Evaluation of a host-protein signature score for differentiating between bacterial and viral infections: real-life evidence from a German tertiary hospital.

PURPOSE: A host-protein signature score, consisting of serum-concentrations of C-reactive protein, tumour necrosis factor-related apoptosis-inducing ligand, and interferon gamma-induced protein 10, was validated for distinguishing between bacterial and viral infections as an antimicrobial stewardship measure for routine clinical practice among adult patients in a German tertiary hospital. METHODS: This single-centre, explorative study prospectively assessed the host-protein signature score, comparing it with serum procalcitonin (PCT) in patients with blood stream infections (BSI) and evaluating its efficacy in patients with viral infections against the standard of care (SOC) to assess the need for antibiotics due to suspected bacterial super/coinfection. Manufacturer-specified threshold scores were used to differentiate viral (< 35) and bacterial (> 65) infections. RESULTS: Ninety-seven patients (BSI [n = 56]; viral infections [n = 41]) were included. The score (cut-off score > 65) tended to detect BSI with higher sensitivity than did PCT (cut-off > 0.5 ng/mL) (87.5% vs. 76.6%). Three patients (5.4%) with BSI had a score < 35. One patient with BSI did not receive antibiotic treatment following SOC prior to positive blood culture results. Among patients with viral infections, 29 (70.7%) had scores > 65, indicating bacterial superinfections. Additionally, 11 patients (26.8%) had scores < 35, indicating no bacterial superinfections. In total, the antibiotic treatment discrepancy in the viral group between the SOC and a host-protein signature score guided approach was 2/41 patients (4.9%). CONCLUSION: The score tended towards a higher sensitivity in detecting BSI than that with PCT. However, its impact on reducing antibiotic use in viral infections was minor compared with that of SOC.

Oral bacteria in infective endocarditis requiring surgery: a retrospective analysis of 134 patients.

OBJECTIVES: It has been reported that bacteria associated with infective endocarditis originate from the oral cavity in 26-45% of cases. However, little is known on the counts and species of periodontal microbiota in infected heart valves. The aim of this study was to identify these aspects of periodontal microbiota in infective endocarditis and to potentially initiate a dental extraction concept for periodontally compromised teeth concerning patients requiring heart valve surgery. MATERIALS AND METHODS: The retrospective study group consisted of tissue samples from infected heart valves of 683 patients who had undergone heart valve surgery. Before patients had undergone cardiac surgery, the following laboratory tests confirmed the occurrence of endocarditis in all patients: blood cultures, echocardiography, electrocardiography, chest X-ray, and electrophoresis of the serum proteins. The specimens were aseptically obtained and deep frozen immediately following surgery. Microbiological diagnosis included proof of germs (dichotomous), species of germs, and source of germs (oral versus other). RESULTS: Microbiota was detected in 134 (31.2%) out of 430 enrolled patients. Oral cavity was supposed to be the source in 10.4% of cases, whereas microbiota of the skin (57.5%) and gastrointestinal tract (GIT, 24.6%) were detected considerably more frequently. Moreover, periodontal bacteria belonged mostly to the Streptococci species and the yellow complex. None of the detected bacteria belonged to the red complex. CONCLUSION: Most frequently, the skin and GIT represented the site of origin of the microbiota. Nevertheless, the oral cavity represented the source of IE in up to 10%. Consequently, it needs to be emphasized that a good level of oral hygiene is strongly recommended in all patients undergoing heart valve surgery in order to reduce the bacterial load in the oral cavity, thereby minimizing the hematogenous spread of oral microbiota. The prerequisites for conservative dental treatment versus radical tooth extraction must always be based on the patient's cooperation, and the clinical intraoral status on a sense of proportion in view of the overall clinical situation due to the underlying cardiac disease. CLINICAL RELEVANCE: The oral cavity is a source of oral microbiota on infected heart valves. Patients requiring heart valve surgery should always undergo a critical evaluation of dental treatment affecting periodontally compromised teeth, favoring a systematic, conservative-leaning recall.

Aspergillus fumigatus cholangitis in a patient with cholangiocarcinoma: case report and review of the literature.

Aspergillus spp. cholangitis is an uncommon presentation of invasive aspergillosis. Only few cases are described in the literature affecting severely immunocompromised patients or patients following biliary surgery. Especially, invasive aspergillosis in non-haematological patients is associated with high mortality rates, caused by atypical presentations, which is associated with a delay in diagnosis and therapy. We report a 72-year-old man with primary diagnosis of cholangiocarcinoma and stent implantation by endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression who developed severe cholangitis with invasive aspergillosis. The patient had no history of prior hospitalisation, no immunosuppressive therapy and no preceding biliary surgery. Furthermore, in this exceptional case of extrapulmonary aspergillosis, there were no signs of pulmonary involvement. From the literature review, only three cases of Aspergillus cholangitis could be identified. Clinical manifestations of invasive aspergillosis can be variable and classical risk factors such as immunosuppression are not mandatorily present. Clinical awareness of these rare cases is of vital importance for initiation of correct therapy.

Fungal brain infection-no longer a death sentence.

The aim of this case series was to provide a modern cohort of patients with cerebral aspergillosis and show the effectiveness of modern treatment concepts. In a 10-year period from January 2009 to January 2019, we identified 10 patients (6 male, 4 female) who received surgery or frameless stereotactic drainage of a cerebral aspergilloma at our center. Patients' and disease characteristics were recorded. The median age was 65 (range 45 to 83). We conducted 133 cranial surgeries in 100 patients due to cerebral brain abscess (BA) during that time, which leads to a percentage of 10% of aspergilloma within BAs in our patient sample. We performed 3.1 surgeries per patient followed by antifungal treatment for 6 months (= median) according to the microbiological findings. Regarding comorbidities, the mean Charlson comorbidity index (CCI) at the time of admission was 5, representing an estimated 10-year survival of 21%. Six (60%) of 10 patients showed conditions of immunosuppression, one suffered endocarditis after replacement of aortic valves. Four patients showed associated frontobasal bone destruction, mycotic aneurysms, or thromboses. The mean duration of hospital stay was 37 days. Mortality was much lower than in literature. Sixty percent of the patients died during the follow-up period. The outcome of the two immunocompetent patients was more favorable. Cerebral aspergillosis is a rare, but still life-threatening, condition, which predominantly occurs in immunosuppressive conditions. Due to radical surgical and antifungal therapy for several months, mortality can be reduced dramatically.

New EUCAST definitions of S, I and R from 2019 - German physicians are largely not aware of the changes.

PURPOSE: On January 1st 2019, the new EUCAST definitions of susceptibility testing categories S, I and R took effect. The changes in the I category have considerable clinical impact because they lead to major changes in the antibiogram, and misinterpretation may result in inappropriate selection and dosing of antibiotics hampering effective treatment of infectious diseases. We assessed if German physicians are aware of the new definitions and their consequences. METHODS: We conducted a nationwide web-based survey to assess the knowledge on the new definitions of S, I and R. The survey was addressed to clinicians across all medical specialties working in Germany and was open from May 9th to July 30th 2019. RESULTS: The answers of 902 participants were included in the analysis. Most participants were employed at hospitals (79.3%) and had already completed specialist training (86.1%). The predominant specialty was internal medicine (50.6%). Of all participants, 45.7% did not know that there was a change in the definitions of S, I and R, and 65.4% did not feel well-informed about the changes. When the participants had to identify true and false statements regarding the new I, substantial knowledge gaps were apparent. Worst results were achieved by those physicians who are not employed in a hospital but work in their own practice. CONCLUSION: Our survey shows that German physicians are insufficiently informed about the new definitions of S, I and R. Further education is strongly needed to ensure optimal treatment of infectious diseases.

Antimicrobial resistance of bacteraemia in the emergency department of a German university hospital (2013-2018): potential carbapenem-sparing empiric treatment options in light of the new EUCAST recommendations.

BACKGROUND: This study investigated predominant microorganisms causing community-onset bacteraemia at the medical emergency department (ED) of a tertiary-care university hospital in Germany from 2013 to 2018 and their antimicrobial susceptibility patterns. METHODS: Antimicrobial resistance patterns in patients with positive blood cultures presenting to an internal medicine ED were retrospectively analysed. RESULTS: Blood cultures were obtained at 5191 of 66,879 ED encounters, with 1013 (19.5%) positive results, and true positive results at 740 encounters (diagnostic yield, 14.3%). The most frequently isolated relevant microorganisms were Enterobacterales (n = 439, 59.3%), Staphylococcus aureus (n = 92, 12.4%), Streptococcus pneumoniae (n = 34, 4.6%), Pseudomonas aeruginosa (n = 32, 4.3%), Streptococcus pyogenes (n = 16, 2.2%), Enterococcus faecalis (n = 18, 2.4%), and Enterococcus faecium (n = 12, 1.6%). Antimicrobial susceptibility testing revealed a high proportion of resistance against ampicillin-sulbactam in Enterobacterales (42.2%). The rate of methicillin-resistant Staphylococcus aureus was low (0.4%). Piperacillin-tazobactam therapy provided coverage for 83.2% of all relevant pathogens using conventional breakpoints. Application of the new European Committee on Antimicrobial Susceptibility Testing (EUCAST) recommendations increased the percentage of susceptible isolates to high-dose piperacillin-tazobactam to 92.8% (p < 0.001). Broad-spectrum carbapenems would only cover an additional 4.8%. The addition of vancomycin or linezolid extended coverage by just 1.7%. CONCLUSIONS: Using an ureidopenicillin-beta-lactamase inhibitor combination at the high dose suggested by the new EUCAST recommendations provided nearly 93% coverage for relevant pathogens in patients with suspected bloodstream infection in our cohort. This might offer a safe option to reduce the empiric use of carbapenems. Our data support the absence of a general need for glycopeptides or oxazolidinones in empiric treatment.

An Open-Labeled Study on Fecal Microbiota Transfer in Irritable Bowel Syndrome Patients Reveals Improvement in Abdominal Pain Associated with the Relative Abundance of Akkermansia Muciniphila.

BACKGROUND/AIMS: The gut microbiota is altered in irritable bowel syndrome (IBS), and microbiota manipulations by diet or antibiotics can reduce its symptoms. As fecal microbiota transfer (FMT) in IBS is still controversial, we investigated the clinical and side effects of FMT in a cohort of IBS patients with recurrent, treatment refractory symptoms, and studied gut microbiota signatures. METHODS: Using an observational, prospective study design, we applied FMTs from one unrelated, healthy donor to 13 IBS patients. Fecal samples of patients and the donor were analyzed by 16S ribosomal RNA amplicon sequencing. RESULTS: On a symptom level, primarily abdominal pain symptoms were reduced after FMT, and no adverse effects were observed. Studying the microbiome, we found an increase in alpha diversity and changes in the composition of the gut microbiota after FMT. Beta diversity changes after FMT were prominent in a subset of 7 patients with microbiota profiles coming very close to the donor. These patients also showed most pronounced visceral pain reduction. The relative abundance of Akkermansia muciniphila was inversely correlated with pain reduction in our cohort. CONCLUSION: Although exploratory in nature and with a pilot character, this study highlights the potential role of microbiota manipulations in IBS and describes a novel association of intestinal Akkermansia and pain modulation.

Clinical characteristics and course of primary brain abscess.

BACKGROUND: Due to improved diagnostic methods, the incidence of brain abscess is still rising. Therefore, clear and evidence-based therapy for the patients who suffer from brain abscesses is necessary. Brain abscesses are potentially life-threatening conditions that possibly lead to permanent injuries even after sufficient healing has taken place. The aims of this study were to analyze the clinical aspects of patients with brain abscesses and thereby to reveal the relevant aspects for the future treatment of the brain lesions. METHODS: We retrospectively identified 47 patients (24 male, 23 female) who had received surgery or undergone the frameless stereotactic drainage of brain abscesses in our center from March 2009 to May 2017. We analyzed the clinical characteristics of the patients, as well as comorbidities and outcomes. RESULTS: The mean age was 58 (range 7 to 86). Focus identification was successful in 28 patients (60%), with the most frequent causes of brain abscesses including the following: sinusitis (25%), dental infections (25%), and mastoiditis (21%). The mean Charlson Comorbidity Index was 1.57. Among the patients, 34% showed immunosuppressive conditions. We performed 1.5 surgeries per patient (53% via craniotomy, 28% biopsies or stereotactic drainage, 19% both procedures), followed by antibiotic treatment for 6.5 weeks (mean). In 30% of patients, no bacteria could be isolated. During the follow-up period (a median of 12 months), 23.4% of the patients died. The mortality rate during the initial hospital stay was 4.3%. CONCLUSION: One third of the patients with brain abscesses showed immunosuppressive conditions, whereas brain abscesses also often occur in patients with good medical conditions. The isolation of the focus of infection is often possible. Surgical procedures showed very good outcomes. Patients over 60 years showed significantly worse clinical outcomes.

Multicentre investigation of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in German hospitals.

Aim of this study was to determine the incidence and molecular epidemiology of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae in Germany. E. coli and K. pneumoniae isolates from clinical samples which were non-susceptible to carbapenems were collected in laboratories serving 20 hospitals throughout Germany from November 2013 to April 2014. The isolates were tested for the presence of carbapenemases by PCR and phenotypic methods and typed by multilocus sequence typing. Risk factors including a previous hospitalization abroad were analysed. Carbapenemases were detected in 24 isolates from 22 patients out of 464,514 admissions. Carbapenemases included OXA-48 (n=14), KPC-2 (n=8) and NDM-1 (n=2). Except for two K. pneumoniae isolates with ST101, all OXA-48 producing strains belonged to different clones. In contrast, half of KPC-2 producing K. pneumoniae were of ST258 and both NDM-1 producing strains were of ST11. Compared to carbapenem-susceptible controls, patients with carbapenemase-producing strains differed by a significantly higher proportion of males, a higher proportion of isolates from wound samples and a more frequent previous stay abroad in univariate analysis. This multicentre study demonstrated an incidence of carbapenemase-producing E. coli and K. pneumoniae from clinical samples in Germany of 0.047 cases per 1000 admissions. OXA-48 was more frequent than KPC-2 and NDM-1 and showed a multiclonal background.

Risk factors for increased antimicrobial resistance: a retrospective analysis of 309 acute cholangitis episodes.

OBJECTIVES: To assess the risk factors for increased antimicrobial resistance among Enterobacteriaceae representing the most common biliary pathogens. METHODS: A retrospective analysis was conducted of 276 patients with acute cholangitis treated at a German tertiary centre between April 1996 and May 2009. The resistance patterns among Enterobacteriaceae isolated from blood/bile cultures were compared and related to age, sex, the genesis of the cholangitis and the type and number of previous interventional procedures [percutaneous transhepatic cholangiography (PTC)/endoscopic retrograde cholangiography (ERC)]. Univariate and multivariate generalized estimation equation models were used to compute ORs with corresponding 95% CIs for the binomial outcomes. RESULTS: According to the univariate analysis, patients undergoing stent therapy had a smaller proportion of Enterobacteriaceae with susceptibility to quinolones (ofloxacin/ciprofloxacin) (184/239 versus 205/221; P < 0.001) and to ceftriaxone (208/239 versus 209/222; P = 0.014). Logistic regression analysis revealed that the odds for acquiring ceftriaxone-resistant Enterobacteriaceae were 4-fold higher than in patients who had not undergone stent therapy (P = 0.039). Furthermore, an increased number of interventional procedures (PTC/ERC) was associated with lower susceptibility. The odds for susceptibility to ampicillin, ampicillin/sulbactam, ceftriaxone, quinolones and co-trimoxazole decreased by 2%, 2%, 4%, 6% and 3%, respectively, per interventional procedure. Age, sex and type of interventional procedure displayed no significant relationship to the development of antimicrobial resistance. CONCLUSIONS: Stent therapy was found to be a risk factor for increased antimicrobial resistance in patients with acute cholangitis, particularly those who had undergone numerous interventional procedures prior to the onset of the cholangitis.

Detection of hidden antibiotic resistance through real-time genomics.

Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the accuracy of genomics-based resistance predictions persist, particularly when compared to traditional, clinically established diagnostic methods. Here, we leverage the case of a multi-drug resistant Klebsiella pneumoniae infection to demonstrate how real-time genomics can enhance the accuracy of antibiotic resistance profiling in complex infection scenarios. Our results show that unlike established diagnostics, nanopore sequencing data analysis can accurately detect low-abundance plasmid-mediated resistance, which often remains undetected by conventional methods. This capability has direct implications for clinical practice, where such "hidden" resistance profiles can critically influence treatment decisions. Consequently, the rapid, in situ application of real-time genomics holds significant promise for improving clinical decision-making and patient outcomes.

Evaluation of Self-Collected Versus Health Care Professional (HCP)-Performed Sampling and the Potential Impact on the Diagnostic Results of Asymptomatic Sexually Transmitted Infections (STIs) in High-Risk Individuals.

Sexually transmitted infections (STIs) are increasing among men who have sex with men (MSM). Screening can improve the detection and outcome of asymptomatic STIs in high-risk populations. Self-sampling may be a resource-optimized strategy; however, its diagnostic reliability compared to testing by healthcare professionals (HCPs) requires further investigation. In this prospective, multicenter cohort study in a high-income country, asymptomatic MSM with a sexual risk profile for STIs were included. Sequential swabs for STI nucleic acid-based diagnosis of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) were performed after randomization, either through self-sampling or HCP-performed sampling. Baseline demographic information, sexual risk behavior, and acceptance and feedback on self-sampling were recorded using an electronic questionnaire. Out of 236 asymptomatic MSM, 47 individuals (19.9%) tested positive for CT and/or NG through self- or HCP-performed sampling. For CT, the sensitivity was 93.3% for both sampling methods, while for NG, it was 90.0% for self-sampling and 95.0% for HCP-performed sampling. Our study demonstrates that self-sampling for asymptomatic STIs has a comparable diagnostic outcome to HCP-performed sampling, with high acceptance in high-risk MSM.

Chlamydophila pneumoniae downregulates MHC-class II expression by two cell type-specific mechanisms.

Chlamydophila pneumoniae was shown to prevent IFN gamma-inducible upregulation of MHC-class II molecules by secreting chlamydial protease-like activity factor (CPAF) into the cytosol of those host cells which support the complete bacterial replication cycle. CPAF acts by degrading upstream stimulatory factor 1 (USF-1). However, in cells like bone marrow-derived macrophages (BMM), which restrict chlamydial replication, we show that CPAF expression is barely detectable and the expression of USF-1 is induced upon infection with C. pneumoniae. Nevertheless, the infection still reduced base line and prevented IFN gamma-inducible MHC-class II expression. Similar results were obtained with heat-inactivated C. pneumoniae. In contrast, reduction of MHC-class II molecules was not observed in MyD88-deficient BMM. Reduction of IFN gamma-inducible MHC-class II expression by C. pneumoniae in BMM was mediated in part by the MAP-kinase p38. Infection of murine embryonic fibroblasts (MEF) with C. pneumoniae, which allow chlamydial replication, induced the expression of CPAF and decreased USF-1 and MHC-class II expression. Treatment of these cells with heat-inactivated C. pneumoniae reduced USF-1 and MHC-class II expression to a much lower extent. In summary, C. pneumoniae downregulates MHC-class II expression by two cell type-specific mechanisms which are either CPAF-independent and MyD88-dependent like in BMM or CPAF-dependent like in MEFs.

Clostridioides (Clostridium) difficile Pacemaker Infection.

Clostridioides difficile is the leading cause of antibiotic-associated nosocomial diarrhea, but extra-intestinal manifestations are rare. We describe the first documented case of bacteraemia with pacemaker pocket and lead infection with the toxigenic C. difficile ribotype 014 with a lack of abdominal symptoms. The patient underwent pacemaker extraction and treatment with intravenous and oral vancomycin. Genotyping and molecular subtyping revealed clonality between pacemaker and intestinal isolates. This case illustrates the risk of intravascular device infections due to C. difficile. Even asymptomatic C. difficile colonization might pose a risk for prosthetic material infection.

Induction of iNOS by Chlamydophila pneumoniae requires MyD88-dependent activation of JNK.

Innate immune cells produce NO via inducible NO synthase (iNOS) in response to certain infections or upon stimulation with cytokines such as IFN-gamma and TNF. NO plays an important role in host defense against intracellular bacteria including Chlamydophila pneumoniae as a result of its microbicidal activity. In MyD88-deficient mice, which succumb to C. pneumoniae infection, iNOS induction is impaired 6 days postinfection, although pulmonary levels of IFN-gamma and TNF are elevated as in wild-type mice at this time-point. Here, we demonstrate that induction of iNOS in macrophages upon C. pneumoniae infection is controlled by MyD88 via two pathways: NF-kappaB activation and phosphorylation of the MAPK JNK, which leads to the nuclear translocation of c-Jun, one of the two components of the AP-1 complex. In addition, phosphorylation of STAT1 and expression of IFN regulatory factor 1 (IRF-1) were delayed in the absence of MyD88 after C. pneumoniae infection but not after IFN-gamma stimulation. Taken together, our data show that for optimal induction of iNOS during C. pneumoniae infection, the concerted action of the MyD88-dependent transcription factors NF-kappaB and AP-1 and of the MyD88-independent transcription factors phosphorylated STAT1 and IRF-1 is required.

Periodontopathogenic bacteria in prosthetic joint infection: a retrospective analysis of 1,673 patients.

OBJECTIVES: Prosthetic joint infection (PJI) is a severe complication for patients and represents an increasing health problem. At present, very limited data are available on the potential role of periodontopathogenic bacteria in PJI. The aim of this analysis was to compare the presence of periodontopathogenic bacteria in surgically treated patients diagnosed with PJI (study) to that of surgically treated infected orthopedic patients without PJI (controls). METHOD AND MATERIALS: Patient records of all orthopedic surgical treatments performed between January 2009 and March 2014 were retrospectively screened. The study group consisted of 996 PJI patients, and the control group of 677 individuals, following surgical treatment of orthopedic infections. During surgery, microbiologic smears were taken and processed by standard procedures for microbiologic diagnosis. RESULTS: Periodontopathogenic bacteria were detected in both groups (4.3% study and 5.6% control group). Nine periodontal pathogenic species from the yellow, violet, and orange complex were identified, without any statistically significant difference between the two groups. CONCLUSIONS: Within their limits, the presented results indicate that periodontal bacteria may contribute similarly to PJI and other surgically treated orthopedic infections. The finding that periodontal pathogenic bacteria were identified in both groups highlights the importance of oral infection control prior to orthopedic surgery.

Value of Diffusion-Weighted Imaging in the Diagnosis of Postoperative Intracranial Infections.

BACKGROUND: Magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is an excellent tool for diagnosing intracranial infection, with limitations in previous neurosurgical intervention. This study aimed to evaluate the accuracy of DWI in the diagnosis of postoperative intracranial infection. METHODS: We retrospectively evaluated all consecutive patients with intracranial infection undergoing a neurosurgical intervention who had preoperative MRI, including DWI. Patients were divided into 2 groups: spontaneous intracranial infection (SI) and postoperative intracranial infection (PI). A control group (CG) of patients who had undergone brain surgery without any signs of subsequent infection was also included. Qualitatively, MRI data were evaluated for the presence of intracranial infection. Sensitivity, specificity, and positive and negative predictive values for PI as opposed to no infection were determined. Quantitatively, areas with diffusion restriction within the surgery/abscess cavity were identified for the 3 groups using semiautomated segmentation. Group differences regarding apparent diffusion coefficient (ADC) ratios were evaluated. Receiver operating characteristic curve analysis was used to identify a point in time beyond which ADC ratios might show reasonable discriminatory power between the PI and CG groups. RESULTS: A total of 78 patients were included (38 in the SI group, 20 in the PI group, 20 in the CG group). Sensitivity, specificity, and positive and negative predictive values in the diagnosis of PI were 80%, 95%, 4%, and 100%, respectively. Median ADC was significantly higher in the PI group compared with the SI group (0.98 vs. 0.69; P < 0.001) but lower compared with the CG group (1.24; P = 0.16). The analysis suggested a possible differentiation of PI and CG after a time interval of approximately 100 days/3 months. CONCLUSIONS: DWI is of limited value in evaluating postoperative brain infection. Our data show a trend toward DWI regaining its validity at approximately 3 months after surgery.

Clinical Characteristics and Course of Postoperative Brain Abscess.

BACKGROUND: Cerebral abscesses after brain surgery are rare but severe and life-threatening complications. We sought to analyze the clinical aspects of those patients and thereby reveal risk factors and the relevant aspects for their future therapy. METHODS: We identified 44 patients (23 male, 21 female) undergoing surgery or frameless stereotactic drainage at our center from March 2009 to January 2018. We conducted 12,101 cranial surgeries during that time. RESULTS: The mean age was 55 years (range 21-82 years). The median duration between brain surgery and the after brain abscess was 1.5 months (range 1-23 months). Previous brain surgeries were emergency procedures in 27% of the cases. The frequency of surgery type was as follows: tumor resection (61%), craniotomy for traumatic brain injury (16%), aneurysm surgery (7%), biopsies (5%), hemicraniectomy after malignant cerebral infarction (5%), and other. We performed 1.3 surgeries per patient followed by antibiotic treatment for 4 weeks (=median) according to the respective germ spectrum. The germ entity was successfully identified in 39 patients (89%). In 18 cases (41%), we identified Staphylococcus aureus. In total, 20.5% of the patients died during the follow-up period. The mortality rate for patients with isolated bacteria was 18% compared with 40% for patients without isolation of specific microorganisms. CONCLUSIONS: Secondary brain abscess is a rare complication and occurs mainly in patients with tumors and patients receiving emergency surgery. In total, 41% of the patients suffered from a S. aureus infection. Isolation of the responsible microorganisms is often possible and leads to improved outcomes.

MyD88-dependent changes in the pulmonary transcriptome after infection with Chlamydia pneumoniae.

Chlamydia pneumoniae, an intracellular bacterium, causes pneumonia in humans and mice. Toll-like receptors and the key adaptor molecule myeloid differentiation factor-88 (MyD88) play a critical role in inducing immunity against this microorganism and are crucial for survival. To explore the influence of MyD88 on induction of immune responses in vivo on a genome-wide level, wildtype (WT) or MyD88(-/-) mice were infected with C. pneumoniae on anesthesia, and the pulmonary transcriptome was analyzed 3 days later by microarrays. We found that the infection caused pulmonary cellular infiltration in WT but not MyD88(-/-) mice. Furthermore, it induced the transcription of 360 genes and repressed 18 genes in WT mice. Of these, 221 genes were not or weakly induced in lungs of MyD88(-/-) mice. This cluster contains primarily genes encoding for chemokines and cytokines like MIP-1alpha, MIP-2, MIP-1gamma, MCP-1, TNF, and KC and other immune effector molecules like immunoresponsive gene-1 and TLR2. Arginase was highly induced after C. pneumoniae infection and was MyD88 dependent. Genes induced by interferons were abundant in a cluster of 102 genes that were only partially MyD88 dependent. Also, lcn2 (lipocalin-2) and timp1 were represented within this cluster. Interestingly, a set of 37 genes including sprr1a was induced more strongly in MyD88(-/-) mice, and most of them are involved in the regulation of cellular replication. In summary, ex vivo analysis of the pulmonary transcriptome on infection with C. pneumoniae demonstrated a major impact of MyD88 on inflammatory responses but not on interferon-type responses and identified MyD88-independent genes involved in cellular replication.

MR and CT Imaging to Optimize CT-Guided Biopsies in Suspected Spondylodiscitis.

BACKGROUND: The diagnostic value of computed tomography (CT)-guided spinal biopsy in patients with suspected spondylodiscitis is reported inconsistently in the literature. Our aim was to evaluate associations between procedural, clinical, and imaging parameters and the diagnostic yield of CT-guided spinal biopsy. METHODS: One hundred and two procedures performed in 87 patients with clinically suggested spondylodiscitis were analyzed retrospectively. Preprocedural magnetic resonance (MR) and CT images were evaluated regarding signal alterations, vertebral destruction, and soft-tissue involvement. The position of the biopsy needle in correlation with MR imaging findings was assessed. Patient characteristics and clinical details were noted. Parameters were compared in patients with positive and negative microbiological and histologic results. RESULTS: Following microbiologic and histologic analysis, infectious spondylodiscitis was diagnosed in 29 and 23 biopsies, respectively. Microbiology results were significantly higher in biopsy specimens with central needle positioning within contrast enhancing tissue in correlation with the MR images (36% vs. 7%; P = 0.005). Biopsy specimens positioned in fluid-equivalent hyperintense discs in T2-weighted sequences yielded significantly lower microbiology results (6% vs. 33%; P = 0.036). Purely lytic endplate destruction and mixed vertebral density as shown by CT increased microbiology results (60% vs. 24%; P = 0.028). Previous antibiotic treatment for any cause did not influence microbiology yields significantly (P = 0.232). CONCLUSIONS: MR imaging is mandatory to determine the optimal biopsy position. No clinical or imaging parameter could rule out a positive biopsy result and thus omit an unnecessary procedure. Biopsy should not be avoided if antibiotic treatment has previously been administered.