Non-neutropenic Group Research Articles

Clinical Characteristics and Outcomes of Neutropenic Sepsis: A Multicenter Cohort Study.

Sepsis is a leading cause of mortality in patients with neutropenia; however, data on whether neutropenic sepsis is associated with distinct clinical characteristics and outcomes are limited. Thus, this study was designed to clarify the clinical characteristics and outcomes of patients with neutropenic sepsis compared with those of patients without neutropenic sepsis diagnosed based on the Third International Consensus Definitions for Sepsis and Septic Shock criteria. We analyzed data from the Korean Sepsis Alliance, a nationwide prospective multicenter cohort study evaluating the clinical characteristics, management, and outcomes of patients with sepsis from September 2019 to February 2020. Eligible patients were divided into the neutropenic (absolute neutrophil count of less than 1,500/mL) and non- neutropenic groups. The characteristics and outcomes were compared between the two groups. During the study period, 2,074 patients were enrolled from 16 tertiary referral or university-affiliated hospitals. Of them, 218 (10.5%) had neutropenia. The neutropenia group was younger and had a lower proportion of patients with chronic diseases compared with the non-neutropenia group. However, solid tumors (50.0% vs. 34.1%; P > 0.001) and hematological malignancies (40.8% vs. 3.8%; P < 0.001) were more common in the neutropenia group. The neutropenia group had a higher incidence of septic shock (43.6% vs. 22.9%; P < 0.001) and higher Sequential Organ Failure Assessment score (7 vs. 5; P < 0.001) than the nonneutropenia group. However, no significant differences in microbiologically confirmed infections and its pathogen distribution and the incidence of multidrug resistance were observed between the two groups. The neutropenic group had a higher hospital mortality than the non-neutropenic group (42.2% vs. 26.3%; P < 0.001), and the Kaplan-Meier survival curve demonstrated a significant difference in survival within 1 week after diagnosing sepsis (log-rank test, P = 0.002). The incidence of adverse events during intensive care unit admission was not different between the two groups. Among hospital survivors, the neutropenic group was more frequently discharged to home (72.2% vs. 57.8%; P = 0.002). Neutropenic sepsis is associated with a higher-grade organ dysfunction during the diagnosis of sepsis and higher mortality without difference in the pathogen isolated.

Outcomes of Neutropenic Patients with Clostridium difficile Infection

Background: Data from Clostridium difficile infection (CDI) in neutropenic patients are still scarce. Objective: To assess outcomes of CDI in patients with and without neutropenia. Methods: The study included a retrospective cohort of adult patients at 3 academic hospitals between January 2013 and December 2017. The 2 study arms were neutropenic patients (neutrophil count &lt;500/mm3) and nonneutropenic patients with confirmed CDI episodes. The primary outcome evaluated the composite end point of all-cause in-hospital mortality, intensive care unit (ICU) admissions, and treatment failure at 7 days. The secondary outcome evaluated hospital length of stay. Results: Of 962 unique cases of CDI, 158 were neutropenic (59% men) and 804 were nonneutropenic (46% men). The median age was 57 years (IQR, 44–64) in the neutropenic group and 68 years (IQR, 56–79) in the nonneutropenic group. The median Charlson comorbidity score was 5 (IQR, 3–7.8) and 4 (IQR, 3–5) in the neutropenic and nonneutropenic groups, respectively. Regarding severity, 88.6% versus 48.9% were nonsevere, 8.2% versus 47% were severe, and 3.2% versus 4.1% were fulminant in the neutropenic and nonneutropenic groups, respectively. Also, 63% of patients (60.9% in nonneutropenic, 65.2% in neutropenic) were exposed to proton-pump inhibitors. A combination CDI treatment was required in 53.2% of neutropenic patients and 50.1% of nonneutropenic patients. The primary composite end point occurred in 27% of neutropenic patients versus 22% of nonneutropenic patients (P = .257), with an adjusted odds ratio of 1.30 (95% CI, 0.84–2.00). The median hospital length of stay after controlling for covariates was 21.3 days versus 14.2 days in the neutropenic and nonneutropenic groups, respectively (P &lt; .001). Complications (defined as hypotension requiring vasopressors, ileus, or bowel perforation) were seen in 6.0% of the nonneutropenic group and 4.4% of the neutropenic group (P = .574), with an adjusted odds ratio of 0.61 (95% CI, 0.28–1.45). Conclusions: Neutropenic patients were younger and their cases were less severe; however, they had lower incidences of all-cause in-hospital mortality, ICU admissions, and treatment failure. Hospital length of stay was significantly shorter in the neutropenic group than in the nonneutropenic group.Funding: NoneDisclosures: None

Pediatric and Neonatal Invasive Candidiasis: Species Distribution and Mortality Rate in a Thai Tertiary Care Hospital.

Invasive candidiasis (IC) is a serious infection among children with underlying medical conditions. A shift from C. albicans to non-albicans Candida has been observed worldwide. This study aims to identify species of Candida and factors associated with the overall 30-day mortality rate. A retrospective chart review was conducted among children with culture-confirmed IC from birth to 15 years of age at King Chulalongkorn Memorial Hospital, Thailand. Multivariate Cox regression analysis was performed to determine associated factors with 30-day mortality. From 2003 to 2019, 102 episodes of IC in pediatric group with a median age of 16 months (interquartile range 4-65) and 12 episodes of IC in neonatal group with a median age of 18 days (interquartile range 12-22). The species distribution were Candida albicans (35%), Candida parapsilosis (26%), Candida tropicalis (22%), Candida glabrata (6%) and other/unspecified species (11%). Antifungal treatment was given in 88% (67% Amphotericin B deoxycholate, 28% Fluconazole). Overall 30-day mortality rates were 28.5% [95% confidence interval (CI) 20.8%-38.4%] and 8.3% (95% CI 1.2%-46.1%) in pediatrics and neonates, respectively. Mortality rate among the neutropenic group was significantly higher than non-neutropenic group (46.4% vs. 20.6%, P = 0.005). Factors associated with 30-day mortality in pediatric IC were shock [adjusted hazard ratio (aHR) 4.2; 95% CI 1.8-9.4], thrombocytopenia (aHR 7.7; 95% CI 1.8-33.9) and no antifungal treatment (aHR 4.6; 95% CI 1.7-12.1). Two-third of children with IC were diagnosed with non-albicans Candida. Children with high mortality rate included those with neutropenia, presented with shock or thrombocytopenia, such that the proper empiric antifungal treatment is recommended.

The evaluation of neutropenia in common variable immune deficiency patients

ABSTRACTObjectives: Common variable immunodeficiency is a primary immunodeficiency disease characterized by hypogammaglobulinemia and heterogeneous clinical features. Neutropenia is a rare complication among CVID patients leading to a higher rate of infections and morbidity. Multiple factors (e.g. autoimmunity, infections, drugs and etc.) are found to underlie this complication.Methods: In the present study, demographic, clinical and laboratory data were compared between two groups of CVID patients with and without neutropenia.Results: Frequency of neutropenia was 8.1%. Infectious complications were the most prevalent clinical manifestations regardless of presence of neutropenia. However, candida infection and septicemia were significantly higher in neutropenic patients (p = 0.001 and p = 0.01, respectively). The most prominent clinical phenotypes of CVID patients with neutropenia were polyclonal lymphocytic infiltration and autoimmunity, both being considerably higher compared to the non-neutropenic group (p = 0.04 and p = 0.009, respectively). The mortality rate in neutropenic patients was higher than in patients without neutropenia (61.1 vs. 25.2%, p = 0.004).Conclusion: Although neutropenia is a rare complication among CVID patients, it is associated with frequent and severe clinical complications, including autoimmunity and lymphoproliferative conditions. Also, its accompaniment with higher mortality frequency in CVID patients indicates a need for more precise attention and consideration regarding specific treatment in neutropenic patients.

Neutropenia in pediatric heart transplant recipients

Neutropenia has been reported in pediatric heart transplant recipients, but its association with infectious morbidity and mortality is unknown. We sought to determine neutropenia's prevalence and impact on infection, rejection, and survival. A retrospective analysis of pediatric heart transplant recipients from March 2005 to August 2015 was performed. Demographics, medications, infection, and rejection data were collected. Of 142 pediatric heart transplant recipients, 77 (54.2%) developed neutropenia within 4.7months [3.3-12.1months] of transplant. In all patients, the adjusted 5-year cumulative incidence of neutropenia was 30.2%. Fifty-one patients (66.2%) had recurrent neutropenia. Six of 14 tested had positive antineutrophil antibodies. Medications associated with neutropenia were decreased in 15 (19.5%) and discontinued in 42 (54.4%) patients with no change in 1-year rejection rates compared to published data. Fifteen patients developed infection within 30days of neutropenia and two from 30days to 1year, with an infection rate similar to the non-neutropenic group. There was no significant difference in survival, ANC, rate of rejection or PTLD in neutropenic patients with and without infection at median follow-up (5.5years). Neutropenia is common in pediatric heart transplant recipients. Neutropenia had <20% risk of associated infection, similar to non-neutropenic patients. Infection in neutropenic patients did not increase mortality.

Risk Factors for Viridans Group Streptococcal Bacteremia in Neutropenic and Non-neutropenic Patients: A Single Center Case-Case-Control Study.

Viridans group streptococcal (VGS) bacteremia is common among neutropenic patients. Although VGS bacteremia occurs in non-neutropenic patients, risk factors are not well established. We conducted a case-case-control study to identify risk factors for VGS among neutropenic and non-neutropenic patients. Patients with VGS bacteremia between January 2009 and December 2014 in our 200-bed clinical research hospital were identified using microbiology records. Neutropenic and non-neutropenic patients at the time of positive culture were matched 1:1 to controls on the basis of neutrophil count (ANC), ward, and length of stay. We extracted demographic, laboratory, medication, and other clinical data from chart reviews. Data were analyzed using McNemar's test, Wilcoxon signed-rank test, and conditional logistic regression modeling. Among 101 patients, 63 were neutropenic and 38 non-neutropenic at the time of VGS bacteremia. In multivariable analysis of neutropenic patients, only lower ANC predicted VGS bacteremia (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.05-0.59; P = 0.006). Recent use of vancomycin was protective (OR, 0.23; 95% CI, 0.07-0.73; P = 0.013). No clinical factors were associated with VGS in the non-neutropenic cases. Only lower ANC nadir increased the risk for VGS bacteremia in the neutropenic group, and vancomycin was protective. Other previously described factors (chemotherapy, radiation, oral conditions) related to neutropenia were not independently associated with VGS bacteremia. No tested clinical factors predicted infection in the non-neutropenic group. Our results suggest that VGS bacteremia should be anticipated when making antimicrobial choices in profoundly neutropenic patients, and merit further exploration in non-neutropenic patients.

Analysis of the Prevalence and Risk Factors of Adult Neutropenia in a Large Cohort in Japan

Background: The prevalence of neutropenia is estimated to be 0.5% to 25% based on the definition of neutrophil count less than 1,500 /μL. The high variety mostly depends on the race. Most of the estimation have been based on the values obtained from one measurement of neutrophil count. The prevalence of "chronic" neutropenia is largely unknown, particularly in adults, with only a few small epidemiological studies of adult chronic neutropenia being found. Here we analyzed the medical-check data from over 30,000 Japanese adults, and report the prevalence and characteristics of neutropenia in Japanese adults referring to chronic cases.Methods: Data of medical-checks including neutrophil count from 2010 to 2014 were collected. The entire cohort included 33,255 adults. Neutropenia was defined as neutrophil count less than 1,500 /μL. Anemia was defined as hemoglobin level less than 13 g/dL in men and 12 g/dL in women, and thrombocytopenia as platelet count less than 100,000 /μL. Data of past histories and comorbidities were based on the self-report by the participants. When simple neutropenia (not necessarily chronic) was analyzed, the minimum neutrophil count was used for those who received more than one medical-checks, and other data at the time of the minimum neutrophil count were adopted. For the statistical analysis for comparison of subjects with and without neutropenia, Student's t-test or Wilcoxon's rank sum test were used for continuous variables, and chi-square test was used for categorical variables. Univariate and multivariate regression analyses were performed for testing the effect of the candidate factors on the neutrophil count. For the analysis of the risk factors of neutropenia, multivariate logistic regression analysis was used. For the analysis of chronic neutropenia, only those who received at least 2 medical-checks with measurement of neutrophil count were included. Those who showed neutropenia at least twice were defined as having chronic neutropenia.Results: After exclusion of the cases with past histories of hematological malignancies, 33,201 cases were included. Among them, 1,391 (4.18%) cases had neutropenia. Frequencies of collagen diseases, hypothyroidism, and under-treatment hyperthyroidism were higher in the neutropenic group than the non-neutropenic group. When the subjects with these diseases were excluded, 1,348 (4.12%) out of 32,695 cases had neutropenia. Among them, frequencies of anemia and thrombocytopenia in the neutropenic group were higher than in the non-neutropenic group (18.7% vs 6.2%, and 0.7% and 0.1%, respectively, p < 0.001). In order to analyze isolated neutropenic cases, the subjects with anemia and/or thrombocytopenia were further excluded from the cohort. As the result, 28,615 cases were analyzed. Among them, 1,083 (3.78%) cases were diagnosed to have neutropenia, in which 1,025 (94.6%) cases had mild neutropenia (1,000 - 1,499 /μL) and 58 (5.4%) had moderate neutropenia (500 - 999 /μL). There were no cases of severe neutropenia (< 500 /μL). The neutropenic group showed older age (52.2 vs 50.2 years old), female predominance (64.2% vs 37.1%), lower bone mass index (BMI) (21.5 vs 23.4), lower smoking habit (23.3% vs 46.5%), lower drinking habit (30.8% vs 38.3%) (p < 0.001 for all). Diabetes mellitus (3.0% vs 4.9%, p = 0.005), hypertension (10.6% vs 15.7%, p < 0.001), and hyperuricemia (1.7% vs 3.3%, p = 0.003) were less frequent, and pollen allergy (6.3% vs 4.2%, p < 0.001) and viral hepatitis (1.1% vs 0.3%, p < 0.001) were more frequent in the neutropenic group. In multivariate regression analysis, female, drinking habit, pollen allergy, and viral hepatitis were associated with decrease in neutrophil count, whereas higher BMI and smoking habit with increase in neutrophil count. Risk factors of neutropenia were female with adjusted odds ratio (OR) 2.18 (p < 0.001), drinking habit (OR 1.31, p < 0.001), pollen allergy (OR 1.32, p = 0.034), and viral hepatitis (OR 3.98, p < 0.001). Higher BMI and smoking habit were negative factors of neutropenia (OR 0.40 and 0.52, respectively, p < 0.001).Among the 18,279 subjects who received at least 2 medical checks with measurement of neutrophil count, the number of chronic neutropenia was 294 (1.61%).Conclusion: The prevalence of isolated neutropenia in Japanese cohort was 3.78%, and chronic neutropenia was seen in 1.61%. Risk factors of neutropenia were female, drinking habit, pollen allergy, and viral hepatitis. DisclosuresNo relevant conflicts of interest to declare.

Mycobacterium mucogenicum bacteremia in immune-compromised patients, 2008–2013

Mycobacterium mucogenicum (MM) is a rapidly growing nontuberculous mycobacterium that may rarely cause bacteremia in immune-compromised hosts. All MM cases from 2008 to 2013 were analyzed across 4 risk groups: stem cell transplantation (SCT), hematologic malignancy, solid tumors, and others. Descriptive analysis was performed, as well as comparative analysis of neutropenic patients (absolute neutrophil count ≤1000/μL) with nonneutropenic patients. Of 39 MM cases, 27 patients had undergone SCT. Neutropenia was present in 12 patients. There was a significant difference in the presence of fever at the time of MM bacteremia between neutropenic and nonneutropenic groups (92% versus 42%; P=0.005). Central venous catheter (CVC) was present in 33 cases. All patients were treated with >1 antibiotic. Most frequently used combination antibiotic regimen involved clarithromycin and amikacin. Median duration of antibiotic treatment was 42days. Bacteremia resolved in all cases with CVC removal and combination antibiotic treatment.

Chemotherapy-induced neutropenia as a biomarker of survival in advanced ovarian carcinoma: An exploratory study of the Gynecologic Oncology Group

ObjectiveTo determine whether chemotherapy-induced neutropenia (C-iN) is associated with improved survival in a population of primary advanced ovarian cancer and peritoneal carcinoma patients treated with a carboplatin plus paclitaxel chemotherapy backbone. MethodsA post-hoc exploratory analysis of Gynecologic Oncology Group (GOG) protocol 182 was performed. Landmark analysis was conducted on all patients with progression-free survival >18weeks from the time of study entry. Neutropenia was defined as the absolute neutrophil count <1000mm3. The occurrence of C-iN was analyzed according to demographic, clinicopathologic, and therapeutic intent, including age, body surface area, and treatment arm. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. The Cox proportional hazards model was used to evaluate independent prognostic factors and to estimate their effects on PFS and OS. ResultsNeutropenic data was available for 3447 patients. Neutropenic (n=3196) and non-neutropenic groups (n=251) were similar in demographic and clinicopathologic characteristics. Neutropenic patients experienced significantly improved survival compared to non-neutropenic patients with the adjusted hazard ratio (HR) for death being 0.86 (95% confidence interval 0.74–0.99; p=0.041). There was no survival benefit associated with any of the treatment arms among patients with C-iN. ConclusionThese data suggest that C-iN may represent a clinical biomarker associated with a survival advantage for patients with untreated advanced ovarian cancer. The absence of C-iN may indicate under-dosing and ultimately attenuated anti-neoplastic effect in vulnerable populations.

Clinical Research On Hematological Malignancies Complicated With Active Tuberculosis:A Single Center Experience In China

ObjectivesLarge sample clinical retrospective studies about infection caused by Mycobacterium tuberculosis (TB) among the patients with hematological malignancies(HM) have rarely been investigated. The aim of this study was to analyze the clinical features and treatment of the HM patients complicated with active TB. MethodsHM patients complicated with active TB in our single center between January 2006 and December 2012 were retrospectively studied. ResultsUp to 4712 HM patients have been diagnosed and treated, sixty-six patients of which were confirmed with active TB, as a result, the prevalence of active TB in HM patients was 1.40%（pulmonary TB 1.10%, extra-pulmonary TB 0.30%）. The prevalence of various subgroups of HM patients were as following: AML 2.02%、ALL 1.22%、CML and CLL 1.38%、MDS 1.85%、Lymphoma 0.58%、MM 1.15%、SAA 1.66%. In addition, the patients with AML had a significantly higher incidence of TB disease than other subtypes of HM (2.02% vs 1.13%, P=0.017).Most of the patients were male patients, with a male：female ratio of 2.67：1, median age 41 years old (range 14 to 78). Among them, the median age of extra-pulmonary TB group was younger than the pulmonary TB group (38 vs 44.5 years), so did the neutropenia group when compared with the non-neutropenic group (38 vs 48years). Fifty-two cases（80.3%）were pulmonary TB, 14 cases were（21.2%）extra-pulmonary TB and other 8 cases（12.1%）presented as both pulmonary and extra-pulmonary TB. In addition, atypical clinical manifestations, such as high fever, cough, malnutrition, pleural effusion were the main clinical manifestations in our patients.Twenty-nine patients(43.9%) were diagnosed with definitely etiological evidence while other 37 patients（56.1%）were diagnosed clinically. The extra-pulmonary TB group had a higher PPD test positive rate than that of the pulmonary TB group（85.7% vs 46.2%，P=0.014）; The main characteristics of chest CT were as follows：mediastinal or hilar lymphadenopathy, nodules, fibrous cord shadow, pleural effusion. The specificity and sensitivity of T-SPOT.TB test were 100% and 83.3% when 14 patients were checked by this test, which was a helpful tool for diagnosis. In addition, finding more ways to put the lesions under pathological examination was beneficial to the diagnosis of extra-pulmonary TB.The efficacy of first-line anti-tuberculosis chemotherapy was 87.3%, but the extra-pulmonary TB group presented a lower response rate than the pulmonary one (64.3% vs 90.4%, P=0.01).Patients with fever needed a median 8–day（3～26 days）anti-tuberculosis chemotherapy before their temperature dropped to normal range ,meanwhile the patients who had suffered from lymphnode TB needed 12 days（7～28 days）to get their enlarged lymphnode shrink. The total course in order to cure TB was around 12 months. Six cases were dead due to TB with a 9.1% attributable mortality, moreover, the rate was especially higher in the extra-pulmonary TB group（28.6% vs 3.8%，P=0.016）.Our study demonstrated that the potential risk factors of HM patients complicated with active TB were as follows: age less than 50 years old, male patients, three months within the diagnosis of HM, intravenous use of immunosuppressive drugs. In addition, age less than 50 years old was the only risk factor of extra-pulmonary TB. ConclusionsThe prevalence of HM patients complicated with active tuberculosis is higher than the general population. Definitely etiological evidence was not easy to collect, which made it difficult for the diagnosis and differential diagnosis of TB. A few characteristics such as age less than 50 years old, male patients, three months within the diagnosis of HM, intravenous use of immunosuppressive drugs were the potential risk factors of HM patients with TB. It was clearly showed that these patients demonstrated good overall responses to the first-line anti-tuberculosis chemotherapy, with relatively lower attributable mortality and good outcome. Disclosures:No relevant conflicts of interest to declare.

Clinical analysis of 44 cases of leukemia complicated with active tuberculosis-a single-center report

To analyze the prevalence, clinical features, diagnosis, potential risk factors, anti-tuberculosis treatment efficacy and prognosis of the patients with leukemia complicated with active tuberculosis (TB). A retrospective study was performed to analyze the clinical characteristics, relevant examination data, diagnosis methods and follow-up data about 44 leukemia cases complicated with active TB from January 2006 to December 2011 in our single center. The prevalence of leukemia complicated with active TB was 1.70% (pulmonary TB 1.35%, extra-pulmonary TB 0.35%) and no statistically significant difference was found between each subgroup of acute and chronic leukemia groups (P>0.05). Most of the patients were men, with a male to female ratio of 2.14:1, the median age of 40 years old (range 16 to 78), presenting as atypical clinical manifestations, such as high fever, cough, and so on. Eighteen patients (40.9%) were diagnosed with definitely etiological evidence while the other 26 patients (59.1%) were diagnosed clinically. The extra-pulmonary TB group had a higher purified protein derivative (PPD) test positive rate than that of the pulmonary TB group (88.9% vs 42.9%, P=0.020). The chest CT and T-cell spot of tuberculosis test (T-SPOT.TB) were helpful tools for diagnosis. The potential risk factors included age, sex, nutritional status, neutropenia, decreased cellular immunity, type and course of leukemia, etc. The significant differences in age, gender, administration route of immunosuppressive drugs were found between neutropenic and non-neutropenic groups (P<0.05). The efficacy of first-line anti-tuberculosis therapy was 83.7% and the total course to cure TB was around 12 months. Four patients were dead due to pulmonary TB with a 9.1% attributable mortality. The prevalence of leukemia complicated with active TB is higher than the general population in our single center. The main characteristics including various potential risk factors, atypical clinical features, diagnoses mainly made by clinical features were found in our patients with leukemia complicated with active TB. However, it showed that these patients demonstrated good responses to the first-line anti-tuberculosis therapy and relative lower attributable mortality.

Distribution of Pathogens in Central Line–Associated Bloodstream Infections among Patients with and without Neutropenia following Chemotherapy Evidence for a Proposed Modification to the Current Surveillance Definition

Many bloodstream infections (BSIs) occurring in patients with febrile neutropenia following cytotoxic chemotherapy are due to translocation of intestinal microbiota. However, these infections meet the National Healthcare Safety Network (NHSN) definition of central line-associated BSIs (CLABSIs). We sought to determine the differences in the microbiology of NHSN-defined CLABSIs in patients with and without neutropenia and, using these data, to propose a modification of the CLABSI definition. Retrospective review. Two large university hospitals over 18 months. All hospital-acquired BSIs occurring in patients with central venous catheters in place were classified using the NHSN CLABSI definition. Patients with postchemotherapy neutropenia (500 neutrophils/mm(3) or lower) at the time of blood culture were considered neutropenic. Pathogens overrepresented in the neutropenic group were identified to inform development of a modified CLABSI definition. Organisms that were more commonly observed in the neutropenic group compared with the nonneutropenic group included Escherichia coli (22.7% vs 2.5%; P < .001) but not other Enterobacteriaceae, Enterococcus faecium (18.2% vs 6.1%; P = .002), and streptococci (18.2% vs 0%; P < .001). Application of a modified CLABSI definition (removing BSI with enterococci, streptococci, or E. coli) excluded 33 of 66 neutropenic CLABSIs and decreased the CLABSI rate in one study hospital with large transplant and oncology populations from 2.12 to 1.79 cases per 1,000 line-days. Common gastrointestinal organisms were more common in the neutropenia group, suggesting that many BSIs meeting the NHSN criteria for CLABSI in the setting of neutropenia may represent translocation of gut organisms. These findings support modification of the NHSN CLABSI definition.

Bloodstream infections in adult patients with cancer: clinical features and pathogenic significance of Staphylococcus aureus bacteremia

The aim of this study was to more precisely delineate the characteristics and outcomes of bloodstream infections in adult cancer patients. Using a database for nationwide surveillance of bacteremia, we analyzed data related to bacteremia in adult patients with cancer in order to evaluate clinical features and outcomes and to define predictive factors for mortality. Of 1,246 patients, 896 (71.9%) had solid tumors, 328 (26.3%) had hematologic malignancies, and 22 (1.8%) had both. The following conditions were more common in the neutropenic group than in the non-neutropenic group: nosocomial acquisition, hematologic malignancy, corticosteroid use, immunosuppressant use, primary bacteremia, and pneumonia (all P < 0.05). The infections were caused by Gram-negative bacilli in 55.6% and by Gram-positive cocci in 32.7%. Gram-negative pathogens were more frequently isolated from neutropenic patients than from non-neutropenic patients (61.9% vs. 53.5%, P = 0.010), with a significant predominance of Escherichia coli and Klebsiella pneumoniae. Among 1,001 patients whose outcomes could be evaluated, the overall 30-day mortality rate was 24.1%, and multivariate analysis showed that Staphylococcus aureus bacteremia was a significant factor associated with mortality (odds ratio (OR), 1.80; 95% confidence interval (CI), 1.03-3.15), along with nosocomial acquisition, pneumonia, severe sepsis or septic shock, and higher Pitt bacteremia score (all P values <0.05). This study represents the comprehensive assessment of bloodstream infections in neutropenic versus non-neutropenic cancer patients. Given the pathogenic significance of S. aureus bacteremia in adult patients with cancer, additional strategies for the management of S. aureus bacteremia in cancer patients are needed to improve outcomes.

Nosocomial Klebsiella pneumoniae bacteraemia in adult cancer patients—characteristics of neutropenic and non-neutropenic patients

Neoplastic diseases are common in patients with nosocomial Klebsiella pneumoniae bacteraemia. This study investigated the clinical characteristics of neutropenic and non-neutropenic adult cancer patients with nosocomial K. pneumoniae bacteraemia. Adult cancer patients with K. pneumoniae bacteraemia were retrospectively analyzed at a medical centre in northern Taiwan over a 3-y period. We compared clinical characteristics of cancer patients with nosocomial K. pneumoniae bacteraemia between neutropenic and non-neutropenic groups and identified risk factors for 14-day mortality. Of the 189 patients recruited, 49 (26%) had neutropenia. Haematological malignancies, advanced cancer stage, chemotherapy treatment within 1 month and unknown origin of bacteraemia were predominant among patients with neutropenia. Patients without neutropenia tended to be older, tended to have solid tumours and tended to have bacteraemia of biliary origin. The overall 14-day mortality rate was 25.4%. There was no significant difference in 14-day mortality rate between patients with neutropenia (24.5%) and those without neutropenia (25.7%) (p = 0.808). The duration and severity of neutropenia, administration of inadequate empirical antibiotics and presence of extended-spectrum β-lactamase-producing strains were not risk factors for mortality due to nosocomial K. pneumoniae. Multivariate analysis showed that septic shock was the only independent risk factor for mortality. Nosocomial bacteraemia due to K. pneumoniae in patients with malignancies had heterogeneous characteristics between neutropenic and non-neutropenic groups. Cancer patients in both groups have a poor prognosis. More attention should be paid to cancer patients with nosocomial bacteraemia due to K. pneumoniae despite treatment with adequate antibiotics.

Deactivation of alveolar macrophages in neutropenic acute respiratory distress syndrome (ARDS) in children with hematologic malignancy

Objective To study the alveolar macrophages (AM) activation in neutropenic ARDS in children with hematologic malignancy. Methods Thirteen patients of ARDS were prospectively enrolled into the study and divided into two groups,neutropenic (5 cases) and nonneutropenic (8 cases). Bronchoalveolar lavage fluid (BALF) samples were analyzed for differential and total cell counts, and alveolar activation marker expression (HLA-DR) was determined. Results In neutropenic patients,the BALF total cell count and the macrophage absolute count were significantly lower compared to those in nonneutropenic group ((62. 6 ±9. 6)/μl vs ( 124. 0 ± 6. 7)/μl,P ＜ 0. 01 and (40. 8 ±4. 3)/μl vs (67. 6 ± 10. 7)/μl,P ＜ 0. 01,respectively). As compared with the nonneutropenic group, the percentage of AM in neutropenic patients was significantly higher (65.9% ±9. 0% vs 54. 6% ± 8. 7% ,P ＜0. 05) ,the mean percentage of AM HLA-DR expression was significantly lower (35. 3% ± 5.8% vs 62. 2% ± 5. 8%, P ＜ 0. 01 ). Conclusion These results suggest an alveolar hypocellularity and a deactivation of AM in neutropenic ARDS in children with hematologic malignancy. Key words: Alveolar macrophage; Acute respiratory distress syndrome; Neutropenia; Human leukocyte antigen-DR

Serum Copper and Neutropenia in Elite Sailors

PURPOSE: Haematological and biochemical monitoring of an Olympic Sailing Squad was undertaken through the Beijing Olympic cycle. One aspect of this was the investigation of serum copper deficiency as a cause of neutropenia in sailors. To the authors' knowledge, this relationship has not been investigated in elite athletes. Neutrophil function has been shown to be impaired in sedentary subjects with marginal and severe copper deficiency (Bonham et al 2002). METHODS: Seventeen males and 11 females comprising the Great Britain Olympic Sailing Team. Blood samples were collected between May 2007 and November 2008; between three and on a maximum of ten occasions as part of haematological and biochemical profiling. Sampling frequency was determined by sailor availability in the U.K., and health concerns and performance. Sailors were sub-divided into a neutropenic (N) group (neutrophil count of ≤1.5) and a non-neutropenic (NN) group (neutrophil counts always ≥1.7). Samples were drawn, fasted, between 8-10 am, and 36-48 hours post training. Blood was collected for haematological analysis in K3 EDTA tubes. Serum copper was drawn into specialised trace element K2EDTA tubes. Routine and serum copper analyses were undertaken at a clinical laboratory. Serum copper (μmol/L) reflects copper status (Harvey et al 2009). Data are represented as mean (SD). The mean copper value between the N and NN groups was compared using an unequal variance unpaired t-test. RESULTS: Over 17 months a total of 28 sailors were sampled, comprising 168 blood samples. This period included the lead into Beijing Olympic Games, and post Games, and the entire Olympic Sailing Squad. The neutrophil count for the whole squad was 2.9± 0.8×103/mm3:- N 1.8 ±0.4×103/mm3; NN 3.2 ±0.6×103/mm3. Serum copper concentration for the entire squad ranged from 10.5 to 22.1μmol/L, with a mean concentration of 15.1 ±1.9 μmol/L. Serum copper for the N and NN groups, was 13.8 ±1.2 μmol/L and 15.4 ±2.0 μmol/L respectively. There was a significant difference in serum copper concentration between the N and NN groups (p<0.05). CONCLUSIONS: Sailors prone to neutropenia had lower serum copper concentrations than the non-neutropenic sailors. Low serum copper may be a cause of impaired immune function in elite athletes.

Comparison of 2 Antibiotics That Inhibit Protein Synthesis for the Treatment of Infection withYersinia pestisDelivered by Aerosol in a Mouse Model of Pneumonic Plague

Intentional release of Yersinia pestis will likely be propagated by aerosol exposure. We explored the effects of neutropenia on the outcome of doxycycline and gentamicin therapy. Female BALB/c mice were exposed to 20 LD(50) of Y. pestis CO92 by aerosol. Treatments were saline (negative control), levofloxacin at 15 mg/kg every 12 h (positive control), doxycycline at 40 mg/kg every 6 h, and gentamicin at 12 mg/kg every 6 h, 24 mg/kg every 12 h, and 48 mg/kg every 24 h in cohorts of normal and neutropenic mice for 5 days. Control mice died. Positive control mice (levofloxacin) had 100% survivorship in both neutropenic and nonneutropenic groups. Doxycycline treatment in the presence of granulocytes yielded 90% survivorship; all neutropenic mice died after the termination of treatment (P<<.001). For gentamicin, survivorship of mice receiving drug every 24, 12, and 6 h was, respectively, 80%, 80%, and 90% for normal mice and 80%, 100%, and 70% for neutropenic mice. No significant differences were seen in the neutropenia versus normal mouse comparison or by schedule. Doxycycline behaves in vivo as a bacteriostatic drug, requiring an intact immune system for clearance of the infection after aerosol challenge with Y. pestis. Gentamicin is bactericidal, even when given on a daily schedule. Neutropenia did not significantly affect survivorship.

Lack of association between neutropenia and the incidence of bacteremia associated with indwelling central venous catheters in febrile pediatric cancer patients

To assess the incidence of bacteremia in pediatric cancer patients with indwelling central venous catheters with fever, we reviewed the records of all 67 such patients sequentially admitted during a 10-month period at our institution. There were a total of 140 episodes of fever in these 67 patients. In 55 of the episodes (39%) patients were nonneutropenic (absolute neutrophil count, greater than 500/mm3); 85 episodes (61%) were associated with neutropenia. Twenty-four percent of all episodes of fever in nonneutropenic patients were related to bacteremia vs. 9.5% of episodes of fever in the presence of neutropenia (P less than 0.05). When clinical evidence of an exit site infection was absent, the incidence of bacteremia in the neutropenic and nonneutropenic groups was similar (11% in the neutropenic group; 10% in the nonneutropenic group). We conclude that bacteremia is frequently observed in febrile pediatric cancer patients with indwelling venous catheters who are not neutropenic, particularly if there is clinical evidence of an exit site infection. Thus empiric antibiotic therapy is warranted in all pediatric oncology patients with indwelling catheters who develop fever.