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Background: Although a significant number of cases of Staphylococcus aureus bacteraemia (SAB) are managed at non-referral community hospitals, the impact of a bundle-of-care intervention in this setting has not yet been explored., Methods: We performed a quasi-experimental before-after study with the implementation of a bundle of care for the management of SAB at five non-referral community hospitals and a tertiary care university hospital. Structured recommendations for the five indicators selected to assess quality of care were provided to investigators before the implementation of the bundle and monthly thereafter. Primary endpoints were adherence to the bundle intervention and treatment failure, defined as death or relapse at 90 days of follow-up., Results: One hundred and seventy patients were included in the pre-intervention period and 103 in the intervention period. Patient characteristics were similar in both periods. Multivariate analysis controlling for potential confounders showed that performance of echocardiography was the only factor associated with improved adherence to the bundle in the intervention period (adjusted OR 2.13; 95% CI 1.13-4.02). Adherence to the bundle, performance of follow-up blood cultures, and adequate duration of antibiotic therapy for complicated SAB presented non-significant improvements. The intervention was not associated with a lower rate of 90 day treatment failure (OR 1.11; 95% CI 0.70-1.77)., Conclusions: A bundle-of-care intervention for the management of SAB at non-referral community hospitals increased adherence to quality indicators, but did not significantly reduce rates of 90 day mortality or relapse., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose of Review: This review describes the latest information in the management of bloodstream infections caused by multidrug-resistant Gram-negative bacilli (MDRGNB) in critically ill patients., Recent Findings: The prevalence of bloodstream infections due to MDRGNB is high, and they pose a significant risk in critically ill patients. Recently, novel antimicrobial agents, including new β-lactam/β-lactamase inhibitor combinations and cefiderocol, have been introduced for treating these infections. Concurrently, updated guidelines have been issued to aid in treatment decisions. Prompt diagnosis and identification of resistance patterns are crucial for initiating effective antibiotic therapy. Current studies, especially with observational design, and with limited sample sizes and patients with bacteremia, suggest that the use of these new antibiotics is associated with improved outcomes in critically ill patients with MDRGNB bloodstream infections., Summary: For critically ill patients with bloodstream infections caused by MDRGNB, the use of newly developed antibiotics is recommended based on limited observational evidence. Further randomized clinical trials are necessary to determine the most effective antimicrobial therapies among the available options., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 ., (© 2023. The Author(s).)

We analyzed risk factors for mortality in febrile neutropenic patients with bloodstream infections (BSI) presenting with septic shock and assessed the impact of empirical antibiotic regimens. A multicenter retrospective study (2010 to 2019) of two prospective cohorts compared BSI episodes in patients with or without septic shock. Multivariate analysis was performed to identify independent risk factors for mortality in episodes with septic shock. Of 1,563 patients with BSI, 257 (16%) presented with septic shock. Those patients with septic shock had higher mortality than those without septic shock (55% versus 15%, P  < 0.001). Gram-negative bacilli caused 81% of episodes with septic shock, Gram-positive cocci caused 22%, and Candida species caused 5%. Inappropriate empirical antibiotic treatment (IEAT) was administered in 17.5% of septic shock episodes. Empirical β-lactam combined with other active antibiotics was associated with the lowest mortality observed. When amikacin was the only active antibiotic, mortality was 90%. Addition of empirical specific Gram-positive coverage had no impact on mortality. Mortality was higher when IEAT was administered (76% versus 51%, P  = 0.002). Age of >70 years (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.2 to 4.7), IEAT for Candida spp. or Gram-negative bacilli (OR, 3.8; 95% CI, 1.3 to 11.1), acute kidney injury (OR, 2.6; 95% CI, 1.4 to 4.9), and amikacin as the only active antibiotic (OR, 15.2; 95% CI, 1.7 to 134.5) were independent risk factors for mortality, while the combination of β-lactam and amikacin was protective (OR, 0.32; 95% CI, 0.18 to 0.57). Septic shock in febrile neutropenic patients with BSI is associated with extremely high mortality, especially when IEAT is administered. Combination therapy including an active β-lactam and amikacin results in the best outcomes.

Objectives: The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia., Methods: We performed a severity matched case-control study (1:1 ratio) nested in a large multicentre prospective cohort of hospitalized adults with COVID-19. Cases with BSI were identified from the cohort database. Controls were matched for age, sex and acute respiratory distress syndrome. A Cox proportional hazard ratio model was performed., Results: Of 2005 patients, 100 (4.98%) presented 142 episodes of BSI, mainly caused by coagulase-negative staphylococci, Enterococcus faecalis and Pseudomonas aeruginosa. Polymicrobial infection accounted for 23 episodes. The median time from admission to the first episode of BSI was 15 days (IQR 9-20), and the most frequent source was catheter-related infection. The characteristics of patients with and without BSI were similar, including the use of tocilizumab, corticosteroids, and combinations. In the multivariate analysis, the use of these immunomodulatory drugs was not associated with an increased risk of BSI. A Cox proportional hazard ratio (HR) model showed that after adjusting for the time factor, BSI was associated with a higher in-hospital mortality risk (HR 2.59; 1.65-4.07; p < 0.001)., Discussion: Hospital-acquired BSI in patients with severe COVID-19 pneumonia was uncommon and the use of immunomodulatory drugs was not associated with its development. When adjusting for the time factor, BSI was associated with a higher mortality risk., (Copyright © 2021. Published by Elsevier Ltd.)

There are scarce data on the efficacy of ertapenem in the treatment of bacteremia due to extended-spectrum-beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) in kidney transplant (KT) recipients. We evaluated the association between treatment with ertapenem or meropenem and clinical cure in KT recipients with nonsevere bacteremic urinary tract infections (B-UTI) caused by ESBL-E. We performed a registered, retrospective, international (29 centers in 14 countries) cohort study (INCREMENT-SOT, NCT02852902). The association between targeted therapy with ertapenem versus meropenem and clinical cure at day 14 (the principal outcome) was studied by logistic regression. Propensity score matching and desirability of outcome ranking (DOOR) analyses were also performed. A total of 201 patients were included; only 1 patient (treated with meropenem) in the cohort died. Clinical cure at day 14 was reached in 45/100 (45%) and 51/101 (50.5%) of patients treated with ertapenem and meropenem, respectively (adjusted OR 1.29; 95% CI 0.51 to 3.22; P  = 0.76); the propensity score-matched cohort included 55 pairs (adjusted OR for clinical cure at day 14, 1.18; 95% CI 0.43 to 3.29; P  = 0.74). In this cohort, the proportion of cases treated with ertapenem with better DOOR than with meropenem was 49.7% (95% CI, 40.4 to 59.1%) when hospital stay was considered. It ranged from 59 to 67% in different scenarios of a modified (weights-based) DOOR sensitivity analysis when potential ecological advantage or cost was considered in addition to outcome. In conclusion, targeted therapy with ertapenem appears as effective as meropenem to treat nonsevere B-UTI due to ESBL-E in KT recipients and may have some advantages.

To test the hypothesis that the addition of an aminoglycoside to a β-lactam antibiotic could provide better outcomes than β-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 (β-lactam plus aminoglycoside) was compared to β-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.

Background: Whether active therapy with β-lactam/β-lactamase inhibitors (BLBLI) is as affective as carbapenems for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infection (BSI) secondary to urinary tract infection (UTI) in kidney transplant recipients (KTRs) remains unclear., Methods: We retrospectively evaluated 306 KTR admitted to 30 centers from January 2014 to October 2016. Therapeutic failure (lack of cure or clinical improvement and/or death from any cause) at days 7 and 30 from ESBL-E BSI onset was the primary and secondary study outcomes, respectively., Results: Therapeutic failure at days 7 and 30 occurred in 8.2% (25/306) and 13.4% (41/306) of patients. Hospital-acquired BSI (adjusted OR [aOR]: 4.10; 95% confidence interval [CI]: 1.50-11.20) and Pitt score (aOR: 1.47; 95% CI: 1.21-1.77) were independently associated with therapeutic failure at day 7. Age-adjusted Charlson Index (aOR: 1.25; 95% CI: 1.05-1.48), Pitt score (aOR: 1.72; 95% CI: 1.35-2.17), and lymphocyte count ≤500 cells/μL at presentation (aOR: 3.16; 95% CI: 1.42-7.06) predicted therapeutic failure at day 30. Carbapenem monotherapy (68.6%, primarily meropenem) was the most frequent active therapy, followed by BLBLI monotherapy (10.8%, mostly piperacillin-tazobactam). Propensity score (PS)-adjusted models revealed no significant impact of the choice of active therapy (carbapenem-containing vs any other regimen, BLBLI- vs carbapenem-based monotherapy) within the first 72 hours on any of the study outcomes., Conclusions: Our data suggest that active therapy based on BLBLI may be as effective as carbapenem-containing regimens for ESBL-E BSI secondary to UTI in the specific population of KTR. Potential residual confounding and unpowered sample size cannot be excluded (ClinicalTrials.gov identifier: NCT02852902)., (© 2020 Wiley Periodicals LLC.)

Background: We aimed to determine whether daptomycin plus fosfomycin provides higher treatment success than daptomycin alone for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia and endocarditis., Methods: A randomized (1:1) phase 3 superiority, open-label, and parallel group clinical trial of adult inpatients with MRSA bacteremia was conducted at 18 Spanish hospitals. Patients were randomly assigned to receive either 10 mg/kg of daptomycin intravenously daily plus 2 g of fosfomycin intravenously every 6 hours, or 10 mg/kg of daptomycin intravenously daily. Primary endpoint was treatment success 6 weeks after the end of therapy., Results: Of 167 patients randomized, 155 completed the trial and were assessed for the primary endpoint. Treatment success at 6 weeks after the end of therapy was achieved in 40 of 74 patients who received daptomycin plus fosfomycin and in 34 of 81 patients who were given daptomycin alone (54.1% vs 42.0%; relative risk, 1.29 [95% confidence interval, .93-1.8]; P = .135). At 6 weeks, daptomycin plus fosfomycin was associated with lower microbiologic failure (0 vs 9 patients; P = .003) and lower complicated bacteremia (16.2% vs 32.1%; P = .022). Adverse events leading to treatment discontinuation occurred in 13 of 74 patients (17.6%) receiving daptomycin plus fosfomycin, and in 4 of 81 patients (4.9%) receiving daptomycin alone (P = .018)., Conclusions: Daptomycin plus fosfomycin provided 12% higher rate of treatment success than daptomycin alone, but this difference did not reach statistical significance. This antibiotic combination prevented microbiological failure and complicated bacteremia, but it was more often associated with adverse events., Clinical Trials Registration: NCT01898338., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

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., (Copyright © 2020 American Society for Microbiology.)

Background: We aimed to describe the current rates of inappropriate empirical antibiotic treatment (IEAT) in oncohematological patients with febrile neutropenia (FN) and its impact on mortality., Methods: This was a multicenter prospective study of all episodes of bloodstream infection (BSI) in high-risk FN patients (2006-2017). Episodes receiving IEAT were compared with episodes receiving appropriate empirical therapy. Adherence to Infectious Diseases Society of America (IDSA) recommendations was evaluated. Multivariate analysis was performed to identify independent risk factors for mortality in Pseudomonas aeruginosa episodes., Results: Of 1615 episodes, including Escherichia coli (24%), coagulase-negative staphylococci (21%), and P. aeruginosa (16%), 394 (24%) received IEAT despite IDSA recommendations being followed in 87% of cases. Patients with multidrug-resistant gram-negative bacilli (MDR-GNB), accounting for 221 (14%) of all isolates, were more likely to receive IEAT (39% vs 7%, P < .001). Overall mortality was higher in patients with GNB BSI who received IEAT (36% vs 24%, P = .004); when considering individual microorganisms, only patients with infection caused by P. aeruginosa experienced a significant increase in mortality when receiving IEAT (48% vs 31%, P = .027). Independent risk factors for mortality in PA BSI (odds ratio [95% confidence interval] were IEAT (2.41 [1.19-4.91]), shock at onset (4.62 [2.49-8.56]), and pneumonia (3.01 [1.55-5.83])., Conclusions: IEAT is frequent in high-risk patients with FN and BSI, despite high adherence to guidelines. This inappropriate treatment primarily impacts patients with P. aeruginosa-related BSI mortality and in turn is the only modifiable factor to improve outcomes., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Mortality rates from Staphylococcus aureus bacteremia are high and have only modestly improved in recent decades. We compared the efficacies of a β-lactam in combination with daptomycin (BL/D-C) and β-lactam monotherapy (BL-M) in improving clinical outcomes in methicillin-susceptible S. aureus (MSSA) bacteremia., Methods: A retrospective cohort study of MSSA bacteremia was performed in a tertiary hospital from January 2011 to December 2017. Patients receiving BL/D-C and BL-M were compared to assess 7-, 30-, and 90-day mortality rates. A 1:2 propensity score matching analysis was performed. Differences were assessed using Cox regression models., Results: Of the 514 patients with MSSA bacteremia, 164 were excluded as they had received combination therapies other than BL/D-C, had pneumonia, or died within 48 hours of admission. Of the remaining 350 patients, 136 and 214 received BL/D-C and BL-M, respectively. BL/D-C patients had higher Pitt scores and persistent bacteremia more often than BL-M patients. In the raw analysis, there were no differences in mortality rates between groups. After propensity score matching, there were no significant differences between the BL/D-C (110 patients) and BL-M (168 patients) groups for all-cause mortality rates at 7 days (8.18% vs 7.74%; P = 1.000), 30 days (17.3% vs 16.1%; P = .922), and 90 days (22.7% vs 23.2%; P = 1.000), even in a subanalysis of patients with high-risk source of infection and in a subgroup excluding catheter-related bacteremia., Conclusions: BL/D-C failed to reduce mortality rates in patients with MSSA bacteremia. Treatment strategies to improve survival in MSSA bacteremia are urgently needed., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose of Review: Infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are increasing worldwide. Carbapenems are usually regarded as the antibiotics of choice for the treatment of serious ESBL infections. However, because of the alarming emergence or carbapenem resistance, interest in effective alternatives has emerged. The present review summarizes the findings published on the antibiotics currently available for treatment of patients with an ESBL-E bloodstream infection (BSI)., Recent Findings: Meropenem and imipenem are the drugs recommended for treatment of ESBL BSIs in critically ill patients, and in infections with high bacterial loads or elevated β-lactam minimum inhibitory concentrations. Ertapenem should be reserved for patients with less severe presentations, and should be used at high doses. In milder presentations or BSIs from low-risk sources, other carbapenem-sparing alternatives could be considered: cephamycins, fluoroquinolones, and particularly a β-lactam/β-lactam inhibitor combination (particularly piperacillin/tazobactam). Optimized dosing of piperacillin/tazobactam is recommended (high doses and extended infusion). There are few data on the use of the promising newly available drugs (e.g. ceftolozane/tazobactam, ceftazidime/avibactam, cefiderocol, and plazomicin), and it seems reasonable to reserve them as last-resort drugs., Summary: Carbapenems should be used in patients with serious infections; alternatives could be used individually, particularly for definitive treatment of patients with milder presentations.

Introduction: Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality., Methods and Analysis: This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic onco-haematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrug-resistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates., Ethics and Dissemination: The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients' personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peer-reviewed publications., Competing Interests: Competing interests: A-SB received grant from Promex Stiftung fur die Forschung (by Carigest SA), and funding by Gilead to assist to the ECCMID Congress (2018). ORS received speaker’s honorarium from MSD, Astellas, Novartis and Pfizer., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To assess the etiology, clinical features and outcomes of bacteremia in older patients with solid tumors., Methods: All episodes of bacteremia in hospitalized patients with solid tumors were prospectively collected. Patients aged ≥70 years were compared to patients aged <70 years. Risk factors for case-fatality rates in older patients were identified., Results: We compared 217 episodes of bacteremia involving older patients and 525 occurring in younger patients. Older patients had more frequently other comorbidities, but were less commonly neutropenic and carried less frequently central venous catheters. Bacteremia from an abdominal source was more common in patients ≥70, whereas an endogenous source and catheter-related infection were less frequently observed. Streptococcus bovis group (3.7% vs. 0.8%, p = .01) and Listeria monocytogenes (4.6% vs. 1.9%, p = .04) were more common in older patients, whereas coagulase-negative staphylococci were less frequently found (1.4% vs. 5.3% p = .01). Infection due to multi-drug resistant (MDR) strains was significantly higher in older patients (17.1% vs. 10.9%, p = .02), who in addition, presented higher overall mortality (35.4% vs 27.7%, p = .04). In older patients, lung tumor, neutropenia, and low grade fever were associated with early mortality, whereas comorbidities, corticosteroids, septic shock and inadequate empirical antibiotic therapy were associated with overall mortality., Conclusions: We identified remarkable differences in the etiology and sources of bacteremia between older and younger cancer patients with bacteremia. Older patients had more frequent infection due to MDR organisms and presented a higher overall mortality. Corticosteroids and inadequate empirical antibiotic therapy are modifiable factors associated with mortality., (Copyright © 2018. Published by Elsevier Ltd.)

Introduction: Case-fatality rates for Staphylococcus aureus bacteremia (SAB) remain unacceptably high and have improved only modestly in recent decades. Treatment of SAB is still a clinical challenge, especially if methicillin-resistant strains are involved. New drugs with anti-staphylococcal activity are currently available, and their role as alternatives to standard therapies is being investigated. Areas covered: In this review, we give an update of the current available antibiotics for the treatment of SAB. We provide information regarding the pharmacological characteristics, the accepted indications, and the most important adverse events of the old and new anti-staphylococcal agents, as well as the existing evidence on their use for the treatment of SAB. Expert opinion: The management of patients with SAB is very complex and needs a multidisciplinary approach. There are currently new available options for the treatment of methicillin-resistant SAB. However, more data from clinical trials are needed to assign specific roles to each antibiotic and to include them in the new antibacterial armamentarium. The role of combination therapy for the treatment of increasingly complex patients with SAB deserves thorough investigation.

Objectives: To assess the current incidence, clinical features, risk factors, aetiology, antimicrobial resistance and outcomes of polymicrobial bloodstream infection (PBSI) in patients with cancer., Methods: All prospectively collected episodes of PBSI in hospitalised patients were compared with episodes of monomicrobial bloodstream infection (MBSI) between 2006 and 2015., Results: We identified 194 (10.2%) episodes of PBSI and 1702 MBSI (89.8%). The presence of cholangitis, biliary stenting, neutropenia, corticosteroids, neutropenic enterocolitis and other abdominal infections were identified as risk factors for PBSI. Overall, Gram-negative organisms were the most frequent aetiology, but Enterococcus spp. were especially frequent causes of Gram-positive PBSI (30.8%). Multidrug-resistant (MDR) organisms were more commonly found in PBSI than in MBSI (20.6% vs 12.9%; p = 0.003). Compared to patients with MBSI, those with PBSI presented with higher early (15% vs 1.4%; p = 0.04) and overall (32% vs 20.9%; p<0.001) case-fatality rates. Risk factors for overall case-fatality were a high-risk MASCC (Multinational Association of Supportive Care in Cancer) index score, corticosteroid use, persistent bacteraemia and septic shock., Conclusions: PBSI is a frequent complication in patients with cancer and is responsible for high mortality rates. Physicians should identify patients at risk for PBSI and provide empiric antibiotic therapy that covers the most frequent pathogens involved in these infections, including MDR strains.

To analyse trends in the aetiology, treatment and outcomes of bloodstream infection (BSI) within the first year post-transplant over the last 10-year period, we prospectively recorded all episodes of BSI occurring in solid organ transplant (SOT) recipients during the first year post-transplant from 2007 to 2016. Trends of factors were analysed by 2-year periods. Of 475 consecutive episodes of BSI, 218 occurred within a year of SOT in 178 SOT recipients. Gram-positive BSI decreased over time (40.5-2.2%). In contrast, there was a steady increase in Gram-negative bacilli (GNB) BSI (54.1-93.3%; P < 0.001), mainly due to Pseudomonas aeruginosa (2.4-20.4%) and Klebsiella pneumoniae (7.1-26.5%). Multidrug-resistant (MDR) GNB (4.8-38.8%; P < 0.001) rose dramatically, especially due to extended-spectrum β-lactamase (ESBL) production (7.1-34.7%). There was a sharp rise in the use of carbapenems, both as empirical (11.9-55.3%; P < 0.001) and as targeted antibiotic treatment (11.9-46.9%; P < 0.001). In conclusion, today, GNB are the leading causative agents of BSI in SOT recipients within the first year after SOT. In addition, MDR GNB have emerged mainly due to ESBL-producing strains. In spite of these changes, length of hospital stay, days of treatment and mortality have remained stable over time., (© 2017 Steunstichting ESOT.)

β-Lactam/β-lactamase inhibitors (BLBLIs) were compared to carbapenems in two cohorts of hematological neutropenic patients with extended-spectrum-β-lactamase (ESBL) bloodstream infection (BSI): the empirical therapy cohort (174 patients) and the definitive therapy cohort (251 patients). The 30-day case fatality rates and other secondary outcomes were similar in the two therapy groups of the two cohorts and also in the propensity-matched cohorts. BLBLIs might be carbapenem-sparing alternatives for the treatment of BSI due to ESBLs in these patients., (Copyright © 2017 American Society for Microbiology.)

Objectives: To asses the clinical features, aetiology, antimicrobial resistance and outcomes of bacteraemic cholangitis in patients with solid tumours (ST)., Methods: All consecutive episodes of bacteraemia in hospitalized patients were prospectively analysed (2006-2015)., Results: Of 1852 episodes of bacteraemia, 750 involved patients with ST. Among them, 173 episodes (23%) were due to cholangitis. The most frequent neoplasms were hepato-biliary-pancreatic tumours (68.2%) and gastrointestinal cancer (18.5%); 57.2% of patients had a biliary stent in place. The most frequent causative agents were Escherichia coli (39.3%) followed by Klebsiella pneumoniae (15.1%) and Enterococcus faecium (7.8%). Forty-one episodes (18.7%) were caused by multidrug-resistant (MDR) microorganisms. Patients with a second episode of cholangitis were more likely to have an MDR isolate and to had received inadequate empirical antibiotic therapy. 7-day and 30-day case-fatality rates were 7.6% and 26%, respectively. The only risk factors independently associated with 30-day case-fatality rate were corticosteroids and malignancy-related complications., Conclusions: Bacteraemic cholangitis is frequent in patients with ST, and is mainly caused by Enterobacteriaceae and E. faecium. The emergence of MDR is of special concern, particularly in patients with a second episode of bacteraemia. Case-fatality rates are high, especially among patients receiving corticosteroids and presenting malignancy-related complications., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Although antibiotic de-escalation is regarded as a measure that reduces selection pressure, adverse drug effects and costs, evidence supporting this practice in community-acquired pneumococcal pneumonia (CAPP) is lacking., Methods: We carried out a retrospective analysis of prospectively collected data of a cohort of hospitalized adults with CAPP. Pneumococcal aetiology was established in patients with one or more positive cultures for Streptococcus pneumoniae obtained from blood, sterile fluids or sputum, and/or a positive urinary antigen test. De-escalation therapy was considered when the initial antibiotic therapy was narrowed to penicillin, amoxicillin or amoxicillin/clavulanate within the first 72 h after admission. The primary outcomes were 30 day mortality and length of hospital stay (LOS). Adjustment for confounders was performed with multivariate and propensity score analyses., Results: Of 1410 episodes of CAPP, antibiotic de-escalation within the first 72 h after admission was performed in 166 cases. After adjustment, antibiotic de-escalation was not associated with a higher risk of mortality (OR = 0.83, 95% CI = 0.24-2.81), but it was found to be a protective factor for prolonged LOS (above the median) (OR = 0.46, 95% CI = 0.30-0.70). Similar results were found in patients classified into high-risk pneumonia severity index classes (IV-V), those with clinical instability and those with bacteraemia. No significant differences were documented in adverse drug reactions or readmission (<30 days)., Conclusions: Antibiotic de-escalation seems to be safe and effective in reducing the duration of LOS, and did not adversely affect outcomes of patients with CAPP, even those with bacteraemia and severe disease, and those who were clinically unstable., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background and Objective: We aimed to assess the clinical features, aetiology and outcomes of bacteraemic pneumonia in neutropenic cancer patients (NCP) in the current era of increasing antimicrobial resistance., Methods: All episodes of bacteraemia occurring in hospitalized patients with cancer, including haematopoietic stem cell transplant recipients, from January 2006 to April 2015 were included., Results: We identified 1723 episodes of bacteraemia, of which 795 occurred in neutropenic patients with cancer, and among them, 55 episodes were identified as bacteraemic pneumonia. The most frequent causative agents were Pseudomonas aeruginosa (39.6%), Streptococcus pneumoniae (20.6%) and Escherichia coli (8.6%). Among the Gram-negative organisms, 12.8% were multidrug resistant (MDR). Eleven patients (20%) required admission to intensive care, and eight (14.8%) underwent invasive mechanical ventilation. Nine patients (16.3%) received inadequate empirical antibiotic therapy, of whom six (66.6%) died; eight of these nine patients had pneumonia caused by resistant microorganisms. The early (48 h) case-fatality rate was 24% and the overall (30 day) case-fatality rate was 46.2%., Conclusion: Bacteraemic pneumonia is a frequent complication among NCP and is mainly caused by P. aeruginosa and S. pneumoniae. The emergence of MDR organisms is of special concern. Despite the improvement in the management of cancer patients, case-fatality rates of NCP with bacteraemic pneumonia remain high. Urgent assessment is needed to identify a better approach for the management and support of these patients., (© 2016 Asian Pacific Society of Respirology.)

Little information is currently available regarding bloodstream infection (BSI) in patients with solid tumors who, for a variety of reasons, are particularly predisposed to develop this condition. In this review we focus on the incidence, epidemiology, clinical features, etiology, antimicrobial resistance, and outcomes of BSI of adult cancer patients with solid tumors. Most episodes of BSI occur in non-neutropenic patients, in whom the site of primary or metastatic tumor often serves as the portal of entry. The urinary tract and the abdomen are the most frequent sources of infection, and cholangitis is the most common recurrent source of BSI. Gram-negative bacilli are becoming the leading cause of BSI in patients with solid tumors, and the rate of multidrug resistance is increasingly being recognized. The case-fatality rate in patients with solid tumors and BSI is high, especially among those with comorbidities, advanced neoplasms, corticosteroid therapy, and shock at presentation.

Although bloodstream infection (BSI) is a major cause of mortality after solid organ transplantation, information regarding its prognostic factors is scarce. To identify risk factors for 30-day mortality in solid organ transplant (SOT) recipients with BSI, we prospectively recorded all episodes of BSI occurring in adult SOT recipients from January 2007 to October 2014 at a university hospital. We identified 361 consecutive episodes of BSI involving 246 patients. The 30-day case-fatality rate from the onset of BSI was 11.4%. Factors independently associated with 30-day mortality in a logistic regression analysis were shock at presentation (OR 13.658; 95% CI 5.985-31.168), acute graft rejection in the previous 6 months (OR 3.681; 95% CI 1.059-12.795), and a platelet count of <50,000 × 10(9)/L (OR 3.070; 95% CI 1.173-8.038). Kidney recipients were the patients with the best prognosis (OR 0.375; 95% CI 0.156-0.900). Our findings may help to identify SOT recipients with BSI who are at the highest risk of death., (Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone., Methods and Analysis: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis., Ethics and Dissemination: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study., Trial Registration Number: NCT01898338., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Background: We sought to determine the risk factors, molecular epidemiology, antibiotic therapy, and outcomes of bacteremia because of extensively drug-resistant (XDR) Pseudomonas aeruginosa in solid organ transplant (SOT) recipients., Methods: All episodes of bacteremia occurring in SOT recipients were prospectively documented from 2007 to 2013., Results: Of 318 episodes of bacteremia, 49 were caused by P. aeruginosa. Thirty-one strains (63%) were XDR defined by nonsusceptibility to at least one agent in all but two or fewer antipseudomonal antimicrobial categories. Time from transplantation to bacteremia was shorter in XDR P. aeruginosa group comparing to other etiologies (median days 66 vs. 278; P=0.03). Factors independently associated with XDR P. aeruginosa bacteremia were prior transplantation, nosocomial acquisition, and septic shock at onset. XDR P. aeruginosa isolates belonged to a single clone (ST-175). Comparing to other etiologies, patients with bacteremia because of XDR P. aeruginosa more often received inadequate empirical antibiotic therapy. Persistence of bacteremia, shock, respiratory failure and intensive care unit admission were more frequent in patients with XDR P. aeruginosa. The overall case-fatality rate was higher among patients with XDR P. aeruginosa bacteremia than in the others (38% vs. 16%; P=0.009)., Conclusion: Bacteremia because of XDR P. aeruginosa should be carefully considered when selecting empirical antibiotic therapy for hospitalized SOT recipients with prior transplantation presenting with septic shock.

Objectives: We sought to identify the characteristics, aetiology, antibiotic resistance and outcomes of bloodstream infection (BSI) in neutropenic patients with haematological malignancies (HM) and in those with solid tumours (ST) and assess their impact on empirical therapy and outcomes., Methods: All episodes of BSI in neutropenic patients with HM and ST were prospectively recorded and compared., Results: Of 579 episodes of BSI, 493 occurred in patients with HM and 86 in patients with ST. An endogenous source and catheter-related infection were more frequent in patients with HM, whereas pneumonia and urinary tract were more common in the ST group. BSI was mainly due to Gram-negative bacilli. Coagulase-negative staphylococci were more frequent in patients with HM, while Pseudomonas aeruginosa was more common in patients with ST and was the leading cause of pneumonia. Multidrug-resistant Gram-negative bacilli (MDRGNB) were more frequently isolated in haematological patients who more often received inadequate empirical therapy than those with ST. Case-fatality rates were higher in patients with ST., Conclusions: We identified significant differences in BSI in neutropenic patients with HM and ST. MDRGNB were more often isolated in patients with HM. Pneumonia due to P. aeruginosa was particularly frequent among patients with ST. Case-fatality rates were higher in patients with ST., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: There is an urgent need for alternative rescue therapies in invasive infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We assessed the clinical efficacy and safety of the combination of fosfomycin and imipenem as rescue therapy for MRSA infective endocarditis and complicated bacteremia., Methods: The trial was conducted between 2001 and 2010 in 3 Spanish hospitals. Adult patients with complicated MRSA bacteremia or endocarditis requiring rescue therapy were eligible for the study. Treatment with fosfomycin (2 g/6 hours IV) plus imipenem (1 g/6 hours IV) was started and monitored. The primary efficacy endpoints were percentage of sterile blood cultures at 72 hours and clinical success rate assessed at the test-of-cure visit (45 days after the end of therapy)., Results: The combination was administered in 12 patients with endocarditis, 2 with vascular graft infection, and 2 with complicated bacteremia. Therapy had previously failed with vancomycin in 9 patients, daptomycin in 2, and sequential antibiotics in 5. Blood cultures were negative 72 hours after the first dose of the combination in all cases. The success rate was 69%, and only 1 of 5 deaths was related to the MRSA infection. Although the combination was safe in most patients (94%), a patient with liver cirrhosis died of multiorgan failure secondary to sodium overload. There were no episodes of breakthrough bacteremia or relapse., Conclusions: Fosfomycin plus imipenem was an effective and safe combination when used as rescue therapy for complicated MRSA bloodstream infections and deserves further clinical evaluation as initial therapy in these infections., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate were the endogenous source of BSI (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.06-12.02), shock at presentation (OR, 3.63; 95% CI, 1.63-8.09), and corticosteroid therapy (OR, 3.245; 95% CI, 1.43-7.32). The independent risk factors for overall case-fatality rate were the presence of a chronic advanced cancer (OR, 35.39; 95% CI, 2.48-504.91), shock at presentation (OR, 25.84; 95% CI, 3.73-179.0), and corticosteroid therapy (OR, 6.98; 95% CI, 1.61-30.21).BSI in patients with solid tumors occurred mainly among those with hepatobiliary cancer, and cholangitis was the most frequent source; gram-negative bacilli were the most frequent causative agents. MDR organisms were relatively common, particularly in patients who had previously received antibiotics and had been hospitalized; these patients were frequently treated with inadequate empirical antibiotic therapy and had a poorer outcome. The case-fatality rate of patients with solid tumors and BSI was high and was associated with chronic advanced cancer, corticosteroid therapy, and shock at presentation.

Purpose: Infection due to the six ESKAPE pathogens has recently been identified as a serious emerging problem. However, there is still a lack of information on bacteremia caused by these organisms in cancer patients. We aimed to assess the epidemiology, antibiotic therapy and outcomes of bacteremia due to drug-resistant ESKAPE pathogens (rESKAPE) in patients with cancer., Methods: All episodes of bacteremia prospectively documented in hospitalized adults with cancer from 2006 to 2011 were analyzed., Results: Of 1,148 episodes of bacteremia, 392 (34 %) were caused by ESKAPE pathogens. Fifty-four episodes (4.7 %) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium 0, methicillin-resistant Staphylococcus aureus (MRSA) 13, extended-spectrum beta-lactamase (ESLB)-producing Klebsiella pneumoniae 7, carbapenem-resistant Acinetobacter baumannii 4, carbapenem- and quinolone-resistant Pseudomonas aeruginosa 18 and derepression chromosomic ß-lactam and ESBL-producing Enterobacter species 12. Risk factors independently associated with rESKAPE bacteremia were comorbidities, prior antibiotic therapy, urinary catheter and urinary tract source. Inappropriate empirical antibiotic therapy was more frequent in patients with rESKAPE bacteremia than in the other cases (55.6 % vs. 21.5 %, p < 0.001). Persistence of bacteremia (25 % vs. 9.7 %), septic metastasis (8 % vs. 4 %) and early case-fatality rate (23 % vs. 11 %) were more frequent in patients with rESKAPE bacteremia than in patients with other etiologies (p < 0.05)., Conclusions: Bacteremia due to rESKAPE pathogens in cancer patients occurs mainly among those with comorbidities who have received prior antibiotic therapy and have a urinary tract source. These patients often receive inappropriate empirical antibiotic therapy and have a poor outcome.

Background: Although infections due to the six ESKAPE pathogens have recently been identified as a serious emerging problem, information regarding bacteremia caused by these organisms in solid-organ transplant (SOT) recipients is lacking. We sought to determine the frequency, risk factors, and outcomes of bacteremia due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart adult transplant recipients., Methods: All episodes of bacteremia prospectively documented in hospitalized SOT recipients from 2007 to 2012 were analyzed., Results: Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium [0], methicillin-resistant Staphylococcus aureus [5], extended-spectrum β-lactamase-producing Klebsiella pneumoniae [10], carbapenem-resistant Acinetobacter baumannii [8], carbapenem- and quinolone-resistant Pseudomonas aeruginosa [26], and derepressed chromosomal β-lactam and extended-spectrum β-lactamase-producing Enterobacter species [5]). Factors independently associated with rESKAPE bacteremia were prior transplantation, septic shock, and prior antibiotic therapy. Patients with rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001)., Conclusions: Bacteremia due to rESKAPE pathogens is frequent in SOT recipients and causes significant morbidity and mortality. rESKAPE organisms should be considered when selecting empirical antibiotic therapy for hospitalized SOT recipients presenting with septic shock, particularly those with prior transplantation and antibiotic use.

We conducted a prospective study to assess the risk factors, molecular epidemiology and outcome of bloodstream infection (BSI) due to Enterococcus faecium in hospitalized cancer patients. Between 2006 and 2012, a significant increase in vancomycin-susceptible E. faecium BSI was observed among cancer patients. Comparison of 54 episodes of BSI due to E. faecium with 38 episodes of BSI due to E. faecalis showed that previous use of carbapenems was the only independent risk factor for E. faecium acquisition (OR 10.24; 95% CI, 1.35-77.66). All E. faecium isolates were susceptible to glycopeptides, whereas 97% showed high-level resistance to ampicillin and ciprofloxacin. All 30 isolates available for genotyping belonged to the hospital-associated E. faecium lineages 17, 18 and 78. After 2009, most of the isolates belonged to ST117 (lineage 78). Patients with E. faecium BSI were more likely to receive inadequate initial empirical antibiotic therapy than patients with E. faecalis BSI, and time to adequate empirical antibiotic therapy was also longer in the former group. No significant differences were found between the two groups regarding early and overall case-fatality rates. Independent risk factors for overall case-fatality were current corticosteroids (OR 4.18; 95% CI, 1.34-13.01) and intensive care unit admission (OR 9.97; 95% CI, 1.96-50.63). The emergence of E. faecium among cancer patients is a concern since there are limited treatment options and it may presage the emergence of vancomycin-resistant enterococci. A rationale approach that combines infection control with antimicrobial stewardship.

Recent changes in the management of patients with haematological malignancies might have influenced the aetiology, characteristics, antimicrobial resistance and outcomes of bloodstream infection (BSI) during neutropenia. We compared 272 episodes of BSI in adult neutropenic patients with cancer prospectively collected from January 1991 to December 1996 (first period), when quinolone prophylaxis was used, with 283 episodes recorded from January 2006 to March 2010 (second period), when antibacterial prophylaxis was stopped. Patients in the second period were significantly older and were more likely to have graft-versus-host disease and a urinary catheter in place, whereas the presence of a central venous catheter, parenteral nutrition, corticosteroids and antifungal and quinolone prophylaxis, were more frequent in the first period. More patients in the first period had mucositis and soft-tissue infection as the origin of BSI, but an endogenous source was more common during the second. Gram-positive BSI was more frequent in the first period (64% versus 41%; p <0.001), mainly due to coagulase-negative staphylococci and viridans group streptococci. In the second period gram-negative BSI increased (28% versus 49%; p <0.001), quinolone susceptibilities were recovered, but multidrug-resistant gram-negative BSI also increased (1% versus 6%; p <0.001). Although patients in the second period were more likely to need admission to the intensive-care unit, overall case-fatality rate was similar in the two periods (19% versus 15%). The aetiology of BSI in neutropenic patients with cancer has shifted from gram-positive to gram-negative organisms. Multidrug resistance among gram-negative bacilli is emerging as a therapeutic challenge. Overall case-fatality rate remains high., (© 2012 The Authors. Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.)

Objectives: In the current era of changing epidemiology of invasive pneumococcal disease, we aimed to assess the clinical features, antimicrobial susceptibility, vaccination status, serotypes, genotypes and outcomes of pneumococcal bacteremia in cancer patients., Methods: Prospective observational analysis of all consecutive cancer adults admitted to a university hospital (January 2006-April 2011)., Results: Of 971 episodes of bacteremia, 63 (6.5%) were caused by Streptococcus pneumoniae. Pneumonia was the most common source of pneumococcal bacteremia (84.1%). Although all isolated pneumococci were penicillin-susceptible, resistance to ceftazidime was high (43%). The serotypes most frequently isolated were 19A and 14, and the most common genotypes were Spain(9V)-ST156 and Denmark(14)-ST230. Only 23% of patients had received the 23-valent polysaccharide pneumococcal vaccine. This polysaccharide vaccine was found to cover 72.4% of the serotypes identified, whereas the 7-valent, 10-valent and the 13-valent conjugate vaccines covered 24.1%, 29.3%, and 53.5% of serotypes respectively. The early case-fatality rate (<48 h) was 4.8% and overall case-fatality rate (<30 days) 14.3%., Conclusions: Pneumococcal bacteremia, which complicates mainly pneumonia, is frequent in cancer patients and causes significant morbidity and case-fatality rate. Resistance to ceftazidime is particularly high. These findings should be considered when selecting antibiotic treatment for cancer patients presenting pneumonia., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

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).

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.

Background: We endeavored to construct a simple score based entirely on epidemiological and clinical variables that would stratify patients who require hospital admission because of community-acquired pneumonia into groups with a low or high risk of developing bacteremia., Methods: Derivation and internal validation cohorts were obtained by retrospective analysis of a database that included 3116 consecutive patients with community-acquired pneumonia from 2 university hospitals. Potential predictive factors were determined by means of a multivariate logistic regression equation applied to a cohort consisting of 60% of the patients. Points were assigned to significant parameters to generate the score. It was then internally validated with the remaining 40% of patients and was externally validated using an independent multicenter cohort of 1369 patients., Results: The overall rates of bacteremia were 12%-16% in the cohorts. The clinical probability estimate of developing bacteremia was based on 6 variables: liver disease, pleuritic pain, tachycardia, tachypnea, systolic hypotension, and absence of prior antibiotic treatment. For the score, 1 point was assigned to each predictive factor. In the derivation cohort, a cutoff score of 2 best identified the risk of bacteremia. In the validation cohorts, rates of bacteremia were <8% for patients with a score 1 (43%-49% of patients), whereas blood culture results were positive in 14%-63% of cases for patients with a score 2., Conclusions: This clinical score, based on readily available and objective variables, provides a useful tool to predict bacteremia. The score has been internally and externally validated and may be useful to guide diagnostic decisions for community-acquired pneumonia.

Staphylococcus aureus caused 30 of 438 (7%) cases of bacteremia in neutropenic patients with cancer during a 10-year study period. Acute leukemia as an underlying disease and severe oral mucositis were more frequent among patients with Staphylococcus aureus bacteremia (57% vs. 33%, P = 0.01, and 32% vs. 12%, P = 0.006, respectively) than among the 151 patients who had gram-negative bacteremia during the same study period. The most frequent source of Staphylococcus aureus bacteremia was the venous catheter (35% vs. 1%; P = 0.00001). Septic metastases were more frequent in patients with Staphylococcus aureus bacteremia (14% vs. 4%, P = 0.03). Attributable mortality was 10% and overall mortality 23%. Staphylococcus aureus bacteremia remains a significant cause of morbidity and mortality in neutropenic patients with cancer.

The prevalence of resistance to cephalosporins among viridans-group streptococci causing 88 (18%) cases among 485 bacteraemias in neutropenic cancer patients was studied. Rates of resistance to ceftriaxone, ceftazidime, cefpirome and cefepime were 22, 53, 14 and 34%, respectively. Previous administration of beta-lactam therapy was the only factor significantly associated with bacteraemia due to cephalosporin-resistant strains; only 11 (16%) of 68 patients infected with cephalosporin-susceptible bacteria had received these antibiotics compared with 10 (50%) of 20 patients infected with cephalosporin-resistant bacteria (P = 0.0052).

We prospectively studied 485 episodes of bacteremia in neutropenic patients with cancer. Viridans streptococci caused a total of 88 episodes (18%). Ten (11%) of these 88 cases were associated with serious complications: acute respiratory distress syndrome (ARDS) plus septic shock (5 cases), ARDS (3), and septic shock (2). Streptococcus mitis was the species most frequently isolated (7 of 10 episodes). Four viridans streptococci showed a diminished susceptibility to penicillin (MICs ranged from 0.25 to 4 microg/mL), and 5 strains were resistant to ceftazidime (MICs ranged from 2 to >32 microg/mL). Patients with viridans streptococcal bacteremia (VSB) who developed serious complications were compared with patients with VSB without complications. Severe oral mucositis (70% vs. 32.5%, respectively; P=.036), high-dose chemotherapy with cyclophosphamide (60% vs. 25%, respectively; P=.043), and allogeneic bone marrow transplantation (40% vs. 10%, respectively; P=.040) were the only variables found to be significantly associated with the development of complications. Neither a specific species of viridans streptococci nor resistance to penicillin was associated with the occurrence of complications. The mortality rate was higher in case patients than in control patients (80% vs. 17.5%, respectively; P<.001). Serious complications associated with VSB occur mainly in patients receiving high-dose chemotherapy with cyclophosphamide before allogeneic bone marrow transplantation who develop severe oral mucositis; these complications are associated with a high mortality rate.

The aim of the present study was to determine the efficacy of an antibiotic-lock technique in preventing endoluminal catheter-related infection with gram-positive bacteria in neutropenic patients with hematologic malignancies. Patients with nontunneled, multilumen central venous catheters were assigned in a randomized, double-blinded manner to receive either 10 U of heparin per ml (57 patients) or 10 U of heparin per ml and 25 microg of vancomycin per ml (60 patients), which were instilled in the catheter lumen and which were allowed to dwell in the catheter lumen for 1 h every 2 days. Insertion-site and hub swabs were taken twice weekly. The primary and secondary end points of the trial were significant colonization of the catheter hub and catheter-related bacteremia, respectively. Significant colonization of the catheter hub occurred in nine (15.8%) patients receiving heparin (seven patients were colonized with Staphylococcus epidermidis, one patient was colonized with Staphylococcus capitis, and one patient was colonized with Corynebacterium sp.), whereas the catheter hubs of none of the patients receiving heparin and vancomycin were colonized (P = 0.001). Catheter-related bacteremia developed in four (7%) patients receiving heparin (three patients had S. epidermidis bacteremia and one patient had S. capitis bacteremia), whereas none of the patients in the heparin and vancomycin group had catheter-related bacteremia (P = 0.05). The times to catheter hub colonization and to catheter-related bacteremia by the Kaplan-Meier method were longer in patients receiving heparin and vancomycin than in patients receiving heparin alone (P = 0.004 and P = 0.06, respectively). Our study shows that a solution containing heparin and vancomycin administered by using an antibiotic-lock technique effectively prevents catheter hub colonization with gram-positive bacteria and subsequent bacteremia during chemotherapy-induced neutropenia in patients with hematologic malignancy.

Background: The aim of this study was to determine the incidence, clinical characteristics and outcome of vancomycin-resistant enterococcal bacteremia., Patients and Methods: We included all cases of enterococcal bacteremia in neutropenic cancer patients documented between January 1986 and December 1995 in a 1,000-bed university hospital, where a prospective surveillance of all cases of bacteremia is regularly done. Molecular typing was performed on all vancomycin-resistant strains with the analysis of chromosomic DNA by macrorestriction., Results: Seventeen cases of enterococcal bacteremia were documented. Seven (41%) were caused by vancomycin-resistant strains (E. faecium 3 and E. gallinarum 4), six of which occurred in the last 5 years of the study period. The average age of patients was 43 years (18-69) and most of them had acute leukemia. Eighty percent of these patients had received vancomycin and/or cephalosporins within 2 weeks prior to bacteremia. Previous administration of antibiotics was more frequent in patients with bacteremia caused by vancomycin-resistant enterococci than in those with bacteremia caused by susceptible strains (86% vs 30%; p < 0.05). The mean number of previous antibiotics (2.4 vs 0.8; p < 0.05) as well as days of treatment (13.6 vs 4.3; p = 0.05) were also higher among patients with resistant enterococcal bacteremia. The overall mortality was 57%., Conclusions: This study shows the emergence of sporadic cases of bacteremia caused by vancomycin-resistant enterococci in neutropenic cancer patients in our area. This fact seems to be related with the previous administration of antibiotics and advice that a rational use of these agents is needed.

Background: Bacteremic pneumonia is a major cause of death among neutropenic patients with cancer., Methods: We analyzed the causes, empirical antibiotic therapy, and outcome of 40 consecutive cases of bacteremic pneumonia identified among 408 episodes of bacteremia in adult neutropenic patients with cancer, prospectively documented from 1986 to 1995., Results: The most frequent causative organisms were Pseudomonas aeruginosa (17 cases), Streptococcus pneumoniae (12 cases), Escherichia coli (5 cases), and Streptococcus mitis (3 cases). Overall, P. aeruginosa and S. pneumoniae caused 72.5% of all episodes of bacteremic pneumonia, compared with 11.4% of bacteremic episodes from other sources (P< .001). Thirty patients received ceftazidime and 10 patients received imipenem as the beta-lactam component of the initial empirical treatment. All strains of P. aeruginosa were susceptible to both agents. Forty-seven percent of streptococcal strains were penicillin resistant and showed a decreased susceptibility to ceftazidime (minimum inhibitory concentration ranged from 1 to 64 microg/mL). Five patients (12.5%) were considered to have received inappropriate empirical antibiotic therapy. Attributable mortality in patients with bacteremic pneumonia was higher than in patients with bacteremia from other sources; 22 (55%) of the 40 patients with bacteremic pneumonia died, whereas 39 (10.6%) of the 368 patients with bacteremia from other sources died (P<.001)., Conclusions: Our data suggest that bacteremic pneumonia in neutropenic cancer patients is associated with a poor outcome and that empirical antibiotic therapy for neutropenic patients with pneumonia should include agents active against both P. aeruginosa and cephalosporin-resistant streptococci.

We identified 17 cases of pneumococcal bacteremia among 340 neutropenic cancer patients with bacteremia. Pneumonia was more frequent in patients with pneumococcal bacteremia than in those with bacteremia due to other organisms: 12 (71%) of 17 patients with pneumococcal bacteremia had pneumonia, whereas only 23 (7%) of 323 patients with nonpneumococcal bacteremia had pneumonia (P < .001). Eight (47%) of the 17 episodes of pneumococcal bacteremia were caused by penicillin-resistant strains (MICs ranged from 0.12 microg/mL to 4 microg/mL); these penicillin-resistant pneumococci showed varying degrees of diminished susceptibility to all beta-lactams studied, especially ceftazidime (MICs of this drug ranged from 1 microg/mL to 64 microg/mL). Imipenem was the beta-lactam agent most active against these organisms (MICs ranged from 0.03 microg/mL to 0.25 microg/mL). Patients with penicillin-resistant pneumococcal bacteremia received inappropriate empirical antibiotic therapy more often than did patients with bacteremia due to susceptible strains (i.e., 4 (50%) of 8 patients vs. 0 of 9, respectively; P < .05). Eight (47%) of the 17 patients with pneumococcal bacteremia died. In areas where penicillin-resistant pneumococci are highly endemic, these findings should be considered in selecting empirical antibiotic therapy for neutropenic patients with cancer who are suspected of having pneumonia.

Intravascular catheters have become essential tools for the management of patients in modern medical practice, but there are complications. In particular, catheter-related infection remains a major cause of nosocomial infection and primary septicemia. The development of preventive strategies to reduce the incidence of catheter-related infection is an important goal for all health providers. Over recent years, significant advances in prophylactic measures for the prevention of catheter-related infection have been made. This paper reviews strategies based on antibiotic prophylaxis such as systemic administration of antibiotics, application of antibiotic ointments to the skin insertion site as well as catheter flushing with antibiotics, the antibiotic-lock technique and the use of antimicrobial impregnated catheters. [ABSTRACT FROM AUTHOR]

Catheter-related bacteremia is a major complication in patients with long-term surgically implanted central venous catheters, which are difficult and expensive to remove. Conventional treatment fails in a significant number of cases, resulting in removal of the device. The antibiotic-lock technique involves instilling a high concentration of antibiotic into the catheter lumen, and allowing it to remain for a period of time. Results of several open studies, mainly involving patients receiving home parenteral nutrition, indicate that this method may be regarded as an alternative to the conservative treatment of noncomplicated intraluminal catheter-related bacteremia, in which infection may be treated without catheter removal. However, many questions about this therapeutic method remain to be resolved, including appropriate concentration of antibiotics, duration of treatment, and whether or not concomitant systemic antibiotic therapy is necessary. Prospective studies comparing the antibiotic-lock technique with conventional treatment are needed. [ABSTRACT FROM AUTHOR]