Vancomycin-resistant enterococci (VRE) colonization is common among patients with acute myeloid leukemia (AML) undergoing intensive chemotherapy. Whether the teicoplanin-defined VRE phenotype, specifically vanA-consistent (teicoplanin-resistant) versus vanB-consistent (teicoplanin-susceptible), is associated with adverse outcomes is unknown. We conducted a retrospective single-center cohort study of 192 VRE-colonized AML patients who received intensive induction chemotherapy between 2015 and 2024. vanA-consistent phenotype (n = 35, 18.2

International guidelines recommend first-generation cephalosporins for preoperative antibiotic prophylaxis in patients undergoing resection for perihilar cholangiocarcinoma (pCCA). Knowledge on the resistance profile of biliary bacteria and its impact on liver-specific complications is limited. This study aimed to evaluate the biliary microbial spectrum, particularly focusing on the impact of resistant bacteria on liver-specific complications following pCCA resection. This is a retrospective, single-center, observational study. All patients with resected pCCA at the University Hospital Frankfurt from July 2005 to December 2022 were included. The microbial spectrum was analyzed using intraoperative bile swabs. From 118 patients, 104 had an intraoperative bile swab taken. Microorganisms (bacteria, fungi) were detected in 89.4

The purpose of this study was to evaluate the outcome of patients with perforated peptic ulcer, stratified by detection of Candida spp. from peritoneal swabs. A retrospective, single-center, observational study was performed. All adult patients with perforated peptic ulcer who underwent surgical therapy were included. Candida spp. detection was defined as the result of culture incubation from peritoneal swabs at the index surgery. Its association with postoperative complications and in-hospital mortality was analyzed. A total of 187 adult patients were included. Intraperitoneal pathogens were detected by microbiological analysis in 96 patients (61.9

Background:In advanced chronic liver disease (ACLD) patients, bacterial infections with multidrug-resistant Gram-negative bacteria (MDRGN) can progress to acute-on-chronic liver failure (ACLF) with high mortality rates. Particularly carbapenem-resistant Gram-negative bacteria (CR-GN) pose a significant threat due to limited antibiotic treatment options. However, non-carbapenem drug-resistant Gram-negative bacteria (NCR-DRGN) are clinically highly relevant, as they occur more frequently and may serve as precursors to CR-GN. This study aims to assess the prevalence, resistance mechanisms, and transmission dynamics of NCR-DRGN in ACLD patients including those with ACLF. Materials and methods:A prospective, single-center study was conducted at University Hospital Frankfurt. Over 32 months, ACLD patients were screened for NCR-DRGN by routine microbiology techniques. Whole-genome sequencing (WGS) of isolated bacteria was performed to analyze genetic diversity, resistance, and transmission patterns. Epidemiological links were explored through patient chart reviews. Results:NCR-DRGN were found in 12.1% (n = 22/182) of ACLD patients, comprising of 44 isolates, predominantly Escherichia coli (n = 40/44; 90.9%). All isolates were phenotypically classified as NCR-DRGN; however, one isolate was found to harbor a bla OXA-244 gene potentially affecting carbapenem treatment efficacy. Genomic analysis revealed significant diversity, with no evidence of clonal outbreaks, although one potential transmission event was identified. Conclusion:NCR-DRGN are prevalent in ACLD patients, with E. coli as the dominant pathogen. Standard hygiene measures appear effective in preventing transmission, emphasizing the importance of routine screening and infection control in this high-risk population.

Aberrant microbial colonization of premature infants is increasingly recognized as a risk factor for severe acute morbidities. The aim of this study was to evaluate the correlation of bacterial upper airway colonization within the first 6 weeks of life in preterm infants <1000g and risk of moderate/severe bronchopulmonary dysplasia (BPD). In this retrospective two-center cohort study postnatal upper airway bacterial colonization of premature infants with a birth weight <1000g was analyzed. Bacteria were categorized into facultative- and highly pathogenic. Within 242 infants, a birth weight cutoff of 800g prevailed as the most relevant discriminator for risk of BPD. Furthermore, center, male sex, duration of antibiotic therapy, and delayed detection of facultative pathogenic bacteria after week 4 was associated with the development of BPD. Using classification tree analyses for the binary outcome, antibiotic therapy was more importance in infants <800g, whereas in those with a birth weight ≥800g, delayed colonization with facultative pathogenic bacteria was more relevant than antibiotic exposure. We add delayed colonization of the upper airway with facultative pathogenic bacteria to the risks for BPD. The variations of microbial colonization should be considered in future studies on the pathogenesis of BPD and new treatment modalities.

Objectives: Infectious diseases and high-consequence infectious diseases (HCID), are often present in febrile travelers. Multiplex polymerase chain reaction (PCR) may help to confirm or rule out HCIDs and thus prevent a delay in treatment or undue isolation. Methods: The BioFire® FilmArray® Global Fever Panel–RUO was evaluated vs conventional methods in diagnostics in febrile returning travelers. Results: Eighty-two patients and three simulated patients with HCIDs were analyzed. A total of 10 of the 19 possible pathogens were detected by multiplex PCR. In 30 samples, at least one pathogen was detected by the multiplex PCR, as compared to 35 with conventional diagnostics. The positive percentage agreement was 85.71% (69.74-95.19) overall: Crimean-Congo hemorrhagic fever virus 1/1, dengue virus 4/4, Ebola virus 1/1, Leptospira 1/2 (50%, 1.26-98.74), Marburg virus 1/1, Plasmodium spp. 22/23 (95.65%, 78.05-99.89), Plasmodium falciparum 19/20 (95%, 75.13-99.89), Plasmodium vivax/ovale 2/2, Salmonella enterica serovar typhi 0/2, and Salmonella enterica serovar Paratyphi 0/1. The overall negative percentage agreement was 96.0% (86.29-99.51). Conclusion: The multiplex PCR detected pathogens from blood with varying levels of specificity and sensitivity in less than 1 hour. For HCID, it could shorten the time to diagnosis. However, Salmonella enterica spp. or Leptospira spp. were detected infrequently.

In December 2023, the World Health Organization reported an Australian nosocomial Ralstonia pickettii outbreak caused by contaminated saline solutions, causing bloodstream infections. The Antibiotic Resistance Surveillance, a Germany-wide laboratory network, has identified five R. pickettii-bacteraemia cases since August 2023 (0–1 annually 2019–2022), prompting an outbreak investigation to identify the source. We defined a case as a person with R. pickettii in any material (possible) or in blood culture (probable), confirmed if in the genetic outbreak cluster. We implemented nationwide R. pickettii surveillance, subjected isolates to core genome multilocus sequence typing, and compared cases by exposure, including medical products. From August 2023 to June 2024, we detected 25 cases. For eighteen cases, isolates were available, and sequences from six cases clustered within 6 allelic differences but showed >43 allelic differences from Australian outbreak-associated sequences. These confirmed cases occurred in three hospitals across three federal states between October 2023 and March 2024, linked only by saline solution exposure. Four products and 11 lots matched across two of three hospitals. Retain sample testing remained negative. The R. pickettii outbreak in Germany was likely linked to saline solutions, although no product/lot was confirmed. Tracing products/lots was particularly challenging. Patient-level documentation of medical products/lots and official mandates for the testing of retained samples could improve product traceback in future outbreaks.

OBJECTIVES:Mycobacterium chelonae is a rapid-growing non-tuberculous mycobacterium that has occasionally been described in connection with foreign material infections, e.g. after orthopaedic joint replacement or cosmetic surgery. In a recent outbreak, several cases of M. chelonae endocarditis associated with biological heart valve prostheses were reported. CASE HISTORY:A 64-year-old female patient with a history of myalgia and recurrent joint swelling presented to our hospital. Initially suspected for rheumatoid arthritis, the patient underwent a series of orthopedic and rheumatologic treatments, including prednisolone and methotrexate. Subsequent history revealed a Ross operation in 2014 and a PET-CT was suspicious of a biological valved conduit infection leading to surgical replacement. Utilizing fluorescence in situ hybridization (FISH) diagnostic techniques, DAPI, Kinyoun and Ziehl-Neelsen staining, mycobacterial infection was confirmed in both the prosthesis and adjacent muscle tissue. Molecular methods identified a mycobacterium most closely related to the M. chelonae/abscessus complex indicating an association to a previously described outbreak of M. chelonae contaminated heart valves. Antimycobacterial therapy was initiated and the patient remains stable at the time of writing. To date, all mycobacterial cultures remained negative. CONCLUSIONS:Non-tuberculous mycobacteria (NTM) are rare and possibly underdiagnosed pathogens in infections of bioprosthetic flap bearing conduits. Mycobacterial foreign-body infections can manifest many years after implantation. As NTM can be difficult to detect, molecular identification methods are of particular importance. Here, modern imaging, molecular and microscopic techniques might be of special use in diagnosing prolonged prosthetic graft infections.

Die Osteomyelitis des Felsenbeins (OF) ist eine seltene entzündliche Erkrankung, die sich vom Gehörgang auf angrenzende Weichteil- und Knochenstrukturen ausbreiten kann. Diese entzündliche Affektion von Nachbarstrukturen stellt eine therapeutische Herausforderung dar und kann lebensbedrohlich verlaufen. Der Nachweis des zugrunde liegenden Erregers ist entscheidend für eine erfolgreiche Therapie. Aktuelle Studien haben ein breites Erregerspektrum bei der OF gezeigt. Unser Studienziel waren die Analyse des mikrobiologischen Spektrums in unserem Patientenkollektiv mit OF und ein Vergleich dieser Daten mit der aktuellen Literatur. In dieser retrospektiven, monozentrischen Studie wurden Patienten eingeschlossen, bei denen in einem 10-Jahres-Zeitraum eine OF diagnostiziert wurde (n=39). Wir analysierten das mikrobiologische Spektrum, die klinischen Symptome, die radiologischen Befunde und den Krankheitsverlauf. Die häufigsten Symptome waren Otalgie (n=29, 74,4%) und Otorrhoe (n=24, 61,5%). In mikrobiologischen Untersuchungen wurde am häufigsten P. aeruginosa (n=21, 53,8%) nachgewiesen. Der Nachweis dieses Erregers korrelierte mit erhöhten CRP-Werten (p<0,05). In computertomografischen Untersuchungen ließ sich bei 38 Patienten (97,4%) eine ausgewaschene Knochentextur des Felsenbeins nachweisen. Während des Nachbeobachtungszeitraums berichteten 10 Patienten (25,6%) über eine Verringerung, 23 Patienten (59,0%) hingegen über eine Persistenz der Symptome. Vier Patienten (10,3%) verstarben. Im Gegensatz zu kürzlich veröffentlichten Daten ist in unserer Patientenkohorte P. aeruginosa nach wie vor der häufigste und herausforderndste Erreger der OF. Daher sollte bei der Auswahl einer empirischen Therapie stets auf deren Wirksamkeit gegen diesen Erreger geachtet werden.

Background/Objectives: Appendicitis caused by multi-drug-resistant pathogens is associated with significant postoperative morbidity. However, prospective data on the microbial spectrum and its clinical impact remain limited. Methods: Adults with acute appendicitis undergoing surgery between April 2022 and July 2023 were prospectively enrolled at a single university-affiliated institution. Bacterial cultures from appendiceal and rectal swabs were analyzed, and clinical outcomes were assessed. A telephone follow-up was conducted 30 days postoperatively. Results: A total of 105 patients were included. Multi-drug-resistant pathogens were identified in the appendiceal swabs of twenty-nine patients (27.6%), while six patients (5.7%) harbored multi-drug-resistant organisms (MDROs; according to the criteria of the CDC). Rectal swabs revealed MDROs in 11.4% of cases but showed a limited correlation with appendiceal samples, indicating that rectal colonization does not reliably predict the presence of MDROs in appendicitis. Patients with multi-drug-resistant infections had significantly higher postoperative complication rates (31% vs. 10.5%, p = 0.017), including more Clavien–Dindo grade 3 complications (17.2% vs. 2.6%, p = 0.007) and abdominal abscesses (10.3% vs. 1.3%, p = 0.03). These patients required more frequent postoperative antibiotic treatment (65.5% vs. 40.8%, p = 0.03) and therapy adjustments (37.9% vs. 15.8%, p = 0.02). Hospital stays were also prolonged in the multi-drug-resistant group (a median of 4 days and IQR of 5 days vs. a median of 3 days and IQR of 3 days; p = 0.03). Conclusions: Colonization with multi-drug-resistant pathogens in appendicitis is associated with worse clinical outcomes. The intraoperative microbiological analysis of appendiceal swabs in complicated cases may enable targeted antibiotic therapy, potentially shortening hospital stays, optimizing patient management and reducing healthcare costs.

Multidrug-resistant (MDR) bacteria pose a significant global health threat. Among these, Acinetobacter baumannii, particularly carbapenem-resistant A. baumannii , is a leading cause of healthcare-associated infections. Emerging evidence links gut colonization to systemic infections, highlighting opportunities for new control strategies. We demonstrate that A. baumannii can survive under anaerobic conditions (≤1%) and shows limited growth under low oxygen conditions (≥1%), underscoring its adaptation to niches in the intestine. However, specific carbohydrates, including maltose, provide the gut bacteria Klebsiella oxytoca with a competitive advantage under anoxic conditions, enabling it to actively suppress A. baumannii through its metabolism. Notably, maltose induces this suppressive capacity in other commensals and complex gut microbiomes as well. Force-feeding experiments in Galleria mellonella larvae corroborate that K. oxytoca in combination with maltose significantly reduces A. baumannii recovery in gut environments. These findings suggest that targeted carbohydrate supplementation could enhance probiotic strategies, creating an environment unfavorable to A. baumannii . ### Competing Interest Statement L.O., T.S. and M.W. filed a patent for the use of K. oxytoca to decolonize MDR Enterobacteriaceae from the gut (EP4259171A1, EP4011384A1, WO002022122825A1, and US020240041950A1). T.S., M.W., L.O. and K.A.W. filed a provisional patent for using E. coli strains to decolonize MDR Enterobacteriaceae from the gut (EP24182102.4/ PCT/ EP2025/060744). All other authors do not declare any competing interest. All data generated or analyzed during this study are included in the published article or its supplementary information. Explanatory graphics were created in BioRender. Supplementary Data are provided with this publication. Additional data are available from the corresponding author upon reasonable request. Federal state Saxony-Anhalt and the European Structural and Investment Funds, ESF, 2014–2020, project number 44 100 32 030 ZS/2016/08/80645 Joint Programming Initiative on Antimicrobial Resistance, 01KI1824 Bundesministerium für Bildung und Forschung, 01KI2131 German Center for Infection Research, project number 06.826 Deutsche Forschungsgemeinschaft (German Research Foundation), EXC 2155—project number 390874280

Bloodstream infections (BSI) due to Candida spp. significantly contribute to morbidity and mortality among cancer patients. Understanding their clinical course, risk factors, and outcomes compared to bacterial BSI is essential. We aim to elucidate the epidemiology and risk factors associated with Candida BSI compared to bacterial BSI in cancer patients. We analyzed epidemiological data of Candida BSI versus bacterial BSI among cancer patients, primarily with hematological malignancies. Blood cultures were obtained upon clinical suspicion, with species identification by VITEK 2 and MALDI-TOF. Susceptibility testing utilized VITEK 2 or antibiotic gradient tests. Candida BSI was associated with higher 30-day mortality compared to bacterial BSI (Hazard ratio (HR) 4.5, 95

Background/purpose Nocardia spp. are rare but clinically relevant pathogens in patients with structural lung disease and/or immunosuppression. Nocardia pneumoniae was first described in 2004; however, its clinical relevance has remained unclear due to the limited number of reported cases to date. Methods Case report and review of the literature. Case presentation We report a case of a 54-year-old female with bronchiectasis who presented with pulmonary exacerbation and was diagnosed with an infection with Nocardia pneumoniae. The current case was successfully treated with trimethoprim-sulfamethoxazole monotherapy over 12 weeks. Conclusion We propose that Nocardia pneumoniae should be considered clinically significant. The management of nocardiosis remains difficult, as reliable evidence on optimal antimicrobial strategies, appropriate treatment duration, and the need for secondary prophylaxis is still lacking.

After 3 cases of Corynebacterium diphtheriae infection associated with intravenous drug use among persons experiencing homelessness (PEH) were reported to the Health Protection Authority in Frankfurt am Main, Germany, in 2023, we examined pathogen spread among PEH. Furthermore, we investigated a possible link with the 2022 outbreak of diphtheria in Europe. From swab samples collected during August-November 2023 from 36 PEH and cutaneous lesions, we detected 3 additional cases of cutaneous toxigenic C. diphtheriae. Sequence type 574 was identified in 5 case-isolates and is genetically associated with 1 of the predominant clusters in identified in the 2022 outbreak. Our findings demonstrate the need for increased detection and monitoring of cutaneous diphtheria and boosting immunity against diphtheria in groups with increased risk for infection. Genomic analyses are valuable for identifying genetic relationships between outbreaks, even when epidemiologic data are scarce.

Bloodstream infections caused by Pseudomonas aeruginosa (PABSI) in hematological patients are associated with high morbidity and mortality. We investigated the epidemiology, risk factors, and outcomes of PABSI at our center. All adult hematological patients with PABSI between January 2013 and July 2023 were included. Demographic and clinical characteristics, antimicrobial susceptibilities, antibiotic therapy, fluoroquinolone-prophylaxis, source of infection, and 30-day outcome were recorded. Descriptive statistics, tests for difference, and logistic regression models were performed. Fifty patients with PABSI were identified with a median age of 58.5 years (range 24–78). 37 patients (74

Introduction. Infectious gastroenteritis is a common reason for consulting a physician. Although most cases of gastrointestinal illness are self-limiting, the identification of the etiologic pathogen by stool specimen analysis is important in cases of more severe illness and for epidemiological reasons. Due to the broad range of causative pathogens, the conventional examination of a stool specimen is labour-intensive and usually requires different diagnostic methods. Multiplex PCR tests [e.g. BioFire Gastrointestinal (GI) Panel] allow the rapid detecting of up to 22 pathogens in one test. Hypothesis. Using a multiplex PCR panel to test stool specimens for infectious gastroenteritis pathogens can improve the detection rate, reduce the time-to-result and hands-on time and lower the costs of a microbiology laboratory. Aim. This study was aimed at evaluating the detection rate, the workflow and associated costs of stool specimen management using the BioFire GI Panel versus conventional methods. Methodology. Stool specimens were evaluated prospectively during the routine operation. Pathogen detection rate, hands-on time, time-to-result and material and personnel costs were determined for the BioFire GI Panel and conventional methods—the latter based on physician request and excluding viral testing. Results. Analysing 333 specimens collected between 2019 and 2020, the detection rate of enteropathogens was significantly higher with a positivity rate of 39.9 % using the multiplex PCR panel compared with 15.0 % using the conventional methods. The BioFire GI Panel presented results in a median time of 2.2 h compared with 77.5 h for culture and 22.1 h for antigen testing, noting that no tests were performed at weekends except for toxinogenic Clostridioides difficile . Based on list prices, the BioFire GI Panel was nine times more expensive compared with conventional methods, whereas hands-on-time was significantly lower using the BioFire GI Panel. Conclusion. Multiplex PCR panels are valuable tools for laboratory identification of infectious agents causing diarrhoea. The higher costs of such a multiplex PCR panel might be outweighed by the higher detection rate, ease of handling, rapid results and most likely improved patient management. However, these panels do not provide information on antimicrobial susceptibility testing. Therefore, if this is necessary for targeted therapy or if outbreak monitoring and control is required, specimens must still be cultured.

Cystic Fibrosis (CF) is the most common autosomal recessive genetic multisystemic disease. In Germany, it affects at least 8000 people. The disease is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene leading to dysfunction of CFTR, a transmembrane chloride channel. This defect causes insufficient hydration of the airway epithelial lining fluid which leads to reduction of the mucociliary clearance.Even if highly effective, CFTR modulator therapy has been available for some years and people with CF are getting much older than before, recurrent and chronic infections of the airways as well as pulmonary exacerbations still occur. In adult CF life, Pseudomonas aeruginosa (PA) is the most relevant pathogen in colonisation and chronic infection of the lung, leading to further loss of lung function. There are many possibilities to treat PA-infection.This is a S3-clinical guideline which implements a definition for chronic PA-infection and demonstrates evidence-based diagnostic methods and medical treatment in order to give guidance for individual treatment options.

AbstractBackgroundTheMycobacterium aviumcomplex (MAC) comprises the most frequent non-tuberculous mycobacteria (NTM) in Central Europe and currently includes twelve species.M. avium(MAV),M. intracellularesubsp.intracellulare(MINT), andM. intracellularesubsp.chimaera(MCH) are clinically most relevant. However, the population structure and genomic landscape of MAC linked with potential pathobiological differences remain little investigated.MethodsWhole genome sequencing (WGS) was performed on a multi-national set of MAC isolates from Germany, France, and Switzerland. Phylogenetic analysis was conducted, as well as plasmids, resistance, and virulence genes predicted from WGS data. Data was set into a global context with publicly available sequences. Finally, detailed clinical characteristics were associated with genomic data in a subset of the cohort.ResultsOverall, 610 isolates from 465 patients were included. The majority could be assigned to MAV (n = 386), MCH (n = 111), and MINT (n = 77). We demonstrate clustering with less than 12 SNPs distance of isolates obtained from different patients in all major MAC species and the identification of trans-European or even trans-continental clusters when set into relation with 1307 public sequences. However, none of our MCH isolates clustered closely with the heater-cooler unit outbreak strain Zuerich-1. Known plasmids were detected in MAV (325/1076, 30.2%), MINT (62/327, 19.0%), and almost all MCH-isolates (457/463, 98.7%). Predicted resistance to aminoglycosides or macrolides was rare. Overall, there was no direct link between phylogenomic grouping and clinical manifestations, but MCH and MINT were rarely found in patients with extra-pulmonary disease (OR 0.12 95% CI 0.04–0.28,p < 0.001 and OR 0.11 95% CI 0.02–0.4,p = 0.004, respectively) and MCH was negatively associated with fulfillment of the ATS criteria when isolated from respiratory samples (OR 0.28 95% CI 0.09-0.7, p = 0.011). With 14 out of 43 patients with available serial isolates, co-infections or co-colonizations with different strains or even species of the MAC were frequent (32.6%).ConclusionsThis study demonstrates clustering and the presence of plasmids in a large proportion of MAC isolates in Europe and in a global context. Future studies need to urgently define potential ways of transmission of MAC isolates and the potential involvement of plasmids in virulence.