Genotypic study documents divergence in the pathogenesis of bloodstream infection related central venous catheters in neonates

ObjectiveTo investigate the pathogenesis of bloodstream infection by Staphylococcus epidermidis, using the molecular epidemiology, in high-risk neonates.MethodsWe conducted a prospective study of a cohort of neonates with bloodstream infection using central venous catheters for more than 24 h. “National Healthcare Safety Network” surveillance was conducted. Genotyping was performed by DNA fingerprinting and mecA genes and icaAD were detected by multiplex-PCR.ResultsFrom April 2006 to April 2008, the incidence of bloodstream infection and central venous catheter-associated bloodstream infection was 15.1 and 13.0/1000 catheter days, respectively, with S. epidermidis accounting for 42.9% of episodes. Molecular analysis was used to document the similarity among six isolates of bloodstream infection by S. epidermidis from cases with positive blood and central venous catheter tip cultures. Fifty percent of neonates had bloodstream infection not identified as definite or probable central venous catheter-related bloodstream infection. Only one case was considered as definite central venous catheter-related bloodstream infection and was extraluminally acquired; the remaining were considered probable central venous catheter-related bloodstream infections, with one probable extraluminally and another probable intraluminally acquired bloodstream infection. Additionally, among mecA+ and icaAD+ samples, one clone (A) was predominant (80%). A polyclonal profile was found among sensitive samples that were not carriers of the icaAD gene.ConclusionsThe majority of infections caused by S. epidermidis in neonates had an unknown origin, although 33.3% appeared to have been acquired intraluminally and extraluminally. We observed a polyclonal profile between sensitive samples and a prevalent clone (A) between resistant samples.     

Bloodstream infections can develop late (after day 100) and/or in the absence of neutropenia in children receiving allogeneic bone marrow transplantation

We retrospectively evaluated the incidence and time from transplantation of bloodstream infections occurring in children receiving bone marrow transplant (BMT) at G Gaslini Children's Hospital between September 1984 and December 1997. During this period the incidence was 35% after allogeneic and 26% after autologous BMT (P=0.08). Among these episodes, 38% after allogeneic BMT and 90% after autologous BMT were detected in the presence of neutropenia within the first 30 days from reinfusion (P < 0.001). Incidence of catheter-related bloodstream infections was 40% after allogeneic and 8% after autologous BMT (P < 0.001). Bloodstream infections in the absence of neutropenia were 55% after allogeneic BMT vs 10% after autologous BMT (P < 0.001) and occurred later after reinfusion (mean 199 vs 41 days, P <0.001). Among the episodes occurring after allogeneic BMT and in the absence of neutropenia, 61% were related to the presence of a central venous catheter, 15% were related to the presence of GVHD, but 23% were not associated with any of major risk factors for infection. Finally, 38% of episodes following allogeneic BMT were detected after day 100 vs 1% after autologous BMT. We concluded that patients receiving allogeneic BMT experience a high incidence of bloodstream infections in the absence of neutropenia and that a significant proportion of these episodes is not clearly associated with well known risk factors such as GVHD or central venous catheters. Moreover, many episodes develop a long time after the transplantation procedure. Therefore, any febrile episode following allogeneic BMT even late and/or in the absence of neutropenia should be intensively managed.     

Chlorhexidine bathing to reduce central venous catheter-associated bloodstream infection: impact and sustainability

BackgroundChlorhexidine bathing has been associated with reductions in healthcare-associated bloodstream infection. To determine the impact and sustainability of the effect of chlorhexidine bathing on central venous catheter-associated bloodstream infection, we performed a prospective, 3-phase, multiple-hospital study.MethodsIn the medical intensive care unit and the respiratory care unit of a tertiary care hospital and the medical-surgical intensive care units of 4 community hospitals, rates of central venous catheter-associated bloodstream infection were collected prospectively for each period. Pre-intervention (phase 1) patients were bathed with soap and water or nonmedicated bathing cloths; active intervention (phase 2) patients were bathed with 2% chlorhexidine gluconate cloths with the number of baths administered and skin tolerability assessed; post-intervention (phase 3) chlorhexidine bathing was continued but without oversight by research personnel. Central venous catheter-associated bloodstream infection rates were compared over study periods using Poisson regression.ResultsCompared with pre-intervention, during active intervention there were significantly fewer central venous catheter-associated bloodstream infections (6.4/1000 central venous catheter days vs 2.6/1000 central venous catheter days, relative risk, 0.42; 95% confidence interval, 0.25-0.68; P < .001), and this reduction was sustained during post-intervention (2.9/1000 central venous catheter days; relative risk, 0.46; 95% confidence interval, 0.30-0.70; P < .001). During the active intervention period, compliance with chlorhexidine bathing was 82%. Few adverse events were observed.ConclusionIn this multiple-hospital study, chlorhexidine bathing was associated with significant reductions in central venous catheter-associated bloodstream infection, and these reductions were sustained post-intervention when chlorhexidine bathing was unmonitored. Chlorhexidine bathing was well tolerated and is a useful adjunct to reduce central venous catheter-associated bloodstream infection.     

Infectious Complication in 314 Patients after High-Dose Therapy and Autologous Hematopoietic Stem Cell Transplantation: Risk Factors Analysis and Outcome

Abstract Background: Infectious complications occur in most of the patients receiving high-dose therapy (HDT) and autologous hematopoietic stem cell transplantation (HSCT). The objective of the study was to analyze of the type and incidence of infectious complications during neutropenia after HDT and autologous HSCT with respect to risk factors related to stem cell transplant setting in patients treated for hematological malignancies in a single center. Patients and Methods: A total number of 314 patients diagnosed for Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL), acute myeloid leukemia (AML), multiple myeloma (MM) or acute lymphoblastic leukemia (ALL) were included in the study. Analysis of risk factors and outcome of infections after HDT and autologous HSCT was performed. Results: Infectious complications during neutropenia after HDT occurred in 92.3% patients. Microbiologically documented infections (MDI) accounted for 38.9% of febrile episodes, clinically documented infections (CDI) for 9.3%, and fever of unknown origin (FUO) for 51.7% cases. Median time to defervescence with antibiotic therapy was seven days for FUO and nine days for documented infections (p < 0.001). Duration of infection correlated with the length of very severe neutropenia (p < 0.001). Response to first-line antibiotic therapy was seen in 34% patients. Infections were fatal in 12 (3.8%) patients. The highest probability of infection was observed for ALL and AML patients, especially these conditioned with total body irradiation (TBI). Conclusion: Patients at high risk of infection after autologous HSCT were identified as those with acute leukemia and those after conditioning with TBI, all with prolonged neutropenia. We suggest that newer prophylactic strategies should be administered to these groups of patients. Lidia Gil and Jan Styczynski contributed equally to this study.     

Preventing catheter-associated infections in the Pediatric Intensive Care Unit: impact of an educational program surveying policies for insertion and care of central venous catheters in a Brazilian teaching hospital

ObjectivesTo determine the impact of an educational program on the prevention of central venous catheter-related infections in a Brazilian Pediatric Intensive Care Unit.Patients and MethodsAll patients admitted to the unit between February 2004 and May 2005 were included in the cohort study in a longitudinal assessment. An educational program was developed based on the Centers for Disease Control and Prevention recommendations for prevention of catheter-associated infections and was adapted to local conditions and resources after an initial observational phase. Incidence of catheter-associated infections was measured by means of on-site surveillance.ResultsOne hundred eighteen nosocomial infections occurred in 253 patients (46.6 infections per 100 admissions) and in 2,954 patient-days (39.9 infections per 1,000 patient-days). The incidence-density of catheter infections was 31.1 episodes per 1.000 venous central catheter-days before interventions, and 16.5 episodes per 1,000 venous central catheter-days afterwards (relative risk 0.53 [95% CI 0.28–1.01]). Corresponding rates for exit-site catheter infections were 8.0 and 2.5 episodes per 1,000 venous central catheter-days [0.32 (0.07–1.49)], and the rates for bloodstream infections were 23.1 and 13.9 episodes per 1,000 venous central catheter-days, before and after interventions [0.61 (0.32–1.14)].ConclusionA prevention strategy targeted at the insertion and maintenance of vascular access can decrease rates of vascular-access infections in pediatric intensive care unit.     

Clinical and microbiologic determinants of serious bloodstream infections in Egyptian pediatric cancer patients: a one-year study.

OBJECTIVES: Bloodstream infections (BSI) remain a major cause of morbidity and death in patients undergoing treatment for cancer. However, all recent epidemiological and therapeutic studies underline the absolute need for knowledge of the factors governing the infections in each center. The aim of this study is to identify the factors affecting BSI in the pediatric service of the National Cancer Institute (NCI) at Cairo University. More tailored policies for the treatment of patients with febrile neutropenia following chemotherapy can then be created. PATIENTS AND METHODS: Over a 12-month period, all children with cancer and fever, with or without neutropenia, who were admitted to the NCI for empirical therapy of febrile episodes and who had a microbiologically confirmed bloodstream infection were studied retrospectively. RESULTS: A total of 328 BSI occurred in 1135 febrile episodes in pediatric cancer patients at the NCI in one year. Gram-positive bacteria were isolated in 168 episodes (51.2%) and 61.9% of the total isolates (either single or mixed), Gram-negative in 97 (29.6%), and mixed infections in 45 (13.7%). The common causative agents of bloodstream infections in this study were coagulase-negative staphylococci (16.2%), Staphylococcus aureus (13.4%), Streptococcus spp. (12.1%) followed by Acinetobacter spp. (6.7%) and Pseudomonas spp. (5.5%). Fungemia was encountered in 18 episodes, being mixed in nine of them. A more serious BSI in terms of a prolonged episode was encountered in 30.2% of the episodes and was significantly associated with patients being hospitalized, having intensified chemotherapy, polymicrobial and fungal infection, lower respiratory tract infections and persistent neutropenia at day seven. CONCLUSIONS: In a large population of children, common clinical and laboratory risk factors were identified that can help predict more serious BSI. These results encourage the possibility of a more selective management strategy for these children.     

Catheter‐associated bloodstream infection incidence and outcomes in congenital cardiac surgery

Objective: Catheter‐associated bloodstream infections complicate and prolong hos‐ pitalizations. The incidence of catheter‐associated bloodstream infections in children undergoing congenital cardiac surgery has not been reported. This study sought to define the incidence of catheter‐associated bloodstream infections after congenital cardiac surgery in neonates and infants ≤12 months old and compare hospital out‐ comes and costs to those who underwent surgery and did not have a catheter‐associ‐ ated bloodstream infections.
Design: Retrospective review of hospital admissions between October 2013 and November 2015 for neonates and infants ≤12 months old at admission with ICD‐9 codes for congenital cardiac surgery from discharge data from Vizient Clinical Data Base/Resource Manager (formerly University HealthSystem Consortium), an ana‐ lytic platform for performance improvement. Hospitals were included if they had >100 congenital cardiac surgery admissions during the study period. Admissions were stratified by age at admission: Neonates (<1 month) and Infants (1‐12 months). Established database flags for catheter‐associated bloodstream infections were uti‐ lized. Length of stay, mortality, and direct costs were compared between admissions with and without catheter‐associated bloodstream infections using t test or χ², as appropriate.
Results: Catheter‐associated bloodstream infections incidence after congenital car‐ diac surgery was higher in Neonates than Infants (1.5 vs 0.8%, P = .024). Length of stay and direct costs were significantly higher for patients with catheter‐associated bloodstream infections in both groups. Mortality was higher in the Infant group with catheter‐associated bloodstream infections compared to those without catheter‐as‐ sociated bloodstream infections.
Conclusion: Neonates develop catheter‐associated bloodstream infections at nearly twice the rate of older infants. For those who develop infection, mortality is 2‐8‐fold greater and hospital costs are 4‐6‐fold higher, which further highlight the importance of catheter‐associated bloodstream infections prevention in this population.     

Interleukin–8 Serum Levels at Fever Onset in Patients with Neutropenia Predict Early Medical Complications

Abstract Background: Previous studies have shown that interleukin–8 serum levels in febrile neutropenic patients are significantly higher in patients with gram–negative bacteremia than in patients with other causes of fever and may indicate unfavorable outcomes. We assessed the value of interleukin–8 serum levels at fever onset to predict clinical complications in order to confirm these earlier findings. Patients and Methods: In a prospective observational study of adult patients receiving cancer chemotherapy, serum samples obtained at the onset of 147 febrile neutropenic episodes were measured by an immunoluminescence assay. Results: Complicated courses of fever including severe sepsis or septic shock, respiratory insufficiency or death were observed in 13 episodes (9%); in six episodes complications had developed within 1 week after fever onset and five of them were associated with bloodstream infections. At an interleukin–8 cutoff level of 1,000 pg/ml, these early complications were predicted with a sensitivity of 83%, a specificity of 97%, a positive predictive value of 50%, and a negative predictive value of 99%, respectively. Conclusion: Interleukin–8 levels at fever onset may be used for the prediction of early medical complications associated with bacteremia and can help identify patients who might benefit from intensive care admission. This paper is dedicated to the founders of the Walter Marget Foundation, D. Adam and F. Daschner, in gratitude for their support of the training in infectious diseases.     

Effects of a Quality Improvement Program to Reduce Central Venous Catheter-Related Infections in Hemodialysis Patients

BackgroundCentral catheter infections are of concern in patients on hemodialysis because of the high risk of catheter-related bloodstream infections, sepsis, and death. Adequate nursing is critical for the prevention of such infections. This study aimed to use the PDCA (plan-do-check-act) method to reduce the incidence of central venous catheter infection using management in the maintenance of central venous catheter in patients on hemodialysis, compared with routine care.MethodsThis pilot study recruited patients on hemodialysis via central venous catheterization at the Blood Purification Center of Ruijin Hospital between November 2017 and November 2018. The patients were randomized to the routine and PDCA groups. All participants received routine nursing. The PDCA group received central venous catheter management by PDCA. The incidence of central venous catheterization-related infections, nursing satisfaction, and quality of life were compared between the two groups.ResultsA total of 122 participants were enrolled in each group. The incidence of central catheter-related bloodstream infection, as the primary outcome, was 0.8 and 8.8 cases per 1000 catheter days in the PDCA and routine groups, respectively (P < 0.001). In addition, as the secondary outcomes, the scores of nursing satisfaction (health guidance, nursing technology, and therapeutic effects) score and quality of life (physiological, psychological, social, and environmental status) were better in the PDCA group than in the routine group (all P < 0.01).ConclusionsThis pilot study suggests that the PDCA cycle model can effectively reduce the incidence of central venous catheter-related infections and improve satisfaction and quality of life in patients on hemodialysis.     

Antibiotic-Resistant Bloodstream Infections in Hospitalized Patients: Specific Risk Factors in a High–Risk Population?

Abstract Background: The aim of this study was to explore characteristics that are associated with bloodstream infections due to specific multiresistant microorganisms (methicillinresitant Staphylococcus aureus, MRSA; vancomycin–resistant enterococci, VRE; third–generation cephalosporin–resistant Enterobacteriaceae) or Candida spp. in hospitalized patients. Patients and Methods: All patients who experienced a bloodstream infection with one of the aforementioned pathogens between September 1999 and October 2001 were included into a statistical analysis of independent risk factors. The possible impact of previous antibiotic and antifungal therapies was evaluated. Results: Of the study population, 22% had two or more episodes with different pathogens. In the 314 patients with a single bloodstream infection MRSA was isolated in 189 patients, VRE in 31, Enterobacteriaceae in 13, and Candida spp. in 80 patients. Crude mortality was high in the study population (overall 40%) and varied between 33% (MRSA bacteremia only) and 58% (VRE bacteremia only). Patients who yielded more than one of the pathogens under surveillance had crude mortalities ranging from 41% to 83% (all four pathogens). In this group of high–risk patients, the following factors were independently associated with the individual pathogen: prior chemotherapy (OR 4.88 CI₉₅ 1.50–15.87) and bronchoscopy (OR 3.17 CI₉₅ 1.05–9.52) for VRE patients; burns (OR 4.50 CI₉₅ 0.90–22.73), presence of a tracheostomy (OR 4.22 CI₉₅ 1.15–15.38) and acute dialysis (OR 3.62 CI₉₅ 0.99–13.16) for patients with Enterobacteriaceae; and an underlying malignant disease (OR 1.98 CI95 0.99–3.97), performance of a bowel endoscopy (OR 2.80 CI₉₅ 1.27–6.13) and presence of a central venous catheter (CVC) (OR 12.34 CI₉₅ 1.63–90.91) for patients with candidemia. Conclusion: Patients with bacteremia due to VRE, Enterobacteriaceae or Candida spp. had more severe risk factors associated with the respective pathogen than patients with MRSA bacteremia. This paper is dedicated to the founders of the Walter Marget Foundation, D. Adam and F. Daschner, in gratitude for their support of the training in infectious diseases.     

Infectious complications in 126 patients treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation

The effect of an extensive prophylactic antimicrobial regimen was prospectively assessed in 126 patients after high-dose chemotherapy and autologous PBSC. They received ciprofloxacin (500 mg/12 h), acyclovir (200 mg/6 h), and itraconazole (200 mg/12 h) orally until neutrophil recovery. Febrile patients received i.v. imipenem (500 mg/6 h) to which vancomycin and amikacin were added if fever persisted for 2-3 and 5 days, respectively. Amphotericin B lipid complex was further given on day 7 or 8 of fever. Median times for a neutrophil count of >0.5 x 10(9)/l and a platelet count of >20 x 10(9)/l were 9 and 11 days. Severe neutropenia (<0.1 x 10(9)/l) lasted for a median of 5 days in which 72% of febrile episodes and 50% of cases of bacteremia occurred. Gram-positive bacteria were isolated in 30 of 40 episodes of bacteremia, 25 of which were caused by Staphylococcus epidermidis. Clinical foci were the intravascular catheter in 35 cases, respiratory infection in 11, cellulitis in two, anal abscess in one, and neutropenic enterocolitis in one. The high incidence of febrile episodes (94%) and bacteremias (31%) may be due to the lack of efficacy of antimicrobial prophylaxis and the persistence of a 5-day period of severe neutropenia.     

Trends in the epidemiology of catheter-related bloodstream infections; towards a paradigm shift,Spain, 2007 to 2019

BackgroundCatheter-related bloodstream infections (CRBSI) are frequent healthcare-associated infections and an important cause of death.AimTo analyse changes in CRBSI epidemiology observed by the Infection Control Catalan Programme (VINCat).MethodsA cohort study including all hospital-acquired CRBSI episodes diagnosed at 55 hospitals (2007–2019) in Catalonia, Spain, was prospectively conducted. CRBSI incidence rates were adjusted per 1,000 patient days. To assess the CRBSI rate trend per year, negative binomial models were used, with the number of events as the dependent variable, and the year as the main independent variable. From each model, the annual rate of CRBSI diagnosed per 1,000 patient days and the incidence rate ratio (IRR) with its 95% confidence intervals (CI) were reported.ResultsDuring the study, 9,290 CRBSI episodes were diagnosed (mean annual incidence rate: 0.20 episodes/1,000 patient days). Patients’ median age was 64.1 years; 36.6% (3,403/9,290) were female. In total, 73.7% (n = 6,845) of CRBSI occurred in non-intensive care unit (ICU) wards, 62.7% (n = 5,822) were related to central venous catheter (CVC), 24.1% (n = 2,236) to peripheral venous catheters (PVC) and 13.3% (n = 1,232) to peripherally-inserted central venous catheters (PICVC). Incidence rate fell over the study period (IRR: 0.94; 95%CI: 0.93–0.96), especially in the ICU (IRR: 0.88; 95%CI: 0.87–0.89). As a whole, while episodes of CVC CRBSI fell significantly (IRR: 0.88; 95%CI: 0.87–0.91), peripherally-inserted catheter CRBSI (PVC and PICVC) rose, especially in medical wards (IRR PICVC: 1.08; 95%CI: 1.05–1.11; IRR PVC: 1.03; 95% 1.00-1.05).ConclusionsOver the study, CRBSIs associated with CVC and diagnosed in ICUs decreased while episodes in conventional wards involving peripherally-inserted catheters increased. Hospitals should implement preventive measures in conventional wards.     

Incidence and Predictors of Bacterial infection in Febrile Children with Sickle Cell Disease

Abstract

Children with sickle cell disease are at increased risk of developing bacteremia and other serious bacterial infections. Fever is a common symptom in sickle cell disease and can also occur with sickle cell crises and viral infections. We aimed to evaluate the incidence and predictors of bacteremia and bacterial infection in children with sickle cell disease presenting with fever to a district hospital and sickle cell center in London. A retrospective analysis was performed on all attendances of children (aged under 16 years) with sickle cell disease presenting with a fever of 38.5?°C or higher over a 1-year period. Confirmed bacterial infection was defined as bacteremia, bacterial meningitis, urinary tract infection (UTI), pneumonia, osteomyelitis or other bacterial infection with positive identification of organism. Children were defined as having a suspected bacterial infection if a bacterial infection was suspected clinically, but no organism was identified. Over a 1-year period there were 88 episodes analyzed in 59 children. Bacteremia occurred in 3.4% of episodes and confirmed bacterial infection in 7.0%. Suspected bacterial infection occurred in 33.0%. One death occurred from Salmonella typhirium septicemia. C-reactive protein (CRP) level and white blood cell (WBC) count were both significantly associated with bacterial infection (p?=?0.004 and 0.02, respectively.) In conclusion, bacterial infections continue to be a significant problem in children with sickle cell disease. C-reactive protein was significantly associated with bacterial infections, and could be included in clinical risk criteria for febrile children with sickle cell disease.     

Combination of Amikacin and either Ampicillin or Cephalotin as Initial Treatment of Febrile Neutropenic Patients

ABSTRACT. A prospective, randomized trial of two antibiotic combinations (amikacin plus either ampicillin or cephalotin) was performed on 39 consecutive episodes of fever in 30 patients with neutropenia and hematological malignancy. Infections were documented as the cause of fever in 37 episodes (95%): in 21 episodes (54%) bacteria or a virus (n=1) were isolated, and in 16 (41% of all episodes) the infection was documented clinically but no pathogen was isolated. The most frequently isolated bacteria were Staph, aureus (38% of all strains), E. coli (13%), and Pseudomonas aeruginosa (13%). Bacteremia occurred in 18% of the febrile episodes. Improvement followed treatment with the combination amikacin plus ampicllin in 73% of 19 cases, and with amikacin plus cephalotin in 55% of 20 cases (p>0.05), giving a total Improvement rate of 64%. Failure of therapy was seen in episodes caused by multiple bacteria or Pseudomonas infections. Mild signs of nephrotoxicity were noted in 13% during both regimens. Audiograms were normal in all but two patients who showed slight high-frequency hearing loss. A second infection occurred in 7 episodes (18%). Thus, the combination of amikacin plus ampidllin was as efficient (but less expensive) as amikacin plus cephalotin in the initial treatment of febrile episodes in neutropenic patients with hematological malignancies.     

Infectious complications of chemotherapy in clinically aggressive mature B and T cell lymphomas

BackgroundScientific literature on infectious complications of chemotherapy in lymphomas is often based on retrospective studies or clinical trials performed with selected patients. This population may not be representative of the routine clinical practice. We aimed to analyse the incidence and type of infections associated to standard chemotherapy in clinically aggressive mature B and T cell lymphomas (AMBTL) and to detect baseline variables predictive of the risk of infection in a cohort of unselected patients.MethodsA prospective observational study of all the patients treated with first line chemotherapy for AMBTL in our Lymphoma Unit, in the setting of a community based teaching hospital, was performed. The statistical methods were univariate and multivariate analyses.Results183 infectious episodes were registered in 97 (49%) of the 198 patients. Seventy-nine of them (43%) were associated to febrile neutropenia (27% of the patients). Microbiological documentation was obtained in 46% and only clinical documentation in 15%; 39% were classified as fever of unknown origin. Gram negative bacilli were the predominant aetiology. There were several variables related to risk of infection, but in multivariate analysis only a poor initial performance status was predictive of the risk of febrile neutropenia and infection during the first line chemotherapy.ConclusionsIn our cohort of AMBTL patients treated with first line chemotherapy, more than half of the relevant infections occurred without febrile neutropenia. A poor performance status was the only independent variable associated with the risk of febrile neutropenia or infection in the course of first line chemotherapy.     

Prospective evaluation of procalcitonin in adults with febrile neutropenia after haematopoietic stem cell transplantation

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin (n = 51), microbiological (n = 26) or clinical (n = 5) documented infection and non-infectious febrile episodes (n = 10). On first day of fever, mean (+/- SD) PCT level was 0.3 ng/ml (0.2) in neutropenic fever of unknown origin, 0.5 ng/ml (0.7) in microbiologically confirmed infections, 0.2 ng/ml (0.2) in clinically documented infections and 1.7 (4.2) in non-infectious fever (P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10.1 ng/ml (6.7)] than all remaining groups (P = 0.027; Kruskal-Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values > or = 3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis.     

Prospective evaluation of risk factors for bloodstream infection in patients receiving home infusion therapy.

BACKGROUND: Intravenous therapy in the outpatient and home settings is commonplace for many diseases and nutritional disorders. Few data are available on the rate of and risk factors for bloodstream infection among patients receiving such therapy. OBJECTIVE: To determine rates of and risk factors for bloodstream infection among patients receiving home infusion therapy. DESIGN: Prospective, observational cohort study. SETTING: Cleveland, Ohio, and Toronto, Ontario, Canada. PATIENTS: Patients receiving home infusion therapy through a central or midline catheter. MEASUREMENTS: Primary laboratory-confirmed bloodstream infection. RESULTS: Among 827 patients (988 catheters), the most common diagnoses were infections other than HIV (67%), cancer (24%), nutritional and digestive disease (17%), heart disease (14%), receipt of bone marrow or solid organ transplants (11%), and HIV infection (7%). Sixty-nine bloodstream infections occurred during 69,532 catheter-days (0.99 infections per 1000 days). In a Cox regression model with time-dependent covariates, independent risk factors for bloodstream infection were recent receipt of a bone marrow transplant (hazard ratio, 5.8 [95% CI, 3.0 to 11.3]), receipt of total parenteral nutrition (hazard ratio, 4.1 [CI, 2.3 to 7.2]), receipt of therapy outside the home (for example, in an outpatient clinic or physician's office) (hazard ratio, 3.6 [CI, 2.2 to 5.9]), use of a multilumen catheter (hazard ratio, 2.8 [CI, 1.7 to 4.7]), and previous bloodstream infection (hazard ratio, 2.5 [CI, 1.5 to 4.2]). Rates of bloodstream infection per 1000 catheter-days varied from 0.16 for patients with none of these 5 risk factors to 6.77 for patients with 3 or more risk factors. Centrally inserted venous catheters were associated with a higher risk than implanted ports were, but the difference was not statistically significant. CONCLUSION: Bloodstream infections seem to be infrequent among outpatients receiving infusions through central and midline catheters. However, the rate of infection increases with bone marrow transplantation, parenteral nutrition, infusion therapy in a hospital clinic or physician's office, and use of multilumen catheters. Compared with implanted ports or peripherally inserted catheters, centrally inserted venous catheters may confer greater risk for bloodstream infection.     

Antibiotic strategy after the empiric phase in patients treated for a hematological malignancy

 Empiric broad-spectrum antibiotic therapy has become a generally accepted strategy in the treatment of febrile neutropenic patients. Particularly in patients with prolonged neutropenia, subsequent adaptation of such a regimen will be the rule rather than exception. Since there are no uniformly accepted guidelines for the modification of antibiotic therapy during the post-empiric phase, we assessed the impact of a set of rules that evolved during the first randomized trials. Evaluation of the clinician's compliance with these rules in 1951 febrile neutropenic episodes was the subject of the present analysis. Treatment was modified in 761 (39%) cases, and these changes were made according to the rules in 76%. For 75% of the alterations in treatment during the evening and night shifts, no reasonable explanation was established, while 93% of the modifications during the normal working hours were made for objective reasons. The empiric regimen was more frequently changed in patients with a clinical focus of infection at the onset of fever than in patients who showed fever as the only symptom of a possible infection. The perceived need for modification amounted to 69% in pulmonary infections, to 51% in skin and soft-tissue infections, to 44% in patients with abdominal complaints, and to 37% in upper respiratory tract infections. Glycopeptides constituted 22% of modifications, particularly in patients with a central venous catheter, and systemically active antifungals were administered in 16% of cases. Especially inexperienced clinicians tend to adjust antibiotic therapy, in spite of the fact that persistence of fever alone seldom reflects inadequate treatment when the clinical condition of the patient is stable or improving. On the other hand, the development of subsequent infectious events emphasizes that a genuine need for modification does frequently exist. Received: 4 December 1995 / Accepted: 7 December 1995     

Nosocomial infections in an oncology intensive care unit

Introduction: Treatment of cancer has contributed to a growing number of immunocompromised patients with life-threatening nosocomial infections (NI). High mortality with considerable cost is observed when they are admitted to the intensive care unit (ICU). Few studies on infection control and surveillance have been undertaken in this population group.Methods: All patients treated at a six-bed medical-surgical oncology ICU for>48 hours were prospectively observed for the development of an NI and the influence of device utilization on infection rates. The analysis used the standard definitions of the National Nosocomial Infection Surveillance System Intensive Care Unit surveillance component.Results: From September 1993 through November 1995, 370 infections occurred in 623 patients during 4034 patient-days, for an overall rate of 50.0 per 100 patients or 91.7 per 1000 patient-days. Pneumonia (28.9%), urinary tract infections (25.6%), and bloodstream infections (24.1%) were the main types of infection. The most common microorganisms isolated were Enterobacteriaceae (29.7%), fungi (22.2%), and Pseudomonas aeruginosa (13.2%). The median device utilization ratios were 0.63, 0.83, and 0.86 for ventilator, indwelling urinary catheter, and central venous catheter, respectively. The highest median device-specific associated infection rate was 41.7 for ventilator. The median for the average length of stay was 8.8 days, and the average severity of illness score was 4.0. There was a strong positive correlation between the overall NI patient rate and device utilization (r = 0.56, p < 0.01), average severity of illness score (r = 0.54, p < 0.01), and average length of stay (r = 0.67, p < 0.01). No correlations were statistically significant when patient-days were used in the denominator. Among the devices only the number of central venous catheter days was significantly correlated with infections (r = 0.51, P = 0.01). The NI patient-day rates were progressively higher the longer the patients stayed in the ICU.Conclusions: The high rates reported in this study may reflect a combination of several factors related to the underlying illness, neutrophil count, and exposure to invasive procedures. The adjusted infection rates described here provide specific surveillance data for further interhospital comparisons and also to assess the influence of invasive medical interventions, allowing the implementation of preventable measures to control infections.     

Predictive factors of septic shock and mortality in neutropenic patients

Neutropenia is a major risk factor for developing a serious infection. Bacteremia still causes significant mortality among neutropenic patients with cancer. The purpose of this study was to identify risk factors for septic shock and for mortality in neutropenic patients with leukemia and bacteremia. Consecutive samples from 20 patients with acute myeloid leukemia and bacteremia were studied during a 1 year period (January-December 2003). All patients received empirical antibiotic therapies for febrile episodes using ceftazidime plus amikacin. About 110 neutropenic febrile episodes were noted: clinically documented 14.54%, microbiologically documented 16.36% and fever of unknown origin 69.09%. Gram-negative organism caused eight febrile episodes: Pseudomonas (5), Klebsiella (3). Gram-positive organism caused 10 episodes: Staphylococcus (6), Streptococci (2), Enterococci (2). Pulmonary infection accounted for 25% of clinically documented infections. About 14 of the 110 febrile episodes were associated with septic shock causing mortality in 7 patients. In a univariate analysis variables associated with septic shock were: pulmonary infection (OR = 17, p = 0.001), serum bicarbonate < 17 mmol/l (OR = 68, p < 0.001) and serum lactate >3 mmol/l (OR = 62, p < 0.001). Variables associated with mortality were: pulmonary infection (OR = 83, p < 0.001) and serum bicarbonate < 17 mmol/l (OR = 61, p < 0.001). In a multivariate analysis two variables were associated with septic shock: pulmonary infection (OR = 5, p = 0.043) and serum lactate >3 mmol/l (OR = 10, p = 0.003). An elevated serum lactate (>3 mmol/l) and low serum bicarbonate ( < 17 mmol/l) at the onset of bacteremia are useful biomarkers in predicting septic shock and mortality in neutropenic patients.