Febrile Neutropenic Cancer Patients Research Articles

Biofilm formation by blood stream staphylococcal isolates from febrile neutropenic cancer patients

Objectives: The aim of this study was to define the main causative organisms of bacteremia in febrile neutropenic patients and to study the prevalence of biofilm forming capability of staphylococci in blood isolates of these patients. Background: Blood stream infections remain the main cause of morbidity and death in patients undergoing treatment for cancer. Researchers showed that the first step of staphylococcal infection is the attachment to surfaces of various materials and biofilm formation. Biofilms render the cells less accessible to the defense system of the host, thus impairing the action of antibiotics. Therefore, methods identifying strains with a capacity for biofilm formation are necessary to develop effective strategies for biofilm control and improve patient care. Patients and methods: The study included 185 participants divided into two groups; group I included 155 cancer patients and group II included 30 healthy participants as control. The participants were subjected to the following: medical history, blood cultures, antimicrobial susceptibilities of the staphylococcal isolates, Congo red agar (CRA) test, and microtiter plate (MTP) test. Results: Positive blood culture represented 33% of cases; of them, gram-positive bacteria represented 78.5% (40 cases staphylococci): 17 cases were of Staphylococcus aureus and 23 cases were of Staphylococcus epidermidis . Biofilm-positive strains of S. aureus were 4/17 (23.6%) when assessed with CRA and 6/17 (35.3%) when assessed with MTP. Biofilm-positive strains of S. epidermidis were 7/23 (30.4%) when assessed with CRA and 10/23 (43.5%) when assessed with MTP. Most strains that form biofilm were more resistant to most antibiotics compared with other strains. Conclusion: There is an association between biofilm production with persistent infection and antibiotic therapy failure. The MTP is the test of choice in detecting biofilm formation among staphylococci.

A comparison of ED and direct admission care of cancer patients with febrile neutropenia

ObjectiveWe compared the quality of care in admitted febrile neutropenic cancer patients presenting through the emergency department (ED) vs those directly admitted (DA) from the clinic or infusion center. We hypothesized that the quality of care would be comparable between these 2 pathways. MethodsWe conducted a retrospective, observational cohort study of all adult cancer patients hospitalized with subjective or objective fever (≥100.4°F) and documented neutropenia (absolute neutrophil count ≤1000/mm3) from January 1, 2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including patient age, sex, race, tumor type, blood culture growth, temperature (actual or reported), pathway to admission (ED or DA), time to antibiotic administration, length of stay, and the Multinational Association for Supportive Care in Cancer (MASCC) risk score. The primary outcome measures were time to antibiotic administration, appropriateness of antibiotic(s) administered based on published guidelines, length of stay, and MASCC score–based risk assessment. We used the t test for the difference between 2 means with unequal population variances to compare these outcome measures between ED and DA patients. ResultsOne hundred twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA visits). Mean time to antibiotic administration, mean length of stay, appropriateness of antibiotics, and MASCC score–based risk assessment were comparable between ED and DA visits (P>.05 for all comparisons). ConclusionThe quality of care for febrile neutropenia in patients presenting through the ED was comparable to those directly admitted to the hospital in this 2-center study.

FEBRILINĖS NEUTROPENIJOS GYDYMO STANDARTAI PEDIATRIJOJE

Managing cancer patients with fever and neutropenia must be considered as a medical emergency since any delay in initiating appropriate empirical antibacterial therapy may result in high rates of mortality and morbidity. Emerging antibacterial resistance in bacterial pathogens infecting febrile neutropenic patients complicates management, and choosing the type of empirical antimicrobial therapy has become a challenge. To further complicate the decision process, not all neutropenic patients are in the same category of susceptibility to develop severe infection. This review gives a brief overview of current antimicrobial regiment strategy in febrile neutropenic cancer patients.

Third generation cephalosporin resistant Enterobacteriaceae and multidrug resistant gram-negative bacteria causing bacteremia in febrile neutropenia adult cancer patients in Lebanon, broad spectrum antibiotics use as a major risk factor, and correlation with poor prognosis.

Introduction: Bacteremia remains a major cause of life-threatening complications in patients receiving anticancer chemotherapy. The spectrum and susceptibility profiles of causative microorganisms differ with time and place. Data from Lebanon are scarce. We aim at evaluating the epidemiology of bacteremia in cancer patients in a university hospital in Lebanon, emphasizing antibiotic resistance and risk factors of multi-drug resistant organism (MDRO)-associated bacteremia.Materials and Methods: This is a retrospective study of 75 episodes of bacteremia occurring in febrile neutropenic patients admitted to the hematology-oncology unit at Makassed General Hospital, Lebanon, from October 2009-January 2012. It corresponds to epidemiological data on bacteremia episodes in febrile neutropenic cancer patients including antimicrobial resistance and identification of risk factors associated with third generation cephalosporin resistance (3GCR) and MDRO-associated bacteremia.Results: Out of 75 bacteremias, 42.7% were gram-positive (GP), and 57.3% were gram-negative (GN). GP bacteremias were mostly due to methicillin-resistant coagulase negative staphylococci (28% of total bacteremias and 66% of GP bacteremias). Among the GN bacteremias, Escherichia coli (22.7% of total, 39.5% of GN organisms) and Klebsiella pneumoniae(13.3% of total, 23.3% of GN organisms) were the most important causative agents. GN bacteremia due to 3GC sensitive (3GCS) bacteria represented 28% of total bacteremias, while 29% were due to 3GCR bacteria and 9% were due to carbapenem-resistant organisms. There was a significant correlation between bacteremia with MDRO and subsequent intubation, sepsis and mortality. Among potential risk factors, only broad spectrum antibiotic intake >4 days before bacteremia was found to be statistically significant for acquisition of 3GCR bacteria. Using carbapenems or piperacillin/tazobactam>4 days before bacteremia was significantly associated with the emergence of MDRO (p < 0.05).Conclusion: Our findings have major implications for the management of febrile neutropenia, especially in breakthrough bacteremia and fever when patients are already on broadspectrum antibiotics. Emergence of resistance to 3GCs and, to a lesser extent, to carbapenems in GN isolates has to be considered seriously in our local guidelines for empiric treatment of febrile neutropenia, especially given that their occurrence was proven to be associated with poorer outcomes.

Update on Healthcare-Associated Blood Stream Infections in Febrile Neutropenic Pediatric Oncology Patients

Background: Continuous surveillance of pattern of blood stream infection is necessary in febrile neutropenia especially with the recent escalating trend in the management of pediatric cancer patients towards intensified regimens and with the increase in infections caused by resistant organisms limiting the choice of antibiotics. Aim: Monitoring if a change has occurred in pattern of blood stream infections (BSI) in febrile neutropenic (FN) pediatric cancer patients. Methods: Surveillance of FN episodes with positive BSI was prospectively monitored and compared to a previous surveillance in the same pediatric oncology unit. Results: A total of 232 BSI positive episodes were documented in 192 patients during a 6 months period. The results of recent surveillance analysis showed an increase in intensified regimens of chemotherapy, antimicrobial resistance, and prolonged duration of episodes when compared to previous surveillance, with a p value of <0.001, 0.005, and <0.001, respectively. There was an apparent decrease in the crude mortality but this was not statistically significant, 6% in 2011 and 10% in 2006. Conclusion: The pattern of BSI at our institution is still inclining towards gram positive organisms but is showing a shift towards more antibiotic resistance and prolonged episodes.

Bacterial Spectrum, Isolation Sites and Susceptibility Patterns of Pathogens in Adult Febrile Neutropenic Cancer Patients at a Specialist Hospital in Saudi Arabia.

BackgroundKnowing local spectrum and sensitivity for bacterial isolates causing febrile neutropenia is important as starting an appropriate empirical antibiotic therapy is considered a medical emergency in these high-risk patients.MethodsA retrospective study of a total of 106 microbiologically febrile episodes in hospitalized adult neutropenic cancer patients, who were admitted from May 2009 to May 2013, at King Fahad Specialist Hospital, Dammam, Saudi Arabia, was conducted.ResultsAmong 106 microbiologically documented febrile neutropenic episodes, the majority of malignancies were solid tumors accounting for 53.8% (57/106) and hematological malignancies accounted for 46.23% (49/106). The most common malignancies were non-Hodgkin’s lymphoma 19.81% (21/106) followed by acute myeloid leukemia 15.09% (16/106), then colorectal cancer 13.21% (14/106), pancreatic cancer and acute lymphoblastic leukemia accounting for 5.66% (6/106) each, multiple myeloma 4.72% (5/106), gall bladder cancer 3.77% (4/106), and lung cancer 2.83% (3/106). A total of 138 bacterial isolates were identified. The overall prevalence of gram-negative bacteria was 65.94% (91/138) and for gram-positive bacteria was 34.06% (47/138). The most common bacterial isolation sites were blood 33.32% (46 isolates), urine 29.71% (41 isolates), wound 19.55% (27 isolates), body fluids 9.41% (13 isolates) and sputum 7.96% (11 isolates). The most predominant pathogens were Escherichia coli 30.43 (42/138), Klebsiella pneumonia 14.49% (20/138), Staphylococcus aureus 13.04% (18/138), Sptreptococcus spp. 7.25% (10/138), Pseudomonas spp. 7.25% (10/138), Enterococcus spp. 5.80% (8/138), Staphylococcus spp. 4.35% (6/138), Corynebacterium spp. 3.62% (5/138), Enterobacter spp. 3.62% (5/138), Acinobacter spp. 2.90% (4/138), Serratia marcescens 2.17% (3/138), Proteus mirabilis 1.45% (2). Aeromonas hydrophylia, Citrobacter freundii, Providencia stuartii, Sphingomonas paucimobilis and Stenotropomonas multipholia contributed to 0.72% with one isolate each. For gram-negative Escherichia coli and Klebsiella pneumonia, the extended-spectrum beta-lactamases producers (ESBLs) rates were 38% and 22.22% respectively. For Pseudomonas aerugenosa imipenem-cilastatin resistance rate was 18.84%. For gram-positive bacteria, methicillin-resistant Staphylococcus aureus (MRSA) rate was 28.62%. The vancomycin-resistant Enterococci (VRE) rate was 1.18%.ConclusionGram-negative bacteria were more prevalent as a cause of infection in adult cancer patients with febrile neutropenia at our institution, with Escherichia coli and Klebsiella pneumonia with high ESBLs rates being the most common pathogens. Blood stream infections followed by urinary tract infections were the most common sites of infection. The use of initial antibiotic therapy in febrile neutropenic episodes should be based on local bacterial spectrum and susceptibility/sensitivity patterns to prevent treatment failure with increased morbidity and mortality.

Oral versus intravenous antibiotic treatment for febrile neutropenia in cancer patients

Fever occurring in a neutropenic patient remains a common life-threatening complication of cancer chemotherapy. The common practice is to admit the patient to hospital and treat him or her empirically with intravenous broad-spectrum antibiotics. Oral therapy could be an alternative approach for selected patients. To compare the efficacy of oral antibiotics versus intravenous (IV) antibiotic therapy in febrile neutropenic cancer patients. The Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 1) in The Cochrane Library, MEDLINE (1966 to January week 4, 2013), EMBASE (1980 to 2013 week 4) and LILACS (1982 to 2007). We searched several databases for ongoing trials. We checked the conference proceedings of the Interscience Conference of Antimicrobial Agents and Chemotherapy (ICAAC) (1995 to 2007), and all references of included studies and major reviews were scanned. Randomised controlled trials (RCTs) comparing oral antibiotic(s) to intravenous antibiotic(s) for the treatment of neutropenic cancer patients with fever. The comparison between the two could be started initially (initial oral) or following an initial course of intravenous antibiotic treatment (sequential). Two review authors independently assessed trial eligibility and methodological quality and extracted data. Data concerning mortality, treatment failures and adverse events were extracted from the included studies assuming an 'intention-to-treat' basis for the outcome measures whenever possible. Risk ratios (RR) with 95% confidence intervals (CI) were estimated for dichotomous data. Risk of bias assessment was also made in line with methodology of The Cochrane Collaboration. Twenty-two trials (3142 episodes in 2372 patients) were included in the analyses. The mortality rate was similar when comparing oral to intravenous antibiotic treatment (RR 0.95, 95% CI 0.54 to 1.68, 9 trials, 1392 patients, median mortality 0, range 0% to 8.8%). Treatment failure rates were also similar (RR 0.96, 95% CI 0.86 to 1.06, all trials). No significant heterogeneity was shown for all comparisons but adverse events. The effect was stable in a wide range of patients. Quinolones alone or combined with another antibiotic were used with comparable results. Adverse reactions, mostly gastrointestinal, were more common with oral antibiotics. Based on the present data, oral treatment is an acceptable alternative to intravenous antibiotic treatment in febrile neutropenic cancer patients (excluding patients with acute leukaemia) who are haemodynamically stable, without organ failure, and do not have pneumonia, infection of a central line or a severe soft-tissue infection. The wide CI for mortality allows the present use of oral treatment in groups of patients with an expected low risk for mortality, and further research should be aimed at clarifying the definition of low risk patients.

Beta-lactam versus beta-lactam-aminoglycoside combination therapy in cancer patients with neutropenia.

Continued controversy surrounds the optimal empirical treatment for febrile neutropenia. New broad-spectrum beta-lactams have been introduced as single treatment, and classically, a combination of a beta-lactam with an aminoglycoside has been used. To compare beta-lactam monotherapy versus beta-lactam-aminoglycoside combination therapy for cancer patients with fever and neutropenia. The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 7, 2012), LILACS (August 2012), MEDLINE and EMBASE (August 2012) and the Database of Abstracts of Reviews of Effects (DARE) (Issue 3, 2012). We scanned references of all included studies and pertinent reviews and contacted the first author of each included trial, as well as the pharmaceutical companies. Randomised controlled trials (RCTs) comparing any beta-lactam antibiotic monotherapy with any combination of a beta-lactam and an aminoglycoside antibiotic, for the initial empirical treatment of febrile neutropenic cancer patients. All cause mortality was the primary outcome assessed. Data concerning all cause mortality, infection related mortality, treatment failure (including treatment modifications), super-infections, adverse effects and study quality measures were extracted independently by two review authors. Risk ratios (RRs) with their 95% confidence intervals (CIs) were estimated. Outcomes were extracted by intention-to-treat (ITT) analysis whenever possible. Individual domains of risk of bias were examined through sensitivity analyses. Published data were complemented by correspondence with authors. Seventy-one trials published between 1983 and 2012 were included. All cause mortality was lower with monotherapy (RR 0.87, 95% CI 0.75 to 1.02, without statistical significance). Results were similar for trials comparing the same beta-lactam in both trial arms (11 trials, 1718 episodes; RR 0.74, 95% CI 0.53 to 1.06) and for trials comparing different beta-lactams－usually a broad-spectrum beta-lactam compared with a narrower-spectrum beta-lactam combined with an aminoglycoside (33 trials, 5468 episodes; RR 0.91, 95% CI 0.77 to 1.09). Infection related mortality was significantly lower with monotherapy (RR 0.80, 95% CI 0.64 to 0.99). Treatment failure was significantly more frequent with monotherapy in trials comparing the same beta-lactam (16 trials, 2833 episodes; RR 1.11, 95% CI 1.02 to 1.20), and was significantly more frequent with combination therapy in trials comparing different beta-lactams (55 trials, 7736 episodes; RR 0.92, 95% CI 0.88 to 0.97). Bacterial super-infections occurred with equal frequency, and fungal super-infections were more common with combination therapy. Adverse events were more frequent with combination therapy (numbers needed to harm 4; 95% CI 4 to 5). Specifically, the difference with regard to nephrotoxicity was highly significant. Adequate trial methods were associated with a larger effect estimate for mortality and smaller effect estimates for failure. Nearly all trials were open-label. No correlation was noted between mortality and failure rates and these trials. Beta-lactam monotherapy is advantageous compared with beta-lactam-aminoglycoside combination therapy with regard to survival, adverse events and fungal super-infections. Treatment failure should not be regarded as the primary outcome in open-label trials, as it reflects mainly treatment modifications.

A Population-Based Study of Bacterial Spectrum in Febrile Neutropenic Patients

Background: Because of great concerns about mortality and morbidity of infection in febrile neutropenic patients, the appropriate empirical antibiotic should be started immediately. Although there are established guidelines for the use of empirical therapy, local microbiological pattern and antibiotic susceptibility should be considered. Objectives: The current study aimed to identify the etiological pathogens in febrile neutropenic cancer patients in Isfahan, Iran. Patients and Methods: This single-centre population-based study was conducted on 81 febrile neutropenic patients referring to Sayed-Al-Shohada hospital, the only referral malignant care center in Isfahan, Iran. Demographic data, duration and kind of malignancy, duration from last chemotherapy, duration of fever, and also physical exam were recorded for each patient. Moreover, procalcitonin, CRP, ESR, white blood cells, hemoglobin, platelet, and absolute neutrophil count were measured. BACTEC and E-test were used for blood culturing and determining the antibiotic susceptibility. Results: Out of 81 participants, 28.4% had positive blood cultures which mostly consisted of Gram-positive microorganisms. In addition, Staphylococcus epidermidis was the most isolated Gram positive bacteria (39.1%). ESR, CRP, and procalcitonin were significantly higher in patients with positive blood culture. The risk of infection increased with raise in duration of hospital stay, catheterization, increased pulse rate, increased oral temperature, low level of oxygen saturation, decreased systolic blood pressure, and low absolute neutrophile count. However, in this case, no relationship was found among the patients’ age, diastolic blood pressure, respiratory rate, duration of diagnosis, duration from last chemotherapy, duration of fever, white blood cells, hemoglobin, platelet, and finally the type of malignancies. Conclusions: It was concluded that Gram-positive bacteria were more prevalent as a cause of infection in the patients with malignancy and the most common pathogen was S. epidermidis. Larger studies are needed to determine the bacterial susceptibility of this center.

The Multinational Association for Supportive Care in Cancer (MASCC) risk index score: 10 years of use for identifying low-risk febrile neutropenic cancer patients

The Multinational Association for Supportive Care in Cancer risk index score developed, through a multinational collaboration, was published in 2000 with the aim to identify patients with chemotherapy-induced febrile neutropenia at low risk of serious medical complication development. It has been endorsed as a reliable tool since 2002 by Infectious Diseases Society of America. Ten years after, we thought worth to review its use, its characteristics in the external validations that occurred after the initial publication and also to review how the recognition of a group of patients at low risk has changed the management of febrile neutropenia. We also raise the issue of identification of high-risk patients that remains a challenge today.

Management of febrile neutropenia in the era of bacterial resistance.

Managing cancer patients with fever and neutropenia must be considered as a medical emergency since any delay in initiating appropriate empirical antibacterial therapy may result in high rates of mortality and morbidity. Emerging antibacterial resistance in bacterial pathogens infecting febrile neutropenic patients complicates management, and choosing the type of empirical antimicrobial therapy has become a challenge. To further complicate the decision process, not all neutropenic patients are in same category of susceptibility to develop severe infection. While low-risk patients may be treated with oral antibiotics in the outpatient setting, high-risk patients usually need to be admitted to hospital and receive parenteral broad-spectrum antibiotics until the neutrophil levels recover. These strategies have recently been addressed in two international guidelines from the Infectious Diseases Society of America (IDSA) and the European Conference on Infections in Leukaemia (ECIL). This review gives a brief overview of current antimicrobial resistance problems and their effects in febrile neutropenic cancer patients by summarizing the suggestions from the IDSA and ECIL guidelines.

There should be no ESKAPE for febrile neutropenic cancer patients: the dearth of effective antibacterial drugs threatens anticancer efficacy

The success of modern anticancer treatment is a composite function of enhanced efficacy of surgical, radiation and systemic treatment strategies and of our collective clinical abilities in supporting patients through the perils of their cancer journeys. Despite the widespread availability of antibacterial therapies, the threat of community- or healthcare facility-acquired bacterial infection remains a constant risk to patients during this journey. The rising prevalence of colonization by multidrug-resistant (MDR) bacteria in the population, acquired through exposure from endemic environments, antimicrobial stewardship and infection prevention and control strategies notwithstanding, increases the likelihood that such organisms may be the cause of cancer treatment-related infection and the likelihood of antibacterial treatment failure. The high mortality associated with invasive MDR bacterial infection increases the likelihood that many patients may not survive long enough to reap the benefits of enhanced anticancer treatments, thus threatening the societal investment in the cancer journey. Since cancer care providers arguably no longer have, and are unlikely to have in the foreseeable future, the antibacterial tools to reliably rescue patients from harm's way, the difficult ethical debate over the risks and benefits of anticancer treatments must now be reopened.

Outcome of Febrile Neutropenic Patients on Granulocyte Colony Stimulating Factor in a Tertiary Care Hospital

Febrile neutropenia is a relatively frequent event in cancer patients treated with chemotherapy and improvement in absolute neutrophil count (ANC) has been linked directly to improved outcome. Evaluation of granulocyte colony stimulating factors (GCSFs) for treatment has shown reduced incidences of episodes of prolonged neutropenia and protracted hospitalization. To determine absolute neutrophil counts with GCSF in febrile neutropenic cancer patients admitted to a tertiary care centre and to co-relate the improvement in ANC with mortality and hospital discharge. A prospective cross sectional study was carried at an oncology ward at Aga Khan University hospital from January 2010 to June 2011. All adult patients who were admitted and treated with GCSF for chemotherapy induced febrile neutropenia were included. Multivariable regression was conducted to identify the factors related with poor outcomes. A total of 131 patients with febrile neutropenia were identified with mean age of 43.2 (18-85) years, 79 (60%) being ≤ 50. Seventy-five (57%) had solid tumors and 56 (43%) hematological malignancies, including lymphoma. Fifty seven (43.5%) had an ANC less 100 cells/mm(3), 34 (26%) one between 100-300 cells/mm(3) and 40 (31%) an ANC greater than 300 cells/mm(3). Thirty (23%) patients showed ANC recovery in 1-3 days, and 74(56%) within 4-7 days. Thirteen (10%) patients showed no recovery. The overall mortality was 18 (13.7%) patients. The mean time for ANC recovery seen in hematological malignancies was 6.34 days whereas for solid tumors it was 4.88 days. Patients with ANC <100 cells/mm(3) were more likely to die than patients with ANC >300 cells/mm(3) by a factor of 4.3. Similarly patients >50 years of age were 2.7 times more likely to die than younger patients. Our study demonstrated that use of GCSF, in addition to intravenous antibiotics, in treatment of patients with chemotherapy induced febrile neutropenia accelerates neutrophil recovery, and shortens antibiotic therapy and hospitalization. We propose to risk classify the patients at the time of admission to evaluate the cost effectiveness of this approach in a resource constrained setup.

The Mild Inflammatory Response in Febrile Neutropenic Lymphoma Patients with Low Risk of Complications is More Pronounced in Patients Receiving Tobramycin Once Daily Compared with Three Times Daily

We evaluated inflammatory markers in febrile neutropenic lymphoma patients undergoing high-dose chemotherapy with autologous stem cell support. Based on MASCC scores, our patients had a low risk of serious complications and a perspective of a benign initial clinical course of the febrile neutropenia. We also studied the impact of tobramycin given once versus three times daily on these immune markers. Sixty-one patients participating in a Norwegian multicentre prospective randomized clinical trial, comparing tobramycin once daily versus three times daily, given with penicillin G to febrile neutropenic patients, constituted a clinically homogenous group. Four patients had bacteraemia, all isolates being Gram-positive. Thirty-two patients received tobramycin once daily, and 29 patients received tobramycin three times daily. Blood samples were taken at the onset of febrile neutropenia and 1-2 days later. All samples were frozen at -70 °C and analysed at the end of the clinical trial for C-reactive protein (CRP), procalcitonin (PCT), complement activation products, mannose-binding lectin (MBL) and 17 cytokines. We found a mild proinflammatory response in this series of patients. CRP was non-specifically elevated. Ten patients with decreased MBL levels showed the same mild clinical and proinflammatory response. Patients receiving tobramycin once daily showed a more pronounced proinflammatory response compared with patients receiving tobramycin three times daily. Overall, febrile neutropenic cancer patients with a benign clinical course show a mild proinflammatory immune response.

Tigecycline plus Standard Therapy is More Effective than Standard Therapy Alone for Treating Infections in Febrile Neutropenic Cancer Patients

Tigecycline, first in a new class of glycylcyclines, in combination with piperacillin/tazobactam, is effective, safe, and well tolerated in high-risk febrile neutropenic oncohematologic patients. This combination therapy may aid in reducing the increase and extensive use of carbapenems, which have been associated with an increase in multidrug-resistant bacteria.

Diagnosis and Antimicrobial Therapy of Lung Infiltrates in Febrile Neutropenic Cancer Patients

Pulmonary infiltrates develop in up to 25% of febrile neutropenic patients and are frequently refractory to broad-spectrum antibacterial therapy. Etiologically, Aspergillus spp., Pneumocystis jiroveci, multi-resistant Gram-negative rods as well as mycobacteria and respiratory viruses may be involved. Taking into account the predominant role of fungal pathogens, typically without microbiological proof, prompt addition of mold-active systemic antifungal therapy improves clinical outcome, while other microorganisms should typically be targeted based upon microbiological test results only. Microbial isolates from blood cultures, bronchoalveolar lavage or respiratory secretions must be critically interpreted with respect to their etiological relevance for pulmonary infiltrates. Non-culture based diagnostic procedures to detect circulating antigens such as galactomannan or 1,3-beta-D-glucan, or PCR techniques to amplify DNA from blood, bronchoalveolar lavage or tissue specimens, may facilitate the diagnosis. For pre-emptive antifungal treatment, voriconazole or liposomal amphotericin B are preferred. Antifungal treatment should be continued for at least 14days before non-response and treatment modification are considered. Primary choice for treatment of Pneumocystis pneumonia remains high-dose trimethoprim-sulfamethoxazole, while cytomegalovirus pneumonia is treated with ganciclovir in the majority of patients affected.

Bloodstream infections and mortality-related factors in febrile neutropenic cancer patients

SummaryBackgroundWe performed a prospective observational cohort study to evaluate the causative bacteria and to identify risk factors for mortality in febrile neutropenic (FN) patients with blood stream infection (BSI).Material/MethodsWe conducted a prospective data collection on all patients with bacteremia or fungemia. The patients were assigned into low-risk and high-risk groups in accordance with the Multinational Association for Supportive Care in Cancer (MASCC) Risk Index.ResultsThroughout the study period, the patients developed 420 FN episodes. Out of 420 episodes, only 90 (21.4%) were found to have bloodstream infection. The mean age of the patients was 45.6±18.4 years and 55.6% of the patients were male. A total of 98 isolates were recovered from the cases of BSI. Coagulase-negative Staphylococcus spp (CoNS) were the most common isolates overall (33.7%). There was a significant increase in the rate of gram-negative bacteria throughout the study period (p=0.028). Overall mortality was 33%. Multivariate analyses showed that MASCC risk scores (p=0.0001, OR=15.1, CI%95 4.5–50.7), ICU wards (p=0.0002, OR= 8.6, Cl%95 1.101–68,157) and CoNS (p=0.004, OR=12.12, CI%95 2.3–64.7) were independent risk factors associated with mortality. BSI due to CoNS was associated with lower mortality; however, MASCC high risk score and ICU stay were associated with higher mortality.ConclusionsThe MASCC risk-index score and emergence of CoNS in positive blood cultures are valuable tools in the management of FN.

Clinical outcome of catheter salvage in neutropenic cancer patients with catheter-related infection

Catheter-related infections (CRI) cause significant morbidity and mortality in cancer patients, particularly during episodes of chemotherapy-induced neutropenia. This study was performed to evaluate clinical features and outcomes of CRI in neutropenic cancer patients. We retrospectively analyzed clinical characteristics and outcome of febrile neutropenic cancer patients with CRI who visited the emergency department from January 1996 to June 2007. A total of 51 neutropenic cancer patients with CRI were identified and 53 organisms were isolated from culture specimens. The mean ± standard deviation patient age was 50 ± 15 y and the most common underlying disease was lymphoma (n = 27, 53%). Gram-positive organisms accounted for 77% of all isolated pathogens (41/53). Initial catheter salvage was attempted in 38 episodes of CRI, of which 20 were successful. In the current study the overall success rate of catheter salvage attempts was 52.6%. The failure rate of catheter salvage was significantly higher in CRI caused by Gram-negative pathogens than by Gram-positive pathogens. Although catheter salvage should be cautiously attempted for cancer patients with CRI, it might not be a treatment option for neutropenic cancer patients with CRI caused by Gram-negative bacteria.

Predicting febrile neutropenic patients at low risk using the MASCC score: does bacteremia matter?

Febrile neutropenic cancer patients represent a heterogeneous population with a limited proportion at risk of serious medical complications. The Multinational Association for Supportive Care in Cancer (MASCC) score has been developed and validated for identifying low-risk patients at the onset of febrile neutropenia. Since bacteremia, although not documented at baseline, is a predictor of pejorative outcome, the purpose of this study was to investigate the possible interaction between the MASCC score and bacteremic status and to assess whether, assuming that bacteremic status could be predicted at onset of febrile neutropenia, adding bacteremia as a covariate in a risk model would improve the accuracy of low-risk patients identification. Two consecutive multicentric observational studies were carried out from 1994 till 2005 involving 2,142 febrile neutropenic patients. The study data bases were retrospectively used for the present analysis. A predictive value was found for the MASCC score in all strata obtained by stratification for the bacteremic status with odds ratios for successful outcome being, in patients with a score ≥21, respectively, 6.06 (95%CI: 4.51-8.15), 3.42 (95%CI: 1.95-5.98), and 6.04 (95%CI: 3.01-12.09) in patients without bacteremia, gram-positive bacteremia, and gram-negative bacteremia. No interaction between the MASCC score and the bacteremic status was present. A clinical prediction rule integrating the MASCC score and the bacteremic status was not helpful in improving the identification of low-risk patients. This rule may then be used in a general population of patients with febrile neutropenia without having concerns for a lower predictive value in bacteremic patients. Our results suggest that the knowledge, provided we could find a model to predict it at fever onset, of a bacteremic etiology of the fever would be of little additional value to the MASCC score when attempting to identify low-risk patients.

Outcome of attempted Hickman catheter salvage in febrile neutropenic cancer patients with Staphylococcus aureus bacteremia

There are limited data on outcomes of Hickman catheter salvage associated with Staphylococcus aureus bacteremia (SAB) in neutropenic cancer patients. We evaluated the outcome of attempted Hickman catheter salvage in these patients who were not given antibiotic lock therapy. Outcomes were retrospectively analyzed in all neutropenic cancer patients with Hickman catheter-related SAB over a 12-year period (56 episodes in 54 patients). Salvage attempts were defined as cases where the catheter was still in place 3 days after initial bacteremia. Salvage attempts were considered successful if catheter was still in place 12 weeks later without recurrent SAB or death. Of the 56 episodes, catheters were immediately removed in eight (14%), and catheter salvage was attempted in 48 (86%). Of these 48 episodes, attempted salvage was successful in 29 (60%) and failed in 14 (29%). Outcome of attempted salvage was indeterminate in five (11%) episodes. In univariate analysis, presence of external signs of catheter infection (p = 0.03), positive follow-up blood culture (p = 0.03), and methicillin resistance (p = 0.04) were significantly associated with catheter salvage failure. In multivariate analysis, presence of external signs of catheter infection (OR 12.0; p = 0.04) and methicillin resistance (OR 5.1; p = 0.04) were independently associated with catheter savage failure. In conclusion, attempted catheter salvage without antibiotic lock therapy was successful in 60% of the patients with Hickman catheter-related SAB. External signs of catheter infection and methicillin resistance were independent risk factors for catheter salvage failure.