Acute Bacterial Infections Research Articles

Antibiotics and Lipid-Modifying Agents: Potential Drug-Drug Interactions and Their Clinical Implications.

Evidence-based prescribing requires taking into consideration the many aspects of optimal drug administration (e.g., dosage, comorbidities, co-administered drugs, etc.). A key issue is the administration of drugs for acute disorders that may potentially interfere with previously prescribed long-term medications. Initiating an antibiotic for an acute bacterial infection constitutes a common example. Hence, appropriate knowledge and awareness of the potential DDIs of antibiotics would lead to proper adjustments, thus preventing over- or under-treatment. For example, some statins, which are the most prescribed lipid-modifying agent (LMA), can lead to clinically important drug-drug interactions (DDIs) with the concurrent administration of antibiotics, e.g., macrolides. This review discusses the clinically significant DDIs of antibiotics associated with co-administrated lipid-lowering therapy and highlights common cases where regimen modifications may or may not be necessary.

Interleukin-8 involved in Nile Tilapia (Oreochromis niloticus) against bacterial infection

Interleukin 8 (IL8) is vital in promoting inflammation and is a crucial mediator in various physiopathological processes while influencing immunological function. The effect of IL8 on the immunological response to acute bacterial infections in Nile tilapia (Oreochromis niloticus) remains unknown. This work found an IL8 gene from Nile tilapia (On-IL8). It includes a 285 bp open reading frame and codes for 94 amino acids. The transcript levels of On-IL8 were highest in the head-kidney tissue and sharply induced by Streptococcus agalactiae and Aeromonas hydrophila. Besides, in vitro experiments revealed that On-IL8 regulated a variety of immunological processes and promoted inflammatory responses. Moreover, On-IL8 suppressed the NF-κB signaling pathway, consistent with in vitro results. These significant findings serve as the basis for further investigation into how IL8 confers protection to bony fish in opposition to bacterial infections.

Common laboratory tests and their correlation with the clinical presentation and prognosis of Lemierre syndrome

IntroductionLemierre syndrome is a thromboembolic complication following an acute bacterial infection of the head/neck area, often due to anaerobes. Data on the prognostic role of laboratory parameters is lacking. MethodsWe analyzed individual-patient level data from a multinational cohort of patients with Lemierre-syndrome. Patients had an infection in the head/neck area, and contiguous vein thrombosis or septic embolism, irrespective of the causal pathogen. We studied the patterns of white blood cell count, platelet count, and C-reactive protein concentration investigating their association with baseline characteristics and in-hospital clinical outcomes (septic embolism, major bleeding, all-cause death). ResultsA total of 447 (63%) patients had complete data for analysis. White blood cells were elevated across all subgroups (median 17 × 103/μL; Q1-Q3:12-21). Median platelet count was 61 × 103/μL (Q1-Q3:30-108) with decreasing levels with increasing age. Males, patients with renal failure or cardiopulmonary impairment, and those with typical Lemierre syndrome (tonsillitis, septic thromboembolism, positivity for Fusobacterium spp.) had the lowest platelet count. Median C-reactive protein was 122 (Q1-Q3:27-248) mg/L with higher values in patients who also had more severe thrombocytopenia. The overall risk of complications was similar across subgroups of patients stratified according to white blood cell and C-reactive protein levels. Patients in the lowest third of platelet count (<42 × 103/μL) had the highest rate of complications (26%), as opposed to those in the highest third (11%), notably septic embolic events. ConclusionsCommon laboratory tests correlate with the clinical presentation of Lemierre syndrome. However, extreme values did not appear to be prognostically relevant for in-hospital complications and potentially able to improve clinical management.

Effectiveness and safety of dalbavancin in France: a prospective, multicentre cohort study

Dalbavancin is a lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections. However, several studies have suggested that it is used mostly for off-label indications. We aimed to describe the use of dalbavancin in patients who received at least one dose of the antibiotic in France. Prospective, observational, multicentre study conducted in France from September 2018 to April 2020. The primary outcome was the clinical response at 30 days after the last dalbavancin dose. A total of 151 patients in 16 centres were included in this study. The main infection sites were bone and joint infections (55.0%), multisite infections (15.9%), and vascular infections (14.6%), and the primary pathogens were coagulase-negative staphylococci (N=82), Staphylococcus aureus (N=51), and enterococci (N=27). Most patients (71.5%) received three previous antibiotic treatments. The number of dalbavancin injections per patient was 1 in 26 patients (17.2%), 2 in 95 patients (62.9%), 3 in 17 patients (11.3%), and more than 3 in 13 patients (8.6%), with a mean cumulative dose of 3089 ± 1461 mg per patient. Among the 129 patients with a complete follow-up, clinical success was achieved in 119 patients (92.2%). At least 1 adverse event was reported in 67 patients (44.4%), including 12 (7.9%) patients with dalbavancin-related adverse events. The results of the study showed that dalbavancin is used mostly for off-label indications and in heavily pretreated patients in France. The clinical response at 30 days after the last dose was favourable in most patients, with a good safety profile.

Updated Review on Clinically-Relevant Properties of Delafloxacin.

The extensive use of fluoroquinolones has been consequently accompanied by the emergence of bacterial resistance, which triggers the necessity to discover new compounds. Delafloxacin is a brand-new anionic non-zwitterionic fluoroquinolone with some structural particularities that give it attractive proprieties: high activity under acidic conditions, greater in vitro activity against Gram-positive bacteria-even those showing resistance to currently-used fluoroquinolones-and nearly equivalent affinity for both type-II topoisomerases (i.e., DNA gyrase and topoisomerase IV). During phases II and III clinical trials, delafloxacin showed non-inferiority compared to standard-of-care therapy in the treatment of acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia, which resulted in its approval in 2017 by the Food and Drug Administration for indications. Thanks to its overall good tolerance, its broad-spectrum in vitro activity, and its ease of use, it could represent a promising molecule for the treatment of bacterial infections.

Severe Acute Bacterial Infections in Children With Sickle Cell Disease in Togo.

Bacterial infections are considered a major cause of morbidity and mortality in patients, especially children, with sickle cell disease. This study aims at determining, a year after the introduction of the 13-valent pneumococcal conjugate vaccine the distribution of severe acute bacterial infections and germs in children with sickle cell disease. Records of children 0 to 15 years of age and admitted from January 1, 2015 to December 31, 2019 (5 y), were examined retrospectively in the four sickle cell monitoring units in Lomé. The main infections found were pleuropulmonary (46.1%), urinary tract (32.8%), and osteoarticular (9.3%). A germ was isolated in 139 of the 265 cases (52.4%). 65.5% of the microorganisms isolated were Gram-negative organisms, with mostly Escherichia coli (31.6%) , and Klebsiella pneumoniae (18%) being the main germs. They were mainly responsible of urinary tract and osteoarticular infections. The majority of these Enterobacteriaceae was Extended-Spectrum Beta-Lactamase-Producing (41.1%, n = 37). Gram-positive cocci were represented by Staphylococcus sp (25.9%), Streptococcus sp (4.3%), Streptococcus pneumoniae (2.9%), and Enterococcus (1.4%). Staphylococcus aureus was the most common germ in pleuropulmonary (40%), osteoarticular (47.3%), and sepsis (28.6%) infections. Even if the infections found remained classic, there is a redistribution of germs with a decline in Salmonella and increase of Escherichia coli , Klebsiella pneumoniae , and Staphylococcus aureus .

Real-World Data Regarding Dalbavancin Use before and during the COVID-19 Pandemic-A Single-Center Retrospective Study.

Dalbavancin is a semisynthetic lipoglycopeptide, which possesses great potential for bactericidal activity similar to antimicrobials with the same mechanism of action, such as vancomycin and teicoplanin. Due to its very prolonged half-life, it can be used in a single or two-dose regimen to treat infections by Gram-positive microorganisms, even resistant ones, such as methicillin-resistant Staphylococcus aureus (MRSA). Currently, it is approved only for the treatment of acute bacterial skin and skin structure infections (ABSSSIs). The aim of this study was to investigate the clinical and microbiological characteristics of patients to whom dalbavancin was administered at the University Hospital of Heraklion and evaluate its use in regard to the COVID-19 pandemic. In total, 146 patients were included in this retrospective cohort study evaluating the use of dalbavancin from the first time it was used in 2017 until the end of 2022. The median age was 68 years (range: 21-96 years), and 86 (59%) patients were male. The most common indications for dalbavancin use were osteoarticular infections in 43%, followed by ABSSSIs in 37%, and cardiovascular infections in 10%. Dalbavancin was used empirically in one out of three patients, most commonly with the indication of ABSSSIs, and most commonly in the post-COVID-19 era. The most frequently isolated pathogens were coagulase-negative staphylococci in 70%, S. aureus in 27%, Enterococcus spp. in 22%, and Streptococcus spp. in 8%, while one out of three infections were polymicrobial. In 12% of patients, the infection was not cured, but no patients died. For patients with ABSSSIs, endocarditis and vascular infections, and bacteremia, the cure rates were more than 90%, and in osteoarticular infections, the cure rate was 76%. Thus, dalbavancin has great potential for use in complicated and invasive infections that may require prolonged intravenous antimicrobial treatment. However, further studies are required to formally investigate its role in such infections.

Biochemical Characterization of a New 10% IVIG Preparation [IgG Next Generation (BT595)/Yimmugo®] Obtained from a Manufacturing Process Preserving IgA/IgM Potential of Human Plasma.

Human plasma is used for the generation of several life-saving drugs and contains valuable antibodies from the immunoglobulin classes IgG, IgM and IgA. Purified intravenous IgG solutions (IVIGs) form the majority of plasma-derived medicine to treat patients with various forms of immunodeficiencies. In conventional IVIG manufacturing processes, immunoglobulin classes IgM and IgA are often discarded as contaminants, but these antibody classes have been proven to be effective for the treatment of acute bacterial infections. Considering the increase in demand for human plasma-derived products and the ethical value of the raw material, a more resource-saving usage of human plasma is needed. Intensive research over the last decades showed that adverse reactions to IVIGs depend on the presence of thrombogenic factors, partially unfolded proteins, non-specific activation of the complement system, and blood group specific antibodies. Therefore, new IVIG preparations with reduced risks of adverse reactions are desirable. A new manufacturing process that yields two biologics was established and quality attributes of the new IVIG solution (Yimmugo®) obtained from this process are presented. Here, we provide a biochemical characterization of Yimmugo®, a new 10%IVIG preparation. It is derived from human blood plasma by a combined manufacturing process, where IgM and IgA are retained for the production of a new biologic (trimodulin, currently under investigation in phase III clinical trials). Several improvements have been implemented in the manufacturing of Yimmugo® to reduce the risk of adverse reactions. Gentle and efficient mixing by vibration (called "vibromixing") during a process step where proteins are at risk to aggregate was implemented to potentially minimize protein damage. In addition, a dedicated process step for the removal of the complement system activator properdin was implemented, which resulted in very low anticomplementary activity levels. The absence of measurable thrombogenic activity in combination with a very high degree of functional monomeric antibodies predict excellent efficacy and tolerability. Yimmugo® constitutes a new high quality IVIG preparation derived from a novel manufacturing process that takes advantage of the full therapeutic immunoglobulin potential of human plasma.

Dalbavancin in Bone and Joint Infections: A Systematic Review.

Approved for acute bacterial skin and skin structure infections, dalbavancin (DBV) has gradually acquired over the years a role as an off-label treatment for several infections caused by Gram-positive bacteria even in other anatomical sites. Osteoarticular (OA) infections are one of the most difficult-to-treat infections and, since the absence of recommendations, clinicians use different and heterogenic DBV dosing schedule regimens for the off-label treatment of osteomyelitis, spondylodiscitis, and septic arthritis. Our aim is to systematically review the current literature to describe DBV administration schedules and their outcome in OA infections. According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the use of DBV in OA infections were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. A total of 23 studies and 450 patients were included, prevalently male (144/195, 73.8%) and diabetic (53/163, 32.5%). Overall, 280 (280/388, 72.2%) osteomyelitis, 79 (79/388, 20.4%) spondylodiscitis, and 29 (29/388, 7.5%) septic arthritis were considered. Staphylococcus aureus (164/243, 67.5%) was the most common pathogen isolated. A previous treatment failure (45/96, 46.9%) was the main reason for a switch to a long-acting antibiotic. Most patients were successfully cured with DBV (318/401, 79.3%). A source control was performed in most patients with a favourable outcome (80.4%), while MRSA was prevalently isolated in people with an unfavourable outcome (57%). While a higher percentage of success was found in people who received three doses of DBV 1 week apart (92.3%), a higher rate of treatment failure was recorded in cases of when the DBV cycle was composed of less than two or more than four doses (27.8%). DBV has shown to be effective as a treatment for OA infections. The most favourable outcome was found in patients receiving three doses of DBV and with an adequate surgical management prior to antibiotic treatment. Although a rigorous administration schedule does not exist, DBV is a viable treatment option in the management of OA infections.

Normoferremia in Patients with Acute Bacterial Infections-A Hitherto Unexplored Field of the Dichotomy between CRP and Ferritin Expression in Patients with Hyper Inflammation and Failure to Increase Ferritin.

Ferritin is an acute phase response protein, which may not rise as expected in acute bacterial infections. This could be due to the time required for its production or to a lack of response of ferritin to the bacterial inflammatory process. Medical records of hospitalized patients with acute hyper inflammation were retrieved and studied, looking closely at two acute phase proteins: C-reactive protein (CRP) and ferritin. The estimated time between symptom onset and the procurement of blood tests was also measured. 225 patients had a median ferritin level of 109.9 ng/mL [IQR 85.1, 131.7] and a median CRP level of 248.4 mg/L [IQR 221, 277.5]. An infectious inflammatory process was identified in 195 patients. Ferritin levels were relatively low in comparison with the CRP in each group, divided according to time from symptom onset until the procurement of blood tests. The discrepancy between high CRP and low ferritin suggests that these two acute phase response proteins utilize different pathways, resulting in a failure to increase ferritin concentrations in a documented state of hyperinflammation. A new entity of normoferremic inflammation accounts for a significant percentage of patients with acute bacterial infections, which enables bacteria to better survive the inflammation and serves as a new "inflammatory stamp".

Coronary Artery Aneurysms Following Stenting

Coronary artery aneurysms are rare complications following stenting and were reported with drug-eluting as well as bare metal stents. They can be asymptomatic or present as acute coronary syndromes and usually detected during coronary angiography. The mechanisms responsible can be vascular trauma, hypersensitivity to drug, polymer, or metal. Rarely, it can be due to acute bacterial infections resulting in mycotic aneurysms. Management depends on symptoms, presentation, and underlying pathology and has to be tailored on a case-to-case basis.

Real-world effectiveness of omadacycline and impact of unapproved omadacycline prescription claims among adult outpatients with community-acquired bacterial pneumonia or acute bacterial skin and skin structure infections.

BACKGROUND: Omadacycline is an amino-methylcycline antibiotic that is indicated for the treatment of adults with community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI). Like many new antibiotics, there are scant real-world effectiveness data for omadacycline. There is also a high potential that an omadacycline prescription is rejected or reversed, and it is not known whether patients who have an unapproved omadacycline claim are at higher risk for 30-day emergency department (ED)/inpatient (IP) visits. OBJECTIVE: To describe the real-world effectiveness of omadacycline and assess the impact of unapproved omadacycline claims among adult outpatients with CABP or ABSSSIs. METHODS: The study population included patients who received 1 or more omadacycline outpatient prescriptions from a large US claims database (October 2018 to September 2020) and had a diagnosis for CABP or ABSSSI. The approval status of omadacycline claims was determined. The proportion of all-cause 30-day ED/IP visits among patients with an approved vs unapproved claim was compared. RESULTS: 404 patients met the inclusion criteria (CABP: 97; ABSSSI: 307). Of the 404 patients, 146 (36%) had an unapproved claim (CABP: 28; ABSSSI: 118). Overall, the proportion of 30-day ED/IP visits (yes/no) for those with an unapproved and approved claim was 28% vs 17%, respectively (P < 0.05). The overall adjusted 30-day ED/IP visits incidence difference was 11% (95% CI = 2 - 19), corresponding to an adjusted number needed to treat of 9 (95% CI = 5 - 43). CONCLUSIONS: A high incidence (36%) of unapproved omadacydine claims was observed in this study. Patients with unapproved daims had an 11% higher incidence of 30-day all-cause ED/IP visits than patients with approved claims. DISCLOSURES This study was funded by Paratek Pharmaceuticals, Inc (King of Prussia, PA). Dr Lodise is a consultant to Paratek Pharmaceuticals, Inc, and has received consultancy payments. Drs Gunter, Sandor, and Berman are employees and shareholders of Paratek Pharmaceuticals, Inc. Dr Mu, Ms Gao, Ms Yang, and Ms Yim are employees of Analysis Group. Analysis Group has received payment from Paratek Pharmaceuticals, Inc, to conduct part of this study.

Antimicrobial susceptibility of Clostridioides difficile to omadacycline and comparator antimicrobials.

Omadacycline is a novel aminomethylcycline tetracycline antimicrobial that was approved for the treatment of community-associated bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) in 2018. Omadacycline has demonstrated a high degree of in vitro activity towards Clostridioides difficile and previous data have hypothesized that use of omadacycline for CABP or ABSSSI may decrease the risk of C. difficile infections. To compare the in vitro antimicrobial activity of omadacycline versus commonly used antimicrobials for the approved indications of use. We compared the antimicrobial activity of eight antimicrobials approved for CABP and ABSSSI against omadacycline by agar dilution on 200 clinically relevant contemporary C. difficile isolates representing local and national prevalent strain types. The in vitro omadacycline geometric mean MIC was 0.07 mg/L. Ceftriaxone resistance was noted in >50% of all isolates tested. The epidemic strain group, identified as restriction endonuclease analysis (REA) group BI, was commonly resistant to azithromycin (92%), moxifloxacin (86%) and clindamycin (78%). REA group DH strains had an elevated trimethoprim/sulfamethoxazole geometric mean MIC of 17.30 mg/L compared with the geometric mean MIC of 8.14 mg/L noted in all other isolates. In the REA group BK isolates that had a doxycycline MIC of ≥2 mg/L, the omadacycline MIC was <0.5 mg/L. Among 200 contemporary C. difficile isolates, there were no notable elevations in the in vitro omadacycline MIC, indicating a high level of activity towards C. difficile in comparison with commonly used antimicrobials for CABP and ABSSSI.

Predictive value of cell population data with Sysmex XN-series hematology analyzer for culture-proven bacteremia.

Cell population data (CPD) parameters related to neutrophils, such as fluorescent light intensity (NE-SFL) and fluorescent light distribution width index (NE-WY), have emerged as potential biomarkers for sepsis. However, the diagnostic implication in acute bacterial infection remains unclear. This study assessed the diagnostic value of NE-WY and NE-SFL for bacteremia in patients with acute bacterial infections, and those associations with other sepsis biomarkers. Patients with acute bacterial infections were enrolled in this prospective observational cohort study. For all patients, a blood sample, with at least two sets of blood cultures, were collected at the onset of infection. Microbiological evaluation included examination of the blood bacterial load using PCR. CPD was assessed using Automated Hematology analyzer Sysmex series XN-2000. Serum levels of procalcitonin (PCT), interleukin-6 (IL-6), presepsin, and CRP were also assessed. Of 93 patients with acute bacterial infection, 24 developed culture-proven bacteremia and 69 did not. NE-SFL and NE-WY were significantly higher in patients with bacteremia than in those without bacteremia (p < 0.005, respectively), and were significantly correlated with the bacterial load determined by PCR (r = 0.384 and r = 0.374, p < 0.005, respectively). To assess the diagnostic value for bacteremia, receiver operating characteristic curve analysis was used. NE-SFL and NE-WY showed an area under the curve of 0.685 and 0.708, respectively, while those of PCT, IL-6, presepsin, and CRP were 0.744, 0.778, 0.685, and 0.528, respectively. Correlation analysis showed that the levels of NE-WY and NE-SFL were strongly correlated with PCT and IL-6 levels. This study demonstrated that NE-WY and NE-SFL could predict bacteremia in a manner that may be different from that of other indicators. These findings suggest there are potential benefits of NE-WY/NE-SFL in predicting severe bacterial infections.

Necessity of vancomycin trough concentrations to manage uncomplicated acute bacterial skin and skin structure infections: a laboratory stewardship analysis.

Recent recommendations by the American Society of Health System Pharmacists and Infectious Disease Society of America have provided guidance regarding vancomycin dosing and monitoring in serious infections (including methicillin-resistant Staphylococcus aureus); however, trough monitoring for uncomplicated acute bacterial skin and skin structure infections (ABSSSI) were not addressed. Vancomycin use appears to lead to a low incidence of acute kidney injury with short durations and a low trough goal (10-15 mg/L). Nevertheless, clinical studies have found no difference in clinical outcomes for ABSSSI regardless of vancomycin level. Therefore, it can be posed whether trough monitoring is necessary in this patient population. This is a retrospective cohort study comparing vancomycin therapy duration for ABSSSI in adult, general medicine patients who received scheduled vancomycin with an initial creatinine clearance rate of ≥50 mL/minute and had at least one vancomycin trough. The objective of this study was to determine if vancomycin treatment duration differs for patients with ABSSSI with a sub-therapeutic vancomycin trough (ST; <10 mg/L) compared with therapeutic trough (TT; ≥10 mg/L). There were 39 (67.2%) patients with ST compared with 19 (32.8%) with TT. A similar median vancomycin treatment duration for ST (48.25 hours) and TT (59.5 hours; p=0.65) was found. There was no statistical difference for hospital duration, time from last trough to vancomycin discontinuation, or incidence of acute kidney injury (p>0.05 for all). Patients with ST and TT had similar vancomycin durations and clinical outcomes. It may be prudent for institutions to address vancomycin trough laboratory stewardship and associated costs.

Modeling and analysis of the transmission of avian spirochetosis with non-singular and non-local kernel

An acute bacterial infection called avian spirochetosis is spread by ticks to a variety of birds. Clinical symptoms can vary greatly and are frequently non-specific. To diagnose a condition, the infectious spirochete must be detected. Here, we structure an epidemic model for the transmission of avian spirochetosis to visualize the interaction between tick and bird populations. The recommended dynamics of avian spirochetosis is illustrated with the help of fractional framework. We inspected the steady-states of the system of the avian spirochetosis for the stability analysis. The next-generation technique is used to evaluate the model’s reproduction parameter R 0 . The infection-free and endemic steady-state of avian spirochetosis were shown to be locally asymptotically stable under the specified conditions. Through mathematical skills, the positivity of solutions is determined. Additionally, evidence supporting the existence and uniqueness of the avian spirochetosis framework solution has been shown. We conduct modified simulations of the suggested avian spirochetosis system with different input factors to study the complex phenomena of avian spirochetosis under the effect of numerous input parameters. Our outcomes illustrate the significance and plausibility of fractional parameter, and they also suggest that this input parameter may adequately account for these kinds of observations.

Chronically hypertensive transgenic mice expressing human AT1R haplotype-I exhibit increased susceptibility to Francisella tularensis.

Age-related illnesses, including hypertension and accompanying metabolic disorders, compromise immunity and exacerbate infection-associated fatalities. Renin-angiotensin system (RAS) is the key mechanism that controls blood pressure. Upregulation of RAS through angiotensin receptor type 1 (AT1R), a G-protein coupled receptor, contributes to the pathophysiological consequences leading to vascular remodeling, hypertension, and end-organ damage. Genetic variations that increase the expression of human AT1R may cause the above pathological outcomes associated with hypertension. Previously we have shown that our chronically hypertensive transgenic (TG) mice containing the haplotype-I variant (Hap-I, hypertensive genotype) of human AT1R (hAT1R) gene are more prone to develop the metabolic syndrome-related disorders as compared to the TG mice containing the haplotype-II variant (Hap-II, normotensive genotype). Since aging and an increased risk of hypertension can impact multiple organ systems in a complex manner, including susceptibility to various infections, the current study investigated the susceptibility and potential effect of acute bacterial infection using a Gram-negative intracellular bacterial pathogen, Francisella tularensis in our hAT1R TG mice. Our results show that compared to Hap-II, F. tularensis-infected aged Hap-I TG mice have significantly higher mortality post-infection, higher bacterial load and lung pathology, elevated inflammatory cytokines and altered gene expression profile favoring hypertension and inflammation. Consistent with worsened phenotype in aged Hap-I mice post-Francisella infection, gene expression profiles from their lungs revealed significantly altered expression of more than 1,400 genes. Furthermore, bioinformatics analysis identified genes associated with RAS and IFN-γ pathways regulating blood pressure and inflammation. These studies demonstrate that haplotype-dependent over-expression of the hAT1R gene leads to enhanced susceptibility and lethality due to F. tularensis LVS infection, which gets aggravated in aged animals. Clinically, these findings will help in exploring the role of AT1R-induced hypertension and enhanced susceptibility to infection-related respiratory diseases.

Tonsillectomy in adults—to do or not to do

Recurrent acute tonsillitis describes the repeated occurrence of acute bacterial infections of palatine tonsils with symptom-free intervals. Acute tonsillitis accounts for around a third of respiratory tract infections in primary care among people of all ages, 1 Petersen I Johnson AM Islam A Duckworth G Livermore DM Hayward AC Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database. BMJ. 2007; 335: 982 Crossref PubMed Scopus (210) Google Scholar with an estimated 600 million symptomatic cases of group A streptococcus tonsillitis worldwide annually. 2 Carapetis JR Steer AC Mulholland EK Weber M The global burden of group A streptococcal diseases. Lancet Infect Dis. 2005; 5: 685-694 Summary Full Text Full Text PDF PubMed Scopus (1995) Google Scholar Recurrent episodes occur in 12% of patients with tonsillitis—ie, around 12 000 per 100 000 people. 3 Kvestad E Kværner KJ Røysamb E Tambs K Harris JR Magnus P Heritability of recurrent tonsillitis. Arch Otolaryngol Head Neck Surg. 2005; 131: 383-387 Crossref PubMed Scopus (26) Google Scholar Beyond the relation to group A streptococcus infections, little is known about risk factors for the development of recurrent acute tonsillitis. 4 Roberts AL Connolly KL Kirse DJ et al. Detection of group A Streptococcus in tonsils from pediatric patients reveals high rate of asymptomatic streptococcal carriage. BMC Pediatr. 2012; 12: 3 Crossref PubMed Scopus (97) Google Scholar Recurrent acute tonsillitis could be a genetic immunosusceptibility disease because patients younger than 12 years show some subclinical antibody deficiency and aberrant T-cell function 5 Dan JM Havenar-Daughton C Kendric K et al. Recurrent group A Streptococcus tonsillitis is an immunosusceptibility disease involving antibody deficiency and aberrant TFH cells. Sci Transl Med. 2019; 11eaau3776 Crossref PubMed Scopus (1) Google Scholar and many undergo tonsillectomy. More than 30 000 tonsillectomies are performed annually in the UK. 6 Keltie K Donne A Daniel M et al. Paediatric tonsillectomy in England: a cohort study of clinical practice and outcomes using Hospital Episode Statistics data (2008–2019). Clin Otolaryngol. 2021; 46: 552-561 Crossref PubMed Scopus (16) Google Scholar Tonsillectomy can produce severe postoperative pain, complicated by postoperative bleeding which can result in death in rare cases. Clearly, we need evidence-based policies to guide health-care professionals for the indication of tonsillectomy. 7 Mandavia R Schilder AGM Dimitriadis PA Mossialos E Addressing the challenges in tonsillectomy research to inform health care policy: a review. JAMA Otolaryngol Head Neck Surg. 2017; 143: 943-947 Crossref PubMed Scopus (10) Google Scholar Unfortunately, not much has changed in the past 40 years. National guidelines are still based on the Paradise criteria from 1984, 8 Paradise JL Bluestone CD Bachman RZ et al. Efficacy of tonsillectomy for recurrent throat infection in severely affected children—results of parallel randomized and nonrandomized clinical trials. N Engl J Med. 1984; 310: 674-683 Crossref PubMed Google Scholar stating that a tonsillectomy is indicated when around seven or more treated tonsillitis episodes occur in 1 year. The Paradise criteria were based on paediatrics clinical trials and later extrapolated for adult guidelines without any justifying research in the adult population. Thus, the 2014 Cochrane Review concluded that the effectiveness of tonsillectomy is low. 9 Burton MJ Glasziou PP Chong LY Venekamp RP Tonsillectomy or adenotonsillectomy versus non-surgical treatment for chronic/recurrent acute tonsillitis. Cochrane Database Syst Rev. 2014; 2014CD001802 PubMed Google Scholar Until now, there was no basis to make confident decisions using national guidelines. 7 Mandavia R Schilder AGM Dimitriadis PA Mossialos E Addressing the challenges in tonsillectomy research to inform health care policy: a review. JAMA Otolaryngol Head Neck Surg. 2017; 143: 943-947 Crossref PubMed Scopus (10) Google Scholar Conservative management versus tonsillectomy in adults with recurrent acute tonsillitis in the UK (NATTINA): a multicentre, open-label, randomised controlled trialCompared with conservative management, immediate tonsillectomy is clinically effective and cost-effective in adults with recurrent acute tonsillitis. Full-Text PDF Open Access

Dalbavancin for the Treatment of Acute Bacterial Skin and Skin Structure Infection in Patients With Obesity or Diabetes: A Subgroup Analysis of Pooled Phase 3 Clinical Trials.

We assessed the efficacy and safety of dalbavancin, a long-acting lipoglycopeptide with activity against Gram-positive pathogens, for treatment of acute bacterial skin and skin structure infections (ABSSSI) in patients with high body mass index (BMI) and/or diabetes. Data from two phase 3 trials of dalbavancin (1000 mg intravenous [IV], day 1; 500 mg IV, day 8) versus comparator and one phase 3b trial of single-dose (1500 mg IV, day 1) versus 2-dose (1000 mg IV, day 1; 500 mg IV, day 8) dalbavancin in adults with ABSSSI were pooled and summarized separately by baseline BMI and diabetes status. Clinical success at 48 to 72 hours (≥20% reduction in lesion size), end of treatment ([EOT] day 14), and day 28 was evaluated in the intent-to-treat (ITT) and microbiological ITT (microITT) populations. Safety data were reported in patients who received ≥1 dose of study drug. In the dalbavancin ITT population (BMI, n = 2001; diabetes, n = 2010), at 48 to 72 hours (and EOT) clinical success was achieved in 89.3% (EOT, 90.9%) of patients with normal BMI and 78.9% to 87.6% (EOT, 91.0% to 95.2%) of patients with elevated BMI. Clinical success after dalbavancin treatment was achieved in 82.4% (EOT, 90.8%) of patients with diabetes and 86.0% (EOT, 91.6%) of patients without diabetes. Similar trends were observed for infections due to methicillin-resistant Staphylococcus aureus or methicillin-susceptible S aureus (microITT population). Dalbavancin is effective, with sustained clinical success rates in patients with obesity or diabetes, with a similar safety profile across patient groups.

Use of C-reactive protein to guide the antibiotic therapy in hospitalized patients: a systematic review and meta-analysis

BackgroundC-reactive protein (CRP) is an inflammatory protein used in clinical practice to identify and monitor inflammatory and infectious processes. Recent data suggest CRP might be useful in guiding antibiotic therapy discontinuation among critical care patients. This meta-analysis analyzed the benefits and risks of CRP-guided protocols to guide antibiotic therapy in hospitalized patients in comparison with standard treatment.MethodsStudies were searched in four databases: CENTRAL, Medline, Embase and LILACS. The search was performed until Jan 25th, 2023. The reference lists of the articles retrieved and related review studies were hand-screened to find eligible trials that might have been missed. Primary endpoints included the duration of antibiotic therapy for the index episode of infection. The secondary endpoint was the all-cause hospital mortality and infection relapses. The risk of bias was evaluated using the Cochrane Risk of Bias 2.0 tool. Random effects were used to pool the mean differences and odds ratio of individual studies. The protocol was registered in PROSPERO (CRD42021259977).ResultsThe search strategy retrieved 5209 titles, out of which three studies met the eligibility criteria and were included in this meta-analysis. 727 adult patients were analyzed, of whom 278 were included in the intervention group and 449 were included in the control group. 55,7% of all patients were women. Meta-analysis indicated that experimental groups (CRP-guided) had a lower duration of antibiotic therapy (days) [MMD = -1.82, 95%IC -3.23; -0.40]; with no difference in mortality [OR = 1.19 95%IC 0.67–2.12] or in the occurrence of infection relapse [OR = 3.21 95%IC 0.85–12.05].ConclusionThe use of CRP-guided protocol reduces the total amount of time required for antibiotic therapy when compared to standard protocols of treatment in hospitalized patients with acute bacterial infection. We did not observe statistical differences regarding mortality and infection relapse rates.