Bacteremic Pneumococcal Community-acquired Pneumonia Research Articles

Nausea Predicts Bacteremia in Immunocompetent Patients with Pneumococcal Community-Acquired Pneumonia: Secondary Data Analysis from a Prospective Cohort.

In pneumococcal community-acquired pneumonia (CAP), bacteremia is associated with increased mortality, but initial clinical severity scores frequently fail to identify bacteremic patients at risk. We have previously shown that gastrointestinal symptoms are common among patients admitted to the hospital with pneumococcal bacteremia. The aim of this study was to examine gastrointestinal symptoms and inflammatory responses in bacteremic and non-bacteremic pneumococcal CAP in a prospective cohort of immunocompromised and immunocompetent patients hospitalized with CAP. Logistic regression analysis was used to estimate the predictive value of gastrointestinal symptoms for pneumococcal bacteremia in patients with CAP. The Mann-Whitney test was used to compare inflammatory responses in patients with bacteremic vs. non-bacteremic pneumococcal CAP. Eighty-one patients with pneumococcal CAP were included, of whom 21 (26%) had bacteremia. Immunocompetent patients with pneumococcal CAP had an odds ratio of 16.5 (95% CI 3.0-90.9, p = 0.001) for bacteremia if nausea was present, whereas no such association was found in the immunocompromised patients (OR 0.22, 95% CI 0.02-2.05, p = 0.18). The serum levels of C-reactive protein, procalcitonin and interleukin 6 were significantly higher in the patients with bacteremic pneumococcal CAP compared to non-bacteremic pneumococcal CAP patients (p < 0.001, p = 0.005, and p = 0.019, respectively). In immunocompetent patients hospitalized with pneumococcal CAP, nausea may be a predictor of bacteremia. Bacteremic pneumococcal CAP patients display an increased inflammatory response compared to non-bacteremic pneumococcal CAP patients.

Bacteraemic pneumococcal pneumonia and SARS-CoV-2 pneumonia: differences and similarities

ObjectiveTo analyse differences in clinical presentation and outcome between bacteraemic pneumococcal community-acquired pneumonia (B-PCAP) and sSvere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pneumonia.MethodsThis observational multi-centre study was conducted on patients hospitalized with B-PCAP between 2000 and 2020 and SARS-CoV-2 pneumonia in 2020. Thirty-day survival, predictors of mortality, and intensive care unit (ICU) admission were compared.ResultsIn total, 663 patients with B-PCAP and 1561 patients with SARS-CoV-2 pneumonia were included in this study. Patients with B-PCAP had more severe disease, a higher ICU admission rate and more complications. Patients with SARS-CoV-2 pneumonia had higher in-hospital mortality (10.8% vs 6.8%; P=0.004). Among patients admitted to the ICU, the need for invasive mechanical ventilation (69.7% vs 36.2%; P<0.001) and mortality were higher in patients with SARS-CoV-2 pneumonia. In patients with B-PCAP, the predictive model found associations between mortality and systemic complications (hyponatraemia, septic shock and neurological complications), lower respiratory reserve and tachypnoea; chest pain and purulent sputum were protective factors in these patients. In patients with SARS-CoV-2 pneumonia, mortality was associated with previous liver and cardiac disease, advanced age, altered mental status, tachypnoea, hypoxaemia, bilateral involvement, pleural effusion, septic shock, neutrophilia and high blood urea nitrogen; in contrast, ≥7 days of symptoms was a protective factor in these patients. In-hospital mortality occurred earlier in patients with B-PCAP.ConclusionsAlthough B-PCAP was associated with more severe disease and a higher ICU admission rate, the mortality rate was higher for SARS-CoV-2 pneumonia and deaths occurred later. New prognostic scales and more effective treatments are needed for patients with SARS-CoV-2 pneumonia.

Comparison of prognostic factors between bacteraemic and non-bacteraemic critically ill immunocompetent patients in community-acquired severe pneumococcal pneumonia: a STREPTOGENE sub-study

BackgroundThe presence of bacteraemia in pneumococcal pneumonia in critically ill patients does not appear to be a strong independent prognostic factor in the existing literature. However, there may be a specific pattern of factors associated with mortality for ICU patients with bacteraemic pneumococcal community-acquired pneumonia (CAP). We aimed to compare the factors associated with mortality, according to the presence of bacteraemia or not on admission, for patients hospitalised in intensive care for severe pneumococcal CAP.MethodsThis was a post hoc analysis of data from the prospective, observational, multicentre STREPTOGENE study in immunocompetent Caucasian adults admitted to intensive care in France between 2008 and 2012 for pneumococcal CAP. Patients were divided into two groups based on initial blood culture (positive vs. negative) for Streptococcus pneumoniae. The primary outcome was hospital mortality, which was compared between the two groups using odds ratios according to predefined variables to search for a prognostic interaction present in bacterial patients but not non-bacteraemic patients. Potential differences in the distribution of serotypes between the two groups were assessed. The prognostic consequences of the presence or not of initial bi-antibiotic therapy were assessed, specifically in bacteraemic patients.ResultsAmong 614 included patients, 274 had a blood culture positive for S. pneumoniae at admission and 340 did not. The baseline difference between the groups was more frequent leukopaenia (26% vs. 14%, p = 0.0002) and less frequent pre-hospital antibiotic therapy (10% vs. 16.3%, p = 0.024) for the bacteraemic patients. Hospital mortality was not significantly different between the two groups (p = 0.11). We did not observe any prognostic factors specific to the bacteraemic patient population, as the statistical comparison of the odds ratios, as an indication of the association between the predefined prognostic parameters and mortality, showed them to be similar for the two groups. Bacteraemic patients more often had invasive serotypes but less often serotypes associated with high case fatality rates (p = 0.003). The antibiotic regimens were similar for the two groups. There was no difference in mortality for patients in either group given a beta-lactam alone vs. a beta-lactam combined with a macrolide or fluoroquinolone.ConclusionBacteraemia had no influence on the mortality of immunocompetent Caucasian adults admitted to intensive care for severe pneumococcal CAP, regardless of the profile of the associated prognostic factors.

Evolution of serotypes in bacteremic pneumococcal adult pneumonia in the period 2001–2014, after introduction of the pneumococcal conjugate vaccine in bizkaia (spain)

The introduction of pneumococcal conjugate vaccines (PCV7 and PCV13) in children has led to a change in the pattern of pneumococcal serotypes causing pneumococcal disease in adults. The aim of this study is to analyze the distribution of pneumococcal serotypes in adults with bacteremic pneumococcal community-acquired pneumonia (BPP) after the introduction of PCVs in childhood, and the impact of age and comorbidity on this distribution. We conducted an observational study of all adults hospitalized with BPP between 2001 and 2014, in two tertiary hospitals. Overall, we identified 451 cases of BPP (2001–2005: 194, 2006–2010: 134, 2011–2014: 123). The rate of appearance of new cases decreased over the study period. In 70% of the cases, the serotypes found were among those included in PCV13. The most prevalent serotypes were 3 (23.1%), 7F (14.6%), 19A (8.4%) and 1 (7.5%). There was a significant trend to decrease in the percentage of BPP cases due to PCV7 from period 2001–2005 to 2011–2014 (p = 0.0166) and a significant trend to increase in the six serotypes added to form PCV 13 (p = 0.0003). Serotype 3 was the most frequent in patients who developed complications during hospitalization. We did not detect a significant increase in cases caused by non-PCV13 serotypes. The most frequent non-PCV13 serotype was 22F. In conclusion, a significant proportion of adults continue to develop BPP with vaccine serotypes despite infant pneumococcal vaccination. There is a need for further strategies to reduce the current burden of this disease on adults.

The potential role of 13-valent pneumococcal conjugate vaccine in preventing respiratory complications in bacteraemic pneumococcal community-acquired pneumonia

IntroductionPneumococcal 13-valent vaccine (PCV-13) has a potential role in preventing bacteraemic pneumococcal pneumonia and its complications, but little is known about its ability to specifically prevent respiratory complications. Our aim were to analyse the pneumococcal serotypes associated with the development of respiratory complications and the potential role of PCV-13 in preventing respiratory complications in bacteraemic pneumococcal pneumonia. Material and methodsWe analysed demographic characteristics, comorbidities, antibiotic resistances and the outcomes of a cohort of 65 vaccine-naïve bacteraemic pneumococcal pneumonias, stratified by the pneumococcal serotypes included in PCV13 vs. those not included. Complications were clustered as follows: respiratory complications (hypoxemic respiratory failure; mechanical ventilation), systemic complications (septic shock; multiorgan failure), suppurative complications (empyema; pleural effusion; lung abscess). ResultsFrom a population of 65 CAP-SP, 47.7% of the isolates belonged to PCV-13 serotypes group. No differences in comorbidities or clinical manifestations were found between groups. With regard to biochemical parameters, we found more profound hypoxemia levels in PCV-13 serotypes group comparing to non-vaccine group [PaO2/FiO2 209 (63) vs. 268 (57); p=0.007]. Global complications were identified in 69.2% (45 patients), and the most frequent were respiratory complications, found in 47.7%. Respiratory complications were detected more frequently in PCV-13 groups compared to non-vaccine groups (61.3% vs. 35.3%; p=0.036). Overall 30-day mortality was 30.8%. Mortality was similar between both groups (25.8% vs. 35.3%; p=0.408). ConclusionsPneumococcal 13-valent conjugate vaccine includes the serotypes which cause more respiratory complications in our series; these serotypes were not associated with higher mortality in our series. PCV-13 may have a potential role in preventing respiratory complications due to bacteraemic pneumonoccal pneumonia.

Bacteremic pneumococcal pneumonia: clinical outcomes and preliminary results of inflammatory response.

Further examination of clinical outcomes and inflammatory response of bacteremic pneumococcal community-acquired pneumonia (CAP) is of great interest to enhance the care of patients with pneumococcal CAP. This is a secondary analysis of the Community Acquired Pneumonia Organization (CAPO) to compare the time to clinical stability (TCS), length of hospital stay (LOS), and in-hospital mortality of hospitalized pneumococcal CAP patients with and without bacteremia. To measure the effect of bacteremia in pneumococcal CAP patients on outcomes, we modeled all-cause in-hospital mortality using a Poisson regression model, and TCS and LOS using Cox proportional hazards models. Adjusted multivariate regression models were also used to predict the probability of occurrence of each of the study outcomes. To investigate the inflammatory response, we measured the plasma levels of pro- and anti-inflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1rα, IL-6, IL-8, IL-10], inflammatory biomarkers [C-reactive protein (CRP), pro-calcitonin (PCT), and B-type natriuretic peptide (BNP)], and peripheral blood neutrophil responses in 10 patients, 4 bacteremic and 6 non-bacteremic pneumococcal CAP, upon admission and every other day during the first 6 days of hospitalization. Functional data were presented as median and standard error of the median (SEM); due to small number of samples no statistical comparisons were performed between groups. From 833 pneumococcal CAP patients, 394 patients (47 %) were bacteremic. Bacteremic pneumococcal CAP were less likely to reach TCS with an adjusted hazard ratio (AHR) of 0.82 (95 % CI 0.69-0.97; p = 0.02) and had higher in-hospital mortality with an AHR of 1.63 (95 % CI 1.06-2.50, p = 0.026). Bacteremic pneumococcal CAP patients had a longer LOS than non-bacteremic pneumococcal CAP (p < 0.003). Higher plasma levels of CRP, PCT, and BNP were found in bacteremic than in non-bacteremic patients. The bacteremic group had consistently higher plasma levels of both pro- and anti-inflammatory cytokines. The blood neutrophil functional responses were similar in both groups of patients. Bacteremic pneumococcal CAP patients were significantly associated with higher in-hospital mortality, lower TCS, and longer LOS. HIV-infected patients showed a greater mortality which was not statistically significant. Bacteremic pneumococcal CAP patients had higher levels of biomarkers and systemic cytokines.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Year in review 2014: Lung cancer, pleural diseases, respiratory infections and tuberculosis, bronchoscopic intervention and imaging.

Effectiveness of the 23-Valent Pneumococcal Polysaccharide Vaccine Against Community-Acquired Pneumonia in the General Population Aged &gt;=60 Years: 3 Years of Follow-up in the CAPAMIS Study

The benefits of using the 23-valent pneumococcal polysaccharide vaccine (PPV23) are controversial. This study assessed clinical effectiveness of PPV23 in preventing community-acquired pneumonia (CAP) among the general population aged ≥ 60 years. This was a population-based cohort study involving 27 204 individuals aged ≥ 60 years in Tarragona, Spain, who were prospectively followed from 1 December 2008 until 30 November 2011. Primary outcomes were hospitalization for pneumococcal CAP (bacteremic and nonbacteremic cases) and all-cause CAP. All CAP cases were radiographically confirmed and validated by checking clinical records. Cox regression was used to evaluate the association between pneumococcal vaccination and the risk of each outcome. Cohort members were followed for a total of 76 033 person-years (29 065 person-years for vaccinated subjects). Incidence rates (per 1000 person-years) were 0.21 for bacteremic pneumococcal CAP (0.14 vs 0.26 among vaccinated and unvaccinated subjects, respectively), 1.45 for nonbacteremic pneumococcal CAP (1.46 vs 1.44), and 7.51 for all-cause CAP (7.19 vs 7.71). In primary analyses including all cohort members, PPV23 did not appear to be effective against any analyzed outcome. However, a beneficial effect emerged in sensitive and stratified analyses. After multivariable adjustments, as compared with those never vaccinated, recent vaccination with PPV23 (<5 years ago) was associated with reduced risks of bacteremic pneumococcal CAP (hazard ratio [HR], 0.38; 95% confidence interval [CI], .09-1.68), nonbacteremic pneumococcal CAP (HR, 0.52; 95% CI, .29-.92), overall pneumococcal CAP (HR, 0.49; 95% CI, .29-.84), and all-cause CAP (HR, 0.75; 95% CI, .58-.98). Our data support a protective effect of recent PPV23 vaccination (within previous 5 years) against both pneumococcal and all-cause CAP.

DNA bacterial load in children with bacteremic pneumococcal community-acquired pneumonia

This study was conducted to evaluate the association between pneumococcal DNA load and parapneumonic pleural effusion (PPE) in children with community-acquired pneumonia. Bacterial load was quantified and related to the presence of PPE with or without empyema in 72 otherwise healthy children aged ≤5 years who were hospitalised because of radiographically confirmed CAP and showed a real-time polymerase chain reaction that was positive for Streptococcus pneumoniae. The proportion of children with a high bacterial load (i.e. ≥265 DNA copies/mL) was larger among the subjects with PPE than those without it. Multivariate analysis showed that a high bacterial load was significantly associated with PPE (OR 8.65; 95% CI 1.10-67.8 vs a bacterial load of <125 copies/mL). Children with infection due to pneumococcal serotype 19A were at highest risk of developing PPE (OR 7.44; 95% CI 1.10-50.4 vs all other typeable serotypes). The patients with CAP due to pneumococcal serotypes that are not included in the 13-valent conjugate vaccine (PCV13) were more frequently affected by PPE than those with infections associated with serotypes included in the vaccine, except for serotype 19A. Bacterial loads of ≥265 DNA copies/mL are significantly associated with PPE, and serotype 19A is significantly associated with a high bacterial load and the development of PPE. The mean bacterial load of the patients with empyema was higher than that of patients with simple PPE. Although further studies are required, it seems that serotypes not included in PCV13 can play a major role in causing a higher bacterial load and PPE.

Impacto de la bacteriemia en una cohorte de pacientes con neumonía neumocócica

Bacteremia is the most common presentation of invasive disease in community-acquired pneumonia (CAP) due to Streptococcus pneumoniae. We investigated whether bacteremia in pneumococcal CAP worsens outcomes and whether it is related to pneumococcal vaccination (PV). Secondary analysis of a cohort of patients with pneumococcal CAP confirmed by blood culture, sputum culture, or urinary antigen testing. Demographic, clinical, radiographic, and biochemical data were collected, as were Acute Physiology and Chronic Health Evaluation II (APACHE II) and pneumonia severity index (PSI) scores, comorbidities, and PV history. We drew comparisons between patients with bacteremic pneumococcal CAP (BPP) and those with non-bacteremic pneumococcal CAP (NBPP). Forty-seven patients had BPP, and 71 had NBPP (confirmed by sputum culture in 45 and by urinary antigen testing in 26); 107 had some indication for PV. None of the BPP patients had received PV, compared with 9 of the NBPP patients (p = 0.043). Among the BPP patients, the mean age was higher (76.4 ± 11.5 vs. 67.5 ± 20.9 years), as were APACHE II and PSI scores (16.4 ± 4.6 vs. 14.1 ± 6.5 and 129.5 ± 36 vs. 105.2 ± 45, respectively), as well as the rate of ICU admission for cardiopathy or chronic renal failure (42.5% vs. 22.5%), whereas hematocrit and plasma sodium levels were lower (35.7 ± 5.8 vs. 38.6 ± 6.7% and 133.9 ± 6.0 vs. 137.1 ± 5.5 mEq/L, respectively), although mortality was similar (29.8% vs. 28.2%). In this population at high risk for CAP due to S. pneumoniae, the PV rate was extremely low (8.4%). Although BPP patients were more severely ill, mortality was similar between the two groups. Because PV reduces the incidence of BPP, the vaccination rate in at-risk populations should be increased.

Bacteremic Pneumococcal Community-acquired Pneumonia in Children Less Than 5 Years of Age in Italy

This study was designed to determine the proportion of bacteremic pneumococcal cases in a group of pediatric subjects with community-acquired pneumonia (CAP), the importance of the different serotypes and the impact of the currently available pneumococcal conjugate vaccines (PCVs). The study involved children who were ≤5 years with radiographically confirmed CAP admitted to hospital in Italy between September 2008 and March 2011. A diagnosis of laboratory-confirmed bacteremic pneumococcal CAP was made in the presence of a culture and/or real-time polymerase chain reaction (PCR) positive for Streptococcus pneumoniae. A total of 510 children were included in the study. Pneumococcal CAP was diagnosed in 73 cases (14.3%): S. pneumoniae was identified by means of positive real-time PCR in 67 cases (91.8%), a positive blood culture in 1 (1.4%) and both in 5 (6.8%). Complicated pneumonia was observed significantly more often in the pneumococcal-positive cases (P=0.02) and empyema was the main complication (P=0.007). Serotype 19A was most frequently encountered (17 cases; 25.8%), followed by serotypes 14 (10 cases, 15.1%), 4 (5 cases, 7.6%) and 3 (4 cases, 6.1%). The theoretical coverage offered by the available PCVs was calculated to be 31% for PCV7, 37% for PCV10 and 71% for PCV13. In Italy, bacteremic pneumococcal CAP accounts for a significant number of CAP cases in children who were ≤5 years, with serotypes 19A and 14 being the most frequent. This suggests that PCV13 is the best means of preventing pneumococcal CAP.

The role of mannose-binding lectin in pneumococcal infection

The role of mannose-binding lectin (MBL) deficiency (MBL2; XA/O and O/O genotypes) in host defences remains controversial. The surfactant proteins (SP)-A1, -A2 and -D, other collectins whose genes are located near MBL2, are part of the first-line lung defence against infection. We analysed the role of MBL on susceptibility to pneumococcal infection and the existence of linkage disequilibrium (LD) among the four genes. We studied 348 patients with pneumococcal community-acquired pneumonia (P-CAP) and 2,110 controls. A meta-analysis of MBL2 genotypes in susceptibility to P-CAP and to invasive pneumococcal disease (IPD) was also performed. The extent of LD of MBL2 with SFTPA1, SFTPA2 and SFTPD was analysed. MBL2 genotypes did not associate with either P-CAP or bacteraemic P-CAP in the case-control study. The MBL-deficient O/O genotype was significantly associated with higher risk of IPD in a meta-analysis, whereas the other MBL-deficient genotype (XA/O) showed a trend towards a protective role. We showed the existence of LD between MBL2 and SP genes. The data do not support a role of MBL deficiency on susceptibility to P-CAP or to IPD. LD among MBL2 and SP genes must be considered in studies on the role of MBL in infectious diseases.

Combination antibiotic therapy for community-acquired pneumonia

Community-acquired pneumonia (CAP) is a common and potentially serious illness that is associated with morbidity and mortality. Although medical care has improved during the past decades, it is still potentially lethal. Streptococcus pneumoniae is the most frequent microorganism isolated. Treatment includes mandatory antibiotic therapy and organ support as needed. There are several antibiotic therapy regimens that include β-lactams or macrolides or fluoroquinolones alone or in combination. Combination antibiotic therapy achieves a better outcome compared with monotherapy and it should be given in the following subset of patients with CAP: outpatients with comorbidities and previous antibiotic therapy, nursing home patients with CAP, hospitalized patients with severe CAP, bacteremic pneumococcal CAP, presence of shock, and necessity of mechanical ventilation. Better outcome is associated with combination therapy that includes a macrolide for wide coverage of atypical pneumonia, polymicrobial pneumonia, or resistant Streptococcus pneumoniae. Macrolides have shown different properties other than antimicrobial activity, such as anti-inflammatory properties. Although this evidence comes from observational, most of them retrospective and nonblinded studies, the findings are consistent. Ideally, a prospective, multicenter, randomized trial should be performed to confirm these findings.

The Fcγ receptor IIA-H/H131 genotype is associated with bacteremia in pneumococcal community-acquired pneumonia*

To assess the potential association of the functional polymorphism rs1801274 in the receptor IIa for the Fc portion of immunoglobin G (FcγRIIa) gene (FCGR2A-H131R) with the susceptibility to and the severity of community-acquired pneumonia (CAP). Multicenter prospective and observational study. Four university hospitals in Spain. FCGR2A-H131R polymorphism was determined in 1,262 patients with CAP and in 1,224 in the subject control group. Severe sepsis was recorded in 366 patients. No significant differences in genotype or allele frequencies were seen among patients with CAP or pneumococcal CAP (PCAP) and controls. Patients with bacteremic PCAP (B-PCAP) had significantly higher frequencies of FCGR2A-H/H131 genotypes than those with nonbacteremic PCAP (p = .00016, odds ratio = 2.9, 95% confidence interval 1.58-5.3). The differences remained significant when adjusting for pneumonia severity index, hospital of origin, and intensive care unit admission (p = .0012, odds ratio = 2.83, 95% confidence interval 1.51-5.32). B-PCAP was associated with a significantly higher severity of the disease, evaluated as sepsis severity (p = .000007, odds ratio = 4.40, 95% confidence interval 2.31-8.39), multiorgan dysfunction syndrome (0.00048, odds ratio = 3.29, 95% confidence interval 1.69-6.41), intensive care unit admission, acute renal failure, and acute respiratory distress syndrome. Our results do not support a role of FCGR2A-H131R polymorphism in susceptibility to CAP or PCAP. However, we provide the insight that homozygosity for FCGR2A-H131 predisposes B-PCAP, which was associated with higher severity in our study.

Outcomes of hospitalized patients with bacteraemic and non-bacteraemic community-acquired pneumonia caused by Streptococcus pneumoniae

In contrast to bacteraemic pneumococcal community-acquired pneumonia (CAP), there is a paucity of data on the clinical characteristics and outcomes of non-bacteraemic pneumococcal CAP. This retrospective study compared the outcome of hospitalized patients with bacteraemic and non-bacteraemic pneumococcal CAP treated at a medical centre from 2004 to 2008. Data on clinical outcomes including all-cause mortality, length of hospital stay, need for intensive-care unit admission and extrapulmonary involvement were analysed. In all, 221 patients with pneumococcal pneumonia (87 bacteraemic, 134 non-bacteraemic) were included. Patients with bacteraemic pneumococcal pneumonia (BPP) were older than those with non-BPP (46·2 ± 30·7 years vs. 21·7 ± 30·8 years, P<0·001) and were more likely to have underlying medical diseases (66·7% vs. 33·6%, P<0·001). The overall mortality rates at 7, 14, and 30 days were significantly higher in BPP than non-BPP patients (12·6% vs. 2·2%, 14·9% vs. 3·7%, 19·5% vs. 5·1%, all P<0·01). Multivariate logistic regression analysis showed that pneumococcal bacteraemia was correlated with extrapulmonary involvement (odds ratio 5·46, 95% confidence interval 1·97-15·16, P=0·001). In conclusion, S. pneumoniae bacteraemia increased the risk of mortality and extrapulmonary involvement in patients with pneumococcal CAP.

Determinants of outcome in patients with bacteraemic pneumococcal pneumonia: Importance of early adequate treatment

We set out to determine the factors influencing mortality in 125 adult patients with bacteraemic pneumococcal community-acquired pneumonia (CAP), assessing the impact on outcomes of early adequate therapy in particular. Presumed prognostic factors with p < 0.1 in the unadjusted model were subjected to multivariate Cox regression analysis, with in-hospital and 90-day mortalities as the dependent variables. A time period of >4 h from admission to start of adequate antibiotic treatment (adjusted hazard ratio (aHR) 2.62, 95% confidence interval (CI) 1.06-6.45; p =0.037) and severe sepsis or septic shock (aHR 5.06, 95% CI 1.63-15.71; p = 0.005) were independently associated with in-hospital mortality. Variables associated with 90-day mortality were Charlson comorbidity index (aHR 1.17, 95% CI 1.02-1.34; p = 0.018), severe sepsis or septic shock (aHR 3.03, 95% CI 1.22-7.51; p = 0.016) and delay of adequate antibiotic therapy >4 h (aHR 2.21, 95% CI 1.01-4.86; p = 0.048). The use of combination therapy was not included in these models but was a protective factor for delayed adequate therapy (aHR 0.53, 95% CI 0.29-0.95; p = 0.033). Administration of adequate antimicrobial therapy within 4 h of arrival is a critical determinant of survival in patients with bacteraemic pneumococcal CAP.

Optimal Pharmacological Therapy for Community-Acquired Pneumonia

The optimal pharmacological therapy of community-acquired pneumonia (CAP) is one of the most ardently debated issues in medicine. Presently, most guidelines recommend either a fluoroquinolone alone or dual therapy with a third-generation cephalosporin plus a macrolide in patients hospitalised with CAP, but few provide clinicians with specific considerations for selecting from these agents. Despite a similar spectrum of activity and favourable resistance patterns (for fluoroquinolones and third-generation cephalosporins) against CAP pathogens, there is emerging evidence that dual therapy may be superior to monotherapy in certain populations.In patients with non-severe CAP, the evidence supports the use of either monotherapy or dual therapy in most patients; however, patients with severe CAP or bacteraemic pneumococcal CAP experience improved survival when treated with dual therapy. It is unclear from this evidence if any specific combination of agents is the most effective, but the combination of a third-generation cephalosporin plus a macrolide is the most extensively studied. Dual therapy was superior to monotherapy irrespective of the susceptibility of the aetiological pathogen, thus insufficient antimicrobial spectrum does not explain the disparity. The most likely explanation for improved outcomes with dual therapy is the combined effect of optimised antimicrobial spectrum (including atypicals), decreased impact of resistance to a single agent and the immunomodulatory effects of macrolides. Increasing resistance in patients with non-severe CAP warrants the consideration of dual therapy and perhaps a reappraisal of agents usually reserved for second-line therapy, including doxycycline, in these populations as well. In light of the available evidence, dual therapy should be strongly considered in all patients with severe CAP, especially when complicated by pneumococcal bacteraemia.

Should all the bacteremic pneumococcal pneumonia patients be considered severe Community-Acquired Pneumonia?

PURPOSE: Community-acquired pneumonia (CAP) is the leading infectious cause of death in the United States. The most common pathogen isolated from CAP patients is Streptococcus pneumoniae. Previous studies considered bacteremic pneumococcal CAP as severe CAP. The primary aim of this study was to examine if patients hospitalized with bacteremic pneumococcal (BP) CAP should be considered to have severe CAP.

Prospective observational study of bacteremic pneumococcal pneumonia: Effect of discordant therapy on mortality.

To evaluate the effect of discordant empirical therapy on outcome in bacteremic pneumococcal community-acquired pneumonia. Prospective observational study. A 600-bed teaching hospital with a reference area of 400,000 inhabitants. All patients aged > or =18 yrs with a diagnosis of community-acquired pneumonia whose blood cultures, obtained within the first 48 hrs of hospitalization, demonstrated growth of Streptococcus pneumoniae were included in the study. Discordant therapy was defined as failure to administer an antibiotic with in vitro activity against the isolated strain within 24 hrs of hospital admission. The 2002 breakpoints recommended for respiratory infections by the National Committee for Clinical Laboratory Standards were used to classify therapy. A total of 100 patients with bacteremic pneumococcal pneumonia were identified. Penicillin- and macrolide-resistant strains were identified in 29 and 18 cases, respectively. Only two strains had minimum inhibitory concentrations of >2 microg/mL for cephalosporins. Discordant therapy was documented in ten patients, five of whom died. Mortality in patients receiving concordant therapy was 14% (13 of 90). Nursing home residence (odds ratio [OR] = 14.8) and immunocompromise (OR = 11.5) were independently (p <.05) associated with discordant therapy. Risk of discordant therapy was significantly higher (p <.05) when empirical therapy did not include cefotaxime or ceftriaxone (OR = 10.4). Discordant therapy (OR = 27.3), multilobar involvement (OR = 14.2), underlying chronic obstructive pulmonary disease (OR = 9.1), and hospitalization during the previous 12 wks (OR = 7.9) were independently associated (p <.05) with death. The excess mortality for initial discordant therapy was estimated to be 35.6% (95% confidence interval, 3.73-67.4). Survival in patients with bacteremic community-acquired pneumococcal pneumonia can be improved by avoiding suboptimal therapy. Using the 2002 breakpoints, it is very unlikely that discordant therapy would be given with ceftriaxone or cefotaxime. Clinical outcome is worse in those patients receiving antimicrobial therapy that in vitro testing suggests would be ineffective.

Bacteremic Pneumococcal Pneumonia: Is Combination Therapy Indicated?

During the last 30 years, mortality from bacteremic pneumococcal community-acquired pneumonia (CAP) has declined little, despite the introduction of