Carolina Garcia-Vidal

Bacteraemia due to multidrug-resistant Gram-negative bacilli in cancer patients: risk factors, antibiotic therapy and outcomes

OBJECTIVES To assess the risk factors, antibiotic therapy and outcomes of multidrug-resistant Gram-negative bacilli (MDRGNB) bacteraemia in hospitalized patients with cancer. METHODS Episodes of MDRGNB bacteraemia were compared with a susceptible control group in a 4 year prospective study. RESULTS Of 747 bacteraemias, 372 (49.7%) were caused by a Gram-negative bacilli (GNB). Fifty-one of these (13.7%) were caused by a multidrug-resistant (MDR) strain. Previous antibiotics [odds ratio (OR) 3.57; 95% confidence interval (CI) 1.63-7.80] and urinary catheter (OR 2.41; 95% CI 1.01-5.74) were identified as independent risk factors for MDRGNB acquisition. The most frequent mechanism of resistance was extended-spectrum β-lactamase (ESBL) production (45%), mainly by Escherichia coli, followed by Amp-C cephalosporinase hyperproduction (24%). Patients with MDRGNB bacteraemia more frequently received inadequate initial antibiotic therapy (69% versus 9%; P < 0.001) and time to adequate therapy was longer in this group (41% versus 4%; P < 0.001). Patients in the resistant group more frequently required intensive care unit (ICU) admission (14% versus 5%; P = 0.023), had greater need for mechanical ventilation (14% versus 3%; P = 0.005) and had a higher overall case-fatality rate (41% versus 21%; P = 0.003). Risk factors for mortality were solid tumour (OR 5.04; 95% CI 2.49-10.19), current corticosteroid use (OR 4.38; 95% CI 2.39-8.05), ICU admission (OR 11.40; 95% CI 3.19-40.74) and MDRGNB bacteraemia (OR 3.52; 95% CI 1.36-9.09). CONCLUSIONS MDRGNB bacteraemia was common among cancer patients, especially in those exposed to antibiotics and urinary catheter. The most frequent mechanism of resistance was ESBL production. Patients with MDRGNB more frequently received inadequate empirical antibiotic therapy and presented poorer outcomes with a higher overall case-fatality rate (within 30 days).

Bacteraemia due to extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) in cancer patients: clinical features, risk factors, molecular epidemiology and outcome

OBJECTIVES To assess the clinical features, risk factors, molecular epidemiology and outcome of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) bacteraemia in hospitalized cancer patients. METHODS Episodes of ESBL-EC bacteraemia were compared with a susceptible control group in a 3 year prospective study. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by PFGE. RESULTS Out of 531 episodes of bacteraemia, 135 were caused by E. coli. Seventeen of these cases involved ESBL-EC-producing strains (12.6%). In the multivariate analysis, female gender [odds ratio (OR) 3.43; 95% confidence interval (CI) 1.03-11.4] and previous antibiotic therapy (OR 3.22; 95% CI 1.00-10.3) were found to be independent risk factors for ESBL acquisition. An analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (59%). Patients with ESBL-EC bacteraemia were more likely to have received an inadequate empirical antibiotic therapy (65% versus 6%; P = 0.000), and the time to adequate therapy was longer in this group (0 versus 1.50 days; P = 0.000). The overall mortality rate was 22%, ranging from 20% to 35% (P = 0.20). Risk factors for mortality were solid tumour (OR 19.41; 95% CI 4.66-80.83), corticosteroid therapy (OR 3.04 95% CI 1.05-8.81) and intensive care unit admission (OR 248.24, 95% CI 18.49-3332.14). In neutropenic patients, ESBL-EC bacteraemia was associated with poorer outcome and a higher overall mortality rate (37.5% versus 6.5%; P = 0.01). CONCLUSIONS In our centre, ESBL-EC bacteraemia is frequent among cancer patients, especially in those exposed to antibiotic pressure. All ESBL-EC strains were unrelated and most of them carried a CTX-M group enzyme. Patients with ESBL-EC bacteraemia received inadequate empirical antibiotic therapy more frequently than patients carrying a susceptible strain, but significant differences in mortality could not be demonstrated.

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.

Early mortality in patients with community-acquired pneumonia: causes and risk factors

The first 48 h of evolution of patients with community-acquired pneumonia (CAP) are critical. The aim of the present study was to determine the frequency, causes and factors associated with early mortality in CAP. Nonimmunocompromised adults hospitalised with CAP were prospectively observed from 1995 to 2005. Early deaths, defined as death due to any cause ≤48 h after admission, were compared with all patients who survived >48 h. Furthermore, early deaths were compared with late deaths (patients who died >48 h) and with survivors. Of 2,457 patients, 57 (2.3%) died ≤48 h after admission. Overall mortality was 7.7%. The main causes of early mortality were respiratory failure and septic shock/multiorgan failure. Independent factors associated with early deaths were increased age, altered mental status at presentation, multilobar pneumonia, shock at admission, pneumococcal bacteraemia and discordant empiric antibiotic therapy. Currently, early mortality is relatively low and is caused by pneumonia-related factors. It occurs mainly among the elderly and in patients presenting with altered mental status, multilobar pneumonia and septic shock. Pneumococcal bacteraemia and discordant antibiotic therapy, mainly due to lack of coverage against Pseudomonas aeruginosa are also significant risk factors.

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 β-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.

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

IntroductionThe benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP.MethodsThis was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo.ResultsOf the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups.ConclusionsMPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission.Trial RegistrationInternational Standard Randomized Controlled Trials Register, ISRCTN22426306.

Pseudomonas aeruginosa in patients hospitalised for COPD exacerbation: a prospective study.

Risk factors for Pseudomonas aeruginosa (PA) isolation in patients hospitalised for chronic obstructive pulmonary disease (COPD) exacerbation remain controversial. The aim of our study was to determine the incidence and risk factors for PA isolation in sputum at hospital admission in a prospective cohort of patients with acute exacerbation of COPD. We prospectively studied all patients with COPD exacerbation admitted to our hospital between June 2003 and September 2004. Suspected predictors of PA isolation were studied. Spirometry tests and 6-min walking tests were performed 1 month after the patients were discharged. High-resolution computed tomography (HRCT) was performed in a randomised manner in one out of every two patients to quantify the presence and extent of bronchiectasis. Patients were followed up during the following year for hospital re-admissions. A total of 188 patients were included, of whom 31 (16.5%) had PA in sputum at initial admission. The BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index (OR 2.18, CI 95% 1.26–3.78; p = 0.005), admissions in the previous year (OR 1.65, CI 95% 1.13–2.43; p = 0.005), systemic steroid treatment (OR 14.7, CI 95% 2.28–94.8; p = 0.01), and previous isolation of PA (OR 23.1, CI 95% 5.7–94.3; p<0.001) were associated with PA isolation. No relationship was seen between bronchiectasis in HRCT and antibiotic use in the previous 3 months. PA in sputum at hospital admission is more frequent in patients with poorer scoring on the BODE index, previous hospital admissions, oral corticosteroids and prior isolation of PA.

Community-acquired Legionella pneumophila pneumonia: a single-center experience with 214 hospitalized sporadic cases over 15 years.

AbstractLegionella pneumophila has been increasingly recognized as a cause of community-acquired pneumonia (CAP) and an important public health problem worldwide. We conducted the present study to assess trends in epidemiology, diagnosis, clinical features, treatment, and outcomes of sporadic community-acquired L. pneumophila pneumonia requiring hospitalization at a university hospital over a 15-year period (1995–2010). Among 3934 nonimmunosuppressed hospitalized patients with CAP, 214 (5.4%) had L. pneumophila pneumonia (16 cases were categorized as travel-associated pneumonia, and 21 were part of small clusters). Since the introduction of the urinary antigen test, the diagnosis of L. pneumophila using this method remained stable over the years (p = 0.42); however, diagnosis by means of seroconversion and culture decreased (p < 0.001 and p = 0.001, respectively).The median age of patients with L. pneumophila pneumonia was 58.2 years (SD 13.8), and 76.4% were male. At least 1 comorbid condition was present in 119 (55.6%) patients with L. pneumophila pneumonia, mainly chronic heart disease, diabetes mellitus, and chronic pulmonary disease. The frequency of older patients (aged >65 yr) and comorbidities among patients with L. pneumophila pneumonia increased over the years (p = 0.06 and p = 0.02, respectively). In addition, 100 (46.9%) patients were classified into high-risk classes according to the Pneumonia Severity Index (groups IV–V). Twenty-four (11.2%) patients with L. pneumophila pneumonia received inappropriate empirical antibiotic therapy at hospital admission. Compared with patients who received appropriate empirical antibiotic, patients who received inappropriate therapy more frequently had acute onset of illness (p = 0.004), pleuritic chest pain (p = 0.03), and pleural effusion (p = 0.05). The number of patients who received macrolides decreased over the study period (p < 0.001), whereas the number of patients who received levofloxacin increased (p < 0.001). No significant difference was found in the outcomes between patients who received erythromycin and clarithromycin. However, compared with macrolide use during hospital admission, levofloxacin therapy was associated with a trend toward a shorter time to reach clinical stability (median, 3 vs. 5 d; p = 0.09) and a shorter length of hospital stay (median, 7 vs. 10 d; p < 0.001).Regarding outcomes, 38 (17.8%) patients required intensive care unit (ICU) admission, and the inhospital case-fatality rate was 6.1% (13 of 214 patients). The frequency of ICU admission (p = 0.34) and the need for mechanical ventilation (p = 0.57) remained stable over the study period, but the inhospital case-fatality rate decreased (p = 0.04). In the logistic regression analysis, independent factors associated with severe disease (ICU admission and death) were current/former smoker (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.01–8.62), macrolide use (OR, 2.40; 95% CI, 1.03–5.56), initial inappropriate therapy (OR, 2.97; 95% CI, 1.01–8.74), and high-risk Pneumonia Severity Index classes (OR, 9.1; 95% CI, 3.52–23.4).In conclusion, L. pneumophila is a relatively frequent causative pathogen among hospitalized patients with CAP and is associated with high morbidity. The annual number of L. pneumophila cases remained stable over the study period. In recent years, there have been significant changes in diagnosis and treatment, and the inhospital case-fatality rate of L. pneumophila pneumonia has decreased.

Aetiology of, and risk factors for, recurrent community-acquired pneumonia

Recurrent community-acquired pneumonia (CAP) requiring hospitalization is a matter of particular concern. However, current information on its prevalence, aetiology and risk factors is lacking. To address these issues, we performed an observational analysis of a prospective cohort of hospitalized adults with CAP. Recurrence was defined as two or more episodes of CAP 1 month apart within 3 years. Patients with severe immunosuppression or local predisposing factors were excluded. Of the 1556 patients, 146 (9.4%) had recurrent CAP. The most frequent causative organism was Streptococcus pneumoniae, both in patients with recurrent CAP and in those without recurrence. Haemophilus influenzae, other Gram-negative bacilli and aspiration pneumonia were more frequent among patients with recurrent CAP, whereas Legionella pneumophila was rarely identified in this group. Independent factors associated with recurrent CAP were greater age, lack of pneumococcal vaccination, chronic obstructive pulmonary disease (COPD) and corticosteroid therapy. In a sub-analysis of 389 episodes of pneumococcal pneumonia, the only independent risk factor for recurrence was lack of pneumococcal vaccination. Recurrence of CAP is not a rare clinical problem and it occurs mainly in the elderly, patients with COPD, and those receiving corticosteroids. Our study provides support for recommending pneumococcal vaccination for adults at risk of pneumonia, including those with a first episode of CAP.

Pathogenesis of invasive fungal infections.

Purpose of review Invasive fungal infection (IFI) is increasingly being recognized as a significant cause of morbidity and mortality in immunosuppressed patients. This review focuses on the latest literature reports concerning the pathogenesis of IFI in this population. Recent findings New virulence factors of Candida and Aspergillus have recently been identified. The past few months have brought significant advances in our understanding of how the immune system acts against fungal infection, especially with regard to the role of mucosa in the innate immune system, the arsenal of innate immune recognition receptors and the pathways connecting innate and adaptive immunity. Summary Knowledge of fungal pathogenesis and host immune response can help to optimize the management of fungal infections. Greater understanding of these processes may aid physicians in developing better prophylactic measures and antifungal or immunomodulatory therapies.