Nyt fra tidsskrifterne

Abstract Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection. …

Abstract We present a rare case of pathology-proven CMV pneumonitis in a patient with HIV infection after presenting with cough and fever. This presentation was complicated by recurrence of symptoms after treatment in the setting of continued uncontrolled HIV infection. This case raised the importance of further discussion regarding best treatment guidelines for CMV pneumonitis for patients with HIV. …

Abstract Background The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country’s epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters’ predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). Methods A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. Results Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P 

Abstract Objective Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj. Methods A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed. Results Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support. Conclusion The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent. …

Abstract Background We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. Methods This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline’s clinical efficacy and safety were performed to control confounding factors. Results For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. Conclusions Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient’s age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM. …

Journal of Medical Virology, Volume 95, Issue 12, December 2023.

American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page e44-e46, December 1, 2023.

Abstract Respiratory syncytial virus (RSV) is the most common pathogen associated with acute lower respiratory tract infections in infants and young children worldwide. RSV commonly presents as bronchiolitis in young children; however, it can sometimes progress to pneumonia, respiratory failure, apnoea and even death. Although mucin1 (MUC1), a type of transmembrane glycoprotein present on airway epithelial surfaces, plays a crucial anti-inflammatory role in airway infections; however, its roles in RSV-associated acute lower respiratory tract infections have rarely been explored. In this study, we first revealed very high MUC1 protein levels in the exacerbation phase in sputum samples from children with RSV bronchiolitis. Because MUC1 is the downstream target of tumour necrosis factor-alpha (TNF-α) in RSV-infected A549 cells, we observed the inhibition of NF-κB activity, main downstream signalling of TNF-α and remarkably reduced levels of MUC1 in RSV-infected and TNF-α treated A549 cells. Furthermore, the cyclic adenosine monophosphate (cAMP) analogue (dbcAMP) downregulated the protein levels of p-IκBα and MUC1 in TNF-α-treated A549 cells. By contrast, a protein kinase A inhibitor (KT5720) up-regulated the levels of those proteins. dbcAMP and KT5720 had the same effects on MUC1 protein levels in RSV-infected A549 cells. In conclusion, we found that the cAMP-PKA-NF-κB pathway may play a role in the regulation of MUC-1 over-expression during RSV infection. …

by Mizan Kindu, Feleke Moges, Degu Ashagrie, Zemene Tigabu, Baye Gelaw Background Intensive care units are units where healthcare-associated infections (HAIs) are common and antimicrobial resistance rates are increasing. Microbial contamination in hospital environment plays an important role in the development of HAIs. Intervention-based improvements in infection prevention and control at national and facility level are critical for the containment of antimicrobial resistance and prevention of HAIs. Objectives This study aimed to determine the distribution of multidrug-resistant and carbapenemase-producing critical gram negative bacteria (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter species) and their antibiotic resistance in intensive care unit environmental surfaces at the University of Gondar and Felege Hiwot Comprehensive Specialized Hospitals. Methods This was multicenter hospital-based cross sectional study. Environmental samples were swabbed from all intensive care units using a normal saline moistened-sterile cotton tip stick. Bacteria culturing and antibiotic susceptibility testing were performed following standard microbiological techniques. Selected meropenem-resistant isolates were phenotypically assessed for carbapenemase production using modified and simplified carbapenem inactivation methods. Results From a total of 384 environmental samples analyzed, 126 (32.8%) showed growth and 162 isolates were identified. K. pneumoniae (79/162, 48.8%) was the commonest isolate followed by Acinetobacter species (51/162, 31.5%), E. coli (19/162, 11.7%) and P. aeruginosa (13/162, 8.0%). Multidrug-resistant and carbapenemase-producing isolates were detected on most hospital environment surface types, especially from the baby bed sets and incubators. The most common multidrug-resistant and principal carbapenemase producer was K. pneumoniae, with rates of 71(89.9%) and 24(85.7%), respectively. Conclusion This study revealed the distribution of multidrug-resistant and carbapenemase-producing critical gram negative bacteria in the environment of intensive care unit. Higher detection rate of multidrug-resistant and carbapenemase-producing K. pneumoniae on most environmental surfaces calls for urgent control action and further attention. …

Abstract We present a rare case of pathology-proven CMV pneumonitis in a patient with HIV infection after presenting with cough and fever. This presentation was complicated by recurrence of symptoms after treatment in the setting of continued uncontrolled HIV infection. This case raised the importance of further discussion regarding best treatment guidelines for CMV pneumonitis for patients with HIV. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background The Omicron variant of SARS-CoV-2, currently the most prevalent strain, has rapidly spread in Jingzhou, China, due to changes in the country’s epidemic prevention policy, resulting in an unprecedented increase in cases. Previous studies reported hematological parameters’ predictive value in COVID-19 severity and prognosis, but their relevance for early diagnosis in patients infected by the Omicron variant, particularly in high-risk pneumonia cases, remains unclear. Our study aimed to evaluate these parameters as early warning indicators for Omicron-infected patients in fever clinics and those with pulmonary infections (PI). Methods A total of 2,021 COVID-19 patients admitted to the fever clinic and infectious disease department of Jingzhou Hospital Affiliated to Yangtze University from November 1, 2022, to December 31, 2022, were retrospectively recruited. Demographic and hematological parameters were obtained from the electronic medical records of eligible patients. These hematological parameters were analyzed by receiver operating characteristic (ROC) curves to determine whether they can be used for early diagnosis of COVID-19 patients in fever clinics and the presence of PI in COVID-19 patients. Results Statistical differences in hematological parameters were observed between COVID-19 patients with fever and PI and control groups (P 

Abstract Objective Droplet digital PCR (ddPCR) is a novel assay to detect pneumocystis jjrovecii (Pj) which has been defined to be more sensitive than qPCR in recent studies. We aimed to explore whether clinical features of pneumocystis pneumonia (PCP) were associated with ddPCR copy numbers of Pj. Methods A total of 48 PCP patients were retrospectively included. Pj detection was implemented by ddPCR assay within 4 h. Bronchoalveolar fluid (BALF) samples were collected from 48 patients with molecular diagnosis as PCP via metagenomic next generation sequencing (mNGS) or quantitative PCR detection. Univariate and multivariate logistic regression were performed to screen out possible indicators for the severity of PCP. The patients were divided into two groups according to ddPCR copy numbers, and their clinical features were further analyzed. Results Pj loading was a pro rata increase with serum (1,3)-beta-D glucan, D-dimmer, neutrophil percentage, procalcitonin and BALF polymorphonuclear leucocyte percentage, while negative correlation with albumin, PaO2/FiO2, BALF cell count, and BALF lymphocyte percentage. D-dimmer and ddPCR copy number of Pj were independent indicators for moderate/severe PCP patients with PaO2/FiO2 lower than 300. We made a ROC analysis of ddPCR copy number of Pj for PaO2/FiO2 index and grouped the patients according to the cut-off value (2.75). The high copy numbers group was characterized by higher level of inflammatory markers. Compared to low copy number group, there was lower level of the total cell count while higher level of polymorphonuclear leucocyte percentage in BALF in the high copy numbers group. Different from patients with high copy numbers, those with high copy numbers had a tendency to develop more severe complications and required advanced respiratory support. Conclusion The scenarios of patients infected with high ddPCR copy numbers of Pj showed more adverse clinical conditions. Pj loading could reflect the severity of PCP to some extent. …

Abstract Background We investigated the associations between the different doses of tigecycline, its efficacy and safety, and the role of tigecycline therapeutic drug monitoring for patients in the intensive care unit. Methods This study was a single-center cohort including patients infected with multidrug-resistant Acinetobacter baumannii (MDR-AB) and multidrug-resistant Klebsiella pneumoniae (MDR-KP) causing pulmonary infections. The steady-state plasma concentration after tigecycline administration was determined by High-Performance Liquid Chromatography (HPLC) in patients admitted to the ICU between October 2020 and December 2021. Multivariate analyses of tigecycline’s clinical efficacy and safety were performed to control confounding factors. Results For this study, we included 45 patients and 45 blood samples to determine steady-state trough concentrations of tigecycline. All patients were divided into the High Dose (HD) and Standard Dose (SD) groups. The median trough concentration of tigecycline was 0.56 μg/mL in the HD group, which was higher than in the SD group (0,21 μg/mL), p = 0.000. There was no significant difference between the two groups of patients in terms of bacterial eradication rate, mortality rate, and clinical efficacy. Multiple regression analysis showed that the ICU days were correlated with mortality OR 1.030(1.005–1.056), p = 0.017. APACHE II was significantly associated with clinical efficacy OR 0.870(0.755–1.002), p = 0.045. The level of fibrinogen decline in the HD group was significantly higher than in the SD group (-3.05 ± 1.67 vs -1.75 ± 1.90), p = 0.038. We identified that age and tigecycline treatment duration influenced fibrinogen decline. Conclusions Tigecycline plasma concentrations are significantly increased when using a high dose. However, the plasma concentration of tigecycline is not correlated with clinical efficacy and adverse reactions. Fibrinogen decline appears to be related to the patient’s age and days of tigecycline. Large sample data are still needed to confirm the clinical guidance significance of tigecycline TDM. …

Despite decades of advances in clinical management protocols and new antibiotics, pneumonia continues to be a leading cause of morbidity and mortality worldwide. The 2019 Global Burden of Disease Study indicated that lower respiratory infections, including pneumonia, were the fourth leading cause of disability-adjusted life-years across all ages.1 People at the extremes of age, specifically children younger than 10 years and older adults (aged ≥75 years), had the highest burden of lower respiratory infections.

The last time that an infectious disease ranked in the top five causes of death in Australia was in 1970 (influenza and pneumonia combined). However, COVID-19, after being successfully kept under control when Australia closed borders between 2020 and 2021, has surged into the top three causes of death in 2022. There were 9859 deaths due to COVID-19 registered in Australia in 2022, and the infection was mentioned as a contributing factor on a further 2782 death certificates. Ischaemic heart disease (19 858 deaths) and dementia, including Alzheimer\'s disease (17 106 deaths), were the only top two causes of death above COVID-19.

Infection and Immunity, Ahead of Print.

Clinical Microbiology Reviews, Ahead of Print.

Ventilator-associated pneumonia (VAP) is a nosocomial pneumonia that occurs in intensive care unit (ICU) patients receiving mechanical ventilation [1]. It is one of the most common healthcare-associated infections (HAIs) with an incidence of 55.3% (95% CI, 0.465-0.657) [2]. VAP may recur more than once, with an overall frequency of 26.8% [3]. As an ICU-acquired infection, VAP comes with a significant financial burden to the health care system due to prolonged ICU length of stay [4]. It is also associated with a high mortality rate (i.e.

Abstract Background The 2017 World Health Organization (WHO) report has listed extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) as critical pathogens for public health and requiring urgently new antibiotics. The aim of this study was to characterize phenotypically and genotypically ESBL-E isolated among clinical samples in Dschang, Cameroon. Methods A cross-sectional study was conducted during a four-month periods from February to May 2022 in the two biggest hospitals of Dschang. Clinical samples were collected and cultured on Eosin Methylene Blue agar. Suspected growing colonies were biochemically identified using the Enterosystem Kit 18R. Antimicrobial susceptibility testing (AST) was done using the Kirby Bauer disc diffusion method and interpretated according to the CA-SFM recommendations. ESBL phenotypes were double screened using CHROMagar™ ESBL and double disk synergy test (DDST). The detection of resistance genes was performed using conventional and multiplex PCR methods. Results were analyzed with SPSS (version 21) and a p-value 

Abstract Purpose Risk scores for community-acquired pneumonia (CAP) are widely used for standardized assessment in immunocompetent patients and to identify patients at risk for severe pneumonia and death. In immunocompromised patients, the prognostic value of pneumonia-specific risk scores seems to be reduced, but evidence is limited. The value of different pneumonia risk scores in kidney transplant recipients (KTR) is not known. Methods Therefore, we retrospectively analyzed 310 first CAP episodes after kidney transplantation in 310 KTR. We assessed clinical outcomes and validated eight different risk scores (CRB-65, CURB-65, DS-CRB-65, qSOFA, SOFA, PSI, IDSA/ATS minor criteria, NEWS-2) for the prognosis of severe pneumonia and in-hospital mortality. Risk scores were assessed up to 48 h after admission, but always before an endpoint occurred. Multiple imputation was performed to handle missing values. Results In total, 16 out of 310 patients (5.2%) died, and 48 (15.5%) developed severe pneumonia. Based on ROC analysis, sequential organ failure assessment (SOFA) and national early warning score 2 (NEWS-2) performed best, predicting severe pneumonia with AUC of 0.823 (0.747–0.880) and 0.784 (0.691–0.855), respectively. Conclusion SOFA and NEWS-2 are best suited to identify KTR at risk for the development of severe CAP. In contrast to immunocompetent patients, CRB-65 should not be used to guide outpatient treatment in KTR, since there is a 7% risk for the development of severe pneumonia even in patients with a score of zero. …

To the Editor A recent JAMA Insights article reviewed indications for Pneumocystis jirovecii pneumonia prophylaxis in immunocompromised adults. The authors commented that patients receiving corticosteroids at doses equivalent to at least 20 mg/d of prednisone for at least 4 weeks who have an additional cause of immunosuppression should receive Pneumocystis pneumonia (PCP) prophylaxis. They also noted there is no consensus for when to initiate PCP prophylaxis among patients with autoimmune disease. Unfortunately, without consensus and with no clear definition of “additional cause of immunosuppression,” confusion may arise regarding the appropriateness of PCP prophylaxis in individual cases. To help decide whether PCP prophylaxis for patients with autoimmune disease is indicated, clinicians can consider the number needed to treat (NNT) to prevent 1 episode of PCP balanced against the number needed to harm (NNH) (ie, occurrence of serious adverse drug reactions resulting from prophylaxis with trimethoprim-sulfamethoxazole). In a systematic review of patients with malignancies, a PCP risk greater than or equal to 6.2% determined the threshold for prophylaxis, likely exceeding the PCP risk among patients with certain autoimmune disorders (eg, the incidence of PCP was calculated to be 0.1% among patients with autoimmune blistering disorders). Among patients with cancer, the NNT was 19 to prevent 1 case of PCP. In a study of patients with rheumatic disease receiving greater than 30 mg/d of prednisone for more than 4 weeks, PCP risk was higher for certain diseases, including microscopic polyangiitis and dermatomyositis, and for initial prednisone doses of greater than 60 mg/d. The NNT for patients receiving a prednisone dose greater than 60 mg/d was 32, whereas the NNT was 215 among patients receiving more than 30 mg/d of prednisone, which is higher than the NNH of 131. In another study of patients with rheumatologic illnesses receiving lower doses of corticosteroids, the NNT for patients receiving greater than or equal to 15 mg/d and less than 30 mg/d of prednisone or the equivalent was 204, exceeding the NNH of 45. However, the NNT fell to 31 for a “high-risk” subgroup, defined as patients with baseline lymphopenia or receiving pulse-dose steroids. It is unknown whether these calculations can be extended to other autoimmune diseases or to patients receiving corticosteroids in combination with newer, targeted biologic therapies, which may be less immunosuppressive. Although steroids are an established risk factor for PCP, there is heterogeneity in the risk conferred by the underlying disease, concomitant immunosuppressive therapies, and patient comorbidities. When available, the NNT and NNH can inform decision-making regarding PCP prophylaxis. When unavailable, careful consideration of the abovementioned factors, in addition to corticosteroid dose and duration, may enable clinicians to balance the risk and benefit of administering PCP prophylaxis.

In Reply Mr Meng and colleagues express concern that testing for H influenzae, S pneumoniae, and M catarrhalis, which are frequently found to colonize the nasal passages of well children, might lead to increased antibiotic use. However, this will occur only if the results from our trial are applied indiscriminately to a population that was not included in our study.

In Reply We agree with Dr Caplan and colleagues that NNTs, where available, can guide decision-making regarding PCP prophylaxis for the heterogeneous group of patients with autoimmune disease, as discussed in their Letter regarding our JAMA Insights article. However, the utility of NNT is limited for several reasons.

ObjectivesPoint-of-care tests (POCTs) for infection offer accurate rapid diagnostics but do not consistently improve antibiotic stewardship (ASP) of suspected ventilator-associated pneumonia. We aimed to measure the effect of a negative PCR-POCT result on intensive care unit (ICU) clinicians’ antibiotic decisions and the additional effects of patient trajectory and cognitive-behavioural factors (clinician intuition, dis/interest in POCT, risk averseness). DesignObservational cohort simulation study. SettingICU. Participants70 ICU consultants/trainees working in UK-based teaching hospitals. MethodsClinicians saw four case vignettes describing patients who had completed a course of antibiotics for respiratory infection. Vignettes comprised clinical and biological data (ie, white cell count, C reactive protein), varied to create four trajectories: clinico-biological improvement (the ‘improvement’ case), clinico-biological worsening (‘worsening’), clinical improvement/biological worsening (‘discordant clin better’), clinical worsening/biological improvement (‘discordant clin worse’). Based on this, clinicians made an initial antibiotics decision (stop/continue) and rated confidence (6-point Likert scale). A PCR-based POCT was then offered, which clinicians could accept or decline. All clinicians (including those who declined) were shown the result, which was negative. Clinicians updated their antibiotics decision and confidence. MeasuresAntibiotics decisions and confidence were compared pre-POCT versus post-POCT, per vignette. ResultsA negative POCT result increased the proportion of stop decisions (54% pre-POCT vs 70% post-POCT, 2(1)=25.82, p

Abstract Purpose Risk scores for community-acquired pneumonia (CAP) are widely used for standardized assessment in immunocompetent patients and to identify patients at risk for severe pneumonia and death. In immunocompromised patients, the prognostic value of pneumonia-specific risk scores seems to be reduced, but evidence is limited. The value of different pneumonia risk scores in kidney transplant recipients (KTR) is not known. Methods Therefore, we retrospectively analyzed 310 first CAP episodes after kidney transplantation in 310 KTR. We assessed clinical outcomes and validated eight different risk scores (CRB-65, CURB-65, DS-CRB-65, qSOFA, SOFA, PSI, IDSA/ATS minor criteria, NEWS-2) for the prognosis of severe pneumonia and in-hospital mortality. Risk scores were assessed up to 48 h after admission, but always before an endpoint occurred. Multiple imputation was performed to handle missing values. Results In total, 16 out of 310 patients (5.2%) died, and 48 (15.5%) developed severe pneumonia. Based on ROC analysis, sequential organ failure assessment (SOFA) and national early warning score 2 (NEWS-2) performed best, predicting severe pneumonia with AUC of 0.823 (0.747–0.880) and 0.784 (0.691–0.855), respectively. Conclusion SOFA and NEWS-2 are best suited to identify KTR at risk for the development of severe CAP. In contrast to immunocompetent patients, CRB-65 should not be used to guide outpatient treatment in KTR, since there is a 7% risk for the development of severe pneumonia even in patients with a score of zero. …

Abstract Purpose Cladophialophora bantiana is a wonted melanized fungus causing brain abscess. In past many cases were reported from Asia, particularly from India. Of late, there is a rise in cases in places besides Asia and hence a review of the cases is warranted. Methods We present a case of fatal cerebral phaeohyphomycosis caused by C. bantiana and conduct a systematic review of culture confirmed brain abscess due to C. bantiana reported between 2015 and 2022. Results Of the 39 cases found, majority (68%) were immunocompromised. The various clinical presentations were headache (53%), hemiparesis (34%), visual disturbance (25%), altered sensorium (18%), aphasia/dysarthria (12%) and seizures (9%). Isolated lesion was observed in 18 (60%) patients. In the sequence of occurrence, the lesions were in frontal (30%), temporal (27%) and parietal (20%) region. There were five cases with coinfections such as concurrent detection of Nocardia pneumonia in two cases, toxoplasma DNA in brain abscess, coexisting pulmonary Cryptococcus neoformans infection and coexisting Candida in a case of brain abscess in one case each. Surgical intervention was performed in 84% cases. Antifungal therapy included voriconazole (80%), liposomal amphotericin B (76%), 5-fluorocytosine (30%), posaconazole (10%), and amphotericin B deoxycholate (6%). The overall mortality was 50% with lower mortality (42%) in regions outside Asia compared to Asia (63.6%) though not statistically significant. Conclusions C. bantiana brain abscess is an emerging infection worldwide. Next generation sequencing is an upcoming promising diagnostic test. Early complete excision of the lesion with effective antifungals may improve the outcome. …

Abstract Purpose Clinical and direct medical cost data on RSV-related hospitalizations are relevant for public health decision-making. We analyzed nationwide data on RSV-coded hospitalizations from Germany in different age and risk groups. Methods Assessment of RSV-coded hospitalizations (ICD-10-GM RSV code J12.1/J20.5/J21.0 as primary discharge diagnosis) from 01/2010 to 12/2019, using remote data retrieval from the Hospital Statistics Database of the German Federal Statistical Office. Results Overall, 130,084 RSV-coded hospitalizations (123,091 children  59 years) were reported (median age 

Infection and Immunity, Ahead of Print.

Abstract Purpose Cladophialophora bantiana is a wonted melanized fungus causing brain abscess. In past many cases were reported from Asia, particularly from India. Of late, there is a rise in cases in places besides Asia and hence a review of the cases is warranted. Methods We present a case of fatal cerebral phaeohyphomycosis caused by C. bantiana and conduct a systematic review of culture confirmed brain abscess due to C. bantiana reported between 2015 and 2022. Results Of the 39 cases found, majority (68%) were immunocompromised. The various clinical presentations were headache (53%), hemiparesis (34%), visual disturbance (25%), altered sensorium (18%), aphasia/dysarthria (12%) and seizures (9%). Isolated lesion was observed in 18 (60%) patients. In the sequence of occurrence, the lesions were in frontal (30%), temporal (27%) and parietal (20%) region. There were five cases with coinfections such as concurrent detection of Nocardia pneumonia in two cases, toxoplasma DNA in brain abscess, coexisting pulmonary Cryptococcus neoformans infection and coexisting Candida in a case of brain abscess in one case each. Surgical intervention was performed in 84% cases. Antifungal therapy included voriconazole (80%), liposomal amphotericin B (76%), 5-fluorocytosine (30%), posaconazole (10%), and amphotericin B deoxycholate (6%). The overall mortality was 50% with lower mortality (42%) in regions outside Asia compared to Asia (63.6%) though not statistically significant. Conclusions C. bantiana brain abscess is an emerging infection worldwide. Next generation sequencing is an upcoming promising diagnostic test. Early complete excision of the lesion with effective antifungals may improve the outcome. …

OBJECTIVES: Diagnosis of pneumonia is challenging in critically ill, intubated patients due to limited diagnostic modalities. Endotracheal aspirate (EA) cultures are standard of care in many ICUs; however, frequent EA contamination leads to unnecessary antibiotic use. Nonbronchoscopic bronchoalveolar lavage (NBBL) obtains sterile, alveolar cultures, avoiding contamination. However, paired NBBL and EA sampling in the setting of a lack of gold standard for airway culture is a novel approach to improve culture accuracy and limit antibiotic use in the critically ill patients. DESIGN: We designed a pilot study to test respiratory culture accuracy between EA and NBBL. Adult, intubated patients with suspected pneumonia received concurrent EA and NBBL cultures by registered respiratory therapists. Respiratory culture microbiology, cell counts, and antibiotic prescribing practices were examined. SETTING: We performed a prospective pilot study at the Cleveland Clinic Main Campus Medical ICU in Cleveland, Ohio for 22 months from May 2021 through March 2023. PATIENTS OR SUBJECTS: Three hundred forty mechanically ventilated patients with suspected pneumonia were screened. Two hundred fifty-seven patients were excluded for severe hypoxia (Fio2 ≥ 80% or positive end-expiratory pressure ≥ 12 cm H2O), coagulopathy, platelets less than 50,000, hemodynamic instability as determined by the treating team, and COVID-19 infection to prevent aerosolization of the virus. INTERVENTIONS: All 83 eligible patients were enrolled and underwent concurrent EA and NBBL. MEASUREMENTS AND MAIN RESULTS: More EA cultures (42.17%) were positive than concurrent NBBL cultures (26.51%, p = 0.049), indicating EA contamination. The odds of EA contamination increased by eight-fold 24 hours after intubation. EA was also more likely to be contaminated with oral flora when compared with NBBL cultures. There was a trend toward decreased antibiotic use in patients with positive EA cultures if paired with a negative NBBL culture. Alveolar immune cell populations were recovered from NBBL samples, indicating successful alveolar sampling. There were no major complications from NBBL. CONCLUSIONS: NBBL is more accurate than EA for respiratory cultures in critically ill, intubated patients. NBBL provides a safe and effective technique to sample the alveolar space for both clinical and research purposes.

Abstract Purpose Clinical and direct medical cost data on RSV-related hospitalizations are relevant for public health decision-making. We analyzed nationwide data on RSV-coded hospitalizations from Germany in different age and risk groups. Methods Assessment of RSV-coded hospitalizations (ICD-10-GM RSV code J12.1/J20.5/J21.0 as primary discharge diagnosis) from 01/2010 to 12/2019, using remote data retrieval from the Hospital Statistics Database of the German Federal Statistical Office. Results Overall, 130,084 RSV-coded hospitalizations (123,091 children  59 years) were reported (median age 

Cefiderocol, a new siderophore cephalosporin, is among the few agents active against carbapenem-resistant Enterobacterales producing metallo-β-lactamases (CRE-MBL) [1]. Emergence of high-level resistance among CRE-MBL has been reported following cefiderocol exposure, mediated by alterations of siderophore receptors involved in cefiderocol uptake [2-4]. However, similar mutants were shown to be affected by fitness defect which might impair their ability to disseminate in absence of selective pressure [2].