Severe Infections Research Articles

Inflammatory Markers as Predictors of Orbital Infection Severity

Purpose: To assess the utility of inflammatory marker levels in defining orbital cellulitis (OC) severity. Methods: A retrospective cohort study was conducted at 2 tertiary care centers using a medical record search of billing codes from January 1, 2000 to January 1, 2023. Patients were categorized into 2 cohorts—uncomplicated OC and OC with complication [subperiosteal abscess (SPA), orbital abscess (OA), or cavernous sinus thrombosis (CST)]. Values at presentation of the following markers were recorded: absolute neutrophil count (ANC), white blood cell count (WBC), platelet count, C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR). Logistic regression, controlled for immunosuppression and age, compared levels between patients with uncomplicated OC versus OC with complication, surgical versus nonsurgical management, and abnormal versus normal presenting and final vision. Results: A total of 785 patients—413 uncomplicated OC (52.6%) and 372 OC with complication (47.4%) (272 SPA [73.2%], 85 OA [22.8%], and 15 CST [4.0%])—met criteria. The sample was majority male (58.2%) and White (65.9%), with a mean age of 31.6 ± 26.4 years. Platelet count, ANC, WBC, and NLR levels were significantly higher in patients with complicated OC (p < 0.001). Levels of ANC, WBC, CRP, and NLR were significantly higher in surgical patients (p < 0.001). Higher levels of NLR and ANC were associated with worse visual acuity and an relative afferent pupillary defect at presentation (p = 0.006 and p = 0.032, respectively) but not at the final follow-up. Conclusions: Levels of NLR, ANC, and WBC at presentation may have clinical utility in identifying severe orbital infections and may aid management.

Post-Marketing Pharmacovigilance of Canakinumab from the FDA Adverse Event Reporting System (FAERS)

Background: Canakinumab, a humanized anti-IL-1β monoclonal antibody, is known for its ability to suppress IL-1β-mediated inflammation. However, continuous monitoring of its safety remains essential. Thus, we comprehensively evaluated the safety signals of canakinumab by data mining from FAERS. Methods: We used a disproportionate analysis to quantify canakinumab-related adverse events (AEs) using four algorithms. Clinical prioritization of the detected signals was assessed with a semiquantitative score method. Serious and non-serious outcomes were compared by statistical methods. Additionally, a stratification analysis of serious infections was conducted at the system organ class (SOC) level. Results: A total of 28,496 canakinumab-related AEs were collected, and 71 suspicious signals detected. Among these, 19 preferred terms (PTs) were identified as unexpected signals, including deafness, appendicitis, brain oedema, cushingoid, cellulitis, and papilledema. Of the AEs, 16 were more likely reported as serious outcomes, such as pneumonia, abdominal pain, deafness, and infection. Based on clinical priority score, 44 PTs were classified as weak, 27 as moderate, and none as strong. Furthermore, 30 PTs demonstrated a high level of evidence, primarily derived from FDA prescribing information, randomized controlled trials, and systematic reviews. Stratification analysis of infections and infestations (serious outcomes) revealed a stronger association of severe infections with canakinumab in older or heavier individuals. All positive signals followed an early failure pattern, with the incidence of canakinumab-associated AEs decreasing over time. Conclusions: We found that most of the suspicious signals were associated with infections. More attention should be paid to serious infections, particularly in males, individuals aged ≥60 years, or those weighing >100 kg, who demonstrated the highest risk of serious infections.

Severe pertussis infections in pediatric intensive care units: a multicenter study.

Pertussis can lead to severe complications and mortality in critically ill infants. Most severe pertussis occurred in young, unimmunized infants. Children admitted with pertussis with high CRP level, high WBC and lymphocyte, and cardiac and respiratory failure can need exchange blood transfusion. • Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis, which primarily affects infants. Despite vaccination efforts, pertussis remains a significant cause of morbidity and mortality in infants, particularly those too young to be fully vaccinated. • In pertussis, exchange blood transfusion may be considered in cases of severe pulmonary hypertension or cardiogenic shock, as indicated by echocardiographic findings, in conjunction with leukocytosis observed on laboratory tests.

State of type 2 diabetic Iraqi patients after hospitalization for COVID-19

Background The coronavirus-19 (COVID-19) pandemic, triggered by the severe acute respiratory syndrome coronavirus 2, has affected over 100 million people and killed around 2 million individuals. One of the most common chronic illnesses in the world is diabetes, which greatly raises the risk of hospitalization and death for COVID-19 patients. Objective This study aims to analyze the novel coronavirus's general characteristics and shed light on COVID-19 and its management in diabetic individuals by measuring some metabolic and inflammatory factors in type 2 diabetic patients with and without COVID-19. Methods One hundred Iraqi patients with type 2 diabetes mellitus (T2DM) were enrolled in the current study; 50 had COVID-19 with the Omicron variant, and 50 weren't. The diagnosis was designed by the consultant medical staff at the clinic. Eligible individuals had a positive nasal swab for reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 infection. They were compared with 50 healthy individuals as a control group. Every participant's anthropometric and clinical features were measured. The study includes the study groups’ glycemic, lipid profile, serum urea, and C-reactive protein (CRP) measurements. Results There were remarkable rises ( p < 0.05) in fasting and random blood glucose, serum lipid, and urea levels in diabetic patients with COVID-19 compared to those without COVID-19 and the control group. Also, a significant elevation ( p = 0.01) was found in fasting serum insulin among diabetic patients with COVID-19 as compared to those without COVID-19 and the control group (32.75 ± 8.63 vs. 25.82 ± 3.50 and 10.65 ± 1.12) µU/L, respectively. Serum CRP levels significantly increased ( p = 0.0001) in diabetic patients with COVID-19 compared to other groups. Conclusion Hyperglycemia, hyperinsulinemia, and dyslipidemia resulting from cytokine storm significantly increased the risk of hospitalization and death among coronavirus disease-19 patients. It has been concluded that T2DM reliably predicts morbidity among COVID-19 patients presenting with symptoms suggestive of severe hyperglycemia. The results also show the temporary and reversible deficiency in insulin secretion associated with severe acute respiratory syndrome coronavirus-2 infection. Consequently, it is recommended to examine variables of insulin sensitivity and pancreatic islet activity among patients with COVID-19 who have a history of diabetes.

Admittance to the intensive care unit due to acute odontogenic cervicofacial infections; a single centre retrospective cohort study.

The aim of this study is to assess the outcome of the patients who required intensive care unit (ICU) admittance after surgical drainage of an odontogenic cervicofacial infection and identify the variables that are able to predict severe infection or a high possibility of complications. This is a retrospective cohort study including all adult patients admitted to our hospital over the period 2011-2020 due to odontogenic cervicofacial infection and required ICU admittance. The study was approved by the hospital's scientific committee (no 814-9/8/2021). 51 patients were included (mean age 43.2 years). 11.7% of the patients had major comorbidities, such as diabetes or immunosuppression. At presentation, fever was recorded in 55% patients and trismus in 92.8%, with a mean delay from symptoms to hospital admission at 3 days. 23% of patients had a post-extraction infection, 61% pericoronitis and 15% other odontogenic infections. The mean duration of hospitalization was 9.16 days whereas the mean ICU length of stay was 3.76 days. 84.3% of patients showed improvement, 13.7% deteriorated with a need of reoperation and one death was reported. ICU length of stay was associated with an 89% reduced rate when positive microbe identification was feasible, whereas rate of complications was 4-fold higher in patients with prolonged ICU length of stay. Patients with deep cervicofacial odontogenic infections who require ICU management have a favourable clinical outcome. A minority of these patients will not improve in a short time frame or develop complications which require further management.

A Review of Emerging Evidence and Clinical Applications of Hyperbaric Oxygen Therapy

Background: Hyperbaric Oxygen Therapy (HBOT) is a medical treatment that involves administering 100% oxygen at increased atmospheric pressure to enhance oxygen delivery to tissues. Initially developed for decompression sickness, HBOT has since been utilized for a wide range of medical conditions, including severe infections, non-healing wounds, and, more recently, COVID-19. Objective: This review explores the historical development of HBOT, its principles, its emerging role in the management of and its outcome as treatment in COVID-19, particularly in mitigating inflammation, hypoxemia, and oxidative stress. Methods: A comprehensive review of the literature was conducted, analyzing case reports and case series that examined the effectiveness of HBOT in various clinical scenarios, with a focus on COVID-19. Results: HBOT has been shown to enhance tissue oxygenation, reduce inflammation, and modulate oxidative stress, thereby improving clinical outcomes in patients with severe COVID-19. The therapy's ability to increase dissolved oxygen levels in blood and tissues, independent of hemoglobin, makes it particularly beneficial in conditions like COVID-19, where hypoxemia and inflammation are prominent. Conclusion: HBOT offers a promising adjunctive treatment for severe COVID-19, with the potential to reduce mortality and improve recovery by targeting key pathophysiological processes such as hypoxemia, inflammation, and oxidative stress. Further research is warranted to optimize treatment protocols and confirm long-term benefits.

Predictors of developing severe COVID-19 among hospitalized patients: a retrospective study

BackgroundBased on the comparative statistical tests, patients with severe COVID-19 were statistically significantly associated with older age and had higher respiratory rate, longer hospital stay, and higher prevalence of diabetes than non-severe cases. This work aimed to explore risk factors for developing severe COVID-19 to enhance the quality of care provided to patients and to prevent complications.MethodsA retrospective study was conducted in Saudi Arabia’s eastern province, including all COVID-19 patients aged 18 years or older who were hospitalized at Prince Saud Bin Jalawi Hospital in July 2020. Comparative tests as well as both univariate and multivariate logistic regression analyses were performed to identify risk factors for developing severe COVID-19 and poor outcomes.ResultsBased on the comparative statistical tests patients with severe COVID-19 were statistically significantly associated with older age and had higher respiratory rate, longer hospital stay, and higher prevalence of diabetes than non-severe cases. They also exhibited statistically significant association with high levels of potassium, urea, creatinine, lactate dehydrogenase (LDH), D-dimer, and aspartate aminotransferase (AST). The univariate analysis shows that having diabetes, having high severe acute respiratory infection chest X-ray scores, old age, prolong hospitalization, high potassium and lactate dehydrogenase, as well as using insulin, heparin, corticosteroids, favipiravir or azithromycin were all statistically significant associated with severe COVID-19. However, after adjustments in the multivariate analysis, the sole predictor was serum LDH (p = 0.002; OR 1.005; 95% CI 1.002–1.009). In addition, severe COVID-19 patients had higher odds of being prescribed azithromycin than non-severe patients (p = 0.001; OR 13.725; 95% CI 3.620–52.043). Regarding the outcomes, the median hospital stay duration was statistically significantly associated with death, intensive care unit admission (ICU), and mechanical ventilation. On the other hand, using insulin, azithromycin, beta-agonists, corticosteroids, or favipiravir were statistically significantly associated with reduced mortality, ICU admission, and need of mechanical ventilation.ConclusionThis study sheds light on numerous parameters that may be utilized to construct a prediction model for evaluating the risk of severe COVID-19. However, no protective factors were included in this prediction model.

From pain to meningitis: bacteria hijack nociceptors to promote meningitis

Bacterial meningitis is a severe and life-threatening infection of the central nervous system (CNS), primarily caused by Streptococcus pneumoniae and Neisseria meningitidis. This condition carries a high risk of mortality and severe neurological sequelae, such as cognitive impairment and epilepsy. Pain, a central feature of meningitis, results from the activation of nociceptor sensory neurons by inflammatory mediators or bacterial toxins. These nociceptors, abundantly present in the meninges, trigger neuroimmune signaling pathways that influence the host immune response. However, the mechanisms by which bacteria hijack these nociceptors to promote CNS invasion and exacerbate the disease remain poorly understood. This review examines the interactions between bacteria and meningeal nociceptors, focusing on their direct and indirect activation via ion channels, such as transient receptor potential vanilloid-1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1), or through the release of neuropeptides like calcitonin gene-related peptide (CGRP). These interactions suppress immune defenses by inhibiting macrophage activity and neutrophil recruitment, thus facilitating bacterial survival and invasion of the CNS. Understanding this neuroimmune axis may open potential therapeutic targets for treating bacterial meningitis by enhancing host defenses and mitigating pain. Further research using advanced methodologies is essential to clarify the role of nociceptor-mediated immune modulation in this disease.

Impact on Mental Health Problems during Coxsackievirus Outbreak in the General Public: A Review

Coxsackievirus group B (CVB), a member of the Picornaviridae family and enterovirus genus, poses risks during pregnancy due to its potential to cause severe fetal and neonatal infections. Transmission primarily occurs through fecal–oral routes, with infections peaking mostly in warmer months. Vertical transmission to the fetus can lead to conditions such as myocarditis, encephalitis, and systemic neonatal disease, presenting clinically as severe myocardial syndromes and neurological deficits. Diagnostic challenges include detecting asymptomatic maternal infections and conducting in utero assessments using advanced techniques like RT-PCR from amniotic fluid samples should be encouraged. Morbidity and mortality associated with congenital CVB infections are notable. Current treatments are limited to supportive care, with emerging therapies showing promise but requiring further study for efficacy. Mental health impact due to this virus results in speech development failure and autistic feature. Future research should aim to fill knowledge gaps in epidemiology, improve diagnostic capabilities, and develop targeted interventions to enhance maternal and fetal outcomes and other health issues due to this virus.

Vitamin D, acute respiratory infections, and Covid-19: The curse of small-size randomised trials. A critical review with meta-analysis of randomised trials.

Randomised trials conducted from 2006 to 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, larger randomised trials published in 2022 did not confirm the health benefits of VDS in COVID-19 patients. To examine through a systematic review with meta-analysis the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and of randomised trials on VDS for the prevention of ARI. A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al. 2021. Groups were formed including trials with total numbers of patients below or above the median size of all trials. The associations between VDS vs no VDS, and admission to ICU were evaluated using random-effects models from which summary odds ratios (SOR) and 95% confidence intervals (CI) were obtained. Meta-analyses were done for all trials and for each group of trials, which allowed testing a possible effect modification of trial size. Publication bias was assessed using the Louis-Furuya-Kanaruori (LFK) index (no bias if index between -1 and +1) and the trim and fill method. Nine trials on VDS for preventing admission to ICU were identified, including 50 to 548 patients. The summary odds ratio (SOR) was 0.61 (95% CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (interaction p = 0.04). The LFK index was -3.79, and after trim and fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention included 25 to 16,000 patients. The SOR was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (interaction p = 0.0001). The LFK index was -3.11, and after trim and fill, the SOR was 0.96 (0.88-1.05). Strong publication bias affected small randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.

Characterization of the Prevalence and Antibiotic Resistance of Staphylococcus Species in an Exercise Facility in Central Kentucky, USA

The spread of methicillin-resistant Staphylococcus aureus (MRSA) in community settings, including fitness/exercise centers, remains relevant for public health. MRSA, a cause of severe infections in some, can be transmitted through shared equipment and skin contact. Understanding its prevalence and the frequency of antibiotic resistance in such environments can be useful for informing hygiene and intervention strategies. For investigating, multiple environmental swabs were collected from 14 different sites within a fitness facility, including equipment and locker rooms. Samples were collected for characterizing the prevalence of staphylococci (including MRSA), E. coli, and carbapenem-resistant Enterobacterales (CRE). Isolated colonies were identified biochemically and evaluated for antibiotic resistance. Logistic regression was applied to assess risk across different surfaces. Among 42 samples, the highest prevalence of Staphylococcus spp. was on locker room surfaces. S. aureus was prevalent on locker room floors and benches. Non-S. aureus species, such as S. saprophyticus and S. haemolyticus, were common. Resistance to oxacillin and penicillin was widespread, particularly among non-S. aureus species. E. coli was detected once, and CRE was not detected. Fitness center surfaces can harbor staphylococci, including MRSA. The results obtained corroborate other studies finding notable antibiotic resistance among staphylococci from fitness center surfaces. Hygiene improvements, including personal hygiene actions, are essential for reducing transmission risks.

SARS-CoV-2 excretion and genetic evolution in nasopharyngeal and stool samples from primary immunodeficiency and immunocompetent pediatric patients

BackgroundPrimary Immunodeficiency disorders (PID) can increase the risk of severe COVID-19 and prolonged infection. This study investigates the duration of SARS-CoV-2 excretion and the genetic evolution of the virus in pediatric PID patients as compared to immunocompetent (IC) patients.Materials and methodsA total of 40 nasopharyngeal and 24 stool samples were obtained from five PID and ten IC children. RNA detection was performed using RT-qPCR, and whole-genome sequencing was conducted with the NexSeq 1000 platform. Data analysis used the nextflow/viralrecon pipeline. Hotspot amino acid frequencies were investigated using GraphPad Prism v10. Phylodynamic analysis was conducted with BEAST software.ResultsIn IC children, the viral excretion period lasted up to 14 days in nasopharyngeal swabs, with an average duration of 7 days, and ranged from 7 to 14 days in stool samples. In PID patients, the viral RNA was detected in nasopharyngeal for periods between 7 and 28 days, with an average duration of 15 days, and up to 28 days in stool samples. Two SARS-CoV-2 variants were detected in PID patients: Delta (AY.122) and Omicron (BA.1.1). Patients with antibody and combined deficiencies, exhibited the most prolonged shedding periods in both nasopharyngeal and stool samples and one patient presented complications and fatal outcome. Specific Hotspot amino acid changes were detected in PID: A2821V and R550H (ORF1ab).ConclusionOur findings underscore the prolonged excretion of SARS-CoV-2 RNA in patients with antibody and combined deficiencies. Thus, specialized care is essential for effectively managing PID patients.

Emphysematous pyelonephritis with rare and severe iliac vascular complications: a case report and review

Emphysematous pyelonephritis (EPN) is a rare but severe necrotizing infection often associated with diabetes, ureteral obstruction, and gas production in the renal parenchyma and perinephric area. This report describes a 54-year-old man with type 2 diabetes who presented with right lumbar pain and was diagnosed with EPN complicated by right ureteral calculi and perinephric gas accumulation. Despite initial improvement with fluid resuscitation, antibiotics, and drainage, inadequate blood glucose control led to a worsening of the infection, eventually involving the psoas major muscle and iliac vessels. This progression resulted in the formation of an iliac aneurysm, which required endovascular surgery. The patient’s recovery was supported by proper blood glucose management and targeted antibiotic therapy. This case highlights the importance of early recognition, appropriate management, and strict glycemic control in preventing severe complications of EPN.

Group a Streptococcus remains viable inside fibrin clots and gains access to human plasminogen for subsequent fibrinolysis and dissemination.

Group A Streptococcus (GAS) is a human-specific bacterial pathogen that causes infections ranging in severity from mild to severe infections that can often be fatal. To protect the host, the innate immune system creates fibrin clots to trap bacteria and prevent deeper spread. GAS produces several factors that can initiate the dissolution of these fibrin clots to spread to deeper tissues, but we lack specific understanding of the timing of these events. Our studies demonstrate for the first time that GAS can delay their escape from fibrin clots to gain access to deeper tissues during infection, suggesting a key strategy that GAS utilize to cause more invasive disease.

Inpatient Hospitalizations for COVID-19 Among Patients With Prader-Willi Syndrome: A National Inpatient Sample Analysis.

Prader-Willi syndrome (PWS) is a genetic disorder associated with baseline respiratory impairment caused by multiple contributing etiologies. While this may be expected to increase the risk of severe COVID-19 infections in PWS patients, survey studies have suggested paradoxically low disease severity. To better characterize the course of COVID-19 infection in patients with PWS, this study analyses the outcomes of hospitalizations for COVID-19 among patients with and without PWS. The National Inpatient Sample, an all-payors administrative claims database of hospitalizations in the United States, was queried for patients with a coded diagnosis COVID-19 in 2020 and 2021. Hospitalizations for patients with PWS compared to those for patients without PWS using Augmented Inverse Propensity Weighting (AIPW). There were 295 (95% CI: 228-362) COVID-19 hospitalizations for individuals with PWS and 4,112,400 (95% CI: 4,051,497-4,173,303) for individuals without PWS. PWS patients had a median age of 33 years compared to 63 for those without PWS. Individuals with PWS had higher baseline rates of obesity (47.5% vs. 28.4%). AIPW models show that PWS diagnosis is associated with increased hospital length of stay by 7.43 days, hospital charges by $80,126, and the odds of mechanical ventilation and in-hospital death (odds ratios of 1.79 and 1.67, respectively). PWS patients hospitalized with COVID-19 experienced longer hospital stays, higher charges, and increased risk of mechanical ventilation and death. These results suggest that PWS should be considered a risk factor for severe COVID-19, warranting continued protective measures and vaccination efforts. Further research is needed to validate coding for PWS and assess the impact of evolving COVID-19 variants and population immunity on this vulnerable population.

Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19

The underlying mechanisms explaining the differential course of SARS-CoV-2 infection and the potential clinical consequences after COVID-19 resolution have not been fully elucidated. As a dysregulated mitochondrial activity could impair the immune response, we explored long-lasting changes in mitochondrial functionality, circulating cytokine levels, and metabolomic profiles of infected individuals after symptoms resolution, to evaluate whether a complete recovery could be achieved. Results of this pilot study evidenced that different parameters of aerobic respiration in lymphocytes of individuals recuperated from a severe course lagged behind those shown upon mild COVID-19 recovery, in basal conditions and after simulated reinfection, and they also showed altered glycolytic capacity. The severe groups showed trends to enhanced superoxide production in parallel to lower OPA1-S levels. Unbalance of pivotal mitochondrial fusion (MFN2, OPA1) and fission (DRP1, FIS1) proteins was detected, suggesting a disruption in mitochondrial dynamics, as well as a lack of structural integrity in the electron transport chain. In serum, altered cytokine levels of IL-1β, IFN-α2, and IL-27 persisted long after clinical recovery, and growing amounts of the latter after severe infection correlated with lower basal and maximal respiration, ATP production, and glycolytic capacity. Finally, a trend for higher circulating levels of 3-hydroxybutyrate was found in individuals recovered after severe compared to mild course. In summary, long after acute infection, mitochondrial and metabolic changes seem to differ in a situation of full recovery after mild infection versus the one evolving from severe infection.

Human bocavirus infections in paediatric patients in a tertiary care hospital in Kerala, India.

Human bocaviruses (HBoVs) can cause respiratory illness in young children. Although the first HBoV infection in India was reported in 2010, very little information is available about its prevalence, clinical features, or geographic distribution in this country. This study was conducted using 136 respiratory samples from paediatric patients in a tertiary care hospital in Kerala, 21 of which tested positive for HBoV1 and were further characterized through VP1/VP2 gene sequencing. We found that different strains of HBoV1 are co-circulating in the region and that HBoV1 can be detected in children with severe acute respiratory infections, either alone or coinfections with other pathogens, without any significant differences in their clinical characteristics.

Long, Synthetic Staphylococcus aureus Type 8 Capsular Oligosaccharides Reveal Structural Epitopes for Effective Immune Recognition.

Staphylococcus aureus is a Gram-positive bacterium that is responsible for severe nosocomial infections. The rise of multidrug-resistant strains, which can pose significant health threats, prompts the development of new treatment interventions, and much attention has been directed at the development of prophylactic and therapeutic vaccination strategies. Capsular polysaccharides (CPs) are key protective elements of the S. aureus cell wall and have been proposed as promising candidate antigens. Thirteen different CP serotypes have been identified to date, of which types 5 and 8 are the most prominent. CP8 is composed of trisaccharide repeating units that are built up from an N-acetyl-4-O-acetyl-β-d-mannosaminuronic acid, that carries a C-4-O-acetyl, an N-acetyl-α-d-fucosamine, and an N-acetyl-α-l-fucosamine. Synthetic oligosaccharides are valuable tools to unravel the immunogenicity of bacterial oligosaccharides at the molecular level. However, the rare monosaccharides, cis-glycosidic linkages, and O-acetylation represent significant challenges for the synthesis of CP8 fragments. Here the stereoselective assembly of well-defined CP8 fragments, comprising a trimer, hexamer, nonamer, and dodecamer, is presented. This is the first time that fragments larger than a single repeating trisaccharide, which has been proven to be insufficient for antigenic activity, have been assembled. Structural studies have revealed a linear conformation for the oligosaccharides, with each trisaccharide repeat tilted ∼90° with respect to the flanking repeats, which is stabilized by the acetyl groups that prevent rotation around the glycosidic linkages. The N-acetyl groups in each repeating unit point in the same direction, generating a hydrophobic flank in the trisaccharide repeats. We applied the oligomers to generate model glycoconjugate vaccine modalities, which we then used to raise anti-CP8 antibodies. The antibody interaction and immunization studies have revealed a clear length dependent structure-activity relationship for the oligosaccharides, with an oligosaccharide of at least three repeating units required for an adequate immune response.

Emerging carbapenem-resistant Klebsiella pneumoniae in a tertiary care hospital in Lima, Peru.

The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant public health threat, particularly in low- and middle-income countries (LMICs) with limited surveillance and treatment options. This study examines the genetic diversity, resistance patterns, and transmission dynamics of 66 CRKP isolates recovered over 5 years (2015-2019) after the first case of CRKP was identified at a tertiary care hospital in Lima, Peru. Our findings reveal a shift from blaKPC-2 to blaNDM-1 as the dominant carbapenemase gene after 2017. Lineage ST45 was the most prevalent and persisted for multiple years, followed by high-risk clones ST11 and ST147. The blaNDM-1 gene was carried almost exclusively by a Tn125-like transposon, similar to the one reported in previous studies from two Peruvian hospitals. Long-read sequencing revealed nearly identical blaNDM-carrying plasmids across the four assessed lineages. A comparative analysis of 1,023 South American CRKP genomes confirmed a unique pattern in Peru, where blaNDM-1 (81.4%) outpaced blaKPC-2, which remained dominant (59.4%) elsewhere. In addition, emerging clones ST45 and ST348 found in Peru were rarely found elsewhere in South America, suggesting potential regional adaptation. In conclusion, our study provides a comprehensive picture of the intra-hospital dynamics of these emerging pathogens and provides a framework for studying their genomic diversity in the understudied South American region.IMPORTANCEThis study provides novel insights into the transmission and genetic diversity of carbapenem-resistant Klebsiella pneumoniae, a bacteria responsible for severe infections, with limited treatment options. By examining isolates recovered over 5 years at a major hospital in Lima, Peru, we demonstrated a shift from one type of resistance gene, blaKPC, to another, blaNDM, which is more challenging to treat. Our findings reveal that specific bacterial lineages carrying the blaNDM gene in a specific plasmid are emerging in Peru, including well-known high-risk strains and others rarely found elsewhere in South America. This pattern highlights an urgent need for targeted surveillance and infection control as these strains pose a significant challenge to healthcare systems. Our study provides crucial data on Klebsiella pneumoniae in Peru, contributing to broader efforts to monitor and control antibiotic-resistant infections in South America and globally.

Pilot study of Clostridioides difficile infection (CDI) in hospitals, Italy, September to December 2022.

BackgroundClostridioides difficile infection (CDI) is a severe infection that needs to be monitored. This infection predominantly occurs in hospitalised patients after antimicrobial treatment, with high mortality in elderly patients.AimWe aimed at estimating the incidence of CDI in Italian hospitals over 4 months in 2022.MethodsWe estimated incidences of hospital-acquired CDI (HA-CDI), community or unknown CDI (CA/UA-CDI), recurrent CDI and overall CDI in 25 Italian hospitals, characterised C. difficile isolates using PCR ribotyping, analysed them for toxin genes and susceptibility to antimicrobials.ResultsClostridioides difficile was detected in 9.7% (655/6,722) of samples from 550 patients, 18 patients died of CDI. The mean overall CDI incidence was 5.0 cases per 10,000 patient days (range: 0.7-11.9). For HA-CDI, mean incidence was 3.7 (range: 0.7-9.2), for CA/UA-CDI 0.8 (range: 0.0-3.2) and for recurrent CDI 0.5 (range: 0.0-3.4). Most patients were female (n = 295; 53.6%), aged ≥ 65 years (n = 422; 76.7%) and previously hospitalised (n = 275; 50.0%). Of the 270 culturable isolates, 267 (98.9%) had toxin A and B genes and 51 (18.9%) the binary toxin genes. Of the 55 PCR ribotypes (RTs) identified, RT 018 (n = 56; 20.7%) and RT 607 (n = 23; 8.5%) were the most common, RT 607 in the northern (p < 0.0001) and RT 018 in the central (p < 0.0001) regions of Italy. Most isolates (n = 158; 58.5%) were antimicrobial-resistant and 119 (44.1%) were multidrug-resistant (MDR).ConclusionHighly virulent and MDR C. difficile types are circulating in Italian hospitals which highlights the need of robust surveillance and stringent prevention and control measures.