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Biomedical subjects

M Karthaus

Publications and source records attributed to M Karthaus.

65 records · Page 4Linked to original sources

Early detection of chronic disseminated Candida infection in leukemia patients with febrile neutropenia: value of computer-assisted serial ultrasound documentation.

Computer tomography (CT) is known to be as sensitive as magnetic resonance imaging (MRI) in detecting fungal microabscesses in chronic disseminated candidiasis. However, all imaging techniques have to be repeated in cases of suspected fungal infection. Therefore, use of the CT or MRI scan is limited. Only ultrasound (US) examinations can be repeated as often as needed. The disadvantage of US is a lack of sufficient documentation. We analyzed the value of computer-assisted documentation in serial ultrasonography of leukemia patients with suspected chronic disseminated candidiasis. From November 1996 until October 1997, a total of 220 ultrasound examinations (Kranzbühler Logiq 500, 3.5 MHz convex array) were performed in 58 patients undergoing intensive chemotherapy. Initial US pictures were stored on a personal computer and compared with the live US at the time of reevaluation in cases of persistent fever. Ultrasound detected microabscesses in liver and/or spleen in eight of the 58 patients. Diagnosis was confirmed by autopsy/biopsy (n = 6), blood culture (n = 1), and a significant Candida antibody titer (n = 1). Focal lesions occurred only after neutrophil recovery. However, a newly evolving nonhomogeneous, micronodular pattern of liver and spleen occurred during febrile neutropenia in three patients, and two of these developed focal lesions subsequently. Follow-up was easy, since US pictures could be compared directly with stored examinations on screen. We conclude that serial US is sensitive in detecting microabscesses in the liver or the spleen. Computer-assisted US documentation proved to be a helpful tool for detection as well as in the follow-up of patients with chronic disseminated candidiasis.

Adolescent↗

Ceftriaxone monotherapy in the treatment of low-risk febrile neutropenia.

UNLABELLED: Febrile neutropenia in patients who have undergone chemotherapy is usually treated with a combination of broad-spectrum antibiotics. There are no exactly defined protocols for single-agent treatment because a clear definition of low risk febrile neutropenia is lacking. This paper examines the safety and efficacy of once-daily ceftriaxone in 376 cases. MATERIAL AND METHODS: In a prospective observational study carried out between February 1992 and January 1996, 959 febrile episodes at 48 hospitals were recorded. Inclusion criteria were neutropenia (absolute neutrophil count, ANC <1,000/ microl) with fever (>/=38.5 degreesC) or a C-reactive protein concentration >1 mg/dl and suspected infection. Nine hundred and one episodes (acute leukemia n = 396, lymphoma n = 220, solid tumors n = 272 and other disorders n = 13) in 828 patients aged between 1 and 97 years were analyzed, of which 876 episodes were evaluable for response. All patients initially underwent empirical treatment with ceftriaxone (adults: 2 g/day; children: 80 mg/kg/day), either alone (376) or in combination with other agents (525). RESULTS: The mean ANC was 423/ microl (SD +/- 316) and the median duration of neutropenia 10 days. Of the 363 episodes treated initially with ceftriaxone alone, 70.8% responded versus 56.9% in the combination therapy group. The favorable response to the initial monotherapy treatment was explained by a low-risk population in the monotherapy group. A KI >6 (p < 0.0001), ANC >/=500/ microl (p = 0.0001) and a duration of ANC <5 days (p < 0.05) were significantly more frequent in the monotherapy arm and were predictive of lower risk at the commencement of treatment. CONCLUSION: Ceftriaxone is effective in febrile neutropenia. Treatment with ceftriaxone alone was safe and highly effective in low-risk patients. Single-agent regimens appear to be a suitable treatment option in low-risk febrile neutropenia.

Adolescent↗

New strategies in the treatment of infectious complications in haematology and oncology: is there a role for out-patient antibiotic treatment of febrile neutropenia?

Febrile neutropenia is associated with a significant risk of complications and mortality. Patients with neutropenia secondary to cytostatic chemotherapy who develop fever are normally admitted to hospital and treated promptly with broad-spectrum antibiotics. Over the last 10 years, chemotherapy for solid tumours has been shifting out of the hospital setting into the ambit of community-based oncologists, and out-patient treatment with complex multidrug protocols is becoming increasingly common. In North America high-dose protocols combined with peripheral blood stem cell transfusion are already being administered on an out-patient basis. With the increase in the numbers of out-patients undergoing multidrug chemotherapy, there has been a corresponding rise in the severity and duration of neutropenia and in the incidence of associated infections. Patients with neutropenia of short duration (<7 days) and fever are at a relatively low risk for complications, and in these circumstances, out-patient antibiotic treatment is an alternative to costly hospitalisation. Drugs, whose antimicrobial coverage and pharmacokinetics make them particularly suitable for out-patient treatment of febrile neutropenia, include intravenous and oral quinolones and, for once-daily dosing, intravenous glycopeptides, ceftriaxone and intravenous aminoglycosides. Response rates of 60-95% have been achieved with such regimens in clinical trials, with hospital admission avoided in 75-95% of the cases. There is no doubt that out-patient treatment improves the quality of life of cancer patients. In Europe, however, there is a need for randomised clinical trials to support the establishment of out-patient-based treatment of febrile neutropenia. Out-patient antibiotic treatment of febrile neutropenia is still not standard practice, and community-based providers of such treatment must be adequately equipped and experienced in the management of this condition.

Anti-Bacterial Agents↗

Antifungal prophylaxis in neutropenic patients with hematologic malignancies: is there a real benefit?

Invasive fungal infections have been reported with an increasing incidence over the last 20 years. Fungal infections are an important cause of morbidity and mortality in patients with hematological malignancies. Therefore, in neutropenic patients different regimens of antifungal prophylaxis have been performed for more than 20 years, but the effect of antifungal prophylaxis is controversial. A long duration of neutropenia, impaired cell-mediated immunity as well as continuous corticosteroid therapy and sustained immunosuppression for graft-versus-host disease in patients treated with allogeneic bone marrow transplantation are known risk factors for invasive mycosis. Since early diagnosis of invasive fungal infection is difficult, strategies to prevent fungal infections seem to be attractive. The introduction of triazoles have provided us with a better armamentarium to prevent fungal infections. In this review, the current strategies of antifungal prophylaxis are discussed. Antifungal prophylaxis has been effective in reducing candida infection, however, there has been no proven successful prevention of invasive aspergillosis. In addition, there is no clearly proven benefit of antifungal prophylaxis regarding the reduction in the overall mortality. Thus the best way to reduce invasive fungal-related mortality will be early diagnosis and preemptive therapeutic approaches.

Antifungal Agents↗

European Surveillance of Infections in Cancer Patients--ESIC.

Major advances in cancer therapy result from development of multidrug chemotherapy regimens. Besides death from tumor progression, infections are currently one of the major causes of mortality and morbidity. Because of the risk of complications and mortality, the treatment for febrile neutropenia is admission to hospital and administration of broad-spectrum antibiotics. Response rates of initial antimicrobial treatment vary considerably (40-92%). Due to the heterogeneity of populations in randomized studies, comparison of efficacy and identification of risk factors is limited. This is the main reason why the European Society of Biomodulation and Chemotherapy (ESBiC) is conducting a surveillance study that concentrates more on the evaluation of risk factors than on the therapeutic outcome of prospective randomized antimicrobial regimens: European Surveillance of Infections in Cancer Patients (ESIC). The present contribution is to determine which cancer patients are at low risk for fever, and can benefit from first-line treatment with treatment options such as monotherapy as well as on an outpatient basis.

Anti-Bacterial Agents↗

Systemic fungal infections in patients with hematologic malignancies: indications and limitations of the antifungal armamentarium.

The rates of fungal infections have increased substantially in Europe as well as in North America. Most frequently Aspergillus spp. and Candida spp. are isolated. Despite the recent introduction of new azoles and lipid-based formulations of amphotericin B, there are relatively few randomized, controlled studies on the use of antifungal drugs in patients with hematological malignancies and invasive fungal infections. Conventional amphotericin B is considered the gold standard for the treatment of invasive fungal infections; however, adverse events limit conventional amphotericin B treatment. The newer azoles, fluconazole and itraconazole, are well tolerated; however, fluconazole has no activity against Aspergillus spp. An additional serious problem is the emerging resistance of nonalbicans Candida spp. to fluconazole. In this situation, lipid formulations of amphotericin B seem to be attractive, since the use of these drugs has been shown to be safe and effective. Considerably higher medical costs limit broader application of lipid formulations of amphotericin B. Because of the rapidly increasing incidence of serious fungal infections, we have reviewed current strategies and the role of newer antifungal drugs for the treatment of deep-organ infections.

Amphotericin B↗

Evaluation of neutropenic fever: value of serum and plasma parameters in clinical practice.

Treatment-related mortality due to infectious complications following potentially curable aggressive chemotherapy remains a major clinical problem. However, the diagnosis of neutropenic infections is difficult. Although it is common practice to institute empirical broad-spectrum antibiotics in neutropenic fever, liberal use of antibiotics may contribute to increasing resistance and superinfection such as systemic mycosis. Clinicians are searching for a highly specific and sensitive marker indicating early infection. Serum concentrations of several acute-phase proteins (C-reactive protein, serum amyloid A), proinflammatory cytokines (TNFalpha, IL-1, IFNgamma, IL-6, IL-8), soluble adhesion molecules (soluble E-selectin, vascular cell adhesion molecule 1, intercellular adhesion molecule 1) and more recently procalcitonin have been investigated as to whether these may contribute to identifying infections as the cause of neutropenic fever. Unfortunately, at present, based on the small and inconsistent amount of data available from the literature one is tempted to conclude that the predictive values of all these parameters are too low to influence the clinically based initial treatment decisions in patients with neutropenic fever.

Biomarkers↗

Intensive intravenous amphotericin B for prophylaxis of systemic fungal infections. Results of a prospective controlled pilot study in acute leukemia patients.

BACKGROUND: Invasive fungal infections are an increasing cause of morbidity in acute leukemia (AL) patients. METHODS: In a prospective pilot trial, the safety and efficacy of antifungal prophylaxis with intravenous (i.v.) amphotericin B (AMB; 1 mg/kg every 48 h) was studied in 46 consecutive cycles. Prophylaxis with i.v. AMB was carried out in patients treated with intensive chemotherapy for AL and compared with a control of 49 cycles without prophylaxis. RESULTS: Pulmonary infiltrates (5 vs. 23; p < 0.001) and fungal microabscesses in the liver or spleen (0 vs. 6; p = 0.014) occurred significantly less frequently in the prophylaxis group. While there were 3 deaths related to systemic fungal infections in the control group, there were none in the prophylaxis group. Escalation to conventional AMB (1.0 mg/kg/day) was significantly less frequent in the prophylaxis group (9 out of 46 cycles) compared with the control arm (29 out of 49 cycles; p = 0.001). A total of 695 mg of AMB per cycle was administered in the prophylaxis arm, compared with 634 mg/cycle for empirical treatment in the control group (p = 0.6). Infusion-related toxicity was documented in 29% of the cycles of prophylaxis compared with 55% of the cycles of empirical treatment with i.v. AMB in the control group. The nephrotoxicity of AMB prophylaxis was moderate, with >/= WHO degree II reported in 1 out of 46 cycles only. CONCLUSION: Intensive i.v. AMB prophylaxis reduced invasive fungal infections and led to a reduction in fungal microabscesses in the liver or spleen, as well as pulmonary infiltrates, in patients treated for AL. The need for escalation to empirical i.v. AMB treatment was significantly reduced. Intensive AMB prophylaxis was feasible, with moderate adverse effects.

Adult↗

Efficacy of a benzalkonium chloride-impregnated central venous catheter to prevent catheter-associated infection in cancer patients.

BACKGROUND: This study was performed to determine the efficacy of a benzalkonium chloride-impregnated central venous catheter (CVC) in preventing catheter-related infection in patients suffering from malignant diseases and undergoing chemotherapy. METHODS: A randomized, prospective clinical trial was carried out to compare the incidence of catheter-related colonization and catheter-related bacteremia using an antiseptic-impregnated CVC (n = 25) with that using a standard triple-lumen CVC (n = 25). RESULTS: All patients were treated with intensive chemotherapy for acute leukemia (n = 28), lymphoma (n = 17) or solid tumors (n = 5). Both study groups presented with similar data in regards to age, insertion site, duration of catheterization and neutropenia period during catheterization, demonstrating a comparable risk for catheter-related colonization. Suspicion of infection led to explantation in 14 versus 15 cases. Catheter-related colonization was proven in 4 cases (16%) and catheter-related bacteremia was observed only once (4%) in both groups. Statistical testing showed no significant differences between the study and control group. CONCLUSIONS: The rate of catheter-related colonization was lower than suspected in this high-risk patient group. The use of benzalkonium chloride-impregnated CVC failed to decrease the incidence of catheter-related colonization and bacteremia in patients with a high risk of infectious complications.

Adult↗

Ceftriaxone for the treatment of febrile episodes in nonneutropenic patients with hematooncological disease or HIV infection: comparison of outpatient and inpatient care.

BACKGROUND: Patients with hematooncological disease or HIV infection and febrile episodes are usually treated in hospital with broad-spectrum antibiotics. The aim of this observational study was to assess the feasibility of ambulatory parenteral antibiotic therapy in hematooncological or HIV-infected patients with confirmed or suspected infection. METHODS: The results in an outpatient treatment group were compared with those obtained in a group initially treated in hospital. Data were gathered on 90 outpatients and 72 inpatients. The inclusion criteria were fever > or =37.5 degrees C with an identified focus of infection, fever > or =38.0 degrees C of suspected bacterial origin with no identified focus of infection, leukocytosis > or =9,000/microl or C-reactive protein elevation > or =10 mg/l. RESULTS: Eighty outpatients and 69 inpatients were evaluable. Treatment in the outpatient group was begun with ceftriaxone. This led to defervescence in 87.5% of cases. The mean treatment duration was 7.1 days. Comparison of results in the outpatients with those initially hospitalized for treatment showed similar success rates. The mean hospital stay in the latter group was 12.9 days. CONCLUSIONS: Ceftriaxone represents an effective treatment for outpatient management of febrile episodes in patients with hematooncological disease or HIV infection. Outpatient treatment is more cost-effective than inpatient care.

Adolescent↗