Publications by authors named "Klaus Heeg"

Third-generation cephalosporin-resistant Enterobacterales is a major threat for newborns in neonatal intensive care units (NICUs). The route of acquisition in a non-outbreak setting should be investigated to implement adequate infection prevention measures. To identify risk factors for colonization with and to investigate the transmission pattern of third-generation cephalosporin-resistant Enterobacterales in a NICU setting.

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Article Synopsis
  • Resistance to cefiderocol, a new antibiotic, in E. coli linked to metallo-β-lactamases like NDM-5 and VIM-1, while KPC-2 and OXA-48 do not contribute.
  • The study involved transferring β-lactamases into E. coli and testing their ability to develop resistance through serial exposure to cefiderocol.
  • Notable changes in the bacterial morphology and the emergence of small-colony variants (SCVs) were observed, potentially affecting how these bacteria evade the immune system and respond to treatment.
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Background: Cefiderocol is a novel siderophore cephalosporin active against MDR Gram-negative bacilli, including MBL-harbouring Enterobacterales. The detection of multiple cefiderocol-resistant blaVIM-carrying Enterobacterales isolates (MIC = 4 mg/L) from a single patient suggested an additional, potentially transferable, resistance determinant as blaVIM typically does not elevate cefiderocol MIC above the resistance threshold.

Methods: Transfer of a mobile genetic element was performed in liquid mating experiments.

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Background: Infectious complications are a major cause of morbidity and mortality after kidney transplantation.

Methods: In this transplant cohort study at the German Center of Infectious Diseases (DZIF), we evaluated all infections occurring during the first year after renal transplantation. We assessed microbial etiology, incidence rates, and temporal occurrence of these infections.

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The severe course of bloodstream infections with Gram-negative bacilli can lead to organ dysfunctions and compromise the integrity of the vascular barrier, which are the hallmarks of sepsis. This study aimed to investigate the potential effect of cefiderocol on the barrier function of vascular endothelial cells (vECs) in an in vitro experimental set-up. Human umbilical vein cells (HUVECs), co-cultured with erythrocyte-depleted whole blood for up to 48 h, were activated with tumor necrosis factor-alpha (TNF-α) or lipopolysaccharide (LPS) to induce endothelial damage in the absence or presence of cefiderocol (concentrations of 10, 40 and 70 mg/L).

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is one of the clinically most relevant pathogens causing infections. Humans are often exposed to . In approximately one-third of the healthy population it can be found on the skin either for long or short periods as colonizing "commensals", without inducing infections or an inflammatory immune response.

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Persistent infections caused by remain a clinical challenge. Adaptational mechanisms of the pathogen influencing infection persistence, treatment success, and clinical outcome in these types of infections by have not been fully elucidated so far. We applied a whole-genome sequencing approach on fifteen isolates retrieved from a persistent infection to determine their genetic relatedness, virulome, and resistome.

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Clinical and laboratory data on newly described staphylococcal species is rare, which hampers decision-making when such pathogens are detected in clinical specimens. Here, we describe Staphylococcus massiliensis detected in three patients at a university hospital in southwest Germany. We report the discrepancy of microbiological findings between matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 16S-rRNA polymerase chain reaction, and whole-genome sequencing for all three isolates.

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is one of the most prevalent pathogens, causing a variety of infections including bloodstream infections. At the same time, it can be found as a commensal, being part of the intestinal microflora. While it is widely accepted that pathogenic strains can evolve from colonizing strains, the evolutionary route facilitating the commensal-to-pathogen transition is complex and remains not fully understood.

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Vascular leakage associated with vascular endothelial cell (vEC) dysfunction is a hallmark of sepsis. Causative for the decreased integrity of the vascular endothelium (vE) is a complex concurrence of pathogen components, inflammation-associated host factors, and the interaction of vECs and activated circulating immune cells. One signaling pathway that regulates the integrity of the vE is the Notch cascade, which is activated through the binding of a Notch ligand to its respective Notch receptor.

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Article Synopsis
  • Cefiderocol is a new antibiotic that targets multidrug-resistant Gram-negative bacteria and is resistant to certain enzymes that typically break down antibiotics.
  • However, there have been instances where bacteria producing metallo-β-lactamases have developed resistance to cefiderocol during treatment.
  • Research showed that a specific enzyme (NDM) helps bacteria gain resistance through mutations, but using dipicolinic acid can inhibit these enzymes and reduce the chances of resistance, highlighting the need for caution in treatment choices.
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  • The study points out that hospitals can be a hotspot for the spread of drug-resistant bacteria, especially carbapenemase-producing Enterobacterales, due to complex plumbing systems and microbial diversity.
  • Researchers analyzed 133 OXA-48-producing Enterobacter cloacae isolates and found that the hospital water was the primary source linked to outbreaks among 41 patients in a hematology unit.
  • While continuous cleaning methods were somewhat effective in reducing bacterial presence, implementing custom shower tubs proved to be more successful in stopping new infections over a year-long period, highlighting the need for physical changes to the environment for better infection control.
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Trimethoprim-sulfamethoxazole (SXT) is a valuable second-line antimicrobial agent to treat methicillin-resistant Staphylococcus aureus infections. Discrepancies between various antibiotic susceptibility testing (AST) methods for SXT susceptibility in S. aureus have been described.

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Objectives: Increasing spread of resistance could jeopardize the use of antifolates against MRSA infections.

Methods: We compared the prevalence of phenotypic trimethoprim/sulfamethoxazole resistance in 20 534 clinical Staphylococcus aureus isolates (19 096 MSSA and 1438 MRSA) of non-redundant patients at Heidelberg University Hospital over 8 years and performed WGS on trimethoprim/sulfamethoxazole-resistant MRSA.

Results: From 2012 to 2019, trimethoprim/sulfamethoxazole resistance in MSSA (674/19 096; 3.

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Importance: Staphylococcus aureus is one of the leading causes of infections in neonatal intensive care units (NICUs). Most studies in this patient group focus on methicillin-resistant S aureus or the outbreak setting, whereas data for methicillin-susceptible S aureus are limited.

Objectives: To identify risk factors for S aureus colonization and infections in hospitalized newborns and to investigate S aureus transmission and its dynamics in a nonoutbreak setting.

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Bleeding associated with endothelial damage is a key feature of severe dengue fever. In the current study, we investigated whether Notch ligands were associated with bleeding in 115 patients with confirmed dengue infection in Vietnam. Soluble Notch ligands were determined by means of enzyme-linked immunosorbent assay.

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Carbapenemase-producing bacteria are a risk factor in clinical settings worldwide. The aim of the study was to accelerate the time to results during an outbreak situation with bla-positive Enterobacter cloacae by using a real-time multiplex quantitative PCR (qPCR) directly on rectal swab specimens and on wastewater samples to detect carbapenemase-producing bacteria. Thus, we analyzed 681 rectal swabs and 947 environmental samples during a five-month period by qPCR and compared the results to culture screening.

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Objectives: The aim was to assess the performance of antigen-based rapid diagnostic tests (Ag-RDTs) for SARS CoV-2 when implemented for large-scale universal screening of asymptomatic individuals.

Methods: This study was a pragmatic implementation study for universal Ag-RDT-based screening at a tertiary care hospital in Germany where patients presenting for elective procedures and selected personnel without symptoms suggestive of SARS-CoV-2 were screened with an Ag-RDT since October 2020. Test performance was calculated on an individual patient level.

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Background: There is a growing interest in the rapid genotypic identification of antimicrobial resistance (AMR). In routine diagnostics, we detected multiple KPC-positive Escherichia coli (KPC-Ec) with discordant phenotypic meropenem susceptibility from a single patient's blood cultures, which prompted a more thorough investigation.

Objectives: We investigated the potential clinical relevance of, and the mechanism behind, discordant phenotypic and genotypic meropenem susceptibility in KPC-Ec.

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Carbapenem-resistant Enterobacterales are a growing problem in healthcare systems worldwide. While whole-genome sequencing (WGS) has become a powerful tool for analyzing transmission and possible outbreaks, it remains laborious, and the limitations in diagnostic workflows are not well studied. The aim of this study was to compare the performance of WGS and real-time multiplex PCR (RT-qPCR) for diagnosing carbapenem-resistant Enterobacterales.

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We report a case of resistance development toward cefiderocol in a patient with intra-abdominal and bloodstream infections caused by carbapenemase-producing Enterobacter cloacae within 21 days of cefiderocol therapy. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, encoding a catecholate siderophore receptor, conferring phenotypic resistance to cefiderocol.

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Fast detection of carbapenemases in Gram-negative bacilli is necessary for accurate antibiotic treatment, prevention of further spreading and surveillance purposes. We analyzed the current occurrence of gene variants and designed two multiplex PCRs with hydrolysis probes. The assay was developed for the BD MAX™ system that combines DNA extraction and PCR in a fully automated procedure providing results within 3 h and was evaluated for detection of carbapenemases from bacterial isolates and directly from rectal swabs.

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Article Synopsis
  • The study focuses on the MRSA strain ST8-t008, particularly the USA300 and USA300-LV variants, which are prevalent in the Americas and are associated with international travel and hospital outbreaks in Europe.
  • Researchers analyzed 19 MRSA samples from Germany, comparing them to global sequences of the same strain found in travelers and other European cases.
  • Results showed that a significant portion of the local strains were related to the USA300 variant, suggesting multiple introductions into Germany and hinting at possible community transmission based on observed clusters.
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As whole genome sequencing is becoming more accessible and affordable for clinical microbiological diagnostics, the reliability of genotypic antimicrobial resistance (AMR) prediction from sequencing data is an important issue to address. Computational AMR prediction can be performed at multiple levels. The first-level approach, such as simple AMR search relies heavily on the quality of the information fed into the database.

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