Presentation of infection in older patients--a prospective study.

BACKGROUND: Traditional wisdom suggests that infections in older patients have atypical presentation, including blunted febrile response. Data are scarce. DESIGN: We analyzed data from a prospectively collected database on presentation of infection in 4,308 patients, and compared the presentation of older patients (≥ 75 years) versus adults (< 75 years). SETTINGS: Single tertiary medical center. PARTICIPANTS: Patients admitted with suspected bacterial infection during 2002-2004 and 2010-2011. MEASUREMENTS: We evaluated clinical presentation on day of admission, including vital signs and laboratory parameters. RESULTS: No difference in fever values as a presenting sign of infection was found between older patients and adults (median fever 38.3°C, interquartile range [IQR] 37.4-39.0°C; and 38.4°C, IQR 37.3-39.0°C, respectively, P = 0.08). Median leukocyte count was significantly higher in older patients (median 11.60, IQR 8.30-15.72 in older patients; 10.84, 7.50-15.00 in adults, P < 0.001). Presentation with septic shock, acute renal failure, and reduced consciousness was significantly more common in older patients. These findings were also consistent in the subgroups of bacteremic patients and patients with microbiologically documented infection. CONCLUSION: Elevated fever and leukocytosis were found to be at least equally common in older patients compared to younger adults as part of the presentation of infection.

The association between infections and chemotherapy interruptions among cancer patients: prospective cohort study.

OBJECTIVES: Adherence to scheduled chemotherapy is important for optimal outcomes of cancer patients. We examined causes for delay or cancellation of planned chemotherapy, focusing on mild respiratory infections during the winter. METHODS: Prospective cohort study. We included all adults with solid or hematologic cancer receiving active chemotherapy treatment during the winter of 2010-2011 in a cancer center. We compared baseline characteristics and outcomes between patients with and without chemotherapy delays, cancellations, or dose-reductions ("chemotherapy delay"). RESULTS: We included 547 patients receiving chemotherapy during the winter of 2011. Of these, 213 (38.9%) patients experienced 306 episodes of chemotherapy delays. The main documented reasons for the chemotherapy delay were neutropenia (84/306, 27.4%), fever or infection (73/306, 23.9%) and thrombocytopenia (26/306, 8.5%). Independent risk factors for chemotherapy delays were upper respiratory infections (OR 1.87, 95% CI 1.27-2.76), lymphopenia, prior hospitalization, peripheral vascular disease and colon cancer relative to hematologic cancer. In the adjusted analysis focusing on chemotherapy delays due to infection alone, upper respiratory infections (OR 5.25, 95% I 2.81-9.84) and age were significant independent risk factors. DISCUSSION: Mild respiratory infections were associated with chemotherapy delays. Our results should encourage modalities to prevent influenza and other upper respiratory infections among cancer patients.

Subcutaneous versus intravenous granulocyte colony stimulating factor for the treatment of neutropenia in hospitalized hemato-oncological patients: randomized controlled trial.

Intravenous (IV) granulocyte colony stimulating factor (G-CSF) might be safer and more convenient than subcutaneous (SC) administration to hospitalized hemato-oncological patients receiving chemotherapy. To compare IV vs. SC G-CSF administration, we conducted a randomized, open-label trial. We included inpatients receiving chemotherapy for acute myeloid leukemia, acute lymphoblastic leukemia, lymphoma or multiple myeloma, and allogeneic or autologous hematopoietic cell transplantation (HCT). Patients were randomized to 5 mcg/kg single daily dose of IV bolus versus SC filgrastim given for its clinical indications. Patients were crossed-over to the alternate study arm on the subsequent chemotherapy course. The primary outcomes were time from initiation of filgrastim to recovery of stable neutrophil count of >500 cells/µL and a composite clinical outcome of infection or death assessed for the first course post-randomization. The study was stopped on the second interim analysis. Of 120 patients randomized, 118 were evaluated in the first treatment course. The mean time to neutropenia resolution was longer with IV G-CSF [7.9 days, 95% confidence interval (CI) 6.6-9.1] compared with SC G-CSF (5.4 days, 95% CI 4.6-6.2), log-rank P = 0.001. Longer neutropenia duration was observed in all patient subgroups, except for patients undergoing autologous HCT. There was no significant difference between groups in the occurrence of infection or death, but more deaths were observed with IV (4/57, 7%) versus SC (1/61, 1.6%) G-CSF administration, P = 0.196. Similar results were observed when all 158 courses following cross-over were analyzed. Patients reported similar pain and satisfaction scores in both groups. Bolus IV administration of G-CSF results in longer neutropenia duration than SC administration, with no difference in clinical or quality-of-life measures.

Clinical effectiveness of seasonal influenza vaccine among adult cancer patients.

BACKGROUND: Patients with cancer are at increased risk of developing complications of influenza. In this study, the authors assessed the effectiveness of influenza vaccination among cancer patients. METHODS: A prospective, noninterventional cohort study was conducted during the 2010 to 2011 influenza season. The cohort included adult cancer patients with solid malignancies who were receiving chemotherapy and hematologic patients who had active disease. Patients who died between October and November 2010 (N = 43) were excluded. A comparison was made between patients who received the 2011 seasonal influenza vaccine with those who did not. The primary outcome was a composite of hospitalizations for fever or acute respiratory infections, pneumonia, and/or infection-related chemotherapy interruptions. All-cause mortality was a secondary outcome. A propensity-matched analysis was conducted based on the propensity for vaccination. RESULTS: Of 806 patients who were included, 387 (48%) were vaccinated. Factors that were associated independently with vaccination included past influenza vaccination, past pneumococcal vaccination, >6 months since cancer diagnosis, country of birth, and cancer type/status. The primary outcome occurred in 111 of 387 (28.7%) vaccinated patients versus 112 of 419 (26.7%) unvaccinated patients (P = .54). No association was observed between vaccination and the primary outcome in a propensity-matched analysis (N = 436) or during peak influenza activity. The mortality rate was 11.9% (46 of 387 patients) in vaccinated patients versus 19.1% (80 of 419 patients) in unvaccinated patients (P = .005). Vaccination retained a significant association with mortality on multivariable analysis (odds ratio, 2.31; 95% confidence interval, 1.4-3.79) and in a propensity-matched analysis (odds ratio, 2.39; 95% confidence interval, 1.32-4.32). CONCLUSIONS: Influenza vaccination was associated with lower mortality among cancer patients, although an association with infection-related complications could not be demonstrated. The current results support efforts to promote influenza vaccination in patients with cancer.

Elevation of CRP precedes clinical suspicion of bloodstream infections in patients undergoing hematopoietic cell transplantation.

OBJECTIVES: We aimed to examine whether C-reactive protein (CRP) elevation precedes the clinical signs and symptoms of infection among patients undergoing allogeneic hematopoietic cell transplantation (HCT). METHODS: Prospective cohort of patients undergoing allogeneic HCT in whom daily blood samples for CRP were taken. In a nested case-control study, cases were defined as patients with clinically-significant bloodstream infection (BSI). Controls were defined as afebrile patients without infection, matched by age, time after transplantation and GVHD status. We calculated the mean difference (MD) between CRP 1 day before clinical suspicion of infection (day -1) and days -2 and -3 (deltaM1M2 and delta M1M3, respectively) and compared cases vs. controls. RESULTS: From January 2010 to April 2012 we identified 46 cases of BSIs. The difference between the mean delta M1M3 and delta M1M2 in cases and controls were significantly higher in patients with BSI compared to controls (MD = 5.9, 95% CI 3.5-8.3, p < .001 and MD = 4.2 mg/dl, 95% CI 2.2-6.2, p < .001, respectively). In the overall cohort, sensitivity, specificity, positive and negative predictive values of a daily delta value >4 mg/dl were 52%, 98%, 66% and 98%, respectively. CONCLUSIONS: A daily increase of CRP blood levels of >4 mg/dl in afebrile HCT recipients should trigger an evaluation for infection.

Characteristics of initial compared with subsequent bacterial infections among hospitalised haemato-oncological patients.

Surveys of bacterial infections among neutropenic cancer patients frequently report pooled antibiotic susceptibility data. Management guidelines address initial antibiotic regimens for febrile neutropenia. In this study, rates of bacterial infection and antibiotic susceptibilities among initial and subsequent or breakthrough episodes of fever were analysed. Prospective surveillance of fever of unknown origin (FUO), clinically documented infection and microbiologically documented infection (MDI) was conducted in the haemato-oncology and haematopoietic stem cell transplantation wards in a single cancer centre in Israel. Subsequent infections were defined as those developing during or after broad-spectrum antibiotic treatment. A total of 567 febrile episodes were documented among 271 patients. Bacterial MDIs were documented in 104/162 (64%) initial febrile episodes and 75/405 (19%) subsequent episodes and Gram-negative bacteria predominated (64% and 71%, respectively). Escherichia coli was the most common species isolated. Higher antibiotic susceptibilities were observed for initial compared with subsequent MDIs for Gram-negative bacteria [ceftazidime 80% vs. 45%, piperacillin/tazobactam (TZP) 86% vs. 40% and meropenem 95% vs.76%] and Gram-positive bacteria. TZP monotherapy was the most commonly used antibiotic and its susceptibility decreased to 22.2% following its use. Appropriate empirical antibiotic treatment was administered in 71/97 (73%) initial and 40/74 (54%) subsequent episodes (P=0.009) and was significantly associated with mortality (adjusted odds ratio=0.4, 95% confidence interval 0.18-0.87). We conclude that previous antibiotic exposure significantly impacts antibiotic susceptibility and that pooled reporting of all infections can be misleading. Treatment guidelines should address the antibiotic treatment of breakthrough fever.