Safety and risk of febrile recurrence after early antibiotic discontinuation in high-risk neutropenic patients with haematological malignancies: a multicentre observational study.

BACKGROUND: Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies. METHODS: A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence. RESULTS: Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P < 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HR = 2.31 (95% CI = 1.4-3.8), P < 0.001] and stage III-IV oral mucositis with bacteraemia [HR = 2.26 (95% CI = 1.22-4.2), P = 0.01]. CONCLUSIONS: After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients.

[Acute kidney failure in differentiation syndrome: a possible complication during therapy with differentiating agents for acute promyelocytic leukemia. A case report].

Differentiation syndrome (DS), previously known as retinoic acid syndrome or ATRA (all-trans retinoic acid) or ATO (arsenic trioxide) syndrome, is a life-threatening complication of the therapy with differentiating agents in patients with acute promyelocytic leukemia (APL). The latter is a rare subtype of acute myeloid leukemia and represents a hematological emergency. The clinical manifestations of DS, after induction therapy with differentiating agents, include unexplained fever, acute respiratory distress with interstitial pulmonary infiltrates, unexplained hypotension, peripheral edema, congestive heart failure and acute renal failure. The therapy is based on early intravenous administration of high-dose dexamethasone, in order to counteract the cytokine storm responsible for the DS. Among the supportive measures for the management of DS, furosemide (in 87% of patients) and dialysis (12% of patients) are used to manage acute renal failure, peripheral and pulmonary edema. We describe a case of acute renal failure, treated with haemodialysis, in a young patient with APL and an early and severe DS after induction therapy. This is a rare condition, not well known among nephrologists, where early recognition and treatment are crucial for the prognosis.

[Diagnostic management of fever]. / Diagnostisches Management von Fieber.

Fever is a symptom of a wide range of diseases. Its diagnostic management is of crucial importance, whereby the interface between general practitioner and hospital plays an important role. The family practitioner is of particular importance in the detection of life-threatening or complex situations involving fever. The diagnostic algorithm presented here can serve as the basis for rapid and targeted diagnostics. Good communication between the doctor and the hospital doctor is mandatory.

Fever of unknown origin (FUO) due to miliary BCG: The diagnostic importance of morning temperature spikes and highly elevated ferritin levels.

Fever of unknown origin (FUO) is defined as prolonged fever of >101 °F for at least 3 weeks that remains undiagnosed after a focused inpatient or outpatient workup. One of the most elusive FUO diagnoses is miliary tuberculosis (TB) which typically has few/no localizing signs/symptoms. Since the introduction of intravesicular Bacille Calmette-Guerin (BCG) treatment for bladder carcinoma, miliary BCG has only rarely been reported as a cause of FUO. As with miliary TB, there are few/no clues to suspect miliary BCG. We present an interesting case of FUO due to miliary BCG without any localizing signs, i.e., no lung, liver or prostate involvement. The only clues to the diagnosis of this FUO due to disseminated BCG were morning temperature spikes and otherwise unexplained highly elevated ferritin levels.

Acute mercury poisoning presenting as fever of unknown origin in an adult woman: a case report.

INTRODUCTION: Mercury intoxication may present in a wide range of clinical forms from a simple disease to fatal poisoning. This article presents a case of acute mercury poisoning, a rare condition that presents challenges for diagnosis with fever of unknown origin. CASE PRESENTATION: A 52-year-old Caucasian woman was admitted to the hospital with high fever, sore throat, a rash over her entire body, itching, nausea, and extensive muscle pain. She had cervical, bilateral axillary and mediastinal lymphadenopathies. We learned that her son and husband had similar symptoms. After excluding infectious pathologies, autoimmune diseases and malignancy were investigated. Multiple organs of our patient were involved and her fever persisted at the fourth week of admission. A repeat medical history elicited that her son had brought mercury home from school and put it on the hot stove, and the family had been exposed to the fumes for a long period of time. Our patient's serum and urine mercury levels were high. She was diagnosed with mercury poisoning and treated accordingly. CONCLUSIONS: Mercury vapor is a colourless and odorless substance. Therefore, patients with various unexplained symptoms and clinical conditions should be questioned about possible exposure to mercury.

Acute pancreatitis induced by methimazole treatment in a 51-year-old korean man: a case report.

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Acute Pancreatitis Induced by Methimazole Treatment in a 51-Year-Old Korean Man: A Case Report

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

Acute Pancreatitis Induced by Methimazole Treatment in a 51-Year-Old Korean Man: A Case Report

Methimazole (MMI)-induced acute pancreatitis is very rare but severe adverse reaction. A 51-yr-old male developed a high fever, chills, and abdominal pain, two weeks after commencement on MMI for the treatment of Graves' disease. There was no evidence of agranulocytosis, and fever subsided soon after stopping MMI treatment. However, 5 hr after taking an additional dose of MMI, abdominal pain and fever developed again. His symptoms, biochemical, and imaging studies were compatible with acute pancreatitis. After withdrawal of MMI, he showed clinical improvement. This is the first case of MMI-induced acute pancreatitis in Korea. Clinicians should be aware of the rare but possible MMI-induced pancreatitis in patients complaining of fever and abdominal pain.

[Neutropenia and fever of unknown origin]. / Neutropenie und Fieber unklarer Genese.

We report a case of a young man presenting with a severe neutropenia together with a mild anemia. The diagnostic work up of such a hematological anomaly is reviewed. It finally revealed a therapy-related acute myeloid leukemia, secondary to previous chemotherapy for a testicular tumor.

[Management of febrile neutropenia]. / Management von neutropenischem Fieber.

Febrile neutropenia is a severe complication of systemic chemotherapy and has a negative effect on morbidity, mortality and prognosis. It is usually caused by bacterial infection. Therefore patients at high risk should prophylactically be given GCSF and a fluoroquinolone. In most cases neutropenic fever requires hospitalization and immediate empiric antibiotic therapy following baseline diagnostics. If there is no improvement after 72-96 h, therapy should be modified and further tests initiated. In these cases fungal or viral infection should be considered.

Multiple myeloma presenting with a fever of unknown origin and development of thrombotic thrombocytopenic purpura post-bortezomib.

Multiple myeloma rarely presents with a fever of unknown origin and diagnosis may be delayed. We describe a case of myeloma presenting in this way with raised serum-free light chains and TP53 deletion on cytogenetics. The patient developed thrombotic thrombocytopenia purpura (TTP) following bortezomib therapy but recovered spontaneously and was successfully re-challenged. We believe this is only the second case to describe this phenomenon post-bortezomib and the first to rechallenge the patient successfully without further recurrence of TTP. Possible mechanisms for this successful rechallenge are discussed.

[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.

[Immunosuppression - too strong or too weak?]. / Immunsuppression - zu stark oder zu schwach?

A 52 year old patient with immunosuppressive therapy for ANCA-negative vasculitis presented with fever and paraparesis of the legs, laboratory findings displayed high inflammatory markers. The differential diagnosis comprised acute infection, an exacerbation of vasculitis or a drug reaction. Despite meticulous diagnostics, including FDG-PET, no definitive cause for the symptoms could be uncovered. Empirical antibiotic treatment in combination with high doses of glucocorticosteroids lead to prompt resolution of fever and inflammatory laboratory markers.

Zuclopenthixol-induced neuroleptic malignant syndrome presenting as fever of unknown origin, hyperglycaemia and acute myocardial infarction in a 60-year-old man.

Neuroleptic malignant syndrome (NMS) is a rare clinical condition and potentially life-threatening complication of antipsychotic medications. We report a patient with an atypical presentation of NMS. A 60-year-old man with schizophrenia was admitted to our hospital with disturbed consciousness, fever and marked extrapyramidal rigidity both in the upper and lower extremities. He had been given i.m. zuclopenthixol 200 mg/month but had not taken the last dose. Laboratory investigations showed that creatinine phosphokinase 428 IU/l (normal up to 130), lactate dehydrogenase 772 IU/l (normal up to 450), blood glucose 256 mg/dl (65-110). Urine analyses revealed ketonuria. White blood cell (WBC) count was 6100 cells/mm(3). Therefore, the patient was diagnosed as having NMS and antipsychotic medications were stopped. Adequate hydration was provided and bromocryptine 5 mg was started three times a day. Despite treatment, the patient died due to acute myocardial infarction after 3 days of hospitalization.

Unexplained high fever in an elderly patient treated with clonidine, duloxetine, and atorvastatin.

BACKGROUND: Drug-induced fever is a clinical diagnosis and should always be considered when the fever is constant and high without a clear source of infection. Although drug-induced fever has been reported with other centrally acting antihypertensive drugs such as methyldopa, published reports of this adverse effect with clonidine in humans were not identified in a search of the literature. CASE SUMMARY: A 66-year-old institutionalized white female with a history of morbid obesity (body mass index, 40 kg/m2), Alzheimer's dementia, hypertension, and depression presented to a hospital in Boston, Massachusetts (Caritas Saint Elizabeth's Medical Center) with generalized weakness and shortness of breath and was found to have a non-ST segment elevation myocardial infarction. Before hospitalization, the patient was taking memantine 10 mg PO BID, donepezil 10 mg PO once daily, duloxetine 60 mg PO once daily, clonidine 0.1 mg PO TID, metoprolol 50 mg PO BID, and amlodipine 10 mg PO once daily. On admission, the patient was initiated on aspirin 325 mg, atorvastatin 80 mg, and clopidogrel 75 mg PO daily. Her dose of clonidine was increased to 0.2 mg PO TID to optimize blood pressure control, and metoprolol and amlodipine were continued at the same doses. The patient developed fever on the third day after the cardiac catheterization. The fever ranged from 99.0 degrees F to 102.7 degrees F. The physical examination, laboratory data analysis, multiple blood cultures, urinalysis, chest radiograph, and a computed tomography of the head, chest, abdomen, and pelvis did not reveal any source of infection. On the sixth day after admission, clonidine was reduced to the baseline dose of 0.1 mg PO TID and on the ninth day it was stopped. The patient was afebrile on the twelfth day and remained so for the duration of her hospitalization. Naranjo scores for her newly initiated concomitant medications were as follows: aspirin, 1; atorvastatin, 3; clonidine, 6; and clopidogrel, 1. The rating of 6 for clonidine suggests that it was probably associated with the fever in this patient. CONCLUSION: We describe a case of drug-induced fever probably associated with clonidine administration. The higher dose of clonidine alone or in interaction with duloxetine and atorvastatin may have contributed to the development of drug-induced fever.