Entamoeba histolytica-associated proctitis and ileitis mimicking Crohn's disease-A case report.

We report about a proctitis and ileitis terminalis, leading to the misdiagnosis of Chron's disease, in a male patient who has sex with men. Molecular multiplex analysis identified Entamoeba histolytica as the underlying cause. We provide diagnostic images, clues and pitfalls for diagnosis of E. histolytica associated proctitis.

Neutrophil-Specific Knockdown of ß2 Integrins Impairs Antifungal Effector Functions and Aggravates the Course of Invasive Pulmonal Aspergillosis.

ß2-integrins are heterodimeric surface receptors that are expressed specifically by leukocytes and consist of a variable α (CD11a-d) and a common ß-subunit (CD18). Functional impairment of CD18, which causes leukocyte adhesion deficiency type-1 results in an immunocompromised state characterized by severe infections, such as invasive pulmonary aspergillosis (IPA). The underlying immune defects have largely been attributed to an impaired migratory and phagocytic activity of polymorphonuclear granulocytes (PMN). However, the exact contribution of ß2-integrins for PMN functions in-vivo has not been elucidated yet, since the mouse models available so far display a constitutive CD18 knockout (CD18-/- or CD18hypo). To determine the PMN-specific role of ß2-integrins for innate effector functions and pathogen control, we generated a mouse line with a Ly6G-specific knockdown of the common ß-subunit (CD18Ly6G cKO). We characterized CD18Ly6G cKO mice in-vitro to confirm the PMN-specific knockdown of ß2-integrins. Next, we investigated the clinical course of IPA in A. fumigatus infected CD18Ly6G cKO mice with regard to the fungal burden, pulmonary inflammation and PMN response towards A. fumigatus. Our results revealed that the ß2-integrin knockdown was restricted to PMN and that CD18Ly6G cKO mice showed an aggravated course of IPA. In accordance, we observed a higher fungal burden and lower levels of proinflammatory innate cytokines, such as TNF-α, in lungs of IPA-infected CD18Ly6G cKO mice. Bronchoalveolar lavage revealed higher levels of CXCL1, a stronger PMN-infiltration, but concomitantly elevated apoptosis of PMN in lungs of CD18Ly6G cKO mice. Ex-vivo analysis further unveiled a strong impairment of PMN effector function, as reflected by an attenuated phagocytic activity, and a diminished generation of reactive oxygen species (ROS) and neutrophil-extracellular traps (NET) in CD18-deficient PMN. Overall, our study demonstrates that ß2-integrins are required specifically for PMN effector functions and contribute to the clearance of A. fumigatus by infiltrating PMN, and the establishment of an inflammatory microenvironment in infected lungs.

German Multicenter Study Analyzing Antimicrobial Activity of Ceftazidime-Avibactam of Clinical Meropenem-Resistant Pseudomonas aeruginosa Isolates Using a Commercially Available Broth Microdilution Assay.

Multidrug resistance is an emerging healthcare issue, especially concerning Pseudomonas aeruginosa. In this multicenter study, P. aeruginosa isolates with resistance against meropenem detected by routine methods were collected and tested for carbapenemase production and susceptibility against ceftazidime-avibactam. Meropenem-resistant isolates of P. aeruginosa from various clinical materials were collected at 11 tertiary care hospitals in Germany from 2017−2019. Minimum inhibitory concentrations (MICs) were determined via microdilution plates (MICRONAUT-S) of ceftazidime-avibactam and meropenem at each center. Detection of the presence of carbapenemases was performed by PCR or immunochromatography. For meropenem-resistant isolates (n = 448), the MIC range of ceftazidime-avibactam was 0.25−128 mg/L, MIC90 was 128 mg/L and MIC50 was 16 mg/L. According to EUCAST clinical breakpoints, 213 of all meropenem-resistant P. aeruginosa isolates were categorized as susceptible (47.5%) to ceftazidime-avibactam. Metallo-ß-lactamases (MBL) could be detected in 122 isolates (27.3%). The MIC range of ceftazidime-avibactam in MBL-positive isolates was 4−128 mg/L, MIC90 was >128 mg/L and MIC50 was 32 mg/L. There was strong variation in the prevalence of MBL-positive isolates among centers. Our in vitro results support ceftazidime-avibactam as a treatment option against infections caused by meropenem-resistant, MBL-negative P. aeruginosa.

Characteristics of bacterial infections and prevalence of multidrug-resistant bacteria in hospitalized patients with liver cirrhosis in Germany.

INTRODUCTION AND OBJECTIVES: Bacterial infections are associated with a dismal prognosis in patients with liver cirrhosis. Data on their prevalence and the associated pathogen spectra in Germany are scarce. This study aimed to evaluate the impact of bacterial infections on mortality in hospitalized patients with liver cirrhosis and to analyze the prevalence of multidrug-resistant (MDR) bacteria in a German tertiary care center. PATIENTS AND METHODS: Consecutive, non-electively hospitalized patients with liver cirrhosis were enrolled in this study between 03/2019-06/2021. All patients underwent clinical, laboratory and microbiological testing to detect potential bacterial infections. Patients were followed for 30 days regarding the composite endpoint of death or liver transplantation (mortality). RESULTS: In total, 239 patients were recruited (median MELD 18). Bacterial infection was detected in 81 patients (33.9%) at study inclusion. A total of 70 patients (29.3%) developed a hospital-acquired infection. When comparing community-acquired and hospital-acquired infections, the pathogen pattern shifted from a gram-negative to a more gram-positive spectrum and showed an increase of Staphylococcus spp.. MDR bacteria were detected in seven infected patients (5.8%). 34 patients reached the composite endpoint during 30-days follow-up. In multivariable logistic regression analysis, the presence of infection during hospitalization remained independently associated with higher mortality (OR 2.522, 95% CI 1.044 - 6.091, p = 0.040). CONCLUSIONS: This study demonstrates that bacterial infections are common in hospitalized patients with liver cirrhosis in Germany and are a major determinant of short-term mortality. Our data highlight the importance of regional differences in MDR bacteria and may guide physicians' decision-making regarding calculated antibiotic treatment.

Lethal systemic and brain infection caused by Prototheca zopfii algae in a patient with acute myeloid leukemia.

Systemic protothecosis is an exceptionally rare cause of sepsis with few available therapeutic options. Here, we report on a female patient with newly diagnosed acute myeloid leukemia who died after start of chemotherapy due to a severe septic shock caused by a disseminated systemic infection with Prototheca zopfii including encephalitis.

Clarithromycin impairs tissue-resident memory and Th17 responses to macrolide-resistant Streptococcus pneumoniae infections.

The increasing prevalence of antimicrobial resistance in pathogens is a growing public health concern, with the potential to compromise the success of infectious disease treatments in the future. Particularly, the number of infections by macrolide antibiotics-resistant Streptococcus pneumoniae is increasing. We show here that Clarithromycin impairs both the frequencies and number of interleukin (IL)-17 producing T helper (Th) 17 cells within the lungs of mice infected with a macrolide-resistant S. pneumoniae serotype 15A strain. Subsequently, the tissue-resident memory CD4+ T cell (Trm) response to a consecutive S. pneumoniae infection was impaired. The number of lung resident IL-17+ CD69+ Trm was diminished upon Clarithromycin treatment during reinfection. Mechanistically, Clarithromycin attenuated phosphorylation of the p90-S6-kinase as part of the ERK pathway in Th17 cells. Moreover, a strong increase in the mitochondrial-mediated maximal respiratory capacity was observed, while mitochondrial protein translation and mTOR sisgnaling were unimpaired. Therefore, treatment with macrolide antibiotics may favor the spread of antimicrobial-resistant pathogens not only by applying a selection pressure but also by decreasing the natural T cell immune response. Clinical administration of macrolide antibiotics as standard therapy procedure during initial hospitalization should be reconsidered accordingly and possibly be withheld until microbial resistance is determined. KEY MESSAGES: • Macrolide-resistant S. pneumoniae infection undergoes immunomodulation by Clarithromycin • Clarithromycin treatment hinders Th17 and tissue-resident memory responses • Macrolide antibiotics impair Th17 differentiation in vitro by ERK-pathway inhibition.

[Results of multimodal treatment of hepatic echinococcosis]. / Ergebnisse der multimodalen Therapie der hepatischen Echinokokkose.

BACKGROUND: Echinococcosis is a rare parasitosis in Germany for which the World Health Organization recommends stage-specific treatment strategies. OBJECTIVE: The aim of this study was to analyze the treatment results of patients with hepatic echinococcosis at a German center of excellence for liver surgery. METHODS: Patients who underwent surgery for hepatic echinococcosis between 2009 and 2018 at the University Hospital of Mainz (UMM) were included in this follow-up examination. The investigation included a magnetic resonance imaging (MRI) of the abdomen, documentation of the quality of life (QoL), serological and laboratory parameters. In addition, an online survey was performed among surgeons from Middle Rhein and gastroenterologists from Rhineland-Palatinate. RESULTS: At the UMM 25 surgical interventions were performed for hepatic echinococcosis: 9 for cystic (CE) and 16 for alveolar echinococcosis (AE). The majority of the interventions were major liver resections with additional vascular and biliary procedures. The 90-day mortality was 0%, and 4 grade 3a and 1 grade 4b complications occurred. In contrast to AE 75% of the postoperative serological results of patients with CE remained positive for more than 1 year postoperatively. Most participants in the survey knew the imaging characteristics and treatment options of AE and CE; however, many participants were unaware of the cost of the treatment. CONCLUSION: From the perspective of surgeons, hepatic echinococcosis is a challenge, which however can be curatively treated with a low morbidity despite advanced disease in many patients. Due to the low incidence of the disease, the state of knowledge about AE and CE is limited among physicians.

Aerococcus urinae Mitral Valve Endocarditis-Related Stroke: A Case Report and Literature Review.

Background. Aerococcus urinae is a rare causative pathogen of infective endocarditis that results in a high risk of embolic events. The mortality rate for A urinae endocarditis is high. Old age and underlying urologic conditions are the best-known risk factors for infection. Case Description. We report the clinical course of the disease in a 49-year-old man who presented symptoms of a urinary tract infection. A few days later, transthoracic echocardiography showed a conspicuous mitral valve with myxomatous alterations. Following the detection of a cerebral embolism with associated stroke symptoms, as well as at the beginning of cardiac failure, the emergency indication for the surgical treatment of mitral valve endocarditis was given. On the second day following the operation, circulatory collapse rapidly developed. Following an unsuccessful attempt at cardiopulmonary resuscitation, the patient died. Review of the Literature. From 1991 to 2017, 29 cases of A urinae-induced endocarditis have been described in PubMed and Medline. One or 2 new cases are published annually. We review all reported cases of A urinae endocarditis, with an emphasis on the predisposing factors, course, and outcomes of the disease. Conclusion. A urinae endocarditis is a rare disease primarily affecting elderly men with urinary tract pathologies and comorbidities. The course of the disease is severe, and the outcome is often fatal. A 16S rDNA polymerase chain reaction investigation of bacterial genome provides proof of the presence of A urinae. Because of the high risk of embolism, rapid treatment should focus on the diseased heart valve. Based on existing data and the experience gained from handling cases, treatment with ß-lactam and aminoglycosides is recommended. It is also recommended that operative therapy take place as soon as possible.

Improvement of a Clinical Score for Necrotizing Fasciitis: 'Pain Out of Proportion' and High CRP Levels Aid the Diagnosis.

Necrotizing fasciitis (NF) is a rare mono-/polymicrobial skin infection that spreads to underlying tissues. NF is quickly progressing and leads to life threatening situations. Immediate surgical debridement together with i.v. antibiotic administration is required to avoid fatal outcome. Early diagnosis is often delayed due to underestimation or confusion with cellulitis. We now compared the initial clinical and laboratory presentation of NF and cellulitis in detail to assess if a typical pattern can be identified that aids timely diagnosis of NF and avoidance of fatal outcome. 138 different clinical and laboratory features of 29 NF patients were compared to those of 59 age- and gender matched patients with severe erysipelas requiring a subsequent hospitalization time of ≥10 days. Differences in clinical presentation were not obvious; however, NF patients suffered significantly more often from strong pain. NF patients exhibited dramatically elevated CRP levels (5-fold, p>0.001). The overall laboratory risk indicator for necrotizing fasciitis (LRINEC) score was significantly higher in NF patients as compared to cellulitis. However, a modification of the score (alteration of laboratory parameters, addition of clinical parameters) led to a clear improvement of the score with a higher positive predictive value without losing specificity. In summary, clinical differentiation of NF from cellulitis appears to be hard. 'Pain out of proportion' may be an early sign for NF. An improvement of the LRINEC score emphasizing only relevant laboratory and clinical findings as suggested may aid the early diagnosis of NF in the future leading to improvement of disease outcome by enabling rapid adequate therapy.

Phase I clinical trial of mixed bacterial vaccine (Coley's toxins) in patients with NY-ESO-1 expressing cancers: immunological effects and clinical activity.

PURPOSE: Mixed bacterial vaccine (MBV, Coley's toxins) is a historical, vaguely defined preparation of heat-inactivated Streptococcus pyogenes and Serratia marcescens used as nonspecific immunotherapy in the treatment of cancer. The mechanism of action is suspected to have an immunologic basis, yet it is poorly defined up to now. We developed a new, biochemically well defined and current good manufacturing practice-compliant MBV preparation, which has been investigated in patients with NY-ESO-1 expressing cancers. EXPERIMENTAL DESIGN: Patients received MBV subcutaneously at a starting dose of 250 EU (endotoxin units) twice a week. The MBV dose was escalated in each patient until a body temperature of 38°C to 39.5°C was induced or up to the maximum dose of 547.000 EU. Changes in serum cytokine levels were determined and immune responses to NY-ESO-1 were evaluated. Tumor response was assessed according to RECIST. RESULTS: Twelve patients were enrolled and 11 of them developed fever after the administration of MBV. Ten of 12 patients showed a consistent increase in serum IL-6 levels with the highest levels coinciding with the highest body temperature. A subgroup of patients showed increasing levels of TNF-α, IFN-γ, and IL1-ß. A patient with metastatic bladder cancer showed a partial tumor response strongly correlated with MBV-induced fever and highly elevated levels of several cytokines. CONCLUSIONS: MBV at fever-inducing dose levels can lead to a massive induction of immunoregulatory cytokines that may be involved in inducing tumor regressions. We propose to further explore the role of MBV as a potent immune modulator at higher dose levels and in conjunction with antigen-specific cancer vaccines.

Use of quantitative microbiological analyses to trace origin of contamination of parenteral nutrition solutions.

In the summer of 2010, parenteral nutrition (PN) admixtures were administered to neonates in the Pediatric Department of the University Medical Center Mainz that provoked severe clinical sequelae. Contamination of a dummy infusion with Enterobacter cloacae and Escherichia hermannii was detected on the day of the incident, and the same isolates were subsequently grown from all PN admixtures as well as from the parent amino acid solution from which the admixtures had been prepared. Quantitative microbiological analyses paired with the determination of endotoxin concentrations enabled the conclusion to be reached that the amino acid solution had represented the primary source of contamination, which must have occurred in the distant past and may have derived from passage of the bacteria through a crack in the glass container. The findings have large implications, and the approaches employed should become of value when similar incidents occur again in the future.

Eosinophilic meningitis due to Angiostrongylus cantonensis in Germany.

We report a case of eosinophilic meningitis due to Angiostrongylus cantonensis in a patient who returned from Thailand. The presence of a compatible epidemiologic history and eosinophilia in cerebrospinal fluid (CSF) lead to the diagnosis, which was confirmed by detection of specific antibodies. After treatment with albendazole and corticosteroids he recovered completely.

Is cell salvage safe in liver resection? A pilot study.

STUDY OBJECTIVE: To investigate the quality of cell salvaged (CS) blood in patients undergoing hemihepatectomy (study group) and compare it with CS-blood from aortic surgery (control group). DESIGN: Observational study. SETTING: Operating room in a university hospital. MEASUREMENTS: 6 patients undergoing hemihepatectomy or aortobifemoral bypass with intraoperative blood loss of more than 800 mL. Samples were drawn from the central venous catheter, from the reservoir of a CS recovery system, and from the processed blood in each patient to determine interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF), complement C3a, and the terminal complement complex C5b-9. Microbiological analysis included colony count after cultivation in aerobic and anaerobic medium as well as enrichment culture for 6 days. MAIN RESULTS: In the hemihepatectomy group, levels of IL-6, C3a, and C5b-9 were significantly higher in the reservoir than in samples obtained from the central venous catheter. After the washing procedure, levels of IL-6, C3a, and C5b-9 were lower in the liver resection group than in each patient's own plasma levels. In all patients undergoing aortobifemoral bypass and in 5 patients undergoing hemihepatectomy, blood samples were sterile or showed growth of commensal skin microflora in low numbers (coagulase-negative staphylococci or propionibacteria). In one patient in the liver resection group, we could not exclude contamination with intestinal flora. CONCLUSION: Cell salvaged blood in liver resection seems to be safe for retransfusion with respect to cytokine release and complement activation, but requires further investigation in regard to bacterial contamination.

Thymidine-dependent Staphylococcus aureus small-colony variants: human pathogens that are relevant not only in cases of cystic fibrosis lung disease.

We report the isolation of thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus from unusual infection sites of patients with chronic soft tissue infection, tympanitis, bronchitis, peritonitis, and septicemia. Furthermore, we provide evidence that the essential growth factor for TD-SCVs, i.e., thymidine, and its metabolite dTMP are present in various human specimens.

Actinomycosis of the jaws--histopathological study of 45 patients shows significant involvement in bisphosphonate-associated osteonecrosis and infected osteoradionecrosis.

Actinomycosis of the jaws is a rare disease, which has been recently described in patients with infected osteoradionecrosis (IORN) and bisphosphonate-associated osteonecrosis (BON). We investigated our archive material for Actinomycosis of the jaws with special regard to underlying disease. Out of a total number of 45 patients with Actinomycosis, 43 (93.5%) suffered from BON (58.7%) or IORN (35.6%), while there were only 3 patients (6.7%) without anti-tumor treatment. In all cases, we found direct association of Actinomyces colonies with bone; in the surrounding medullary space, mixed inflammatory infiltrates with variable amounts of osteoclasts were a typical finding. Pseudoepitheliomatous hyperplasia occurred in 60.9% of patients. Cell-rich vessel obliteration was seen in less than 25.9% of BON patients, while hyalinized vessel obliteration was obtained in 37.5% of IORN patients. Additionally performed polymerase chain reaction (PCR) on paraffin-embedded and ethylene diamine tetracetic acid (EDTA)-decalcified tissue specimens confirmed the presence of Actinomyces israelii in seven of seven cases analyzed. We conclude that Actinomycosis of the jaws is a particular complication in patients with BON and/or IORN. Patients with Actinomycosis of the jaws during or after these forms of anti-cancer therapy are suggested to represent a distinct patient cohort with a relevant impairment of their general condition.

Diagnosing Helicobacter pylori in vivo by confocal laser endoscopy.

BACKGROUND & AIMS: Confocal laser endomicroscopy enables subsurface microscopic imaging of living tissue during ongoing endoscopy. This case report describes the in vivo detection of Helicobacter pylori by endomicroscopy. METHODS: Endomicroscopy (Pentax, Tokyo, EC-3870CIFK) was performed by using two different contrast stains: Topical Acriflavine in addition to intravenously applied fluorescein netted the surface and allowed identification of focal accumulation of Helicobacter pylori at the surface and in deeper layer of the gastric epithelium. Biopsies were performed at the antrum and corpus for urease testing and histology. In addition, biopsies were cultured for Helicobacter pylori. Cultured bacteria were re-assessed ex vivo using confocal microscopy with and without acriflavine staining. RESULTS: Helicobacter pylori infection could be detected in a 70-year-old male by endomicroscopy. Accumulated, as well as single bacteria, could be observed and the distinct shape and flagella of Helicobacter pylori could be identified. Helicobacter pylori infection was proved by histology. Furthermore, ex vivo examination of cultures proved the presence of Helicobacter pylori and the active uptake of acriflavine into the bacteria. CONCLUSIONS: Endomicroscopy is a new diagnostic approach, which enables the immediate diagnosis of Helicobacter pylori in vivo during standard video endoscopy.