New evidence shows that antibiotic prophylaxis in neutropenic patients reduces mortality, febrile episodes, and bacterial infections. For patients with acute leukemia or those who undergo bone marrow transplantation, prophylaxis with fluoroquinolones diminished the risk of death from any cause by 33% (95% confidence interval [95% CI], 2-54%). Thus, 55 patients who have acute leukemia or who undergo bone marrow transplantation must receive prophylaxis to prevent 1 death. In 4 studies that included patients with solid tumors or lymphoma, prophylaxis reduced the rate of death during the first month (relative risk, 0.51; 95% CI, 0.27-0.97), and 82 patients had to receive prophylaxis to prevent 1 death. The main argument brought against prophylaxis is the induction of resistance. Patients who received prophylaxis did not experience more infections caused by resistant strains than patients in the control group. The recent GIMEMA study was conducted in a population with a nearly 50% resistance to fluoroquinolones in all pathogens and 20% resistance in gram-negative isolates, thus indicating that prophylaxis should be offered in settings with similar or less resistance. Prophylaxis with fluoroquinolones was efficacious in reducing infections caused by gram-positive bacteria. Patients who are treated for acute leukemia should be offered prophylaxis with ciprofloxacin or levofloxacin. Prophylaxis to cover the expected period of neutropenia may be considered for the first cycle of treatment in patients with solid tumors or lymphoma who regularly receive regimens that cause severe neutropenia. Excessive local levels of resistance to fluoroquinolones or high local incidence of infections caused by Clostridium difficile and related to fluoroquinolones should prompt a reconsideration of this policy.

A sample of 100 consecutive febrile neutropenic episodes in cancer patients in Kuwait was studied. Acute leukaemias (44%) and lymphomas (29%) were the most frequent underlying cancers; 21 bacteraemis (gram-positive 10, gram-negative 9, polymicrobial 2) were encountered. Staphylococcous epidermidis and Escherichia coli were the commonest organisms. Urinary tract infection occurred in 30% of the microbiologically documented cases. A total of 84 episodes responded to therapy and 9 of the 14 deaths were secondary to infection.

OBJECTIVE: To determine the incidence of nosocomial infections (NIs) and fever of unknown origin among adult hematology-oncology patients. DESIGN: Prospective surveillance study. SETTING: The 18-bed hematology-oncology unit at the University Hospital Bonn, Bonn, Germany. PATIENTS: All hematology-oncology patients admitted during a total of 8 months in 1998 and 1999. METHODS: Standardized surveillance system based on the Centers for Disease Control and Prevention's National Nosocomial Infections Surveillance system. Rates of NI and fever of unknown origin were calculated for patient-days and patient-days at risk (ie, days with neutropenia of < 500/mm3 or leukopenia of < 1,000/mm3). RESULTS: Of 116 patients hospitalized for a total of 4,002 days (172 admissions; mean length of stay, 25.2 days), 32 (27.6%) had a total of 44 documented NIs (19 bloodstream infections, 15 pneumonias, 7 urinary tract infections, and 3 others). In addition, 33 fevers of unknown origin were documented in 28 patients. No patient had thrush while receiving antifungal prophylaxis. The overall rates for NI and fever of unknown origin were 11.0 and 8.2 per 1,000 patient-days (25.3 and 15.4 per 1,000 patient-days at risk), respectively. The risks for NI and fever of unknown origin were significantly higher during neutropenic days, with 34 (77.3%) of the 44 NIs and 22 (66.7%) of the 33 fevers of unknown origin occurring during 1,345 patient-days at risk. CONCLUSIONS: Prospective surveillance for NIs on hematology-oncology units should include fever of unknown origin as the single most common and clinically important entity. For a meaningful comparison of surveillance data for hematology-oncology patients, the reported infection rates should include rates based on days with neutropenia, for which days with leukopenia could serve as a surrogate marker under routine conditions.

The relevancy of the urinary tract as a source of infection during febrile neutropenia is not known. The authors sought to determine the frequency of urinary tract infections (UTIs) in pediatric cancer patients with febrile neutropenia. Urine was collected from a mid-stream void before the administration of antibiotics. Demographic, clinical, and laboratory data were collected. The frequency of UTI and usefulness of urinalysis and localizing signs in predicting UTI in pediatric cancer patients with fever and neutropenia were determined. Forty-five patients had 58 febrile neutropenic episodes eligible for study participation. No patient presented with localizing signs. The urinalysis was negative in 53 episodes and positive in 5 episodes. Four patients had 5 UTIs. The frequency of UTI was 8.6% (5 of 58 febrile neutropenia episodes). Four patients had bacteremia, none of whom had a UTI. The sensitivity, specificity, and negative predictive value of urinalysis was 40%, 94%, and 94%, respectively, and for localizing signs was undefined, 100%, and 91%, respectively. UTI is as common as bacteremia in the current pediatric cancer patients with fever and neutropenia. Urinalysis and urine culture should be obtained routinely as part of the diagnostic evaluation of patients with fever and neutropenia.

The increased frequency of infections caused by Gram-positive microorganisms, and the expansion of resistant pathogens resulting from institutional therapeutic practices, represent some of the emerging issues of empirical drug treatment of cancer patients with febrile neutropenia. However, the therapeutic strategies for the treatment of these patients have progressed remarkably over the last decade. Individual therapy in the light of the principal clinical features (in particular, the degree and estimated duration of neutropenia, as well the presence of other potential factors favouring infection such as long-standing intravascular catheters) and local microbial ecology have emerged as the leading concepts. Empirical drug monotherapy has been recognised as a feasible alternative to combination therapy, at least in selected low-risk patients. The indiscriminate use of empirical glycopeptides should be discouraged to prevent the emergence of resistant bacteria, especially in centres where methicillin-resistant staphylococci have not yet become a major issue. Empirical antifungal therapy with amphotericin B is still essential for a successful outcome in case of fever persistence or recurrence. Finally, selected febrile neutropenic patients who exhibit a better prognosis can be handled on an outpatient basis. The prophylactic use of haemopoietic growth factors has been shown to augment cost savings substantially in the management of neutropenic patients via a reduction in the duration and severity of the neutropenia, as well as infectious complications. Although data from economic analyses are not yet available, some cost-containment strategies such as outpatient treatment, monotherapy, and use of more convenient antibiotic combinations may lead to a reduction of therapy expenditures for febrile episodes in these patients.

BACKGROUND: This study was carried out to assess the isolation rate of bacterial and fungal causative agents in Mexican neutropenic adults with hematological neoplasia. METHODS: A prospective observational survey involving 120 consecutive episodes of febrile neutropenia during 1 year was carried out. These episodes were observed in 630 patients discharged with diagnoses of leukemia or lymphoma, or after bone-marrow transplantation. RESULTS: At least one pathogen was isolated in 42 of 120 episodes (35%), and was present in 39 patients with acute myeloid leukemia (AML) (43%), acute lymphoblastic leukemia (ALL) (23%), and in patients who underwent bone-marrow transplantation (20%). Primary bacteremia was the most frequent cause of fever (24 episodes, 57%), followed by intravascular device-related infections (5 episodes, 17%), and soft-tissue infections (5 episodes, 15%). Escherichia coli (33%) was the most frequently isolated agent of primary bacteremia, followed by coagulase-negative Staphylococcus (29%), and Klebsiella oxytoca (16%). Fungal infection was responsible for five events (4%): two episodes of pneumonia (Penicillium marneffei and Aspergillus fumigatus, one event each); two cases of fungemia, one due to Candida tropicalis and one to Rhodotorula gluttinis, and one cryptococcal meningitis event. CONCLUSIONS: The isolation rate, approximately 30%, was in accordance with previous reports; similar percentages of Gram-positive and Gram-negative isolates were found. A remarkably low rate of viridans group streptococci and fungal agents was observed, despite the fact that neutropenia is the main risk factor for infection due to these agents. Studies reporting local microbiological findings are necessary because they support an antibiotic choice for prophylaxis or therapy more accurately than reports from other areas.

This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia.
Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving.
What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens.
Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care-associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.

OBJECTIVE: To describe the distribution and temporal trends of the quality and strength of evidence supporting recommendations in the Infectious Diseases Society of America (IDSA) clinical practice guidelines. METHODS: Guidelines either issued or endorsed by IDSA from March 1994 to July 2009 were evaluated using the IDSA-US Public Health Service Grading System. In this system, the letters A-E signify the strength of the recommendation, and numerals I-III indicate the quality of evidence supporting these recommendations. The distribution of the guideline recommendations among strength of recommendation and quality of evidence classes was quantified. Temporal changes between the first and current guideline version were evaluated. RESULTS: Approximately one-half (median, 50.0%; interquartile range [IQR], 38.1%-58.6%) of the recommendations in the current guidelines are supported by level III evidence (derived from expert opinion). Evidence from observational studies (level II) supports 31% of recommendations (median, 30.9%; IQR, 23.3%-43.2%), whereas evidence based on >/= 1 randomized clinical trial (level I) constitutes 16% of the recommendations (median, 15.8%; IQR, 5.8%-28.3%). The strength of recommendation was mainly distributed among classes A (median, 41.5%; IQR, 28.7%-55.6%) and B (median, 40.3%; IQR, 27.1%-47.9%). Among guidelines with >/= 1 revised version, the recommendations moved proportionately toward more level I evidence (+12.4%). Consequently, there was a proportional increase in class A recommendations (+11.1%) with a decrease in class C recommendations (-23.5%). CONCLUSIONS: The IDSA guideline recommendations are primarily based on low-quality evidence derived from nonrandomized studies or expert opinion. These findings highlight the limitations of current clinical infectious diseases research that can provide high-quality evidence. There is an urgent need to support high-quality research to strengthen the evidence available for the formulation of guidelines.

Background: Clinical practice guidelines are developed to assist in patient care. Physicians may assume that following such guidelines means practicing evidence-based medicine. However, the quality of supporting literature can vary greatly.
Methods: We analyzed the strength of recommendation and overall quality of evidence behind 41 Infectious Diseases Society of America (IDSA) guidelines released between January 1994 and May 2010. Individual recommendations were classified based on their strength of recommendation (levels A through C) and quality of evidence (levels I through III). Guidelines not following this format were excluded from further analysis. Evolution of IDSA guidelines was assessed by comparing 5 recently updated guidelines with their earlier versions.
Results: In the 41 analyzed guidelines, 4218 individual recommendations were found and tabulated. Fourteen percent of the recommendations were classified as level I, 31% as level II, and 55% as level III evidence. Among class A recommendations (good evidence for support), 23% were level I (>= 1 randomized controlled trial) and 37% were based on expert opinion only (level III). Updated guidelines expanded the absolute number of individual recommendations substantially. However, few were due to a sizable increase in level I evidence; most additional recommendations had level II and III evidence.
Conclusions: More than half of the current recommendations of the IDSA are based on level III evidence only. Until more data from well-designed controlled clinical trials become available, physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions. Arch Intern Med. 2011;171(1):18-22

To investigate the diagnostic significance of a normal urine sediment in the work-up for fever of unknown origin in neutropenia. Urinary tract infection was defined as >= 10(5) urinary pathogens in the absence of another focus. Pyuria was found in only 1/23 neutropenic episodes compared to 21/31 in controls (P < 0.0001). Pediatr Blood Cancer 2011;56:868-870. (C) 2010 Wiley-Liss, Inc.

BACKGROUND: Early identification of children with cancer at risk for death during a febrile neutropenic (FN) episode may increase their possibility for survival. Our aim was to identify at the time of admission, clinical and laboratory variables differing significantly among children who survived or died during a FN episode. METHODS: In a prospective, multicenter study, children admitted with a high-risk FN episode were uniformly evaluated at enrollment and managed according to a national consensus protocol. Medical charts of children who died were evaluated to determine whether the death could be associated with an infection. Admission clinical and laboratory variables significantly associated with death were identified. RESULTS: A total of 393 (70%) of 561 FN episodes evaluated from June 2004 to December 2005 were classified as high risk for invasive bacterial infection, of which 14 (3.6%) resulted in an infectious-related death. Deaths occurred from 2 to 27 days after admission, and most dying children were admitted with relapse of acute lymphocytic leukemia (36%), hypotension (71%), and a diagnosis of sepsis (79%), compared with surviving children (16%, 20%, and 5% respectively, P < 0.001). Children who died were admitted with lower absolute neutrophil count (P < 0.001) and absolute monocytes count levels (P = 0.008), higher blood urinary nitrogen (P = 0.03) and C-reactive protein values (P < 0.001), and had more positive cultures (79% versus 32%, P = 0.008). CONCLUSIONS: We identified early clinical and laboratory findings significantly associated with death occurring at a later stage. Routine evaluation of these variables may prove to be useful in the early identification of children with a high-risk FN episode at risk for death.

PURPOSE: There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital. METHODS: All haematology inpatients over a 5-year period (2011-2015) were retrospectively reviewed for episodes of FN (neutrophil count < 0.5 x 10(9)/L and fever > 37.5 degrees C). For each episode, demographic data, urinary tract symptoms and signs (absence of which was termed 'asymptomatic'), urinalysis and urine culture results, antibiotic therapy and duration, and patient outcomes were collected. A urine culture was considered positive if > 10(5) colony forming units (CFU)/L were detected. Empiric antibiotic therapy for FN consisted of intravenous piperacillin/tazobactam in stable patients, with the addition of vancomycin and a single dose of gentamicin if systemically compromised. RESULTS: Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p < 0.0001). A change in antibiotic management due a positive urine culture occurred in only 5 episodes (1.4%): 3 of 48 (6.3%) symptomatic and 2 of 314 (0.6%) asymptomatic episodes respectively (RR = 9.8, p = 0.01). CONCLUSION: Routine urine cultures in FN patients without urinary symptoms who are already receiving protocolised broad spectrum antibiotics rarely impact subsequent antibiotic management.

Asymptomatic bacteriuria, also called asymptomatic urinary infection, is a common finding in healthy women, and in women and men with abnormalities of the genitourinary tract. The characterization and introduction of the quantitative urine culture in the 1950s first allowed the reliable recognition of asymptomatic bacteriuria. The observations that a substantial proportion of patients with chronic pyelonephritis at autopsy had no history of symptomatic urinary infection, and the high frequency of pyelonephritis observed in pregnant women with untreated asymptomatic bacteriuria, supported a conclusion that asymptomatic bacteriuria was harmful. Subsequent screening and long term follow-up programs for asymptomatic bacteriuria in schoolgirls and women reported an increased frequency of symptomatic urinary tract infection for subjects with asymptomatic bacteriuria, but no increased morbidity from renal failure or hypertension, or increased mortality. Treatment of asymptomatic bacteriuria did not decrease the frequency of symptomatic infection. Prospective, randomized, comparative trials enrolling premenopausal women, children, elderly populations, patients with long term catheters, and diabetic patients consistently report no benefits with antimicrobial treatment of asymptomatic bacteriuria, and some evidence of harm. Several studies have also reported that antimicrobial treatment of asymptomatic bacteriuria increases the short term risk of pyelonephritis. Current investigations are exploring the potential therapeutic intervention of establishing asymptomatic bacteriuria with an avirulent Escherichia coli strain to prevent symptomatic urinary tract infection for selected patients.

A complete urinalysis includes physical, chemical, and microscopic examinations. Midstream clean collection is acceptable in most situations, but the specimen should be examined within two hours of collection. Cloudy urine often is a result of precipitated phosphate crystals in alkaline urine, but pyuria also can be the cause. A strong odor may be the result of a concentrated specimen rather than a urinary tract infection. Dipstick urinalysis is convenient, but false-positive and false-negative results can occur. Specific gravity provides a reliable assessment of the patient's hydration status. Microhematuria has a range of causes, from benign to life threatening. Glomerular, renal, and urologic causes of microhematuria often can be differentiated by other elements of the urinalysis. Although transient proteinuria typically is a benign condition, persistent proteinuria requires further work-up. Uncomplicated urinary tract infections diagnosed by positive leukocyte esterase and nitrite tests can be treated without culture.

Neutropaenia and immunosuppression place children on treatment for malignancies at a high risk for infections. We undertook to determine the prevalence of urinary tract infection (UTI) in children on treatment for cancer at the Kenyatta National Teaching and Referral hospital. With the understanding that many laboratories in the rural areas of the country lack appropriate facilities for confirmation of UTI, it was also important to evaluate simple and inexpensive screening methods against a

Most uncomplicated urinary tract infections occur in women who are sexually active, with far fewer cases occurring in older women, those who are pregnant, and in men. Although the incidence of urinary tract infection has not changed substantially over the last 10 years, the diagnostic criteria, bacterial resistance patterns, and recommended treatment have changed. Escherichia coli is the leading cause of urinary tract infections, followed by Staphylococcus saprophyticus. Trimethoprim-sulfamethoxazole has been the standard therapy for urinary tract infection; however, E. coli is becoming increasingly resistant to medications. Many experts support using ciprofloxacin as an alternative and, in some cases, as the preferred first-line agent. However, others caution that widespread use of ciprofloxacin will promote increased resistance.

Objectives: There are a substantial number of unnecessary urine culture requests. We aimed to investigate whether urine dipstick and microscopy results could accurately rule out urinary tract infection (UTI) without urine culture.
Design and methods: The study included a total of 32 998 patients (11 928 men and 21 070 women, mean age: 39 +/- 32 years) with a preliminary diagnosis of UTI and both urinalysis and urinary culture were requested. All urine cultures were retrospectively reviewed; association of culture positivity with a positive urinalysis result for leukocyte esterase (LE) and nitrite in chemical analysis and pyuria (WBC) and bacteriuria in microscopy was determined. Diagnostic performance of urinalysis parameters for detection of UTI was evaluated.
Results: In total, 758 (2.3%) patients were positive by urine culture. Out of these culture positive samples, ratios of positive dipstick results for LE and nitrite were 71.0% (n = 538) and 17.7% (n = 134), respectively. The positive microscopy results for WBC and bacteria were 68.2% (n = 517) and 78.8% (n = 597), respectively. Negative predictive values for LE, nitrite, bacteriuria and WBC were very close to 100%.
Conclusions: Most of the samples have no or insignificant bacterial growth. Urine dipstick and microscopy can accurately rule out UTI. Automated urinalysis is a practicable and faster screening test which may prevent unnecessary culture requests for majority of patients. (c) 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc.