Innere Medizin (Heidelberg, Germany)最新文献

Shortening the duration of antibiotic therapy in various infections is safe and effective, as supported by evidence from randomized controlled trials. This strategy not only reduces antibiotic consumption and clinical side effects, but also shortens the length of hospital stay without affecting mortality and recurrence rates. This review summarizes current evidence from randomized controlled trials on the optimal treatment duration of bacteremia, pneumonia, urinary tract infections and other infections. For bacteremia with established source control, 7 days of antibiotic treatment is sufficient for most pathogens. For community-acquired pneumonia, 5-7 days, and for hospital-acquired pneumonia, 7-8 days are recommended by national guidelines. Certain infections still require longer treatment, with examples including endocarditis, bone and joint infections and tuberculosis.

Background: Staphylococcus aureus bacteremia (SAB) is a heterogeneous and difficult-to-treat disease with a high mortality rate.

Objectives: Presentation of the challenges of randomized controlled trials (RCTs) on SAB, and an overview of the current state of research and future studies.

Methods: Search for RCTs on SAB in PubMed and clinicaltrials.gov over the past 20 years.

Results: The design and implementation of RCTs on SAB is complex. Current RCTs incorporate new developments such as pragmatic study design, adaptive platform studies, endpoints with a desirability of outcome ranking (DOOR) and enrichment of clinical phenotypes. The latest results regarding therapy show that cefazolin is not inferior to flucloxacillin in the treatment of methicillin-susceptible S. aureus (MSSA)-SAB and is less nephrotoxic. There is no general recommendation for combination therapy. In low-risk SAB, early oral switch therapy is possible after 5-7 days.

Conclusions: RCTs on SAB therapy require careful planning and inclusion of subgroups. Further RCTs are necessary to optimize therapy.

Outpatient parenteral antimicrobial therapy (OPAT) enables the intravenous administration of anti-infective agents outside the hospital, within the patient's home environment, and can thereby shorten or even avoid inpatient stays. Internationally, OPAT has been well established for years, whereas its implementation in Germany has remained limited. The K‑APAT study demonstrated feasibility, efficacy, safety, and acceptance of this treatment model in Germany as well, showing a significant reduction in hospital days. Since 2024, an S1 guideline has, for the first time, provided a structured recommendation for performing OPAT. The approach is considered for infections without suitable oral treatment options and requires careful selection of appropriate patients. Key success factors include adherence to antimicrobial stewardship principles, guideline-based drug selection, adequate catheter management, and structured monitoring. Despite low complication rates, insufficient reimbursement structures and the lack of nationwide networks currently pose major barriers to broader implementation in Germany. Given current challenges-particularly the increasing number of complex infectious diseases alongside the ongoing shift to outpatient care, as well as persistent staff shortages and limited healthcare resources-OPAT represents a forward-looking, patient-centered model of care. The further development of standardized structures combined with health economic analyses within the German healthcare system forms the essential basis for sustainable implementation.

Increasing antimicrobial resistance (AMR) is one of the greatest threats to global health. In 2021, 4.71 million deaths worldwide were closely associated with AMR, and 1.14 million deaths could be directly attributed to infections caused by multidrug-resistant organisms (MDROs), particularly multidrug-resistant Gram-negative bacteria (MDRGN). Enterobacterales (e.g., Escherichia coli and Klebsiella spp.) resistant to third-generation cephalosporins and carbapenems, multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii (CRAB) have been identified by the World Health Organization as the most problematic pathogens. In addition to new diagnostic methods for the rapid identification of AMR, several new antibiotics have been approved in the last 10 years, expanding the treatment options, particularly for MDRGN infections. Pharmaceutical strategies have so far focused primarily on modifying already known classes of antibiotics with the aim of circumventing class-specific resistance mechanisms and reducing resistance rates. In addition to cefiderocol, the first siderophore cephalosporin, new combinations of β‑lactam antibiotics and β‑lactamase inhibitors (BLIs) such as ceftolozan/tazobactam, ceftazidime/avibactam, cefepime/enmetazobactam, imipenem/cilastatin/relebactam, and meropenem/vaborbactam, as well as the monobactam/BLI combination aztreonam/avibactam, have been approved and successfully implemented in clinical care. In addition, there is the synthetic tetracycline antibiotic eravacycline, which has a broad spectrum of activity against Gram-positive, Gram-negative (particularly clinically relevant Enterobacterales), anaerobic, and multidrug-resistant bacteria, and the new glycopeptide antibiotic dalbavancin, which is effective against Gram-positive bacteria. Since a change in legislation in 2021, the Joint Federal Committee (Gemeinsamer Bundesausschuss, G‑BA) in Germany has been authorized to classify newly approved antibiotics as reserve antibiotics. This classification allows for an exception to the regular additional benefit assessment as part of the early benefit assessment. The pipeline of antibiotics in development with novel targets and chemical structures-which had almost completely dried up-has been re-filled with new candidates for clinical trials. Some of these agents have already been tested with promising results in smaller phase 1/2 studies. In addition, monoclonal antibodies, antimicrobial peptides, small molecules, microbiome-modifying biotherapeutics, and bacteriophages, all enabling targeted and personalized treatment, are currently being investigated in studies.

Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women. The disease often manifests through nonspecific symptoms, such as fever, fatigue, and arthralgia; the skin and kidneys are also frequently affected. Management is guided by the treat-to-target (T2T) principle, with the goal of achieving a state of remission as quickly as possible. An increasing selection of medications is available for this purpose, the use of which is further detailed in the new S3 guideline on SLE and in new international recommendations. The objective of this article is to convey the central aspects concerning the pathogenesis, diagnosis, and management of SLE and to reduce uncertainties in dealing with affected patients.

Background: Demographic change is leading to an ever-increasing prevalence of multimorbidity and polypharmacy. At the same time, older people are excluded from randomized controlled approval studies. Due to this age-blind approach, there is a lack of evidence regarding the efficacy, safety, and suitability for older people of many drugs used by the main consumers of medicinal products. To solve this problem, many different list approaches and tools have been developed, often using a combination of existing evidence and expert opinion.

Materials and methods: A narrative evaluation of deprescribing and represcribing was conducted based on current literature.

Results: Most of the tools developed focus on discontinuing potentially inappropriate medication (PIM; i.e., deprescribing) and disregard the patient's clinical condition and the need for useful age-appropriate medication or potentially omitted medication (POM). Represcribing is a further development that encompasses both the deprescribing of PIMs and the prescribing of POMs that are useful and safe for older people. Clinical validation of available tools in a few randomized controlled trials with relevant clinical endpoints, such as the occurrence of adverse drug reactions, suggests that represcribing is more feasible and successful than deprescribing.

Conclusion: The goal of age-appropriate drug therapy in geriatric patients should not only be to reduce the number of medications or eliminate polypharmacy, but also to transition from poor polypharmacy to good polypharmacy through individualization and represcribing.

Difficulties with polypharmacy are a recognized problem in geriatric patients suffering from multimorbidity. Clinical science has developed several solutions to this problem. The most widely endorsed approach is the use of medication lists, which methodically categorize substances or substance classes. The risk of drug interactions or prescription cascades increases with the number of medications. In the case of severe frailty or life-limiting disease within a palliative context, modification of treatment objectives is imperative. Reevaluation of the existing pharmacotherapy is required. In order to correspond most individually to patients' wishes and values, substantial knowledge of patients' needs and contextual factors (physical and psychological symptom burden, availability of care, social situation) is essential. This is necessary for a good risk-benefit analysis under patients' involvement.

Background: Polypharmacy is common among older adults. Renal effects can range from mild functional increases in creatinine to structural tubular injury.

Objective: The aim of the study was to systematically describe nephrotoxicity in the context of polypharmacy, identify typical pharmacokinetic and pharmacodynamic constellations, and introduce the concept of "nephrotoxic burden" as a potential tool for quantitative risk assessment.

Materials and methods: A selective review of the literature on drug-induced nephrotoxicity and drug-drug interactions was performed.

Results: Pharmacokinetic interactions leading to renal adverse drug reactions typically occur when dose-dependent nephrotoxic agents such as calcineurin inhibitors reach toxic concentrations through cytochrome P450 3A4 (CYP3A4) inhibition (e.g., by macrolides, azoles, or ritonavir). Pharmacodynamic interactions associated with renal effects are observed, for example, with the combination of nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors, and diuretics, or with combinations of vancomycin and aminoglycosides or piperacillin. The concept of nephrotoxic burden addresses the risk of acute kidney injury (AKI) from concurrent use of multiple nephrotoxic drugs but currently lacks adequate differentiation between underlying mechanisms.

Conclusions: In patients receiving calcineurin inhibitors, any additional prescriptions should be carefully reviewed for potential interactions and accompanied by dose adjustment and close therapeutic drug monitoring where appropriate. The concurrent use of several agents with structural tubular toxicity generally increases risk, whereas functional mechanisms, such as those seen with combined ACE inhibitor and sodium-glucose cotransporter 2 inhibitor (SGLT2) inhibitor therapy, are usually well tolerated. The concept of nephrotoxic burden shows promise but requires further refinement and prospective validation before it can serve as a practical tool for risk stratification in polypharmacy.