[Fatal neurological side effect of anti-CD20 antibody treatment]. / Fatale neurologische Nebenwirkung einer Anti-CD20-Antikörper-Therapie.

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal infection of the central nervous system caused by reactivation of John Cunningham virus (JCV). The case of a 59-year-old woman presenting with neurological disorders after treatment of her relapsed lymphoma with rituximab, among others, is reported. Magnetic resonance imaging showed fast-growing white matter lesions of both hemisphere and cerebellar that were neither space-consuming nor enhancing contrast media. Clinical and radiological suspicion of PML was confirmed by detection of JCV-DNA in cerebrospinal fluid. The patient died from devastating neurological decline only 11 days after the diagnosis was made. Due to the wider indication of monoclonal antibodies in almost every medical specialty we must always consider iatrogenic PML in addition to classic PML associated with acquired immunodeficiency syndrome (AIDS).

Proof-of-Concept Standardized Approach Using a Single-Disk Method Analogous to Antibiotic Disk Diffusion Assays for Routine Phage Susceptibility Testing in Diagnostic Laboratories.

Application of bacteriophages is increasingly being implemented in clinical therapies. Prior susceptibility testing should be regarded as mandatory, but standards are lacking. The objective of this research was to develop a highly standardized methodology to facilitate phage susceptibility testing (PST) in clinical microbiology routine laboratories. Therefore, EUCAST methods established for single disk-based antibiotic susceptibility testing (AST) were adapted. In a first step, basic parameters were evaluated using well-studied Escherichia phage T4-Escherichia coli combinations. In addition, test results were compared to those from conventional spot test and efficiency of plating (EOP) approaches. In a second step, the applicability of the methodology and the most promising test parameters were demonstrated for five other frequently isolated clinical bacterial species and their corresponding phages. At present, the method predominantly leads to qualitative rather than quantitative results. This disk-based approach provides a standardized, easy-to-handle, reproducible and reliable PST protocol by relying on well-established routine procedures in diagnostic laboratories. IMPORTANCE Application of bacteriophages in clinical therapies is attractive due to increasing rates of isolation of multidrug-resistant bacteria worldwide. As the phage effect is highly specific, prior susceptibility testing of target bacteria is mandatory. Of note, established standards are lacking. In this research, we adapted the single-disk method for antibiotic susceptibility testing to phage susceptibility testing (PST) in order to provide a standardized, easy-to-handle, reproducible, and reliable PST protocol for application in diagnostic routine laboratories.

Local Treatment of Driveline Infection with Bacteriophages.

Drive line infections (DLI) are common infectious complications after left ventricular assist devices (LVAD) implantation. In case of severe or persistent infections, when conservative management fails, the exchange of the total LVAD may become necessary. We present a case of successful treatment of DL infection with a combination of antibiotics, debridement and local bacteriophage treatment.

Imaging and Clinical Parameters for Distinction between Infected and Non-Infected Fluid Collections in CT: Prospective Study Using Extended Microbiological Approach.

The aim of this investigation was to evaluate predictive CT imaging features and clinical parameters to distinguish infected from sterile fluid collections. Detection of infectious agents by advanced microbiological analysis was used as the reference standard. From April 2018 to October 2019, all patients undergoing CT-guided drainages were prospectively enrolled, if drainage material volume was at least 5 mL. Univariate analysis revealed attenuation (p = 0.001), entrapped gas (p < 0.001), fat stranding (p < 0.001), wall thickness (p < 0.001) and enhancement (p < 0.001) as imaging biomarkers and procalcitonin (p = 0.003) as clinical predictive parameters for infected fluid collections. On multivariate analysis, attenuation > 10 HU (p = 0.038), presence of entrapped gas (p = 0.027) and wall enhancement (p = 0.028) were independent parameters for distinguishing between infected and non-infected fluids. Gas entrapment had high specificity (93%) but low sensitivity (48%), while wall enhancement had high sensitivity (91%) but low specificity (50%). CT attenuation > 10 HU showed intermediate sensitivity (74%) and specificity (70%). Evaluation of the published proposed scoring systems did not improve diagnostic accuracy over independent predictors in our study. In conclusion, this prospective study confirmed that CT attenuation > 10 HU, entrapped gas and wall enhancement are the key imaging features to distinguish infected from sterile fluid collections on CT.

Bacteriophages for the Treatment of Graft Infections in Cardiovascular Medicine.

Bacterial infections of vascular grafts represent a major burden in cardiovascular medicine, which is related to an increase in morbidity and mortality. Different factors that are associated with this medical field such as patient frailty, biofilm formation, or immunosuppression negatively influence antibiotic treatment, inhibiting therapy success. Thus, further treatment strategies are required. Bacteriophage antibacterial properties were discovered 100 years ago, but the focus on antibiotics in Western medicine since the mid-20th century slowed the further development of bacteriophage therapy. Therefore, the experience and knowledge gained until then in bacteriophage mechanisms of action, handling, clinical uses, and limitations were largely lost. However, the parallel emergence of antimicrobial resistance and individualized medicine has provoked a radical reassessment of this approach and cardiovascular surgery is one area in which phages may play an important role to cope with this new scenario. In this context, bacteriophages might be applicable for both prophylactic and therapeutic use, serving as a stand-alone therapy or in combination with antibiotics. From another perspective, standardization of phage application is also required. The ideal surgical bacteriophage application method should be less invasive, enabling highly localized concentrations, and limiting bacteriophage distribution to the infection site during a prolonged time lapse. This review describes the latest reports of phage therapy in cardiovascular surgery and discusses options for their use in implant and vascular graft infections.

How to Handle CT-Guided Abscess Drainages in Microbiological Analyses? Sterile Vials vs. Blood Culture Bottles for Transport and Processing.

The aim of this investigation was to compare microbiological analyses of 100 computed tomography-guided drainages from infectious foci (thoracic, abdominal, musculoskeletal), transported and analyzed by two widely established techniques, that are (i) sterile vials or (ii) inoculated blood culture bottles. The mean number of detected microorganisms from blood culture (aerobic/anaerobic) or conventional method (sterile vial, solid and broth media) per specimen were comparable with 1.29 and 1.41, respectively (p = 1.0). The conventional method showed a trend towards shorter time-to-result (median 28.62 h) in comparison to blood culture incubation (median 43.55 h) (p = 0.0722). Of note, detection of anaerobes (13% vs. 36%) and the number of detected microorganisms in polymicrobial infections (2.76 vs. 3.26) differed significantly with an advantage towards conventional techniques (p = 0.0015; p = 0.035), especially in abdominal aspirations. Despite substantially overlapping results from both techniques, the conventional approach includes some benefits which justify its role as standard approach.

Molecular Epidemiology of Multidrug-Resistant Bacteria Isolated from Libyan and Syrian Patients with War Injuries in Two Bundeswehr Hospitals in Germany.

INTRODUCTION: We assessed the molecular epidemiology of multidrug-resistant bacteria colonizing or infecting war-injured patients from Libya and Syria who were treated at the Bundeswehr hospitals Hamburg and Westerstede, Germany. METHODS: Enterobacteriaceae and Gram-negative rod-shaped nonfermentative bacteria with resistance against third-generation methoxyimino cephalosporins or carbapenems as well as methicillin-resistant Staphylococcus aureus (MRSA) from war-injured patients from Libya and Syria were assessed by molecular typing, i.e., spa typing for MRSA strains and rep-PCR and next-generation sequencing (NGS) for Gram-negative isolates. RESULTS: A total of 66 isolates were assessed - comprising 44 Enterobacteriaceae, 16 nonfermentative rod-shaped bacteria, and 6 MRSA from 22 patients - and 8 strains from an assessment of the patient environment comprising 5 Enterobacteriaceae and 3 nonfermentative rod-shaped bacteria. Although 24 out of 66 patient strains were isolated more than 3 days after hospital admission, molecular typing suggested only 7 likely transmission events in the hospitals. Identified clonal clusters primarily suggested transmission events in the country of origin or during the medical evacuation flights. CONCLUSIONS: Nosocomial transmissions in hospital can be efficiently prevented by hygiene precautions in spite of heavy colonization. Transmission prior to hospital admission like on evacuation flights or in crises zones needs further assessment.

Comparison of the etiological relevance of Staphylococcus haemolyticus and Staphylococcus hominis.

The study was performed to assess potential differences in the etiological relevance of two coagulase-negative staphylococci (CoNS), Staphylococcus haemolyticus and Staphylococcus hominis, in an observational single-center study. Over a 5-year interval, patients in whom there was detected S. haemolyticus or S. hominis of presumed etiological relevance were assessed for the primary endpoint death during hospital stay and the secondary endpoint transfer to an intensive care unit (ICU) after the detection of S. haemolyticus or S. hominis. Patients with S. haemolyticus or S. hominis died in 11.3% (50 out of 444) and 9.5% (60 out of 631) of cases, respectively, and were transferred to ICU after S. haemolyticus and S. hominis detection in 8.7% (19 out of 219) and 11.7% (44 out of 377) of cases, respectively. There was no significance for species-related influence on the primary outcome parameter (P > 0.1), while ICU transfers were more likely for patients with S. hominis detections (P = 0.016). Delayed diagnosis of both CoNS species was associated with an increased probability of death (P = 0.009). The study revealed comparable morbidity caused by S. haemolyticus and S. hominis identified in a clinically relevant context.