Bloodstream Infections In Neutropenic Patients Research Articles

Levofloxacin prophylaxis for pediatric leukemia patients: monitoring of outcomes for sustained benefit and consequences.

Levofloxacin prophylaxis reduces bloodstream infections in neutropenic patients with acute myeloid leukemia or relapsed acute lymphoblastic leukemia. A retrospective, longitudinal cohort study compares incidence of bacteremia, multidrug-resistant organisms (MDRO), and Clostridioides difficile (CDI) between time periods of levofloxacin prophylaxis implementation. Benefits were sustained without increasing MDRO or CDI.

Characteristics, Outcomes, and Clinical Indicators of Bloodstream Infections in Neutropenic Patients with Hematological Malignancies: A 7-Year Retrospective Study.

The aim of this study was to investigate the current epidemiology, its changes during the study years, and inflammatory biomarkers of bacterial bloodstream infections (BSIs) in neutropenic patients with hematological malignancies. We assessed mortality risk factors and multidrug-resistant (MDR) gram-negative BSI predictors. We conducted a retrospective study from January 2015 to December 2021, which included adult neutropenic oncohematological patients with confirmed BSIs. We used univariable and multivariable analyses to analyze the risk factors. Each index's reliability for bacterial BSI diagnosis was assessed using the receiver-operating characteristic curve and area under the curve. A total of 514 isolates were obtained from the 452 patients. The average mortality was 17.71%. Gram-negative organisms were the predominant causes of BSI. Escherichia coli was the most common microorganism (49.90%). The overall variation trend of the isolation rate of MDR and carbapenem-resistant gram-negative bacteria increased. Multivariate analysis indicated that: 1) neutropenia that lasted for more than 7 days, patients ≥ 60 years of age, septic shock, hospitalization for >20 days, BSI with a carbapenem-resistant strain, and treatment with linezolid or vancomycin in infections lasting less than 30 days were independent mortality risk factors; 2) severe neutropenia exceeding 7 days, unreasonable empirical therapy, and receipt of aminoglycosides or 3rd or 4th generation cephalosporins in infections lasting less than 30 days were independent risk factors of MDR gram-negative bacteria. Procalcitonin, absolute neutrophil count, and white blood cell indicate higher diagnostic accuracy for BSIs. Moreover, bacteria time to detection was better at differentiating Gram-negative and Gram-positive bacterial infections. We analyzed the risk factors for BSI neutropenic patients with hematological malignancies, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians with novel insights into the diagnosis and treatment of BSI to improve future clinical outcomes.

EPIDEMIOLOGY, PREDISPOSING FACTORS AND OUTCOME OF STAPHYLOCOCCUS AUREUS BACTEREMIA IN NEUTROPENIC PATIENTS

Staphylococcus aureus is a common cause of bloodstream infection in neutropenic patients. We analyzed trends in incidence, epidemiology, predisposing factors and outcome of S. aureus bacteremia (SAB) in febrile neutropenic patients. We reviewed a database of febrile neutropenia at a single institution in Brazil in a 30-year period (January 1991 to December 2020). We divided in 3 periods: 1991-1994 (period 1), 2001-2010 (period 2) and 2011-2020 (period 3), and looked at incidence rates, risk factors and mortality. Risk factors and prognostic factors were evaluated by univariate (Fisher or Chi-square for categorical variables and Wilcoxon test for continuous variables) and multivariate (logistic regression) analysis. We diagnosed 62 (3%) episodes of SAB in 2,243 episodes of febrile neutropenia, 23 (38%) of which were caused by methicillin-resistant S. aureus (MRSA). The incidence of SAB per 1,000 days of neutropenia was 1.57, 2.53 and 1.50 in periods 1, 2 and 3, respectively (p > 0.05), and of MRSA was 0.49, 0.84 and 1.07, respectively (p > 0.05). Most infections (70%) were diagnosed in the first day of fever and the clinical presentation were skin infection (19%), catheter-related infection (14%) and pneumonia (3%). Complications like endocarditis or osteomyelitis were not observed. The only factor associated with S. aureus bacteremia by multivariate analysis was cellulitis at site of catheter exit site or tunnel on day 1 of fever (odds ratio [OR] 4.34, 95% confidence interval [CI] 2.05 – 9.16), whereas quinolone prophylaxis was protective (OR 0.37, 95% CI 0.18 - 0.74). The crude mortality of SAB was 30.6%, compared 13.8% in patients without this infection (p < 0.001). However, early mortality (within 3 days of start of empiric antibiotic therapy) was not significantly different (4.8% vs. 1.9%, p = 0.08). The mortality with MRSA was higher than with methicillin-susceptible S. aureus (47.8% vs. 13.9%, p < 0.001), but no difference was found regarding early mortality (5.0 vs 1.7%, p = 0.27). Among various predictors of death during febrile neutropenia MRSA bacteremia (but not methicillin-sensitive) was associated with an increased risk of death by multivariate analysis. The median time from febrile neutropenia to death in MRSA episodes was 19 days. The incidence of SAB over the period remained stable. Complication of SAB were not common. Although the crude mortality was higher with SAB (including MRSA), it was not associated with early deaths, thus not demanding anti-staphylococcal coverage in the first day of febrile neutropenia. MRSA bacteremia was associated with increased risk of death, with most deaths occurring after 2 weeks of febrile neutropenia.

Rapid DNA visual detection of polymicrobial bloodstream infection using filter paper

Bloodstream infection (BSI) is a major complication in patients with cancers due to therapy-induced neutropenia and underlying conditions, which increases hospitalization time and mortality rate. Targeted and timely antimicrobial management is crucial to save the patients’ lives and reduce the social and economic burdens. Blood culture is a routine clinical diagnostic method of BSI with a long turnaround time, and generally identifies monomicrobial BSI. Thus, polymicrobial BSI often goes undetected although it occurs more frequently in these patients and results in more severe outcomes compared to monomicrobial BSI. In this work, we apply glutaric anhydride, N-hydroxysuccinimide and N,N′-dicyclohexylcarbodiimide to fabricate a functional surface on cellulose filter paper. Targeting three pathogens (Escherichia coli, Saccharomyces cerevisiae, and human cytomegalovirus) commonly occurring in BSI in neutropenic patients, we demonstrate rapid and accurate triplex pathogen DNA detection using the functionalized paper. All three pathogen DNA was identified in 1–5 min with a detection limit of 0.1–0.5 ng/µL. The developed test tool has the potential to provide rapid polymicrobial BSI diagnosis in support of timely, accurate antimicrobial treatment, and could be integrated into an automatic sample-to-result portable equipment.

1364. Effect of Cefepime Prophylaxis on Bacterial Bloodstream Infections in Neutropenic Patients with Acute Myelogenous Leukemia

BackgroundBacteremia is a major cause of morbidity and mortality among children with acute myelogenous leukemia (AML) and chemotherapy-induced neutropenia. Data evaluating the utility of bacterial prophylaxis in this pediatric population are limited. In April 2014, Children’s Health (CH) implemented the use of cefepime bacterial prophylaxis for AML patients undergoing induction and intensification chemotherapy. The objective of this study was to evaluate the impact of this practice on the frequency of documented bacterial bloodstream infections (BSIs).MethodsThis was an observational, retrospective cohort study of patients < 21 years of age with AML admitted at CH from January 2010 through December 2018. The primary outcome was frequency of documented BSIs before (PRE; Jan 2010 to Mar 2014) and after (POST; Apr 2014 to Dec 2018) implementation of routine bacterial prophylaxis. Secondary outcomes included differences in total antibiotic days per neutropenia days and the occurrence of neutropenia-associated C. difficile infection between groups.ResultsOf 90 patients with AML who met the cohort inclusion criteria, 38 and 52 were treated during the PRE and POST prophylaxis periods, respectively. The incidence rate of documented BSIs per 1000 neutropenia days decreased from 15.5 to 2.8 after the implementation of routine cefepime prophylaxis (incidence rate ratio 0.18, Poisson regression 95% CI 0.09 to 0.33, P< 0.001). Patients were more likely to have febrile neutropenia in the PRE group (OR 11.9, 95% CI 6.6 to 20.8). The POST group had more antibiotic days per total neutropenia days (0.76 PRE vs 0.97 POST, P< 0.0001), but the frequency of first-episode C. difficile infection was not significantly different between groups (OR 0.36, 95% CI 0.1 to 1.4).ConclusionUniversal cefepime prophylaxis for children with AML and chemotherapy-induced neutropenia was associated with a significant reduction in the incidence of febrile neutropenia and neutropenia-associated BSIs without increasing the incidence of C. difficile infection.Disclosures All Authors: No reported disclosures

Características clínicas y microbiológicas de infecciones del torrente sanguíneo en pacientes adultos neutropénicos

Bloodstream infections (BI) are relevant in neutropenic patients because they are associated with an increased number of complications and death. The objective was determinate the epidemiologic and microbiologic features of the BI in neutropenic patients with solid neoplasm (SN) and hematologic neoplasm (HN). Retrospective study in two third level hospitals between 2009 and 2016. They were included all the patients older than 18 years-old with active oncologic disease and neutropenia, who had BI. Patients with dermatologic cancer other than melanoma where excluded. A total of 143 BI in neutropenic were observed, of which 80.4% occurred in HN. Around 97.9% of the patients had a high-risk neutropenia without differences between both groups. The most frequent site of BI was primary bacteremia (46.9%) and catheter-associated infection (21%), without significant differences between the two groups. The gram negatives bacilli (GNB) predominated over the gram positive cocci (GPC) and they represented 74.1% of the isolated bacteria, being Escherichia coli the most frequent (32.8%). Among the gram positive cocci, Staphylococcus aureus (28.1%) was the most frequent isolated, followed by coagulase-negative Staphylococci (CNS). There were no differences in microbiological isolates between both groups. With regard to the antimicrobial susceptibility 67.5% of the CNS, 17.6% of the E. coli and 27.6% of the Klebsiella pneumoniae were multiresistant with no differences between both groups. Only 11.1% of S. aureus isolates were methicillin resistant. In conclusion BI of the neutropenic patients where most frequents within patients with HN, GNB were the main microbiological isolates. High mortality was observed in neutropenic patients with BI.

Bloodstream infections in neutropenic patients with haematological malignancies.

Patients with haematological malignancies have higher risk of acquiring bloodstream infection (BSI). Neutropenia resulting from cytotoxic chemotherapy is the most common risk factor. Infections can progress rapidly with poor outcomes. Understanding the epidemiology may enable prevention and effective management. We investigated and compared the incidence of BSI amongst patients with haematological malignancies and neutropenia and examined the changing spectrum of organisms, and their antimicrobial profiles. BSI data between July 1st 2009 and June 30th 2015 was reviewed. Three hundred and fifty five BSI were identified in 255 neutropenic patients. Acute myeloid leukaemia (AML) accounted for 40%, Non-Hodgkin's lymphoma for 22% and Acute lymphocytic leukaemia (ALL) for 11.8%. A neutrophil count of <500 cells/μL was present in 93.2%. The overall incidence was 5.40 BSI per 1000 Haematology Occupied Bed days (OBD). Viridans streptococci and Enterococcus species were the most predominant Gram-positives. Vancomycin resistant Enterococcus faecium (VRE) emerged as the predominant Enterococcus species during the study period. Escherichia coli was the most predominant Gram-negative and Extended-spectrum beta-lactamases (ESBL) were detected in 7.1% of isolates. Amongst the Enterobacteriaceae and Pseudomonas aeruginosa dual resistance to Piperacillin-tazobactam and Gentamicin was detected in 5.4%. Our incidence of BSI was 5.40 per 1000 OBD, however variability in reporting of rates in neutropenic patients with haematological malignancies makes comparison between studies difficult, highlighting the need for rate reporting standardization. The epidemiology of organisms causing BSI has changed over time. There is a trend towards an increasing incidence of VRE and multidrug resistant Gram-negatives.

Prevalence of bloodstream infections in neutropenic patients with bacteriuria

Prevalence of bloodstream infections in neutropenic patients with bacteriuria

Whole-Genome Sequencing Accurately Identifies Resistance to Extended-Spectrum β-Lactams for Major Gram-Negative Bacterial Pathogens

There is marked interest in using DNA-based methods to detect antimicrobial resistance (AMR), with targeted polymerase chain reaction (PCR) approaches increasingly being incorporated into clinical care. Whole-genome sequencing (WGS) could offer significant advantages over targeted PCR for AMR detection, particularly for species where mutations are major drivers of AMR. Illumina MiSeq WGS and broth microdilution (BMD) assays were performed on 90 bloodstream isolates of the 4 most common gram-negative bacteria causing bloodstream infections in neutropenic patients. The WGS data, including both gene presence/absence and detection of mutations in an array of AMR-relevant genes, were used to predict resistance to 4 β-lactams commonly used in the empiric treatment of neutropenic fever. The genotypic predictions were then compared to phenotypic resistance as determined by BMD and by commercial methods during routine patient care. Of 133 putative instances of resistance to the β-lactams of interest identified by WGS, only 87 (65%) would have been detected by a typical PCR-based approach. The sensitivity, specificity, and positive and negative predictive values for WGS in predicting AMR were 0.87, 0.98, 0.97, and 0.91, respectively. Using BMD as the gold standard, our genotypic resistance prediction approach had a significantly higher positive predictive value compared to minimum inhibitory concentrations generated by commercial methods (0.97 vs 0.92; P = .025). These data demonstrate the potential feasibility of using WGS to guide antibiotic treatment decisions for patients with life-threatening infections for an array of medically important pathogens.

Risk Factors and Outcomes of Vancomycin-Resistant vs. Vancomycin-Sensitive Enterococcal Blood Stream Infections in Patients with Acute Myeloid Leukemia

BackgroundEnterococci are commensal of the gastrointestinal tract known to cause blood stream infections (BSIs). Studies have shown increased mortality from enterococcal BSI in neutropenic patients, indicating Vancomycin-resistant Enterococcal (VRE) infections causing increased mortality. Whether these differences in mortality apply to AML patients is unknown. The objectives of this study are to compare the risk factors and outcomes between VRE & VSE BSIs in AML patients.MethodsWe conducted a single center, retrospective cohort study of patients with enterococcal BSIs at H. Lee Moffitt Cancer Center from July 2011 to October 2015. Records were searched to identify AML patients with enterococcal BSI. Enterococcal species, neutropenia duration, Vancomycin exposure, VRE colonization, 7 and 30 day mortality, age, sex, length of stay, stem cell transplant & central line status were compared. We conducted statistical tests and Kaplan-Meier plot to analyze mortality trends.ResultsThere were a total of 77 AML patients with enterococcal BSI. Forty-two (54.5%) were caused by VRE. E. faecalis and E. faecium accounted for 28.5% and 62.3% of BSI respectively. The E. faecalis isolates were more likely to be VSE (83% vs. 8.3 %, P < 0.001) and E. fecium isolates to be VRE (71% vs. 29%, P < 0.001). Duration of neutropenia was significantly longer (27.3 vs. 20.7 days, P < 0.005) among AML patients with VRE BSI. Recent Vancomycin use and VRE colonization were significantly associated with VRE BSI. There were no significant differences in duration of bacteremia, length of stay and 7 and 30-day mortality between VRE vs. VSE BSI.Conclusion Enterococcal infections among AML patients are significantly more likely to be caused by Vancomycin-resistant E. faecium. The risk is increased by VRE colonization and Vancomycin exposure. The absence of statistical difference in 7 or 30-day mortality between VRE and VSE enterococcal BSI in our AML patients could indicate that in a homogenous group of patients, host and treatment-related factors may influence mortality more than species or susceptibility of the isolates. Our finding confirms VRE colonization as risk factor of VRE BSI for AML patients. This finding is important for future patient education and development of preventive and treatment protocols.Disclosures All authors: No reported disclosures.

Prevalence of Bloodstream Infections in Neutropenic Patients with Bacteriuria

Prevalence of Bloodstream Infections in Neutropenic Patients with Bacteriuria

A randomized trial on chlorhexidine dressings for the prevention of catheter-related bloodstream infections in neutropenic patients

Central venous catheter (CVC)-related bloodstream infections (CRBSI) are a frequent cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Chlorhexidine containing catheter securement dressings may prevent CRBSI. A multicenter randomized, controlled trial was conducted at 10 German hematology departments. We compared chlorhexidine-containing dressings with non-chlorhexidine control dressings in neutropenic patients. The primary end point was the incidence of definite CRBSI within the first 14 days (dCRBSI14) of CVC placement. Secondary end points included combined incidence of definite or probable CRBSI within 14 days (dpCRBSI14), overall (dpCRBSI), incidence of unscheduled dressing changes and adverse events. From February 2012 to September 2014, 613 assessable patients were included in the study. The incidence of dCRBSI14 was 2.6% (8/307) in the chlorhexidine and 3.9% (12/306) in the control group (P = 0.375). Both dpCRBSI14 and dpCRBSI were significantly less frequent in the study group with dpCRBSI14 in 6.5% (20/307) of the chlorhexidine group when compared with 11% (34/306) in the control group (P = 0.047), and dpCRBSI in 10.4% (32/307) versus 17% (52/306), respectively (P = 0.019). The frequency of dressing intolerance with cutaneous and soft tissue abnormalities at the contact area was similar in both groups (12.4% and 11.8%; P = 0.901). Although the trial failed its primary end point, the application of chlorhexidine containing catheter securement dressings reduces the incidence of definite or probable CRBSI in neutropenic patients. NCT01544686 (Clinicaltrials.gov).

Bacterial Landscape of Bloodstream Infections in Neutropenic Patients via High Throughput Sequencing.

BackgroundBloodstream infection (BSI) is a common and potentially life-threatening complication in patients with hematological malignancies and therapy-induced neutropenia. Administration of broad spectrum antibiotics has substantially decreased the mortality rate in febrile neutropenia, but bacterial infection is documented in only one-third or fewer of the cases. BSI is typically diagnosed by blood culture; however, this method can detect only culturable pathogens.MethodsIn the present study, a total of 130 blood samples from hematological patients receiving dose-intensive antitumoural treatment were subjected to 16S rRNA PCR and 62 of them were cultured. PCR positive samples were processed to high throughput sequencing by amplifying the V1-V3 regions of the 16S rRNA gene to obtain a full spectrum of bacteria present in BSI.ResultsFive phyla and 30 genera were identified with sequencing compared to 2 phyla and 4 genera with culture. The largest proportion of bacteria detected by sequencing belonged to Proteobacteria (55.2%), Firmicutes (33.4%) and Actinobacteria (8.6%), while Fusobacteria (0.4%) and Bacteroidetes (0.1%) were also detected. Ninety-eight percent of the bacteria identified by sequencing were opportunistic human pathogens and 65% belonged to the normal human microbiota.ConclusionsThe present study indicates that BSIs in neutropenic hosts contain a much broader diversity of bacteria, likely with host origin, than previously realized. The elevated ratio of Proteobacteria in BSI corroborates the results found in other systemic inflammatory diseases, such as inflammatory bowel disease or mucosal infections. This knowledge may become of value for tailoring antimicrobial drug administration.

Factors influencing mortality in neutropenic patients with haematologic malignancies or solid tumours with bloodstream infection

The purpose of this study was to identify factors influencing mortality in neutropenic patients with haematologic malignancies or solid tumours with bloodstream infection (BSI). All episodes of BSI occurring in adult neutropenic patients with haematologic malignancies or solid tumours were prospectively recorded from January 2006 to December 2013. We analysed the factors influencing mortality in both groups of patients. We documented 602 consecutive episodes of BSI; 510 occurred in patients with haematologic malignancies and 92 in patients with solid tumours. The overall case-fatality rates were 12% and 36%, respectively. Independent risk factors associated with a higher case-fatality rate in patients with haematologic malignancies were: intensive care unit admission (odds ratio (OR), 15.2; 95% confidence interval (CI), 5.4–42.7), advanced neoplasm (OR, 8.7; 95% CI, 2.9–25.7), corticosteroid therapy (OR, 7.0; 95% CI, 3–16.4), multidrug-resistant Gram-negative BSI (OR, 3.8; 95% CI, 1.2–11.8) and a Multinational Association for Supportive Care in Cancer risk score of <21 (OR, 3.1; 95% CI, 1.3–7.4). By contrast, coagulase-negative staphylococci BSI (OR, 0.04; 95% CI, 0.004–0.5) and empirical antibiotic combination therapy (OR, 0.1; 95% CI, 0.05–0.3) were found to be protective. Independent risk factors for overall case-fatality rate in patients with solid tumours were: shock at presentation (OR, 14.3; 95% CI, 3.2–63.8), corticosteroid therapy (OR, 10; 95% CI, 2.3–44) and advanced neoplasm (OR, 7.8; 95% CI, 1.4–41.4). Prognostic factors identified in this study may help to detect those patients at higher risk of death in each group. Medical intervention addressing some of these factors might improve the outcome of BSI in neutropenic patients with haematologic malignancies or solid tumours.

Bloodstream infections in neutropenic patients with cancer: Differences between patients with haematological malignancies and solid tumours

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. All episodes of BSI in neutropenic patients with HM and ST were prospectively recorded and compared. 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. 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.

Development and validation of a clinical model to predict the presence of β-lactam resistance in viridans group streptococci causing bacteremia in neutropenic cancer patients.

Concern for serious infection due to β-lactam-resistant viridans group streptococci (VGS) is a major factor driving empiric use of an anti-gram-positive antimicrobial in patients with febrile neutropenia. We sought to develop and validate a prediction model for the presence of β-lactam resistance in VGS causing bloodstream infection (BSI) in neutropenic patients. Data from 569 unique cases of VGS BSI in neutropenic patients from 2000 to 2010 at the MD Anderson Cancer Center were used to develop the clinical prediction model. Validation was done using 163 cases from 2011 to 2013. In vitro activity of β-lactam agents was determined for 2011-2013 VGS bloodstream isolates. In vitro resistance to β-lactam agents commonly used in the empiric treatment of febrile neutropenia was observed only for VGS isolates with a penicillin minimum inhibitory concentration (MIC) of ≥ 2 µg/mL. One hundred twenty-nine of 732 patients (17%) were infected with VGS strains with a penicillin MIC ≥ 2 µg/mL. For the derivation and validation cohorts, 98% of patients infected by VGS with a penicillin MIC of ≥ 2 µg/mL had at least 1 of the following risk factors: current use of a β-lactam as antimicrobial prophylaxis, receipt of a β-lactam antimicrobial in the previous 30 days, or nosocomial VGS BSI onset. Limiting empiric anti-gram-positive therapy to neutropenic patients having at least 1 of these 3 risk factors would have reduced such use by 42%. Simple clinical criteria can assist with targeting of anti-gram-positive therapy to febrile neutropenic patients at risk of serious β-lactam-resistant VGS infection.

The emergence of vancomycin-resistant enterococcal bacteremia in hematopoietic stem cell transplant recipients

As antimicrobial resistance increases, understanding the current epidemiology of bloodstream infections (BSIs) in hematopoietic stem cell transplant (HSCT) recipients is essential to guide empirical antimicrobial therapy. We therefore reviewed microbial etiologies, timing and outcomes of BSIs in patients who were transplanted from September 2007 to December 2011. Vancomycin-resistant enterococci (VRE) were the most common pathogens in allogeneic HSCT recipients and the fourth most common after autologous transplant. VRE did not cause any of 101 BSIs in neutropenic patients who were not receiving antibacterials, but caused 32 (55%) of 58 BSIs in neutropenic patients receiving a broad-spectrum β-lactam agent (p < 0.001). Rates of septic shock and 7-day mortality were 5% and 0% for streptococcal bacteremia, 12% and 18% for VRE bacteremia, and 20% and 14% for Gram-negative bacteremia. In conclusion, VRE bacteremia was the most common BSI in allogeneic HSCT recipients, occurred primarily in neutropenic patients receiving broad-spectrum β-lactams and was associated with poor outcomes.

Changing aetiology, clinical features, antimicrobial resistance, and outcomes of bloodstream infection in neutropenic cancer patients

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.

Bloodstream infections in neutropenic patients: early detection of pathogens and directed antimicrobial therapy due to surveillance blood cultures

Bloodstream infections (BSIs) are frequent infectious complications in neutropenic patients. In order to determine the efficacy of surveillance blood cultures (BCs) to detect BSIs prior to clinical manifestation we performed a prospective trial. One hundred patients with haematological malignancies and long-term neutropenia following intensive cytotoxic therapies were recruited. BCs were taken thrice weekly during neutropenia. Forty-two patients were diagnosed with BSI. In 18 (43%) of those patients surveillance BC results were positive and identified microorganisms prior to onset of fever. In patients with positive surveillance BCs modification of the clinical management (specific antimicrobial therapy, CVC removal) resulted in a shorter time to defervescence (median 1.5 days) compared with patients with BCs positive after onset of fever (median 3.5 days, P = 0.004). In conclusion we detected causative microorganisms in more than one-third of BSIs prior to onset of clinical manifestation. The impact of surveillance BCs on the outcome has to be assessed in randomized studies.

Daptomycin in the treatment of vancomycin-resistant Enterococcus faecium bacteremia in neutropenic patients

Vancomycin resistant enterococcal (VRE) blood stream infection (BSI) in neutropenic patients is associated with poor outcome. We report our experience in treating VRE BSI in febrile, neutropenic patients with daptomycin, a recently licensed lipopeptide with bactericidal activity against VRE. Patients with fever, neutropenia and VRE BSI were treated with more than one dose of daptomycin (either 6 mg/kg/day or 4 mg/kg/day) in an open label, emergency-use trial. Patients were then assessed for clinical and microbiological cures and survival. MIC's of isolates to daptomycin were determined. Nine febrile, neutropenic patients with VRE BSI received daptomycin. Four of 9 courses (44%) had clinical and/or microbiologic cure. Two of the 5 who failed cure died within 3 days of initiation of daptomycin. Five subjects survived to 30 days after the onset of BSI. Use of daptomycin in neutropenic patients with VRE BSI deserves further study as a treatment for VRE BSI in neutropenic patients.