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.

Treatment Strategies for Filamentous Fungi Keratitis.

INTRODUCTION: This research aims to describe clinical findings, epidemiology and treatment outcomes in patients with filamentous fungi keratitis of a tertiary centre in Germany over a 7-year period and to compare the efficacy of different antifungal treatments and the effect of additive topical steroids. METHODS: This retrospective study included 25 eyes of 23 patients from October 2013 to December 2020 with cultural isolates of filamentous fungi and corresponding keratitis. Best-corrected visual acuity (BCVA), clinical signs, symptoms, risk factors and outcome were extracted from medical records. RESULTS: Improvement of BVCA was noted in 68% of eyes. Mean BCVA of the study population increased from 0.75 logMAR [median 0.40, standard deviation (SD) 0.82, range 0-2.3] to 0.48 logMAR (median 0.10, SD 0.88, range - 0.1 to 3). The most commonly used antifungal topical treatment was a combination of natamycin 5% and voriconazole 2% (44% of eyes), followed by voriconazole 2% in 36% of cases. An antiinflammatory topical steroid was applied in 52%. In 16% of the eyes, penetrating keratoplasty (pKP) was performed. CONCLUSION: Diagnosis of filamentous fungi keratitis is often difficult or delayed. Outcomes can be poor even with intensive treatment because of high resistance to common antifungals. Access to natamycin 5% seems to lead to favourable outcomes in filamentous fungi keratitis.

CD4+CD8αlow T cells in rheumatoid arthritis are clonally expanded and dependent on co-stimulation.

OBJECTIVES: CD4+CD8+ T cells are increased in patients with rheumatoid arthritis (RA). They are not only associated with joint erosions in established disease, but are also present in the pre-clinical stages of RA. This study aims to further investigate their expansion in the context of T cell clonality in patients with RA, as well as their responsiveness to T cell targeted treatment. METHODS: Single-cell-(sc)RNA- and scTCR-sequencing data were used to determine co-receptor expression and T cell receptor sequences to assess clonality of CD4+CD8+ T cells in RA (n=3) patients and healthy controls (n=2). Peripheral CD4+CD8+ T cells and their subpopulations were measured in patients with RA (n=53), PsA (n=52) and healthy donors (n=50) using flow cytometry. In addition, changes in CD4+CD8+ T cell frequency were prospectively followed in RA patients receiving therapy with abatacept for 12 weeks. RESULTS: We observed an increase of CD4+ T cells expressing CD8α in RA patients, both in comparison to PsA patients and to healthy controls. Clonality analysis revealed, that these CD4+CD8αlow T cells are part of large T cell clones, which cluster separately from CD4+CD8- T cell clones in the scRNA-seq gene expression analysis. Treatment with abatacept significantly reduced the frequency of peripheral CD4+CD8αlow T cells, and this was linked to reduction in disease activity. CONCLUSION: In RA, clonal expansion of CD4+ T cell clones culminates in the emergence of peripheral CD4+CD8αlow T cells, which are associated with disease activity and diminished upon abatacept treatment, and which could contribute to disease pathogenesis.

LINAS-Score: prognostic model for mortality assessment in patients with cirrhotic liver and infected ascites.

BACKGROUND AND AIM: Patients with liver cirrhosis often face a grave threat from infected ascites (IA). However, a well-established prognostic model for this complication has not been established in routine clinical practice. Therefore, we aimed to assess mortality risk in patients with liver cirrhosis and IA. METHODS: We conducted a retrospective study across three tertiary hospitals, enrolling 534 adult patients with cirrhotic liver and IA, comprising 465 with spontaneous bacterial peritonitis (SBP), 34 with bacterascites (BA), and 35 with secondary peritonitis (SP). To determine the attributable mortality risk linked to IA, these patients were matched with 122 patients with hydropic decompensated liver cirrhosis but without IA. Clinical, laboratory, and microbiological parameters were assessed for their relation to mortality using univariable analyses and a multivariable random forest model (RFM). Least absolute shrinkage and selection operator (Lasso) regression model was used to establish an easy-to-use mortality prediction score. RESULTS: The in-hospital mortality risk was highest for SP (39.0%), followed by SBP (26.0%) and BA (25.0%). Besides illness severity markers, microbiological parameters, such as Candida spp., were identified as the most significant indicators for mortality. The Lasso model determined 15 parameters with corresponding scores, yielding good discriminatory power (area under the receiver operating characteristics curve = 0.89). Counting from 0 to 83, scores of 20, 40, 60, and 80 corresponded to in-hospital mortalities of 3.3%, 30.8%, 85.2%, and 98.7%, respectively. CONCLUSION: We developed a promising mortality prediction score for IA, highlighting the importance of microbiological parameters in conjunction with illness severity for assessing patient outcomes.

Cryopreserved bone flaps from decompressive craniectomies: a microbiological analysis.

PURPOSE: Surgical site infection (SSI) is a serious complication after cranioplasty. Due to the relatively frequent occurrence of post-cranioplasty SSI, the utility of autologous bone flap swab cultures surrounding cryopreservation as a reliable predictor has been the subject of an ongoing debate. This bicentric study aims to contribute to this topic by conducting an in-depth analysis of bone flaps obtained via decompressive craniectomies. This study had three major aims: assessments of 1) bacterial contamination of bone flaps after decompressive craniotomy, 2) impact of cryoconservation on contamination rates and 3) potential effectiveness of anti-infective treatment to reduce the germ load prior to cranioplasty. METHODS: Cryopreserved bone flaps from two centers were used. Microbiological cultivations of swabs prior to and after cryopreservation were taken and assessed for aerobic and anaerobic growth over a 14-day incubation period. Additionally, in a subset of bone flaps, swab testing was repeated after thorough rinsing with an anti-infectant (octenidine-phenoxyethanol) followed by saline. RESULTS: All 63 bone flaps (patients median age at surgery: 59 years) were obtained via decompressive craniectomies. Swabs done prior to cryopreservation revealed a 54% infection rate with Propionibacterium acnes being the most common microorganism in 65% of those cases. After thorough disinfection of the preserved bone flaps, all but one case showed no bacterial growth in swab testing. Furthermore, no relevant risk factors for bacterial contamination could be identified. CONCLUSION: This retrospective study showed the common presence of bacterial growth in cryopreserved bone flaps before and after freezing. Rinsing with octenidine-phenoxyethanol and saline effectively prevented bacterial growth in a notable percentage of cases, suggesting a potential strategy to reduce contamination. However, persistent bacterial growth in some cases underscores the need for further research to optimize antiseptic measures during autologous cranioplasty.

Cotrimoxazole and targeted antibiotic prophylaxis for transrectal prostate biopsy: a single-center study.

PURPOSE: The recent restriction on the use of fluoroquinolones for prophylaxis by the European Commission has left a gap in clear recommendations for practical antibiotic prophylaxis (PAP) for transrectal prostate biopsy (TRPB). This analysis investigated the viability of cotrimoxazole for PAP in TRPB. METHODS: This analysis included n = 697 patients who underwent TRPB for suspected prostate cancer (PCa). All patients received either empiric PAP with four doses of cotrimoxazole 960 mg or targeted antibiotic prophylaxis in case of a positive rectal or urine screening for multiresistant gram-negatives. Infectious complications after TRPB, microbiological findings, and clinical characteristics were evaluated. A multivariable logistic regression model was calculated to identify variables associated with infectious complications. RESULTS: Of the cohort, 86% (600/697) received PAP with cotrimoxazole, 1% (8/697) received cotrimoxazole plus an additional antibiotic, 4% (28/697) received amoxicillin + clavulanic acid, 4% (28/697) received fluoroquinolones, and 5% (33/697) received a single shot intravenous antibiotic prophylaxis with meropenem or piperacillin + tazobactam due to multiresistant microbiological findings in either pre-interventional urine culture or rectal swab. Infectious complications occurred in 2.6% (18/697) of patients. Fever was noted in 89% (16/18) of cases. Inpatient treatment was given to 67% (12/18) of affected patients, with 38% (7/18) having positive blood cultures, identifying cotrimoxazole-resistant E. coli strains in six out of seven cases. Multivariable logistic regression analysis revealed no clinically significant variables, including PAP with cotrimoxazole, as independent risk factors for an infectious complication. CONCLUSIONS: Using cotrimoxazole as PAP for TRPB in cases without multiresistant gram-negatives in pre-interventional urine cultures or rectal swabs seems feasible and practical.

Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

IMPORTANCE: The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

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.

Galactomannan-Antigen Testing from Non-Directed Bronchial Lavage for Rapid Detection of Invasive Pulmonary Aspergillosis in Critically Ill Patients: A Proof-of-Concept Study.

Invasive pulmonary aspergillosis is associated with high mortality. For diagnosis, galactomannan-antigen in serum and bronchoalveolar lavage fluid is recommended, with higher sensitivity in bronchoalveolar lavage fluid. Because of invasiveness, bronchoalveolar lavage might be withheld due to patients' or technical limitations, leading to a delay in diagnosis while early diagnosis is crucial for patient outcome. To address this problem, we performed an analysis of patient characteristics of intubated patients with invasive pulmonary aspergillosis with comparison of galactomannan-antigen testing between non-directed bronchial lavage (NBL) and bronchoalveolar lavage fluid. A total of 32 intubated ICU patients with suspected invasive pulmonary aspergillosis could be identified. Mycological cultures were positive in 37.5% for A. fumigatus. Galactomannan-antigen in NBL (ODI 4.3 ± 2.4) and bronchoalveolar lavage fluid (ODI 3.6 ± 2.2) showed consistent results (p-value 0.697). Galactomannan-antigen testing for detection of invasive pulmonary aspergillosis using deep tracheal secretion showed comparable results to bronchoalveolar lavage fluid. Because of widespread availability in intubated patients, galactomannan-antigen from NBL can be used as a screening parameter in critical risk groups with high pretest probability for invasive aspergillosis to accelerate diagnosis and initiation of treatment. Bronchoalveolar lavage remains the gold standard for diagnosis of invasive aspergillosis to be completed to confirm diagnosis, but results from NBL remove time sensitivity.

Bacterial content of the human pancreatic duct: An observational study.

Background: Pancreatic fistula/PF is a challenging surgical complication. We could recently show that intestinal bacteria such as Enterobacterales colonize the PF fluid even after a "sterile" operation like distal pancreatectomy/DP. Therefore, we explored the bacterial flora of the human pancreatic duct in a patient collective undergoing pancreatic surgery. Methods: In this observational study, upon transection of the pancreas during surgery, a swab was inserted into the main duct, and the micro-organismal content was correlated with clinical characteristics. Results: Between February 2017 and February 2020, an intraoperative swab from the pancreatic duct was obtained from a total of 54 patients who underwent pancreatico-duodenectomy/PD or DP. The swabs were sterile in 39 cases (72.2%), detected intestinal bacteria in 10 cases (18.5%), and other bacteria in 5 cases (9.3%). There was no correlation of the micro-organismal content of the pancreatic duct swab with bacteria detected in the PF fluid or bile. Preoperative ERCP was associated with a higher frequency of bacterial colonization of the pancreatic duct (33.3% vs. 6.7%, p = 0.005). There was no correlation of the pancreatic duct swabs with postoperative complications. Discussion: The human main pancreatic duct is usually sterile, and its bacterial colonization does not correlate with the occurrence of PF. Therefore, the mechanisms leading to infection of PF warrant in-depth, mechanistic investigation.

A Novel Machine Learning-Based Point-Score Model as a Non-Invasive Decision-Making Tool for Identifying Infected Ascites in Patients with Hydropic Decompensated Liver Cirrhosis: A Retrospective Multicentre Study.

This study is aimed at assessing the distinctive features of patients with infected ascites and liver cirrhosis and developing a scoring system to allow for the accurate identification of patients not requiring abdominocentesis to rule out infected ascites. A total of 700 episodes of patients with decompensated liver cirrhosis undergoing abdominocentesis between 2006 and 2020 were included. Overall, 34 clinical, drug, and laboratory features were evaluated using machine learning to identify key differentiation criteria and integrate them into a point-score model. In total, 11 discriminatory features were selected using a Lasso regression model to establish a point-score model. Considering pre-test probabilities for infected ascites of 10%, 15%, and 25%, the negative and positive predictive values of the point-score model for infected ascites were 98.1%, 97.0%, 94.6% and 14.9%, 21.8%, and 34.5%, respectively. Besides the main model, a simplified model was generated, containing only features that are fast to collect, which revealed similar predictive values. Our point-score model appears to be a promising non-invasive approach to rule out infected ascites in clinical routine with high negative predictive values in patients with hydropic decompensated liver cirrhosis, but further external validation in a prospective study is needed.

Does the Duration of Perioperative Antibiotic Prophylaxis Influence the Incidence of Postoperative Surgical-Site Infections in Implant-Based Breast Reconstruction in Women with Breast Cancer? A Retrospective Study.

BACKGROUND: Perioperative antibiotic prophylaxis is an established concept to reduce the risk of surgical-site infections; however, the optimal treatment duration in prosthetic breast reconstruction is still controversial. This study evaluated a potential association between the perioperative antibiotic prophylaxis duration (≤24 hours versus >24 hours) and incidence of postoperative surgical-site infections in immediate implant-based breast reconstruction in breast cancer patients. METHODS: A descriptive, retrospective analysis of surgical-site infections after immediate implant-based breast reconstruction in breast cancer patients between January of 2011 and December of 2018 was performed. The incidence of postoperative surgical-site infections in patients with more than 24 hours of perioperative antibiotic prophylaxis was compared to patients treated for 24 hours or less. RESULTS: A total of 240 patients who met criteria were included. There were no relevant epidemiologic, clinical, or histopathologic differences between groups. Surgical-site infections as defined by the Centers for Disease Control and Prevention criteria occurred in 25.8 percent. A risk factor-adjusted analysis by a prespecified multiple logistic regression model showed that 24 hours or less of perioperative antibiotic prophylaxis was not inferior to treatment for more than 24 hours. The upper limit of the one-sided 95 percent confidence interval of the risk difference was 9.4 percent (below the prespecified noninferiority margin of 10 percent leading to statistical significance). Risk factors for a surgical-site infection included obesity and postoperative wound complications. CONCLUSIONS: The study found no association between short-course perioperative antibiotic prophylaxis (≤24 hours) and an increased rate of postoperative surgical-site infection. This is of high clinical relevance because short-course treatment can help reduce side effects and the emergence of antimicrobial resistance and prevent surgical-site infections as effectively as a prolonged perioperative antibiotic prophylaxis course. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Practical Assessment of an Interdisciplinary Bacteriophage Delivery Pipeline for Personalized Therapy of Gram-Negative Bacterial Infections.

Despite numerous advances in personalized phage therapy, smooth logistics are challenging, particularly for multidrug-resistant Gram-negative bacterial infections requiring high numbers of specific lytic phages. We conducted this study to pave the way for efficient logistics for critically ill patients by (1) closely examining and improving a current pipeline under realistic conditions, (2) offering guidelines for each step, leading to safe and high-quality phage supplies, and (3) providing a tool to evaluate the pipeline's efficiency. Due to varying stipulations for quality and safety in different countries, we focused the pipeline on all steps up to a required phage product by a cell-free extract system. The first of three study runs included patients with respiratory bacterial infections from four intensive care units, and it revealed a cumulative time of up to 23 days. Ultimately, adjustment of specific set points of the vulnerable components of the pipeline, phage isolation, and titration increased the pipeline's efficiency by 15% and decreased the maximum required time to 13 days. We present a site-independent practical approach to establish and optimize pipelines for personalized phage delivery, the co-organization of pipeline components between different institutions, non-binding guidelines for every step, and an efficiency check for phage laboratories.

Danger signal extracellular calcium initiates differentiation of monocytes into SPP1/osteopontin-producing macrophages.

The danger signal extracellular calcium is pathophysiologically increased in the synovial fluid of patients with rheumatoid arthritis (RA). Calcium activates the NLRP3-inflammasome via the calcium-sensing receptor in monocytes/macrophages primed by lipopolysaccharide, and this effect is mediated by the uptake of calciprotein particles (CPPs) formed out of calcium, phosphate, and fetuin-A. Aim of the study was to unravel the influence of calcium on monocytes when the priming signal is not present. Monocytes were isolated from the blood of healthy controls and RA patients. Macrophages were characterized using scRNA-seq, DNA microarray, and proteomics. Imaging flow cytometry was utilized to study intracellular events. Here we show that extracellular calcium and CPPs lead to the differentiation of monocytes into calcium-macrophages when the priming signal is absent. Additional growth factors are not needed, and differentiation is triggered by calcium-dependent CPP-uptake, lysosomal alkalization due to CPP overload, and TFEB- and STAT3-dependent increased transcription of the lysosomal gene network. Calcium-macrophages have a needle-like shape, are characterized by excessive, constitutive SPP1/osteopontin production and a strong pro-inflammatory cytokine response. Calcium-macrophages differentiated out of RA monocytes show a stronger manifestation of this phenotype, suggesting the differentiation process might lead to the pro-inflammatory macrophage response seen in the RA synovial membrane.

Expansion of CD4+CD8+ double-positive T cells in rheumatoid arthritis patients is associated with erosive disease.

OBJECTIVES: CD4+CD8+ double-positive (DP) T cells are expanded in the peripheral blood of a subset of patients with RA. This study examines the clinical significance of DP T cells in RA. METHODS: In 70 RA patients, DP T cells were measured by flow cytometry. Clinical data were obtained, and hand and feet radiographs were scored according to the Sharp/van der Heijde (SvdH) method. The association between DP T cell frequency and erosive joint destruction was analysed by correlation and multiple logistic regression analysis. RESULTS: Nineteen RA patients (27.1%) displayed increased DP T cell frequencies, which correlated with age (r = 0.288, P =0.016). Expansion of DP T cells was associated with the occurrence of erosions (94,7% vs 43,1%, P <0.001), with a higher SvdH joint damage score (24.5 vs 6, P =0.008) and with more frequent use of biologic or targeted-synthetic DMARDs (68.4% vs 38%, P =0.02). In patients with non-erosive disease, DP T cell frequencies correlated with the joint space narrowing score (n = 28, r = 0.44, P =0.02). Logistic regression revealed DP T cells to be associated with erosive disease (OR 1.90, P <0.05). CONCLUSION: Expansion of DP T cells is associated with joint damage and frequent escalation of therapy, possibly suggesting a contribution to more severe RA.

[Antibiotic prophylaxis for transrectal prostate biopsy : In the context of restricted indications for fluoroquinolones and antibiotic stewardship]. / Antibiotikaprophylaxe bei transrektaler Prostatabiopsie : Im Kontext von Fluorchinolon-Indikationsrücknahme und Antibiotic Stewardship.

BACKGROUND: Transrectal prostate biopsy (TRPB) is the gold standard for prostate cancer diagnosis and among the most common urological interventions. Short-term antibiotic prophylaxis (PAP) is recommended for TRPB. Fluoroquinolone-PAP as standard of care needs to be revaluated due to the restrictions on the use of fluoroquinolone antibiotics by the German Federal Institute for Drugs and Medical Devices. OBJECTIVES: The aim of the study was to analyze clinical practice of PAP for TRPB with focus on infectious complications and potential differences between fluoroquinolone-PAP and cotrimoxazole-PAP. METHODS: We performed a retrospective monocentric study of clinical and microbiological characteristics of patients with TRPB between 3 January 2019 and 28 January 2021. RESULTS: A total of 508 men were included; median age was 68 years. In all, 55.9% of our cohort received cotrimoxazole-PAP and 40.0% fluoroquinolone-PAP. Postinterventional complications occurred in 5.5%, of those 50.0% were infectious complications. Complication rate did not differ between patients with fluoroquinolone-PAP and cotrimoxazole-PAP. Urinary cultures in case of postinterventional complications yielded pathogens with antimicrobial resistance against the used PAP substance indicating selection of resistant bacteria. CONCLUSION: Cotrimoxazole-PAP for TRPB is not associated with an increase of infectious complications compared to fluoroquinolone-PAP. Cultures obtained prior to TRPB to identify antimicrobial resistance facilitate targeted PAP and therefore can reduce complications.

Dexamethasone therapy and rates of secondary pulmonary and bloodstream infections in critically ill COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a pandemic. Bacterial superinfections seem to be associated with higher mortality in COVID-19 patients in intensive care units (ICUs). However, details on the prevalence and species distribution of secondary infections are limited. Moreover, the increasing use of dexamethasone may pose an additional risk of superinfections. METHODS: We performed a single-center retrospective study of the clinical and microbiological characteristics of 154 COVID-19 patients admitted to the ICU between March 2020 and January 2021, focusing on bacterial infections, use of antimicrobial agents and dexamethasone therapy. RESULTS: The median age was 68 years; 67.5% of the patients were men. Critically ill COVID-19 patients were treated with dexamethasone since July 2020 (second wave), which was not common during the first wave of the pandemic. In the dexamethasone group (n=90, 58.4%), respiratory pathogens were detected more frequently, as were multidrugresistant pathogens. The number of patients with polymicrobial detection of respiratory pathogens was significantly increased (p=0.013). The most frequently detected species were Enterobacterales, Staphylococcus aureus, and Aspergillus fumigatus. The rates of bloodstream infections did not differ between the groups. The use of dexamethasone in ICU COVID-19 patients was associated with higher rates of respiratory infectious complications. CONCLUSIONS: Secondary infections are present in a substantial fraction of critically ill COVID-19 patients. Respiratory pathogens were detectable in the majority of COVID-19 ICU patients. The use of dexamethasone poses a potential risk of secondary pulmonary infections. Infectious complications in patients with dexamethasone therapy could be associated with worse outcomes.

Evaluation of a multiplex PCR screening approach to identify community-acquired bacterial co-infections in COVID-19: a multicenter prospective cohort study of the German competence network of community-acquired pneumonia (CAPNETZ).

PURPOSE: Thorough knowledge of the nature and frequency of co-infections is essential to optimize treatment strategies and risk assessment in cases of coronavirus disease 2019 (COVID-19). This study aimed to evaluate the multiplex polymerase chain reaction (PCR) screening approach for community-acquired bacterial pathogens (CABPs) at hospital admission, which could facilitate identification of bacterial co-infections in hospitalized COVID-19 patients. METHODS: Clinical data and biomaterials from 200 hospitalized COVID-19 patients from the observational cohort of the Competence Network for community-acquired pneumonia (CAPNETZ) prospectively recruited between March 17, 2020, and March 12, 2021 in 12 centers in Germany and Switzerland, were included in this study. Nasopharyngeal swab samples were analyzed on hospital admission using multiplex real-time reverse transcription (RT)-PCR for a broad range of CABPs. RESULTS: In total of 200 patients Staphylococcus aureus (27.0%), Haemophilus influenzae (13.5%), Streptococcus pneumoniae (5.5%), Moraxella catarrhalis (2.5%), and Legionella pneumophila (1.5%) were the most frequently detected bacterial pathogens. PCR detection of bacterial pathogens correlated with purulent sputum, and showed no correlation with ICU admission, mortality, and inflammation markers. Although patients who received antimicrobial treatment were more often admitted to the ICU and had a higher mortality rate, PCR pathogen detection was not significantly related to antimicrobial treatment. CONCLUSION: General CABP screening using multiplex PCR with nasopharyngeal swabs may not facilitate prediction or identification of bacterial co-infections in the early phase of COVID-19-related hospitalization. Most patients with positive PCR results appear to be colonized rather than infected at that time, questioning the value of routine antibiotic treatment on admission in COVID-19 patients.

Clinical and microbiological features and outcomes of mucormycosis in critically ill patients.

INTRODUCTION: Mucormycosis is a rare invasive fungal infection with high mortality in patients with severe underlying predisposing factors causing immunosuppression. The exact incidence of mucormycosis and the optimal therapeutic approach is difficult to determine, especially in severe cases, due to the rarity of the disease. The new second-generation triazole isavuconazole provides an alternative treatment option which may represent a potential benefit in severe cases. MATERIALS AND METHODS: A retrospective case series was conducted of patients with a positive laboratory culture for Mucorales and consistent clinical findings who required intensive care treatment. Patient characteristics including demographics, comorbidities, microbiological analysis, specific antifungal therapy and clinical outcome were analysed. RESULTS: Fifteen critically ill patients with Mucorales detected between 2016 and 2019 were included in this study; the crude mortality rate was 100%. At the time of diagnosis of mucormycosis, 80% of subjects had relevant medical immunosuppression and 53.3% of subjects had neutropenia. Manifestation of mucormycosis was pulmonary in 53.3% of subjects, rhino-orbital in 20% of subjects and disseminated in 26.7% of subjects. Notably, 40% of all patients had received antifungal prophylaxis prior to mucormycosis, mainly with posaconazole due to underlying haematological malignancy, thus possibly representing break-through infections. Antifungal therapy for invasive mucormycosis was administered in 80% of subjects for a median duration of 16 days. CONCLUSION: In this retrospective cohort analysis of intensive care patients, the prognosis of mucormycosis was extremely poor. An aggressive strategy for diagnosis and treatment is essential for intensive care patients with mucormycosis. There is a need for further research to determine if combination therapy in higher dosages or prompt surgery is beneficial in severe critically ill patients.