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Objectives: Lefamulin (Xenleta™), a pleuromutilin antibiotic, was approved for the oral and IV treatment of community-acquired bacterial pneumonia (CABP) in adults in 2019/2020. This study evaluated the in vitro activity of lefamulin and comparators against 19 584 unique bacterial isolates collected from patients with community-acquired respiratory tract infections and hospitalized patients with pneumonia within the global SENTRY Antimicrobial Surveillance Program during 2015-21., Methods: Isolates were susceptibility tested by the CLSI broth microdilution method, and resistance mechanisms were investigated in isolates with elevated lefamulin MICs., Results: Lefamulin exhibited potent antibacterial activity against the most common and typical CABP pathogens tested, including Streptococcus pneumoniae [MIC50/90, 0.06/0.25 mg/L; 99.9% susceptible (S)], Staphylococcus aureus (MIC50/90, 0.06/0.12 mg/L; 99.6% S), Haemophilus influenzae (MIC50/90, 0.5/2 mg/L; 99.1% S) and Moraxella catarrhalis (MIC50/90, 0.06/0.12 mg/L; 100.0% S). Potent activity was also observed against the less common pneumonia pathogens: β-haemolytic (MIC50/90 of 0.03/0.06 mg/L) and viridans group Streptococcus spp. (MIC50/90 of 0.06/0.25 mg/L) and Haemophilus parainfluenzae (MIC50/90 of 1/4 mg/L). Lefamulin's activity was not adversely affected by resistance to macrolides, penicillin, tetracyclines, fluoroquinolones and other resistance phenotypes. Non-susceptibility/resistance to lefamulin was rare and primarily determined by ribosomal protection through vga(A) variants in S. aureus, overexpression of AcrAB-TolC efflux pump in H. influenzae or modifications in L3, L4 and 23SrRNA in Streptococcus spp., Conclusions: Based on the coverage of the most important CABP pathogens and lacking cross-resistance, lefamulin may represent a valuable empirical treatment option for ambulatory and hospitalized patients with CABP, particularly in settings with high prevalence of resistance., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This study aimed to examine the clinical and microbiological characteristics of female patients with recurrent acute pyelonephritis (APN)., Methods: A retrospective cohort study was conducted at a tertiary care hospital in South Korea from July 2019 to December 2021. All female patients aged ≥ 19 years who were diagnosed with community-acquired APN on admission were enrolled. The recurrent group included patients with APN who experienced urinary tract infections within the previous year. The clinical characteristics, types of causative organisms, major antibiotic resistance, and molecular characteristics of Escherichia coli strains were compared between the recurrent and non-recurrent groups., Results: A total of 285 patients with APN were analyzed, including 41 (14.4%) in the recurrent group. Compared to the non-recurrent group, the recurrent group had a higher Charlson Comorbidity Index (1.8 ± 2.1 vs. 1.1 ± 1.5; P = 0.01) and a higher proportion of bladder abnormalities, such as neurogenic bladder (12.2% vs. 2.0%; P = 0.001) and urinary catheterization (12.2% vs. 1.6%; P < 0.001). Escherichia coli was the most common causative organism in both groups. The proportion of Klebsiella pneumoniae (17.1% vs. 4.7%; P = 0.007) and Pseudomonas aeruginosa (5.7% vs. 0.5%; P = 0.014) as a causative organism was higher in the recurrent group. Regarding the microbiological characteristics of Escherichia coli, there were no significant differences in the proportion of antibiotic resistance, phylogenetic groups, resistance genes, and virulence factors between the two groups. Multivariable analysis showed that neurogenic bladder and a history of admission or antibiotic use during 1 year prior to inclusion were significantly associated with recurrent APN., Conclusions: The proportion of causative organisms except Escherichia coli was higher in the recurrent group than in the non-recurrent group. Neurogenic bladder and a history of admission or antibiotic use during 1 year prior to inclusion were risk factors for recurrent APN., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

To investigate potential respiratory pathogens in children with community-acquired pneumonia (CAP) and risk factors for severe disease. This prospective study was conducted among 467 children at the Thai Binh Paediatric Hospital, Vietnam between 1 July 2020 and 30 June 2021. Clinical data and laboratory results were collected. Twenty-four respiratory microorganisms were tested from nasopharyngeal swabs using real-time PCR. Logistical regression was used to estimate a factor's adjusted odd ratios of the severity of disease. Mean age of patients = 15.4 ± 13.3 months, 63.0% were male. Over 97% of patients had a positive PCR result. 87% of patients were positive for multiple (up to eight) microorganisms. Rhinovirus (46%), respiratory syncytial virus (RSV) (24%), enterovirus (17%), and parainfluenza viruses-3 (13%) were the most frequent viruses. H. influenzae (61%), S. pneumoniae (45%) and M. catarrhalis (30%) were the most common bacteria. 128 (27%) cases were classified as severe pneumonia. Presence of smokers at home (aOR 2.11, 95% CI 1.27-3.52, P value = 0.004), CRP level ≥ 50 mg/dL (aOR  6.11, 95% CI  3.86-9.68, P value < 0.0001), RSV (aOR  1.78, 95% CI  1.07-2.96, P value = 0.03) and H. influenzae (aOR  1.66, 95% CI  1.03-2.67, P value = 0.04) PCR detection associated with a higher risk of severe pneumonia; ,. Causative agents of pneumonia in children are complex. Children positive with RSV and H. influenzae need to be closely monitored to prevent severe pneumonia., (© 2024. The Author(s).)

Objective: To study the etiological characteristics of community-acquired pneumonia (CAP) combined with type 2 diabetes (T2D), providing a reference for early clinical diagnosis and treatment of the disease., Methods: We selected a total of 93 patients with CAP and analyzed their metagenomics nextgeneration sequencing (mNGS) data. The case group comprised 46 patients with combined CAP/T2D, and the control group comprised 47 patients without diabetes. We analyzed the pathogenic findings of the two groups., Results: There were statistically significant differences in age between the two groups (P = 0.001). Leukocytes (P = 0.012), blood platelets (P = 0.034), fibrinogen (P = 0.037), D-dimer (P = 0.000), calcitonin ogen (P = 0.015), ultrasensitive C-reactive protein or C-reactive protein (CRP) (P = 0.000), serum amyloid A (P = 0.000), and erythrocyte sedimentation rate (P = 0.003) were higher in the case group than in the control group. Albumin was lower in the case group than in the control group. All differences were statistically significant. The infection rates of Klebsiella pneumoniae (P = 0.030), Pseudomonas aeruginosa (P = 0.043), and Candida albicans (P = 0.032) were significantly different between the two groups., Conclusion: Compared with those without diabetes, the infection rates of Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were higher in patients with combined CAP/T2D., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Infections caused by anaerobic bacteria occur frequently and can be serious and life-threatening. Anaerobes are a rare cause of community-acquired pneumonia with Streptococcus pneumonia and respiratory viruses being the most frequently detected pathogens. We, herein, report a case of Fusobacterium/Peptostreptococcus parapneumonic effusion with empyema in a patient without risk factors for aspiration pneumonia. This case presents an opportunity to discuss an unusual case of community-acquired empyema secondary to anaerobic infection in a patient without the common risk factors for aspiration.

Case Presentation: A 59-year-old male patient without significant past medical history apart from a twenty-five-year history of smoking presented due to left flank pain and shortness of breath. Findings of a complicated parapneumonic effusion were found on imaging, resulting in surgical decortication and prolonged antibiotic therapy.

Discussion: Parapneumonic effusions and empyema are relatively common complications of pneumonia. It is important to note that the incidence of anaerobic empyema has been on the rise due to more modern culturing techniques.

Conclusion: This case highlights an unusual presentation of community-acquired empyema secondary to anaerobes without any risk factors for aspiration pneumonia. Therefore, clinicians should consider the possibility of anaerobic coverage in the treatment of community-acquired empyema in the appropriate setting.

Objectives: This study aimed to investigate the etiology, clinical features, and outcomes of community-acquired pneumonia (CAP) in adults. Understanding the causative pathogens is essential for effective treatment and prevention., Design: Between 2016-2018, 518 hospitalized adults with CAP and 241 controls without symptoms were prospectively enrolled. Urine samples were collected for pneumococcal urinary antigen tests and nasopharyngeal swabs for viral and bacterial analysis, combined with routine diagnostic care., Results: Among the included CAP patients, Streptococcus pneumoniae was the most common pathogen, detected in 28% of patients, followed by Haemophilus influenzae in 16%. Viruses were identified in 28%, and concurrent viruses and bacteria were detected in 15%. There was no difference in mortality, length of stay, or symptoms at hospitalization when comparing patients with bacterial, viral, or mixed etiologies. Among the control subjects without respiratory symptoms, S. pneumoniae , H. influenzae , or Moraxella catarrhalis were detected in 5-7%, and viruses in 7%., Conclusion: Streptococcus pneumoniae emerged as the predominant cause of CAP, followed closely by viruses and H. influenzae . Intriguingly, symptoms and outcome were similar regardless of etiology. These findings highlight the complexity of this respiratory infection and emphasize the importance of comprehensive diagnostic and treatment strategies. Clinical Trial Registration : ClinicalTrials.gov, identifier [NCT03606135]., Competing Interests: KR reports an unrestricted grant from Pfizer during the conduct of the study outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hansen, Yamba Yamba, Wasserstrom, Rünow, Göransson, Nilsson, Ahl and Riesbeck.)

We present the case of a pregnant woman with community-acquired methicillin-resistant Staphylococcus aureus bacteremia who required combined treatment with daptomycin and cefazolin for control after failure of an initial treatment with vancomycin. She had a favorable evolution, and the study of family contacts revealed a phenotypic and genetically similar isolate in a nasal sample from his mother. The carriage study on three household cats was negative. This case reveals that bacteremia caused by methicillin-resistant Staphylococcus aureus can affect pregnant women, and that the use of combined therapies may be necessary for its control. Sometimes, family contacts can carry this agent, and an eradication treatment is suggested..

Invasive infection caused by hypervirulent Klebsiella pneumoniae (HvKP) has been reported worldwide. Most of the patients are community population, related to diabetes mellitus (DM), chronic liver disease and other basic diseases, which prone to systemic migratory infection. In this study, we collected 377 patients with community acquired Klebsiella pneumoniae liver abscess in our hospital from January 2013 to December 2018, 65.8% of whom were male, and 49.6% had DM. Patients with DM are prone to eye and central nervous system (CNS) infection, which need continuous local abscess drainage during treatment. Among them, patients with poor blood glucose control have a higher rate of blood stream infections (BSI). 219 strains of HvKP were obtained, with K1/K2 Serotype accounted for 81.7%. The incidence of BSI in K2 patients was higher than that in K1 patients. The PCR results indicate that the carrying rate of virulence genes (rmpA、areo、kfu、allS、iroN、magA、uge、wcaG) in K1/K2 type strains is significantly higher than that in non K1/K2 type strains. ST23 and ST65 are the most common multilocus sequence typing (MLST), which belong to K1 and K2 Serotype respectively. All of HvKP strains showed high sensitivity to commonly used clinical antibiotics other than ampicillin, with 54.3% of the strains exhibiting high viscosity characteristics. Meanwhile, 35 classic Klebsiella pneumoniae (cKP) strains were collected, and their serum typing is mainly non K1/K2. The carrying rate of virulence genes and viscosity degree in HvKP are significantly higher than those in cKP. Primary liver abscess caused by HvKP is prone to multiple tissue and organ infections, but it shows higher sensitivity to most commonly used antibiotics in clinical practice except for ampicillin. After effective treatment, the overall prognosis of patients is better. This study analyzes the pathogenic characteristics of HvKP and elaborates on the clinical characteristics of patients, which can provide reference for clinical and scientific research work.

Objective: Bacterial culture and drug sensitivity testing have been the gold standard for confirming community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in breast abscess with a long history. However, these tests may delay treatment and increase the risk of nosocomial infections. To handle and improve this critical situation, this study aimed to explore biomarkers that could facilitate the rapid diagnosis of CA-MRSA infection., Methods: This study for the first time applied label-free quantitative proteomics and non-targeted metabonomics to identify potential differentially expressed proteins (DEPs) and differentially expressed metabolites (DEMs) in breast abscess infected with CA-MRSA compared to methicillin-susceptible S. aureus (MSSA). The two omics data were integrated and analyzed using bioinformatics, and the results were validated using Parallel Reaction Monitoring (PRM). Receiver operating characteristic (ROC) curves were generated to evaluate the predictive efficiency of the identified biomarkers for diagnosing CA-MRSA infection., Results: After using the above-mentioned strategies, 109 DEPs were identified, out of which 86 were upregulated and 23 were downregulated. Additionally, a total of 61 and 26 DEMs were initially screened in the positive and negative ion modes, respectively. A conjoint analysis indicated that the amino acid metabolism, glycosphingolipid biosynthesis, and glycerophospholipid metabolism pathways were co-enriched by the upstream DEPs and downstream DEMs, which may be involved in structuring the related network of CA-MRSA infection. Furthermore, three significant DEMs, namely, indole-3-acetic acid, L-(-)-methionine, and D-sedoheptulose 7-phosphate, displayed good discriminative abilities in early identification of CA-MRSA infection in ROC analysis., Conclusion: As there is limited high-quality evidence and multiple omics research in this field, the explored candidate biomarkers and pathways may provide new insights into the early diagnosis and drug resistance mechanisms of CA-MRSA infection in Chinese women., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yin, Cao, Zhang, Li, Sun, Ma, Liu, Li, Yu and Guan.)

Background: There have been many epidemiologic studies on community-acquired pneumonia (CAP) among children, most of which had substantial limitations. This study investigated the etiologic distribution and clinical characteristics of CAP in Korean children for 5 years before the coronavirus disease 2019 (COVID-19) pandemic., Methods: A retrospective analysis of children hospitalized for CAP at 4 referral hospitals during 2015-2020 was performed. Cases in which bronchiolitis was suspected or pulmonary infiltration was not evident on chest radiography (CXR) were excluded. Viruses and atypical bacteria were defined as detected when positive in the polymerase chain reaction test performed for respiratory specimens. Serologic testing result for Mycoplasma pneumoniae was incorporated with strict interpretation. Pyogenic bacteria were included only when cultured in blood, pleural fluid, or bronchoalveolar lavage, but those cultured in endotracheal aspirate or sputum when the case was clinically evident bacterial pneumonia were also included., Results: A total of 2,864 cases of suspected pneumonia were selected by diagnosis code and CXR findings. Medical chart and CXR review excluded nosocomial pneumonia and cases without evident infiltration, resulting in 517 (18.1%) CAP cases among 489 children. Regarding clinical symptoms, high fever was present in 59.4% and dyspnea in 19.9% of cases. Respiratory support was required for 29.2% of patients, including mechanical ventilation for 3.9%. Pathogens were detected in 49.9% of cases, with viruses in 32.3%, atypical bacteria in 17.8%, and pyogenic bacteria in 2.3% of cases. As single pathogens, M. pneumoniae (16.8%) and respiratory syncytial virus (RSV, 13.7%) were the most common. Parenteral β-lactam and macrolide antibiotics were administered in 81.6% and 50.7% of cases, respectively. A total of 12 (2.3%) cases resulted in poor outcomes, including 3 deaths., Conclusion: M. pneumoniae and RSV were the most commonly detected pathogens of pediatric CAP, which was selected by strict clinical and radiologic criteria. It is necessary to carefully decide whether to use parenteral antibiotics based on the epidemiology and clinical features of CAP in children., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background: Community-Acquired Pneumonia (CAP) is the primary cause of hospitalization in the United States and the third leading cause of death in Brazil. The gold standard for diagnosing the etiology of CAP includes blood culture, Gram-stained sputum, and sputum culture. However, these methods have low sensitivity. No studies investigating the etiology of CAP have been conducted in Brazil in the last 20-years, and the empirical choice of antimicrobials is mainly based on the IDSA guidelines. This is the first national study with this aim, and as a result, there's potential for the Brazilian consensus to be impacted and possibly modify its guidelines rather than adhering strictly to the IDSA's recommendations., Methods: The aim of this study is to identify the main microorganisms implicated in CAP by employing a multiplex Polymerase Chain Reaction (mPCR) at the foremost public hospital in Brazil. All patients who were admitted to the emergency department and diagnosed with severe CAP underwent an mPCR panel using nasopharyngeal and oropharyngeal swabs, with the aim of detecting 13 bacterial and 21 viral pathogens., Results: A total of 169 patients were enrolled in the study. The mPCR panel identified an etiological agent in 61.5% of patients, with viruses being the most common (42.01%), led by Rhinovirus, followed by Influenza and Coronavirus (non-SARS-CoV-2). Bacterial agents were identified in 34.91% of patients, with S. pneumoniae being the most common, followed by H. influenzae, M. catarrhalis, and S. aureus. Additionally, we found that the prescription for 92.3% of patients could be modified, with most changes involving de-escalation of antibiotics and antiviral therapy., Conclusion: Our study revealed different etiological causes of CAP than those suggested by the Brazilian guidelines. Using molecular diagnostic tests, we were able to optimize treatment by using fewer antibiotics., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2023 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Clostridioides difficile infection (CDI) is a common healthcare-associated infection and leading cause of gastroenteritis-related mortality worldwide. However, data on CDI-associated mortality are scarce. We aimed to examine the association between CDI and all-cause and cause-specific mortality. We additionally explored contributing causes of mortality, including recurrent CDI, hospital- or community-acquired CDI, chronic comorbidities, and age., Methods: This nationwide population-based cohort study (from 2006 to 2019) compared individuals with CDI with the entire Swedish background population using standardized mortality ratios. In addition, a matched-cohort design (1:10), utilizing multivariable Poisson-regression models, provided incidence rate ratios (IRRs) with 95% CIs., Results: This study included 43 150 individuals with CDI and 355 172 controls. In total, 69.7% were ≥65 years, and 54.9% were female. CDI was associated with a 3- to 7-fold increased mortality rate (IRR = 3.5, 95% CI: 3.3-3.6; standardized mortality ratio = 6.8, 95% CI: 6.7-6.9) compared with the matched controls and Swedish background population, respectively. Mortality rates were highest for hospital-acquired CDI (IRR = 2.4, 95% CI: 1.9-3.2) and during the first CDI episode (IRR = 0.2, 95% CI: 0.2-0.3 for recurrent versus first CDI). Individuals with CDI had more chronic comorbidities than controls, yet mortality remained higher among CDI cases even after adjustment and stratification for comorbidity; CDI was associated with increased mortality (IRR = 6.1, 95% CI: 5.5-6.8), particularly among those without any chronic comorbidities., Discussion: CDI was associated with elevated all-cause and cause-specific mortality, despite possible confounding by ill health. Mortality rates were consistently increased across sexes, all age groups, and comorbidity groups., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Urinary tract infections (UTIs) are primarily caused by uropathogenic Escherichia coli (UPEC). This study aims to elucidate the role of the virulence factor HlyF in the epidemiology and pathophysiology of UTIs and investigate the dissemination of plasmids carrying the hlyF gene., Methods: An epidemiological analysis was conducted on a representative collection of 225 UPEC strains isolated from community-acquired infections. Selected hlyF+ strains were fully sequenced using a combination of Illumina and Nanopore technologies. To investigate the impact of HlyF, a murine model of UTI was utilized to compare clinical signs, bacterial loads in the bladder, kidney, and spleen, onset of bacteraemia, and inflammation through cytokine quantification among wild-type hlyF+ strains, isogenic mutants, and complemented mutants., Results: Our findings demonstrate that 20% of UPEC encode the HlyF protein. These hlyF+ UPEC strains exhibited enhanced virulence, frequently leading to pyelonephritis accompanied by bloodstream infections. Unlike typical UPEC strains, hlyF+ UPEC strains demonstrate a broader phylogroup distribution and possess a unique array of virulence factors and antimicrobial resistance genes, primarily carried by ColV-like plasmids. In the murine UTI model, expression of HlyF was linked to the UPECs' capacity to induce urosepsis and elicit an exacerbated inflammatory response, setting them apart from typical UPEC strains., Discussion: Overall, our results strongly support the notion that HlyF serves as a significant virulence factor for UPECs, and the dissemination of ColV-like plasmids encoding HlyF warrants further investigation., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Streptococcus pneumoniae (S. pneumoniae) is a bacterial species often associated with the occurrence of community-acquired pneumonia (CAP). CAP refers to a specific kind of pneumonia that occurs in individuals who acquire the infection outside of a healthcare setting. It represents the leading cause of both death and morbidity on a global scale. Moreover, the declaration of S. pneumoniae as one of the 12 leading pathogens was made by the World Health Organization (WHO) in 2017. Antibiotics like β -lactams, macrolides, and fluoroquinolones are the primary classes of antimicrobial medicines used for the treatment of S. pneumoniae infections. Nevertheless, the efficacy of these antibiotics is diminishing as a result of the establishment of resistance in S. pneumoniae against these antimicrobial agents. In 2019, the WHO declared that antibiotic resistance was among the top 10 hazards to worldwide health. It is believed that penicillin-binding protein genetic alteration causes β -lactam antibiotic resistance. Ribosomal target site alterations and active efflux pumps cause macrolide resistance. Numerous factors, including the accumulation of mutations, enhanced efflux mechanisms, and plasmid gene acquisition, cause fluoroquinolone resistance. Furthermore, despite the advancements in pneumococcal vaccinations and artificial intelligence (AI), it is not feasible for individuals to rely on them indefinitely. The ongoing development of AI for combating antimicrobial resistance necessitates more research and development efforts. A few strategies can be performed to curb this resistance issue, including providing educational initiatives and guidelines, conducting surveillance, and establishing new antibiotics targeting another part of the bacteria. Hence, understanding the resistance mechanism of S. pneumoniae may aid researchers in developing a more efficacious antibiotic in future endeavors.

Introduction: Urinary tract infections (UTIs) are common in children. UTIs can lead to serious and permanent damage to the urinary tract if treatment is delayed or insufficient, particularly in repeated infections. Knowledge of antibiotic resistance trends aids in the selection of appropriate empiric antibiotics. There is limited data regarding this in Saudi Arabia. This study aimed to investigate uropathogens and their antibiotic resistance patterns in the pediatric community in a tertiary care center., Methodology: The study population included children aged 0 to 14 years old who had culture-proven UTIs evaluated in the Department of Pediatrics, King Abdulaziz University Hospital in Jeddah, Saudi Arabia from February 2019 to September 2021., Results: Out of 510 UTI episodes, Escherichia coli (54.5%) was the predominant causative pathogen. Of the total episodes, 137 (26.8%) were caused by extended spectrum beta-lactamase (ESBL) producers. In general, the highest resistance was observed against ampicillin (73.2%), cefazolin (54.6%), co-trimoxazole (46%), and cefuroxime (40.6%), whereas amikacin (0.4%), imipenem (0.8%), and meropenem (0.8%) showed the lowest rates of resistance., Conclusions: Antibiotic resistance is a major concern worldwide due to misuse of antibiotics and subsequent rise of multidrug resistant organisms. Our findings highlight the rise in antibiotic resistance, particularly in E. coli strains. Furthermore, ESBL-producing bacteria were responsible for approximately one-third of UTIs. Our study emphasizes the importance of local antibiograms for pediatric community-acquired infections, as it guides clinicians in every center in the choice of appropriate empiric antibiotic treatment., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Mohammed A Alsubaie, Abdullah Z Alsuheili, Mohammed N Aljehani, Abdulrahman A Alothman, Abdulaziz S Alzahrani, Hamza A Mohammedfadel, Mazin A Alshehry, Abeer A Alnajjar.)

Background: Antimicrobial resistance poses a public health threat for the treatment of community-acquired urinary tract infections. This study determined the susceptibility patterns of uropathogens and associated risk factors among outpatients diagnosed with urinary tract infections at the Kanifing General Hospital in the Gambia., Methods: A cross-sectional analytic study was conducted among patients with suspected urinary tract infections at Kanifing General Hospital from March to May 2021. Data on socio-demographic and other risk factors were collected from the study participants using a structured pre-tested questionnaire. Mid-stream urine samples were collected, and bacteria identification and antimicrobial susceptibility testing done using standard microbiological methods. Descriptive and inferential statistical analysis were done to determine factors associated with urinary tract infection at 95% confidence level and a p -value < 0.05., Results: A total of 422 patients were enrolled with 82.5% (348/422) being females. The prevalence of community acquired urinary tract infection was 12.8% (54/422). Escherichia coli was the most prevalent isolate (74.1%, 40/54), followed by Klebsiella spp (8.5%, 10/54). Antimicrobial resistance was highest for Ampicillin (87.0%, 47/54), Trimethoprim/Sulfamethoxazole (77.8%, 42/54) and Tetracycline (75.9%, 41/54). Uropathogens sensitivity was 77.8% (42/54) for Nitrofurantoin and 75.9% (41/54) for Ceftazidime. Being female (aOR 5.90 95% CI = 1.48-23.67), previous history of urinary tract infection (aOR 2.34, 95% CI = 1.06-5.14), use of unprescribed antibiotics (aOR 2.0, 95% CI = 1.05-3.62) and having no formal education (aOR 8.02, 95% CI = 1.04-62.0) were significant factors associated for having uropathogenic bacterial infection., Conclusion: E. coli was the most prevalent uropathogen isolated. Ciprofloxacin, Nitrofurantoin and Ceftazidime were the most sensitive antibiotics. Routine surveillance of susceptibility of uropathogenic bacteria would be helpful to update clinicians on the choice of antibiotics., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Klebsiella pneumoniae is a hospital-associated pathogen primarily causing urinary tract infections (UTIs), pneumonia, and septicemia. Two challenging lineages include the hypervirulent strains, causing invasive community-acquired infections, and the carbapenem-resistant classical strains, most frequently isolated from UTIs. While hypervirulent strains are often characterized by a hypermucoid phenotype, classical strains usually present with low mucoidy. Since clinical UTI isolates tend to exhibit limited mucoidy, we hypothesized that environmental conditions may drive K. pneumoniae adaptation to the urinary tract and select against mucoid isolates. We found that both hypervirulent K. pneumoniae and classical Klebsiella UTI isolates significantly suppressed mucoidy when cultured in urine without reducing capsule abundance. A genetic screen identified secondary mutations in the wzc tyrosine kinase that overcome urine-suppressed mucoidy. Over-expressing Wzc variants in trans was sufficient to boost mucoidy in both hypervirulent and classical Klebsiella UTI isolates. Wzc is a bacterial tyrosine kinase that regulates capsule polymerization and extrusion. Although some Wzc variants reduced Wzc phospho-status, urine did not alter Wzc phospho-status. Urine does, however, increase K. pneumoniae capsule chain length diversity and enhance cell-surface attachment. The identified Wzc variants counteract urine-mediated effects on capsule chain length and cell attachment. Combined, these data indicate that capsule chain length correlates with K. pneumoniae mucoidy and that this extracellular feature can be fine-tuned by spontaneous Wzc mutations, which alter host interactions. Spontaneous Wzc mutation represents a global mechanism that could fine-tune K. pneumoniae niche-specific fitness in both classical and hypervirulent isolates. IMPORTANCE Klebsiella pneumoniae is high-priority pathogen causing both hospital-associated infections, such as urinary tract infections, and community-acquired infections. Clinical isolates from community-acquired infection are often characterized by a tacky, hypermucoid phenotype, while urinary tract isolates are usually not mucoid. Historically, mucoidy was attributed to capsule overproduction; however, recent reports have demonstrated that K. pneumoniae capsule abundance and mucoidy are not always correlated. Here, we report that human urine suppresses K. pneumoniae mucoidy, diversifies capsule polysaccharide chain length, and increases cell surface association. Moreover, specific mutations in the capsule biosynthesis gene, wzc , are sufficient to overcome urine-mediated suppression of mucoidy. These Wzc variants cause constitutive production of more uniform capsular polysaccharide chains and increased release of capsule from the cell surface, even in urine. These data demonstrate that K. pneumoniae regulates capsule chain length and cell surface attachment in response host cues, which can alter bacteria-host interactions., Competing Interests: The authors declare no conflict of interest.

Composition of pulmonary microbiome of patients with severe pneumonia is poorly known. The aim of this work was to analyse the lung microbiome of patients admitted to the intensive care unit  (ICU) with severe community acquired pneumonia (CAP) between 2019 and 2021 in comparison with a control group of 6 patients undergoing digestive surgery. As a second objective, the diagnostic capabilities of metagenomics was also studied in a small group of selected patients. The lung microbiome of patients with viral (5 with Influenza A and 8 with SARS-CoV-2) pneumonia at admission showed a similar diversity as the control group (p = 0.140 and p = 0.213 respectively). Contrarily, the group of 12 patients with pneumococcal pneumonia showed a significant lower Simpson´s index (p = 0.002). In the control group (n = 6) Proteobacteria (36.6%), Firmicutes (24.2%) and Actinobacteria (23.0%) were the predominant phyla. In SARS-CoV-2 patients (n = 8), there was a predominance of Proteobacteria (mean 41.6%) (Moraxella and Pelomonas at the genus level), Actinobacteria (24.6%) (Microbacterium) and Firmicutes (22.8%) mainly Streptococcus, Staphylococcus and Veillonella. In patients with Influenza A pneumonia (n = 5) there was a predominance of Firmicutes (35.1%) mainly Streptococcus followed by Proteobacteria (29.2%) (Moraxella, Acinetobacter and Pelomonas). In the group of pneumococcal pneumonia (n = 12) two phyla predominated: Firmicutes (53.1%) (Streptococcus) and Proteobacteria (36.5%) (Haemophilus). In the 7 patients with non-pneumococcal bacterial pneumonia Haemophilus influenzae (n = 2), Legionella pneumophila (n = 2), Klebsiella pneumoniae, Streptococcus pyogenes and Leptospira were detected by metagenomics, confirming the diagnosis done using conventional microbiological techniques. The diversity of the respiratory microbiome in patients with severe viral pneumonia at ICU admission was similar to that of the control group. Contrarily, patients with pneumococcal pneumonia showed a lower grade of diversity. At initial stages of SARS-CoV-2 infection, no important alterations in the pulmonary microbiome were observed. The analysis of bacterial microbiome showed promising results as a diagnostic tool., (© 2023. Springer Nature Limited.)

Objectives: This meta-analysis examined the effect of macrolides on resolution of community-acquired pneumonia (CAP) and interpretation of clinical benefit according to microbiology; emphasis is given to data under-reported countries (URCs)., Methods: This meta-analysis included 47 publications published between 1994 and 2022. Publications were analysed for 30-d mortality (58 759 patients) and resolution of CAP (6465 patients). A separate meta-analysis was done for the prevalence of respiratory pathogens in URCs., Results: Mortality after 30 d was reduced by the addition of macrolides (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.51-0.82). The OR for CAP resolution when macrolides were added to the treatment regimen was 1.23 (95% CI 1.00-1.52). In the CAP resolution analysis, the most prevalent pathogen was Streptococcus pneumoniae (12.68%; 95% CI 9.36-16.95%). Analysis of the pathogen epidemiology from the URCs included 12 publications. The most prevalent pathogens were S. pneumoniae (24.91%) and Klebsiella pneumoniae (12.90%)., Conclusion: The addition of macrolides to the treatment regimen led to 35% relative decrease of 30-d mortality and to 23% relative increase in resolution of CAP., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The usefulness of an induced sputum in the identification of causative bacteria of community-acquired pneumonia (CAP) in young children is controversial. This study aimed to investigate the significance of the implementation of an induced sputum culture among children with CAP and the impact of prior use of antimicrobial agents on the quality of the sample and result of the culture., Methods: This prospective study included 96 children hospitalized for acute bacterial CAP whose sputum samples were collected by suctioning from the hypopharynx through the nose. The samples were evaluated for their quality using Geckler classification, and the result of this conventional culture method was compared to that of a clone library analysis of the bacterial 16S rRNA gene sequence for each sample., Results: The concordance between bacteria isolated by sputum culture and the most predominant bacteria identified by a clonal library analysis was significantly higher in the samples judged as a good quality (Geckler 5, 90%) than in others (70%). The rate of good-quality sputum sample was significantly higher in samples collected from patients without prior antimicrobial therapy (70%) than in those from patients with it (41%). The concordance between the two methods was significantly higher in the former (88%) than in the latter population (71%)., Conclusion: Bacteria isolated by the culture using good-quality sputum samples collected from children with CAP were more likely to be causative pathogens. Sputum samples collected before starting antimicrobial therapy showed better quality and higher probability of the identification of causative pathogens., (Copyright © 2023. Published by Elsevier B.V.)

Syndromic PCR-based analysis of lower respiratory tract (LRT) samples in patients with community-acquired pneumonia (CAP) improves the bacterial yield and time-to-results compared to culture-based methods. However, obtaining adequate sputum samples can be challenging and is frequently not prioritized in the emergency department (ED). In this study, we assess the concordance of microbiological detections between oropharyngeal- (OP) and LRT samples from patients presenting to the ED with CAP using a syndromic PCR-based respiratory panel [Biofire FilmArray Pneumonia plus (FAP plus )]. Paired OP- and high-quality LRT samples were collected from 103 patients with confirmed CAP, who had been included in a randomized controlled trial (NCT04660084) or a subsequent observational study at Haukeland University Hospital, and analyzed using the FAP plus . The LRT samples were obtained mainly by sputum induction (88%). Using the LRT samples as a reference standard, the positive percent agreement (PPA), negative percent agreement (NPA), and overall percent agreement for the most common bacterial pathogens in CAP, Streptococcus pneumoniae and Haemophilus influenzae , were 85%, 99% and 95%, and 86%, 98% and 93%, respectively. For Moraxella catarrhalis, the PPA was lower (74%), while the NPA was 100%. For bacteria that are less likely causes of uncomplicated CAP (e.g., Staphylococcus aureus and Enterobacterales) the results were more divergent. In conclusion, the FAP plus detects the most common CAP pathogens S. pneumoniae and H. influenzae from OP samples with high PPAs and excellent NPAs when compared with LRT samples. For these pathogens, the PPAs for OP samples were higher than previous reports for nasopharyngeal samples. This suggests that analysis of OP samples with syndromic PCR panels could represent an alternative approach for rapid microbiological testing in the ED, especially in patients where LRT samples are difficult to obtain. Divergent results for bacteria that are less likely to cause uncomplicated CAP do, however, emphasize the need for clinical evaluation of positive test results., Competing Interests: The authors declare no conflict of interest.

Objectives: To assess the clinical profile of infants with late onset sepsis admitted in a tertiary care hospital in North-East India., Methods: Prospective observational study was carried out in Department of Paediatrics, Regional Institute of Medical Sciences hospital during a period of 2 years (September 2019-August 2021)., Results: A total of 109 patients were included in the study, of which 80 were community-acquired and 29 infants were hospital-acquired cases of late onset sepsis (LOS). The major risk factors were low socioeconomic status, prematurity, low birth weight, a history of intervention (mechanical ventilation, umbilical venous catheter, total parenteral nutrition, resuscitation) and lack of exclusive breastfeeding. The most common presenting features were decreased feeding, lethargy and respiratory distress. Blood cultures were positive in 33% of patients. Klebsiella was the most common hospital-acquired pathogen while Escherichia coli was the most common isolate in community-acquired cases. Thrombocytopenia was the most common complication. The in-hospital mortality rate was 13.7%., Conclusion: Low socioeconomic status, low birth weight, prematurity, invasive interventions and lack of exclusive breastfeeding are the major risk factors of LOS. The clinical signs and symptoms are varied and subtle. The mean C-reactive protein in the hospital-acquired group was significantly higher as compared to the community-acquired group. There is substantial morbidity and mortality, resulting in an increased toll on resources, therefore, an aggressive preventive and treatment approach is recommended for late onset sepsis., (© The Author(s) [2023]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Staphylococcus aureus bloodstream infection (SAB) is a common and severe infection. This study aims to describe temporal trends in numbers, epidemiological characteristics, clinical manifestations, and outcomes of SAB., Methods: We performed a post-hoc analysis of three prospective SAB cohorts at the University Medical Centre Freiburg between 2006 and 2019. We validated our findings in a large German multi-centre cohort of five tertiary care centres (R-Net consortium, 2017-2019). Time-dependent trends were estimated using Poisson or beta regression models., Results: We included 1797 patients in the mono-centric and 2336 patients in the multi-centric analysis. Overall, we observed an increasing number of SAB cases over 14 years (6.4%/year and 1000 patient days, 95% CI: 5.1% to 7.7%), paralleled by an increase in the proportion of community-acquired SAB (4.9%/year [95% CI: 2.1% to 7.8%]) and a decrease in the rate of methicillin-resistant-SAB (-8.5%/year [95% CI: -11.2% to -5.6%]). All of these findings were confirmed in the multi-centre validation cohort (6.2% cases per 1000 patient cases/year [95% CI: -0.6% to 12.6%], community-acquired-SAB 8.7% [95% CI: -1.2% to 19.6%], methicillin-resistant S. aureus-SAB -18.6% [95% CI: -30.6 to -5.8%]). Moreover, we found an increasing proportion of patients with multiple risk factors for complicated/difficult-to-treat SAB (8.5%/year, 95% CI: 3.6% to 13.5%, p < 0.001), alongside an overall higher level of comorbidities (Charlson comorbidity score 0.23 points/year, 95% CI: 0.09 to 0.37, p 0.005). At the same time, the rate of deep-seated foci such as osteomyelitis or deep-seated abscesses significantly increased (6.7%, 95% CI: 3.9% to 9.6%, p < 0.001). A reduction of in-hospital mortality by 0.6% per year (95% CI: 0.08% to 1%) was observed in the subgroup of patients with infectious diseases consultations., Discussion: We found an increasing number of SAB combined with a significant increase in comorbidities and complicating factors in tertiary care centres. The resulting challenges in securing adequate SAB management in the face of high patient turnover will become an important task for physicians., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: The Japanese Respiratory Society (JRS) atypical pneumonia score is a useful tool for the rapid presumptive diagnosis of atypical pneumonia. We investigated the clinical features of community-acquired pneumonia (CAP) due to Chlamydia psittaci and validated the JRS atypical pneumonia score in patients with C. psittaci CAP., Methods: This study was conducted at 30 institutions and assessed a total of 72 sporadic cases with C. psittaci CAP, 412 cases with Mycoplasma pneumoniae CAP, and 576 cases with Streptococcus pneumoniae CAP., Results: Sixty-two of 72 patients with C. psittaci CAP had a history of avian exposure. Among the six parameters of the JRS score, matching rates of four parameters were significantly lower in the C. psittaci CAP than the M. pneumoniae CAP in the following parameters: age <60 years, no or minor comorbid illness, stubborn or paroxysmal cough, and absence of chest adventitious sounds. The sensitivity of the diagnosis of atypical pneumonia in patients with C. psittaci CAP was significantly lower than the M. pneumoniae CAP (65.3% and 87.4%, p < 0.0001). When the diagnostic sensitivity was analyzed for different ages, the diagnostic sensitivities for the C. psittaci CAP were 90.5% for non-elderly patients and 30.0% for elderly patients., Conclusions: The JRS atypical pneumonia score is a useful tool for distinguishing between C. psittaci CAP and bacterial CAP in patients aged <60 years, but not in patients aged ≥60 years. A history of avian exposure in middle-aged patients with normal white blood cell count may be suggestive of C. psittaci pneumonia., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Introduction: Omadacycline is a new analog of the tetracycline class active against atypical bacteria, as well as against staphylococci, including methicillin-resistant strains, and Streptococcus pneumoniae ., Areas Covered: This review has summarized the available clinical evidence on the use of oral omadacycline in the treatment of community-acquired pneumonia (CAP) and described the mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) parameters in healthy and special populations and the latest research on omadacycline., Expert Opinion: The available clinical evidence on oral omadacycline for the treatment of CAP shows that its properties provide reliable empirical coverage for pathogens such as Haemophilus influenzae , Moraxella catarrhalis , and species of Legionella , Chlamydia , and Mycoplasma . Omadacycline is also active against methicillin-resistant Staphylococcus aureus (MRSA); penicillin-resistant and multidrug-resistant Streptococcus pneumoniae , Streptococcus pyogenes , and Streptococcus agalactiae ; and vancomycin-resistant Enterococcus spp. A dose of 450 mg orally once daily is recommended, followed by a maintenance dose of 300 mg orally once daily. Importantly, omadacycline does not require dose adjustment for patients based on BMI, age, gender, or renal or hepatic impairment.

Background: Community-acquired bacterial meningitis is a rare but severe central nervous system infection that may be associated with cerebrovascular complications (CVC). Our objective is to assess the prevalence of CVC in patients with community-acquired bacterial meningitis and to determine the first-48 h factors associated with CVC., Methods: We analyzed data from the prospective multicenter cohort study (COMBAT) including, between February 2013 and July 2015, adults with community-acquired bacterial meningitis. CVC were defined by the presence of clinical or radiological signs (on cerebral CT or MRI) of focal clinical symptom. Factors associated with CVC were identified by multivariate logistic regression., Results: CVC occurred in 128 (25.3%) of the 506 patients in the COMBAT cohort (78 (29.4%) of the 265 pneumococcal meningitis, 17 (15.3%) of the 111 meningococcal meningitis, and 29 (24.8%) of the 117 meningitis caused by other bacteria). The proportion of patients receiving adjunctive dexamethasone was not statistically different between patients with and without CVC (p = 0.84). In the multivariate analysis, advanced age (OR = 1.01 [1.00-1.03], p = 0.03), altered mental status at admission (OR = 2.23 [1.21-4.10], p = 0.01) and seizure during the first 48 h from admission (OR = 1.90 [1.01-3.52], p = 0.04) were independently associated with CVC., Conclusions: CVC were frequent during community-acquired bacterial meningitis and associated with advanced age, altered mental status and seizures occurring within 48 h from admission but not with adjunctive corticosteroids., (© 2023. The Author(s).)

Background: To have country-wide information about multidrug resistance (MDR) in isolates from community-acquired urinary tract infections (CAUTI) of Turkey, in terms of resistance rates and useful options., Methods: We used a geocode standard, nomenclature of territorial units for statistics (NUTS), and a total of 1588 community-acquired isolates of 20 centres from 12 different NUTS regions between March 2019 and March 2020 were analysed., Results: Of the 1588 culture growths, 1269 (79. 9%) were Escherichia coli and 152 (9.6%) were Klebsiella spp. Male sex, advancedage, and having two or more risk factors showed a statistically significant relation with MDR existence (p < 0.001, p: 0.014, p < 0.001, respectively) that increasing number of risk factors or degree of advancing in age directly affects the number of antibiotic groups detected to have resistance by pathogens. In total, MDR isolates corresponded to 36.1% of our CAUTI samples; MDR existence was 35.7% in E. coli isolates and 57.2% in Klebsiella spp. isolates. Our results did not show an association between resistance or MDR occurrence rates and NUTS regions., Discussion: The necessity of urine culture in outpatient clinics should be taken into consideration, at least after evaluating risk factorsfor antibacterial resistance individually. Community-acquired UTIs should be followed up time- and region-dependently. Antibiotic stewardship programmes should be more widely and effectively administrated.

Background: Streptococcus pneumoniae continues to be an important bacterial pathogen associated with invasive (e.g. bacteraemia, meningitis) and non-invasive (e.g. community-acquired respiratory tract) infections worldwide. Surveillance studies conducted nationally and globally assist in determining trends over geographical areas and allow comparisons between countries., Objectives: To characterize invasive isolates of S. pneumoniae in terms of their serotype, antimicrobial resistance, genotype and virulence and to use the serotype data to determine the level of coverage by different generations of pneumococcal vaccines., Methods: SAVE (Streptococcus pneumoniae Serotyping and Antimicrobial Susceptibility: Assessment for Vaccine Efficacy in Canada) is an ongoing, annual, national collaborative study between the Canadian Antimicrobial Resistance Alliance (CARE) and the National Microbiology Laboratory, focused on characterizing invasive isolates of S. pneumoniae obtained across Canada. Clinical isolates from normally sterile sites were forwarded by participating hospital public health laboratories to the Public Health Agency of Canada-National Microbiology Laboratory and CARE for centralized phenotypic and genotypic investigation., Results: The four articles in this Supplement provide a comprehensive examination of the changing patterns of antimicrobial resistance and MDR, serotype distribution, genotypic relatedness and virulence of invasive S. pneumoniae obtained across Canada over a 10 year period (2011-2020)., Conclusions: The data highlight the evolution of S. pneumoniae under pressure by vaccination and antimicrobial usage, as well as vaccine coverage, allowing both clinicians and researchers nationally and globally to view the current status of invasive pneumococcal infections in Canada., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease., Methods: National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis., Findings: Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years)., Interpretation: Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy., Funding: China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Omadacycline is approved in the United States for the treatment of patients with community-acquired bacterial pneumonia or acute bacterial skin and skin structure infections. Analyses were undertaken to evaluate pharmacokinetic differences among subjects or patients stratified by comorbidities. Differences in clearance by smoking status, history of diabetes mellitus, chronic lung disease, hypertension, heart failure, or coronary artery disease were evaluated using a Welch two-sample t test. Smoking was the only significant comorbidity after correction for sex, with a clinically insignificant difference of 13%. Omadacycline dose adjustments based on these comorbidities do not appear to be warranted.

Introduction: The bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins., Methods: We present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival., Results: We found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models., Discussion: These findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens., Competing Interests: FV and JPR report research funding outside the scope of the present study by bioMérieux. FV reports two patents pending in antimicrobial resistance detection. FV, JL and J-PR report shares in Weezion. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2023 Pivard, Bastien, Macavei, Mouton, Rasigade, Couzon, Youenou, Tristan, Carrière, Moreau, Lemoine and Vandenesch.)

Background: The 2019 Infectious Disease Society of America (IDSA) guidelines for the management of community-acquired bacterial pneumonia encourage the identification of locally validated risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa to guide empiric therapy decisions for patients with community-acquired pneumonia (CAP). The guidelines urge clinicians to perform local validation to determine prevalence and risk factors pertinent to their institution. Objective: To determine the percentage of community-acquired pneumonia caused by multidrug-resistant organisms (MDROs) and assess risk factors potentially associated with multidrug-resistant organisms CAP at our hospital. Methods: This was a retrospective case control study analyzing patients admitted to the 344-bed community hospital with bacterial community-acquired pneumonia between January 1, 2019 and December 31, 2019. Univariate analysis and multivariate regression were performed to assess potential risk factors for MDRO pathogens. Results: MDROs were isolated in 41.3% of patients with culture-positive CAP (n=19/46), and 3.6% of patients with microbiological culture data within 48 hours of admission (19/527). Among patients with culture-positive CAP, hospitalization in the previous 90 days and receipt of antibiotics in the previous 90 days occurred more frequently in MDRO patients than non-MDRO patients (37% vs 11%, P =.032). No risk factors reached statistical significance in the multivariate regression. There were no differences in clinical outcomes between MDRO and non-MDRO patients. Conclusions: This study demonstrated a low overall prevalence of MDRO pathogens in patients with CAP. Potential risk factors for MDRO included hospitalization within the past 90 days and antibiotic use within the past 90 days.

Objectives: To assess the aetiology, clinical features, diagnostic studies and outcomes of community-acquired pneumonia (CAP) in a French cohort of hospitalized kidney transplant recipients., Methods: We performed a retrospective, multicentre study in kidney transplant recipients admitted to ten French centres for CAP from January 2016 to December 2018. CAP discharge diagnoses were clinically and radiologically validated. We assessed a descriptive analysis of all confirmed CAP including medical ward and intensive care unit admissions., Results: One hundred sixty-five CAP episodes in 132 patients were included. Median time from transplantation to admission was 6.4 (interquartile range, 1.6-12.3) years, with corticosteroid exposure in 112/165 (67.9%) cases. Sputum culture was performed in 47/165 (28.5%) cases including 7/47 (14.9%) positive samples. Bronchoscopy was performed in 87/165 (52.7%) cases with pathogens identified in 39/87 (44.8%) cases. Microbiological studies led to identifying a respiratory pathogen in 64/165 (38.8%) CAP episodes including 11/64 (17.2%) polymicrobial cases. Among these 64 episodes, 75 microorganisms were identified; 46/75 (61.3%) were core respiratory pathogens and 29/75 (38.7%) were opportunistic or drug-resistant organisms including Pneumocystis jirovecii 9/75 (12%), Pseudomonas aeruginosa 5/75 (6.7%), multidrug-resistant Enterobacteriaceae 4/75 (5.3%), and Aspergillus 4/75 (5.3%). Patients required intensive care unit admission in 26/165 (15.8%) episodes, invasive ventilation in 20/165 (12.1%) cases, and 22/165 (13.3%) needed in-hospital dialysis., Discussion: CAP episodes occurred in kidney transplant recipients with a long history of immunosuppressive drug exposure. Diagnostic studies identified a microorganism in more than one-third of CAP episodes, including drug-resistant and opportunistic pathogens., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Nasopharyngeal swabs are taken to determine the causative agent of community acquired pneumonia (CAP), while the reliability of upper respiratory tract sampling as a proxy for lower respiratory tract infections is still unclear., Methods: Nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid samples and clinical data were collected from 153 hospitalized children between 3 months and 14 years of age with severe CAP, enrolled from March to June 2019. Written informed consent for the storage and use of the samples for further studies was obtained from the parents or caregivers. Putative pathogens were detected using a sensitive, high-throughput GeXP-based multiplex PCR and qPCR., Results: The same bacterial species in paired samples were found in 29 (23.4%) and the same viral species in 52 (27.5%) of the patients. moderate concordance was found for Mycoplasma pneumoniae (ĸ=0.64), followed by Haemophilus influenzae (ĸ=0.42). The strongest discordance was observed for human adenovirus and also for Pseudomonas aeruginosa, the latter was exclusively detected in BAL samples. In the adenovirus cases strong concordance was associated with high viral loads in the NP swabs., Conclusion: The variation in concordance in pathogen detection in the upper and lower respiratory tract of children with severe pneumonia is generally high but varies depending on the species. Novel and impactful insights are the concordance between NP and BAL detection for M. pneumoniae and H. influenzae and the strong correlation between high adenoviral loads in NP swabs and detection in BAL fluid., (© 2023. The Author(s).)

Introduction: Omadacycline is approved for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and soft tissue infection (ABSSSI). The integration of newer agents into clinical use involves understanding the nuances of clinical decision-making. This review will provide an in-depth focus on omadacycline in clinical practice., Areas Covered: Literature review of omadacycline utilizing PubMed was performed to provide a comprehensive evaluation of omadacycline pharmacology, microbiology, registrational Phase 3 clinical trials, and post-marketing clinical studies. In addition, the immunomodulatory and other attributes of tetracycline class of antibiotics, of which omadacycline is a member, are reviewed, introducing the concept of antibiotic selection with attention to the bacterial pathogen and human host relationship., Expert Opinion: Omadacycline builds upon the favorable attributes of tetracycline antibiotics and provides very reliable empiric coverage for both Staphylococcus aureus and Streptococcus spp. Clinicians require a more robust understanding of antibiotics, including omadacycline, in order to optimize patient outcomes, streamline care, and reduce medical costs.

Objectives: To assess whether having a pet in the home is a risk factor for community-acquired urinary tract infections associated with extended-spectrum β-lactamase (ESBL)- or AmpC β-lactamase (ACBL)- producing Enterobacterales., Methods: An unmatched case-control study was conducted between August 2015 and September 2017. Cases (n = 141) were people with community-acquired urinary tract infection (UTI) caused by ESBL- or ACBL-producing Enterobacterales. Controls (n = 525) were recruited from the community. A telephone questionnaire on pet ownership and other factors was administered, and associations were assessed using logistic regression., Results: Pet ownership was not associated with ESBL- or ACBL-producing Enterobacterales-related human UTIs. A positive association was observed for recent antimicrobial treatment, travel to Asia in the previous year, and a doctor's visit in the last 6 months. Among isolates with an ESBL-/ACBL-producing phenotype, 126/134 (94%) were Escherichia coli, with sequence type 131 being the most common (47/126)., Conclusions: Companion animals in the home were not found to be associated with ESBL- or ACBL-producing Enterobacterales-related community-acquired UTIs in New Zealand. Risk factors included overseas travel, recent antibiotic use, and doctor visits., Competing Interests: Conflict of interest The authors have no conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Antimicrobial resistance and emerging spectrum-β-lactamase (ESBL) infections are a rising concern in public health. Despite the increasing prevalence of community-acquired (CA) ESBL-E. coli UTIs, there is little data on the antibiotic resistance profiles of this bacterial strain in the pediatric population. We review antibiotic resistance profile and rising trend in pediatric ESBL-E. coli UTI presentation at our pediatric hospital., Methods: This retrospective study reviewed data drawn from the infectious disease database at our pediatric hospital for all patients whose urine culture grew ESBL-E. coli from 01/2015 to 01/2021. Demographic information and antimicrobial susceptibility test results for ESBL-E. coli isolates from CA-UTIs were collected. Annual changes in resistance to antimicrobial agents and average annual percent change in ESBL-E. coli UTI presentation over the study period are reported., Results: From 01/2015 to 01/2021, 6403 urine cultures at our hospital grew E. coli. Of these, 169 urine cultures from 135 children grew ESBL-E. coli. The study population was 57% male (77) with a mean age of 6.9 ± 6.2 years and multiethnic. CA-UTI by ESBL-producing E. coli accounted for 2.62% of total E. coli UTIs within the study period and increased from 0.97% in 2015 to 3.54% in 2020 by an average of 0.51% each year., Conclusions: These findings demonstrate an increase in CA-ESBL E. coli UTIs in children. We observed most isolates demonstrated multidrug resistance. As CA-ESBL E. coli UTIs are associated with prolonged hospitalization and increased morbidity, our findings highlight the rising trend in pediatric CA-ESBL E. coli UTI., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: This study aimed to evaluate the demographics, clinical characteristics, risk factors, and antibiotic resistance of pediatric community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing and non-ESBL-producing uropathogens., Methods: This retrospective study was conducted at a tertiary care hospital in Saudi Arabia, among children aged between 0 and 14 years, with a culture-proven diagnosis of community-acquired UTI between February 2019 and September 2021. Patients were divided into two groups based on whether or not their UTI was caused by ESBL-producing bacteria., Results: A total of 383 patients with community-acquired UTI were evaluated. Escherichia coli was detected in 72.6% of cultures. Extended-spectrum beta-lactamase-producing organisms were responsible for 35.7% of UTI episodes. Of these 69% and 31% were caused by E. coli and Klebsiella pneumoniae, respectively. There were no significant differences between the two groups with regard to clinical presentation or urine analysis. The resistance rates in the ESBL-producing group were 39.4% for amoxicillin/clavulanic acid, 65.7% for ciprofloxacin, 72.3% for co-trimoxazole, 32.8% for nitrofurantoin, 21.2% for gentamicin, and 0.7% for amikacin and carbapenems. In the non-ESBL-producing group, it was 22.4% for amoxicillin/clavulanic acid, 22.4% for ciprofloxacin, 38.2% for co-trimoxazole, 23.6% for nitrofurantoin, 6.1% for gentamicin, and zero for amikacin and carbapenems. The presence of renal abnormalities (p = 0.014) and male gender (p = 0.026) were determined to be independent risk factors for ESBL UTIs., Conclusions: Recognizing risk factors and antibiotic resistance for ESBL-producing bacteria may aid in tailoring an antibiotic regimen for pediatric patients at high risk of ESBL-UTIs., (© 2023 Japan Pediatric Society.)

Background: In this study, we aimed to investigate the results of intraoperative culture and antibiogram in children who underwent surgery with the diagnosis of community-acquired intraabdominal infections (CA-IAIs) to determine the causative microorganisms and antibiotic susceptibility of the bacterial agents., Methods: Antibiotic susceptibility of isolated bacteria was investigated with disk diffusion method according to EUCAST (European Committee on Antimicrobial Susceptibility Testing) suggestions directly from the patients' intraabdominal peritoneal fluid or tissues, aged <18 years., Results: Bacterial growth was found in 17 (34%) of the blood cultures taken before the operation and 38 (76%) of the intraoperative abdominal cultures. According to the isolated strains; 44 (80%) were Gram-negative and 11 (20%) were Gram-positive, however, the most commonly isolated microorganisms were Escherichia coli (52.72%), Klebsiella pneumonia (14.54%), and Enterobacter cloacae (5.45%); extended-spectrum beta-lactamase (ESBL) resistance was detected in 12 of the Escherichia coli strains (41.38%) and the rates of ampicillin-sulbactam, ceftriaxone, and cefotaxime resistance were 43.2%, 40.9%, and 6.8%, respectively., Conclusion: In our study, ESBL-resistant gram-negative microorganisms in CA-IAIs presented as primary agents to be considered. Ampicillin-sulbactam, ceftriaxone and cefotaxime should not be preferred in the monotherapy of complicated CA-IAIs due to their high resistance rates, but they can be combined with aminoglycosides. Quinolones can be included in the treatment because of their low resistance rates. It is considered that routine intraoperative culture and evaluation of antibiotic susceptibility in complicated CA-IAIs will provide an insight into the outcomes of empirical treatment., Key Words: Antimicrobial resistance, Intraabdominal infection, Surgery.

Community-acquired pneumonia (CAP) is a serious clinical concern. A lack of accurate diagnosis could hinder pathogen-directed therapeutic strategies. To solve this problem, we evaluated clinical application of nested multiplex polymerase chain reaction (PCR) in children with severe CAP. We prospectively enrolled 60 children with severe CAP requiring intensive care between December 2019 and November 2021 at a tertiary medical center. Nested multiplex PCR respiratory panel (RP) and pneumonia panel (PP) were performed on upper and lower respiratory tract specimens. We integrated standard-of-care tests and quantitative PCR for validation. The combination of RP, PP, and standard-of-care tests could detect at least one pathogen in 98% of cases and the mixed viral-bacterial detection rate was 65%. The positive percent agreement (PPA), and negative percent agreement (NPA) for RP were 94% and 99%; the PPA and NPA for PP were 89% and 98%. The distribution of pathogens was similar in the upper and lower respiratory tracts, and the DNA or RNA copies of pathogens in the lower respiratory tract were equal to or higher than those in the upper respiratory tract. PP detected bacterial pathogens in 40 (67%) cases, and clinicians tended to increase bacterial diagnosis and escalate antimicrobial therapy for them. RP and PP had satisfactory performance to help pediatricians make pathogenic diagnoses and establish therapy earlier. The pathogens in the upper respiratory tract had predictive diagnostic values for lower respiratory tract infections in children with severe CAP., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: The prevalence of community-acquired methicillin-resistant S. aureus (CA-MRSA) has been increasing worldwide. We aimed to investigate the prevalence of MRSA in community-acquired S. aureus infections, the risk factors for CA-MRSA infection and the clinical features of CA-MRSA., Methods: A multi-center study with prospective and retrospective sections was conducted. Patients ≥ 3 months old and ≤18 years of age who were diagnosed with community-acquired S. aureus infections were included in this study and the patients` information were reviewed from the medical and microbiological database of the hospital. A standard question form about living conditions and exposure risk factors was administered to the parents of patients. The CA-MRSA infections were compared with the methicillin-susceptible S. aureus (CAMSSA) infections in terms of the queried risk factors and clinical variables., Results: We identified 334 pediatric patients with S. aureus infection, 58 (17.4%) had an infection with CAMRSA. The refugee rate was higher in the CA-MRSA group. There was no significant difference regarding the exposure risk. The treatment modalities and outcomes were similar., Conclusions: The study was not able to show reliable clinical variables or epidemiological risk factors except for being a refugee for CA-MRSA infections. Empirical antibiotic treatment should therefore be determined according to the local CA-MRSA prevalence in patients presenting with a possible staphylococcus infection.

All modern advances notwithstanding, pneumonia remains a common infection with substantial morbidity and mortality. Understanding of the etiology of pneumonia continues to evolve as new techniques enable identification of already known organisms and as new organisms emerge. We now review the etiology of pneumonia (at present often called "community-acquired pneumonia") beginning with classic bacteriologic techniques, which identified Streptococcus pneumoniae as the overwhelmingly common cause, to more modern bacteriologic studies, which emphasize Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Enterobacteriaceae , Pseudomonas, and normal respiratory flora. Urine antigen detection is useful in identifying Legionella and pneumococcus. The low yield of bacteria in recent studies is due to the failure to obtain valid sputum samples before antibiotics are administered. The use of high-quality sputum specimens enables identification of recognized ("typical") bacterial pathogens as well as a role for commensal bacteria ("normal respiratory flora"). Nucleic acid amplification technology for viruses has revolutionized diagnosis, showing the importance of viral pneumonia leading to hospitalization with or without coinfecting bacterial organisms. Quantitative PCR study of sputum is in its early stages of application, but regular detection of high counts of bacterial DNA from organisms that are not seen on Gram stain or grown in quantitative culture presents a therapeutic dilemma. This finding may reflect the host microbiome of the respiratory tract, in which case treatment may not need to be given for them. Finally, host transcriptional signatures might enable clinicians to distinguish between viral and bacterial pneumonia, an important practical consideration.

Introduction: Community acquired pneumonia (CAP) is a leading cause of under-five mortality in India and Streptococcus pneumoniae is the main bacterial pathogen for it. Pneumococcal Conjugate Vaccine 13 (PCV13) has been introduced in a phased manner, in the national immunization program of India since 2017/2018. The primary objective of this study was to evaluate the effectiveness of PCV13 on chest radiograph (CXR)-confirmed pneumonia, in children hospitalized with WHO-defined severe CAP., Methods: This prospective, multi-site test-negative study was conducted in a hospital-network situated in three districts of Northern India where PCV13 had been introduced. Children aged 2-23 months, hospitalized with severe CAP and with interpretable CXR were included after parental consent. Clinical data was extracted from hospital records. CXRs were interpreted by a panel of three independent blinded trained radiologists. Exposure to PCV13 was defined as ≥2 doses of PCV13 in children aged ≤ 12 months and ≥ 1 dose(s) in children > 12 months of age. Our outcome measures were CXR finding of primary endpoint pneumonia with or without other infiltrates (PEP±OI); vaccine effectiveness (VE) and hospital mortality., Results: From 1st June 2017-30th April 2021, among 2711 children included, 678 (25.0%) were exposed to PCV1. CXR positive for PEP±OI on CXR was found in 579 (21.4%), of which 103 (17.8%) were exposed to PCV. Adjusted odds ratio (AOR) for PEP±OI among the exposed group was 0.69 (95% CI, 0.54-0.89, p = 0.004). Adjusted VE was 31.0% (95% CI: 11.0-44.0) for PEP±OI. AOR for hospital mortality with PEP±OI was 2.65 (95% CI: 1.27-5.53, p = 0.01)., Conclusion: In severe CAP, children exposed to PCV13 had significantly reduced odds of having PEP±OI. Since PEP±OI had increased odds of hospital mortality due to CAP, countrywide coverage with PCV13 is an essential priority., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright: © 2022 Awasthi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This study aimed to observe the impact of the coronavirus disease 2019 (COVID-19) pandemic on the incidence of non-COVID-19 community-acquired pneumonia (CAP) in Shenzhen of China, offering new ideas for evaluating the effects of non-pharmaceutical interventions., Methods: A retrospective analysis was conducted of inpatients with pneumonia from 2017 to 2021. Epidemiological characteristics of CAP and effects from the COVID-19 pandemic were analyzed by the basic characteristics, time distribution, etiology and disease burden., Results: There were a total of 5746 CAP inpatient cases included from 2017 to 2021. The number of CAP hospitalizations decreased during the pandemic from 2020 to 2021, with seasonal variations of being higher in spring and winter and lower in summer and autumn, whereas it was prevalent throughout the year prior to the pandemic. The children group decreased significantly during the pandemic, with a 15% decrease in the share of CAP inpatients. The detection rates of bacteria and mycoplasma decreased in CAP patients, while the detection rate of the virus increased, and the number of moderate and severe cases reduced more than that of the mild., Conclusion: Non-pharmaceutical interventions from COVID-19 have led to a decrease in the number of CAP inpatients, especially for children, with a specific seasonal prevalence in spring and winter, when the prevention interventions should be strengthened further for adults during the pandemic., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The human bocavirus (HBoV) is an agent of upper and lower respiratory infections, affecting mainly children under 5 years of age. Community-acquired pneumonia (CAP) is an important public health problem in developing countries, representing one of the main causes of hospitalizations and deaths in children. The aim of this study was to describe the prevalence of HBoV and the clinical and epidemiological characteristics in children diagnosed with CAP. For this purpose, nasopharyngeal aspirates were collected from 545 children aged 0 to 60 months diagnosed with CAP between January 2013 and December 2014 in a reference pediatric hospital in Fortaleza, Ceará, Brazil. The samples were subjected to PCR for detection of HBoV and parainfluenza 4 (PIV4) and indirect immunofluorescence for detection of respiratory syncytial virus (RSV), adenovirus (AdV), influenza A and B (FLU A and FLU B), and parainfluenza 1, 2, and 3 (PIV1, PIV2, PIV3). Clinically, most CAP were non-complicated (487/545; 89.3%); however, 10.7% (58/545) of children were treated in the ICU/resuscitation sector. Among the total samples analyzed, 359 (65.8%) were positive for at least one virus surveyed and 105 (19.2%) samples had two or more viruses. HBoV was detected in 87 samples (15.9%), being the second most prevalent virus. RSV, AdV, FLU A, FLU B, and PIV 1-3 were detected in 150 (27.5%), 45 (8.2%), 30 (5.5%), 3 (0.5%), and 131 (24%) samples, respectively. The age average was 12.1 months in children infected with HBoV, and the most frequent symptoms were dyspnea and cough. In addition, 90.6% of HboV-positive children received antibiotics as empirical treatment. HBoV did not show any circulation pattern; however, it seemed to be more frequent in the first half of the year, totaling 68.9% of the cases. HBoV is a frequent agent of pneumonia in the child population studied., (© 2022. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Objectives: The usefulness of routine microbiological testing for rationalising antibiotic use in hospitalised patients with community-acquired pneumonia (CAP) continues to be a subject of debate. We aim to determine the effect of positive microbiological testing on antimicrobial de-escalation and clinical outcomes in CAP., Methods: A retrospective analysis of a prospectively collected cohort of non-immunosuppressed adults hospitalised with CAP was performed. The primary study outcome was antimicrobial de-escalation. Secondary outcomes included 30-day case-fatality rate, adverse events, and CAP recurrence. Adjustment for confounders was performed by inverse probability weighting propensity score, logistic regression, and cause-specific Cox model., Results: Of 3677 patients with CAP, 1924 (52.3%) had any positive microbiological test. Antimicrobial de-escalation was performed in 648/1924 (33.7%) of patients with positive microbiological testing and in 179/1753 (10.2%) of those with non-positive results. When propensity score was entered into the multivariate analysis, positive microbiological testing (adjusted OR (AOR)], 2.59; 1.96-3.41) and clinical stability at day 3 (AOR 1.87; 1.45-2.10) were two of the main factors independently associated with antimicrobial de-escalation. After applying an adjusted cause-specific Cox model, antimicrobial de-escalation was not associated with a higher 30-day case-fatality rate (adjusted hazard ratio (AHR), 0.44 (95% CI, 0.14-1.43)), higher frequency of adverse events (AHR, 0.77 (95% CI, 0.53-1.12)), or CAP recurrence (AHR, 0.65 (95% CI, 0.35-1.14))., Discussion: Antimicrobial de-escalation was more often performed in hospitalised patients with CAP who had positive microbiological tests than in those with non-positive results, and it did not adversely affect relevant clinical outcomes., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)