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Biomedical subjects

G Fätkenheuer

Publications and source records attributed to G Fätkenheuer.

At least 19 recordsLinked to original sources

[A vascular pedicled duplicated fibula transplant for treatment of lumbar instability following tuberculous spondylodiscitis].

Operative treatment of tuberculous spondylodiscitis is still an important part of the treatment for lumbar spine instability. We report on a patient who suffered an extensive relapse with microbiological confirmation of tuberculous spondylodiscitis following operative spinal treatment for unspecific spondylodiscitis. X-Ray examination showed development of pronounced lumbar instability, which was first treated with the aid of an external fixateur and later by means of a doubled fibular bone graft with a vascularised stem with no dorsal instrumentation, which led to bony consolidation.

Aged↗

CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). METHODS: We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. RESULTS: A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). CONCLUSIONS: Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].).

AIDS-Related Opportunistic Infections↗

Rapid improvement of liver function in a patient with HIV and hepatitis B coinfection treated with lamivudine and tenofovir.

Since the introduction of HAART, the clinical importance of hepatitis virus infection and its complications in human immunodeficiency virus (HIV)-infected persons have continuously grown. Coinfection with hepatitis B virus (HBV) and HIV is one of the leading causes of morbidity and mortality. To date, neither the optimal time point for initiation of anti-HBV therapy nor the best therapeutic approach has been clearly defined. We report the case of a 22-year-old African woman infected with HBV- and HIV-1 coinfection and severe impairment of liver function. HAART including lamivudine and tenofovir was started. Three weeks later, the patient achieved not only a restoration of her clinical situation and liver function, but she also demonstrated a complete suppression of both viruses. This impressive clinical course might be explained by the application of antiviral combination therapy including lamivudine and tenofovir. Tenofovir has shown a higher activity against HBV than other drugs. In addition, combination therapy for chronic hepatitis B might be more effective than monotherapy. Future studies need to clarify the value of combination treatment for patients with chronic hepatitis B.

Adenine↗

[New kinds of AIDS drugs inhibit HIV entry into the cell. Entry inhibitors soon for oral administration].

Entry inhibitors include a variety of drugs with different points of attack and with the common objective of preventing the entry of HIV into the cell. Whereas the only previously approved medication from this group, enfuvirtide, can be only injected subcutaneously and, thus, is indicated for only treatment-experienced patients, the CCR5 antagonists represent a group of experimental medications whose use is conceivable at all stages of the HIV infection. According to the available data, they are effective and also very well tolerated and, therefore, are one of the most promising future classes of drugs. At the moment, the prospective importance of substances possessing other mechanisms of action (attachment inhibitors, CXCR4 inhibitors) can not yet be predicted.

Administration, Oral↗

A randomized, placebo-controlled study of the use of filgrastim in non neutropenic patients with nosocomial pneumonia.

Pneumonia remains the number one cause of death from infectious diseases in Western Europe and the United States despite the introduction of potent broad-spectrum antibiotics. Granulocyte colony-stimulating factor is considered to improve host defense during infection and may be an effective adjunctive in the treatment of severe infections. We examined the efficacy of granulocyte colony-stimulating factor (r-metHUG-CSF, filgrastim) with regard to clinical response in non-neutropenic ICU patients with nosocomial pneumonia in a prospective, randomized, placebo-controlled trial. 28 patients with newly diagnosed nosocomial pneumonia were randomly assigned to receive 300-480 microg filgrastim or placebo subcutaneously for up to seven days. Study endpoints were death within 15 days, duration of antibiotic therapy and occurrence of serious adverse events (SAE). No significant differences were observed in respect of 15-day (filgrastim1/12 vs. placebo 2/16) or 30-day mortality (1/12 vs.4/16, p=0.355), and length of antibiotic treatment (13.5 vs.11.5 days, p=0.985). Sepsis developed in 1/12 patients in the filgrastim and 6/16 patients in the placebo group (p=0.184). None of the patients developed ARDS or any other SAE related to the study medication. Filgrastim is safe in non-neutropenic ICU patients with nosocomial pneumonia. A benefit of filgrastim with regard to clinical endpoints could not be observed, while there was a trend toward reduced sepsis rate.

Adult↗

Imported leishmaniasis in Germany 2001-2004: data of the SIMPID surveillance network.

Leishmaniasis is a rare, non-notifiable disease in Germany. Epidemiological and clinical data, therefore, are scarce. Most infections seen in Germany are contracted outside the country. The German surveillance network for imported infectious diseases (Surveillance Importierter Infektionen in Deutschland, or SIPMID) recorded 42 cases of imported leishmaniasis (16 visceral, 23 cutaneous, and 3 mucocutaneous) from January 2001 to June 2004. Although most infections were acquired in European Mediterranean countries, the risk of infection was highest for travelers to Latin America. HIV coinfection was observed significantly more often in patients with visceral leishmaniasis than in patients with cutaneous/mucocutaneous leishmaniasis (31 vs. 4%, p=0.02). The median time to a definitive diagnosis was 85 days in cases of visceral leishmaniasis and 61 days in cases of cutaneous/mucocutaneous leishmaniasis, reflecting the unfamiliarity of German physicians with leishmanial infections. Visceral leishmaniasis was treated most frequently with amphotericin B, whereas cutaneous/mucocutaneous leishmaniasis was treated with a variety of local and systemic therapies. The findings presented here should serve to increase awareness as well as improve clinical management of leishmaniasis in Germany.

Adolescent↗

Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy.

BACKGROUND: Highly active antiretroviral therapy (HAART) has improved the prognosis of HIV-infected patients. We studied the changes in the incidence and prognosis of cytomegalovirus (CMV) disease preceding and during the first few years of HAART in a clinic cohort. PATIENTS AND METHODS: All patients with CMV disease diagnosed between 1993 and 1999 from a clinic cohort in Cologne, Germany, were included. The patients were followed until death or until December 31, 2001. The time period from 1993-1996 was classified as pre-HAART, the period from 1997-1999 as the HAART era. Survival was analyzed with a Cox-proportional hazard model. RESULTS: From a total of 1,279 HIV-infected patients, 127 patients with CMV disease were enrolled. The incidence of CMV disease declined rapidly and significantly from 7.34 cases per 100 patient years (py) in the pre-HAART era to 0.75 cases per 100 py in the HAART era. The median survival time in the pre-HAART era was 9.5 months; the median survival was not yet reached at 4 years of follow-up in the HAART era. The only risk factors influencing survival were CD4-cell count and antiretroviral therapy before and after diagnosis of CMV disease. Treatment naive patients had a better prognosis than pretreated patients and patients treated with triple combination therapy survived longer than patients with other treatment modalities. CONCLUSION: A rapid decline in the incidence of new CMV manifestations and a better prognosis of patients with CMV disease, especially if they were treatment naive and treated with triple combination therapy, were observed in the HAART era.

AIDS-Related Opportunistic Infections↗

AIDS-related progressive multifocal leukoencephalopathy in the era of HAART: report of two cases and review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system. It is caused by the JC virus (JCV), a human polyomavirus replicating in human glial cells. PML is the result of the reactivation of latent JCV infection that usually occurs in the setting of cellular immunodeficiencies such as HIV-1 infection. Epidemiologic data suggest that the impact of highly active antiretroviral therapy (HAART) on the incidence of PML is less profound than seen with other opportunistic infections. Given the lack of an effective and specific therapy for PML, HAART remains the only therapeutic option in patients with PML. However, a significant number of cases appear unresponsive to antiretroviral therapy. Moreover, there is growing data on unexpected inflammatory cases of PML after initiation of HAART. Thus, PML will remain a relevant cause of morbidity and mortality in HIV- 1-infected patients. Here we report two cases of PML, along with a concise review of the literature on this important disease.

AIDS-Related Opportunistic Infections↗

Successful administration of aggressive chemotherapy concomitant to tuberculostatic and highly active antiretroviral therapy in a patient with AIDS-related Burkitt's lymphoma.

Treatment of AIDS-related malignant lymphoma (ARL) remains a therapeutic challenge. There are concerns not only about infectious and haematological complications in HIV-infected patients during intensive chemotherapy, but also about potential interactions between chemotherapy and highly active antiretroviral therapy (HAART). Current data on patients treated concomitantly with intensive chemotherapy and HAART are limited, and no data exist on patients with ARL suffering from active opportunistic infections. We report the case of a 38-year-old man with advanced HIV-1 infection, pulmonary tuberculosis and Burkitt's lymphoma. Intensive chemotherapy was administered in parallel with tuberculostatic therapy and HAART. Six months later, the patient achieved not only a complete remission of Burkitt's lymphoma and sustained viral suppression, but also a full recovery from tuberculosis. This case report provides some useful observations on the successful application of intensive chemotherapy in addition to tuberculostatic therapy and HAART in HIV-infected patients.

AIDS-Related Opportunistic Infections↗

Primary drug-resistance in HIV-positive patients on initiation of first-line antiretroviral therapy in Germany.

BACKGROUND: Resistance against antiretroviral drugs in previously untreated HIV-infected persons is of growing relevance. The aim of the study is to determine the prevalence of resistance-associated mutations in this patient group. METHODS: In a prospective multicenter-study in Nordrhein-Westfalen, Germany, genotypic resistance testing was performed in untreated HIV-positive patients before administration of first-line highly active antiretroviral therapy (HAART). RESULTS: Between January 2001 and August 2002 resistance testing was performed in 184 therapy-naive individuals. HAART was initiated in 143 patients, who were included into the study. 70.6 % were males, mean age was 39 years, mean duration of diagnosis of HIV-infection was 1.5 years. The proportion of cases at CDC stage C was 45.4%, mean CD4-cell count was 199 /ml, mean viral load was 206,855 copies/ml. Resistance-associated mutations were detected in 20 patients (14.0%). 10.5% showed mutations indicating nucleoside reverse transcriptase inhibitor- (NRTI) resistance (M41L, E44D, D67N, T69D/N, L74V, V118I, M184V, L210W, K219Q), 2.8% showed non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance (K103N, V108I, Y181C), and 2.1% showed protease-inhibitor- (PI) associated resistance (V82A, L90M), respectively. Multi-class-resistance was found in 2.1%, mutations indicating revertant variants of resistant strains were found in 4.2% (T215C/E/L/S). 86.7% of the isolates showed secondary mutations in the protease gene. No significant difference in the distribution of the parameters age, sex, duration of HIV diagnosis, CDC stage, CD4-cell count, and viral load, between groups with and without resistance was identified. CONCLUSION: The prevalence of primary resistant virus strains can be estimated at 14% in chronically infected HAART-naive HIV-patients in Germany. The majority of these cases show NRTI-associated resistance. Resistance against NNRTI or PI as well as multi-class-resistance is of low prevalence. No risk factor of predictive value can be identified for the diagnosis of resistance mutations in the individual. In conclusion, routine genotypic resistance testing in untreated HIV-positive patients should be performed before administration of first-line HAART in this region.

Adult↗

Long-term outcome and quality of care of patients with Staphylococcus aureus bacteremia.

To assess the long-term outcome and influence of clinical management of patients with Staphylococcus aureus bacteremia (SAB), 229 patients with blood cultures positive for Staphylococcus aureus between January 1997 and December 2000 were retrospectively identified and followed up. Risk factors, source of infection, treatment, clinical course, and outcome were recorded by chart review. For the assessment of 1-year survival, a questionnaire was sent to family doctors and government registration offices. Time of initial antibiotic therapy, duration of antibiotic treatment and performance of echocardiography were regarded as indicators of the quality of the clinical management of SAB. Among the 229 patients studied, 218 were evaluable for 1-year survival. Crude mortality after 1 year was 37.6% year. Within 30 days 43 (19.7%) patients had died, and 39 (17.9%) additional patients died thereafter. Using multivariate analysis, the following variables were associated with death: malignant disease (odds ratio [OR] 4.8; 95% confidence interval [CI], 2.6-8.9), pneumonia (OR, 3.6; 95%CI, 1.2-10.2), age >60 years (OR, 2.6; 95%CI, 1.5-4.5), and known source of infection (OR, 2.3; 95%CI, 1.3-4.1). Among 160 patients with a completely assessable treatment course 73 (46%) had received antibiotics for at least 14 days. A delay of antibiotic treatment of 1 day or more after microbiological diagnosis was observed in 28.3% of patients (i.e., 60 of 212 patients who received at least 1 dose of antibiotics). Echocardiography was performed in 101 (44.1%) cases. Overall, the findings indicate that standard guidelines for the management of SAB are followed only in part in clinical practice. In order to reduce the considerable mortality associated with SAB and to improve short- and long-term outcome, efforts should be made to increase adherence to recommendations.

Adult↗

Combination therapy of disseminated Fusarium oxysporum infection with terbinafine and amphotericin B.

A case of disseminated infection with Fusarium oxysporum following chemotherapy of acute myelogenous leukemia is reported. Antifungal treatment was successful with a 13-day course of oral terbinafine 250 mg t.i.d. in combination with amphotericin B deoxycholate 1.0-1.5 mg/kg qd and subsequently intravenous liposomal amphotericin B 5 mg/kg qd. Preceding monotherapy with amphotericin B deoxycholate 1.0-1.5 mg/kg qd had not stopped the progression of infection. The combination therapy described here represents a novel approach to the treatment of Fusarium spp. in the immunocompromised host in whom Fusarium spp. are known to cause disseminated infection with high mortality.

Amphotericin B↗

Age as a risk factor for severe manifestations and fatal outcome of falciparum malaria in European patients: observations from TropNetEurop and SIMPID Surveillance Data.

Previous studies have indicated that age is a risk factor for severe falciparum malaria in nonimmune patients. The objectives of this study were to reevaluate previous findings with a larger sample and to find out how strongly clinical outcomes for elderly patients differ from those for younger patients. Results of adjusted analyses indicated that the risks of death due to falciparum malaria, of experiencing cerebral or severe disease in general, and of hospitalization increased significantly with each decade of life. The case-fatality rate was almost 6 times greater among elderly patients than among younger patients, and cerebral complications occurred 3 times more often among elderly patients. Antimalarial chemoprophylaxis was significantly associated with a lower case-fatality rate and a lower frequency of cerebral complications. Women were more susceptible to cerebral complications than were men. Our study provides evidence that falciparum malaria is more serious in older patients and demonstrates that clinical surveillance networks are capable of providing quality data for investigation of rare events or diseases.

Age Factors↗

Superior virological efficacy of ritonavir-boosted protease inhibitor regimens compared to single protease inhibitor therapy.

Low dose-ritonavir boosted protease inhibitors are increasingly being used for the first-line antiretroviral treatment, though their virological efficacy has just poorly been compared to alternative antiretroviral therapies. Here, we retrospectively investigated the virological responses of 316 protease inhibitor-naive HIV patients receiving highly active antiretroviral treatment based on a single (n = 256) or a ritonavir-boosted protease inhibitor (n = 60), both in the background of two nucleoside analogues. - By intent-to-treat analysis, a complete initial virological response was achieved in 71.8% of all patients in the single protease inhibitor group (indinavir: 76%, ritonavir: 67.5%, nelfinavir: 70.6%) and in 88.3% (p = 0.008) of patients treated with a boosted protease inhibitor (saquinavir/r: 71.4%, indinavir/r: 92.1%, lopinavir/r: 86.6%). The multivariate risk analysis identified boosted PI treatment as an independent predictor of a complete virological response (OR = 2.8, p=0.02). Viral rebound after an initial complete virological response was observed in 28% and 17% (p = 0.06) of patients receiving a single or a dual protease inhibitor, respectively. The rate of durable viral suppression over 12 months was 44.5% and 56.7% (p = 0.09) in the respective study cohorts. Ritonavir-boosted protease inhibitors therefore seem to induce a superior virological response rate and a higher degree of sustained virological suppression.

Adult↗

[A 41 year-old male patient with fever of unknown origin and bacteremia with actinobacillus actinomycetemcomitans].

A 41-year-old male patient presented with fever of unknown origin which had been present for 5 months. The primary diagnostic procedures did not identify an infectious focus. After a lag phase of 13 days, blood cultures became positive for Actinobacillus actinomycetemcomitans, which belongs to the HACEK group of microorganisms. According to the DUKE criteria, infective endocarditis was diagnosed despite negative transesophageal echocardiography (TEE). The sensitivity of TEE is estimated between 86 and 94%. An infected tooth was extracted as a possible focus, and the patient was treated with i.v. antibiotics for 5 weeks according to the guidelines of the AHA and ACC. The fever was permanently terminated, and the further course of the patient was uneventful. Despite negative TEE, the diagnosis "infective endocarditis" should not be rejected, and blood cultures should be grown for up to 30 days.

Actinobacillus Infections↗

Regional and temporal changes in AIDS in Europe before HAART.

In a prospective observational study 4,485 patients from 46 clinical centres in 17 European countries were followed between April 1994 and November 1996. Information on AIDS-defining events (ADEs) were collected together with basic demographic data, treatment history and laboratory results. The centres were divided into four geographical regions (north, central, south-west and south-east) so that it was possible to identify any existing regional differences in ADEs. The regional differences that we observed included a higher risk of all forms of Mycobacterium tuberculosis infections (Tb) and wasting disease in the south-west and an increased risk of infections with the Mycobacterium avium complex (MAC) in the north. In Cox multivariable analyses, where north was used as the reference group, we observed hazard ratios of 6.87, 7.77, 2.29 and 0.16 (P < 0.05 in all cases) for pulmonary Tb, extrapulmonary Tb, wasting disease and MAC respectively in the south-west. Pneumocystis carinii pneumonia (PCP) was less commonly diagnosed in the central region (RH = 0.51, 95% CI 0 32-0.79, P = 0.003) and most common in the south-east (RH = 1.04, 95% CI 0.71-1.51, P = 0.85). Comparisons with a similar 'AIDS in Europe' study that concentrated on the early phase of the epidemic reveal that most of the regional differences that were observed in the 1980s still persist in the mid-1990s.

AIDS-Related Opportunistic Infections↗