No Impact of Dietary Restrictions on the Risk for Infection in Pediatric Patients With Cancer: A Monocenter Analysis.

PURPOSE: Prophylactic anti-infective strategies are used in patients with cancer to decrease the risk for infection. Dietary restrictions do not allow raw vegetables and fresh fruits to limit the introduction of potentially harmful pathogens in the gastrointestinal tract, but the efficacy is unclear. PATIENTS AND METHODS: In this study analyzing the impact of the dietary restrictions on infectious complications, all children treated between April 2014 and March 2018 for ALL and AML or non-Hodgkin lymphoma (NHL) were included. Dietary restrictions were standard until March 2016, but were stopped in April 2016. Patients with dietary restrictions (treated April 2014-March 2016) and patients not advised for dietary restrictions (treated April 2016-March 2018) were compared regarding infectious complications, including bloodstream infection, pneumonia, diarrhea, and fever of unknown origin (FUO). RESULTS: Eighty-six patients (25 female; 62 ALL; nine AML, 15 NHL) experienced 223 infections. The 46 patients with dietary restrictions and the 40 patients without food restrictions did not significantly differ regarding the number of infections per patient, bloodstream infections, pneumonia, diarrhea, FUO, admission to intensive care, and death. CONCLUSION: Our data suggest that dietary restrictions do not affect the risk for infectious complications. Therefore, the indication of dietary restrictions should be reconsidered in pediatric patients with cancer.

Comparison of two different anti-infectious approaches after high-dose chemotherapy and autologous stem cell transplantation for hematologic malignancies in a 12-year period in British Hospital, Uruguay.

Autologous stem cell transplant (ASCT) is a widely used and safe procedure to treat mostly hematologic diseases. These patients are at risk of infectious complications, which represents a major cause of morbidity and it is the second cause of mortality. This retrospective 12-year analysis of the incidence, type, and severity of infections in 266 consecutive unselected ASCT patients at our institution provides novel information addressing this issue. We included 266 ASCT procedures. Patients included in the 2006-2013 period are referred to as group 1 (ciprofloxacin prophylaxis and ceftazidime-amikacin as empirical antibiotics), and those in the 2013-2017 period are group 2 (levofloxacin prophylaxis and meropenem as empirical antibiotics). The incidence of febrile neutropenia was 72% in group 1 and 86.2% in group 2 (p = 0.004). The majority of infectious episodes were associated with fever of unknown origin: 55% in group 1 and 59% in group 2. Febrile of unknown origin episodes were 82.6% in group 1 and 80% in group 2. Significant differences between both groups were found in age, hypogammaglobulinemia, and advanced disease at ASCT. No differences were found between groups regarding the most common agent documented in positive blood cultures (Gram+ were 66.6% in group 1 and 69% in group 2 (p = 0.68)). Mortality within 100 days of transplant was low, 1.87%. Regardless of the prophylactic regimen used, most patients experience febrile episodes in the ASCT setting, fever of unknown origin is the most common infection complication, and Gram+ agents are prevalent in both groups. Mortality rates were low. According to our results, ASCT is a safe procedure and there is no clear benefit in favor of levofloxacin versus ciprofloxacin prophylaxis. Both anti-infectious approaches are acceptable, yielding similar outcomes.

Haemophagocytic syndrome in an adult suffering from pyrexia of unknown origin: an uncommon presentation of tuberculosis: a case report.

BACKGROUND: Tuberculosis is common, can involve various organs of the body and may have diverse presentations. Haemophagocytic syndrome is one of the rare presentations of tuberculosis carrying a very high mortality. Early detection and institution of anti-tuberculosis medications can be life-saving. CASE PRESENTATION: A 23-year-old Bengali man presented with prolonged fever, weight loss, hepatosplenomegaly, pancytopenia and altered liver function. He had high erythrocyte sedimentation rate, positive tuberculin test, granuloma in liver biopsy, and haemophagocytosis was evidenced by histopathological examination of bone marrow. He recovered with anti-tuberculosis therapy. CONCLUSION: This case demonstrates that consideration of tuberculosis as an underlying cause of haemophagocytic syndrome could be rewarding and life-saving in this rapidly fatal condition.

Lack of Effectiveness of Neutropenic Diet and Social Restrictions as Anti-Infective Measures in Children With Acute Myeloid Leukemia: An Analysis of the AML-BFM 2004 Trial.

PURPOSE: Although nonpharmacologic anti-infective measures are widely used in children treated for acute myeloid leukemia (AML), there is little evidence of their effectiveness. PATIENTS AND METHODS: We analyzed infectious complications in children during intensive treatment of AML according to the AML-BFM 2004 trial and surveyed sites on institutional standards regarding recommended restrictions of social contacts (six items), pets (five items), and food (eight items). A scoring system was developed with a restriction score for each item. Multivariable Poisson regression adjusted for sex, age, weight group, risk stratification, and prophylactic antibiotics was used to estimate the impact of the restrictions on the incidence ratios of fever of unknown origin, bacteremia, pneumonia, and gastroenteritis. RESULTS: Data on recommendations of nonpharmacologic anti-infective measures and infectious complications were available in 339 patients treated in 37 institutions. Analyses did not demonstrate a significant benefit of any of the restrictions regarding food, social contacts, and pets on the risk of fever, bacteremia, pneumonia, and gastroenteritis. In contrast, age, weight group, risk stratification, and nonabsorbable antibiotics had some influence on infections complications. CONCLUSION: The lack of effectiveness of dietary restrictions and restrictions regarding social contacts and pets should result in reconsideration of anti-infective policies.

[A 55-year-old woman with cough, fever, swelling of joints, and exanthema after a trip to Ecuador]. / 55-jährige Patientin mit Husten, Fieber, Gelenkschwellungen und Exanthem nach einem Urlaub in Ecuador.

A 55-year-old woman presented 18 months after a trip to Ecuador with night sweat, malaise, and an unclear lesion of the lung. Computed tomography of the lung showed a nodular lesion of 14 mm. Antibodies against Histoplasma capsulatum were detected in the complement fixation text (CFT) and IgG western blot. Re-examination of a formalin fixed paraffin embedded (FFPE) lung-biopsy revealed yeasts after silver staining, compatible with H. capsulatum , which was verified by extraction and amplification of DNA from FFPE. After therapy with itraconazole 400 mg/day, the patient showed an uneventful clinical recovery without regression of the lung lesion. The serological follow-up examination after 17 months showed CFT without pathological findings.

[Fever, atrial fibrillation, and angina pectoris in a 58-year-old man]. / Fieber, Vorhofflimmern und Angina pectoris bei einem 58-jährigen Patienten.

Primary cardiac lymphoma (PCL) respresents a very rare type of cardiac tumour. This report illustrates a case of PCL in an immunocompetent 58-year-old man presenting with atrial fibrillation and febrile syndrome. Comprehensive imaging [computer tomography (CT), cardiac magnetic resonance imaging (cMRI), 3-dimensional transesophageal echocardiography (3D-TEE)] identified a large right atrial tumour, leading to pericardial effusion. Isolated cardiac involvement was confirmed by positron emission tomography (PET)-CT. A diffuse large B-cell lymphoma (DLBCL) was diagnosed based on the results of a TEE-guided biopsy. A normalized PET scan (PETAL study) indicated complete remission following R-CHOP 14 immunochemotherapy. Thus, an interdisciplinary and multimodal approach avoided unnecessary cardiac surgery.

[A 55-year-old man with abdominal pain and fever]. / 55-jähriger Patient mit abdominellen Schmerzen und Fieber.

A 55-year-old man was admitted for evaluation of chronic abdominal pain and fever. Computed tomography demonstrated a retroperitoneal inflammatory process involving the mesenteric root. Adipose tissue biopsy showed panniculitis mesenterica with granulomas. Further examinations confirmed the diagnosis of plasmocytoma type IgG kappa. Treatment with steroids (prednisolone), resulted in immediate improvement of pain and fever. Mesenteric panniculitis represents a paraneoplastic syndrome associated with non-Hodgkin lymphoma.

Effectiveness of a Protective Environment implementation for cancer patients with chemotherapy-induced neutropenia on fever and mortality incidence.

In a quasiexperimental study conducted to evaluate the impact of a Protective Environment implementation, febrile neutropenia (P = .009), overall mortality (P = .001), and 30-day adjusted mortality (P = .02) were reduced in cancer patients with chemotherapy-induced neutropenia. Our study highlights the potential success of a set of prevention measures mainly designed to reduce invasive environmental fungal infections in allogeneic hematopoietic stem cell transplant patients, in reducing fever and mortality among neutropenic cancer patients.

[Hyperthyroidism, eosinophilia, and fever in a 64-year-old patient]. / Hyperthyreose, Eosinophilie und Fieber bei einem 64-jährigen Patienten.

We report on a male patient suffering from loss of weight, fatigue, fever, eosinophilia, and hyperthyreoidism. The echocardiogram revealed a left atrial mass originating from the posterior mitral leaflet. In combination with the constitutional symptoms a left atrial myxoma was diagnosed. The tumor was surgically removed. Postoperatively therapy with corticosteroids and thiamazole was stopped. During follow-up, eosinophilia and hyperthyreodism could no longer be detected.

Randomized controlled trial of taurolidine citrate versus heparin as catheter lock solution in paediatric patients with haematological malignancies.

BACKGROUND: A catheter lock solution containing 1.35% taurolidine and 4% citrate could potentially disrupt bacterial surface adherence and consecutive biofilm production due to the anti-adherence properties of taurolidine and the anticlotting and chelator activities of both compounds. AIM: To compare the impact on microbial catheter colonization and infectious complications of heparin and taurolidine citrate as central venous catheter (CVC) lock solutions in paediatric patients with haematological malignancies. METHODS: Seventy-one patients aged 1.4-18 years were randomized to two treatment groups using either heparin (N = 36) or taurolidine citrate (N = 35). Infectious complications and clinical side-effects were prospectively monitored and microbial colonization of catheters was assessed at the time of removal. FINDINGS: There were two bloodstream infections in the taurolidine citrate group versus nine in the heparin group (0.3 vs 1.3 infections per 1000 catheter-days; P = 0.03). Fever of unknown origin and catheter occlusions were observed with a similar frequency in both groups. Microbial colonization was found in 25.4% catheters. The time of no-lock use, but not the type of lock solution or time of observation, was a significant predictor of catheter colonization (P = 0.004). Colonization was not observed in CVCs used immediately with taurolidine citrate lock. Seven patients in the taurolidine citrate group (20%) experienced side-effects (nausea, vomiting, abnormal taste sensations). CONCLUSION: The use of taurolidine citrate lock solution was associated with a significant reduction in bloodstream infection in immunocompromised paediatric patients. Taurolidine citrate may prevent colonization of CVCs if used from the time of insertion, but not after a period of no-lock catheter use.

The role of prophylactic antimicrobials during autologous stem cell transplantation: a single-center experience.

The aim of this study was to investigate the efficacy of antibiotic prophylaxis in patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma and non-Hodgkin lymphoma. Among 232 ASCT cases performed at the Asan Medical Center, 114 cases underwent treatment with ciprofloxacin, fluconazole, and acyclovir (between January 2001 and August 2005), while 118 cases were performed without antimicrobial prophylaxis (between February 2004 and June 2008). The two-rate χ2 test was applied to accommodate the differences in neutropenia duration. The incidence of febrile episodes was 9.8 cases per 100 person-days in the prophylactic group, while it was 16.2 cases in the no-prophylactic group (p<0.001). The rate of unexplained fever was 8.0 cases per 100 person-days in the prophylactic group, while it was 13.8 cases in the no-prophylactic group (p<0.001). The rate of clinically and microbiologically documented infection was 1.7 cases per 100 person-days in the prophylactic group, while it was 2.3 cases in the no-prophylactic group (p=0.404). There were fewer cases of methicillin-susceptible Staphylococcus aureus infection and a greater number of quinolone-resistant Escherichia coli in the prophylactic group compared with the no-prophylactic group (p=0.056 and p=0.040, respectively). The prophylactic antimicrobials reduced the incidence rate of febrile episodes, especially unexplained fever, despite there being no difference in the incidence of documented infection. Resistant microbe infection occurred more frequently in the prophylactic group.

[Unexplained fever and B-symptoms in a young male Black African]. / Unklares Fieber und B-Symptome bei einem jungen Schwarzafrikaner.

An immunocompetent Nigerian developed a fulminant hemophagocytic lymphohistiocytosis due to Epstein-Barr virus reactivation. The patient initially presented with fever, hepatosplenomegaly and pancytopenia. The clinical status of our patient deteriorated quickly despite treatment with corticoids. Escalation of immunosuppressive treatment was not possible. He died of lung, liver and circulatory failure in our intensive care unit.Hemophagocytic lymphohistiocytosis is a rare disease characterized by inflammation due to prolonged and excessive activation of antigen-presenting cells. High plasma ferritin levels and phagocytosis of hematopoetic cells in bone marrow, spleen and liver lead to the diagnosis. Hemophagocytic lymphohistiocytosis should therefore be included in the differential diagnosis in patients with persistent fever, hepatosplenomegaly and cytopenia.

[Intermittent fever under iatrogenic immunosuppression]. / Intermittierendes Fieber unter iatrogener Immunsuppression.

Prolonged fever of unknown origin together with night sweats in the elderly requires a systematic search for malignant and infectious foci. Here we present a case of fever of unknown origin which ultimately led us to the diagnosis of everolimus-induced fever. After changing the immunosuppressive regime it resolved rapidly.

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.

[Pegfilgrastim vs filgrastim in primary prophylaxis of febrile neutropenia in patients with breast cancer after chemotherapy: a cost-effectiveness analysis for Germany]. / Pegfilgrastim vs. Filgrastim zur Primärprophylaxe der febrilen Neutropenie bei Brustkrebspatientinnen nach Chemotherapie: Eine Kosten-Effektivitäts-Analyse für Deutschland.

OBJECTIVE: Febrile neutropenia (FN) is a common toxic side effect of myelosuppressive chemotherapy. The cost-effectiveness of primary prophylaxis (PP) of FN with granulocyte colony stimulating growth factor (G-CSF) filgrastim for six or eleven days was compared to single dose pegfilgrastim in patients with early breast cancer receiving chemotherapy (>or= 20 % FN risk) as simulated in a model. METHODS: Based on a decision-analytical model we conducted a cost-effectiveness analysis (CEA) and a cost-utility analysis (CUA) from the perspective of the Statutory Health Insurance (SHI) in Germany. The model simulated three clinical alternatives being built on each other, that pegfilgrastim and filgrastim had differential impact on (1) the risk of FN, (2) on FN-related mortality, and (3) on the achieved chemotherapy relative dose intensity (RDI) leading to gain in long-term survival. RESULTS: Assuming a 5.5 % lower risk of FN for PP with pegfilgrastim than an 11-day course of filgrastim provided - from the perspective of the SHI - a cost saving of Euro 2,229. A gain of 0.039 quality-adjusted life-years (QALY) resulted when the third alternative was used. Assuming a 10.5 % lower risk of FN for PP with pegfilgrastim than a 6-day filgrastim course, the third alternative showed an incremental cost-effectiveness ratio (ICER) of Euro 17.165 per life-year gained (LYG) and Euro 18.324 per QALY with 0.074 QALYs gained. CONCLUSION: These results indicate that PP with pegfilgrastim is cost saving compared to 11-day use of filgrastim and cost-effective compared to 6-day use of filgrastim in patients with breast cancer treated in Germany.

[Fever, redness, swelling, and pain in the submental region]. / Fieber, Rötung, Schwellung und Schmerzen submental.

A 76-year-old woman presented with fever, redness, swelling, and pain under the chin. Some submental lymph nodes were detected by ultrasound and computed tomography. The diagnosis was a submental phlegmon, for which surgery was performed. The lymph nodes were removed, and antibiotic therapy with daily lavage was done. The histology of the lymph nodes suggested giant cell arteritis.

[A 39-year-old patient with maculopapular rash, recurrent fever, and arthralgia]. / 39-Jährige mit makulopapulösem Exanthem, Fieberschüben und Arthralgien.

Adult-onset Still's disease is a rare disorder of unknown etiology. We report the case of a 39-year-old patient who showed the characteristic symptoms: recurrent attacks of fever, arthralgia, maculopapular rash, sore throat, and lymphadenopathy. After the possibility of an infectious or paraneoplastic process was excluded and the laboratory findings were evaluated (increased C-reactive protein, liver values, and ferritin level), the diagnosis was established according to the criteria of Yamaguchi. Therapy with steroids and nonsteroidal anti-inflammatory drugs was started successfully.

Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia.

PURPOSE: A neutropenic diet is often used to prevent infection in patients with acute myeloid leukemia (AML). Although such a diet potentially entails inconvenience, its value is uncertain. PATIENTS AND METHODS: One hundred fifty-three patients admitted to a high-efficiency particulate air-filtered room (protected environment [PE]) to receive induction therapy for newly diagnosed AML were randomly assigned to a diet containing no raw fruits or vegetables (cooked diet) or to a diet containing fresh fruit and fresh vegetables (raw diet). Stratification was based on the patients' early risk of mortality (ERM) score. All patients received antibacterial and antifungal prophylaxis and remained on study until they were discharged from the PE. The outcomes of principal interest were major infection (pneumonia, bacteremia, or fungemia) and death; if the true probability of either event was 20% on the cooked arm and 40% on the raw arm, then the probability that the cooked arm would be selected as superior was 83%. RESULTS: Seventy-eight patients were randomly assigned to the cooked arm, and 75 were assigned to the raw arm. The two groups were similar with respect to age, ERM, chemotherapy received, and days at risk. Twenty-nine percent of patients in the cooked group and 35% of patients in the raw group developed a major infection (P = .60). Time to major infection and survival time were similar in the two groups. Fever of unknown origin occurred in 51% of the cooked group and 36% of the raw group. CONCLUSION: In patients treated in a PE, a neutropenic diet did not prevent major infection or death.

Clinical guidelines for the management of neutropenic patients with unexplained fever in Japan: validation by the Japan Febrile Neutropenia Study Group.

The Japan Febrile Neutropenia Study Group (JFNSG) Trial was a multicenter, open, randomized study designed to validate the first Japanese guidelines for the management of neutropenic cancer patients with unexplained fever issued in 1998. The trial compared cefepime monotherapy with cefepime plus amikacin combination therapy in febrile neutropenic patients with hematological disorders. The JFNSG found that monotherapy with cefepime was, in general, as effective as combination therapy. In terms of subset analyses, defervescence appeared to occur more frequently in leukemic patients and in those with profound neutropenia treated with the dual combination. The conclusion of the trial was that the 1998 guidelines were applicable to the Japanese febrile neutropenic patient population. The JFNSG met again in 2003 to revise these guidelines. An important addition to the guidelines was a distinction between low- and high-risk patients. Low-risk febrile neutropenic patients can receive oral ciprofloxacin or levofloxacin, with or without amoxicillin/clavulanic acid, on an outpatient basis, or intravenous (i.v.) monotherapy with cefepime, ceftazidime or a carbapenem. High-risk patients can receive i.v. cefepime, ceftazidime or a carbapenem, or an i.v. dual combination with cefepime, ceftazidime or a carbapenem plus an aminoglycoside. Those patients with a documented infection with methicillin-resistant Staphylococcus aureus should also receive a glycopeptide. It remains to be determined whether existing assessment scoring systems apply to Japanese patients; whether a broad-spectrum cephalosporin plus an aminoglycoside combination is required as the initial management of patients with acute leukemia and/or profound neutropenia; which antibacterial drugs should be used when first- and second-line agents fail; what are the appropriate oral agents and dosing regimens for low-risk patients; whether serology or the polymerase chain reaction should be the preferred marker for initiating preemptive antifungal therapy; and whether the azoles or the candins should be the preferred antifungal agents.