Infections In Febrile Neutropenic Patients Research Articles

Antimicrobial Stewardship in Patients with Cancer

Consensus guidelines recommend antimicrobial stewardship in all hospitals with the following goals in mind: appropriate and judicious use of antimicrobial agents leading to increased drug safety, reduced antimicrobial utilization, reduction in the development and selection of resistant organisms, cost containment, and improved patient outcomes. Patients with cancer, especially those with hematologic malignancies and neutropenia, develop serious infections often and receive antimicrobial therapy frequently. Consequently, there is considerable opportunity to practice antimicrobial stewardship in this population. Several antimicrobial stewardship strategies such as antimicrobial restriction, cycling, prospective audit and feedback, and de-escalation have been evaluated in patients with cancer. The primary focus has been on the prevention and treatment of bacterial infections in febrile neutropenic patients. These efforts should be expanded to include fungal, viral, and other infections.

Secondary infections in cancer patients with febrile neutropenia.

Objective: Patients with neutropenia due to cancer chemotherapy are prone to severe infections. Cancer patients canexperience >1 infectious episode during the same period of neutropenia. This study aimed to determine the etiologicaland clinical characteristics of secondary infectious episodes in cancer patients with febrile neutropenia and to identifythe factors associated with the risk of secondary infectious episodes.Material and Methods: All cancer patients that received antineoplastic chemotherapy at Ankara University, School ofMedicine, Department of Hematology between May 2004 and May 2005 and developed neutropenia were included in thestudy. Data were collected using survey forms that were completed during routine infectious diseases consultation visits.Categorical data were analyzed using the chi-square test, whereas Student’s t-test was used for continuous variables.Multivariate logistic regression analysis was performed to identify independent predictors of secondary infections (SIs).Results: SIs were observed during 138 (53%) of 259 febrile neutropenic episodes. Of the 138 episodes, 89 (64.5%)occurred in male patients with a mean age of 40.9 years (range: 17-76 years). In total, 80% of the SIs were clinically ormicrobiologically documented. Factors on d 4 of the initial febrile episode were analyzed via a logistic regression model. The presence of a central intravenous catheter (OR: 3.01; P<0.001), acute myeloid leukemia (AML) as the underlyingdisease (OR: 2.12; P=0.008), diarrhea (OR: 4.59; P=0.005), and invasive aspergillosis (IA) during the initial febrileepisode (OR: 3.96; P=0.009) were statistically significant risk factors for SIs.Conclusion: Among the cancer patients with neutropenia in the present study, AML as the underlying disease, thepresence of a central venous catheter, diarrhea, and IA during the initial febrile episode were risk factors for thedevelopment of SIs.

The Evaluation of Procalcitonin as a Diagnostic and Prognostic Marker of Bacterial Infections in Febrile Neutropenic Patients

The Evaluation of Procalcitonin as a Diagnostic and Prognostic Marker of Bacterial Infections in Febrile Neutropenic Patients

New molecular and surrogate biomarker-based tests in the diagnosis of bacterial and fungal infection in febrile neutropenic patients

Prompt diagnosis of infection in febrile neutropenia hosts with hematological malignancy is essential in directing therapy. We highlight experience using modern molecular and biomarker-based methods to diagnose bacterial and fungal bloodstream infections and invasive aspergillosis in these patients. Nucleic acid amplification-based strategies are used to detect and identify pathogens from blood cultures or from blood/clinical specimens; the latter are more likely to influence clinical management. Advances in DNA extraction include standardization of isolation of Aspergillus DNA from blood. Broad-range and/or multiplex PCR generally have greater clinical utility than pathogen-specific assays. However, Aspergillus-PCR assays are useful in confirming/excluding disease and monitoring high-risk patients for invasive aspergillosis. Commercial real-time PCR/peptide nucleic acid fluorescent in-situ hybridization systems, used as adjuncts to blood cultures, to detect bacteria and fungi in blood cultures (or blood), are as sensitive as culture and enable earlier institution of targeted therapy. Yet there are no data indicating that molecular detection of bacterial/fungal pathogens influences patient outcomes. Positive serum Aspergillus galactomannan and 1,3-β-D-glucan tests are useful biomarkers in the diagnosis/screening of fungal infection, and have potential as measures of response to antifungal therapy. Serum procalcitonin levels can help differentiate infectious, from noninfectious, fever. Combined molecular and nonmolecular testing likely offers optimal diagnostic accuracy. Numerous PCR-based and biomarker tools are available for the diagnosis and screening of infection in febrile neutropenia hosts. The optimal approach remains to be resolved by prospective studies examining the impact of one or more of tests on patient outcomes.

Susceptibility to Teicoplanin among Coagulase-Negative Staphylococci Isolated from Catheter Related Bloodstream Infections in Febrile Neutropenic Patients

Susceptibility to Teicoplanin among Coagulase-Negative Staphylococci Isolated from Catheter Related Bloodstream Infections in Febrile Neutropenic Patients

Incidence of vancomycin-resistant enterococci (VRE) infection in high-risk febrile neutropenic patients colonized with VRE

This study seeks to determine the incidence of vancomycin-resistant enterococci (VRE) infection in high-risk neutropenic fever patients colonized with VRE and to determine patient characteristics associated with VRE infection. We conducted a retrospective, single-center, unmatched case-control study. Fifty-three VRE-colonized, high-risk patients with neutropenic fever were identified between January 2006 and February 2009. The two most common diagnoses/conditions included acute myeloid leukemia and hematopoietic stem cell transplantation. Data collected included days of neutropenia, days of fever, demographic data, culture results, and antimicrobial therapy. Twenty of the 53 patients (38%) with VRE colonization developed a VRE infection. The most common VRE infections were bacteremias (26%). The presence of neutropenia lasting longer than 7 days was associated with the development of VRE infection in this high-risk population colonized with VRE. The timeframe to develop VRE infection varied from 1 day to 2 weeks. For patients colonized with VRE, approximately 38% of high-risk neutropenic patients developed a VRE infection. This is the first study to specifically evaluate the incidence of VRE infections in febrile neutropenic patients colonized with VRE. Future research into the use and efficacy of empiric VRE coverage is needed.

Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults

BackgroundProcalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile.Methods52 adult patients were enrolled in the study. Blood sample was collected in order to determine the serum concentrations of PCT, CRP and other hematological parameters at the onset of fever. The patients were divided into 2 groups, one with severe infection (n = 26) and the other in which the patients did not present such an infection (n = 26). Then PCT and CRP concentrations at the fever onset were compared between groups using non parametric statistical tests, ROC curve, sensitivity, specificity, likelihood ratio, and Spearman's correlation coefficient.ResultsThe mean of PCT was significantly higher in the group with severe infection (6.7 ng/mL versus 0.6 ng/mL – p = 0.0075) comparing with CRP. Serum concentrations of 0.245 ng/mL of PCT displayed 100% de sensitivity and 69.2% specificity. PCT concentrations of 2,145 ng/mL presented a likelihood ratio of 13, which was not observed for any concentration of CRP.ConclusionPCT seems to be an useful marker for the diagnosis of systemic infection in febrile neutropenic patients, probably better than CRP.

Bloodstream infections in febrile neutropenic patients at a tertiary care center in Lebanon: a view of the past decade

Previous studies from Lebanon have shown Gram-negative organisms to be the predominant agents in febrile neutropenic patients. The objective of this study was to evaluate the most current epidemiological trends among patients with neutropenic fever. This prospective observational cohort study, the largest to date in the country, was conducted at the American University of Beirut Medical Center between January 2001 and December 2003, with the objective of describing the characteristics of patients with neutropenic fever and to assess temporal trends. We included 177 episodes of neutropenic fever. The most common underlying malignancy was lymphoma (42.4%). Gastrointestinal and abdominal infections were predominant (31.6%) and 23.7% of cases represented fever of unknown origin. Gram-negative organisms were responsible for 78.8% (26/33) of bloodstream infections compared to 33.3% (11/33) with Gram-positive organisms. The in-hospital mortality rate in this study (12.1%) was considerably lower than in previous years. Gram-negative organisms are persistently predominant in our center. In a developing country like Lebanon with limited resources, lower mortality rates commensurate with worldwide reports were successfully achieved in this high-risk patient population. Protocols and guidelines should be adapted to the characteristics of individual institutions to ensure delivery of appropriate care to febrile neutropenic patients.

Point: Fluoroquinolone-Based Antibacterial Chemoprophylaxis in Neutropenic Cancer Patients Works for Defined Outcomes in Defined Populations, but Must Be Used Wisely

Fluoroquinolone-based antibacterial chemoprophylaxis administered in situations in which the prevalence of fluoroquinolone-resistant Escherichia coli is low (< 3% to 5%) can reliably reduce the risk for invasive gram-negative bacillary infection, and, if supplemented by gram-positive agents such as rifampin, penicillin, or macrolides, can reduce the risk of developing invasive infections caused by gram-positive microorganisms, including Viridans streptococci and coagulase-negative staphylococci. In the published literature, fluoroquinolone-based chemoprophylaxis does not reliably reduce the incidence of febrile neutropenic episodes, neutropenic episode-related mortality, or physician-initiated systemic antimicrobial prescribing behavior. Prophylaxis should only be prescribed in defined patient populations from the first day of cytotoxic therapy until neutrophil regeneration in environments in which the prevalence of gram-negative bacillary resistance to the prophylaxis strategy is low. Small phase II clinical trials suggest that empirical antibacterial therapy of unexplained fevers in neutropenic patients receiving effective fluoroquinolone-based prophylaxis under defined epidemiologic circumstances may be safely discontinued early. Better discriminators of infection in febrile neutropenic patients are needed.

Epidemiology and Risk Factors for Gram‐Positive Coccal Infections in Neutropenia: Toward a More Targeted Antibiotic Strategy

The objective of this study was to evaluate the risk of acquiring gram-positive coccal infections in febrile neutropenic patients and to develop risk indexes for gram-positive and streptococcal infections. This prospective, multicenter study included 513 patients. The prevalence of gram-positive coccal infections was 21% (14% were staphylococcal infections and 7.8% were streptococcal infections). The mortality rate during the month after study enrollment was 5%. On multivariate analysis, the occurrence of gram-positive coccal infections was significantly associated with receipt of high-dose cytarabine therapy, proton pump inhibitors, and gut decontamination with colimycin without glycopeptides and presence of chills. Staphylococcal infection was significantly associated with use of nonabsorbable colimycin, and streptococcal infection was associated with diarrhea, use of nonabsorbable antifungals, receipt of high-dose cytarabine, and gut decontamination with colimycin. The relative risks for streptococcal infection were 2.9, 13.2, and 20.7 in the presence of 1, 2, and > or =3 parameters, respectively. Risk factors for staphylococcal and streptococcal infections differ among neutropenic patients. A simple scoring system for predicting streptococcal infection is proposed.

Mannose-binding lectin in prediction of susceptibility to infection

The idea that distinct haplotypes and single nucleotide polymorphisms in an important molecule of innate immunity, mannose-binding lectin (MBL), may modify susceptibility to infection in febrile neutropenic patients is introduced in two papers in today's Lancet. The findings in these two papers combine the new promise of genetic prediction of disease with classic biology. Deficiency of mannose-binding lectin and burden of infection in children with malignancy: a prospective studyMBL deficiency seems to have an important influence on the duration of febrile neutropenic episodes in children with malignancy. This finding suggests that MBL infusions could represent a new therapeutic approach which would aid the management of chemotherapy-induced complications in this population of children. Full-Text PDF Association between deficiency of mannose-binding lectin and severe infections after chemotherapyThe plasma protein mannose-binding lectin (MBL) activates the complement system by binding to carbohydrate structures presented by microorganisms and thus could be an important component of the innate immune defence system. We measured MBL in patients with leukaemia who were scheduled to undergo chemotherapy (ie, a population especially susceptible to infection) and related the results to severity of infection after chemotherapy. We showed a significant association between low concentrations of MBL and serious infections related to chemotherapy (p<0·0001). Full-Text PDF

Susceptibility Surveillance among Gram-Negative Bacilli at a Cancer Center

We conducted a survey of susceptibility among 758 gram-negative bacilli (GNB; collected from cancer patients over a 3-month period) to commonly used antibiotics. The overall resistance among GNB was least for piperacillin/tazobactam and meropenem (5 and 6%, respectively) followed by cefepime (8%), imipenem (9%), amikacin (12%), ofloxacin (13%), ciprofloxacin, ceftazidime and ticarcillin/clavulanate (14% each), aztreonam (18%) and tobramycin (24%). In comparison to data on antibiotic resistance to ceftazidime, imipenem, ciprofloxacin and aztreonam in similar studies in 1985 and 1994, resistance has significantly increased to all four antibiotic classes. Based on our current study, meropenem, cefepime, imipenem and piperacillin/tazobactam would be the most appropriate choices in our institution for empiric therapy of GNB infections in febrile neutropenic patients.

Antifungal therapy in 'bone marrow failure'.

Antifungal therapy in 'bone marrow failure'.

C-Reactive Protein: A Valuable Aid for the Management of Febrile Children with Cancer and Neutropenia

The usefulness of determining serum levels of C-reactive protein (CRP) for the identification of bacterial infections in febrile neutropenic patients with cancer was evaluated. Two hundred children with cancer were monitored prospectively for the occurrence of neutropenia and fever; serum was collected from these children for determining baseline levels of CRP. Of these 200 children, 75 had 85 febrile neutropenic episodes; serum was collected daily from these 75 children for CRP analysis by nephelometry. Children were included into one of the three following groups by physicians blinded to results of CRP analysis: group I, demonstrated bacterial infection (24 episodes); group II, probable bacterial infection (31 episodes); and group III, viral infection or no infection (30 episodes). Baseline CRP values were low (mean, 9 mg/L; range, 0-35 mg/L) irrespective of tumor type or stage of therapy. Mean CRP values on day 1 for children in groups I and II (194 and 143 mg/L, respectively) were higher than those for children in group III (29 mg/L) (P < .001). A CRP value of > 40 mg/L discriminated children with a demonstrated bacterial infection (sensitivity, 100%; specificity, 76.6%). Children with an unfavorable outcome had persistently high levels of serum CRP. For children with cancer, neutropenia, and fever, determination of the serum CRP level is useful for early diagnosis of bacterial infections and for monitoring the course of infection.

Piperacillin and netilmicin combination therapy for febrile episodes in neutropenic patients

We assessed the efficacy of a piperacillin (3 x 4 g/d) and netilmicin (5 mg/kg/d) combination therapy for infections in febrile neutropenic patients. The study was conducted over a 30-month period and 203 patients were included. Bone marrow transplant recipients were not included in this study. Origin of infection was documented in 101 (50%) episodes: 33 fungal, viral or parasitic infections and 68 bacterial infections mainly composed of septicemia. Of the 169 evaluable patients with proved bacterial infections or non-documented infections, 129 (76%) recovered with the piperacillin and netilmicin combination treatment. All gram-positive bacterial infections failing first line therapy were cured after the addition of vancomycin. Piperacillin and netilmicin appeared very effective in this large monocentric prospective study. It does not seem necessary to include vancomycin in first line therapy of infections of the neutropenic patients in our institution; however, vancomycin must be added early in the case of suspected or documented staphylococcal infection failing empiric treatment.

Antithrombin III in the diagnosis of infection in febrile neutropenic patients

Antithrombin III levels in plasma were measured in 29 febrile neutropenic patients (31 episodes). They were lowest on day 2 in 62.5% of febrile patients and then increased or were normal in 81.3%. Low levels were present on day 2 in only 28.6% of patients with gram-negative infections, as compared with 33% of patients with doubtful infections.