Impact of the Inclusion of an Aminoglycoside to the Initial Empirical Antibiotic Therapy for Gram-Negative Bloodstream Infections in Hematological Neutropenic Patients: a Propensity-Matched Cohort Study (AMINOLACTAM Study).

To test the hypothesis that the addition of an aminoglycoside to a ß-lactam antibiotic could provide better outcomes than ß-lactam monotherapy for the initial empirical treatment of hematological neutropenic patients with subsequently documented Gram-negative bacillus (GNB) bloodstream infection (BSI), a multinational, retrospective, cohort study of GNB BSI episodes in hematological neutropenic patients in six centers (2010 to 2017) was conducted. Combination therapy (ß-lactam plus aminoglycoside) was compared to ß-lactam monotherapy. The primary endpoint was the case fatality rate, assessed at 7 and 30 days from BSI onset. Secondary endpoints were nephrotoxicity and persistent BSI. Propensity score (PS) matching was performed. Among 542 GNB BSI episodes, 304 (56%) were initially treated with combination therapy, with cefepime plus amikacin being most common (158/304 [52%]). Overall, Escherichia coli (273/304 [50.4%]) was the main etiological agent, followed by Pseudomonas aeruginosa, which predominated in the combination group (76/304 [25%] versus 28/238 [11.8%]; P < 0.001). Multidrug resistance rates were similar between groups (83/294 [28.2%] versus 63/233 [27%]; P = 0.95). In the multivariate analysis, combination therapy was associated with a lower 7-day case fatality rate (odds ratio [OR], 0.37; 95% CI, 0.14 to 0.91; P = 0.035) with a tendency toward lower mortality at 30 days (OR, 0.56; 95% CI, 0.29 to 1.08; P = 0.084). After PS matching, these differences remained for the 7-day case fatality rate (OR, 0.33; 95% CI, 0.13 to 0.82; P = 0.017). In addition, aminoglycoside use was not significantly associated with renal function impairment (OR, 1.12; 95% CI, 0.26 to 4.87; P = 0.9). The addition of an aminoglycoside to the initial empirical therapy regimen for febrile neutropenic hematological patients should be considered.

Clinical Predictive Model of Multidrug Resistance in Neutropenic Cancer Patients with Bloodstream Infection Due to Pseudomonas aeruginosa.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. Of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. The rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR], 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa The application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development.

Preoperative oral antibiotic prophylaxis reduces Pseudomonas aeruginosa surgical site infections after elective colorectal surgery: a multicenter prospective cohort study.

BACKGROUND: Healthcare-associated infections caused by Pseudomonas aeruginosa are associated with poor outcomes. However, the role of P. aeruginosa in surgical site infections after colorectal surgery has not been evaluated. The aim of this study was to determine the predictive factors and outcomes of surgical site infections caused by P. aeruginosa after colorectal surgery, with special emphasis on the role of preoperative oral antibiotic prophylaxis. METHODS: We conducted an observational, multicenter, prospective cohort study of all patients undergoing elective colorectal surgery at 10 Spanish hospitals (2011-2014). A logistic regression model was used to identify predictive factors for P. aeruginosa surgical site infections. RESULTS: Out of 3701 patients, 669 (18.1%) developed surgical site infections, and 62 (9.3%) of these were due to P. aeruginosa. The following factors were found to differentiate between P. aeruginosa surgical site infections and those caused by other microorganisms: American Society of Anesthesiologists' score III-IV (67.7% vs 45.5%, p = 0.001, odds ratio (OR) 2.5, 95% confidence interval (95% CI) 1.44-4.39), National Nosocomial Infections Surveillance risk index 1-2 (74.2% vs 44.2%, p < 0.001, OR 3.6, 95% CI 2.01-6.56), duration of surgery ≥75thpercentile (61.3% vs 41.4%, p = 0.003, OR 2.2, 95% CI 1.31-3.83) and oral antibiotic prophylaxis (17.7% vs 33.6%, p = 0.01, OR 0.4, 95% CI 0.21-0.83). Patients with P. aeruginosa surgical site infections were administered antibiotic treatment for a longer duration (median 17 days [interquartile range (IQR) 10-24] vs 13d [IQR 8-20], p = 0.015, OR 1.1, 95% CI 1.00-1.12), had a higher treatment failure rate (30.6% vs 20.8%, p = 0.07, OR 1.7, 95% CI 0.96-2.99), and longer hospitalization (median 22 days [IQR 15-42] vs 19d [IQR 12-28], p = 0.02, OR 1.1, 95% CI 1.00-1.17) than those with surgical site infections due to other microorganisms. Independent predictive factors associated with P. aeruginosa surgical site infections were the National Nosocomial Infections Surveillance risk index 1-2 (OR 2.3, 95% CI 1.03-5.40) and the use of oral antibiotic prophylaxis (OR 0.4, 95% CI 0.23-0.90). CONCLUSIONS: We observed that surgical site infections due to P. aeruginosa are associated with a higher National Nosocomial Infections Surveillance risk index, poor outcomes, and lack of preoperative oral antibiotic prophylaxis. These findings can aid in establishing specific preventive measures and appropriate empirical antibiotic treatment.

Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.

The prognostic factors and optimal therapy for invasive pulmonary aspergillosis (IPA) after kidney transplantation (KT) remain poorly studied. We included in this multinational retrospective study 112 recipients diagnosed with probable (75.0% of cases) or proven (25.0%) IPA between 2000 and 2013. The median interval from transplantation to diagnosis was 230 days. Cough, fever, and expectoration were the most common symptoms at presentation. Bilateral pulmonary involvement was observed in 63.6% of cases. Positivity rates for the galactomannan assay in serum and bronchoalveolar lavage samples were 61.3% and 57.1%, respectively. Aspergillus fumigatus was the most commonly identified species. Six- and 12-week survival rates were 68.8% and 60.7%, respectively, and 22.1% of survivors experienced graft loss. Occurrence of IPA within the first 6 months (hazard ratio [HR]: 2.29; p-value = 0.027) and bilateral involvement at diagnosis (HR: 3.00; p-value = 0.017) were independent predictors for 6-week all-cause mortality, whereas the initial use of a voriconazole-based regimen showed a protective effect (HR: 0.34; p-value = 0.007). The administration of antifungal combination therapy had no apparent impact on outcome. In conclusion, IPA entails a dismal prognosis among KT recipients. Maintaining a low clinical suspicion threshold is key to achieve a prompt diagnosis and to initiate voriconazole therapy.

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case-control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09-90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08-10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04-339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63-456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.

Diagnosis and antimicrobial therapy of lung infiltrates in febrile neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO).

Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, ß-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.

Effect of long-term prophylaxis in the development of cytomegalovirus-specific T-cell immunity in D+/R- solid organ transplant recipients.

BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.

Donor-transmitted malaria after heart transplant managed successfully with artesunate.

Donor-transmitted malaria is a rare complication in solid organ transplantation, which causes high mortality. Data concerning the use of artesunate in solid organ transplant recipients are lacking. We report a heart transplant patient who developed donor-derived severe Plasmodium falciparum malaria, successfully treated with artesunate. Transmission of malaria to 2 of the other transplant recipients from the same donor was also documented.

Candida arteritis occurring in a liver transplant recipient.

We report the first case, to our knowledge, of Candida arteritis in a liver transplant recipient. The patient presented with hemorrhagic shock requiring emergency arterial repair. As Candida albicans, Candida tropicalis, and Candida glabrata were growing in the arterial tissue, the patient received antifungal therapy for 5 months, but died because of chronic graft dysfunction. No evidence of fungal infection was found in the tissue on postmortem examination.

Prevention strategies for cytomegalovirus disease and long-term outcomes in the high-risk transplant patient (D+/R-): experience from the RESITRA-REIPI cohort.

BACKGROUND: Cytomegalovirus (CMV)-negative recipients of a graft from a CMV-positive donor (D+/R-) are at high risk of CMV disease. Current preventive strategies include universal prophylaxis (UP) and preemptive therapy (PT). However, the best strategy to prevent CMV disease and achieve better long-term outcomes remains a matter of debate. METHODS: We analyzed the incidence of CMV disease and long-term outcomes including graft dysfunction and patient mortality at 5 years after transplantation with both preventive strategies. High-risk (D+/R-) kidney and liver transplant recipients from the RESITRA cohort were included. RESULTS: Of 2410 kidney or liver transplant patients, 195 (8.3%) were D+/R-. The final cohort included 58 liver and 102 kidney recipients. UP was given in 92 patients and 68 received PT; 10.9% and 36.8% developed CMV disease, respectively (P < 0.01). The independent risk factors for CMV disease were PT strategy (hazard ratio [HR], 3.30; 95% confidence interval [CI], 1.6-6.9), kidney transplantation (HR, 3.8; 95% CI, 1.4-9.9), and cyclosporine immunosuppression (HR, 2.4; 95% CI, 1.2-4.7). PT strategy was also a risk factor for CMV disease in both liver transplantation (HR, 11.0; 95% CI, 1.2-98.7) and kidney transplantation (HR, 2.7; 95% CI, 1.3-6.0), independently. The development of CMV replication during the first 2 years after transplantation was a risk factor for graft dysfunction at 5 years after transplantation (odds ratio, 3.4; 95% CI, 1.3-9.0). Nevertheless, no significant differences were seen in either graft dysfunction or mortality between the 2 strategies. CONCLUSIONS: The study supports the benefit of the UP strategy to prevent CMV disease in D+/R- liver or kidney transplant patients. The development of CMV replication during the first 2 years after transplantation was associated with graft dysfunction at 5 years after transplantation.

Prolonged vs short-term infusion of ß-lactam antibiotics for the treatment of febrile neutropenia: A systematic review and meta-analysis.

BACKGROUND: The optimisation of the use of ß-lactam antibiotics (BLA) via prolonged infusions in life-threatening complications such as febrile neutropenia (FN) is still controversial. This systematic review and meta-analysis aim to evaluate the efficacy of this strategy in onco-haematological patients with FN. METHODS: A systematic search was performed of PubMed, Web of Science, Cochrane, EMBASE, World Health Organization, and ClinicalTrials.gov, from database inception until December 2022. The search included randomised controlled trials (RCTs) and observational studies that compared prolonged vs short-term infusions of the same BLA. The primary outcome was all-cause mortality. Secondary outcomes were defervescence, requirement of vasoactive drugs, length of hospital stay and adverse events. Pooled risk ratios were calculated using random effects models. RESULTS: Five studies were included, comprising 691 episodes of FN, mainly in haematological patients. Prolonged infusion was not associated with a reduction in all-cause mortality (pRR 0.83; 95% confidence interval 0.47-1.48). Nor differences were found in secondary outcomes. CONCLUSIONS: The limited data available did not show significant differences in terms of all-cause mortality or significant secondary outcomes in patients with FN receiving BLA in prolonged vs. short-term infusion. High-quality RCTs are needed to determine whether there are subgroups of FN patients who would benefit from prolonged BLA infusion.

Efficacy and safety of high-flow nasal cannula therapy in elderly patients with acute respiratory failure.

INTRODUCTION: To assess the efficacy and safety of high-flow nasal cannula (HFNC) in elderly patients with acute respiratory failure (ARF) not due to COVID-19, refractory to treatment with conventional oxygen therapy and/or intolerant to noninvasive ventilation (NIV) or continuous positive airway pressure (CPAP) and without criteria for admission to intensive care units (ICU). METHODS: Prospective observational study of patients with ARF treated with HFNC who presented clinical and arterial blood gas deterioration after 24 h of medical treatment and oxygenation by conventional systems. The degree of dyspnoea, gas exchange parameters (arterial O2 pressure/inspired O2 fraction ratio (PaO2/FiO2); oxygen saturation measured by oximetry/ inspired fraction of oxygen (Sp02/Fi02), ROX index), degree of patient tolerance and mortality were evaluated. These were measured at discharge from the emergency department (ED), 24 h after treatment with conventional oxygenation and 60, 120 min and 24 h after initiation of HFNC. The results were analyzed for all patients as a whole and for patients with hypercapnia (arterial carbon dioxide tension (PaCO2) < 45 mmHg) separately. RESULTS: 200 patients were included in the study between November 2019 and November 2020, with a mean age of 83 years, predominantly women (61.9%), obese (Body Mass Index (BMI) 31.1), with high comorbidity (Charlson index 4) and mild-moderate degree of dependence (Barthel 60). A number of 128 patients (64%) were hypercapnic. None had respiratory acidosis (pH 7.39). Evaluation at 60 min, 120 min and 24 h showed significant improvement in all patients and in the subgroup of hypercapnic patients with respect to baseline parameters in respiratory rate (RR), dyspnoea, ROX index, PaO2/FiO2, SpO2/FiO2 and patient comfort. No changes in PaCO2 or level of consciousness were observed. HFNC was well tolerated. Ten patients (5%) died due to progression of the disease causing ARF. CONCLUSIONS: HFNC is an effective and safe alternative in elderly patients with ARF not due to COVID-19, refractory to treatment with conventional oxygen therapy and/or intolerant to NIV or CPAP and without criteria for admission to ICU.

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.

Successful outcome of ganciclovir-resistant cytomegalovirus infection in organ transplant recipients after conversion to mTOR inhibitors.

Ganciclovir-resistant (GanR) cytomegalovirus (CMV) infection after organ transplantation is emerging as a significant therapeutic challenge. We report two cases of GanR CMV infection successfully managed by switching immunosuppression from calcineurin inhibitors to an mTOR inhibitor-based regimen. This salvage therapy should be considered when other options are not available.

Bacterial urinary tract infection after solid organ transplantation in the RESITRA cohort.

BACKGROUND: Urinary tract infection (UTI) is the most common infection in renal transplant patients, but it is necessary to determine the risk factors for bacterial UTI in recipients of other solid organ transplants (SOTs), as well as changes in etiology, clinical presentation, and prognosis. METHODS: In total, 4388 SOT recipients were monitored in 16 transplant centers belonging to the Spanish Network for Research on Infection in Transplantation (RESITRA). The frequency and characteristics of bacterial UTI in transplant patients were obtained prospectively from the cohort (September 2003 to February 2005). RESULTS: A total of 192 patients (4.4%) presented 249 episodes of bacterial UTI (0.23 episodes per 1000 transplantation days); 156 patients were kidney or kidney-pancreas transplant recipients, and 36 patients were liver, heart, and lung transplant recipients. The highest frequency was observed in renal transplants (7.3%). High frequency of cystitis versus pyelonephritis without related mortality was observed in both groups. The most frequent etiology was Escherichia coli (57.8%), with 25.7% producing extended-spectrum ß-lactamase (ESBL). In all transplants but renal, most cases occurred in the first month after transplantation. Cases were uniformly distributed during the first 6 months after transplantation in renal recipients. Age (odds ratio [OR] per decade 1.1, 95% confidence interval [CI] 1.02-1.17), female gender (OR 1.74, 95% CI 1.42-2.13), and the need for immediate post-transplant dialysis (OR 1.63, 95% CI 1.29-2.05) were independent variables associated with bacterial UTI in renal and kidney-pancreas recipients. The independent risk factors identified in non-renal transplants were age (OR per decade 1.79, 95% CI 1.09-3.48), female gender (OR 1.7, 95% CI 1.43-2.49), and diabetes (OR 1.02, 95% CI 1.001-1.040). CONCLUSIONS: UTI was frequent in renal transplants, but also not unusual in non-renal transplants. Because E. coli continues to be the most frequent etiology, the emergence of ESBL-producing strains has been identified as a new problem. In both populations, most cases were cystitis without related mortality. Although the first month after transplantation was a risk period in all transplants, cases were uniformly distributed during the first 6 months in renal transplants. Age and female gender were identified as risk factors for UTI in both populations. Other particular risk factors were the need for immediate post-transplant dialysis in renal transplants and diabetes in non-renal transplants.

Correction to: Early Stepdown From Echinocandin to Fluconazole Treatment in Candidemia: A Post Hoc Analysis of Three Cohort Studies.

[This corrects the article DOI: 10.1093/ofid/ofab250.].

Predictive factors, microbiology and outcome of patients with parapneumonic effusion.

We aimed to determine the incidence, clinical consequences and microbiological findings related to the presence of pleural effusion in community-acquired pneumonia, and to identify predictive factors for empyema/complicated parapneumonic effusion. We analysed 4,715 consecutive patients with community-acquired pneumonia from two acute care hospitals. Patients were classified into three groups: no pleural effusion, uncomplicated parapneumonic effusion and empyema/complicated parapneumonic effusion. A total of 882 (19%) patients had radiological evidence of pleural fluid, of whom 261 (30%) met criteria for empyema/complicated parapneumonic effusion. The most important event related to the presence of uncomplicated parapneumonic effusion was a longer hospital stay. Relevant clinical and microbiological consequences were associated with empyema/complicated parapneumonic effusion. Five independent baseline characteristics could predict the development of empyema/complicated parapneumonic effusion: age < 60 yrs (p = 0.012), alcoholism (p = 0.002), pleuritic pain (p = 0.002), tachycardia >100 beats·min⁻¹ (p = 0.006) and leukocytosis >15,000 mm⁻³ (p < 0.001). A higher incidence of anaerobes and Gram-positive cocci was found in this subgroup of patients. We conclude that only the development of empyema/complicated parapneumonic effusion carried relevant consequences; this condition should be suspected in the presence of some baseline characteristics and managed by using antimicrobials active against Gram-positive cocci and anaerobes.

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 ß-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).

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.

Risk factors for, and clinical relevance of, faecal extended-spectrum ß-lactamase producing Escherichia coli (ESBL-EC) carriage in neutropenic patients with haematological malignancies.

The purpose of this study was to assess the risk factors for, and the clinical relevance of, faecal carriage by extended-spectrum ß-lactamase producing Escherichia coli (ESBL-EC) in neutropenic cancer patients (NCP). An observational prospective multicentre cohort study was conducted over 2 years at two teaching hospitals. Patients with acute leukaemia or undergoing stem cell transplantation were included during neutropenia episodes. Rectal swabs were obtained at hospital admission and weekly thereafter until discharge or death. ESBL-EC colonized episodes were compared with non-colonized episodes. ESBL-EC strains were studied by PCR and isoelectric focusing, and molecular typing was performed by pulsed field gel electrophoresis (PFGE). Among 217 episodes of neutropenia, the prevalence of ESBL-EC faecal carriage was 29% (14% at hospital admission). Multivariate analysis identified previous antibiotics as the only independent risk factor for ESBL-EC faecal colonization (OR 5.38; 95% CI 2.79-10.39). Analysis of ESBL-EC isolates revealed a polyclonal distribution with CTX-M predominance (81.3%). E. coli bacteraemia was mainly caused by non-ESBL producing strains and its rate was similar in both groups (13% vs. 11%). We found no association between ESBL-EC carriage and an increased risk of ESBL-EC bacteremia or a negative influence on other clinical outcomes, including length of hospitalisation, early and overall mortality rates. ESBL-EC faecal colonization is frequent in NCP but difficult to identify by epidemiological or clinical features on presentation. Prior antibiotic therapy is the major associated risk factor. In this setting colonization does not appear to have a significant clinical relevance. Thus, routine testing for ESBL-EC faecal carriage does not seem to be beneficial.