Outcome Of Neutropenic Patients Research Articles

Outcomes of Neutropenic Patients with Severe Infections Treated with Granulocyte Transfusions: The USC Experience

Introduction Despite major progress in antimicrobial and supportive measures, prolonged disease-associated or treatment-related neutropenia is a leading cause of mortality and morbidity in patients after stem cell transplantation or with hematologic malignancies or bone marrow failure. Intuitively, a granulocyte transfusion should be as effective as a platelet or red cell transfusion. However, efforts to prove the effectiveness of granulocyte transfusions have been disappointing. Due to the lack of adequately powered randomized controlled trials, it is difficult to prove or refute the effectiveness of granulocyte transfusions in neutropenic patients. Therefore, they are likely underutilized or used inappropriately as a last resort. To better understand the utility of this treatment modality, we reviewed the outcomes of patients with hematologic conditions who received granulocyte transfusions at our institutions during the treatment of neutropenic sepsis. Methods We identified 20 patients with severe neutropenia who received a granulocyte transfusion at Norris Comprehensive Cancer Center or Keck Hospital of USC in Los Angeles, California between 2014-2022. 19 of these patients received a total of 166 transfusions for treatment of suspected or confirmed sepsis. One patient received a prophylactic dose of granulocytes and was excluded from this study. Granulocyte donors were mobilized with 480 mcg G-CSF and a minimum yield of 4 x 10 10 granulocytes was obtained. The primary outcome was attainment of “clinical improvement” defined as either safe discharge from the hospital or resolution of symptoms. Descriptive statistics were presented as counts and percentages for categorical variables and as means with standard deviations for continuous variables. Categorical variables were accessed by Chi-square test or Fischer's exact test when appropriate. For continuous variables, Kruskal-Wallis test was used. P-values of ±0.05 were regarded as significant and all tests were two-tailed and analyzed with SAS (9.4). Results In our cohort, 47.4% were male, ages ranged from 20-70, and 57.9% identified as Hispanic. The most common diagnosis was acute myeloid leukemia (AML) (n=13), followed by aplastic anemia (n=3), myelodysplastic syndrome (MDS) (n=2), and acute lymphoblastic leukemia (ALL) (n=1). The most common infections were fungal or presumed fungal (n=9) and mixed fungal and bacterial (n=7). Prior to the start of granulocyte transfusions, 63.2% of patients were neutropenic (ANC <500) for at least 30 days and 84.2% had an absolute neutrophil count (ANC) <100. In surviving patients, the average number of days from the first transfusion to clinical improvement was 17.5 days. 47.4% of patients had a reported reaction to the granulocytes, with the most common being fever and tachycardia. Of the 19 patients treated, seven (37%) died from infection. Of those who died, two (29%) died from E. coli bacteremia and five (71%) from mixed bacterial and fungal sepsis. All nine patients with acute fungal infections without concomitant bacterial infections survived. Conclusion In this cohort, granulocyte transfusions appear to have had a positive effect with 63% of critically ill patients attaining clinical improvement from infection. All patients who had a purely fungal infection achieved clinical improvement and all patients who died had bacterial or mixed infection. Time to transfusion from initial infection, number of transfusions, and demographic variables did not appear to impact overall survival. Granulocyte transfusion could be an effective therapeutic modality in the treatment of infection in patients with prolonged severe neutropenia, especially those with fungal infections. Adequately powered randomized controlled trials are the next step in determining the effectiveness of this treatment.

46. Antimicrobial Stewardship’s Selective Antibiotic Suppression Does Not Lead to Adverse Outcomes in Neutropenic Patients with Gram-Negative Bacteremia

BackgroundAn antimicrobial stewardship program (ASP) strategy to minimize the use of overly broad antimicrobials is to suppress specific antimicrobial susceptibility results when isolates are sensitive to narrow antibiotics. There is limited data on possible adverse outcomes of this method. Patients with febrile neutropenia (FN) and gram-negative bacteremia (GNB) whose culture is sensitive to non-pseudomonal antibiotics still require broader pseudomonal coverage to treat the syndrome of FN. We evaluated if ASP suppression of anti-pseudomonal antibiotics adversely affects patients with FN and GNB.MethodsIn February 2018, our institution’s ASP began suppressing cefepime and meropenem susceptibility results from E. coli, Klebsiella spp, and Proteus spp when sensitive to cefepime (MIC ≤ 2), ceftriaxone and ceftazidime. We performed a retrospective analysis of patients with FN and GNB from 2016 – 2020 to evaluate the appropriateness of antibiotic regimens before and after the ASP intervention. Antibiotic regimens were deemed inappropriate if the patient was de-escalated to a narrow-spectrum, non-pseudomonal agent while neutropenic. Of 338 inpatient encounters identified with any bacteremia and FN, 49 were due to non-Pseudomonas, non-ESBL GNB, 20 before and 29 after the intervention. Sixteen of the 29 post-intervention patients were excluded, as their isolates did not meet suppression criteria. This resulted in a total of 13 patients in the post-intervention group.ResultsAfter culture susceptibility reports were released, 3 out of 20 patients in the pre-intervention group (15%) and 4 out of 13 patients in the post-intervention group (30.8%) were inappropriately tailored to narrow-spectrum antibiotics (p=0.39). There was no significant difference in 30-day mortality, 10.0% pre- and 0% post-intervention (p=0.50), or amount of meropenem prescribed, 45% pre- and 38.5% post-intervention (p=0.74). ConclusionThese data show no significant difference in inappropriate antibiotic regimens prescribed for patients with FN and GNB after ASP antibiotic suppression was implemented. 30-day mortality was also not affected. The ASP intervention did not decrease meropenem prescriptions in this patient group, which may be appropriate. Larger studies are needed to verify these findings.DisclosuresRyan K. Dare, MD, MS, Accelerate Diagnostics, Inc (Research Grant or Support) Mary Burgess, MD, Pfizer Inc (Grant/Research Support)

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 <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 < .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

2474. The 10 Years Scientific Contribution of the Cologne Cohort of Neutropenic Patients (CoCoNut) for Evaluating Treatment and Outcome of Healthcare-associated Infections

BackgroundHealthcare-associated infections (HAIs) are a leading cause for morbidity and mortality in neutropenic patients.MethodsThe Cologne Cohort of Neutropenic Patients (CoCoNut) is an ongoing, prospective, longitudinal cohort, collecting inpatient data for analysis of epidemiology, risk factors, and outcome of neutropenic patients (at least one day of absolute neutrophil count < 500/µL) at risk for HAIs. The CoCoNut contains comprehensive data, i.e. patient characteristics, medication, chemotherapy, clinical data (e.g., diarrhea, body temperature), as well as laboratory, microbiological, virologic, and radiological results. The purpose of this cohort is to improve the knowledge on HAIs and management of anti-infective prophylaxis and therapy.ResultsTo date, the CoCoNut includes 8,176 inpatient stays from 3,354 neutropenic patients treated at the hematology/oncology department of the University Hospital of Cologne between January 2009 and December 2018. Hodgkin and Non-Hodgkin lymphoma (32%), acute leukemia (28%), and chronic leukemia (10%) were the predominant underlying diseases; comprising 843/8,176 (10%) inpatient stays with allogenic stem cell transplantation. The overall number of neutropenic days and fever days (body temperature ≥ 38 °C) was 56,824 and 25,347, respectively. Blood stream infections (occurrence of fever and positive blood culture) occurred in 1,283/8,176 (16%) inpatient stays, and the overall mortality rate was 9% (n = 716/8,176). By now, 17 peer-reviewed articles analyzing epidemiology, treatment, and outcome of HAIs were published based on data from the CoCoNut.ConclusionData extracted from the CoCoNut underlines the important role of evaluating innovative treatment strategies. Considering the remaining high infection rate for HAIs of neutropenic patients, the growing development of antimicrobial drug resistance, and the existing powerful methods for data processing (e.g., artificial intelligence), we will continue to utilizing and expanding the CoCoNut in the future.Disclosures All authors: No reported disclosures.

Granulocyte transfusions in patients with skin and soft tissues infections and leukemia: Are they useful?

7022 Background: Granulocyte transfusions (GTX) have been proposed to improve clinical outcome of neutropenic patients (pts) with serious infections. We evaluated the impact of unirradiated GTX in pts with skin and soft tissue infections (SSTI) and leukemia. Methods: We did a retrospective analysis of pts with leukemia and SSTI that received GTX from 2014 to 2018. We analyzed infection outcome and changes in ANC after GTX. Donors were mobilized using G-CSF plus oral dexamethasone 12 hours prior to apheresis. Results: Twenty-seven pts received 141 GTX for 33 SSTI. Transfusions were unirradiated, except for 10 (7%) radiated units administered due to availability. Twenty pts were male (74%); median age was 59 yrs (20–83 yrs). Hematologic diagnoses included AML (23, 70%), MDS (3, 9%), ALL (3, 9%), CLL (2, 6%), CML (1, 3%), and MF (1, 3%). In 24 (73%) SSTI, pts had a baseline ANC&lt;0.5 x109/L, 3 (9%) had ANC between 0.51x109L to 0.99 x 109L, and 6 (18%) with ANC &gt;1 x109/L. After GTX, ANC increased in 99 (70%) cases by a median of 0.7 x 109/L (0.02 to 10.03) with a median peak time of 9 hrs (4 to114 hrs), with a median time from GTX to first drop of 34 hrs (10 to 136 hrs). ANC decreased in 27 (19%) (by a median -0.5 x 109/L,-0.02 to -2.41). There was no change of ANC in 15 (11%). Improvement was determined by reduction in fever and inflammation, or resolution of SSTI 7 days after first GTX. Twenty-seven (82%) episodes improved. In those improved, ANC remained &lt;1.5x109/L in 15 (56%) episodes after last GTX and after improvement. Main adverse reactions were fever in 21% (29), and respiratory complications in 6% (9) (pulmonary effusion, respiratory distress and acute hypoxemia). One pt (3%) required intubation. There was no transfusion-related GVHD. Cumulative survival from first GTX on each SSTI by Kaplan-Meier Survival was 82% (8) at 30 days, 49% (17) at 90 days, 41% (17) at 180 days, and 24% (12) at 360 days. Eight of this pts died of infections, 4 of which were SSTI described on this paper. Conclusions: GTX have a beneficial effect on clinical improvement in patients with SSTI and underlying hematological malignancies and severe neutropenia. It can be safely administered without GVHD. Further prospective studies are warranted.

Clostridium difficile treatment in neutropenic patients: Clinical outcomes of metronidazole, vancomycin, combinations, and switch therapy.

Clostridium difficile infection treatment guidelines exist for immunocompetent patients; however, there is a paucity of data evaluating clinical outcomes and time to C. difficile-associated diarrhea resolution in neutropenic patients. To assess clinical outcomes in neutropenic patients treated with metronidazole, oral vancomycin, the combination of metronidazole plus oral vancomycin, and switch of metronidazole to oral vancomycin. This retrospective, observational cohort study assessed adult neutropenic inpatients with C. difficile-associated diarrhea treated with metronidazole, oral vancomycin, combination (metronidazole and oral vancomycin), or switch therapy (metronidazole to oral vancomycin). The primary outcome was time to diarrhea resolution based on treatment regimen. Secondary outcomes included C. difficile-associated diarrhea resolution of diarrhea by day 14, recurrence, and occurrence of major complications. Overall, 44 patients met full inclusion criteria (52.2% metronidazole monotherapy, 22.7% combination, and 25.0% switch therapy). Two patients on oral vancomycin monotherapy were excluded due to insufficient sample size. Overall time to C. difficile-associated diarrhea resolution was 9.1 ± 10.7 days. The Cox regression results suggested both switch and combination therapy were associated with 65.5% (p = 0.002) and 65.9% (p = 0.046) longer time to C. difficile-associated diarrhea resolution compared to metronidazole monotherapy, respectively. An increasing absolute neutrophil count was associated with an increase in C. difficile-associated diarrhea resolution (p = 0.007). Switch or combination therapy was associated with a prolonged time to C. difficile-associated diarrhea resolution. The decision to use switch or combination therapy may represent a surrogate marker for more severe disease and need for therapy escalation. It is unknown if initial therapy with oral vancomycin would provide better outcomes as this could not be assessed.

Predictive Models of Fever and Adverse Outcomes in Hospitalized Patients with Neutropenia

BackgroundNeutropenia is a clinical condition associated with adverse outcomes such as fever, mortality, and ICU admission. Since early intervention can decrease mortality in this population, validated early warning scores (EWS) to identify at-risk patients could result in improved outcomes. Consequently, we aimed to create optimized predictive models of fever, mortality, and adverse events in hospitalized patients with neutropenia.MethodsUsing the University of Virginia (UVA) electronic health record (EHR) data, we identified all neutropenic patients ≥18 years who were admitted to inpatient wards over a five-year period. Neutropenia was defined as an absolute neutrophil count <500 cells/mm3. Adverse outcomes were defined as 1) development of fever 2) ICU transfer or 3) mortality during hospital stay. We then used Bayesian model averaging to build predictive models for fever and mortality utilizing readily-available clinical laboratory and vital sign data. Finally, we built a combined adversity model (fever and/or ICU transfer and/or mortality) in the same cohort. All models were valideated using a 60:40 testing/training method.ResultsWe identified 1056 patients with neutropenia admitted to UVA from 2010 to 2015. Fever occurred in 427 (40.4%) patients and 95 (8.9%) patients died. The final neutropenic fever model had a c-statistic of 0.75 and included the following variables: temperature, pulse rate, white blood cell count, and platelets. The model identified patients a median of 9.6 hours before onset of fever. The final neutropenic mortality model had a c-statistic of 0.79 and included the following variables: sodium, creatinine, potassium, ALT, platelets, albumin, and magnesium. The combined adversity model had a c-statistic of 0.69 and included the following variables: pulse, temperature, respiration, platelets, white blood cells, and albumin. The model identified patients a median of 9.3 hours before onset of fever.ConclusionWe created predictive models for fever, mortality, and adverse outcomes in neutropenic patients. These models could easily be implemented into the EHR as an EWS to facilitate early intervention and improved outcomes in the neutropenic patient population.Disclosures All authors: No reported disclosures.

Effect of hospital volume on mortality rates amongst neutropenic cancer patients within the United States.

6600Background: Hospital Volume is associated with improved outcomes in cancer surgery, and some aspects of cancer care. The influence of hospital volume on outcomes in neutropenic patients is unkn...

Carbapenemase-producing Klebsiella pneumoniae bloodstream infections in neutropenic patients with haematological malignancies or aplastic anaemia: Analysis of 50 cases

Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) are currently among the most important nosocomial pathogens in many geographic regions. A retrospective study was conducted between 2010 and 2014 in four hospitals located in a high-prevalence area (Athens, Greece) to describe the clinical features, treatment and outcomes of neutropenic patients with haematological diseases complicated with CP-Kp bloodstream infections. A total of 50 patients were identified, including 48 with haematological malignancies and 2 with aplastic anaemia. All patients had neutropenia (<500cells/mm3), of whom 40 had <100neutrophils/mm3. The probable source of bacteraemia was identified in 9 patients; in the remaining 41 patients the bacteraemia was considered primary. For definitive treatment, 30 patients received combination therapy (two or more active drugs), 10 received monotherapy (one active drug) and 4 received therapy with no active drug; the remaining 6 patients died within 48h after the onset of bacteraemia. The 14-day all-cause mortality rate was 50%, 38% and 33% for those who received one, two or three active drugs respectively. In the Cox proportional hazards model, unresolved neutropenia [hazard ratio (HR)=19.28, 95% confidence interval (CI) 2.31–160.69; P=0.006], septic shock (HR=3.04, 95% CI 1.06–8.78; P=0.04) and treatment with one active drug (HR for monotherapy versus combination therapy=3.95, 95% CI 1.23–12.65; P=0.02) were independent predictors of death, whilst combination therapy was associated with lower mortality. These findings may assist physicians in making treatment decisions for neutropenic patients with CP-Kp infections.

Abstract LB-A17: Hospital volume determines mortality amongst neutropenic cancer patients within the United States

Abstract Introduction: Hospital Volume is associated with improved outcomes in cancer surgery, and some aspects of cancer care. The influence of hospital volume on outcomes in neutropenic patients is unknown. Neutropenia secondary to bone-marrow suppression is a common, and dangerous complication of cancer treatment. Known factors associated with increased mortality include age, race and co-morbidities. We hypothesized that large-volume hospitals would have reduced mortality rates for neutropenic patients compared with small-volume institutions. Methods: We utilized the NIS database of the Healthcare Cost and Utilization Project, focusing on the years 2000-2006. Only inpatient episodes with a diagnosis of both neutropenia and cancer were included in the study. Hospital volume was defined as the number of neutropenic cancer episodes listed for each institution per year. Mortality was defined as death during admission. Results: 155,512 hospitalizations were included in the study, from 3049 different institutions. Median age was 60 years. The overall inpatient mortality was 7.1%. Mortality increased with patient age, for instance amongst those aged 30-39 years it was 4.3% compared to 10.7% for those aged 70-79 years. The average number of “neutropenic” inpatient episodes in each institution per year ranged from less than one to 225 (median 22.7). The population was split into four equal groups based upon hospital volume. Mortality was 8.5%, 7.7%, 7.0% and 5.2% for each group (from lowest to highest volume), likewise% discharged home was 77.3%, 82.4%, 85.2% and 90.1% (for both p&amp;lt;0.001). In a logistic regression model incorporating age, race and sex, ‘hospital volume’ remained statistically associated with reduced mortality (p&amp;lt;0.001). Conclusion: Neutropenic patients hospitalized in large-volume institutions have a substantially lower mortality and a higher likelihood of returning home compared to those hospitalized at low-volume institutions. Our findings have implications for the setting in which phase I/II clinical trials of combination treatments with new biological agents and cytotoxic therapies be performed. Citation Format: Yaacov Richard Lawrence, Damian Urban, Tal Sella, Jair Bar, Raanan Berger, Jeffrey Goldstein, Einat Shacham-Shmueli, Zvi Symon, Talia Golan. Hospital volume determines mortality amongst neutropenic cancer patients within the United States. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-A17.

1210A Phase 3, Randomized, Double-Blind, Non-inferiority Trial to Evaluate Efficacy and Safety of Isavuconazole versus Voriconazole in Patients with Invasive Mold Disease (SECURE): Outcomes in Neutropenic Patients

1210A Phase 3, Randomized, Double-Blind, Non-inferiority Trial to Evaluate Efficacy and Safety of Isavuconazole versus Voriconazole in Patients with Invasive Mold Disease (SECURE): Outcomes in Neutropenic Patients

Outcomes of neutropenic patients with severe sepsis on a specialist cancer ICU

The hospital survival rate for patients with septic shock remains at approximately 50% [1]. Critically ill cancer patients have often been considered poor candidates for ICU management due to the perception of poor outcomes for this group, in particular in the presence of neutropenia. There is a paucity of data supporting this. The objective of this study was to describe clinical outcomes for a group of septic neutropenic patients admitted to a cancer ICU.

Outcomes of Dental Extractions in the Neutropenic Patient

Oral and maxillofacial surgeons are frequently consulted in the hospital setting for the evaluation of neutropenic patients. Often they are asked to rule out an odontogenic source of infection in the setting of fevers of unknown origin. If a possible odontogenic source is detected, a decision must be made as to what is the best management for these medically compromised patients. There is a paucity of data regarding the effect of severe neutropenia on outcomes following dental extractions. Our study retrospectively reviewed outcomes in neutropenic patients undergoing dental extractions at Mayo Clinic. IRB approval was obtained prior to chart review. Search criteria included all patients undergoing extractions who also had concurrent diagnoses of neutropenia, pancytopenia, aplastic anemia, or malignant neoplasms of the lymphatic and hematopoietic tissues. Chart review was then performed to identify patients who were neutropenic (< 1.5 × 109/L) at the time of dental extraction. Complications including local infection, delayed healing, bleeding, bacteremia, and fever were recorded. Preliminary chart reviews of 200 patients, who underwent extractions between 2007 and 2010, revealed 27 patients that met full inclusion for this study. Descriptive statistical analysis was performed using JMP 8.0 software. Patient demographics were: 14 males/13 females, mean age 53.7 years (range 6-93). The mean absolute neutrophil count at the time of extractions was 0.633 × 109/L (range 0-1.48), and mean platelet count was 94.9 (range 21-389). Clinical findings pre-extractions included: 63% of patients with radiographic caries, 74% with radiographic periapical radiolucencies, 44% with radiographic evidence of local periodontal disease, 48% with clinical caries, 52% with pain on percussion, 22% with clinical evidence of dental abscess, and 56% with complaints of spontaneous oral pain. Mean number of teeth extracted per patient was 2.96 (range 1-11) with 48% coded as simple extractions, 44% as surgical extractions, and 7% as extractions of impacted teeth. Median post-operative follow up was 163 days (range 4-1,404). Post-operative complications were found in 5/27 cases including 2 patients with delayed healing (although both patients had a history of BRONJ), 2 with pain after healing, and 1 with minor transient bleeding. No local infections were noted at the extraction sites. Three patients had pre-operative fever, of which two had resolution of fever within seven days of extractions. This retrospective study revealed no significant complications following dental extractions in neutropenic patients. Specific antibiotic regimens were not controlled for, although most patients received wide-spectrum antibiotics during the post-operative period as part of their medical management. Of five patients with post-operative complications, three consisted of pain or minor transient bleeding while the other two represented delayed healing in patients with a BRONJ history. The lack of local post-operative infection in this study is notable. Although this preliminary review lacks sufficient sample size for definitive conclusions, it appears that the benefits associated with extraction of indicated teeth in severely neutropenic patients may outweigh the associated risks. A broader study, with larger sample size, is underway to better characterize outcomes following dental extractions in the severely neutropenic patient population.

Utility of fiberoptic bronchoscopy in neutropenic patients admitted to the intensive care unit with pulmonary infiltrates.

To analyze the impact of fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) on guiding the treatment and intensive care unit (ICU) clinical outcome in neutropenic patients with pulmonary infiltrates admitted to the ICU. Prospective collection of data. Medical ICU in a teaching hospital. During a 6-yr period, we analyzed the results of 93 fiberoptic bronchoscopies plus BALs performed in 93 consecutive neutropenic ICU patients. We separated the patients into two groups according to the cause of neutropenia (high-dose chemotherapy [n = 41] or stem cell transplantation [SCT; n = 52]). Of the 93 BALs, 53 were performed to evaluate diffuse infiltrates and 42 were performed on mechanically ventilated patients. Forty-nine percent of BALs (46 patients) were diagnostic, with a significantly better yield in ICU patients with high-dose chemotherapy-induced neutropenia (26 of 41 BALs). The number of cases of proven infectious pneumonia was significantly higher in this group of ICU neutropenic patients. In patients who underwent SCT, diffuse infiltrates were statistically correlated with a negative result of BAL. Twenty-six patients who underwent diagnostic BALs changed therapy. Sixteen complications (17%) occurred with only two intubations. The overall mortality rate in the ICU and the mortality rate in mechanically ventilated neutropenic patients were 71% and 93%, respectively. In neutropenic patients who underwent SCT, the mortality rate was statistically higher in patients in whom no diagnosis was established. Patients who had a diagnostic BAL that changed therapy did not have an increased probability of survival compared with patients who had a BAL that did not change therapy. The use of routine diagnostic BAL in ICU neutropenic patients with pulmonary infiltrates is difficult to establish, even if BAL is helpful in the management of these critically ill patients. BAL in our ICU neutropenic patient population had an acceptable overall diagnostic yield (49%), which was higher in ICU patients with chemotherapy-induced neutropenia. Nevertheless, in the ICU, if BAL had a low complication rate, it had infrequently led to changed treatment and was not associated with improved patient survival.

Ostéoarthrite à Pseudallescheria boydii chez un patient porteur de leucémie aiguë lymphoblastique : à propos d'un cas

Pseudallescheria boydii arthritis in a patient with acute lymphoblastic leukemia: a case report. Introduction. — The outcome of neutropenic patients with Pseudallescheria boydii infection is poor. Exegesis. — We report the first case of Pseudallescheria boydii hip arthritis in a patient treated for acute lymphoblastic leukemia. In vitro susceptibility testing showed that the strain was resistant to amphotericin B, fluorocytosine and nystatin, but susceptible to itraconazole. The patient received oral itraconazole (600 mg/day) and clinical symptoms initially resolved. Two months later, after a course of chemotherapy and high-dose steroids while receiving oral itraconazole treatment, the patient developed fever, skin lesions and disseminated lung infiltrates due to Pseudallescheria boydii and finally died. Conclusion. — This case illustrates the severity of fungal infections due to Pseudallescheria boydii despite a presumably well-conducted antifungal therapy.

Aetiology, cost of antimicrobial therapy and outcome in neutropenic patients who developed bacteraemia during antimicrobial prophylaxis: a case-control study

Sixty four episodes of bacteraemia that appeared during antimicrobial prophylaxis with an oral quinolone plus an azole in neutropenic cancer patients were compared with 128 cases of bacteraemia in a cohort of controls matched for age, sex, underlying disease, neutropenia and vascular catheter in situ to assess differences in aetiology, cost of therapy and outcome. Patients who received prophylaxis had breakthrough bacteraemias of a different aetiology compared with the control group: they had significantly fewer multiply-resistant strains (21.9 vs. 51.5, P<0.04) and a longer afebrile neutropenic period (9.55 days vs. 4.1, P<0.001). Patients who received prophylaxis also had bacteraemias that were significantly more frequently caused by viridans streptococci (9.4% vs. 1.7%, P<0.01), enterococci (15.6% vs. 7.2%, P<0.05) and Stenotrophomonas maltophilia (17.2% vs. 3.4%, P<0.01). The cost of antimicrobial therapy per case (37 401 SKK (1091 USD) vs. 31 808 SKK (899 USD), P<0.05) was also significantly higher in cases than controls; however, the number of administred antibiotics (4.18 vs. 3.21 per case, P=NS) was similar in both groups. There were no differences in outcome between both groups. However patients who received prophylaxis had significantly longer periods of afebrile neutropenia (9.55 days vs. 4.1, P<0.001) and bacteraemia developed later than in controls. Also, the incidence of polymicrobial bacteraemia caused by multiresistant strains was lower among cases (21.9 vs. 51.5, P<0.04).