Despite the rising global CPE rates, carbapenem resistance among clinical Escherichia coli and Klebsiella pneumoniae isolates has remained minimal in some countries like Finland (0.0% of blood cultures in 2023) [1,2]. However, recent reports from many low-prevalence countries indicate rising CPE numbers [3-5] and even some local spread without recent travel abroad [2-5]. Likewise, in our clinical practice in Finland, we observed an increase in CPE rates, prompting us to investigate the sources and epidemiology, and to identify symptomatic infections.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background The co-occurrence of Lemierre’s syndrome, primarily triggered by Fusobacterium necrophorum following oropharyngeal infection, with diabetic ketoacidosis (DKA) in diabetes mellitus (DM) patients, underscores a rare but life-threatening clinical scenario. Lemierre’s syndrome induced DKA is extremely rare, with only one case report in adult and no case yet reported in elderly. Case Presentation We reported a case of a 69-year-old female who presented with DKA triggered by deep neck space infection (DNSI), leading to rapid clinical deterioration within 6 h that necessitated high flow nasal cannula (HFNC) and antibiotic administration. Laboratory findings included leukocytosis, elevated serum C-reactive protein, hyperglycemia, ketonemia, and severe metabolic acidosis. Culture of the fluid from a neck mass puncture drainage and blood were positive for Klebsiella pneumoniae. The patient was further complicated by thrombosis of the left internal jugular vein with extension to the sigmoid and a neck abscess surrounding the carotid artery sheath, consistent with Lemierre’s syndrome. This condition was managed aggressively with fluid resuscitation, insulin therapy, surgical drainage, antibiotics, and anticoagulation led to a significant improvement in her condition. Following a 13-day hospitalization, there was significant clinical improvement, culminating in the patient’s discharge. Conclusions The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of DKA and Lemierre’s syndrome among clinicians. Early recognition and treatment are crucial to prevent mortality in such complex cases. …

ObjectivesDiagnosis and assessment of chronic obstructive pulmonary disease (COPD) rely extensively on spirometry, which necessitates patient cooperation. The clinical value of impulse oscillometry (IOS) as a non-volitional method in patients with COPD remains uncertain. DesignThis retrospective observational study was conducted using patient data from between January 2014 and December 2015. SettingFive public hospitals in China: West China Hospital, Nuclear Industry 416 Hospital, Suining Central Hospital, Affiliated Hospital, Medical College of Chengdu University and 363 Hospital. ParticipantsThe study included 6307 participants aged>40 years, comprising 2109 COPD patients and 4198 general non-COPD individuals, according to the Global Initiative for Obstructive Lung Disease (GOLD) spirometry standard. Participants with lung cancer, pulmonary tuberculosis, pneumonia or those who underwent lung resection were excluded from the study. Outcome measures and analysisDemographic data, spirometry results and IOS results were collected. Spearman’s correlation analysis was used to examine the correlation between the IOS and spirometry parameters. Receiver operating characteristic curve analysis was used to evaluate the IOS performance in COPD diagnosis and severity staging. ResultsPatients with COPD exhibited significant increases in Z5, R5, R20, R5–R20, Fres and Rp, but a decrease in X5 compared with non-COPD subjects (p

OBJECTIVES: We aimed to summarize the most significant and impactful publications describing the pharmacotherapeutic care of critically ill patients in 2023. DATA SOURCES: PubMed/MEDLINE and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials and prospective studies of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2023, and December 31, 2023, were eligible for inclusion in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included. An a priori defined three-round modified Delphi process was employed to achieve consensus on the most impactful publications based on the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update returned a total of 1202 articles, of which 1164 were excluded. The remaining 38 articles underwent a three-round modified Delphi process. In each round, articles were independently scored based on overall contribution to scientific knowledge and novelty to the literature. Included articles are summarized and their impact discussed. Article topics included hydrocortisone for severe community-acquired pneumonia, inhaled amikacin for prevention of ventilator-associated pneumonia, methylene blue for septic shock, restrictive vs. liberal fluid management for sepsis-induced hypotension, andexanet alfa for major bleeding associated with factor Xa inhibitors, and early administration of four-factor prothrombin complex concentrate in patients with trauma at risk for massive transfusion. CONCLUSIONS: This review provides a summary and perspective on the potential impact of the most relevant articles in 2023 describing advances in the pharmacotherapeutic care of critically ill patients.

Abstract Cefiderocol is a new siderophore-beta-lactam antibiotic used for the treatment of severe multidrug-resistant infections like sepsis, hospital-acquired and ventilator-associated pneumonia in adults, but there are only single reports on its use in the neonatal population. We describe the successful cefiderocol treatment of a newborn with pneumogenic sepsis due to Stenotrophomonas maltophilia. …

Abstract We report a case of disseminated cryptococcosis, an uncommon fungal infection predominantly affecting the lungs and central nervous system, with the rare involvement of adrenal cryptococcosis, compounded by meningitis and pneumonia. The patient, previously diagnosed with primary myelofibrosis and undergoing oral Ruxolitinib treatment, exhibited immunosuppression. Imaging via chest and abdominal CT scans revealed inflammation in the right lung’s middle lobe, splenomegaly, a splenic lesion, and a left adrenal mass, initially prompting considerations of pheochromocytoma. However, unilateral adrenalectomy and subsequent pathological examination disclosed extensive infiltration by inflammatory and multinucleate giant cells, with Periodic acid-Schiff (PAS) staining confirming the diagnosis. The identification of adrenal cryptococcosis was further supported by positive adrenal pus culture and significantly elevated capsular antigens in both serum and cerebrospinal fluid, at titers of 1:2560. Following a month of oral antifungal treatment, marked reductions in capsular antigen levels were noted, to 1:640 and 1:160 in serum and cerebrospinal fluid, respectively. The patient was discharged on a regimen of oral amphotericin B, flucytosine, and fluconazole, with regular outpatient follow-ups showing no signs of recurrence or dissemination. …

Abstract Cefiderocol is a new siderophore-beta-lactam antibiotic used for the treatment of severe multidrug-resistant infections like sepsis, hospital-acquired and ventilator-associated pneumonia in adults, but there are only single reports on its use in the neonatal population. We describe the successful cefiderocol treatment of a newborn with pneumogenic sepsis due to Stenotrophomonas maltophilia. …

Abstract Background This study aims to investigate the frequency of cas1 and cas3 and CRISPR1,2,3 genes in Klebsiella pneumoniae isolates, as well as their connection with antibiotic resistance. Materials and methods 106 K. pneumoniae isolates were identified by biochemical assays and PCR. The susceptibility to antibiotics was determined by Kirby–Bauer disk diffusion method. Screening of ESBLs was undertaken by using double disk diffusion and standard disk diffusion methods. The E-test and mCIM techniques was used to confirm the disc diffusion-based carbapenem resistance profiles. CRISPR-Cas system genes were identified using PCR. Results ESBL production was found in 19% of isolates. Carbapenemase production was found in 46% of the isolates. Furthermore, the bacteria were classified as multidrug (76%), extensively drug-resistant (4%), or pan-drug-resistant (2%). When CRISPR/Cas systems were present, antibiotic resistance was lower; conversely, when they were absent, resistance was higher. Conclusions If the CRISPR/Cas modules aren’t present, the bacteria can still acquire foreign DNA, including antibiotic resistance genes. K. pneumoniae isolates with a CRISPR-Cas system were less likely to carry antibiotic-resistance genes than those lacking this defense system. …

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), led to a global pandemic from 2020. In Thailand, five waves of outbreaks were recorded, with the fourth and fifth waves driven by the Delta and Omicron variants, resulting in over 20,000 new confirmed cases daily at their peaks. Methods This cross-sectional study investigated the associations between clinical symptoms, vaccination status, antibody responses, and post-COVID-19 sequelae in COVID-19 patients. Plasma samples and clinical data were collected from participants admitted to hospitals in Thailand between July 2021 and August 2022, with follow-ups conducted for one year. The study included 110 participants infected with either the Delta (n = 46) or Omicron (n = 64) variants. Virus genotypes were confirmed by RT-PCR of nasal swab RNA and partial nucleotide sequencing of the S gene. IgG and IgA antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 Delta and Omicron variants were measured in plasma samples using ELISA. Results Pneumonia was found to be associated with Delta variant infections, while sore throat, congestion or runny nose, and headache were linked to Omicron infections. Vaccination with fewer than two doses and diabetes mellitus were significantly associated with higher disease severity. Specific IgG and IgA antibodies against the RBD of the Delta variant generally rose by day 14 and were maintained for up to two months, whereas the pattern of antibody response to the Omicron variant was less clear. Antibody risings were found to be positively associated with pneumonia, certain underlying conditions (obesity, hypertension, dyslipidemia, and diabetes mellitus), and age ≥ 60 years. Delta variant infections were associated with forgetfulness, hair loss, and headache during the 1-year post-infection period. Females were more likely to experience hair loss, forgetfulness, and joint pain, while older age was associated with joint pain. Conclusions This study enhances our understanding of SARS-CoV-2 infections in Thais, particularly concerning the Delta and Omicron variants. The findings can inform public health planning and response strategies for future outbreaks of SARS-CoV-2 or other emerging viral diseases. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

by Miriana d’Alessandro, Paolo Cameli, Caroline V. Cotton, Janine A. Lamb, Laura Bergantini, Sara Gangi, Sarah Sugden, Lisa G. Spencer, Bruno Frediani, Robert P. New, Hector Chinoy, Elena Bargagli, Edoardo Conticini Background Interstitial lung disease (ILD) may complicate the course of systemic autoimmune rheumatic disease (SARD) and diagnostic biomarkers are needed. Krebs von den Lungen-6 (KL-6), ferritin (FER) and interleukin 6 (IL-6) have been involved in the ILD development. Our study aimed to compare KL-6, FER, IL-6 and soluble mesothelin-related peptide (SMRP) concentrations in a cohort of idiopathic and SARD-ILD. Methods 3169 patients were enrolled in the “UK Biomarkers in Interstitial Lung Disease (UK-BILD) Study”. We selected patients affected by SARD-ILD and idiopathic ILD (usual interstitial pneumonia-idiopathic pulmonary fibrosis and fibrotic non-specific interstitial pneumonia). Serum marker concentrations were measured through chemiluminescent assays (Fujirebio Europe, Ghent, Belgium). Results 1013 patients were selected for the study: 520 (51.3%) had idiopathic ILD and 493 (48.7%) SARD-ILD. Idiopathic ILD patients displayed higher KL-6 values than SARD-ILD (p = 0.0002). FER and SMRP, though within normal ranges, were significantly higher in idiopathic ILD (p…

Abstract Background The severity of infectious disease outcomes is dependent on the virulence factors of the pathogen and the host immune response. CARD8 is a major regulator of the innate immune proinflammatory response and has been suggested to modulate the host response to common inflammatory diseases. In the present study, the C10X genetic polymorphism in the CARD8 gene was investigated in relation to bacterial meningitis. Methods A total of 400 clinically suspected meningitis patients hospitalized at the University of Gondar Hospital were enrolled in the study. Cerebrospinal fluid (CSF) and blood samples were collected for laboratory investigations. The collected CSF was cultured, and all the results obtained from the culture were confirmed using direct RT‒PCR. Genotyping of whole-blood samples was performed using a TaqMan assay. The results were compared with apparently healthy controls and with PCR-negative meningitis suspected patients. Results Of the included patients, 57% were men and the most common clinical signs and symptoms were fever (81%), headache (80%), neck stiffness (76%), nausea (68%), and vomiting (67%). Microbiology culture identified 7 patients with bacterial meningitis caused by Neisseria meningitidis (n = 4) and Streptococcus pneumoniae (n = 3). The RT-PCR revealed 39 positive samples for N. meningitidis (n = 10) and S. pneumoniae (n = 29). A total of 332 whole-blood samples were genotyped with the following results: 151 (45.5%) C10X heterozygotes, 59 (17.7%) C10X homozygotes and 122 (36.7%) wild genotypes. The polymorphic gene carriers among laboratory confirmed, clinically diagnosed meningitis and healthy controls were 23(46%), 246(40%), and 1526(39%), respectively with OR = 1.27 (0.7–2.3) and OR = 1.34 (0.76–2.4). The presence of the C10X polymorphism in the CARD8 gene was more prevalent in suspected meningitis patients than in healthy controls (OR 1.2; 1.00-1.5). Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease. The presence of viable or active bacterial infection was found to be associated with the presence of heterozygous C10X carriers. Conclusions A greater proportion of C10X in the CARD8 gene in confirmed bacterial meningitis patients and clinically diagnosed meningitis patients than in healthy controls. Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease than heterozygote gene carriers and healthy controls. …

Abstract Background Omadacycline is a new generation of tetracycline antibiotics, and its clinical application is increasing. We report the first case of acute pancreatitis possibly induced by omadacycline. Case presentation The patient was admitted to the emergency intensive care unit due to community-acquired pneumonia. The initial treatment consisted of meropenem combined with levofloxacin, and the regimen was subsequently switched to omadacycline combined with cefoperazone/sulbactam due to sputum culture showing carbapenem-resistant Acinetobacter baumannii. Seven days after the administration of omadacycline, abdominal tenderness occurred, and CT scan revealed an enlarged gallbladder with exudation from the pancreatic head. The patient was diagnosed with acute pancreatitis and improved after dis-continuing omadacycline. Conclusions Omadacycline, like other tetracycline antibiotics, may cause pancreatitis. Combination medications can be an important factor in this adverse reaction. …

American Journal of Respiratory and Critical Care Medicine, Volume 210, Issue 7, Page 919-930, October 1, 2024.

Abstract Background The severity of infectious disease outcomes is dependent on the virulence factors of the pathogen and the host immune response. CARD8 is a major regulator of the innate immune proinflammatory response and has been suggested to modulate the host response to common inflammatory diseases. In the present study, the C10X genetic polymorphism in the CARD8 gene was investigated in relation to bacterial meningitis. Methods A total of 400 clinically suspected meningitis patients hospitalized at the University of Gondar Hospital were enrolled in the study. Cerebrospinal fluid (CSF) and blood samples were collected for laboratory investigations. The collected CSF was cultured, and all the results obtained from the culture were confirmed using direct RT‒PCR. Genotyping of whole-blood samples was performed using a TaqMan assay. The results were compared with apparently healthy controls and with PCR-negative meningitis suspected patients. Results Of the included patients, 57% were men and the most common clinical signs and symptoms were fever (81%), headache (80%), neck stiffness (76%), nausea (68%), and vomiting (67%). Microbiology culture identified 7 patients with bacterial meningitis caused by Neisseria meningitidis (n = 4) and Streptococcus pneumoniae (n = 3). The RT-PCR revealed 39 positive samples for N. meningitidis (n = 10) and S. pneumoniae (n = 29). A total of 332 whole-blood samples were genotyped with the following results: 151 (45.5%) C10X heterozygotes, 59 (17.7%) C10X homozygotes and 122 (36.7%) wild genotypes. The polymorphic gene carriers among laboratory confirmed, clinically diagnosed meningitis and healthy controls were 23(46%), 246(40%), and 1526(39%), respectively with OR = 1.27 (0.7–2.3) and OR = 1.34 (0.76–2.4). The presence of the C10X polymorphism in the CARD8 gene was more prevalent in suspected meningitis patients than in healthy controls (OR 1.2; 1.00-1.5). Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease. The presence of viable or active bacterial infection was found to be associated with the presence of heterozygous C10X carriers. Conclusions A greater proportion of C10X in the CARD8 gene in confirmed bacterial meningitis patients and clinically diagnosed meningitis patients than in healthy controls. Homozygote C10X polymorphic gene carriers were more susceptible to infectious disease than heterozygote gene carriers and healthy controls. …

Concerns regarding “a cluster of pneumonia cases of unknown origin” in Wuhan, China, were globally disseminated in December, 2019. By Jan 25, 2020, Public Health England (now the UK Health Security Agency) had warned the UK Government that person-to-person transmission of the new pathogen (the ‘Wuhan coronavirus’, later named SARS-CoV-2) had been identified outside of China and that the first case had been confirmed in Europe. In the few months that followed, SARS-CoV-2 and the resulting disease, COVID-19, spread across the globe, causing an estimated 22 million excess deaths by the end of the pandemic; a global mortality level not experienced with a respiratory pathogen since the H1N1 influenza pandemic in 1918–20.

Abstract Background Omadacycline is a new generation of tetracycline antibiotics, and its clinical application is increasing. We report the first case of acute pancreatitis possibly induced by omadacycline. Case presentation The patient was admitted to the emergency intensive care unit due to community-acquired pneumonia. The initial treatment consisted of meropenem combined with levofloxacin, and the regimen was subsequently switched to omadacycline combined with cefoperazone/sulbactam due to sputum culture showing carbapenem-resistant Acinetobacter baumannii. Seven days after the administration of omadacycline, abdominal tenderness occurred, and CT scan revealed an enlarged gallbladder with exudation from the pancreatic head. The patient was diagnosed with acute pancreatitis and improved after dis-continuing omadacycline. Conclusions Omadacycline, like other tetracycline antibiotics, may cause pancreatitis. Combination medications can be an important factor in this adverse reaction. …

Abstract Introduction Nephrotic syndrome (NS) is a common chronic kidney disease that is often accompanied by a state of immunodeficiency. Immunosuppression increases the risk of infections, with Pneumocystis jirovecii and Nocardia brasiliensis being two opportunistic pathogens that can cause severe infections in patients with compromised immune function. This study presents a case of a middle-aged male patient with NS concurrently infected with Pneumocystis jirovecii and Nocardia brasiliensis. It aims to synthesize the pertinent diagnostic approaches and treatment experiences. Notably, there have been no reported cases of NS occurring simultaneously with both Pneumocystis jirovecii pneumonia and Nocardia pneumonia. Case presentation A 58-year-old male farmer presented to the hospital with a one-week history of persistent fever, cough, and sputum production. His maximum body temperature was recorded at 39 °C, and he produced yellow viscous sputum. This patient had a one-year history of NS, managed with long-term oral corticosteroid and cyclophosphamide therapy. Admission chest computed tomography displayed interstitial changes in both lungs. After failing to detect any pathogens through routine etiological tests, we successfully identified Nocardia brasiliensis, Pneumocystis jirovecii, and Lodderomyces elongisporus using bronchoscopy-guided sputum samples through metagenomic next-generation sequencing (mNGS) technology. Subsequently, we initiated a combined treatment regimen for the patient using trimethoprim-sulfamethoxazole, meropenem, and moxifloxacin, which yielded remarkable therapeutic outcomes. Conclusion The adoption and promotion of mNGS technologies have significantly resolved the difficulty in early pathogen detection, guiding clinicians from empirical to genomic diagnosis, achieving prevention before treatment, and thereby enhancing patient survival rates. …

by Monica Dwi Hartanti, Novaria Sari Dewi Panjaitan, Sunarno Sunarno, Nathalia Ningrum, Armedy Ronny Hasugian, Rita Marleta Dewi, Sarwo Handayani, Masri Sembiring Maha, Firda Fairuza, Meiriani Sari, Dita Setiati, Christina Safira Whinie Lestari Bordetella pertussis infection is a highly contagious respiratory disease that can cause complications such as pneumonia and death. A total of 62,646 cases of pertussis worldwide were reported by WHO in 2022. This study aimed to obtain the pertussis seroprevalence and sociodemographic data in children aged 1–14 years and its association factors in the community based on Riskesdas 2013 and 2018. Bivariate and multivariate analysis was carried out on data from 12,753 children aged 1–14 years collected from Riskesdas 2013 and 2018 in Indonesia. Pertussis serology data was obtained based on the results of the ELISA examination which was categorized as seropositive if anti-pertussis toxin IgG ≥ 100 IU/mL or anti-pertussis IgG > 11 NTU. Pertussis seropositive indicated recent pertussis infection if no pertussis vaccine was received within the last twelve months. Pertussis seroprevalence was found at 9.8% and 33.4% in Riskesdas 2013 and 2018 respectively. While 10.1% of children aged 5–14 years were found pertussis seropositive by excluding the possible effect of vaccination in the last twelve months in Riskesdas 2013. The most important associated factor in seropositive pertussis at ages 1–4 years and 5–14 years was a history of pneumonia in the last month (OR = 2.709, 95%CI: 2.592–2.831 in Riskesdas 2013 and OR = 2.421, 95%CI: 2.299–2.550 in Riskesdas 2018). In the adjusted analysis for respondents’ characteristics, low maternal education was the predictive factor that most influenced pertussis seropositivity, especially in the 2013 Riskesdas (APOR = 2.983, 95%CI: 2.670–3.333). In conclusion, the results of this study showed that the seroprevalence of pertussis was high, especially in children aged 5–14 years, so that pertussis vaccine booster administration could be considered. Because the most influencing factor towards pertussis seropositive was low maternal education, the groups of children with low-educated mothers should be targets for strengthening complete vaccination coverage and disease control.

by Igor Loncaric, Michael P. Szostak, Adriana Cabal-Rosel, Olivia M. Grünzweil, Alina Riegelnegg, Dusan Misic, Elke Müller, Andrea T. Feßler, Sascha D. Braun, Stefan Schwarz, Stefan Monecke, Ralf Ehricht, Werner Ruppitsch, Joachim Spergser, Ashli Lewis, Peter H. Bloom, Miguel D. Saggese In the present study, the presence of the Enterobacterales, Staphylococcus spp., Mammaliicoccus spp., and Enterococcus spp. in cloacal samples of nestling ospreys (Pandion haliaetus), a fish-eating specialist, from Mono Lake, California, USA was examined by a multiphasic approach, including antimicrobial and biocide susceptibility testing, genotyping, and whole genome sequencing of selected isolates. The most commonly detected species was Escherichia coli, followed by Mammaliicoccus sciuri, Staphylococcus delphini, Enterococcus faecalis, Enterococcus faecium, Hafnia alvei, Klebsiella pneumoniae, Citrobacter braakii and single isolates of Edwardsiella tarda, Edwardsiella albertii, Klebsiella aerogenes, Plesiomonas shigelloides and Staphylococcus pseudintermedius. Multi-drug resistance (MDR) was observed in two E. coli isolates and in an Enterococcus faecium isolate. The MDR blaCTX-M-55-positive E. coli belonged to the pandemic clone ST58. The results of the present study suggest that nestling ospreys are exposed to MDR bacteria, possibly through the ingestion of contaminated fish. Ospreys may be good biosentinels for the presence of these microorganisms and antibiotic resistance in the local environment and the risk for other wildlife, livestock and humans.

A 57-year-old woman with a 12-h history of fever and severe pain in her back, pelvis, and thighs attended our hospital. 24 h earlier, the patient had the first dose of inotuzumab ozogamicin at 0·8 mg/m2 intravenously for primary refractory B-cell acute lymphoblastic leukaemia. 2 months earlier, she had presented with pneumonia and was found to have anaemia, thrombocytopenia, and circulating B-lymphoblasts in her peripheral blood. Bone marrow biopsy confirmed a diagnosis of Philadelphia chromosome-negative B-lymphoblastic leukaemia with low hypodiploidy; she had been treated according to a modified Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol—excluding pegaspargase.

Abstract Background Serum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. Methods This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden’s index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. Results Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG’s area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer’s 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p 

Abstract Background Ventilator-associated pneumonia (VAP) is a challenging nosocomial problem in low- and middle-income countries (LMICs) that face barriers to healthcare delivery and resource availability. This study aimed to examine the incidence and predictors of VAP in Egypt as an example of an LMIC while considering death as a competing event. Methods The study included patients aged ≥ 18 years who underwent mechanical ventilation (MV) in an intensive care unit (ICU) at a tertiary care, university hospital in Egypt between May 2020 and January 2023. We excluded patients who died or were transferred from the ICU within 48 h of admission. We determined the VAP incidence based on clinical suspicion, radiological findings, and positive lower respiratory tract microbiological cultures. The multivariate Fine-Gray subdistribution hazard model was used to examine the predictors of VAP while considering death as a competing event. Results Overall, 315 patients were included in this analysis. Sixty-two patients (19.7%) developed VAP (17.1 per 1000 ventilator days). The Fine-Gray subdistribution hazard model, after adjustment for potential confounders, revealed that emergency surgery (subdistribution hazard ratio [SHR]: 2.11, 95% confidence interval [CI]: 1.25–3.56), reintubation (SHR: 3.74, 95% CI: 2.23–6.28), blood transfusion (SHR: 2.23, 95% CI: 1.32–3.75), and increased duration of MV (SHR: 1.04, 95% CI: 1.03–1.06) were independent risk factors for VAP development. However, the new use of corticosteroids was not associated with VAP development (SHR: 0.94, 95% CI: 0.56–1.57). Klebsiella pneumoniae was the most common causative microorganism, followed by Pseudomonas aeruginosa. Conclusion The incidence of VAP in Egypt was high, even in the ICU at a university hospital. Emergency surgery, reintubation, blood transfusion, and increased duration of MV were independently associated with VAP. Robust antimicrobial stewardship and infection control strategies are urgently needed in Egypt. …

Proceedings of the National Academy of Sciences, Volume 121, Issue 39, September 2024.

ObjectivesTo analyse annual trends of the under-five mortality rate (U5MR) and main cause-specific U5MR in China from 1996 to 2020 and to assess the potential correlation of the healthcare system and health expenditure with the U5MR in China. DesignA retrospective observational study using national data from 1996 to 2020. Joinpoint regression was employed to model U5MR trends and Pearson correlation analysis was conducted to examine the relationship between healthcare system factors, health expenditure and U5MR. SettingNationwide study covering both rural and urban populations across China over a 25-year period. ResultsThe U5MR in China experienced a three-stage decline from 1996 to 2020 with an average annual percentage rate change (AAPC) of –7.27 (p

by Buthenia A. Hasoon, Dahlia M. A. Hasan, Kareem H. Jawad, Saaud S. Shakaer, Ghassan M. Sulaiman, Nehia N. Hussein, Hamdoon A. Mohammed, Mosleh M. Abomughaid, Thotakura Ramesh The increasing prevalence of multi-drug resistance in pathogenic bacteria has rendered antibiotics ineffective, necessitating the exploration of alternative antibacterial approaches. Consequently, research efforts have shifted towards developing new antibiotics and improving the efficacy of existing ones. In the present study, novel core shell graphene oxide@platinum nanoparticles (GRO@Pt-NPs) and their unchanging form have been synthesized using the two-step pulsed laser ablation in liquid (PLAL) technique. The first step involved using the graphene target to create graphene nanoparticles (GRO-NPs), followed by the ablation of GRO-NPs inside platinum nanoparticles (Pt-NPs). To characterize the nanoparticles, various methods were employed, including UV-VIS, transmission electron microscopy (TEM), energy dispersive X-ray (EDX), mapping tests, and X-ray diffraction (XRD). The anti-bacterial and anti-biofilm properties of the nanoparticles were investigated. TEM data confirm the creation of GRO@Pt-NPs. The average particle size was 11 nm for GRO-NPs, 14 nm for Pt-NPs, and 26 nm for GRO@Pt-NPs. The results demonstrate that the created GRO@Pt-NPs have strong antibacterial properties. This pattern is mostly produced through the accumulation of GRO@Pt-NPs on the bacterial surface of Klebsiella pneumoniae (K. pneumoniae) and Enterococcus faecium (E. faecium). The inhibition zones against K. pneumoniae and E. faecium when GRO-NPs were used alone were found to be 11.80 mm and 11.50 mm, respectively. For Pt-NPs, the inhibition zones of E. faecium and K. pneumoniae were 20.50 mm and 16.50 mm, respectively. The utilization of GRO@Pt-NPs resulted in a significant increase in these values, with inhibitory rates of 25.50 mm for E. faecium and 20.45 mm for K. pneumoniae. The antibacterial results were more potent in the core–shell structure than the GRO-NPs alone or Pt-NPs alone. The current work uses, for the first time, a fast and effective technique to synthesize the GRO@Pt-NPs by PLAL method, and the preparation has high clinical potential for prospective use as an antibacterial agent.

by Ploy Pattanakitsakul, Chanya Pongpatipat, Chavachol Setthaudom, Mongkol Kunakorn, Thiantip Sahakijpicharn, Anannit Visudtibhan, Nopporn Apiwattanakul, Surapat Assawawiroonhakarn, Uthen Pandee, Chonnamet Techasaensiri, Sophida Boonsathorn, Sujittra Chaisavaneeyakorn Globally, cases of children’s coronavirus disease 2019 (COVID-19) have been reported since the pandemic started. Most children have an asymptomatic or mild infection. Therefore, the incidence rate of COVID-19 in children might have been underestimated. This study aimed to determine (1) the seroprevalence (and seroconversion rates) of COVID-19, including associated risk factors, in pediatric patients visiting hospitals; and (2) the immunological responses to COVID-19. This was a prospective, cross-sectional study. Patients aged 0–18 years who visited the hospital from September 2020 to February 2022 were included. Demographic, clinical, and laboratory data were reviewed. A total of 1,443 pediatric patients were enrolled. Of these, 323 (22.6%) had a history of COVID-19. In the pre-Delta period, the seroprevalence increased from 4.1% to 70.6% in all included patients and from 0.5% to 10% in patients without a known history of COVID-19 compared with the Delta-Omicron period. The seroconversion rate was 6.8% (19 per 100 person-years) in pediatric patients with COVID-19. Risk factors for COVID-19 seropositivity were respiratory symptoms, being in an outpatient department setting, and infection during the Delta-Omicron period. Exposure to household members with confirmed COVID-19 was a risk factor for seropositivity and seroconversion. Infection during the Delta-Omicron period and testing conducted >2 weeks after the onset of symptoms was associated with spike immunoglobulin (Ig) M and spike and nucleocapsid IgG, respectively. High nucleocapsid IgG levels were associated with pneumonia in pediatric patients with COVID-19. Pediatric patients exposed to household members with COVID-19 and respiratory symptoms should be tested for COVID-19. Nucleocapsid IgG can be used as a surrogate marker to identify patients who may have experienced pneumonia from COVID-19 and as a screening tool for the COVID-19 outbreak, regardless of COVID-19 vaccination status.

Earlier in 2024, the World Health Organization (WHO) issued a request for information after several countries reported an increase in isolates identified as carbapenem-resistant hypervirulent Klebsiella pneumonia (hvKp). Now WHO has issued a warning after 16 of 43 responding countries reported the presence of hvKp, 12 of which also reported carbapenem resistance.

About 57% of US veterans hospitalized and treated for pneumonia had a discrepancy in their pneumonia diagnosis between intake and discharge, according to a cohort study published in the Annals of Internal Medicine.

Abstract Purpose Infective endocarditis caused by non-HACEK gram-negative bacilli (GNB-IE) is rare but associated with significant morbidity and case fatality. Evidence on optimal treatment and management is limited. We aimed to describe the characteristics and management of GNB-IE patients, investigating factors associated with disease acquisition and unfavorable outcomes. Methods We conducted a retrospective descriptive single-center study (tertiary care and referral hospital) between 2015 and 2021, including adult patients with definite GNB-IE. We reviewed demographic, clinical and microbiological data, focusing on predisposing factors, clinical outcomes and 1-year mortality. Results Of 1093 patients with probable or definite IE, 19 patients (median age 69 years) had definite GNB-IE, with an increasing incidence throughout the study period. Median age-adjusted Charlson Comorbidity Index score was 4 points. Prosthetic valve IE (PVIE) was present in 7/19 (37%) patients. Nosocomial acquisition occurred in 8/19 (42%) patients. Escherichia coli and Klebsiella pneumoniae were the most common pathogens. Beta-lactam (BL) based combination therapy was applied in 12/19 (63%) patients (58% BL + fluoroquinolone, 42% BL + aminoglycoside). Cardiac surgery was required in 8/19 (42%) patients (PVIE 71%, native valve IE 25%), primarily for embolism prevention and heart failure. Complications occurred in 14/19 (74%) patients. The in-hospital mortality rate was 21% (4/19); the one-year mortality rate was 44% (7/16). One-year mortality did not significantly differ between patients who underwent cardiac surgery and patients managed with anti-infective treatment alone (p = 0.633). Conclusions GNB-IE affects elderly patients with high comorbidity levels and recent health-care exposure. GNB-IE was associated with high complication rates and high mortality. …

Abstract Purpose Infective endocarditis caused by non-HACEK gram-negative bacilli (GNB-IE) is rare but associated with significant morbidity and case fatality. Evidence on optimal treatment and management is limited. We aimed to describe the characteristics and management of GNB-IE patients, investigating factors associated with disease acquisition and unfavorable outcomes. Methods We conducted a retrospective descriptive single-center study (tertiary care and referral hospital) between 2015 and 2021, including adult patients with definite GNB-IE. We reviewed demographic, clinical and microbiological data, focusing on predisposing factors, clinical outcomes and 1-year mortality. Results Of 1093 patients with probable or definite IE, 19 patients (median age 69 years) had definite GNB-IE, with an increasing incidence throughout the study period. Median age-adjusted Charlson Comorbidity Index score was 4 points. Prosthetic valve IE (PVIE) was present in 7/19 (37%) patients. Nosocomial acquisition occurred in 8/19 (42%) patients. Escherichia coli and Klebsiella pneumoniae were the most common pathogens. Beta-lactam (BL) based combination therapy was applied in 12/19 (63%) patients (58% BL + fluoroquinolone, 42% BL + aminoglycoside). Cardiac surgery was required in 8/19 (42%) patients (PVIE 71%, native valve IE 25%), primarily for embolism prevention and heart failure. Complications occurred in 14/19 (74%) patients. The in-hospital mortality rate was 21% (4/19); the one-year mortality rate was 44% (7/16). One-year mortality did not significantly differ between patients who underwent cardiac surgery and patients managed with anti-infective treatment alone (p = 0.633). Conclusions GNB-IE affects elderly patients with high comorbidity levels and recent health-care exposure. GNB-IE was associated with high complication rates and high mortality. …

Abstract Background Serum (1,3)-β-D-glucan (BDG) detection for diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-human immunodeficiency virus (HIV) immunocompromised patients lacks intensive care unit (ICU)-specific data. We aimed to assess its performance and determine the optimal cutoff for PJP in ICU population. Methods This retrospective study included critically ill non-HIV immunocompromised patients admitted to a medical ICU with suspected pneumonia, undergoing simultaneous microbiological testing for P. jirovecii on lower respiratory tract specimens and serum BDG. Confounders affecting BDG positivity were explored by multivariable logistic regression. Optimal cut-offs were derived from Youden’s index for the entire cohort and subgroups stratified by confounders. Diagnostic performance of serum BDG was estimated at different cutoffs. Results Of 400 patients included, 42% were diagnosed with PJP and 58.3% had positive serum BDG. Serum BDG’s area under the receiver operating characteristic curve was 0.90 (0.87–0.93). At manufacturer’s 150 pg/ml cut-off, serum BDG had high sensitivity and negative predictive value (94%), but low specificity and positive predictive value (67%). Confounders associated with a positive serum BDG in PJP diagnosis included IVIG infusion within 3 days (odds ratio [OR] 9.24; 95% confidence interval [CI] 4.09–20.88, p 

Abstract Background Ventilator-associated pneumonia (VAP) is a challenging nosocomial problem in low- and middle-income countries (LMICs) that face barriers to healthcare delivery and resource availability. This study aimed to examine the incidence and predictors of VAP in Egypt as an example of an LMIC while considering death as a competing event. Methods The study included patients aged ≥ 18 years who underwent mechanical ventilation (MV) in an intensive care unit (ICU) at a tertiary care, university hospital in Egypt between May 2020 and January 2023. We excluded patients who died or were transferred from the ICU within 48 h of admission. We determined the VAP incidence based on clinical suspicion, radiological findings, and positive lower respiratory tract microbiological cultures. The multivariate Fine-Gray subdistribution hazard model was used to examine the predictors of VAP while considering death as a competing event. Results Overall, 315 patients were included in this analysis. Sixty-two patients (19.7%) developed VAP (17.1 per 1000 ventilator days). The Fine-Gray subdistribution hazard model, after adjustment for potential confounders, revealed that emergency surgery (subdistribution hazard ratio [SHR]: 2.11, 95% confidence interval [CI]: 1.25–3.56), reintubation (SHR: 3.74, 95% CI: 2.23–6.28), blood transfusion (SHR: 2.23, 95% CI: 1.32–3.75), and increased duration of MV (SHR: 1.04, 95% CI: 1.03–1.06) were independent risk factors for VAP development. However, the new use of corticosteroids was not associated with VAP development (SHR: 0.94, 95% CI: 0.56–1.57). Klebsiella pneumoniae was the most common causative microorganism, followed by Pseudomonas aeruginosa. Conclusion The incidence of VAP in Egypt was high, even in the ICU at a university hospital. Emergency surgery, reintubation, blood transfusion, and increased duration of MV were independently associated with VAP. Robust antimicrobial stewardship and infection control strategies are urgently needed in Egypt. …

Abstract Purpose The prevalence of biliary tract diseases, which are common gastrointestinal disorders, is steadily rising. If it progresses to sepsis or septic shock, it can endanger the patient\'s life. Therefore, it is crucial to promptly diagnose bacterial infection in individuals suffering from biliary diseases and comprehend the risk factors associated with infection. The objective of this study was to examine the types of bacteria present in the bile of patients with biliary tract diseases, assess any alterations in their susceptibility to antimicrobial agents, and identify the risk factors contributing to the development of infection in these patients. Patients and methods From June 2019 to November 2022, 317 patients of biliary tract diseases with positive bile culture were included in this hospital-based descriptive analysis. The hospital\'s computerized medical records were used to collect data on demographic information (including gender, age, and occupation), laboratory, and clinical findings, physical examination results, comorbidities, basic diseases, treatment history, complications, and in-hospital outcomes. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) principles. Results Of the 317 patients with positive biliary tract diseases, 247 had benign diseases and 70 had malignant diseases. Patients with benign disease experienced a higher prevalence of statistically significant symptoms such as abdominal pain (81.4% vs. 57.1%, P = 0.000), nausea (31.2% vs. 14.3%, P = 0.005), vomiting (30.0% vs. 12.9%, P = 0.004), and chills (10.9% vs. 2.9%, P = 0.039), while jaundice (12.6% vs. 37.1%, P = 0.000) was more common in patients with malignant disease. At the species level, Escherichia coli (105; 40.5%), Klebsiella pneumoniae (41; 15.8%), and Pseudomonas aeruginosa (30; 11.6%) were the most commonly found Gram-negative bacterial strains in biliary tract infection. Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa were most susceptible to tigecycline, ertapenem and ceftazidime/avibactam, respectively. Conclusion Gram-negative bacteria are the most commonly isolated biliary bacteria. Clinical doctors should pay attention to patients with malignant diseases with low hemoglobin, high total bilirubin and high alkaline phosphatase. Carbapenems, tigecycline, and minocycline are the recommended antibiotics for Enterobacteriaceae. In recent years, the proportion of enterococcus has gradually increased, and clinical attention should be paid to enterococcus infection. Linezolid and vancomycin were recommended for the treatment of Enterococci infections. Overall, this work can provide reference for clinical diagnosis, treatment and effective interventions. …

Abstract Background It is difficult to detect the outbreak of emergency infectious disease based on the exiting surveillance system. Here we investigate the utility of the Baidu Search Index, an indicator of how large of a keyword is in Baidu’s search volume, in the early warning and predicting the epidemic trend of COVID-19. Methods The daily number of cases and the Baidu Search Index of 8 keywords (weighted by population) from December 1, 2019 to March 15, 2020 were collected and analyzed with times series and Spearman correlation with different time lag. To predict the daily number of COVID-19 cases using the Baidu Search Index, Zero-inflated negative binomial regression was used in phase 1 and negative binomial regression model was used in phase 2 and phase 3 based on the characteristic of independent variable. Results The Baidu Search Index of all keywords in Wuhan was significantly higher than Hubei (excluded Wuhan) and China (excluded Hubei). Before the causative pathogen was identified, the search volume of “Influenza” and “Pneumonia” in Wuhan increased with the number of new onset cases, their correlation coefficient was 0.69 and 0.59, respectively. After the pathogen was public but before COVID-19 was classified as a notifiable disease, the search volume of “SARS”, “Pneumonia”, “Coronavirus” in all study areas increased with the number of new onset cases with the correlation coefficient was 0.69 ~ 0.89, while “Influenza” changed to negative correlated (rs: -0.56 ~ -0.64). After COVID-19 was closely monitored, the Baidu Search Index of “COVID-19”, “Pneumonia”, “Coronavirus”, “SARS” and “Mask” could predict the epidemic trend with 15 days, 5 days and 6 days lead time, respectively in Wuhan, Hubei (excluded Wuhan) and China (excluded Hubei). The predicted number of cases would increase 1.84 and 4.81 folds, respectively than the actual number of cases in Wuhan and Hubei (excluded Wuhan) from 21 January to 9 February. Conclusion The Baidu Search Index could be used in the early warning and predicting the epidemic trend of COVID-19, but the search keywords changed in different period. Considering the time lag from onset to diagnosis, especially in the areas with medical resources shortage, internet search data can be a highly effective supplement of the existing surveillance system. …

Between 2020–2024, the global spread of Streptococcus pyogenes emm lineage M1UK has been identified as an emerging public health concern [1–4]. The strain was first described in the UK, where it was associated with an increase in scarlet fever cases from 2014 to 2018 [5]. One key aspect of this specific variant is a significantly high incidence of severe community-acquired pneumonia complicated by empyema, which has been reported in several countries [6–8]. Precedent or concurrent respiratory viral infection, mostly caused by influenza viruses, has been suggested to trigger pulmonary invasive group A Streptococcus (PiGAS) infections [6-9].

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background The intricate interplay between genetics and immunology often dictates the host’s susceptibility to various diseases. This study explored the genetic causal relationship between natural killer (NK) cell-related traits and the risk of infection. Methods Single-nucleotide polymorphisms (SNPs) significantly associated with NK cell-related traits were selected as instrumental variables to estimate their genetic causal effects on infection. SNPs from a genome-wide association study (GWAS) on NK cell-related traits, including absolute cell counts, median fluorescence intensities reflecting surface antigen levels, and relative cell counts, were used as exposure instruments. Summary-level GWAS statistics of four phenotypes of infection were used as the outcome data. The exposure and outcome data were analyzed via the two-sample Mendelian randomization method. Results Each one standard deviation increase in the expression level of human leukocyte antigen (HLA)-DR on HLA-DR+ NK cells was associated with a lower risk of pneumonia (P 

by Zhaolei Wang, Haixia Du, Haofang Wan, Jiehong Yang, Haitong Wan Methicillin-resistant Staphylococcus aureus (MRSA) is an opportunistic pathogen that can cause severe bacterial pneumonia. Amygdalin is the main active pharmaceutical ingredient of bitter almond, which has broad-spectrum antibacterial, anti-inflammatory, anti-oxidation and immunomodulatory effects. It is also the main ingredient of Yinhua Pinggan granule, which is commonly used to moisten the lung and relieve cough. However, little is known about the effects of amygdalin on MRSA. In this study, we found that amygdalin exhibited good antimicrobial activity in vitro against MRSA. Amygdalin has a protective effect on MRSA infected cells, and the effect is better when combined with levofloxacin. It also can reduce the adhesion and invasion of MRSA to cells. Amygdalin has anti-inflammatory and antioxidant effects, which can significantly reduce the increase of inflammatory factors and the production of ROS caused by infection. The protective mechanism of amygdalin on cells may be related to inhibiting the expression of NLRP3, ASC and IL-1β pyroptosis pathways. Taken together, our study suggests that amygdalin exerts antibacterial effects by affecting biofilm formation, the expression of virulence factors, and drug resistance genes. Amygdalin combined with levofloxacin has a protective effect on A549 cells infected with MRSA, and the mechanism may be related to the inhibition of inflammatory response, oxidative damage and pyroptosis.

IMPORTANCE: Acute respiratory distress syndrome (ARDS) is associated with high mortality and morbidity. Extracorporeal membrane oxygenation (ECMO) is one of the interventions that have been in practice for ARDS for decades. OBJECTIVES: The purpose of the study was to investigate the outcomes of ECMO in pediatric trauma patients who suffered from ARDS. DESIGN: Observational cohort study. SETTING AND PARTICIPANTS: The Trauma Quality Improvement Program database for years 2017 to 2019 and 2021 through 2022 was accessed for the study. All children younger than 18 years old who were admitted to the hospital after trauma and suffered from ARDS were included in the study. Other variables included in the study were patients’ demographics, clinical characteristics, Injury Severity Score (ISS), Glasgow Coma Scale (GCS) score, comorbidities, and outcomes. MAIN OUTCOMES AND MEASURES: ECMO is the exposure, and the outcomes are in-hospital mortality and hospital complications (acute kidney injury [AKI], pneumonia and deep vein thrombosis [DVT]). RESULTS: Of 453 patients who qualified for the study, propensity score matching found 50 pairs of patients. There were no significant differences identified between the groups, ECMO+ vs. ECMO– on patients’ age in years (16 yr; interquartile range [IQR], 13.25–17 yr vs. 16 yr [14.25–17 yr]), race (White; 62.0% vs. 66.0%), sex (male; 78% vs. 76%), ISS (23 [IQR, 9.25–34] vs. 22 [9.25–32]), and GCS (15 [IQR, 3–15] vs. 13.5 [3–15]), mechanism of injury; and comorbidities. There was no difference between the groups, ECMO+ vs. ECMO–, in-hospital mortality (10.0% vs. 20.0%; p = 0.302), hospital complications (AKI 12.0% vs. 2.0%; p = 0.131), pneumonia (10.0% vs. 20.0%; p = 0.182 > ), and DVT (16% vs. 6%; p = 0.228). CONCLUSIONS AND RELEVANCE: No difference in mortality was observed in injured children who suffered from the ARDS and were placed on ECMO when compared with patients who were not placed on ECMO. Patients with trauma and ARDS who require ECMO have comparable outcomes to those who do not receive ECMO. A larger sample size study is needed to find the exact benefit of ECMO in this patients’ cohort.

Abstract Background X-linked agammaglobulinemia (XLA), also referred to as Bruton’s tyrosine kinase deficiency, is a rare genetic disorder that affects the immune system. We conducted genetic analysis on patients suffering from immunodeficiency by utilizing Next-Generation Sequencing techniques, as well as their closest relatives, to facilitate accurate diagnosis, offer genetic counseling services, and enhance our comprehension of XLA. …

Abstract Background There are multiple antibiotic regimens for the treatment of carbapenem-resistant Acinetobacter baumannii (CRAB) in clinical practice. We conducted this meta-analysis to compare the efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. Methods Two authors independently searched the PubMed, Web of Science, Embase, and Cochrane databases from their establishment to April 15, 2024, to search for randomized controlled trials (RCTs) or cohort studies, and compared the clinical efficacy and safety of cefiderocol-based regimens and colistin-based regimens in the treatment of CRAB infections. The Newcastle Ottawa Scale (NOS) checklist was used to evaluate the quality of the included studies. The primary outcome was all-cause mortality, and subgroup analysis was conducted on the basis of the site of infection and the risk of bias in the studies. Trial sequential analysis (TSA) was then conducted. Results Six observational studies were included, with 251 cases in the cefiderocol-based group and 372 cases in the colistin-based group. Compared to the colistin-based group, the cefiderocol-based group had lower all-cause mortality (RR = 0.71, 95% CI: 0.54–0.92, P = 0.01) and 30-day mortality (RR = 0.64, 95% CI: 0.43–0.95, P = 0.03). However, for the 14-day and 28-day mortality rates, there was no statistically significant difference between two groups. According to the subgroup analysis, among patients with bloodstream infection (BSI), the cefiderocol-based group had lower all-cause mortality, but it did not reduce the mortality of ventilator-associated pneumonia (VAP) patients. The result of TSA showed that our conclusions are reliable. There was no significant statistical difference in the microbiological cure rate, clinical cure rate, or duration of hospitalization. In addition, the cefiderocol-based group did not have an increased incidence of acute kidney injury (AKI). Conclusions Compared with the colistin-based regimens, the cefiderocol-based regimens were significantly associated with a lower risk of mortality in CRAB-infected patients, especially for patients with BSI. However, they did not show any advantages in terms of the clinical cure rate or microbiological cure rate, nor did they reduce the incidence of AKI. PROSPERO registration number CRD42023487213. …

Abstract There have been increasing reports of Klebsiella pneumoniae resistant to β-lactam antibiotics. This study aimed to determine the prevalence of some selected carbapenemase genes among clinical isolates of Klebsiella pneumoniae recovered from patients attending a private tertiary hospital in Southwestern Nigeria. The study was conducted over two months (February-March 2024). A total of 50 clinical isolates of Klebsiella pneumoniae from different clinical specimens were obtained from the Medical Microbiology Department, Babcock University Teaching Hospital (BUTH). The clinical isolates were then characterized using standard microbiological procedures and were tested for susceptibility to meropenem and other classes of antibiotics according to Clinical and Laboratory Standards Institute (CLSI) guidelines. Polymerase Chain Reaction (PCR) detection for OXA-48 and NDM-1 carbapenemase genes was performed on the 50 clinical isolates. PCR analysis showed that 9 (18%) clinical isolates were positive for the OXA-48 gene, 22 (44%) were positive for the NDM-1 gene, 4 (8%) possessed both the OXA-48 and NDM-1 genes, and 23 (46%) possessed neither the OXA-48 nor NDM-1 genes. Antibiotic Susceptibility Testing (AST) revealed that all the clinical isolates were resistant to meropenem. In conclusion, this study demonstrates the presence of OXA-48 and NDM-1 genes in clinical isolates of Klebsiella pneumoniae recovered from patients attending a private tertiary hospital in Southwestern Nigeria, highlighting the role of ESBL (extended-spectrum beta-lactamase) as a major resistance mechanism alongside other mechanisms. Population-based surveillance programs should be implemented to monitor the prevalence and epidemiology of Klebsiella pneumoniae infections at the community level, facilitating early detection of outbreaks and identification of emerging antimicrobial resistance patterns. Core Tip This study highlights the significant prevalence of NDM-1 and OXA-48 carbapenemase genes among Klebsiella pneumoniae clinical isolates in a private tertiary hospital in Southwestern Nigeria, with 44% and 18% of isolates harboring these genes, respectively. Notably, 46% of isolates were resistant to carbapenems despite lacking these genes, suggesting alternative resistance mechanisms. The findings underscore the urgent need for enhanced surveillance, infection control measures, and antibiotic stewardship programs to combat the spread of multidrug-resistant Klebsiella pneumoniae in healthcare settings. …

ObjectivesWe aimed to evaluate hospital mortality rates, readmission rates and length of hospital stay (LOS) among adult medical patients admitted to a teaching hospital in Ethiopia. DesignWe performed a retrospective study using routinely collected electronic data. SettingData were collected from Yekatit 12 Hospital Medical College between January 2021 and July 2023. ParticipantsThe analysis included 3499 (4111 admissions) adult medical patients with complete data. Outcome measuresWe used mortality rates, readmission rates and LOS to measure the quality of the outcomes for the top 15 admission diagnoses. A multivariable Cox proportional hazard model was used to identify the statistically significant predictors of mortality with p values

Abstract Background Antiviral drugs show significant efficacy in non-severe COVID-19 cases, yet there remains a subset of moderate COVID-19 patients whose pneumonia continues to progress post a complete course of treatment. Plasma-activated water (PAW) possesses anti-SARS-CoV-2 properties. To explore the potential of PAW in improving pneumonia in COVID-19 patients following antiviral treatment failure, we conducted this study. Methods This was a randomized, controlled trial. Moderate COVID-19 patients with antiviral treatment failure were randomly assigned to the experimental group or the control group. They inhaled nebulized PAW or saline respectively. This was done twice daily for four consecutive days. We assessed improvement in chest CT on day 5, the rate of symptom resolution within 10 days, and safety. Results A total of 23 participants were included, with 11 receiving PAW and 12 receiving saline. The baseline characteristics of both groups were comparable. The experimental group showed a higher improvement rate in chest CT on day 5 (81.8% vs. 33.3%, p = 0.036). The cumulative disappearance rate of cough within 10 days was higher in the experimental group. Within 28 days, 4 patients in each group progressed to severe illness, and no patients died. No adverse reactions were reported from inhaling nebulized PAW. Conclusion This pilot trial preliminarily confirmed that nebulized inhalation of PAW can alleviate pneumonia in moderate COVID-19 patients with antiviral treatment failure, with no adverse reactions observed. This still needs to be verified by large-scale studies. Trial registration Chinese Clinical Trial Registry; No.: ChiCTR2300078706 (retrospectively registered, 12/15/2023); URL: www.chictr.org.cn. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Abstract Background and objective Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP. Methods We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis. Results A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality. Conclusion Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP. …