Immunosuppressed patients with pandemic influenza A 2009 (H1N1) virus infection.

The purpose of this paper was to prospectively characterize the clinical manifestations and outcomes of confirmed influenza A 2009 (H1N1) virus infection in immunosuppressed patients with hospital admission and compare them with those of a general population. A multicenter prospective cohort study was carried out. All adult patients admitted to 13 hospitals in Spain with confirmed influenza A 2009 (H1N1) virus infection from June 12, 2009 to November 11, 2009 were included. Risk factors for complicated influenza infection were studied in immunosuppressed patients. Overall, 559 patients were included, of which 56 were immunosuppressed, nine with solid or hematological malignancies, 18 with solid-organ transplant recipients, 13 with corticosteroid therapy, and six with other types of immunosuppression. Clinical findings at diagnosis were similar in both groups. Nineteen immunosuppressed patients had pneumonia (33.9%). Immunosuppressed patients with pandemic influenza had bacterial co-infection more frequently (17.9% vs. 6.4%, p = 0.02), specifically, gram-negative bacilli and Staphylococcus aureus infections. Mortality was higher in immunosuppressed patients (7.1% vs. 1.8%, p < 0.05). The only modifiable risk factor of complicated influenza A 2009 (H1N1) was delayed antiviral therapy. In immunosuppressed patients, influenza A 2009 (H1N1) virus infection has higher mortality than in non-immunosuppressed individuals. Bacterial co-infection is common in complicated cases.

Effect of statins on outcomes in immunosuppressed patients with bloodstream infection.

Although it has been suggested that statins have a beneficial effect on the outcome of bloodstream infection (BSI) in immunosuppressed patients, prospective studies testing this hypothesis are lacking. We performed an observational analysis of consecutive cancer patients and transplant recipients hospitalized at two tertiary hospitals in Spain (2006-2009). The first episode of BSI occurring in statin users was compared with those occurring in non-statin users. During the study period, 668 consecutive episodes of BSI in 476 immunosuppressed patients were recorded. Underlying diseases were solid tumor (46.2%), hematologic malignancy (35.1%), and transplantation (18.7%). Fifty-nine (12.4%) patients were receiving statins at the onset of BSI. Comparing with statin non-users, patients on statin treatment were older (67.3 vs. 58.7 years; p < 0.001) and had higher frequency of comorbidities (74.6% vs. 40.6%; p < 0.001). There were no significant differences in intensive care unit admission (6.8% vs. 7.7%; p = 1) and overall mortality (15.3% vs. 24%; p = 0.13) between groups. In a multivariate analysis, prior statin use was not associated with increased survival (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.22-1.23; p = 0.14). In conclusion, prior statin use is not associated with increased survival in immunosuppressed patients with BSI. Caution is warranted in attributing beneficial effects to statin use in infections among immunocompromised patients.

Pneumococcal pneumonia presenting with septic shock: host- and pathogen-related factors and outcomes.

BACKGROUND: Host- and pathogen-related factors associated with septic shock in pneumococcal pneumonia are not well defined. The aim of this study was to identify risk factors for septic shock and to ascertain patient outcomes. Serotypes, genotypes and antibiotic resistance of isolated strains were also analysed. METHODS: Observational analysis of a prospective cohort of non-severely immunosuppressed hospitalised adults with pneumococcal pneumonia. Septic shock was defined as a systolic blood pressure of <90 mm Hg and peripheral hypoperfusion with the need for vasopressors for >4 h after fluid replacement. RESULTS: 1041 patients with pneumococcal pneumonia diagnosed by Gram stain and culture of appropriate samples and/or urine antigen test were documented, of whom 114 (10.9%) had septic shock at admission. After adjustment, independent risk factors for shock were current tobacco smoking (OR, 2.11; 95% CI, 1.02 to 4.34; p = 0.044), chronic corticosteroid treatment (OR, 4.45; 95% CI, 1.75 to 11.32; p = 0.002) and serotype 3 (OR, 2.24; 95% CI, 1.12 to 4.475; p = 0.022). No significant differences were found in genotypes and rates of antibiotic resistance. Compared with the remaining patients, patients with septic shock required mechanical ventilation more frequently (37% vs 4%; p<0.001) and had longer length of stay (11 vs 8 days; p<0.001). The early (10% vs 1%; p<0.001) and overall case fatality rates (25% vs 5%; p<0.001) were higher in patients with shock. CONCLUSIONS: Septic shock is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Current tobacco smoking, chronic corticosteroid treatment and infection caused by serotype 3 are independent risk factors for this complication.

Statins for community-acquired pneumonia: current state of the science.

In spite of the many advances in the diagnosis and management of community-acquired pneumonia (CAP), the mortality associated with this infection remains high. In recent years scientific evidence has emerged that shows that an excessive inflammatory response is a major cause of unfavorable outcome in patients with CAP, especially in the first few days. The use of immunomodulation appears to be an appealing option for improving prognosis in CAP. It has recently been demonstrated that statins have immunomodulatory, antioxidative and anticoagulant effects, and the beneficial effects of these drugs in sepsis have been discussed. Experimental studies have shown their effect in the modulation of the cytokine cascade and in the organization of the immunological response to respiratory infection. Most observational studies published to date support the idea that the use of statins may improve the prognosis of CAP. Randomized controlled trials are needed to validate these findings.

Predictors of multidrug-resistant Pseudomonas aeruginosa in neutropenic patients with bloodstream infection.

OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.

Levofloxacin versus azithromycin for treating legionella pneumonia: a propensity score analysis.

OBJECTIVES: Concerns have arisen regarding the equivalence of levofloxacin and some macrolides for treating community-acquired legionella pneumonia (LP). We aimed to compare the outcomes of current patients with LP treated with levofloxacin, azithromycin and clarithromycin. METHODS: Observational retrospective multicentre study of consecutive patients with LP requiring hospitalization (2000-2014) conducted in two hospitals. The primary outcome assessed was 30-day mortality. To control for confounding, therapy was assessed by multivariate analysis. RESULTS: We documented 446 patients with LP, of which 175 were treated with levofloxacin, 177 with azithromycin and 58 with clarithromycin. No significant differences in time to defervescence (2 (interquartile range (IQR) 1-4) versus 2 (IQR 1-3) days; p 0.453), time to achieve clinical stability (3 (2-5) versus 3 (2-5) days; p 0.486), length of intravenous therapy (3 (2-5.25) versus 4 (3-6) days; p 0.058) and length of hospital stay (7 (5-10) versus 6 (5-9) days; p 0.088) were found between patients treated with levofloxacin and those treated with azithromycin. Patients treated with clarithromycin had longer intravenous antibiotic treatment (3 (2-5.25) versus 5 (3-6.25) days; p 0.002) and longer hospital stay (7 (5-10) versus 9 (7-14) days; p 0.043) compared with those treated with levofloxacin. The overall mortality was 4.3% (19 patients). Neither univariate nor multivariate analysis showed a significant association of levofloxacin versus azithromycin on mortality (4 (2.3%) versus 9 (5.1%) deaths; p 0.164). The results did not change after incorporation of the propensity score into the models. CONCLUSIONS: In our study, no significant differences in most outcomes were found between patients treated with levofloxacin and those treated with azithromycin. Due to the small number of deaths, results regarding mortality should be interpreted with caution.

Predictors for individual patient antibiotic treatment effect in hospitalized community-acquired pneumonia patients.

OBJECTIVE: Our objective was to identify clinical predictors of antibiotic treatment effects in hospitalized patients with community-acquired pneumonia (CAP) who were not in the intensive care unit (ICU). METHODS: Post-hoc analysis of three prospective cohorts (from the Netherlands and Spain) of adult patients with CAP admitted to a non-ICU ward having received either ß-lactam monotherapy, ß-lactam + macrolide, or a fluoroquinolone-based therapy as empirical antibiotic treatment. We evaluated candidate clinical predictors of treatment effects in multiple mixed-effects models by including interactions of the predictors with empirical antibiotic choice and using 30-day mortality, ICU admission and length of hospital stay as outcomes. RESULTS: Among 8562 patients, empirical treatment was ß-lactam in 4399 (51.4%), fluoroquinolone in 3373 (39.4%), and ß-lactam + macrolide in 790 (9.2%). Older age (interaction OR 1.67, 95% CI 1.23-2.29, p 0.034) and current smoking (interaction OR 2.36, 95% CI 1.34-4.17, p 0.046) were associated with lower effectiveness of fluoroquinolone on 30-day mortality. Older age was also associated with lower effectiveness of ß-lactam + macrolide on length of hospital stay (interaction effect ratio 1.14, 95% CI 1.06-1.22, p 0.008). CONCLUSIONS: Older age and smoking could influence the response to specific antibiotic regimens. The effect modification of age and smoking should be considered hypothesis generating to be evaluated in future trials.

Declining mortality among hospitalized patients with community-acquired pneumonia.

Little information is available on the changes over time in community-acquired pneumonia (CAP) management and their impact on 30-day mortality in hospitalized patients. We performed a prospective, observational study of non-severely immunosuppressed hospitalized adults with CAP from 1995 to 2014. A total of 4558 patients were included. Thirty-day mortality decreased from 9.6% in the first study period (1995-99) to 4.1% in the last period (2010-14); with a progressive downward trend (-0.2% death/year; p for trend = 0.003). Over time, patients were older (p 0.02), had more co-morbidities (p 0.037), more frequently presented severe illness according to the Pneumonia Severity Index (p <0.001) and septic shock (p <0.001), and more often required intensive care unit admission (p <0.001). Combination antibiotic therapy (p <0.001) and fluoroquinolone use (p <0.001) increased. Factors independently associated with 30-day mortality were increasing age (OR 1.04; 95% CI 1.03-1.05), co-morbidities (OR 1.48; 95% CI 1.04-2.11), shock at admission (OR 4.95; 95% CI 3.49-7.00), respiratory failure (OR 1.89; 95% CI 1.42-2.52), bacteraemia (OR 2.16; 95% CI 1.58-2.96), Gram-negative bacilli aetiology (OR 4.79; 95% CI 2.52-9.10) and fluoroquinolone use (OR 0.45; 95% CI 0.29-0.71). When we adjusted for a propensity score to receive fluoroquinolones, the protective effect of fluoroquinolone use was not confirmed. In conclusion, 30-day mortality decreased significantly over time in hospitalized patients with CAP in spite of an upward trend in patient age and other factors associated with poor outcomes. Several changes in the management of CAP and a general improvement in global care over time may have caused the observed outcomes.

Impact of pre-hospital antibiotic use on community-acquired pneumonia.

Information on the influence of pre-hospital antibiotic treatment on the causative organisms, clinical features and outcomes of patients with community-acquired pneumonia (CAP) remains scarce. We performed an observational study of a prospective cohort of non-immunosuppressed adults hospitalized with CAP between 2003 and 2012. Patients were divided into two groups: those who had received pre-hospital antibiotic treatment for the same episode of CAP and those who had not. A propensity score was used to match patients. Of 2179 consecutive episodes of CAP, 376 (17.3%) occurred in patients who had received pre-hospital antibiotic treatment. After propensity score matching, Legionella pneumophila was more frequently identified in patients with pre-hospital antibiotic treatment, while Streptococcus pneumoniae was less common (p <0.001 and p <0.001, respectively). Bacteraemia was less frequent in pre-treated patients (p 0.01). The frequency of positive sputum culture and the sensitivity and specificity of the pneumococcal urinary antigen test for diagnosing pneumococcal pneumonia were similar in the two groups. Patients with pre-hospital antibiotic treatment were less likely to present fever (p 0.02) or leucocytosis (p 0.001). Conversely, chest X-ray cavitation was more frequent in these patients (p 0.04). No significant differences were found in the frequency of patients classified into high-risk Pneumonia Severity Index classes, in intensive care unit admission, or in 30-day mortality between the groups. In conclusion, L. pneumophila occurrence was nearly three times higher in patients who received pre-hospital antibiotics. After a propensity-adjusted analysis, no significant differences were found in prognosis between study groups. Pre-hospital antibiotic use should be considered when choosing aetiological diagnostic tests and empirical antibiotic therapy in patients with CAP.

Timing of antibiotic administration and outcomes of hospitalized patients with community-acquired and healthcare-associated pneumonia.

The effects of antibiotic timing on outcomes of patients with community-acquired pneumonia (CAP) are controversial. Moreover, no information is available regarding this issue in healthcare-associated pneumonia (HCAP). We aimed to determine the impact of antibiotic timing on 30-day mortality of patients with CAP and HCAP. Non-immunocompromised adults admitted to hospital through the emergency department (ED) with community-onset pneumonia were prospectively observed from 2001 to 2009. Patients who received prior antibiotics were excluded. Of 1593 patients with pneumonia who were analyzed, 1274 had CAP and 319 HCAP. The mean time from patient arrival at the ED until antibiotic administration was 5.8 h (standard deviation (SD) 3.5) in CAP and 6.1 h (SD 3.8) in HCAP (p 0.30). Mortality was higher in patients with HCAP (5.5% vs. 13.5%; p <0.001). After adjusting for confounding factors in a logistic regression analysis, the antibiotic administration ≤4 h was not associated with decreased 30-day mortality in patients with CAP (odds ratio (OR) 1.12, 95% confidence interval (CI) 0.57-2.21) and in patients with HCAP (OR 0.59, 95% CI 0.19-1.83). Similarly, antibiotic administration ≤8 h was not associated with decreased 30-day mortality in CAP (OR 1.58, 95% CI 0.64-3.88) and HCAP patients (OR 0.59, 95% CI 0.19-1.83). In conclusion, antibiotic administration within 4 or 8 h of arrival at the ED did not improve 30-day survival in hospitalized adults for CAP or HCAP.

Changes in epidemiology, clinical features and severity of influenza A (H1N1) 2009 pneumonia in the first post-pandemic influenza season.

Although the influenza A (H1N1) 2009 virus is expected to circulate as a seasonal virus for some years after the pandemic period, its behaviour cannot be predicted. We analysed a prospective cohort study of hospitalized adults with influenza A (H1N1) 2009 pneumonia at 14 teaching hospitals in Spain to compare the epidemiology, clinical features and outcomes of influenza A (H1N1) 2009 pneumonia between the pandemic period and the first post-pandemic influenza season. A total of 348 patients were included: 234 during the pandemic period and 114 during the first post-pandemic influenza season. Patients during the post-pandemic period were older and more likely to have chronic obstructive pulmonary disease, chronic kidney disease and cancer than the others. Septic shock, altered mental status and respiratory failure on arrival at hospital were significantly more common during the post-pandemic period. Time from illness onset to receipt of antiviral therapy was also longer during this period. Early antiviral therapy was less frequently administered to patients during the post-pandemic period (22.9% versus 10.9%; p 0.009). In addition, length of stay was longer, and need for mechanical ventilation and intensive-care unit admission were significantly higher during the post-pandemic period. In-hospital mortality (5.1% versus 21.2%; p <0.001) was also greater during this period. In conclusion, significant epidemiological changes and an increased severity of influenza A (H1N1) 2009 pneumonia were found in the first post-pandemic influenza season. Physicians should consider influenza A (H1N1) 2009 when selecting microbiological testing and treatment in patients with pneumonia in the upcoming influenza season.

Low incidence of multidrug-resistant organisms in patients with healthcare-associated pneumonia requiring hospitalization.

Healthcare-associated pneumonia (HCAP) includes a broad spectrum of patients who acquire pneumonia through outpatient contact with the health system. Although limited prospective data exist, it has been suggested that all patients with HCAP should receive empirical therapy with a multidrug regimen directed against drug-resistant organisms. We aimed to determine the differences in aetiology and outcomes between HCAP groups and a community-acquired pneumonia (CAP) group, and to assess the presence of antibiotic-resistant bacteria. All consecutive non-immunocompromised adults hospitalized with pneumonia were prospectively included from 2001 to 2009. Patients who had had recent contact with the health system through nursing homes, home healthcare programmes, haemodialysis clinics or prior hospitalization were considered to have HCAP. A total of 2245 patients with pneumonia were hospitalized through the emergency room, of whom 577 (25.7%) had HCAP. Significant differences in causative pathogens were found between groups. Antibiotic-resistant organisms, including methicillin-resistant Staphylococcus aureus, resistant strains of Pseudomonas aeruginosa, and extended-spectrum ß-lactamase-producing Enterobacteriaceae, were scarce in all groups. In contrast, aspiration pneumonia was particularly frequent. No differences were found regarding inappropriate initial empirical antibiotic therapy between groups. Overall mortality was higher in patients who attended a hospital or haemodialysis clinic or received intravenous chemotherapy in the 30 days before pneumonia, and among patients who resided in a nursing home or long-term-care facility. In conclusion, most HCAP patients could be treated in the same way as patients with CAP, after carefully ruling out the presence of aspiration pneumonia.

Factors associated with severe disease in hospitalized adults with pandemic (H1N1) 2009 in Spain.

The risk factors for complications in patients with influenza A (H1N1)v virus infection have not been fully elucidated. We performed an observational analysis of a prospective cohort of hospitalized adults with confirmed pandemic influenza A (H1N1)v virus infection at 13 hospitals in Spain, between June 12 and November 10, 2009, to identify factors associated with severe disease. Severe disease was defined as the composite outcome of intensive-care unit (ICU) admission or in-hospital mortality. During the study period, 585 adult patients (median age 40 years) required hospitalization because of pandemic (H1N1) 2009. At least one comorbid condition was present in 318 (54.4%) patients. Pneumonia was diagnosed in 234 (43.2%) patients and bacterial co-infection in 45 (7.6%). Severe disease occurred in 75 (12.8%) patients, of whom 71 required ICU admission and 13 (2.2%) died. Independent factors for severe disease were age <50 years (OR, 2.39; 95% CI, 1.05-5.47), chronic comorbid conditions (OR, 2.93; 95% CI, 1.41-6.09), morbid obesity (OR, 6.7; 95% CI, 2.25-20.19), concomitant and secondary bacterial co-infection (OR, 2.78; 95% CI, 1.11-7) and early oseltamivir therapy (OR, 0.32; 95% CI 0.16-0.63). In conclusion, although adults hospitalized for pandemic (H1N1) 2009 suffer from significant morbidity, mortality is lower than that reported in the earliest studies. Younger age, chronic comorbid conditions, morbid obesity and bacterial co-infection are independent risk factors for severe disease, whereas early oseltamivir therapy is a protective factor.