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Gert Höffken

Publications and source records attributed to Gert Höffken.

11 recordsLinked to original sources
PubMed2006

Monotherapy versus Combination Therapy in Patients Hospitalized with Community-Acquired Pneumonia.

Current international guidelines for the management of community acquired pneumonia (CAP) recommend therapy with a beta-lactam plus a macrolide or a 'respiratory' fluoroquinolone alone in patients hospitalized in a medical ward, and combination therapy with a beta-lactam plus a macrolide or a fluoroquinolone in patients hospitalized in the intensive care unit. However, which of the available options should be preferred remains a matter of debate, and there are surprisingly few prospective randomized trials strictly comparing mono- versus dual therapy strategies in CAP patients. Thus, the recommendation of combining a macrolide with a beta-lactam rather than using a beta-lactam alone in hospitalized patients is derived mainly from observational data, and the suggested combination of a beta-lactam with a fluoroquinolone in severe CAP has been rarely examined in a clinical trial.As there have been sound theoretical arguments for and against combination therapy regimens, the rationale for the different options is discussed and available clinical trial data are reviewed in this article. A final conclusion about the superiority of one antibacterial regimen over another in hospitalized patients with CAP cannot be drawn on the basis of the limited data available. So far, combination therapy probably should be preferred in all patients presenting with severe pneumonia, whereas in general, combination therapy is not necessary in patients in a medical ward, and combination therapy with a beta-lactam plus a macrolide or monotherapy with a respiratory fluoroquinolone should be considered equivalent in this latter patient group. On the other hand, the available data demonstrate that empirical coverage of atypical bacteria in all patients with mild-to-moderate CAP seems unnecessary, and beta-lactam monotherapy might perform equally well when compared with respiratory fluoroquinolones in patients with non-severe CAP. Thus, the alternative use of a beta-lactam alone at adequate dosage in clinically stable patients seems justified, if CAP due to Legionella pneumophila is unlikely.

Anti-Bacterial Agents↗
PubMed2005

Clinical efficacy and survival with first-line inhaled iloprost therapy in patients with idiopathic pulmonary arterial hypertension.

AIMS: To describe the long-term clinical efficacy of inhaled iloprost as first-line vasodilator mono-therapy in patients with idiopathic pulmonary arterial hypertension (IPAH). METHODS AND RESULTS: Seventy-six IPAH patients were prospectively identified and treated with inhaled iloprost. Clinical, haemodynamic, and exercise parameters were obtained at baseline, after 3 and 12 months of therapy and yearly thereafter. Four endpoints were prospectively defined as follows: (i) death, (ii) transplantation, (iii) switch to intravenous (i.v.) therapy, or (iv) addition of or switch to other active oral therapy. During follow-up (535+/-61 days), 11 patients died, six were transplanted, 25 were switched to i.v. prostanoids, 16 received additional or other oral therapy, and 12 patients discontinued iloprost inhalation for other reasons. Event-free survival at 3, 12, 24, 36, 48, and 60 months was 81, 53, 29, 20, 17 and 13%, respectively. Among haemodynamic and exercise parameters, mixed venous oxygen saturation (P<0.001), right atrial pressure (P<0.001), and peak oxygen uptake (P=0.002) were associated with event-free survival. CONCLUSION: In this study, only a minority of patients could be stabilized with inhaled iloprost mono-therapy during a follow-up period of up to 5 years. In the presence of multiple treatment options, chronic iloprost inhalation as mono-therapy appears to have a limited role.

Administration, Inhalation↗
PubMed2005

Short-course antimicrobial therapy for community-acquired pneumonia.

Management of community-acquired pneumonia (CAP) remains surprisingly controversial. Optimal duration of antimicrobial therapy reflects one of the open questions due to the lack of sufficient randomized clinical trial data. Recently, there have been efforts to rationalize antimicrobial therapy of this disease. Trials addressing the issue of short-course antimicrobial therapy for CAP have revealed no adverse outcomes with a treatment duration of 5 days when compared with conventional courses of 7-10 days. There is accumulating evidence that a shorter duration of antimicrobial therapy may have benefits in patients with CAP, as it might enhance compliance, decrease the development of antimicrobial resistance, decrease the incidence and shorten the duration of adverse drug effects, reduce treatment costs and improve patient satisfaction with therapy. Nevertheless, remaining questions regarding the influence of patient selection, disease severity or choice of antimicrobial for short-course therapy indicate the need for further randomized controlled clinical trials in this area of research. This article summarizes current evidence for short-course therapy in patients with CAP and draws conclusions for clinical practice.

Anti-Bacterial Agents↗
PubMed2004

[Treatment of severe pneumonia--community-acquired and "early onset" nosocomial].

BACKGROUND: Pneumonia in hospitalized patients-community-acquired (CAP) or nosocomial (NAP)-remains an important cause of morbidity and mortality. Because of the substantial mortality, particularly among the elderly or in patients with specific underlying diseases, it is essential that initial antimicrobial therapy covers the most likely causative organism(s). RISK STRATIFICATION: Elderly patients are prone to be colonized with enteric gramnegative rods, especially patients with immunosuppression, prolonged hospital stay, and concomitant medical illnesses. An increasing incidence of gramnegative rod pneumonia and polymicrobial pneumonia including anaerobic bacteria due to aspiration is observed in community-, nursing home- and hospital-acquired lower respiratory tract infections. The spectrum of causative pathogens in elderly CAP patients with underlying diseases is similar to the spectrum in patients with hospital-acquired nosocomial pneumonia "early onset" (before day 5 of hospitalization). THERAPEUTIC MANAGEMENT: Several retrospective studies have shown the importance of the early, adequate initial empirical antibiotic treatment for a favorable clinical outcome and initial adequate and/or effective antimicrobial therapy initiated before definitive etiologic diagnosis is associated with an improved outcome. In addition to the expected pathogens and patient-specific risk factors, the local resistance pattern has to be considered. Especially in elderly patients with underlying diseases, concomitant medication is often mandatory; therefore, initial antimicrobial treatment should also have to take the risk of potential interactions and contraindications into account.

Adult↗
PubMed2004

Update on glycopeptide use in german university hospitals.

BACKGROUND: A previous study has shown considerable variation in glycopeptide use from 1992 through 1994 among four university hospitals in southern Germany. Active antimicrobial management in one of the hospitals was associated with the containment of glycopeptide consumption in the medical and surgical service at < 1.5 defined daily doses (DDD)/100 patient days in the subsequent period. In the present study, more recent data on comparative glycopeptide use in German university hospitals were analyzed. MATERIALS AND METHODS: Hospital pharmacy records from 1998 through 2000 were evaluated. The number of DDD (definition according to the World Health Organization [WHO]/Anatomic and Therapeutic Classification [ATC] index) per 100 patient days was calculated to compare glycopeptide use in different medical and surgical service areas between eight German university hospitals. RESULTS: The 3-year averages in recent glycopeptide use for the eight hospitals ranged between 1.3 and 8.8 DDD/100 patient days in the medical services, and between 0.7 and 1.8 DDD/100 patient days in the surgical services. Only one of the eight hospitals showed medical service glycopeptide use of < 1.5 DDD/100 patient days. In most hospitals, glycopeptide use was higher in the medical intensive care units (ICU) (median 8.6; range 4.3 to 12 DDD/100 patient days, data for the year 2000) than in the surgical ICUs (median 6.7; range 1.2 to 8.6 DDD/100 patient days, data for the year 2000). High use was also observed for hematology-oncology services (median 7.5; range 2.7 to 15.7 DDD/100 patient days, data for the year 2000). CONCLUSION: These recent data from a larger hospital sample confirm large variations in glycopeptide use, identify hematology-oncology services as a significant prescribing source along with ICUs, and indicate areas of probable overuse of glycopeptide antibiotics. The data may be useful as a benchmark for further focused drug use control interventions.

Anti-Bacterial Agents↗
PubMed2003

Adrenocortical hormones in survivors and nonsurvivors of severe sepsis: diverse time course of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol.

OBJECTIVE: Activation and suppression of immune responses are crucial events during sepsis. Based on substantial new data, a complex picture of differential immune-enhancing and immunosuppressive actions of adrenocortical steroids is emerging. The adrenal androgen dehydroepiandrosterone and its precursor, dehydroepiandrosterone-sulfate, show a considerable decrease with increasing age and serve as functional antagonists to endogenous glucocorticoids. Therefore, we examined time-dependent changes in dehydroepiandrosterone, dehydroepiandrosterone-sulfate, cortisol, adrenocorticotropin, and inflammatory variables in surviving and nonsurviving patients with severe sepsis. DESIGN: Prospective observational study in consecutive patients. SETTING: Medical and interdisciplinary intensive care units in two university hospitals and one city hospital. PATIENTS: Thirty nonsurgical patients (25 men and 5 women) with severe sepsis (American College of Chest Physicians/Society of Critical Care Medicine criteria); 15 survivors (mean age, 54 +/- 14 yrs; Acute Physiology and Chronic Health Evaluation III score, 59 +/- 35) and 15 nonsurvivors (mean age, 63 +/- 15 yrs; Acute Physiology and Chronic Health Evaluation III score, 67 +/- 24) were included. Hormones were compared individually and between survivors/nonsurvivors by sequential blood drawings from early sepsis till time of recovery/death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During early sepsis, cortisol (nmol/L) was not significantly higher in survivors than nonsurvivors (750 +/- 121 vs. 454 +/- 92, p <.08) and decreased in survivors (p <.01) during late sepsis. During early sepsis, dehydroepiandrosterone-sulfate (percentage of age-matched normal levels) was higher in survivors than nonsurvivors (85 +/- 19 vs. 22 +/- 7, p <.01). Dehydroepiandrosterone-sulfate decreased in survivors (p =.0001) but remained low in nonsurvivors during late sepsis. Dehydroepiandrosterone (percentage of age-matched normal levels) was not significantly elevated in survivors compared to nonsurvivors during early sepsis (282 +/- 42 vs. 214 +/- 63, p <.08). Dehydroepiandrosterone decreased in survivors (p <.01) but not in nonsurvivors during late sepsis. Linear regression for dehydroepiandrosterone levels showed a reconstitution of age dependence only in survivors during recovery. Adrenocorticotropin levels did not change. The dehydroepiandrosterone-sulfate/cortisol ratio decreased significantly in both survivors and nonsurvivors, whereas dehydroepiandrosterone/cortisol ratio only decreased in survivors during course of sepsis. CONCLUSIONS: During sepsis, adrenal androgens and glucocorticoids show a diverse time-dependent course in survivors and nonsurvivors.

APACHE↗
PubMed2002

Early therapy with the neuraminidase inhibitor oseltamivir maximizes its efficacy in influenza treatment.

Influenza illness is an important cause of severe morbidity and mortality in the population. Oseltamivir, the first oral neuraminidase inhibitor, has proven efficacy. In children of 1 year and older (weight-dependent dosing: 30 mg, 45 mg, 60 mg or 75 mg BID for 5 days) and adults (75 mg BID for 5 days), oseltamivir reduces the duration and severity of acute influenza. Furthermore, it decreases the incidence of secondary complications such as otitis media, bronchitis, pneumonia and sinusitis. Oseltamivir has been shown to prevent influenza when given for long-term prophylaxis or for post-exposure prophylaxis. Because oseltamivir blocks the neuraminidase, an enzyme crucial to influenza virion liberation from the host cell, it is only effective during the replication phase. Clinical benefits are only seen, when oseltamivir is applied within 48 h after onset of symptoms, and clinical efficacy in acute influenza is highly dependent on the beginning of treatment. Treatment within 12 h after onset of symptoms reduces the duration of illness by an additional 74.6 h, and treatment within 24 hours an additional 53.9 h compared to the benefit seen with an intervention at 48 h. In conclusion, clinical efficacy of oseltamivir can be maximized by early start of treatment. Resistance of influenza virus against oseltamivir has rarely been observed and seems to be of no clinical relevance due to reduced transmissibility and pathogenicity of mutants. Oseltamivir is generally well tolerated. About 10% of the patients complain of transient upper gastrointestinal events, which resolved within 1-2 days, and which could be reduced when the medication was taken with a light snack.

Acetamides↗
PubMed2002

Efficacy and safety of zanamivir in patients with influenza--impact of age, severity of infections and specific risk factors.

Influenza infections occur primarily in the winter season and may lead to serious morbidity and mortality, predominantly in patients with increased risk of complications; these include those with advanced age or with chronic clinical conditions. In this group, the rate of influenza-related hospitalization or death is considerably increased. New treatment options have been introduced for treatment of influenza infection, with the neuraminidase inhibitors zanamivir and oseltamivir being the most promising substances for treatment and prevention of influenza. Numerous double-blind, randomized, placebo-controlled trials in otherwise healthy individuals have demonstrated that zanamivir, when administered orally inhaled for 5 days, produced a statistically significant reduction (by 1.5 days) in the time to alleviation of influenza-related symptoms by compared to inhaled placebo (lactose). The time to alleviation was reduced by 2.5 days in high-risk patients and by 3.25 days in these patients with fever at enrollment. Likewise, the time to alleviation could be reduced by 2 days in patients with severe influenza-related symptoms aged under 50 years and by 7 days in the patient population aged over 50 years compared to placebo. In patients with asthma or chronic pulmonary disease, zanamivir demonstrated a comparable efficacy, reduced the rate of pulmonary complications and did not adversely affect pulmonary function. Zanamivir was well tolerated. In conclusion, zanamivir has proven to be efficacious in treating influenza infection: this was true especially in high-risk patient groups, e.g., patients with advanced age, underlying chronic medical conditions or presenting with severe influenza-related symptoms.

Administration, Oral↗
PubMed2002

Assessment of survival in patients with primary pulmonary hypertension: importance of cardiopulmonary exercise testing.

BACKGROUND: Primary pulmonary hypertension (PPH) is a life-threatening disease. Prognostic assessment is an important factor in determining medical treatment and lung transplantation. Whether cardiopulmonary exercise testing data predict survival has not been reported previously. METHODS AND RESULTS: We studied 86 patients with PPH (58 female, age 46+/-2 years, median NYHA class III) between 1996 and 2001 who were followed up in a tertiary referral center. Right heart catheterization was performed and serum uric acid levels were measured in all patients. Seventy patients were able to undergo exercise testing. At the start of the study, the average pulmonary artery pressure was 60+/-2 mm Hg, average pulmonary vascular resistance was 1664+/-81 dyne x s x cm(-5), average serum uric acid level was 7.5+/-0.35 mg/dL, and average peak oxygen uptake during exercise (peak VO(2) was 11.2+/-0.5 mL x kg(-1) x min(-1). During follow-up (mean: 567+/-48 days), 28 patients died and 16 underwent lung transplantation (1-year cumulative event-free survival: 68%; 95% CI 58 to 78). The strongest predictors of impaired survival were low peak VO(2) (P<0.0001) and low systolic blood pressure at peak exercise (peak SBP; P<0.0001). In a multivariable analysis, serum uric acid levels (all P<0.005) and diastolic blood pressure at peak exercise independently predicted survival (P<0.05). Patients with peak VO(2) < or =10.4 mL x kg(-1) x min(-1) and peak SBP < or =120 mm Hg (ie, 2 risk factors) had poor survival rates at 12 months (23%), whereas patients with 1 or none of these risk factors had better survival rates (79% and 97%, respectively). CONCLUSIONS: Peak VO(2) and peak SBP are independent and strong predictors of survival in PPH patients. Hemodynamic parameters, although also accurate predictors, provide no independent prognostic information.

Exercise Test↗
PubMed2002

Nosocomial pneumonia: the importance of a de-escalating strategy for antibiotic treatment of pneumonia in the ICU.

Nosocomial pneumonia is the second most frequent nosocomial infection and represents the leading cause of death from infections that are acquired in the hospital. In the last decade, a large body of data has accumulated that points to the substantial impact of inadequate antibiotic treatment as a major risk factor for infection-attributed mortality in ventilator-associated pneumonia (VAP) patients. In most instances, high-risk pathogens (eg, highly resistant Gram-negative bacilli, such as Pseudomonas aeruginosa and Acinetobacter spp, as well as methicillin-resistant staphylococci) are the predominant microorganisms causing excess mortality. Among various risk factors for mortality from VAP, which include the severity of the underlying disease and the degree of functional physiologic impairment caused by the pulmonary infectious process, only inappropriate antibiotic therapy is directly amenable to modification by clinicians. Secondary modifications of an initially failing antibiotic regimen do not substantially improve the outcome for these critically ill patients. Therefore, the best approach for reducing infection-related mortality seems to be the initial institution of an adequate and broad-spectrum antibiotic regimen in severely ill patients, which should be modified in a de-escalating strategy when the results from microbiologic testing become available. To circumvent the inherent danger of the emergence of resistance in ICU patients, additional measures have to be implemented and tested in clinical trials to reduce antibiotic consumption, shorten the duration of antibiotic treatment, and reduce the selection pressure on the ICU flora. This latter goal could be met by new antibiotic strategies including scheduled changes of recommended empiric antibiotic regimens at fixed intervals on a rotating basis.

Anti-Bacterial Agents↗