has exhibited high sensitivity and specificity. We aimed to compare the pneumococcal pneumonias diagnosed as invasive disease with pneumococcal pneumonias defined by UAT results. METHODS: A prospective observational study of consecutive nonimmunosuppressed patients with community‐acquired pneumonia was performed from January 2000 to December 2014. Patients were stratified into two groups: invasive pneumococcal pneumonia (IPP) defined as a positive blood culture or pleural fluid culture result and noninvasive pneumococcal pneumonia (NIPP) defined as a positive UAT result with negative blood or pleural fluid culture result. RESULTS: We analyzed 779 patients (15%) of 5,132, where 361 (46%) had IPP and 418 (54%) had NIPP. Compared with the patients with IPP, those with NIPP presented more frequent chronic pulmonary disease and received previous antibiotics more frequently. Patients with IPP presented more severe community‐acquired pneumonia, higher levels of inflammatory markers, and worse oxygenation at admission; more pulmonary complications; greater extrapulmonary complications; longer time to clinical stability; and longer length of hospital stay compared with the NIPP group. Age, chronic liver disease, mechanical ventilation, and acute renal failure were independent risk factors for 30‐day crude mortality. Neither IPP nor NIPP was an independent risk factor for 30‐day mortality. CONCLUSIONS: A high percentage of confirmed pneumococcal pneumonia is diagnosed by UAT. Despite differences in clinical characteristics and outcomes, IPP is not an independent risk factor for 30‐day mortality compared with NIPP, reinforcing the importance of NIPP for pneumococcal pneumonia.

Lymphopenic Community Acquired Pneumonia (L-CAP), an Immunological Phenotype Associated with Higher Risk of Mortality

The role of neutrophil and lymphocyte counts in blood as prognosis predictors in Community Acquired Pneumonia (CAP) has not been adequately studied. This was a derivation-validation retrospective study in hospitalized patients with CAP and no prior immunosuppression. We evaluated by multivariate analysis the association between neutrophil and lymphocyte counts and mortality risk at 30-days post hospital admission in these patients. The derivation cohort (n = 1550 patients) was recruited in a multi-site study. The validation cohort (n = 2846 patients) was recruited in a single-site study. In the derivation cohort, a sub-group of lymphopenic patients, those with < 724 lymphocytes/mm3, showed a 1.93-fold increment in the risk of mortality, independently of the CURB-65 score, critical illness, and receiving an appropriate antibiotic treatment. In the validation cohort, patients with < 724 lymphocytes/mm3 showed a 1.86-fold increment in the risk of mortality. The addition of 1 point to the CURB-65 score in those patients with < 724 lymphocytes/mm3 improved the performance of this score to identify non-survivors in both cohorts. In conclusion, lymphopenic CAP constitutes a particular immunological phenotype of the disease which is associated with an increased risk of mortality. Assessing lymphocyte counts could contribute to personalized clinical management in CAP.

Twenty-year trend in mortality among hospitalized patients with pneumococcal community-acquired pneumonia

Background There is only limited information on mortality over extended periods in hospitalized patients with pneumococcal community-acquired pneumonia (CAP). We aimed to evaluate the 30-day mortality and whether is changed over a 20-year period among immunocompetent adults hospitalized with pneumococcal CAP. Methods We conducted a retrospective observational study of data that were prospectively collected at the Hospital Clinic of Barcelona of all adult patients hospitalized with diagnosis of pneumococcal CAP over a 20-year period. To aid analysis, results were divided into four periods of 5 years each (1997–2001, 2002–2006, 2007–2011, 2012–2016). The primary outcome was 30-day mortality, but secondary outcomes included intensive care unit (ICU) admission, lengths of hospital and ICU-stays, ICU-mortality, and need of mechanical ventilation. Results From a cohort of 6,403 patients with CAP, we analyzed the data for 1,120 (17%) adults with a diagnosis of pneumococcal CAP. Over time, we observed decreases in the rates of alcohol consumption, smoking, influenza vaccination, and older patients (age ≥65 years), but increases in admissions to ICU and the need for non-invasive mechanical ventilation. The overall 30-day mortality rate was 8% (95% confidence interval, 6%–9%; 84 of 1,120 patients) and did not change significantly between periods (p = 0.33). Although, we observed a decrease in ICU-mortality comparing the first period (26%) to the second one (10%), statistical differences disappeared with adjustment (p0.38). Conclusion Over time, 30-day mortality of hospitalized pneumococcal CAP did not change significantly. Nor did it change in the propensity-adjusted multivariable analysis. Since mortality in pneumococcal pneumonia has remained unaltered for many years despite the availability of antimicrobial agents with proven in vitro activity, other non-antibiotic strategies should be investigated.

Treatment with macrolides and glucocorticosteroids in severe community-acquired pneumonia: A post-hoc exploratory analysis of a randomized controlled trial

Background Systemic corticosteroids have anti-inflammatory effects, whereas macrolides also have immunomodulatory activity in addition to their primary antimicrobial actions. We aimed to evaluate the potential interaction effect between corticosteroids and macrolides on the systemic inflammatory response in patients with severe community-acquired pneumonia to determine if combining these two immunomodulating agents was harmful, or possibly beneficial. Methods We performed a post-hoc exploratory analysis of a randomized clinical trial conducted in three tertiary hospitals in Spain. This trial included patients with severe community-acquired pneumonia with high inflammatory response (C-reactive protein [CRP] >15 mg/dL) who were randomized to receive methylprednisolone 0.5 mg/kg/tpd or placebo. The choice of antibiotic treatment was at the physicians discretion. One hundred and six patients were classified into four groups according to antimicrobial therapy combination (β-lactam plus macrolide or β-lactam plus fluoroquinolone) and corticosteroid arm (placebo or corticosteroids). The primary outcome was treatment failure (composite outcome of early treatment failure, or of late treatment failure, or of both early and late treatment failure). Results The methylprednisolone with β-lactam plus macrolide group had more elderly patients, with comorbidities, and higher pneumonia severity index (PSI) risk class V, but a lower proportion of intensive care unit admission, compared to the other groups. We found non differences in treatment failure between groups (overall p = 0.374); however, a significant difference in late treatment failure was observed (4 patients in the placebo with β-lactam plus macrolide group (31%) vs. 9 patients in the placebo with β-lactam plus fluoroquinolone group (24%) vs. 0 patients in the methylprednisolone with β-lactam plus macrolide group (0%) vs. 2 patients [5%] in the methylprednisolone with β-lactam plus fluoroquinolone group overall p = 0.009). We found a significant difference for In-hospital mortality in the per protocol population (overall p = 0.01). We did not find significant differences in treatment failure, early or late; or In-hospital mortality after adjusting for severity (PSI), year and centre of enrolment. Conclusions In this exploratory analysis, we observed that the glucocorticosteroids and macrolides combination had no statistically significant association with main clinical outcomes compared with other combinations in patients with severe community acquired pneumonia and a high inflammatory response after taking account potential confounders. Trial registration Clinicaltrials.gov NCT00908713.

Mycobacterium kansasii as the Primary Etiology of Pulmonary Infections due to Non-Tuberculous Mycobacterium (NTM) in Patients Without Human Immunodeficiency Virus (HIV): Experience from a Center in Buenos Aires, Argentina

Introduction: Pulmonary diseases due to non-tuberculous mycobacterium (NTM) lung infection in HIV-negative patients are rarely described in the literature. Currently, NTM consist of more than 150 species, and they are globally ubiquitous in both natural and man-made environments.The objective of this study was to define the most frequent species of NTM causing pulmonary disease in HIVnegative patients in the city of Buenos Aires, Argentina. The prevalence of pulmonary diseases caused by NTM is difficult to determine since the isolation of NTM does not necessarily indicate disease. Methods: A retrospective review of all the respiratory cultures positive for NTM in the Bacteriology Laboratory of Posadas Hospital between January 2010 and December 2015 was performed. 31 patients without Human Immunodeficiency Virus (HIV) from whom NTM was isolated in respiratory samples, which fulfilled diagnostic criteria for NTM disease were included. Results: The mean age was 50 years at the time of the diagnosis (SD ± 17.2); and 19 patients (61.3%) were males. Mycobacterium kansasii was the most commonly isolated NTM (68%) followed by Mycobacterium avium Complex (MAC) (19%). M. kansasii was the most common cause of pulmonary infection by NTM in these HIV-negative patients. Cultures should be performed to identify the species and to treat accordingly. 46% of the patients included in the study, there was no evidence of risk factors. Only 32% of the subjects had respiratory comorbidities, and the most common radiologic finding was cavitation (55%). Discussion: Our study indicates that M. kansasii is the primary etiology of NTM pulmonary disease in HIV-negative patients in our service area in Buenos Aires. This finding supports the consideration that patients with symptoms compatible with pulmonary tuberculosis should also be evaluated for NTM with appropriate acid-fast bacilli cultures, as treatment regimens differ vastly according to the specific pathogen isolated, although clinical and radiographic presentations may have overlapping features. The possibility of M. kansasii pulmonary disease or other NTM should be considered in patients treated empirically for TB without appropriate clinical response. DOI: 10.18297/jri/vol2/iss1/5 Received Date: February 12, 2018 Accepted Date: March 17, 2018 Website: https://ir.library.louisville.edu/jri Affiliations: 1Alejandro Posadas National Hospital, Buenos Aires, Argentina ©2018, The Author(s). 21 ULJRI Vol 2, (1) 2018 ORIGINAL RESEARCH *Correspondence To: Alejandra González Work Address: Alejandro Posadas National Hospital, Buenos Aires, Argentina, Work Email: alestork@yahoo.com.ar common NTM cause of pulmonary disease worldwide [5]. It is difficult to compare the incidence and prevalence of NTM diseases across geographic areas. Because reporting NTM disease to public health authorities is not required in most countries, studies of the incidence and prevalence of NTM disease are performed differently in different countries. To compare reports regarding changes in the incidence and prevalence of NTM disease over time in a limited geographic area, one must compare reports that used the same methods. Many epidemiological reports and reviews have shown that NTM disease have been increasing since the 1950s [1,6]. The clinical significance of NTM isolation is not always clear and it is difficult to assess the incidence or prevalence of NTM disease due to several factors, notably its difficulty in differentiation from colonization. Although the detection of NTM colonies has been increasing since the 1950s [6] it is unclear why NTM disease have been increasing in humans. There are several potential contributing factors, such as, (i) an increase of mycobacterial infection sources in the environment, (ii) an increase in susceptible individuals, such as those Human Immunodeficiency Virus (HIV) positive, (iii) improvements in detection methods and laboratory equipment sensitivities (iv) an increasing life expectancy of those with chronic structural pulmonary disease (v) an increased awareness of NTM diseases [1,7]. In many countries, especially those in high-burden areas for TB, the diagnosis of TB is mainly based on the detection of acid-fast bacilli in a sputum smear, as well as on their symptoms and the results of a chest X-ray [1]. Pulmonary diseases caused by NTM could be presumptively treated as pulmonary tuberculosis (TB) as the microbiologic smear of the sputum does not distinguish NTM from TB, and the clinical manifestations are similar. In Latin America the prevalence of NTM is estimated to be much lower than that of TB. The incidence of tuberculosis in Argentina is of 23,91/ 100,000 inhabitants with wide regional variations. In the province of Buenos Aires, it is 30,27/100,000 inhabitants. There are differences in the relative abundances of mycobacterial species that cause NTM diseases across geographic areas, the NTM distribution is most notably associated with variants in environmental factors such as, soil and water distribution systems [1,7]. Pulmonary diseases due to NTM in HIV-negative patients are rarely described in the literature [8]. The objective of this study was to define the most frequent species of NTM causing pulmonary disease in HIV-negative patients in the city of Buenos Aires, Argentina. Materials and Methods A retrospective review of all the respiratory cultures positive for NTM in the Bacteriology Laboratory of Posadas Hospital between January 2010 and December 2015 was performed. Posadas Hospital is a high complexity hospital with 500 admission beds and a service area covering a population of approximately 4,400,000. IRB approval was obtained for this study. Patients older than 15 years old that fulfilled the ATS/IDSA diagnostic criteria for pulmonary disease due to NTM were included in the study [2]. All patients in the study were screened for HIV and we excluded those who presented with positive HIV serology. The method utilized to perform the cultures was the BACTEC MGIT (fluorescence) in addition to solid culture media (Lowenstein Jensen). Lateral flow immunoassay (LFA) were performed on positive cultures to differentiate NTM from TB. The following variables were analyzed: age, sex, NTM species, and clinical and radiological characteristics. For the categorical variables, we used percentages as frequency measurements. The continuous variables were expressed as mean or median depending on the sample distribution. Statistical analysis was performed using the computing environment R version 3.4.3 software [9].

Impact of bronchiectasis on outcomes of hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: A propensity matched analysis

The coexistence of both Chronic Obstructive Pulmonary Disease (COPD) and bronchiectasis (BE) define an emerging phenotype with a worse prognosis; however, data about these patients do not consider baseline characteristics as confounders. We evaluate the impact of BE on outcomes of hospitalized patients with acute exacerbation of COPD (AECOPD). We prospectively considered AECOPD patients, analysed using a propensity score matching (PSM) method. The outcomes included length of hospital stay, use of non-invasive and invasive mechanical ventilation, intensive care unit admission, and mortality up to 3-years. Out of the 449 patients enrolled, 160 had associated BE. AECOPD with BE were older, had lower body mass index and greater functional impairment and severity of symptoms than AECOPD without BE. After PSM, 91 patients were considered for each group and no significant differences were found for all baseline characteristics. In full cohort, the cumulative mortality rate, the survival time, the Kaplan-Meier survival curves and the risk of death were worse in AECOPD with BE in the follow-up of 6-months, 1-year and 3-years. After PSM, data on mortality were similar between AECOPD with and without BE. In conclusion, in AECOPD patients the presence of BE does not influence mortality in a long-term follow-up.

Community-Acquired Legionella Pneumonia in Human Immunodeficiency Virus–Infected Adult Patients: A Matched Case-Control Study

We investigate whether the clinical presentations and outcomes of Legionella pneumonia in human immunodeficiency virus (HIV)-infected patients were comparable to those seen in non-HIV-infected patients (case-control design). HIV-infected individuals presented neither a more severe disease nor a worse clinical outcome than matched HIV-negative control patients.