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G Silling

Publications and source records attributed to G Silling.

At least 19 recordsLinked to original sources
PubMed2006

A prospective, randomized multicenter trial of the empirical addition of antifungal therapy for febrile neutropenic cancer patients: results of the Paul Ehrlich Society for Chemotherapy (PEG) Multicenter Trial II.

BACKGROUND: The aim of the study was to compare the efficacy of empirical antifungals in combination with broad spectrum antibiotics with that of antibiotics alone in high risk febrile neutropenic cancer patients not responding to initial antibacterial therapy. PATIENTS AND METHODS: A prospective, randomized controlled trial was conducted at 22 cancer centers in Germany. Patients with fever of unknown origin were randomized to either piperacillin (Pip) plus an aminoglycoside (AMG) (arm A) or a third generation cephalosporin (Ceph) plus AMG (arm B). Patients not responding after 4-6 days were randomized to either imipenem (Imi) plus glycopeptide (GLP) (arm C), or Imi/GLP plus amphotericin B deoxycholate (AmB) plus 5-flucytosine (5-FC) (arm D), or Imi/GLP plus fluconazole (Fluco) (arm E). A successful outcome was defined as resolution of fever. RESULTS: In arm A, 192 of 373 patients (51.5%) responded as compared to 176 of 344 patients (51.2%) in arm B. The response rates of 155 patients randomized for further empirical treatment were 55.6%, 77.8% and 62.5% in arm C, D and E, respectively. The difference between arm C and D was of borderline statistical significance (p = 0.06) after correction for multiple testing. CONCLUSION: In neutropenic cancer patients with persistent fever the combination of antibiotics with AmB/5-FC is superior to salvage antibacterial therapy alone. There is no difference in efficacy between Pip and third generation Ceph given as initial empirical therapy in combination with an AMG.

Adolescent↗
PubMed2005

Caspofungin treatment in severely ill, immunocompromised patients: a case-documentation study of 118 patients.

BACKGROUND: Caspofungin has shown efficacy in empirical antifungal therapy in neutropenic patients, refractory invasive Aspergillus infections and invasive candidiasis. Here we report the currently largest series of patients treated with caspofungin outside clinical trials. METHODS: Centres in Germany that were known to treat patients with invasive fungal infections were asked to fill out detailed questionnaires for all patients treated with caspofungin. No effort was made to influence the decision to use caspofungin. RESULTS: A total of 118 patients were evaluable (median age 48 years, interquartile range 38-58), out of which 41 (35%) suffered from acute leukaemia, 31 (26%) had allogeneic stem cell transplants, 16 (14%) lymphoma or myeloma, 8 (7%) autologous stem cell transplants and 22 (19%) other causes for immunosuppression. One hundred and six patients were evaluable for efficacy out of which 68 (64%) patients achieved a complete or partial remission. A total of 81 out of 115 (70%) patients were alive 30 days after the end of caspofungin therapy. Response rates were similar in proven (20/32, 63%) and probable (27/46, 59%) infections, in neutropenic patients (41/55, 75%) and in patients who were (44/70, 63%) or were not (24/36, 67%) refractory to antifungal pre-treatment. The response rate in mechanically ventilated patients was 29% (7/24). Caspofungin was well tolerated, even in 14 patients, who were concomitantly treated with ciclosporin A, no drug-related elevations of bilirubin, alanine aminotransferase or creatinine were found. CONCLUSIONS: This open case study of severely ill patients with invasive fungal infections demonstrates both excellent efficacy and very low toxicity of caspofungin.

Adult↗
PubMed2005

Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the german society of haematology and oncology.

Patients undergoing allogeneic stem cell transplantation are at high risk for infection with a variety of pathogens during different phases of the procedure. Bacteria and fungi predominate the first phase until engraftment. During the second phase, from engraftment to about day 100, major infectious problems are caused by fungi and cytomegalovirus. Both pathogens remain important under continued immunosuppression, however, in the late post-transplantation period infections with encapsulated bacteria may become a problem. In this review the Infectious Diseases Working Party of the DGHO gives recommendations for prophylaxis of infections under allogeneic stem cell transplantation with drugs and other measures. The aim of the group was to do this on an evidence-based-medicine rating, if possible.

Anti-Infective Agents↗
PubMed2005

[Antimicrobial agents in pediatric cancer patients with hepatic or renal impairment].

Antimicrobial agents are among the most frequently prescribed therapeutics in the supportive care of children and adolescents with cancer or following hematopoietic stem cell transplantation. Most of these agents are cleared from the body by elimination of unchanged drug by the kidney and/or metabolism by the liver. Impaired renal and hepatic function may have profound effects on the pharmacokinetics and pharmacodynamics of antimicrobial agents, necessitating modification of the dosage regimen in order to avoid toxicity through accumulation of the parent and/or its metabolites. Key to minimize such toxicities is a thorough understanding of the antimicrobial drug armamentarium and a careful evaluation of benefits and risks of antimicrobial interventions. This article reviews the mechanisms of renal and hepatic drug clearance in the normal state and in the state of functional impairment, their implications for antimicrobial therapy and dosage recommendations for pediatric cancer patients with impaired renal or hepatic function.

Adolescent↗
PubMed2003

["Problem-based learning--inflammation and transplantation": an integrated, subject-centred course in the clinical section of the medical curriculum at the medical school of the University of Muenster].

Conventional medical curricula present information pertinent to chronic inflammatory diseases, infectious diseases and transplantation, via systematic lectures and courses in medical specialties without any integrated approach. The authors report on a 3-week model course that attempts to provide students with an overview of clinical presentation, diagnostics, and therapy of representative disease entities with particular emphasis on the interdisciplinary approach to these problems in hospital practice. In addition to problem-based learning in small groups, the model course comprises interdisciplinary concept lectures, practical demonstrations of specific diagnostic procedures, and bedside teaching. In the meantime, the course "Problem-Based Learning--Inflammation and Transplantation" has been held twice successfully as a mandatory course in the clinical part of the curriculum at the Muenster Medical School.

Autoimmune Diseases↗
PubMed2002

Treatment of severe Candida infections in high-risk patients in Germany: consensus formed by a panel of interdisciplinary investigators.

Now that modern medicine can provide increasing chances of cure to patients with formerly incurable disorders, therapy-related complications play the key role in outcome. Thus, among opportunistic infections, severe candidiasis remains a challenge. A multidisciplinary panel of 20 investigators was formed to find a consensus on antifungal strategies for various underlying conditions in neutropenic and non-neutropenic patients. To record their preferences, the investigators used an anonymous voting system. Among antifungal agents, fluconazole emerged as the major alternative to the classic amphotericin B, being therapeutically at least equivalent but clearly less toxic. Factors that restrict the use of fluconazole include pretreatment with azoles, involvement of resistant species like Candida krusei, and an inability to exclude aspergillosis. Flucytosine can be reasonably combined with both amphotericin B and fluconazole. Within the limited antifungal armamentarium, amphotericin B lipid formulations and itraconazole also appear useful and require further investigation. The general consensus of the group is that antifungal agents should be administered at sufficient dosages, rather early, and often empirically.

Antifungal Agents↗
PubMed2002

Fluconazole: optimized antifungal therapy based on pharmacokinetics.

Fluconazole, a triazole, inhibits synthesis of ergosterol. The key enzyme of antifungal activity is C-14-Demethylase, which itself depends on Cytochrom-P-450. So drugs that inhibit or induce this enzyme lead to interactions that have to be considered when dosing fluconazole. Oral bioavailability is more than 90% after a 50 mg dose, peak levels are reached after 0.5-1.5 h (empty stomach) or 4 h (with nutrition). A loading dose on the first day leads to steady state levels on the second day. Because of the hydrophilic properties fluconazole penetrates very well into body fluids and tissues. With the M27 method conditions regarding susceptibility testing have been standardized and minimal inhibitory concentrations (MICs) have been established for fluconazole. The linear relation between dose and concentration offers the possibility to treat less susceptible fungi with higher doses, but only when MICs correlate with efficacy and higher doses are tolerated as well. Prospectively randomized studies are rare. With the limited data indications as consensus recommendations are demonstrated. Data regarding high dose therapy with fluconazole in surgical or intensive care patients demonstrate efficacy and tolerability. In addition dosage has to be adjusted in case of haemofiltration or haemodialysis. At last future options for high dose fluconazole are discussed.

Antifungal Agents↗
PubMed1999

Early empiric antifungal therapy of infections in neutropenic patients comparing fluconazole with amphotericin B/flucytosine.

We compared the efficacy and tolerability of fluconazole (FCA) with amphotericin B/flucytosine (ABF) in neutropenic patients with haematological malignancies. Antifungal therapy started on day 4 when fever was unresponsive to antibiotics or on day 1 together with the antibiotics, if there was evidence of mycosis. If patients did not respond to FCA after 7 days they switched to ABF. 98 patients, 51 FCA and 47 ABF were included in the study. Response to fever was achieved in 28/51 FCA patients and in another 16 after switching to ABF. So in overall 44/51 (86.2%) of the FCA and 37/47 (78.8%) of the ABF group defervescence was observed. 46 patients (21 FCA, 25 ABF) developed radiological signs of pneumonia. Resolution of infiltrates was achieved in 5/21 FCA and 20/25 ABF patients, and another 10 of 15 initially not responding patients showed regression when switched to ABF, 5 of these had highly suspected aspergillosis. Adverse events occurred in 19.6% of FCA and 97.9% of ABF patients. In conclusion fluconazole and amphotericin B/flucytosine seem to be equally effective. In view of its lower toxicity fluconazole may be preferred as first line empiric antifungal agent, but in case of nonresponse, pneumonia or aspergillosis it may be replaced by amphotericin B combined with flucytosine.

Adolescent↗
PubMed1983

Canine transposition--approaches to treatment.

Transposition, an infrequently occurring dental anomaly, almost always involves the canines. Transposition occurs in either jaw, bilaterally or unilaterally, and in most cases the primary canine is still present. The canine may transpose with the lateral incisor or the first premolar. In the maxilla, transposition with the first premolar occurs more frequently. In the mandible, as far as can be determined, the canine always transposes with the lateral incisor. Several causative factors have been discussed. When cases of incipient transposition are detected early enough they can sometimes be treated interceptively. When seen at later stages, the positions of the root apexes are important for a decision about where to move the transposed teeth.

Adolescent↗
PubMed1979

The significance of cephalometrics in treatment planning.

Twenty-four orthodontists were asked to provide a treatment plan for a series of six cases of malocclusion. In certain types of cases there was high or total agreement on treatment planning whether or not a cephalometric radiograph and analysis was available. In view of these findings, it may be appropriate for orthodontists to reassess their routine use of cephalograms.

Cephalometry↗