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Biomedical subjects

B Salzberger

Publications and source records attributed to B Salzberger.

At least 19 recordsLinked to original sources
PubMed2006

Virological and immunological outcomes at 3 years after starting antiretroviral therapy with regimens containing non-nucleoside reverse transcriptase inhibitor, protease inhibitor, or both in INITIO: open-label randomised trial.

BACKGROUND: Antiretroviral therapy has greatly reduced HIV mortality and morbidity. However, the best sequence of regimens and implications of initial regimen for long-term therapeutic success are not well defined. METHODS: In INITIO, a large international randomised trial, we compared antiretroviral therapy with two nucleoside analogue reverse transcriptase inhibitors (didanosine+stavudine) plus either a non-nucleoside reverse transcriptase inhibitor (efavirenz, EFV) or a protease inhibitor (nelfinavir, NFV), or both (EFV/NFV), in patients with HIV-1 infection who had not previously received antiretroviral drugs. Primary outcomes were proportion with undetectable HIV RNA in plasma, and change in CD4 count from baseline at 3 years. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN44582462. FINDINGS: We followed up 911 participants (297 EFV, 311 NFV, 303 EFV/NFV). At 3 years, the proportion with HIV RNA less than 50 copies per mL was highest in the EFV group (188 [74%] EFV, 162 [62%] NFV, 155 [62%] EFV/NFV; p=0.004). Mean (95% CI) increases in CD4 count were 316x10(6) cells per L (288-343) for EFV, 289x10(6) cells per L (262-316) for NFV, and 274x10(6) cells per L (231-291) for EFV/NFV (p=0.1). Fewer participants in the EFV group than in the other groups stopped adequate antiretroviral therapy for more than 30 days (p=0.005). Participants in the EFV/NFV group had shorter time to stopping the initial regimen (p<0.0001) and to a treatment modifying adverse event (p=0.04) than those in the other groups. INTERPRETATION: Starting antiretroviral therapy with a three-drug/two-class regimen including efavirenz was better than starting with regimens including nelfinavir or efavirenz plus nelfinavir in terms of virological suppression and durability of the initial regimen. The shorter time on adequate antiretroviral therapy or to a treatment-modifying adverse event might explain the absence of additional benefit for the four-drug regimen.

Acquired Immunodeficiency Syndrome↗
PubMed2006

[Antiviral therapy: from influenza to Pfeiffer's disease].

Antiviral drug therapy has rapidly evolved in recent years. A large number of specific inhibitors against newly detected viral targets has been developed. Viral infections except HIV and viral hepatitis infections are clinically relevant mostly in severely immunocompromised patients. Especially respiratory viral infections and herpes virus infections are associated with high morbidity and mortality in these patients. Therapeutic and preventive strategies have been developed for a number of these infections. There is high priority for the development of new substances for a number of viruses not yet treatable and substances active against resistant viral strains.

Amantadine↗
PubMed2005

TLR-4 surface display on human monocytes is increased in septic patients.

BACKGROUND: Sepsis is a serious condition, most often occurring as a complication of bacterial infections. The Toll-like receptors (TLR)-2 and TLR-4 have been identified as key molecules in response to Gram-positive and Gram-negative bacteria. This study aimed to assess possible alterations of the surface display of TLR-2 and TLR-4 on monocytes and granulocytes derived from patients with sepsis in comparison with healthy controls. - METHODS: We have utilized flow-cytometry to determine the presence of TLR-2 and TLR-4 on the cell surface at baseline and in response to LPS (40 ng/ml) in vitro. - RESULTS: We found no significant differences of TLR-2 display on monocytes and granulocytes from septic patients compared to controls. Surface display of TLR-4 on monocytes from septic patients at baseline was significantly higher than in healthy controls but there was no further response to LPS, whereas controls showed a significant increase of TLR-4 display on the cell surface after LPS stimulation. In contrast, TLR-4 baseline cell surface display on granulocytes was significantly lower in septic patients than in controls and there was no response to LPS in both groups. - CONCLUSION: Our data suggest a complex relationship between TLR-4 display and bacterial challenge in vivo and in vitro.

Adult↗
PubMed2005

[Salvage therapy for HIV infection].

Drug therapy of HIV infection has become more effective in the last years. The rates of viral suppression one year after initiation of treatment have increased, and the mean duration of the first combination therapy is now over 24 months. Nowadays, for patients with a failing regimen, in most cases a second or even third combination of drugs can achieve long term viral suppression. In comparison, the treatment of patients with drug resistances to three or more active substance classes is still a challenge that demands an individual and selective approach. Options for these patients include an intensification of therapy, maintaining a partially effective regimen, a temporary interruption in the therapy or the very careful planning of the use of new or investigational drugs. To maximize the use of new drugs, new treatment sequences should ideally include at least two new drugs. Realistically, long-term suppression of viral replication cannot be achieved in the majority of these patients; here the goal must be to optimize the clinical prognosis and to delay the progression of the HIV infection as long as possible.

Anti-HIV Agents↗
PubMed2005

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↗
PubMed2005

Healthcare-associated outbreaks and community-acquired infections due to MRSA carrying the Panton-Valentine leucocidin gene in southeastern Germany.

In response to several isolations of methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leucocidin gene (PVL-MRSA), the present study was conducted to document the spread of infection in a small region of southeastern Germany. During a 9-month period, two healthcare-associated outbreaks with PVL-MRSA occurred, affecting 83 patients, personnel and contacts of personnel, and 34 additional cases were detected in the community. The clinical spectrum ranged from colonization to skin infection and necrotizing pneumonia. The findings represent the largest number of PVL-MRSA cases detected in Germany so far, and demonstrate the potential of this emerging pathogen to spread within the community and in healthcare institutions.

Adolescent↗
PubMed2005

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↗
PubMed2005

Cytokine and nitric oxide responses of monocyte-derived human macrophages to microsporidian spores.

Microsporidia are obligate intracellular parasites that emerged as opportunistic pathogens since the onset of the AIDS pandemic. They are capable of disseminating through the body using macrophages as vehicles. We incubated human macrophages with spores of all three Encephalitozoon spp. as well as with Vittaforma corneae, and the number of intracellular spores per cell was determined by fluorescence microscopy. Cell culture supernatants were collected and the content of TNF-alpha, INF-gamma, IL-10, and of nitric oxide was determined. Microsporidian spores did not induce a nitric oxide response in macrophages and there was a negative correlation between the number of intracellular spores and the amount of nitric oxide. TNF-alpha, INF-gamma, and IL-10 increased after simulation of macrophages with microsporidian spores but for TNF-alpha and INF-gamma no clear correlation of cytokine levels with the number of intracellular spores could be observed. A modulation of the nitric oxide response by intracellular microsporidia may contribute to the survival of microsporidia within the macrophage by a mechanism yet unknown.

Animals↗
PubMed2005

Cell invasion and intracellular fate of Encephalitozoon cuniculi (Microsporidia).

Microsporidia are obligate intracellular parasites that utilize a unique mechanism to infect host cells, which is one of the most sophisticated infection mechanisms in biology. Microsporidian spores contain a long coiled polar tube that extrudes from the spores and penetrates the membranes of new host cells. We have initiated a study to investigate the invasive process and intracellular fate of the microsporidium Encephalitozoon cuniculi. Here we show that relatively few cells were infected through the traditional penetration of the polar tube from outside. Rather, phagocytosis of spores occurred at least 10 times more frequently than injection of sporoplasms. Some spores extruded their polar tube inside the cells following phagocytosis. Membranes of the vacuoles surrounding the internalized spores were positive for late endosomal and lysosomal markers. Spores that remained inside these compartments disappeared within 3 days. Thus, our studies demonstrate that in addition to the unique way in which microsporidia infect host cells, E. cuniculi spores can also gain access to host cells by phagocytosis. The presence of intracellular spores that have extruded their polar tube shows that some spores germinate after phagocytosis, thus escaping from the phagosomes that mature into lysosomes.

Animals↗
PubMed2004

German-Austrian recommendations for the antiretroviral therapy of HIV-infection (status May 2004).

The availability and application of effective antiretroviral combination therapies have now almost become routine. More than 20 antiretroviral substances in four classes have been approved. Although an almost incalculable number of combinations can be conceived, it must be stressed, that only a small number of the theoretically possible combinations are actually applicable. As a result of the broad therapeutic armamentarium, HIV infection can be better treated. However, the decisions to start, monitor and change therapy have become even more difficult because the indication for treatment, the selection of the most suitable therapy for an individual, the information and counselling of the patient, and the monitoring of the success of treatment all demand a high level of knowledge and experience. This guideline evaluates the indication and selection of the initial antiretroviral therapy for HIV infection.

Anti-Retroviral Agents↗
PubMed2004

[Salvage therapy in HIV infection].

Today, initial treatment of an HIV infection usually leads to a prolonged suppression of viral replication, and to an improvement in the prognosis. However, the number of patients in whom such treatment is not, or not lastingly, successful is constantly increasing. Salvage therapy, that is, therapy employed after initial therapy failure, has a good chance of revitalizing success. If several combination therapies have failed, treatment is considerably more difficult, in particular when multiple resistances to all antiretroviral subclasses have developed. Available options in such a case are intensive salvage therapy with multi-drug regimens, partially effective treatment or interruption of treatment. The aim of antiretroviral therapy must therefore be to prevent therapy failures or to delay them for as long as possible. Cohort studies offering an opportunity to select good candidates for such long-term therapeutic strategies are currently ongoing.

Anti-HIV Agents↗
PubMed2004

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↗
PubMed2004

[IKOP-Infection control in the operating theatreConsensus on the theme "Barrier measures during operations and invasive procedures"].

Postoperative surgical site infections remain frequent despite intensive control programs. With rising numbers of operations and invasive procedures in the outpatient setting and in immunocompromised patients, the prevention of wound infections presents a rapidly growing challenge to the medical community. Barrier measures including drapes and surgical gowns to prevent wound contamination, have clearly reduced the rate of wound infections. The optimal material characteristics for operating gowns and drapes are well defined, but there is still a long running controversy on the use of single-use versus reusable materials. We review the efficacy and ecological impacts of these different approaches. Currently no superiority of any of these approaches with regard to either efficacy or ecological impact can be found. The European Union has recently published a series of mandatory standards to specify material characteristics of barrier materials used in operating theatres (EN 13795). Their scope include production standards of these materials as well as specific processes in auditing their characteristics. The implementation of these norms will clearly present a challenge to European hospitals but will lead to better material characteristics in the end.

Europe↗
PubMed2003

Unusual and severe symptomatic impairment of neutrophil function after one cycle of temozolomide in patients with malignant glioma.

Temozolomide, a recently approved cytotoxic agent for the treatment of malignant glioma, has shown promising results in the treatment studies published so far. However, cytopenia and related infectious complications have been reported in 2-8% of cases. Here we present three treatment-naive patients with malignant glioma experiencing cytopenia and/or infectious complications after the first cycle of temozolomide. Neutrophils obtained from each patient up to 6 weeks after the end of the temozolomide application showed normal phagocytic capacity but decreased oxygen radical production and thus impairment of microcidal activity. Our data suggest that a prolonged impairment of the immunological defense may occur in temozolomide-treated patients.

Antineoplastic Agents, Alkylating↗
PubMed2003

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↗
PubMed2003

BEACOPP therapeutic regimen for patients with Hodgkin's disease and HIV infection.

BACKGROUND: Hodgkin's disease (HD) is the most common non-AIDS-defining tumor diagnosed in HIV-infected patients. Antineoplastic treatment is difficult considering the underlying immunodeficiency caused by HIV itself and may increase the risk of opportunistic infections. The purpose of this study was to evaluate the efficacy and safety of the chemotherapeutic regimen bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in HIV-infected patients with HD (HIV-HD). PATIENTS AND METHODS: Twelve patients with HIV-HD were scheduled to receive six cycles of BEACOPP. Five patients received concomitant antiretroviral therapy. Two patients received additional radiotherapy. Restaging was carried out after three and six cycles of chemotherapy. CD4 counts and HIV RNA levels were regularly monitored during the course of chemotherapy. RESULTS: Complete remission (CR) was achieved in all patients. Of 12 patients, eight patients received the intended six cycles of BEACOPP. Two patients died of opportunistic infections within the treatment period, one patient died of a relapse after 26 months. The other nine patients remain in CR for their individual follow-up period, median 49 months (range 13-108). The most commonly observed toxicity was bone marrow suppression with National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3/4 leukopenia in 75% of all cases. The mean decline of CD4+ lymphocytes was 238 +/- 230/ micro l, with a mean recovery of 272 +/- 329/ micro l 6 months after the last cycle. Plasma levels of HIV RNA increased moderately or even declined under chemotherapy if highly active anti-retroviral therapy was given concomitantly with BEACOPP. CONCLUSIONS: The BEACOPP regimen is feasible and highly effective in HIV-HD patients. With respect to its overall moderate toxicity, BEACOPP is a safe regimen even in the immunocompromised patient.

AIDS-Related Opportunistic Infections↗