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1.
Ann Oncol ; 29(6): 1354-1365, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29688266

ABSTRACT

Infectious complications are a significant cause of morbidity and mortality in patients with malignancies specifically when receiving anticancer treatments. Prevention of infection through vaccines is an important aspect of clinical care of cancer patients. Immunocompromising effects of the underlying disease as well as of antineoplastic therapies need to be considered when devising vaccination strategies. This guideline provides clinical recommendations on vaccine use in cancer patients including autologous stem cell transplant recipients, while allogeneic stem cell transplantation is subject of a separate guideline. The document was prepared by the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) by reviewing currently available data and applying evidence-based medicine criteria.


Subject(s)
Anti-Infective Agents/therapeutic use , Communicable Diseases/drug therapy , Hematologic Neoplasms/therapy , Neoplasms/therapy , Practice Guidelines as Topic/standards , Stem Cell Transplantation/adverse effects , Vaccination/standards , Communicable Diseases/etiology , Humans , Prognosis
2.
Eur J Clin Microbiol Infect Dis ; 36(3): 565-573, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27838792

ABSTRACT

Influenza virus infections (IVI) may pose a vital threat to immunocompromised patients such as those suffering from malignancies, but specific data on epidemiology and outcome in these patients are scarce. In this study, we collected data on patients with active cancer or with a history of cancer, presenting with documented IVI in eight centres in Germany. Two hundred and three patients were identified, suffering from haematological malignancies or solid tumours; 109 (54 %) patients had active malignant disease. Influenza A was detected in 155 (77 %) and Influenza B in 46 (23 %) of patients (genera not determined in two patients). Clinical symptoms were consistent with upper respiratory tract infection in 55/203 (27 %), influenza-like illness in 82/203 (40 %), and pneumonia in 67/203 (33 %). Anti-viral treatment with oseltamivir was received by 116/195 (59 %). Superinfections occurred in 37/203 (18 %), and admission on an intensive care unit was required in 26/203 (13 %). Seventeen patients (9 %) died. Independent risk factors for death were delayed diagnosis of IVI and bacterial or fungal superinfection, but not underlying malignancy or ongoing immunosuppression. In conclusion, patients with IVI show high rates of pneumonia and mortality. Early and rapid diagnosis is essential. The high rate of pneumonia and superinfections should be taken into account when managing IVI in these patients.


Subject(s)
Influenza, Human/epidemiology , Influenza, Human/pathology , Neoplasms/complications , Aged , Antiviral Agents/therapeutic use , Critical Care , Female , Germany/epidemiology , Humans , Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/mortality , Influenza, Human/virology , Male , Middle Aged , Oseltamivir/therapeutic use , Risk Factors , Societies , Superinfection/epidemiology , Survival Analysis , Treatment Outcome
3.
Bone Marrow Transplant ; 50(5): 679-84, 2015 May.
Article in English | MEDLINE | ID: mdl-25642765

ABSTRACT

Prognosis is poor for patients with biologically aggressive Non-Hodgkin lymphoma (NHL), refractory to chemotherapy or relapsed after autologous transplantation, especially when no disease control before allogeneic transplantation is achieved. In 16 patients (median age 53, median prior regimes 5) with relapsed or refractory non-remission NHL, we analysed retrospectively the efficacy of a sequential therapy comprising clofarabine re-induction followed by a reduced-intensity conditioning with fludarabine, CY and melphalan, and T-cell-replete HLA-haploidentical transplantation. High-dose CY was utilized post-transplantation. All patients engrafted. Early response (day +30) was achieved in 94%. Treatment-related grade III-IV toxicity occurred in 56%, most commonly transient elevation of transaminases (36%), while there was a low incidence of infections (19% CMV reactivation, 19% invasive fungal infection) and GVHD (GVHD: acute III-IV: 6%; mild chronic: 25%). One-year non-relapse mortality was 19%. After a median follow-up of 21 months, estimated 1- and 2-year PFS was 56 and 50%, respectively, with 11 patients (69%) still alive after 2 years. In summary, sequential therapy is feasible and effective and provides an acceptable toxicity profile in high-risk non-remission NHL. Presumably, cytotoxic reinduction with clofarabine provides enough remission time for the graft-versus lymphoma effect of HLA-haploidentical transplantation to kick in, even in lymphomas that are otherwise chemo-refractory.


Subject(s)
Adenine Nucleotides/administration & dosage , Antimetabolites, Antineoplastic/administration & dosage , Arabinonucleosides/administration & dosage , HLA Antigens , Hematopoietic Stem Cell Transplantation , Lymphoma, Non-Hodgkin , Adult , Aged , Allografts , Clofarabine , Disease-Free Survival , Female , Humans , Lymphoma, Non-Hodgkin/mortality , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Recurrence , Retrospective Studies , Survival Rate
4.
Ann Oncol ; 26(1): 21-33, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24833776

ABSTRACT

Up to 25% of patients with profound neutropenia lasting for >10 days develop lung infiltrates, which frequently do not respond to broad-spectrum antibacterial therapy. While a causative pathogen remains undetected in the majority of cases, Aspergillus spp., Pneumocystis jirovecii, multi-resistant Gram-negative pathogens, mycobacteria or respiratory viruses may be involved. In at-risk patients who have received trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis, filamentous fungal pathogens appear to be predominant, yet commonly not proven at the time of treatment initiation. Pathogens isolated from blood cultures, bronchoalveolar lavage (BAL) or respiratory secretions are not always relevant for the etiology of pulmonary infiltrates and should therefore be interpreted critically. Laboratory tests for detecting Aspergillus galactomannan, ß-D-glucan or DNA from blood, BAL or tissue samples may facilitate the diagnosis; however, most polymerase chain reaction assays are not yet standardized and validated. Apart from infectious agents, pulmonary side-effects from cytotoxic drugs, radiotherapy or pulmonary involvement by the underlying malignancy should be included into differential diagnosis and eventually be clarified by invasive diagnostic procedures. Pre-emptive treatment with mold-active systemic antifungal agents improves clinical outcome, while other microorganisms are preferably treated only when microbiologically documented. High-dose TMP/SMX is first choice for treatment of Pneumocystis pneumonia, while cytomegalovirus pneumonia is treated primarily with ganciclovir or foscarnet in most patients. In a considerable number of patients, clinical outcome may be favorable despite respiratory failure, so that intensive care should be unrestrictedly provided in patients whose prognosis is not desperate due to other reasons.


Subject(s)
Anti-Infective Agents/therapeutic use , Bronchoalveolar Lavage Fluid , Lung Diseases/diagnosis , Lung Diseases/drug therapy , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/parasitology , Bronchoalveolar Lavage Fluid/virology , Drug Combinations , Fever , Humans , Lung/microbiology , Lung/parasitology , Lung/virology , Lung Diseases/microbiology , Neutropenia , Sulfadoxine/therapeutic use , Suppuration/microbiology , Suppuration/parasitology , Suppuration/virology , Trimethoprim/therapeutic use
6.
Bone Marrow Transplant ; 49(7): 895-901, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24820212

ABSTRACT

Haploidentical haematopoietic SCT (HSCT) using T-cell-replete grafts and post-transplant high-dose CY has found increasing acceptance. Our purpose was to evaluate the feasibility and outcome of this strategy as second HSCT incorporating donor change for acute leukaemia relapse after a first allogeneic transplantation. The courses of 20 consecutive adults (median age 37 years, 12 male) with AML (n=14), ALL (n=5) and acute bi-phenotypic leukaemia (n=1) were analysed retrospectively. Conditioning consisted of fludarabine, CY and either melphalan or TBI or tresosulfan+/-etoposide. Engraftment was achieved in 17 (85%), and a second remission was induced in 15 patients (75%) on day +30. The rate of grade II-IV acute GvHD was 35%, while chronic GvHD occurred in five patients. Most commonly observed grade III-IV toxicities were mucositis (30%), hyperbilirubinemia (20%), elevation of transaminases (20%) and creatinine (20%), while invasive fungal infection affected 30%. One-year non-relapse mortality (NRM) was 36%. At a median follow-up of 17 months, estimated 1-year OS was 45%, and 1-year relapse-free survival was 33%. This strategy was feasible and allowed for successful engraftment with a moderate rate of toxicity. Early outcome and NRM are at least comparable with results after a second HSCT from HLA-matched donors without donor change at HSCT2.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Leukemia/therapy , Transplantation Conditioning/methods , Acute Disease , Adult , Female , Humans , Male , Middle Aged , Recurrence , Tissue Donors , Transplantation, Homologous , Young Adult
7.
Leukemia ; 28(5): 1001-7, 2014 May.
Article in English | MEDLINE | ID: mdl-24150216

ABSTRACT

Chemomodulation of cytarabine by fludarabine has been attributed with a higher antileukemic efficacy, but randomized trials to address this question are rare. We therefore conducted a multicenter, randomized phase III study to evaluate the antileukemic efficacy of adding fludarabine to sequential high-dose cytarabine+idarubicin (SHAI) re-induction chemotherapy in relapsed or refractory acute myeloid leukemia (AML). Patients (n=326, of which 281 were evaluable) were randomly assigned to SHAI (cytarabine, 1 g/m(2) bid, days 1-2 and 8-9 (3 g/m(2) for patients ≤ 60 years with refractory AML or ≥ 2nd relapse); idarubicin 10 mg/m(2) daily, days 3-4 and 10-11) or F-SHAI (SHAI with fludarabine, 15 mg/m(2), 4 h before cytarabine). Although complete remission (CR) rates (35% SHAI and 44% F-SHAI) and overall survival did not differ between both regimens, fludarabine prolonged time to treatment failure from 2.04 to 3.38 months (median, P<0.05). Twenty-seven percent of patients proceeded to allogeneic stem cell transplantation, with a significantly higher number of patients in CR or incomplete remission in the F-SHAI group (22 vs 10%, P<0.01). In conclusion, fludarabine has a beneficial, although moderate, impact on the antileukemic efficacy of high-dose cytarabine-based salvage therapy for relapsed and refractory AML.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cytarabine/administration & dosage , Female , Humans , Male , Middle Aged , Prognosis , Recurrence , Survival Analysis , Vidarabine/administration & dosage , Vidarabine/analogs & derivatives , Young Adult
8.
Mycoses ; 55(6): 514-20, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22471310

ABSTRACT

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51,517 in the IFD group and €30,454 in the control group. Incremental costs of €21,063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.


Subject(s)
Health Care Costs , Leukemia, Myeloid, Acute/economics , Mycoses/drug therapy , Mycoses/economics , Myelodysplastic Syndromes/economics , Adult , Aged , Aged, 80 and over , Antifungal Agents/economics , Antifungal Agents/therapeutic use , Female , Germany , Humans , Length of Stay/economics , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/drug therapy , Male , Middle Aged , Mycoses/complications , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/drug therapy , Retrospective Studies , Young Adult
9.
Pediatr Radiol ; 41(11): 1421-8, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21904830

ABSTRACT

BACKGROUND: Subglottic haemangioma causes progressive and life-threatening stridor, typically manifesting at age 2-3 months. Standard diagnosis is by laryngoscopy. Larynx sonography is rarely used but allows assessment of the presence and extension of a mass that impinges on the subglottic airway. The additional use of colour Doppler enables demonstration of the vascular nature of such masses. OBJECTIVE: To compare US and endoscopic findings in infants with subglottic haemangioma and to evaluate accuracy of US and colour Doppler imaging in this diagnosis. MATERIALS AND METHODS: We report eight infants with subglottic haemangioma seen in our institution over the last decade. They presented with laryngeal stridor and were all investigated with both US and endoscopy. Six infants underwent colour Doppler sonography. RESULTS: US and endoscopic findings showed excellent anatomical correlation in lateral subglottic haemangioma. Colour Doppler imaging was deemed helpful in four infants. CONCLUSION: Larynx sonography with complementary colour Doppler imaging was non-invasive and helpful in the diagnosis of subglottic haemangioma.


Subject(s)
Hemangioma/diagnosis , Laryngeal Neoplasms/diagnosis , Ultrasonography, Doppler, Color , Child, Preschool , Female , Hemangioma/diagnostic imaging , Humans , Infant , Laryngeal Neoplasms/diagnostic imaging , Male , Ultrasonography, Doppler
10.
Klin Padiatr ; 223(1): 22-6, 2011 Jan.
Article in English | MEDLINE | ID: mdl-20862631

ABSTRACT

BACKGROUND: As diagnostic methods for primary ciliary dyskinesia are not generally available, we tested whether clinical criteria allow to preselect patients with a high probability of this disease, who should be further investigated in a specialized centre. PATIENTS AND METHODS: In patients with chronic cough we compared parameters of the case history with the finding of a reduced ciliary beat frequency (CBF). Data sheets of 323 patients (133 females, 190 males) aged 1 week through 40 years (median age 4.5 years) were available for analysis. Of these patients 46 (14%) had a reduced CBF. RESULTS: In this group the following features were found significantly more frequently compared to patients with normal CBF: neonatal respiratory disorder (odds ratio (OR) 9.0; 95% confidence interval (95% CI) 3.2;25), situs inversus (OR 8.1; 95% CI 2.5;26), retention of airway secretions (OR 6.7; 95% CI 2.4;19), recurrent pneumonia (OR 4.1; 95% CI 1.8;9.5), bronchiectasis (OR 3.5; 95% CI 1.2;11), asthma with poor response to treatment (OR 2.4; 95% CI 1.1;5.3). At least one of these potential indicators was present in 91% of the patients with reduced CBF. CONCLUSIONS: In patients with chronic cough specific parameters of the case history indicate a high probability of a reduced ciliary beat frequency which is an indicator for primary ciliary dyskinesia. If none of these findings is present, a reduced CBF is highly unlikely.


Subject(s)
Cough/etiology , Kartagener Syndrome/diagnosis , Mass Screening , Surveys and Questionnaires , Adolescent , Adult , Child , Child, Preschool , Chronic Disease , Diagnosis, Differential , Female , Humans , Infant , Infant, Newborn , Male , Probability , Risk Factors , Young Adult
11.
Internist (Berl) ; 50(6): 685-90, 2009 Jun.
Article in German | MEDLINE | ID: mdl-19404586

ABSTRACT

Fever is a common symptom in patients with malignancies. On the one hand it may be an (initial) symptom of cancer, on the other hand it may occur as a side effect of chemotherapy. Often a precise cause of fever can not be established and in these cases febrile temperatures >38.3 degrees C without proof of infection or relapse/progress of tumor is defined as fever of unknown origin. Especially hematologic neoplasias are accompanied by fever. Here, neoplastic fever must be distinguished from fever following immunosuppressive chemotherapy. In the latter severe infections due to neutropenia induced by cytoreductive chemotherapy is often identified as the cause of fever. These patients display a high morbidity and mortality, especially if an empiric anti-infectious treatment is not administered in time. A meticulous diagnostic work-up is therefore necessary, and until proven otherwise, an infectious cause must be considered and empiric antibiotic treatment initiated.


Subject(s)
Fever of Unknown Origin/diagnosis , Fever of Unknown Origin/etiology , Neoplasms/complications , Neoplasms/diagnosis , Diagnosis, Differential , Humans
12.
Transpl Infect Dis ; 11(3): 220-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19298239

ABSTRACT

BACKGROUND: Bacterial, viral, and fungal pathogens frequently cause severe, life-threatening infections in immunocompromised patients after allogeneic hematopoietic stem cell transplantation (SCT). OBJECTIVE: To compare the frequency of infections in patients with matched-related (Group A) or with human leukocyte antigen (HLA)-matched-unrelated donors (Group B). PATIENTS AND METHODS: Patients treated at our transplantation unit between April 2004 and April 2005 were enrolled into this analysis. Documentation comprised demographic data, conditioning treatment, stem cell source, clinical course, as well as microbiological and clinical data and mortality. RESULTS: We analyzed 59 patients, 22 in Group A and 37 in Group B. Both groups were well balanced regarding demographic data. Diagnoses were acute myeloid leukemia (30 of 59 patients, 50.8%), multiple myeloma (15.2%), acute lymphoblastic leukemia (11.9%), and chronic myeloid leukemia (10.2%). Patients in Group A developed infections in 95.5% of the cases compared with 97.3% in patients in Group B. Most frequently detected pathogens were Staphylococcus species, human herpesvirus-6, and Epstein-Barr virus. Three proven fungal infections were detected in Group A compared with 9 proven fungal infections in Group B. Lung infiltrations were observed in equivalent incidence in both groups. Two years after transplantation, 55.9% of patients were alive (Group A: 68.2%; Group B: 48.6%, not significant). CONCLUSION: Allogeneic SCT from HLA-matched-unrelated donors does not have a higher infection risk than patients transplanted from matched-related donors.


Subject(s)
Bacterial Infections/epidemiology , Donor Selection , Mycoses/epidemiology , Stem Cell Transplantation/adverse effects , Transplantation, Homologous/adverse effects , Virus Diseases/epidemiology , Adult , Bacterial Infections/diagnosis , Bacterial Infections/etiology , Female , Histocompatibility Testing , Humans , Incidence , Male , Middle Aged , Mycoses/diagnosis , Mycoses/etiology , Risk Assessment , Virus Diseases/diagnosis , Virus Diseases/etiology
13.
Pediatr Allergy Immunol ; 19(4): 348-54, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18167160

ABSTRACT

Cow's milk protein allergy (CMPA) is best treated by complete elimination of cow's milk from the diet. For infants with CMPA who cannot be breast-fed, formulas based on extensively hydrolyzed proteins or on amino acids are the preferred substitutes for cow's milk-based formulas. In this study, we compared the tolerance and growth of infants with CMPA who were fed a new extensively hydrolyzed formula containing lactose (eHF) with those who were fed an amino acid formula (AAF). This was a prospective, multi-center, randomized, reference-controlled study. Seventy-seven infants <12 months old with suspected CMPA were enrolled. In 66 of these, CMPA was confirmed by oral challenge in a double-blind, placebo-controlled food challenge (DBPCFC) or by a medical history of severe allergic reaction to cow's milk and a positive skin prick test. These infants were then tested for their reaction to eHF and AAF in a DBPCFC. All infants tolerated both formulas and were randomized to receive either eHF (n = 34) or AAF (n = 32) for 180 days. Growth (weight, length, and head circumference) and tolerance [skin, gastro-intestinal, and respiratory tract symptoms of allergy] were evaluated after 30, 60, 90, and 180 days. There were no significant differences between the two groups in any of the growth measurements. Length and head circumference were similar to Euro-growth standards, but weight was slightly lower. Gastro-intestinal and respiratory tract symptoms of allergy were also similar in the two groups. However, whereas SCORAD scores for atopic dermatitis remained constant throughout the study in infants-fed eHF, there was a slight decrease in those fed AAF. Infants-fed eHF had significantly fewer incidents of vomiting than infants-fed AAF and a significantly higher frequency of soft stools. The new eHF is safe and well tolerated in infants diagnosed with CMPA.


Subject(s)
Infant Formula , Milk Hypersensitivity , Milk/adverse effects , Protein Hydrolysates/adverse effects , Animals , Cattle , Female , Growth , Humans , Infant , Infant Formula/administration & dosage , Infant Formula/metabolism , Infant, Newborn , Male , Skin Tests
14.
Support Care Cancer ; 16(6): 599-606, 2008 Jun.
Article in English | MEDLINE | ID: mdl-17943326

ABSTRACT

GOALS OF WORK: Immunocompromised patients with malignant diseases often suffer from pulmonary infections. Early detection of these life-threatening infections is crucial to start effective treatment. The gold standard for the diagnosis of these disorders is high-resolution computed tomography (HR-CT) of the chest. This method, however, has limitations, for instance, in the discrimination of early interstitial infiltrates and the use of X-rays. We conducted a study to determine the feasibility and sensitivity of magnetic resonance imaging (MRI) of the lung compared to HR-CT in immunocompromised patients with persistent fever in neutropenia and suspected pneumonia. MATERIALS AND METHODS: Between January 2003 and July 2004, 50 consecutive neutropenic patients with fever of unknown origin and negative chest X-ray were examined with HR-CT of the lungs. Patients with pulmonary infiltrates were further examined with MRI of the chest within 24 h after HR-CT using a specific lung protocol. In addition, microbiological testing was performed for the characterization of the causative pathogen. RESULTS: Of 50 patients, 35 had pulmonary infiltration according to HR-CT; these were examined with MRI of the lungs. MRI showed a high correlation (91%) with the findings in HR-CT. Both HR-CT and MRI were feasible in 94% of the examined patients. In 12 of 35 patients, fungal pathogens were identified in microbiological testing. CONCLUSIONS: MRI of the lungs is feasible in neutropenic patients with suspected pulmonary infection. Compared to HR-CT, MRI displays a high sensitivity in the detection of pulmonary infiltrates. MRI offers the opportunity of follow-up examinations without repeated X-ray exposure to the patient.


Subject(s)
Fever/diagnosis , Magnetic Resonance Imaging , Neoplasms/complications , Neutropenia/diagnosis , Pneumonia/diagnosis , Adult , Aged , Aged, 80 and over , Early Diagnosis , Feasibility Studies , Female , Fever/etiology , Humans , Male , Middle Aged , Neutropenia/etiology , Pneumonia/etiology , Sensitivity and Specificity , Tomography, X-Ray Computed
15.
Nucleic Acids Res ; 35(22): e151, 2007.
Article in English | MEDLINE | ID: mdl-18073198

ABSTRACT

Expression profiling of stem cells is challenging due to their small numbers and heterogeneity. The PCR colony (polony) approach has theoretical advantages as an assay for stem cells but has not been applied to small numbers of cells. An assay has been developed that is sensitive enough to detect mRNAs from small numbers of ES cells and from fractions of a single mouse blastocyst. Genes assayed include Oct3, Rex1, Nanog, Cdx2 and GLUT-1. The assay is highly sensitive so that multiple mRNAs from a single blastocyst were easily detected in the same assay. In its present version, the assay is an attractive alternative to conventional RT-PCR for profiling small populations of stem cells. The assay is also amenable to improvements that will increase its sensitivity and ability to analyze many cDNAs simultaneously.


Subject(s)
Blastocyst/metabolism , Embryonic Stem Cells/metabolism , Gene Expression Profiling/methods , RNA, Messenger/analysis , Animals , Cell Line , Mice , Organic Cation Transport Proteins/genetics , Polymerase Chain Reaction
16.
Dtsch Med Wochenschr ; 132(40): 2062-6, 2007 Oct.
Article in German | MEDLINE | ID: mdl-17899499

ABSTRACT

BACKGROUND: Activity and efficacy of liposomal amphotericin B have been established for the treatment of severe fungal infections. Nephrotoxic side effects, especially during prolonged administration, are regarded as a major disadvantage. In this study we examined the response rates and side effects, particularly nephrotoxicity, of treatment with liposomal amphotericin B in a large cohort of patients. PATIENTS AND METHODS: 406 patients treated with liposomal amphotericin B between January 1999 and August 2003 in participating German hospitals were included. Documentation included demographic and clinical data, reason for the treatment with liposomal amphotericin B, length of treatment, response to antifungal treatment and side effects. RESULTS: 42.4% of the 406 patients were females. Their ages ranged from 1 day to 77 years. 83 % of the patients had malignancies and 65.5 % had fever of unknown origin (FUO). Mean duration of treatment with liposomal amphotericin B was 20 +/- 20 days, at an average dose of 2.3 mg/kg/d. 209 patients (51.5 %) showed complete response (CR),105 patients (25.9 %) partial response (PR) and 51 (12.6 %) patients died during the observation. 80.0 % of patients with FUO showed complete or partial response of symptoms. Mean serum creatinine increased from 0.9 mg/kg before start of therapy with liposomal amphotericin B to 1.1 mg/kg during treatment. Side effects (common toxicity criteria > grade 1) occurred in 94 patients (23/2 %). Among these hypokalemia (6.2 %) and liver damage (5,2 %) were the most common. Nephrotoxicity was documented in 17 patients (4.2 %). CONCLUSION: Liposomal amphotericin B is a safe and efficacious antifungal drug in the treatment of severe invasive fungal infections and fever of unknown origin. Nephrotoxicity is usually not a limiting factor when using liposomal amphotericin B, if it is administered in approved dosage.


Subject(s)
Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Mycoses/drug therapy , Adolescent , Adult , Aged , Amphotericin B/adverse effects , Antifungal Agents/adverse effects , Child , Child, Preschool , Cohort Studies , Female , Fever of Unknown Origin/complications , Fever of Unknown Origin/drug therapy , Humans , Infant , Infant, Newborn , Kidney/drug effects , Liposomes , Male , Middle Aged , Mycoses/complications , Mycoses/mortality , Neoplasms/complications , Prospective Studies , Treatment Outcome
17.
Eur J Clin Microbiol Infect Dis ; 26(11): 843-5, 2007 Nov.
Article in English | MEDLINE | ID: mdl-17690928

ABSTRACT

A neutropenic patient with acute myeloid leukaemia experienced a breakthrough infection of Trichosporon asahii during posaconazole treatment. After treatment was changed to a combination therapy with voriconazole and liposomal amphotericin B, the infection resolved. Posaconazole works effectively as an antifungal prophylaxis and salvage therapy in rare invasive fungal infections. This case however illustrates that breakthrough infections with T. asahii may occur during posaconazole treatment.


Subject(s)
Cross Infection/microbiology , Leukemia, Myeloid, Acute/complications , Mycoses/microbiology , Triazoles/therapeutic use , Trichosporon/drug effects , Trichosporon/isolation & purification , Aged , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Cross Infection/drug therapy , Drug Therapy, Combination , Humans , Male , Mycoses/drug therapy , Pyrimidines/therapeutic use , Voriconazole
18.
Pneumologie ; 61(8): 499-508, 2007 Aug.
Article in German | MEDLINE | ID: mdl-17525913

ABSTRACT

BACKGROUND: Children with interstitial pneumonitis (IP) of unknown origin often have to undergo open lung biopsy to establish a final diagnosis. Open lung biopsy is an invasive procedure with major potential complications. In the meantime, CT-guided transthoracic lung biopsy (TLB) has become a common diagnostic procedure in adults. OBJECTIVE: The aim of this study was to retrospectively evaluate the efficacy and radiation exposure of low-dose CT-guided TLB in children with non-infectious IP of unknown origin. METHODS: Twelve children (7-males, age range: 7 months-15 years) with non-infectious IP of unknown origin and inconclusive clinical tests underwent CT-guided TLB with a 20-gauge biopsy instrument. A low-dose protocol with acquisition of single slices was used on a 16-row CT scanner: 80 kVp, 20 mAs, slice thickness 10 mm. Biopsy specimens were processed by standard histopathological and immunohistochemical techniques and effective doses were individually calculated. RESULTS: All biopsies were performed without major complications. Two children (17 %) developed a small pneumothorax/pulmonary haemorrhage that resolved spontaneously. A final diagnosis could be established in 9/12 patients (75 %) by CT-guided TLB. In 2 patients (17 %) the results of TLB were inconclusive; however, the clinical suspicion could be disproved. Open lung biopsy was performed in 1 patient (8 %), which demonstrated idiopathic pulmonary fibrosis. On average, the effective dose of CT-guided TLB was 0.78 mSv (0.4 - 1.1 mSv). CONCLUSION: Low-dose CT-guided TLB can be a helpful method for investigating children with non-infectious IP of unknown origin thus making open lung biopsy unnecessary. Application of a low-dose protocol leads to a significant reduction of radiation exposure in CT-guided TLB.


Subject(s)
Lung Diseases, Interstitial/pathology , Lung/pathology , Tomography, X-Ray Computed/methods , Adolescent , Biopsy , Child , Child, Preschool , Female , Humans , Image Processing, Computer-Assisted , Infant , Lung/diagnostic imaging , Lung Diseases, Interstitial/diagnostic imaging , Male , Radionuclide Imaging
19.
Klin Padiatr ; 218(5): 283-6, 2006.
Article in German | MEDLINE | ID: mdl-16947097

ABSTRACT

BACKGROUND: Exposure to environmental tobacco smoke at home increases the risk for numerous diseases in childhood. In this study we asked if maternal tobacco consumption can be reduced by a written advice of the paediatrician. PATIENTS AND METHODS: In a paediatrician's practice we recruited 40 mothers who smoked ten or more cigarettes per day according to their own statement. The paediatrician's intervention consisted in a short written advice to reduce tobacco consumption. At the beginning of the study and six weeks later we obtained urine samples of the mothers in order to measure the concentrations of the nicotine metabolite cotinine. A subgroup of the study population was informed about the initial concentration of cotinine, the other subgroup was not informed. MAIN RESULTS: Following the written advice of the paediatrician mothers reduced their consumption of tobacco products according to their own information as well as according to the concentrations of cotinine. Confronting mothers with their initial concentrations of cotinine was not found to be an additional factor reducing tobacco consumption. CONCLUSIONS: Maternal consumption of tobacco products can be reduced significantly by an advice of the paediatrician at least for a short time.


Subject(s)
Correspondence as Topic , Mothers/education , Pediatrics , Physician's Role , Smoking Cessation , Tobacco Smoke Pollution/adverse effects , Adult , Child , Cotinine/urine , Female , Follow-Up Studies , Humans
20.
Klin Padiatr ; 218(4): 213-20, 2006.
Article in German | MEDLINE | ID: mdl-16819702

ABSTRACT

BACKGROUND: During the last twenty years the incidence of measles and mumps decreased after introduction of vaccinations in the industrial nations. The vaccination rate of the population in Germany lies currently under the required elimination rate. The epidemiological situation has changed altogether. The illness age has on the one hand moved up, teenager and adult suffer more frequent these so-called children's diseases with an increased complication rate. On the other hand illness cases in infancy seeming to increase. It was aim of this study to examinate the current serological situation for measles and mumps antibody status in women in childbed and their healthy newborns at birth time and during the first seven to nine life months. PATIENTS AND METHOD: 237 healthy newborns, born in 1999 in Bochum, West-Germany and their mothers were included. The mothers were asked if and when they did suffer from measles and mumps or were questioned to active vaccinations against these diseases. Immediately antepartal from all mothers was taken a venous blood sample. Immediately postpartal from all newborn childs umbilical cord blood was taken and again a blood sample in the age of six to eight months. In the serum tests the measle and mumps IgG antibody concentrations were examined quantitatively with ELISA methods. In cases with negative or borderline positive values the plaque neutralization test was also used for measuring of the measle antibodies. CONCLUSIONS: Between the maternal and neonatal titers results the knownly positive correlation. Maternal lending immunity against measle and mumps lasts more less into infancy as generally suspected. An earlier first active immunization against measles and mumps could be discussed. The strict realisation of the present vaccinating recommendations should be operated as a matter of priority to lead to the desired measles and mumps eradication.


Subject(s)
Antibodies, Viral/blood , Immunity, Maternally-Acquired/immunology , Immunoglobulin G/blood , Infant, Newborn/immunology , Measles virus/immunology , Mumps virus/immunology , Adult , Age Factors , Female , Humans , Infant , Male , Measles/immunology , Measles/prevention & control , Measles Vaccine/administration & dosage , Measles Vaccine/immunology , Mumps/immunology , Mumps/prevention & control , Mumps Vaccine/administration & dosage , Mumps Vaccine/immunology , Pregnancy , Pregnancy Trimester, Third
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