Predictors of Diagnostic Contributions and Spontaneous Remission of Symptoms Associated with Positron Emission Tomography with Fluorine-18-Fluorodeoxy Glucose Combined with Computed Tomography in Classic Fever or Inflammation of Unknown Origin: a Retrospective Study.

BACKGROUND: In patients with fever or inflammation of unknown origin (fever of unknown origin [FUO] or inflammation of unknown origin [IUO], respectively), expert consensus recommends the use of positron emission tomography with fluorine-18-fluorodeoxy glucose combined with computed tomography (FDG-PET/CT) when standard work-up fails to identify diagnostic clues. However, the clinical variables associated with successful localization of the cause by FDG-PET/CT remain uncertain. Moreover, the long-term outcomes of patients with unexplained FUO or IUO after negative FDG-PET/CT results are unknown. Therefore, we assessed predictors of successful diagnosis of FUO or IUO caused by FDG-PET/CT and associations of spontaneous remission of symptoms with FDG-PET/CT results. METHODS: All patients with FUO or IUO, who underwent FDG-PET/CT from 2013 to 2019 because diagnostic work-up failed to identify a cause, were retrospectively included. We calculated the diagnostic yield and performed multivariable logistic regression to assess characteristics previously proposed to be associated with successful localization of FUO or IUO causes. We also assessed whether the FDG-PET/CT results were associated with spontaneous remissions. RESULTS: In total, 50 patients with diagnostically challenging FUO or IUO (35 with FUO and 15 with IUO) were assessed. Other than one case of infection, all the identified causes were either malignancy or non-infectious inflammatory diseases (each with 18 patients), and FDG-PET/CT correctly localized the cause in 29 patients (diagnostic yield = 58%). None of the proposed variables was associated with successful localization. All 13 patients with sustained unexplained cause remained alive (median follow-up, 190 days). Spontaneous remission was observed in 4 of 5 patients with a negative FDG-PET/CT, and 1 of 8 with a positive result (P = 0.018). CONCLUSION: In the current cohort, the proposed variables were not predictive for successful localization by FDG-PET/CT. A negative FDG-PET/CT scan may be prognostic for spontaneous remission in patients with sustained FUO or IUO.

Comparison of mortality between nosocomial and community-acquired febrile neutropenia patients treated initially with cefazolin plus tobramycin: retrospective chart review.

Cefazolin plus tobramycin have been determined to be effective for community-acquired FN, but have not been evaluated in the treatment of nosocomial FN. This study compared the incidence of mortality from 2002 to 2004 with 2008 to 2009 in patients with nosocomial FN treated with cefazolin plus tobramycin and compared characteristics of patients with nosocomially acquired FN to community acquired FN. A retrospective chart review of 45 nosocomial FN episodes from 2008 to 2009, and 54 episodes from 2002 to 2004 treated with cefazolin plus tobramycin was conducted. Data on the community acquired FN episodes was obtained from our previous research. Nosocomial FN mortality increased from 4% in 2002-2004 to 13% in 2008-2009 (p = 0.08). The nosocomial cohort was at higher risk of medical complications and mortality than the community-acquired cohort based on several variables (neutrophil nadir, duration of neutropenia and fever, hematological malignancy, MASCC and Talcott score; p < 0.05). As a result, the nosocomial cohort was treated with longer courses of antibiotic therapy (14 days vs 7 days; p < 0.0001) and were more likely to require broader spectrum antibiotics (64 out of 99 vs 34 out of 96; p < 0.0001). There was an observed increased risk of mortality from 2002 to 2004 compared with 2008 to 2009 in patients treated with cefazolin plus tobramycin for nosocomial FN, this was notable despite not attaining statistical significance. Therefore, this regimen is not appropriate for nosocomial FN.

Empirical therapy with ceftazidime combined with levofloxacin or once-daily amikacin for febrile neutropenia in patients with neoplasia: a prospective comparative study.

Combination antimicrobial therapy represents common practice in the treatment of febrile neutropenia aiming to broaden the antimicrobial spectrum against Gram-negative pathogens. We did a prospective, non-randomized, comparative study to evaluate ceftazidime plus either levofloxacin or once-daily amikacin as empirical regimens for febrile neutropenia in patients with solid tumor or hematopoietic neoplasm in a region of high baseline resistance prevalence. We included 285 febrile neutropenic episodes in 235 individual patients. One hundred forty-eight cases received levofloxacin and 137 received amikacin, both in combination with ceftazidime. More cases in the levofloxacin than the amikacin group had underlying hematological malignancy; most other characteristics of the two groups were well balanced. Nephrotoxicity requiring treatment discontinuation occurred in one case in the amikacin group. No difference in clinical success (79.7% vs. 80.3%, p>0.99) or all-cause mortality (12.8% vs. 11.7%, p=0.86) was noted between the levofloxacin and the amikacin groups, even after adjustment for the independent predictor variables for each endpoint. Sepsis at presentation, presence of localizing symptoms/signs of infection, and isolation of a non-susceptible Gram-negative pathogen independently predicted both clinical success and all-cause mortality. Additionally, underlying solid tumor independently predicted clinical success, while poor prognosis of the underlying neoplasia and skin/soft tissue infection independently predicted mortality. Ceftazidime plus levofloxacin had similar effectiveness to ceftazidime plus amikacin as empirical regimens for febrile neutropenia. Nephrotoxicity with once-daily amikacin was minimal. Inappropriate empirical therapy was associated with worse prognosis.

Is cefepime safe for clinical use? A Bayesian viewpoint.

Cefepime hydrochloride is approved for pneumonia, empirical therapy for febrile neutropenia, uncomplicated and complicated urinary tract infections, uncomplicated skin and skin structure infections and complicated intra-abdominal infections. A recent meta-analysis by Yahav et al. (Lancet Infect Dis 2007; 7: 338-48) concluded that cefepime was associated with a statistically significant increase in mortality (risk ratio 1.26, 95% confidence interval 1.08-1.49) when compared with other antibiotics. The US FDA decided to re-evaluate the meta-analysis data in collaboration with the drug sponsor. Two years later the FDA Alert summarized that 'data do not indicate a higher rate of death in cefepime-treated patients. Cefepime remains an appropriate therapy for its approved indications.' However, a thorough evaluation of the 52-page FDA report still shows that safety remains an unresolved issue. A Bayesian re-appraisal of the findings by the FDA and by Yahav et al. indicates that there is a 90.9% (by FDA trial-level meta-analysis), 80.8% (by FDA patient-level meta-analysis) and 99.2% (by Yahav et al. meta-analysis) probability that cefepime raises mortality in neutropenic fever patients, which translates into the following numbers needed to harm (NNH), i.e. to cause one extra death with the use of cefepime: FDA trial-level meta-analysis, NNH = 109; FDA patient-level meta-analysis, NNH = 76; Yahav et al. meta-analysis, NNH = 54. A similar harmful probability was observed with skin structure infections but not with pneumonias, intra-abdominal infections and urinary tract infections. In conclusion, cefepime should be avoided in patients with neutropenic fever or with skin structure infections.

Systematic review and mixed treatment comparison of randomized evidence for empirical, pre-emptive and directed treatment strategies for invasive mould disease.

Randomized controlled trials (RCTs) provide the most reliable estimates of the effects of treatments. However, not all treatments are compared in available RCTs, making comparison of treatments problematic. Mixed treatment comparisons (MTCs) can provide estimates of the comparative effects of treatments across a range of available therapeutic options. MTCs use networks of available direct comparisons to estimate differences in treatments that have not been estimated in trials via a common comparator. We conducted a systematic review and MTCs of comparative RCTs in haematological patients of anti-mould active agents used for the empirical treatment of febrile neutropenia (Analysis 1), and pre-emptive therapy (Analysis 2) of invasive mould diseases. In addition, we summarized the evidence available associated with the use of directed treatment strategies (Analysis 3). For empirical therapy, caspofungin proved superior to amphotericin B, liposomal amphotericin B, amphotericin B lipid complex and voriconazole in the outcome of survival, but no agents showed superiority for treatment response. There was no evidence of a difference between pre-emptive and empirical strategies on mortality outcomes. For directed therapy, voriconazole was superior to amphotericin B for overall survival, and both voriconazole and liposomal amphotericin B were superior to amphotericin B and amphotericin B colloidal dispersion on the outcome of response. While limited to some degree by the availability of RCTs, the MTCs reported here provide the best available evidence of relative therapeutic success for different available treatment strategies.

Neutrophil CD64: diagnostic accuracy and prognostic value in patients presenting to the emergency department.

The purpose of this study was to evaluate the diagnostic accuracy and prognostic value of neutrophil CD64 expression for bacterial infection in febrile adult patients presenting to our hospital emergency department. We prospectively included 132 patients with fever ≥ 38ºC (≥ 100.4ºF) during the last 24 hours and we measured CD64 expression on neutrophils the day after admission at the emergency department. We followed the patients until full recovery or death. There were 115 (87%) patients with bacterial infection and 108 (94%) of them survived. There were 17 (13%) patients without bacterial infection and 12 (71%) of them survived. Patients with bacterial infection and patients who survived showed a CD64 index higher when compared with patients without bacterial infection and patients who died, respectively (3.7 ± 3.2 vs. 2.5 ± 2.3; p = 0.03; and 3.7 ± 3.1 vs. 1.7 ± 0.6; p = 0.002; Mann-Whitney U test). The receiver operating characteristic (ROC) curve analysis for detecting bacterial infection and predicting survival with the CD64 index showed an area under curve (AUC) of 0.66 (95% CI, 0.52-0.8; p = 0.03) and 0.71 (95% CI, 0.57-0.85; p = 0.01), respectively. Diagnostic accuracy and prognostic value of CD64 expression was good in adult patients with fever.

Use of procalcitonin (PCT) to guide discontinuation of antibiotic use in an unspecified sepsis is an antimicrobial stewardship program (ASP).

Clinicians have used procalcitonin (PCT) (biomarker to differentiate bacterial from non-bacterial sepsis) to guide use of antibiotics in patients. As the data for utility of PCT to discontinue antibiotics in an antimicrobial stewardship program (ASP) are lacking, we aim to describe the outcomes of patients in whom PCT was used to discontinue antibiotics under our ASP. An antimicrobial stewardship (AS) team intervened to discontinue antibiotics in patients with persistent fever or leucocytosis, source of sepsis unknown or negative bacteriological cultures, who had completed an adequate course of antibiotic therapy and had a PCT of <0.5 µg/L. Main outcomes evaluated were 14-day re-infection, 30-day mortality and readmission. Antibiotic therapy was discontinued in 42 patients in 1 year. Unknown source of sepsis was found in 38% of the patients (including possible malignant fever) and culture-negative pneumonia was found in 21%. Two patients died of advanced cancer. One patient decided for comfort care and died one week later. One patient died due to a second episode of pneumonia 37 days after first PCT test. Six patients were readmitted within 30 days due to non-infectious causes. Three patients were readmitted due to culture-negative pneumonia. None had a 14-day re-infection. PCT used to discontinue antibiotics under our ASP did not compromise patients' outcome.

Meta-analysis of a possible signal of increased mortality associated with cefepime use.

BACKGROUND: On the basis of meta-analyses, concern has been raised regarding a possible signal of increased mortality associated with the use of cefepime versus other beta-lactam antibiotics. To further investigate this possible signal, we accessed findings and data from published and unpublished cefepime clinical trials. METHODS: We performed meta-analyses using trial- and patient-level data from comparative trials. Trial-level analyses were performed using summary data from all patients in the trials, and patient-level analyses were performed on trials for which patient-level data were available. Thirty-day, all-cause mortality was analyzed using the Mantel-Haenszel adjusted risk difference (ARD) method. RESULTS: The trial-level meta-analysis was based on 88 trials (9467 cefepime patients and 8288 comparator patients). The 30-day, all-cause mortality rates were 6.21% (588/9467) for the cefepime patients and 6.00% (497/8288) for comparator patients (ARD per 1000 population, 5.38; 95% confidence interval [CI], -1.53 to 12.28). In the patient-level analysis (35 trials, 5058 cefepime patients, and 3976 comparator patients), 30-day, all-cause mortality rates were 5.63% (285/5058) for cefepime patients and 5.68% (226/3976) for comparator patients (ARD per 1000 population, 4.83; 95% CI, -4.72 to 14.38). A sensitivity analysis based solely on the 24 febrile neutropenia trials did not show a statistically significant increase in mortality with cefepime use (ARD per 1000 population, 9.67; 95% CI, -2.87 to 22.21). CONCLUSIONS: In both trial-level and patient-level meta-analyses, we did not identify a statistically significant increase in mortality among cefepime-treated patients, compared with those treated with other antibacterials.

Healthcare-associated infections in pediatric cancer patients: results of a prospective surveillance study from university hospitals in Germany and Switzerland.

BACKGROUND: Pediatric cancer patients face an increased risk of healthcare-associated infection (HAI). To date, no prospective multicenter studies have been published on this topic. METHODS: Prospective multicenter surveillance for HAI and nosocomial fever of unknown origin (nFUO) with specific case definitions and standardized surveillance methods. RESULTS: 7 pediatric oncology centers (university facilities) participated from April 01, 2001 to August 31, 2005. During 54,824 days of inpatient surveillance, 727 HAIs and nFUOs were registered in 411 patients. Of these, 263 (36%) were HAIs in 181 patients, for an incidence density (ID) (number of events per 1,000 inpatient days) of 4.8 (95% CI 4.2 to 5.4; range 2.4 to 11.7; P < 0.001), and 464 (64%) were nFUO in 230 patients. Neutropenia at diagnosis correlated significantly with clinical severity of HAI. Of the 263 HAIs, 153 (58%) were bloodstream infections (BSI). Of the 138 laboratory-confirmed BSIs, 123 (89%) were associated with use of a long-term central venous catheter (CVAD), resulting in an overall ID of 2.8 per 1,000 utilization days (95% CI 2.3 to 3.3). The ID was significantly lower in Port-type than in Hickman-type CVADs. The death of 8 children was related to HAI, including six cases of aspergillosis. The attributable mortality was 3.0% without a significant association to neutropenia at time of NI diagnosis. CONCLUSION: Our study confirmed that pediatric cancer patients are at an increased risk for specific HAIs. The prospective surveillance of HAI and comparison with cumulative multicenter results are indispensable for targeted prevention of these adverse events of anticancer treatment.

Diagnostic splenectomy in patients with fever of unknown origin and splenomegaly.

OBJECTIVE: To review the diagnostic significance, safety and possible risk factors of splenectomy in fever of unknown origin (FUO) with splenomegaly. METHODS: The records of 54 patients with FUO and splenomegaly who underwent splenectomy in our hospital in the past 20 years were reviewed retrospectively. Pathologic findings, morbidity, mortality and possible risk factors were analyzed. RESULTS: Histologic findings included 29 cases of non-Hodgkin lymphoma, 4 cases of spleen tuberculosis, 3 cases of Hodgkin lymphoma, 1 case of Castleman disease and 2 cases of hemophagocytic syndrome. An etiologic diagnosis was made in 72.2% of the patients undergoing splenectomy. Surgical complications occurred in 25.9% of the patients and 1-month operative mortality was 16.7%. The mortality rate 1 month after surgery was significantly associated with serous cavity effusion (46.2 vs. 7.5%, p = 0.006) and spleen weight >1,500 g (50.0 vs. 9.1%, p = 0.007). There was no significant difference in the mortality rate of the patients with or without jaundice, pancytopenia, elevated serum alanine aminotransferase (ALT) or elevated LDH (p > 0.5). Multivariate analysis revealed serous cavity effusion (odds ratio 21.0; 95% confidence interval 2.2-212.8; p = 0.01) and spleen weight >1,500 g (odds ratio 18.0; 95% confidence interval 1.9-173.8; p = 0.01) as independent risk factors. CONCLUSION: Splenectomy is an effective diagnostic modality for FUO presenting with splenomegaly. The presence of serous cavity effusions and spleen weight >1,500 g identifies patients with the greatest operative risk.

Long-term prognosis, treatment, and outcome of patients with fever of unknown origin in whom no diagnosis was made despite extensive investigation: A questionnaire based study.

In 30-50% of patients with fever of unknown origin (IUO) no explanation for the fever can be found. Prognosis and effects of empirical treatment of these patients are largely unknown.With this retrospective, questionnaire based corort study in all unexplained FUO patients in an expert center between 2003 and 2014 we studied mortality and outcome.In 131 of 274 FUO patients, FUO remained unexplained. Ninety-nine of them responded to the long-term follow up questionnaire. Adter a median duration of follow-up of 60 months, spontaneous remission of fever occured in 47.3%. Empirical treatment was effective in 66.7% of patients. Mortality was 6.9%. The cause of death was considered not to be related to the febrile disease in five out of six patients. Ten out of 99 responders reported to have received a final explanation for FUO after evaluation in the expertise center, but this diagnosis could not be confirmed in six cases and was considered to be an unlikely explanation for FUO in four out of six cases.We conclude that mortality in unexplained FUO is low en mostly unrelated to the febrile disease. Spontaneous resolution of fever is common. Empirical treatment prescribed by an expert physician is often effective, but should be avoided untill all diagnostic possibilities have been exhaused.

Early discontinuation of empirical antibacterial therapy in febrile neutropenia: the ANTIBIOSTOP study.

INTRODUCTION: Immediate empirical antibiotic therapy is mandatory in febrile chemotherapy-induced neutropenia, but its optimal duration is unclear, especially in patients with fever of unknown origin (FUO). OBJECTIVES: The primary objective of this 20-month prospective observational study was to evaluate the feasibility and safety of short-term antibiotic treatment in afebrile or febrile patients exhibiting FUO, irrespective of their neutrophil count. The secondary objective was to describe the epidemiology of all episodes of febrile neutropenia. METHODS: In the first phase of the study, empirical antibiotic therapy in FUO patients was stopped after 48 h of apyrexia, in accordance with European Conference on Infections in Leukaemia guidelines (n = 45). In the second phase of the study, antibiotics were stopped no later than day 5 for all FUO patients, regardless of body temperature or leukocyte count (n = 37). RESULTS: Two hundred and thirty-eight cases of febrile neutropenia in 123 patients were included. Neither the composite endpoint (p = .11), nor each component (in-hospital mortality (p = .80), intensive care unit admission (p = 0.48), relapse of infection ≤48 h after discontinuation of antibiotics (p = .82)) differed between the two FUO groups. Violation of protocol occurred in 17/82 episodes of FUO without any major impact on statistical results. Twenty-six (57.3%) and 22 (59.5%) FUO episodes did not relapse during hospital-stay (p = 1), and nine (20%) and five (13.5%) presented another FUO, respectively. One hundred and fifty-six episodes of febrile neutropenia (65.5%) were clinically or microbiologically documented, including 85 bacteremia. CONCLUSIONS: These results suggest that early discontinuation of empirical antibiotics in FUO is safe for afebrile neutropenic patients.

[Fever in patients of a Service of Internal Medicine: prospective study in 204 cases]. / Fiebre en pacientes hospitalizados en un Servicio de Medicina Interna: análisis prospectivo de 204 casos.

OBJECTIVES: Fever in hospitalized patients (FHP) is a difficult problem. We study clinical characteristics and predictive parameters of infection, sepsis and outcome. PATIENTS AND METHODS: Prospective study of 204 patients with fever > 38 degrees C admitted in an Internal Medicine ward. In each patient clinical evaluation, complete blood count (CBC) urinalysis (UA), C-reactive protein (CRP), chest X- ray (CXR), blood and urine cultures were performed. RESULTS: 115 patients suffered infection (75.9% nosocomial, 7.4% sepsis), 35 had a non-infectious etiology and 54 an unknown cause. CBC and CRP did not distinguish infection, bacteremia or sepsis. In UA, positive nitrites, leukocytes and bacteriuria were predictive of infection. 18.6% of the patients were diagnosed by CXR. 18% of urine cultures and 13% of blood cultures were positive. 71.6% received antibiotics (deemed unnecessary in 18%). Microbiological results modified 25% of initial treatments. Average hospital stay was 17 days; 16.7% died. Chronic lung disease, fever duration, dysphagia and urinary tract alterations predict infection. Obesity, diabetes mellitus, liver failure, immunocompromised host, central vascular access, fever duration and nosocomial infection predict bacteremia. Sepsis is more prevalent in males, with malignancy and vascular or nosocomial infection. Chronic liver disease, nosocomial infection, severe lung infection and sepsis increase mortality. CONCLUSIONS: Clinical diagnosis of FHP is inaccurate. Infection is it s most frequent cause; UA, CXR, and blood and urine cultures are useful. FHP increases mortality and hospital stay. We have established predictable models of infection, bacteremia, sepsis and mortality. However, its sensibility and specificity are low.

Long-term follow-up of patients with undiagnosed fever of unknown origin.

BACKGROUND: A casual diagnosis cannot be established in 10% to 25% of the patients who are studied for fever of unknown origin (FUO). The long-term clinical outcome of these patients cannot be inferred from the literature. This study describes the results of a 5-year follow-up of 61 patients studied for FUO and discharged from the hospital with no causal diagnosis being established. METHODS: Patients meeting the classic criteria for FUO who were studied in the 1980s and discharged from the hospital without a casual diagnosis were followed up for at least 5 years or until death. Follow-up was performed by review of the patients' medical records or by consulting the treating physician and occasionally the patients themselves. The final diagnosis, clinical course (resolution of the fever and required treatments), and morality rate were studied. RESULTS: Of a cohort of 199 patients with FUO, 61 individuals (30%) were discharged from the hospital without a final diagnosis being established. A definite diagnosis could be established in 12 cases, mostly (eight of 12) within 2 months after discharge. Thirty-one individuals became symptom free during hospitalization or shortly following discharge. Eighteen patients had persisting or recurring fever for several months or even years after discharge, but 10 of them were considered to be finally cured. Four patients were treated with corticosteroids and six patients required intermittent therapy with nonsteroidal anti-inflammatory agents. Six patients died, but the cause of death was considered to be related to the disease that caused FUO in only two cases. CONCLUSION: No single disease, particularly not tuberculosis, was found to be a cause of undiagnosed FUO. Most cases resolved spontaneously, and corticosteroids were seldom required. Most symptomatic patients could be treated with nonsteroidal anti-inflammatory drugs. The mortality rate in patients with undiagnosed FUO who were followed up for 5 years or more was only 3.2%.

Fever of unknown origin caused by multiple myeloma: a report of 9 cases.

BACKGROUND: Most authorities regard multiple myeloma as a rare cause of fever and not a cause of fever of unknown origin (FUO). OBJECTIVE: To describe a series of patients with FUO caused by multiple myeloma. METHODS: We reviewed the clinical features of 9 patients seen at Mayo Clinic from January 1, 1975, to February 1, 2001, with FUO caused by multiple myeloma. RESULTS: Fever of unknown origin caused by multiple myeloma was found in 9 patients (6 men and 3 women). All patients satisfied accepted criteria for FUO. The mean +/- SD time from the onset of fevers to the initial physician evaluation was 4.8 +/- 2.0 weeks. The mean time from the initial physician evaluation to the diagnosis of multiple myeloma was 11.4 +/- 6.5 weeks. The mean age at diagnosis of multiple myeloma was 55.9 +/- 6.9 years. All 9 patients were anemic. Peripheral blood smears were available for 8 patients, and all had rouleaux formations. All 9 patients underwent exhaustive testing to determine the cause of fevers. Further testing was done in 6 patients subsequent to the diagnosis of multiple myeloma. Acetaminophen or nonsteroidal anti-inflammatory drugs or both relieved fevers in all patients who received them. All 8 patients who received chemotherapy experienced resolution of fevers. The median actuarial survival of the patient cohort was 38 months. CONCLUSIONS: Multiple myeloma can cause FUO. When appropriate, clinicians should include multiple myeloma in the differential diagnosis of FUO to reduce unnecessary testing, rapidly establish the diagnosis, and initiate effective treatments.

Children with fever of unknown origin in Argentina: an analysis of 113 cases.

The aim of this study was to determine the causes of fever of unknown origin, to evaluate new diagnostic tests and to elucidate risk factors for chronic or life-threatening disorders. The medical records of 113 children who had undiagnosed fever for at least 3 weeks were reviewed. Infection (N = 41) was the most frequent cause of fever of unknown origin. Respiratory tract infections were the most common causes in infants and endocarditis and tuberculosis were more frequent in older children. Neoplastic disorders (N = 11) occurred in children older than one year. Juvenile rheumatoid arthritis (N = 9) was the most common collagen-vascular disorder (N = 15). Miscellaneous disorders and factitious fever occurred in 21 and 4 cases, respectively. Twenty-two patients remained undiagnosed. History and physical examination led to a final diagnosis in 81% of cases. Abdominal ultrasonography was performed in 71 patients (61%) and was helpful for diagnosis in 15%. Children with life-threatening or chronic disorders (N = 58) were older than those with self-limiting conditions (N = 55; P = 0.017). Cardiovascular and articular signs and symptoms were more frequent in the former group (P = 0.01).

Waiting for microbiologic data to direct therapy against nosocomial infections in febrile surgical patients: are outcomes worsened?

HYPOTHESIS: Allowing adequate time for laboratory and culture results before initial treatment may be associated with a worse outcome in nosocomial infections. DESIGN: Cohort study of all episodes of nosocomial infection from December 10, 1996, to October 28, 1998. SETTING: Surgical services at a university hospital. PATIENTS AND METHODS: In surgical patients presenting with fever, 372 episodes of nosocomial infection were evaluated. Nosocomial infections were divided by time from fever to intervention (< or =12, 13-24, and >24 hours). These groups were subdivided by Acute Physiology and Chronic Health Evaluation II (APACHE II) scores into low (< or =10 [n = 114]), moderate (11-20 [n = 169]), and high severity of illness (>20 [n = 89]). Pneumonia and bloodstream infections were divided by APACHE II scores into low (< or =15 [n = 55 and n = 56, respectively]) or high severity of illness (>15 [n = 84 and n = 77, respectively]). MAIN OUTCOME MEASURES: Mortality, length of stay. RESULTS: No difference in outcome was seen between different time intervals from fever to intervention for nosocomial infections in patients with APACHE II scores of no more than 10. Patients treated more than 24 hours after fever were significantly younger than those treated at no more than 12 and 13 to 24 hours with APACHE II scores of 11 to 20 (P<.05) and more than 20 (P<.05). Mortality and length of stay for patients treated at later time intervals were comparable with those of patients treated earlier with similar APACHE II scores. There was no difference in outcome for patients with pneumonia or bloodstream infection. CONCLUSIONS: Episodes of infection in which treatment was withheld until initial microbiologic data were available (24 hours) did not have worse outcomes compared with those treated earlier. Waiting for laboratory and culture results to direct antibiotic therapy for nosocomial infections does not appear harmful and may be potentially beneficial.

Empiric antimicrobial therapy of febrile neutropenic patients undergoing haematopoietic stem cell transplantation.

This study was conducted to assess the efficacy and toxicity of intravenous (i.v.) ceftazidime and ciprofloxacin in neutropenic febrile patients undergoing high dose myeloablative therapy and hematopoietic stem cell transplantation (HSCT). All patients undergoing HSCT for leukaemia, lymphoma, multiple myeloma and solid tumours received open-label ceftazidime 2 g i.v. every 8 h and ciprofloxacin 400 mg i.v. every 12 h if they developed fever while they were neutropenic. Success with or without modification of this regimen was defined as survival through the neutropenic period; failure was defined as death secondary to infection. Of 106 patients treated with this regimen, the success rate was 99%. Sixty-one of the patients (57.5%) defervesced within 48-72 h and remained afebrile without regimen modification. In 41.5% of the cases (44/106), the regimen was modified because of persistent fever. One patient died secondary to sepsis. The combination of ceftazidime and ciprofloxacin as initial empiric antibacterial therapy in febrile neutropenic patients undergoing myeloablative therapy and HSCT is highly effective and is associated with minimal toxicity.

Extreme hyperpyrexia in childhood. Presentation similar to hemorrhagic shock and encephalopathy.

The authors report the cases of five previously well children, aged 8 to 33 months, who were seen over a 14-year period, with admission temperatures in excess of 42.0 degrees C (107.6 degrees F). Four of the patients died. Each child had a similar clinical illness in which the hyperpyrexia played a critical role. Negative blood, cerebrospinal fluid, and stool cultures excluded bacterial sepsis as a possible etiology. This illness is similar, if not identical, to the newly described syndrome of hemorrhagic shock and encephalopathy (HSES) reported in European and American infants.

Infections in acute lymphoblastic leukaemia.

We did a retrospective study of all acute lymphoblastic leukaemia (ALL) patients on United Kingdom ALL protocol who were admitted for febrile neutropenia. The aim of the study was to document the types of infections and aetiological agents associated with febrile neutropenia and to document the factors affecting mortality. Over the 8 1/2-year period from 1986 to June 1995, there were 77 episodes in 32 children with a mean of 2.4 episodes. Morbidity due to infection was 61%; unknown causes of fever contributed 39%. Of the microbiologically documented infections, majority were Gram-negative bacteraemia. There were 7 deaths (22%) during the study period, 3 (9%) of which were due to overwhelming sepsis, with 4 contributed by the relapse status of the leukaemia. Mortality was increased by prolonged neutropenia, relapse of the leukaemia and invasive fungal infection.