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Prospective characterisation of drug-resistant bloodstream infections in Africa and Asia (ACORN2): a surveillance network assessment.

BACKGROUND: Antimicrobial resistance (AMR) is a major global health threat, but there is scarcity of laboratory surveillance data linked to clinical information to determine burden and inform interventions, especially from low-income and middle-income countries. The ACORN2 study sought to address this through prospective case-based surveillance in 19 hospitals across Africa and Asia to characterise drug-resistant infections by origin, clinical syndrome, patient age, outcome, and geographical location. METHODS: Patients were enrolled on selected wards and clinical data were collected daily for community-acquired infections (CAIs). Point prevalence surveys for hospital-acquired infections (HAIs) were conducted weekly. Mortality was assessed at discharge and after 28 days. Linked microbiology data were extracted from local laboratory databases. Primary descriptive analyses focused on WHO Global Antimicrobial Resistance and Use Surveillance System pathogen (target organism) bloodstream infections (BSIs). Comparisons were adjusted for clustering by site using random effects models. FINDINGS: Over 31 months, 41&#x2009;907 infections were characterised from 41&#x2009;032 admissions. Two-thirds were children (19&#x2009;351; 47&#xb7;2%) or neonates (6649; 16&#xb7;2%). There were marked differences in pathogen incidence and antibiotic resistance when clinical infections were stratified by patient age category and infection origin (CAI/HAI). The highest rates of target organism AMR BSI were third-generation cephalosporin-resistant (3GC-R) Escherichia coli (718&#xb7;56/100&#x2009;000 blood cultured infection episodes), meticillin-resistant Staphylococcus aureus (586&#xb7;89/100&#x2009;000 blood cultured infection episodes), and 3GC-R Klebsiella pneumoniae (364&#xb7;92/100&#x2009;000 blood cultured infection episodes). In-hospital mortality was 13&#xb7;1% (166/1265) in patients with target organism BSI versus 6&#xb7;2% (1357/21&#x2009;845) in those with negative blood cultures, p<0&#xb7;0001. INTERPRETATION: ACORN2 has shown practical implementation of collecting linked clinical-laboratory AMR data in low-income and middle-income countries and identified a significant burden of WHO GLASS BSI. Adoption of the ACORN2 approach at scale might enhance use of diagnostic microbiology and improve the volume of clinical data included in national and global AMR surveillance datasets. FUNDING: Wellcome.

Humans

Phage therapy for Klebsiella pneumoniae: Understanding bacteria-phage interactions for therapeutic innovations.

Klebsiella pneumoniae (KP) is a Gram-negative bacterium that commonly resides in the human gastrointestinal tract and can also act as an opportunistic pathogen and cause extra-intestinal infections. KP poses a global health threat because it causes both hospital- and community-acquired infections in immune-competent and immunocompromised hosts. These infections can be multidrug-resistant and/or hypervirulent, making KP infections difficult to treat and deadly. In the absence of effective treatments for recalcitrant KP infections, bacteriophage (phage) therapy is gaining attention as a promising alternative. In this review, we evaluate KP epidemiology and epitope diversity, discuss interactions between KP-targeting phages and their bacterial hosts from an eco-evolutionary perspective, and summarize recent efforts in phage therapy for treating KP infections. We also discuss novel approaches, including genetic engineering and machine learning, as initial steps toward developing KP-targeting phage therapy as a precision medicine approach for an emerging and dangerous pathogen.

Phage Therapy

Emerging food- and waterborne pathogen Arcobacter in wastewater: diversity and antibiotic resistance.

Arcobacter spp. are emerging food- and waterborne pathogens frequently detected in wastewater. Despite their high abundance in wastewater, Arcobacter diversity, antibiotic resistance, and genomic traits remain poorly characterized. To address these knowledge gaps, we conducted a comprehensive study of Arcobacter spp. in influent, effluent, and activated sludge from a Finnish wastewater treatment plant using full-length 16S rRNA gene sequencing, isolate-based genomics, and phenotypic antibiotic susceptibility testing. Arcobacter spp. were highly abundant in raw sewage but substantially removed during treatment. Four Arcobacter species were identified, dominated by Arcobacter cryaerophilus and Arcobacter suis. A proportion of amplicon sequence variants unclassified to species-level revealed potentially unexplored Arcobacter diversity. For the first time, we observed intragenomic variability in 16S rRNA gene copies of A. cryaerophilus, highlighting the importance of integrating culture-based and culture-independent approaches. Phenotypic testing revealed high proportions of non-wild-type isolates for clinically relevant antibiotics, including ampicillin, cefotaxime, tetracycline, and erythromycin. Genomic analyses showed that antibiotic resistance profiles were primarily mediated by chromosomally encoded determinants, including &#x3b2;-lactamases, efflux systems, and point mutations. Additionally, a broad arsenal of chromosomal and plasmid-borne resistance genes to heavy metals, biocides, and organic solvents was detected, reflecting adaptations to the wastewater environment. These findings provide novel insights into Arcobacter species-level diversity, resistance mechanisms, and ecological adaptations in anthropogenically influenced environments. The study highlights the significance of Arcobacter for public health and establishes a foundation for further research.IMPORTANCEArcobacter spp. are emerging human and animal pathogens that exhibit increasing resistance to clinically relevant antibiotics. Most community-acquired infections are linked to exposure through contaminated food and water, yet studies investigating their occurrence and diversity in wastewater remain scarce. Here, we focus on wastewater as an abundant source of Arcobacter spp. and a potential dissemination route contributing to downstream contamination of surface waters, irrigated soils, and possibly the food chain. By characterizing the species-level diversity, genomic traits, and antibiotic resistance profiles of Arcobacter spp. in wastewater, this study provides critical insights into the ecology and epidemiology of this ubiquitous genus.

Arcobacter

Genomic, virulent and phenotypic characterization of a cerebrospinal fluid-derived ST86-KL2 hypervirulent Klebsiella pneumoniae isolate from a patient with meningitis and diabetes mellitus.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKP) is an important cause of invasive community-acquired infection, particularly in individuals with diabetes mellitus. However, cerebrospinal fluid (CSF)-derived hvKP isolates, especially those belonging to the ST86-KL2 lineage, remain poorly characterized at the integrated clinical, genomic, and phenotypic levels. METHODS: A K. pneumoniae isolate, designated BP9811, was recovered from the CSF of a patient with meningitis and diabetes mellitus and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and 16&#xa0;S rRNA sequencing. Antimicrobial susceptibility testing and whole-genome sequencing were performed to define its resistance, virulence, sequence type (ST), capsular type, and plasmid content. Virulence was evaluated using the Galleria mellonella infection model. In addition, interaction with human cerebral microvascular endothelial cells was preliminarily assessed using adhesion, gentamicin protection, and transmission electron microscopy assays, together with measurement of relative ompA transcription by reverse transcription-quantitative polymerase chain reaction. Comparative phylogenetic analyses were performed using publicly available CSF-derived and KL2 K. pneumoniae genomes. RESULTS: BP9811 was identified as a hypermucoviscous ST86-KL2 hvKP isolate that remained susceptible to all tested antimicrobial agents. Whole-genome sequencing revealed an IncHI1B virulence plasmid carrying canonical hvKP-associated determinants, including rmpA/rmpA2, peg-344, iucABCD, and iroBCD. In the Galleria mellonella model, BP9811 showed high virulence comparable to that of the hypervirulent reference strain NTUH-2044. In HCMEC/D3 cells, BP9811 exhibited increased adhesion and intracellular recovery under the tested conditions, and transmission electron microscopy confirmed bacterial internalization. BP9811 also showed higher ompA transcript levels than the control strain. Phylogenetic analysis indicated that BP9811 was genetically distinct from currently available CSF-derived isolates and occupied a related branch within the KL2 population. CONCLUSIONS: This study provides an integrated clinical, genomic, and phenotypic characterization of BP9811, a CSF-derived ST86-KL2 hvKP isolate recovered from a patient with meningitis and diabetes mellitus. BP9811 carried a canonical hvKP virulence plasmid, displayed marked virulence-associated phenotypes, and showed enhanced interaction with human cerebral microvascular endothelial cells in vitro under the tested conditions. These findings expand the limited isolate-level evidence on central nervous system-associated hvKP and provide a basis for future comparative and mechanistic studies.

Humans

Investigating the zoonotic origins of ESBL-producing E. coli in community-acquired urinary tract infections in Ecuador.

Extended-spectrum &#x3b2;-lactamase-producing Escherichia coli (ESBL-producing E. coli) pose a growing global health threat. Although Latin America has been identified as a global hotspot of antimicrobial resistance, the zoonotic contribution to drug-resistant infections in the region remains poorly defined. We analyzed 137 clinical ESBL-producing E. coli isolates from urinary tract infections (UTIs) in Quito, Ecuador, applying a Bayesian latent class model informed by host-associated mobile genetic elements to estimate the fraction of infections attributable to food-animal sources. We estimated that 25.5% (35/137) of UTI isolates were putative zoonotic cases. This proportion rose to 42.5% after excluding ST131-H30, a human-associated pandemic lineage. Putative zoonotic isolates were enriched for animal-associated &#x3b2;-lactamase genes (e.g., blaTEM-1B, blaCTX-M-65), lacked human-associated markers such as blaOXA-1, and exhibited diverse antimicrobial resistance gene profiles resembling those observed among food-animal isolates. These isolates were also enriched for ColV-associated virulence genes typically linked to avian pathogenic E. coli. Putative zoonotic strains contributed substantially to third-generation cephalosporin-resistant UTIs in Quito, Ecuador, challenging assumptions derived from high-income settings that such infections are driven predominantly by human-to-human transmission. These findings highlight the importance of integrated One Health surveillance and mitigation, particularly in low- and middle-income countries where gaps in water, sanitation, and hygiene (WASH) may interact with antimicrobial use in food production to amplify antimicrobial resistance transmission.IMPORTANCEESBL-producing E. coli have rapidly emerged as a major global antimicrobial resistance threat. In Latin America, cephalosporins are commonly used in food-animal production, fueling the emergence of ESBL-producing E. coli. In low- and middle-income countries, excessive antimicrobial use driven by poorly regulated over-the-counter sales, combined with inadequate water, sanitation, and hygiene (WASH) infrastructure, can facilitate antimicrobial-resistant pathogen transmission from food animals to humans. Using a novel statistical-genomic approach, we found that over one in four cephalosporin-resistant UTIs in Quito, Ecuador, may be caused by E. coli strains originating from food animals. Our findings highlight the public health risks associated with antimicrobial use in food-animal production and the role of environmental and infrastructure-related vulnerabilities. As global demand for animal protein continues rising in middle-income countries, controlling zoonotic antimicrobial resistance transmission becomes increasingly urgent for protecting human health through integrated One Health strategies.

ESBL-producing E. coli

Methicillin-resistant Staphylococcus aureus (MRSA) infection in hospitalized patients is dominated by community-acquired strains: genomic epidemiological evidence.

OBJECTIVE: This study aimed to systematically investigate the molecular epidemiological characteristics of methicillin-resistant Staphylococcus aureus (MRSA) in Ningxia hospitals, to elucidate their genetic evolutionary relationships, and to delineate the genomic and phenotypic profiles of the dominant lineages. METHODS: Clinical isolates of MRSA strains collected between 01/01/2024 and 30/06/2024 were analyzed, employing second-generation gene sequencing technology, combined with MLST and SCCmec typing, along with evaluation of drug resistance and virulence genes. A phylogenetic tree was constructed to analyze strain homology. RESULTS: A total of 74 non-duplicate Staphylococcus aureus strains (67 MRSA and 7 MSSA) were collected. The most common clonal strain was ST59-IVa, accounting for 46.27%. This strain exhibited a high prevalence of resistance genes mecA and blaZ, at 91.04%. All five ST22-IVa strains were found to lack mecA and erm genes but showed &#x3b2;-lactam resistance, while possessing both lukS/F-PV (PVL) and tsst-1 virulence genes, indicating a significant toxicity risk. Genetic evolution analysis revealed that ST3355, ST4513, and ST59 were closely related, all belonging to SCCmec types IVa; the other ST types exhibited mutations at various loci, with ST5 as the central node, resulting in a wider array of ST and SCCmec typing. CONCLUSION: The ST59-IVa clone is the predominant MRSA strain in Ningxia hospitals, exhibiting multidrug resistance and virulence gene profiles consistent with national trends. However, the emergence of hypervirulent ST22-IVa strains with atypical resistance mechanisms warrants increased vigilance. We recommend enhancing the rational use of antibiotics in hospitals and implementing molecular surveillance for these highly virulent strains.

Methicillin-Resistant Staphylococcus aureus

Trends of serotypes and resistance among Streptococcus pneumoniae in the UK and Ireland (1999-2019).

OBJECTIVES: This study aimed to report the serotype distribution of Streptococcus pneumoniae isolates from UK and Irish patients with bacteraemia or community-associated lower respiratory tract infections (CA-LRTI). Depending upon the year, these were from 23 to 39 sentinel laboratories and were collected between 1999 and 2019, thus spanning the introduction of pneumococcal conjugate vaccines, PCV7 and PCV13. METHODS: Pneumococcal identification, susceptibility testing and serotyping were undertaken by a central laboratory. Changes in serotype distributions and among the predominant types showing antibiotic non-susceptibility were reviewed in relation to vaccine deployment. RESULTS: Following the introduction of PCV7 (2006) and PCV13 (2010), major shifts occurred in serotype prevalence for both bacteraemia and CA-LRTI. PCV7 types and most PCV13 types (but not 3 and 19A) were largely or wholly displaced. Many of the displaced types (e.g. 6B, 9V, 14, 19F and 23B) had been internationally prevalent and were associated with antibiotic resistance. Other serotypes-many included within the older pneumococcal polysaccharide vaccine, PPV23-expanded into the space, with serotype 8 becoming especially prominent in bacteraemia, though not respiratory infections. Further increasingly prevalent types included 9N, 10A, 12F and 22F. Serotype 15A, often multi-resistant, rose then fell in relative importance after deployment of PCV13. Among the currently most prevalent types, serotype 3 is rarely resistant to agents besides tetracyclines and bloodstream serotype 8 isolates mostly are fully susceptible. CONCLUSIONS: These data offer a comparison of serotypes associated with bacteraemia and respiratory disease over two decades in the UK and Ireland.

Humans

The British Society for Antimicrobial Chemotherapy Resistance Surveillance Project: methods and limitations.

OBJECTIVES: The BSAC Bacteraemia and Respiratory Resistance Surveillance Programmes provided long-term surveillance of antibiotic resistance in key pathogens of bloodstream and both community- and hospital-acquired respiratory infections in the UK and Ireland. This paper details the methodologies used. Data limitations are discussed. METHODS: Sentinel laboratories across the UK and Ireland contributed up to a fixed annual quota of isolates of defined bacterial groups. For each Programme, a Central Laboratory confirmed bacterial identifications, measured MICs by the BSAC agar dilution method, investigated mechanisms of resistance and determined serotypes of Streptococcus pneumoniae. Identification methods evolved over time, e.g. with adoption of MALDI-TOF. Classification of susceptibility and resistance follows the 2022 (not contemporaneous) EUCAST guidance. RESULTS: Seventy-nine laboratories contributed 30&#x200a;716 community respiratory isolates from 1999/2000 to 2018/19; 65 laboratories contributed 13&#x200a;508 hospital respiratory isolates from 2008/09 to 2018/19; 81 laboratories contributed 56&#x200a;064 bacteraemia isolates from 2001 to 2019. Although large and teaching hospitals were over-represented, the resistance rates for bacteraemia organisms collected in England mirror more extensive (but less standardized or detailed) national data gathered from laboratories by the UK Health Security Agency and its predecessor organizations, which provided a bespoke data extract. CONCLUSIONS: These surveillance Programmes have provided comprehensive and reliable information on antibiotic susceptibility in the UK and Ireland over two decades. Detailed results, showing resistance trends and mechanisms of antibiotic resistance, are presented in five papers in this Supplement.

Antimicrobial Stewardship

Genomic analysis of community-associated multidrug-resistant Klebsiella quasipneumoniae subsp. similipneumoniae and the identification of the ST2059-KL1 clone in the U.S.

UNLABELLED: Klebsiella quasipneumoniae subsp. similipneumoniae is an important member of the K. pneumoniae species complex (KpSC) and is increasingly reported as multidrug-resistant (MDR) in healthcare- and community-associated infections. Since clinical laboratories do not routinely distinguish K. quasipneumoniae subsp. similipneumoniae from K. pneumoniae, national prevalence estimates, particularly for MDR, are lacking. In this study, a total of 2,006 community-associated MDR KpSC isolates were collected from 42 U.S. states, with 30 K. quasipneumoniae subsp. similipneumoniae isolates originating from 12 states identified using whole genome sequencing. All isolates were resistant to ceftriaxone and exhibited high rates of resistance to other antimicrobial agents, including ampicillin-sulbactam (56.7%, 17/30), levofloxacin (75.9%, 22/29), and trimethoprim-sulfamethoxazole (53.3%, 16/30). Notably, five isolates were also carbapenem-resistant. Genomic analysis resolved 10 sequence types (STs), with ST2059 (n = 13) and ST414 (n = 9) predominating. Ceftriaxone resistance in most isolates (90%, 27/30) was conferred by an extended-spectrum &#x3b2;-lactamase gene, predominantly blaCTX-M-15 (73.3%, 22/30); the remaining isolates carried either a carbapenemase (blaKPC-3) or an AmpC &#x3b2;-lactamase (blaCMY-2). Nanopore sequencing identified blaCTX-M-15 harbored on two types of IncFIB(Kpn3) antimicrobial resistance (AMR) plasmids, either with or without the conjugative tra gene cluster. Interestingly, the KL1 locus, associated with canonical hypervirulent K. pneumoniae strains, was detected in all ST2059 isolates. Further analysis of public genomic data showed that the KL1 locus is widely distributed across KpSC. KL1 phylogenetic analyses indicated frequent intrasubspecies recombination but limited intersubspecies exchange of KL1. The identification of the dominant MDR K. quasipneumoniae subsp. similipneumoniae KL1-ST2059 clone in the U.S. underscores the importance of ongoing genomic surveillance. IMPORTANCE: Klebsiella quasipneumoniae subsp. similipneumoniae is an underrecognized member of the Klebsiella pneumoniae species complex that is frequently misidentified in clinical laboratories, leading to an incomplete understanding of its role in antimicrobial resistance. In this study, we used large-scale genomic surveillance of community-associated multidrug-resistant isolates across the U.S. to identify this subspecies as a reservoir of clinically relevant resistance plasmids. Notably, we detected a widely distributed ST2059 lineage carrying the K1 capsular locus, a feature traditionally associated with hypervirulent K. pneumoniae. These findings highlight the convergence of resistance and virulence-associated traits in an overlooked species and underscore the need for genomic surveillance to monitor emerging high-risk lineages in community settings.

Drug Resistance, Multiple, Bacterial

Antimicrobial resistance among agents of community-associated lower respiratory tract infection in the UK and Ireland: trends from 1999/2000 to 2018/2019.

OBJECTIVES: The BSAC Respiratory Surveillance Programme examined resistance trends among Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis from patients with community-acquired lower respiratory tract infection (CA-LRTI). METHODS: Quotas of isolates were sought per collecting site from 1999/00 to 2018/19; an annual October start date captured winter infection peaks within single years. MIC testing was by BSAC agar dilution. &#x3b2;-Lactamase detection with nitrocefin and pneumococcal serotyping by classical methods or WGS. RESULTS: Resistances were uncommon, except that &#x3b2;-lactamases occurred in c. 20% of H. influenzae from 2012/13 following earlier rises, and in >90% of M. catarrhalis throughout. Only 0.11% (12/10881) of S. pneumoniae were fully resistant to penicillin; co-amoxiclav inhibited 97.8% of 13526 H. influenzae and >99.9% of 6309 M. catarrhalis isolates. Cefotaxime inhibited >99% of all isolates at breakpoint, as did relevant fluoroquinolones in the fewer years tested. Tetracycline inhibited >98% of H. influenzae and M. catarrhalis and 85% of S. pneumoniae. Significant shifts were: (i) fluctuating resistances to tetracyclines, macrolides and penicillin in pneumococci, reflecting serotype replacements; (ii) expansion, from 2012/13, in the proportion of H. influenzae with &#x3b2;-lactamase-independent amoxicillin/co-amoxiclav resistance; and (iii) increasing high-level amoxicillin resistance (MIC &#x200a;>&#x200a;64&#x2005;mg/L) among &#x3b2;-lactamase-positive H. influenzae. MIC differentials were seen for cephalosporins between &#x3b2;-lactamase-positive and &#x3b2;-lactamase-negative M. catarrhalis, greatest (512-fold) for ceftaroline. CONCLUSIONS: CA-LRTI remains eminently treatable, yet shifts are occurring in the serotypes of S. pneumoniae most associated with resistance and in the nature of amoxicillin resistance in H. influenzae. &#x3b2;-Lactamase-related cephalosporin MIC differentials for M. catarrhalis are striking but their clinical significance remains uncertain.

Humans

Metagenomic-based quantification of Pseudomonas aeruginosa burden links microbiome collapse to mortality in severe community-acquired pneumonia.

BACKGROUND: Severe community-acquired pneumonia (sCAP) remains a major cause of mortality in critically ill patients, Pseudomonas aeruginosa (P. aeruginosa) is a frequent pathogen associated with poor prognosis in this population. While metagenomic next-generation sequencing (mNGS) is widely used for pathogen detection, its value in quantifying pathogen abundance and linking it to lung microbiome alterations remains unclear. OBJECTIVES: This study investigated the association between P. aeruginosa abundance quantified by mNGS and lung microbiome alterations and clinical outcomes in sCAP patients. METHODS: This multicenter retrospective study included 130 patients with sCAP caused by P. aeruginosa from five hospitals (September 2021-June 2025). Patients were stratified into low, medium, and high abundance groups according to mNGS-derived reads per ten million (RPTM) values of P. aeruginosa. Lung microbiome diversity and community structure were analyzed, and differences between groups were assessed using appropriate statistical methods. The association between P. aeruginosa abundance and clinical outcomes was evaluated using correlation analysis, sankey diagram, receiver operating characteristic curve, grey zone analysis and logistic regression. RESULTS: A total of 130 patients with sCAP due to P. aeruginosa were stratified into low, medium, and high abundance groups based on mNGS-derived RPTM value. Microbial diversity decreased progressively with increasing abundance, and community structures differed significantly among groups (all P&#x2009;<&#x2009;0.05). P. aeruginosa became increasingly dominant, accounting for up to 95.99% of the microbiota in the high abundance group. Higher P. aeruginosa abundance was associated with increased disease severity, including longer mechanical ventilation, prolonged hospital stay, and higher 28-day mortality. Sankey diagram showed a progressive decline in treatment effectiveness and an increase in mortality with increasing P. aeruginosa abundance. P. aeruginosa_RPTM showed moderate predictive value for mortality (AUC&#x2009;=&#x2009;0.761, Sens&#x2009;=&#x2009;69.40%, Spec&#x2009;=&#x2009;75.30%, cutoff: 41122, grey zone: 2287-220339) and remained independently associated with 28-day mortality in multivariable analysis [2.219 (1.509 to 3.262), P&#x2009;<&#x2009;0.001]. CONCLUSION: In patients with sCAP, higher P. aeruginosa_RPTM measured by mNGS was associated with reduced lung microbiome diversity and unfavorable clinical outcomes. RPTM-based risk stratification may help identify patients at increased risk of poor prognosis.

Humans

The spatial and temporal distribution of Staphylococcus aureus along a tropical Hawaiian watershed.

Staphylococcus aureus is a leading cause of community-acquired skin and soft-tissue infections worldwide. One major route of exposure is recreating in marine waters, but knowledge is limited regarding the drivers of S. aureus in surface waters that discharge into marine environments. This study explores spatial and temporal distributions of S. aureus, including antimicrobial-resistant and virulence genes, using both culture-dependent and molecular techniques across a tropical Hawaiian watershed with a gradient of human influence. Negative binomial generalized linear mixed models revealed that the interaction between spatial and temporal factors was the strongest predictor of S. aureus and associated genes. Cultured S. aureus was highest at mid-watershed sites in summer, which included a popular swimming hole, suggesting human shedding as a significant source. Molecular detection of S. aureus (femA gene) yielded concentrations two orders of magnitude higher than cultured concentrations and peaked at estuarine sites with the greatest nutrients and water residence times. In the winter at upstream sites with no public access, staphylococci antibiotic-resistant (mecA) and S. aureus virulence gene (etb) were elevated, indicating highly pathogenic S. aureus strains in surface waters may originate from zoonotic sources. Our findings indicate that human and zoonotic sources contribute antibiotic-resistant and virulent S. aureus to watersheds, with streams facilitating environmental transmission to marine waters. This watershed-scale assessment enables the prediction of spatial and temporal conditions associated with elevated S. aureus concentrations, thereby reducing exposure and infections.

Staphylococcus aureus

Factors associated with positive blood cultures in children in nine African and Asian countries: the ACORN2 surveillance network.

BACKGROUND: Blood culture (BC) in children has relatively low diagnostic yield and high contamination rates, limiting cost-effectiveness. We aimed to determine readily available baseline characteristics to identify hospitalised children with a likelihood of higher diagnostic yield in low- and middle-income countries. METHODS: We used data from ACORN2, a prospective clinical surveillance network including 19 hospitals across Africa and Asia. We included participants <18 years, hospitalised for a suspected infection, prescribed parenteral antibiotics and with a BC sample. Sociodemographic and clinical data were recorded for each infection episode and linked to routine microbiology data. We described true pathogen (non-contaminant) BC positivity proportion and performed mixed-effects logistic regression, with study site and patient as the random effect, to identify factors associated with BC positivity. RESULTS: Of the 26 407 paediatric infection episodes, 17 815 (67%) had a BC sample and 15 384 were included in the analysis. BC results were: true pathogens in 689 (4.5%), contaminants in 1399 (9%) and uncertain pathogens in 143 (0.9%). In the multivariable model, factors associated with a positive BC were age (29 days-12-month-olds OR 1.33, 95% CI 1.06 to 1.66 and 5-18 year-olds OR 1.62, 95% CI 1.30 to 2.01 vs 1-4 year-olds), number of clinical severity signs (OR 1.29, 95% CI 1.18 to 1.40 per one sign) and hospital acquired infection (OR 3.05, 95% CI 2.30 to 4.06 vs community-acquired). Suspected diagnosis of sepsis (OR 2.09, 95% CI 1.67 to 2.61), gastrointestinal/abdominal (OR 2.36, 95% CI 1.78 to 3.13), skin and soft tissue or bone (OR 3.64, 95% CI 2.57 to 5.14) and genitourinary infection (OR 2.22, 95% CI 1.39 to 3.56) were more likely to have a positive BC, compared with respiratory infections. CONCLUSION: We confirmed the low BC yield among hospitalised children. We identified groups for which diagnostic stewardship efforts to increase BC uptake should be prioritised and others in which it could be limited in times of financial or logistic constraints.

Humans

Genomic characterization of methicillin-resistant Staphylococcus aureus isolated from patients attending regional referral hospitals in Tanzania.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization increases the risk of subsequent infection by MRSA strain complex interlinking between hospital and community-acquired MRSA which increases the chance of drug resistance and severity of the disease. OBJECTIVE: Genomic characterization of Staphylococcus aures strains isolated from patients attending regional referral hospitals in Tanzania. METHODOLOGY: A laboratory-based cross-sectional study using short read-based sequencing technology, (Nextseq550,Illumina, Inc. San diego, California, USA). The samples used were collected from patients attending selected regional referral hospitals in Tanzania under the SeqAfrica project. Sequences were analyzed using tools available in the center for genomic and epidemiology server, and visualization of the phylogenetic tree was performed in ITOL 6.0. SPSS 28.0 was used for statistical analysis. RESULTS: Among 103 sequences of S. aureus, 48.5% (50/103) carry the mecA gene for MRSA. High proportions of MRSA were observed among participants aged between 18 and 34 years (52.4%), in females (54.3%), and among outpatients (60.5%). The majority of observed MRSA carried plasmids rep5a (92.0%), rep16 (90.0%), rep7c (90.0%), rep15 (82.0%), rep19 (80.0%) and rep10 (72.0%). Among all plasmids observed rep5a, rep16, rep20, and repUS70 carried the blaZ gene, rep10 carried the erm(C) gene and rep7a carried the tet(K) gene. MLST and phylogeny analysis reveal high diversity among MRSA. Six different clones were observed circulating at selected regional hospitals and MRSA with ST8 was dominant. CONCLUSION: The study reveals a significant presence of MRSA in Staphylococcus aureus strains from Tanzanian regional hospitals, with nearly half carrying the mecA gene. MRSA is notably prevalent among young adults, females, and outpatients, showing high genetic diversity and dominance of ST8. Various plasmids carrying resistance genes indicate a complex resistance profile, highlighting the need for targeted interventions to manage MRSA infections in Tanzania.

Humans

From decline to resurgence: current perspectives on Mycoplasma pneumoniae.

SUMMARYMycoplasma pneumoniae pneumonia (MPP) is an acute respiratory infection caused by Mycoplasma pneumoniae (MP) and constitutes the primary cause of community-acquired pneumonia (CAP) among children aged 5 years and older in China. The clinical manifestations of MP-associated respiratory disease in children are diverse, ranging from mild upper respiratory symptoms to life-threatening pneumonia. Notably, during the implementation of nonpharmaceutical interventions (NPIs) aimed at curbing SARS-CoV-2 transmission, there was a significant decline in MP infection rates. However, a pronounced global resurgence of MP infections was documented in 2023-2024. The increasing global prevalence of macrolide resistance, particularly in China, coupled with limited alternative antibiotic options for children, increasing rates of coinfections, and the absence of a preventive vaccine, collectively exacerbate treatment challenges and increase the disease burden. Furthermore, the insufficient availability of MP nucleic acid testing and antimicrobial resistance surveillance in primary healthcare settings, coupled with the absence of a comprehensive epidemiological monitoring network, results in a vicious public health cycle. Recent advances and emerging genomic data have provided new insights into its pathogenesis and clinical management. Therefore, in this narrative review, we aim to (i) synthesize the current understanding of the etiological characteristics of MP and the present status of MPP diagnosis and treatment; (ii) analyze recent advances and drivers behind the global resurgence of MP infections; and (iii) propose integrated prevention and control strategies to increase the recognition of MPP and prevent unanticipated outbreaks.

Humans

The agroenvironmental-clinical link of Proteus mirabilis: Genomic epidemiology, clonal relationships, and shared resistance and virulence profiles.

Proteus mirabilis is an opportunistic pathogen frequently associated with urinary tract infections (UTIs), with its pathogenicity driven by coordinated virulence traits such as adhesion, biofilm formation, and toxin production. The systemic emergence of antimicrobial resistance (AMR) within this species raises critical concerns regarding its persistence across clinical and environmental niches. This study investigated the virulence profiles, AMR determinants, and molecular epidemiology of P. mirabilis isolates recovered from retail vegetables and human community-acquired UTIs (CA-UTIs) in southern Brazil. A total of 310 isolates were analyzed (110 from vegetables and 200 from UTIs). Multidrug resistance was observed in 36.6-42.0% of vegetable isolates and 16.0% of UTI isolates, while extended-spectrum &#x3b2;-lactamase (ESBL) production reached 32.0% in the vegetable group. Notably, the carbapenemase gene blaKPC-2 was identified in vegetable isolates, representing a critical food safety concern. High-consequence resistance genes, including blaCTX-M variants, fosA3, and qnrD, were widely distributed. Furthermore, all isolates harbored multi-element virulence profiles-particularly genes encoding fimbriae, proteases, and iron acquisition systems-and exhibited strong or very strong biofilm-forming phenotypes. Clonal analysis revealed tight genetic relatedness between vegetable and clinical isolates, including indistinguishable profiles. Whole-genome sequencing identified shared sequence types (STs), most notably the high-risk clone ST773, alongside internationally reported lineages such as ST135 and ST336. Moreover, conserved mobile genetic environments flanking blaKPC-2 were structurally characterized. These findings demonstrate that food-associated P. mirabilis serves as an active agroenvironmental reservoir for virulent and multidrug-resistant lineages, posing an unmonitored risk for zoonotic dissemination and human infection within the One Health framework.

bla KPC&#x2212;2

Cefoxitin versus cefotaxime as empirical treatment of spontaneous bacterial peritonitis in liver cirrhotic patients: randomized controlled clinical trial.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhosis requiring immediate empirical antibiotic therapy. Third-generation cephalosporins are the traditional agents of choice; however, increasing clinical failure rates necessitate the evaluation of alternative antibiotics to ensure optimal therapeutic outcomes. The aim was to investigate the efficacy of cefoxitin versus cefotaxime for SBP treatment. METHODS: A randomized clinical trial was conducted on 140 cirrhotic patients with community-acquired SBP at Al-Rajhy Liver University Hospital, Assiut, Egypt. Patients were randomized to receive either cefotaxime (n&#x200a;=&#x200a;70) or cefoxitin (n&#x200a;=&#x200a;70), 2&#x2005;g every 8&#x2005;h for 5&#x2005;days. Polymorphonuclear neutrophil (PMN) counts were measured upon admission, on Day 2 and on Day 5. Clinical response rates at Days 2 and 5, development of hepatorenal syndrome, length of stay and mortality were assessed. RESULTS: According to intention-to-treat analysis, clinical response rates at Day 2 were 74.2% in the cefotaxime group and 80% in the cefoxitin group, while at Day 5, they were 71.4% and 74.3%, respectively (P&#x200a;=&#x200a;0.704). The PMN counts at Days 0, 2 and 5 showed no significant differences between the cefotaxime and cefoxitin groups (P&#x200a;=&#x200a;0.889, 0.909 and 0.360, respectively). The incidence of hepatorenal syndrome was 7.1% in the cefotaxime group compared with 8.6% in the cefoxitin group (P&#x200a;=&#x200a;0.753), and mortality was 15.7% and 12.9%, respectively (P&#x200a;=&#x200a;0.629). CONCLUSIONS: Cefoxitin showed comparable effectiveness to cefotaxime but may be utilized in selected clinically stable SBP patients.

Humans