Empiric Broad-spectrum Antibiotic Therapy Research Articles

Early stoppage of empirical antibiotic therapy at clinical improvement in paediatric leukaemia patients with high-risk febrile neutropenia (ESAT-HR-FN study): Study protocol of a single centre investigator initiated randomised open label non-inferiority trial

Background and rationaleFebrile neutropenia (FN) is one of the major causes of early mortality among children undergoing induction chemotherapy for haematological malignancies. FN occurs in up to 80 % of the children undergoing intensive chemotherapy and FN specific mortality is as high as 10 %. The management of high-risk FN (HR-FN) is by early initiation of broad-spectrum empirical antibiotic therapy (EAT) which is continued till blood count recovery. Adverse effects of prolonged EAT among children without proven infective focus have questioned the rationale behind the duration of EAT. The non inferiority of early stoppage of EAT in patients with low-risk FN (LR-FN) when afebrile for 48 h, irrespective of marrow recovery, is proven among adults and children. However, there is paucity of data regarding the same in children with HR-FN. This study aims to determine whether early discontinuation of EAT in children with HR-FN without proven infective focus who become afebrile and awaiting marrow recovery, would reduce antibiotic duration and their adverse effects without any negative consequences for patients. ObjectiveTo compare the rates of recurrent fever in paediatric patients (2–18 years) with HR-FN when EAT is continued till marrow recovery (control group) versus when stopped early at defervescence irrespective of marrow recovery (study group). MethodologyThis is the study protocol of a phase 3, single centre, randomized, open label, non-inferiority clinical trial. The primary outcome is the rate of fever recurrence among patients with HR-FN, when EAT is stopped early irrespective of marrow recovery (study group) and will be compared to the rate of fever recurrence on continuation of EAT till marrow recovery which is defined as an absolute neutrophil count (ANC) ≥ 500/mm3 (control group). Secondary outcomes include the comparison of duration of antibiotic use, mortality rates, hospital re-admission rates, requirement of multiple broad-spectrum antibiotics, therapeutic anti-fungal usage and need for organ support between the study and the control groups. A total of 280 children with acute leukaemia undergoing EAT for grade 3 or severe FN (ANC <500/μL) without clinico-laboratory evidence of infective foci are being randomized in the ratio of 1:1 between the study and the control group after defervescence for 48 h. The patients will be followed up for primary outcome (fever recurrence) till the end of induction period (day 35) or recovery of ANC ≥500/mm3 whichever is earlier. Expected outcomeESAT-HR FN study is the first large phase 3 randomised study to assess the impact of early stoppage of EAT irrespective of marrow recovery among a homogenous paediatric cohort of HR-FN in the setting of induction chemotherapy for acute leukaemia. This study will be seminal in addressing the duration of EAT in HR-FN among children without infective foci and if proven to be non-inferior this strategy will help to reduce the adverse effects from prolonged antibiotic use, the emergence of drug resistance, decrease hospital stay length and overall health care costs.

Bloodstream infections due to multi-drug resistant bacteria in the emergency department: prevalence, risk factors and outcomes-a retrospective observational study.

Multidrug-resistant organisms (MDROs) are prevalent in patients admitted to the Emergency Department (ED) and increase the risk of inappropriate empirical antibiotic therapy. Risk stratification for MDRO infection is essential to early identify patients requiring empirical broad-spectrum antibiotic therapy, but it remains challenging for emergency physicians. This study aimed to evaluate prevalence, risk factors, and outcomes of patients admitted to the ED with a bloodstream infection (BSI) caused by MDROs. A retrospective observational study enrolling all consecutive adult patients admitted with a BSI to the ED of Niguarda Hospital, Italy, from January 2019 to December 2021 was performed. 757 patients were enrolled, 14.1% with septic shock. 156 (20%) patients had a BSI caused by MDRO: extended-spectrum beta-lactamase (ESBL) producing Enterobacterales were the most prevalent followed by methicillin-resistant Staphylococcus aureus (MRSA). Risk factors for BSI due to MDRO and specifically for ESBL were chronic renal failure (OR 2.2; 95%CI 1.4-3.6), nursing home residency (OR 4.4; 95%CI 1.9-10.2) and antibiotic therapy in the last 90-days (OR 2.6; 95%CI 1.7-4), whereas for MRSA were dialysis (OR 12.3; 95%CI 1.8-83), antibiotic therapy and/or hospital admission in the past 90-days (OR 3.6; 95%CI 1.2-10.6) and ureteral stent or nephrostomy (OR 7.8; 95%CI 1.5-40.9). Patients with BSI due to MDRO had a higher rate of inappropriate empirical antibiotic therapy (50%) and longer length of stay, but no higher in-hospital mortality. Among patients admitted to the ED with a BSI, MDROs are frequent and often associated with inappropriate empirical antibiotic therapy. Specific updated risk factors for MDRO may help clinicians to better identify patients requiring a broader antibiotic therapy in the ED, while awaiting microbiological results.

An Emerging Threat: A Systematic Review of Endocarditis Caused by Gemella Species.

Infective endocarditis caused by Gemella species is increasingly recognized as an emerging clinical entity. Gemella species are fastidious gram-positive cocci that are typically commensal organisms but can become opportunistic pathogens. This systematic review aimed to provide a comprehensive overview of endocarditis due toGemellaspecies by synthesizing existing evidence. A total of 52 case reports were identified through a rigorous search and selection process. The most prevalent causative species were G. morbillorum (46.3%) and G. haemolysans (25.9%), with a striking male predominance (79.6%). The clinical presentation was largely nonspecific, mirroring typical infective endocarditis. However, the indolent nature of the illness and fastidious growth requirements of Gemella species often led to diagnostic delays. Echocardiography, particularly transesophageal echocardiography, played a crucial role in the diagnosis, enabling the detection of valvular vegetation and the assessment of complications. Management posed significant challenges, including the need for broad-spectrum empirical antibiotic therapy and increasing antimicrobial resistance among Gemella isolates. Surgical intervention was frequently required for severe valvular dysfunction, persistent infection, or embolic complications. Despite advances in diagnosis and treatment, endocarditis due toGemellaspeciesremains associated with significant morbidity and mortality, underscoring the importance of early recognition and multidisciplinary management. This review highlights the emerging clinical significance of Gemella species as causative agents of infective endocarditis and identifies areas for further research.

Group B Streptococcus Meningitis in an Adult Woman with Type 2 Diabetes and Ethmoid Roof Defect. Impact on "frontal" Cognitive Functions.

Community-acquired bacterial meningitis in adults represents one of the most severe infectious diseases worldwide with potentially life-threatening medical complications. Several infectious agents can cause acute meningitis. Although group B Streptococcus is more prevalent in newborns, infection can also lead to meningitis in older adults, particularly those with underlying health issues. A 53-year-old woman with a body mass index of 28.7 kg/m2, type 2 diabetes mellitus, and dyslipidaemia presented to the emergency department of Santa Maria della Stella Hospital (Orvieto, Italy) with confusion, low-grade fever, echolalia, and hyperglycaemia. Computed tomography scans of the brain revealed a hypodensity in the left anterior frontal lobe and an osteodural defect of the rhinobase. Meningitis was suspected and empiric broad-spectrum antibiotic therapy with corticosteroids and insulin were administered while the results of the cerebrospinal fluid analysis confirmed the diagnosis of group B Streptococcus meningitis. Repeat imaging at 48 hours revealed enlargement of the hypodense lesion. The frontal assessment battery indicated deficits in executive functions. Prompt treatment led to rapid clinical improvement. Following the restoration of euglycemic status and hemodynamic stabilization, a follow-up magnetic resonance imaging confirmed the ischaemic lesion and showed cerebrospinal fluid in the sella turcica. The patient was then transferred to neurorehabilitation. The complex interactions among multiple risk factors resulted in an atypical clinical case of group B Streptococcus meningitis, which was promptly treated with empiric antibiotic therapy to mitigate neurocognitive deficits. Group B Streptococcus can cause meningitis in adults with poorly controlled type 2 diabetes mellitus and should be promptly treated with empiric broad-spectrum antibiotics.An osteodural defect of the ethmoid roof together with idiopathic intracranial hypertension may result in empty sella turcica and CSF rhinorrhoea, promoting the dissemination of the pathogen.Meningitis patients with pre-existing diabetic cerebral vasculopathy may develop cerebrovascular complications and cognitive impairments.

Anatomical Therapeutic Chemical / Define Daily Dose for evaluation of bronchopneumonia pediatric antibiotics use at Roemani Muhammadiyah Hospital

The increase in repeat hospitalizations after the covid19 pandemic with bronchopneumonia diagnoses in pediatric patients is the first rank. Therapeutic management was associated with the length of hospitalization. Pediatric bronchopneumonia is the case with antibiotic therapy. Current guidelines recommend first-line and alternative options in the management of antibiotic therapy for pneumonia in hospitalized pediatric patients. Empirical broad-spectrum antibiotic therapy for acute infections with consideration of the common etiology of possible pneumococcal involvement The risk of resistance increases with the massive use of antibiotics. The study had an observational descriptive design with retrospective data collection from 280 samples of pediatric patients, aiming to evaluate the use of antibiotics with the ATC/DDD method. Based on empirical selected therapy DDD (Define Daily Dose)/100 patient days, the quantity of antibiotics that are widely used is ceftriaxon 38.36 DDD /100 patient days followed by Cefoperazon sulbactam 3.88 DDD /100 patient days, Cefotaxime 3.77 DDD /100 patient days, Gentamicin 2.57 DDD /100 patient days, Amikacin 1. 70 DDD /100 patient days, Azithromycin 0.76 DDD /100 patient days, Ampicillin Sulbactam 0.50 DDD /100 patient days, Cefixime 0.27 DDD /100 patient days, and Meropenem 0.13 DDD /100 patient days. Drug data included in DU90% are Ceftriaxon, Cefoperzon Sulbactam, Cefotaxime. From the research conducted, the highest DDD/100 patient days value was Ceftriaxon. DDD value indicates high use of antibiotics, does not mean unreasonable use of drugs, so a qualitative review must be done.

The prevalence and clinical context of antimicrobial resistance amongst medical inpatients at a referral hospital in Rwanda: a cohort study

BackgroundAntimicrobial resistance (AMR) is a growing global concern. AMR surveillance is a crucial component of the international response; however, passive surveillance of laboratory data is limited without corresponding patient-level clinical data. This study sought to examine the burden of AMR amongst medical inpatients in Rwanda, in the context of their clinical presentations and prior antibiotic exposures.MethodsThis cohort study was conducted over a 9-month period at a tertiary referral hospital in Kigali, Rwanda. We enrolled 122 adult medical inpatients with a history of fever and a positive microbiological culture result. Data were collected regarding the clinical and microbiological aspects of their admission.ResultsThe most common diagnoses were urinary tract infection (n = 36, 30%), followed by pneumonia (n = 30, 25%) and bacteraemia (11 primary [9%] and 10 catheter-related [8%]). The most common pathogens were E. coli (n = 40, 33%) and Klebsiella pneumoniae (n = 36, 30%). The cohort were heavily antibiotic-exposed at the time of culture with 98% of patients (n = 119) having received an antibiotic prior to culture, with a median exposure of 3 days (IQR 2–4 days). Eighty patients (66%) were specifically prescribed ceftriaxone at the time of culture. Gram-negative organisms predominated (82% [100/122]) and exhibited high rates of resistance, with only 27% (21/77) being susceptible to ceftriaxone, 2.4% (2/82) susceptible to co-amoxiclav and 44% (8/18) susceptible to ciprofloxacin. Susceptibility amongst Gram-negatives was relatively preserved to amikacin (91%, 79/87) and imipenem (85%, 70/82). There were no cases of methicillin-resistant Staphylococcus aureus (0/12) or vancomycin-resistant enterococci (0/2). Discordant antibiotic therapy was significantly associated with in-hospital mortality (OR 6.87, 95%CI 1.80–45.1, p = 0.014).ConclusionsThis cohort highlights high rates of resistance amongst Gram-negative organisms in Rwanda, including the presence of carbapenem resistance. Nonetheless, the detailed prescribing data also highlight the challenges of using routine laboratory data to infer broader AMR prevalence. The significant exposure to empiric broad-spectrum antibiotic therapy prior to culturing introduces a selection bias and risks over-estimating the burden of resistant organisms. Broadening access to microbiological services and active surveillance outside of teaching hospitals are essential to support national and international efforts to curb the growth of AMR in low-resource settings.

Accuracy of the GeneXpert® MRSA/SA SSTI test to diagnose methicillin-resistant Staphylococcus spp. infection in bone fixation and fusion and management of infected non-unions

IntroductionThe GeneXpert® MRSA/SA SSTI (Methicillin Resistant Staphylococcus aureus/S. aureus skin and soft tissue infection) PCR test allows early detection of methicillin resistance in staphylococci. This test was developed for skin infections and has been evaluated for prosthetic joint infections but, to our knowledge, has not been evaluated for hardware infections outside of arthroplasties. Furthermore, we conducted a retrospective study in patients with non-prosthetic osteosynthesis hardware aiming: (1) to identify the diagnostic values of the PCR test compared to conventional cultures and the resulting rate of appropriate antibiotic therapy; (2) to identify the rate of false negative (FN) results; (3) to identify and compare the rates of failure of infectious treatment (FN versus others); (4) to search for risk factors for FN of the PCR test. HypothesisThe PCR test allowed early and appropriate targeting of antibiotic therapy. Material and methodsThe results of PCR tests and conventional cultures for osteoarticular infections of non-prosthetic hardware over four years (2012–2016) were compared to identify the diagnostic values of using the results of conventional culture as a reference and the rate of appropriate antibiotic therapies. Infectious management failures between the results of the FN group and the others were compared, and variables associated with a FN of the PCR test were identified. ResultsThe analysis of 419 PCR tests allowed us to establish a sensitivity of 42.86%, a specificity of 96.82%, a positive predictive value of 60% and a negative predictive value of 93.83%. Using the results of the PCR test for the targeting of postoperative antibiotic therapy, it was suitable for staphylococcal coverage in 90.94% (381/419). The rates of patients for whom infectious treatment failed were not significantly different between the FN group and the other patients (20.8% versus 17.7%, respectively; Hazard Ratio=1.12 (95%CI 0.47-2.69, p=0.79)). A skin opening during the initial trauma (p=0.005) and a polymicrobial infection were significantly associated with a risk of FN from the PCR test (p<0.001). ConclusionThe PCR test makes it possible to reduce the duration of empirical broad-spectrum antibiotic therapy during the treatment of an infection of osteosynthesis hardware but causes a lack of antibiotic coverage in 9.06% of cases. Level of evidenceIII; diagnostic case control study.

Can high procalcitonin levels be a biomarker for detecting multidrug-resistant Gram-negative bacteremia?

Aims: Clinicians prefer broad-spectrum empirical antibiotic therapy in patients with suspected bloodstream infection (BSI) due to long test turnaround times of conventional methods. We aimed to assess the contribution of procalcitonin (PCT) to the selection of antibiotics to be used in empirical treatment.&#x0D; Methods: The results of inpatients whose blood cultures and samples for PCT tests had been sent simultaneously between 2018 and 2022 were analyzed retrospectively. Antibiotic susceptibility results of Enterobacteriaceae, Acinetobacter baumannii complex and Pseudomonas aeruginosa, were evaluated for multidrug-resistance (MDR). &#x0D; Results: Results of 1206 patients who met the inclusion criteria were included in the study. The PCT median value in BSIs caused by the Gram-negative bacteria found to be statistically significantly higher than those caused by the Gram-positive bacteria, fungal and polymicrobial infections (p

A 20-Year Study of Intracranial Pyogenic Complications of Sinusitis in Children.

Intracranial pyogenic complications of sinusitis in children can lead to serious sequelae. We characterize the clinical, epidemiologic and microbiologic characteristics of children with such complications over a 20-year period. Single-center retrospective chart review. Cases were identified based on International Classification of Diseases diagnostic codes (ICD)-9 and ICD-10 depending on the year and by reviewing all intracranial microbiologic samples. A total of 104 cases of complicated sinusitis were included after review of 1591 charts. Median age was 12 (IQR 9-14); 72 were male (69%). The most frequent complications were epidural empyema (n = 50, 48%), subdural empyema (n = 46, 44%) and Pott's puffy tumor (n = 27, 26%). 52% (n = 54) underwent neurosurgery and 46% (n = 48) underwent otolaryngologic surgery. The predominant pathogen isolated from sterile site specimens was Streptococcus anginosus (n = 40, 63%), but polymicrobial growth was common (n = 24; 38%). The median duration of intravenous antibiotic therapy was 51 days (IQR 42-80). Persistent neurologic sequelae (or death, n = 1) were found in 24% (n = 25) and were associated with the presence of cerebritis and extensive disease on neuroimaging ( P = 0.02 and P = 0.04, respectively). Intracranial complications of sinusitis continue to cause significant morbidity in children. Polymicrobial infections are common, which reinforces the need for broad-spectrum empiric antibiotic therapy and cautious adjustment of the antibiotic regimen based primarily on sterile site cultures. The association of neurologic sequelae with the presence of cerebritis and extensive intracranial involvement on neuroimaging suggest that delayed diagnosis may be a contributor to adverse outcome.

The role of culture-negative infection among infectious complications after total knee arthroplasty

Introduction Diagnosis of chronic periprosthetic joint infection (PJI) is difficult with the clinical signs of periprosthetic inflammation showing no growth of microorganism in the biomaterial. The frequency of culture-negative infection can reach 42.1 %. The objective of the study was to analyze outcomes of two-stage treatment of chronic PJI of the knee joint depending on the etiology of the infectious process.Material and methods A retrospective analysis of outcomes was produced for 103 patients: group I (n=30) showing no growth of microorganisms and group II (n = 73) demonstrating positive growth of pathogens. Knee PJI was diagnosed according to the 2018 ICM criteria. A favorable outcome suggested absence of recurrence for at least two years after reimplantation of endoprosthesis, arthrodesis, “life with a spacer” without signs of infection.Results Culture-negative infection was detected in 29.1 % (n = 30). Patients in the group were 1.5 times more likely to receive antibiotic therapy prior to admission and had average levels of CRP, ESR and articular leukocyte count being 1.5-2 times less than those in group II. Staphylococci (69.8 %) including MRSE (75 %) was the leading pathogen in group II. Recurrence of infection was 3.4 % in group I and 16.9 % in group II (p = 0.0928), the two-stage treatment was successful in 96.7 % and 74 %, respectively (p = 0.0064).Discussion Causes for the lack of growth of microorganisms in biological materials included previous antibiotic therapy, wound drainage, violations of the rules for sampling of biological material, absence of media for the growth of atypical microorganisms and the ability of microorganisms to form biofilms on implant surfaces. An emergency histological examination of the affected tissues was practical during surgery in doubtful situations for adequate surgical approach. The results of a meta-analysis (2023) showed that the replacement of an infected endoprosthesis was more effective for the treatment of a culture-negative infection compared to debridement and preservation of implant.Conclusion The culture-negative infection group in our series showed better success rate of a two-stage treatment of PJI using implant replacement and broad-spectrum empiric antibiotic therapy at a two-year follow-up period. The negative microbiological result in the group could be caused by antibacterial drugs administered prior to diagnosis of PJI.

Aggressive abscesses in the head and neck region of probable odontogenic origin – two case reports

Odontogenic infections are the most common type of infections of the head and neck among adults. They usually spread continuously from the mandible and/or maxilla into the sublingual, submandibular or masticatory spaces, then directly into the parapharyngeal space. They require comprehensive diagnostic and therapeutic management, as they may potentially lead to life-threatening complications. We present two clinical manifestations of aggressive abscesses in the head and neck region of probable odontogenic origin and discuss different therapeutic approaches. The first patient, a 31-year-old man, was admitted because of a tumor-like lesion within the right maxillary sinus. He complained of purulent nasal discharge of two weeks duration despite antibiotic therapy. In the Caldwell-Luc operation a cyst filled with puss was displayed, the sac of the cyst and the polypoid mass were removed. The second patient, a 28-year-old man, was admitted due to an abscess of the left half of the neck and viscerocranium, with a large edema of this area, neck pain, fever, dyspnea and lockjaw. The patient was qualified for surgery. During intubation, a purulent collection emptied into the oral cavity and throat. In both cases, simultaneously with the surgery, an empirical broad-spectrum antibiotic therapy was administered. Microbiological analysis of the material collected during the operations revealed Prevotella melaninogenica in the first case, and Streptococcus group C in the second. Treatment of aggressive odontogenic infections must take a comprehensive approach, including both surgical intervention and antibiotic therapy covering Gram-positive as well as Gram-negative aerobic and anaerobic pathogens.

Bacteraemia caused by Lactobacillus casei in a patient after cardiac surgery. A case report

BackgroundBacteria of the Lactobacillus family are a part of the physiological flora of the oral cavity, gastrointestinal tract, and urinary tract. We have used them in the food industry as probiotics and supplements. In some settings, rod-shaped lactic acid bacteria may become pathogenic. It may occur in immunocompromised or heart disease patients after cardiac surgery, patients with disturbed intestinal wall permeability, or those treated with broad-spectrum antibiotics.Case presentationWe present rare bacteraemia induced by the probiotic bacterium Lactobacillus casei in a 63-year-old patient after the attempted removal of ICD electrodes, complicated by acute regurgitation of the tricuspid valve. The patient underwent urgent cardiac surgery, the electrode elements were removed, and the tricuspid valve was replaced with a biological prosthesis. After surgery, the patient required intensive, multidisciplinary treatment with mechanical ventilation, continuous renal replacement therapy, broad-spectrum empirical antibiotic therapy, parenteral nutrition, and blood product transfusion because of multiple organ failure. On the 14th day of hospitalisation, the clinical symptoms of septic shock were observed. The microbiological investigation was performed, and Lactobacillus casei was cultured from a dialysis catheter sample. Dedicated antimicrobials were administered, and the patient was discharged home in good overall condition.ConclusionsThe present case shows that the promoted use of probiotics must be cautiously administered to patients in severe conditions, especially when accompanied by reduced immune system efficiency symptoms.

Appropriateness of Empirical Antibiotic Therapy in Hospitalized Patients with Bacterial Infection: A Retrospective Cohort Study.

The incidence of inappropriate and excessive empirical antibiotic therapy is unclear. The aim of this study was to determine the prevalence of different empirical antibiotic therapy prescriptions, related factors, and outcomes in hospitalized patients with bacterial infection. A retrospective cohort study was performed and patients with bacterial infection who were admitted between October 1, 2019, and September 30, 2020, were included. Multivariable analysis was performed by the logistic regression model. A total of 536 (42.6%) of the 1257 included patients received inappropriate empirical antibiotic therapy (IEAT), and 368 (29.3%) patients received appropriate but unnecessarily broad-spectrum empirical antibiotic therapy (AUEAT). MDRO (adjusted OR 2.932 [95% CI 2.201~3.905]; p < 0.001) and fever on admission (adjusted OR 0.592 [95% CI 0.415~0.844]; p = 0.004) were correlates of IEAT; sepsis (adjusted OR 2.342 [95% CI 1.371~3.999]; p = 0.002), age (adjusted OR 1.019 [95% CI 1.008~1.030]; p < 0.001), MDRO (adjusted OR 0.664 [95% CI 0.469~0.941]; p = 0.021), and urinary tract infection (adjusted OR 0.352 [95% CI 0.203~0.611]; p < 0.001) were correlates of AUEAT. Patients who received AUEAT were more likely to have a poor prognosis (63 [17.8%] vs 101 [27.4%]; p = 0.002). Both IEAT (median [IQR], 24,971 [13,135-70,155] vs 31,489 [14,894-101,082] CNY; p = 0.007) and AUEAT (median [IQR], 24,971 [13,135-70,155] vs 30,960 [16,475-90,881] CNY; p = 0.002) increased hospital costs. 45.3% (570/1257) of patients were infected with MDRO and 62.9% of them received IEAT. Inappropriate and excessive empirical antibiotic use was widely prevalent among hospitalized patients. Either inappropriate or excessive use of antibiotics may increase the burden of healthcare costs, the latter of which may be associated with poor prognosis. Clinicians need to be more judicious in choosing antibiotic(s). The MDRO epidemic was severe, especially in patients who received IEAT. It is imperative to take effective measures to improve the current situation of antibiotic abuse and antimicrobial resistance.

Fear of Missing Organisms (FOMO): the discordance among broad-spectrum empiric antibiotic therapy, microbiologic results, and definitive antibiotic therapy for diabetic foot infections and lower extremity osteomyelitis.

Empiric broad-spectrum antibiotic therapy is commonly prescribed for patients hospitalized with diabetic foot infections (DFI) and lower extremity osteomyelitis (OM). The primary objective was to evaluate the concordance between empiric antibiotic therapy, microbiologic results, and definitive antibiotic therapy with a focus on methicillin-resistant Staphylococcus aureus (MRSA) and resistant gram-negative organisms. The secondary objective was to evaluate the negative predictive values (NPV) of select risk factors for MRSA and resistant gram-negative organisms for microbiologic results with these organisms. Retrospective cohort study. Safety-net health system in Ohio. Adults hospitalized and receiving antibiotic therapy for DFI or lower extremity OM in 2021. For 259 unique patients, empiric therapies with activity against MRSA and resistant gram-negative organisms were administered to 224 (86.5%) and 217 (83.8%) patients, respectively. Definitive therapies with activity against MRSA and resistant gram-negative organisms were administered to 91 (35%) and 74 (28.6%) patients, respectively. Of 234 patients with microbiologic testing, 29 (12.4%) had positive cultures with MRSA and 41 (17.5%) with resistant gram-negative organisms. The NPVs of risk factors for MRSA and resistant gram-negative organisms for the absence of these organisms in culture were 91% and 85%, respectively. For patients hospitalized with DFI and lower extremity OM, our data suggest opportunities for substantial reductions in empiric therapies with activity against MRSA and resistant gram-negative organisms. The absence of risk factors for these organisms was reasonably good at predicting negative cultures with these organisms.

Are There Any Changes in the Causative Microorganisms Isolated in the Last Years from Hip and Knee Periprosthetic Joint Infections? Antimicrobial Susceptibility Test Results Analysis.

PJIs following total hip and knee arthroplasty represent severe complications with broad implications, and with significant disability, morbidity, and mortality. To be able to provide correct and effective management of these cases, an accurate diagnosis is needed. Classically, acute PJIs are characterized by a preponderance of virulent microorganisms, and chronic PJIs are characterized by a preponderance of less-virulent pathogens like coagulase-negative staphylococci or Cutibacterium species. This paper aims to analyze if there are any changes in the causative microorganisms isolated in the last years, as well as to provide a subanalysis of the types of PJIs. In this single-center study, we prospectively included all retrospectively consecutive collected data from patients aged over 18 years that were hospitalized from 2016 through 2022, and patients that underwent a joint arthroplasty revision surgery. A standardized diagnostic protocol was used in all cases, and the 2021 EBJIS definition criteria for PJIs was used. 114 patients were included in our analysis; of them, 67 were diagnosed with PJIs, 12 were acute/acute hematogenous, and 55 were chronic PJIs. 49 strains of gram-positive aerobic or microaerophilic cocci and 35 gram-negative aerobic bacilli were isolated. Overall, Staphylococcus aureus was the most common isolated pathogen, followed by coagulase-negative staphylococci (CoNS). All cases of acute/acute hematogenous PJIs were caused by gram-positive aerobic or microaerophilic cocci pathogens. Both Staphylococcus epidermidis and methicillin-resistant S. aureus were involved in 91.66% of the acute/acute hematogenous PJIs cases. 21.8% of the chronic PJIs cases were caused by pathogens belonging to the Enterobacterales group of bacteria, followed by the gram-negative nonfermenting bacilli group of bacteria, which were involved in 18.4% of the cases. 12 chronic cases were polymicrobial. Based on our findings, empiric broad-spectrum antibiotic therapy in acute PJIs could be focused on the bacteria belonging to the gram-positive aerobic or microaerophilic cocci, but the results should be analyzed carefully, and the local resistance of the pathogens should be taken into consideration.

Necrotizing Fasciitis due to Streptococcus constellatus in a Patient with Uncontrolled Diabetes and Bilateral Diabetic Foot Ulceration

Introduction. Streptococcus constellatus is commensal flora of the oropharyngeal, gastrointestinal, and genitourinary tracts with a proclivity for abscess formation. Bacteremia due to S constellatus is rare; however, rising incidences have been reported, particularly in patients with diabetes. Prompt surgical debridement and antibiotic therapy with a cephalosporin are the mainstays of treatment. Case Report. The case presented here involves a patient with poorly controlled diabetes who had necrotizing soft tissue infection secondary to S constellatus. The infection originated from bilateral diabetic foot ulcerations that led to bacteremia and sepsis. Conclusion. Immediate source control with wide and aggressive surgical debridement, initial empiric broad-spectrum antibiotic therapy followed by tailored treatment based on deep operative cultures, and staged closure led to effective limb-salvage and life-sparing intervention for this patient.

665 THE UNFORSEEN MECHANISM: A CASE OF DISTRIBUTIVE SHOCK SECONDARY TO REACTIVE HAEMOPHAGOCYTIC SYNDROME LEADING TO SEVERE REVERSIBLE BIVENTRICULAR DYSFUNCTION.

Abstract Distributive shock comprises a variety of processes causing dysregulated vasodilation with consequent life-threatening end-organ dysfunction. While sepsis constitutes by far its most common aetiology, other pathological mechanisms with different therapeutic targets may lead to a similar haemodynamic picture. We hereby present the case of a 35-year-old male with no past cardiological history and a recent diagnosis of stage IVsB Hodgkin's lymphoma relapse 10 years after effective disease eradication with first-line chemotherapy. Shortly after a single cycle of second-line chemotherapy, the patient presented with high fever, acute chest pain and dyspnea associated with marked hypotension and sinus tachycardia. Laboratory tests revealed pancytopenia and raised inflammatory markers as well as evidence of acute kidney injury and hepatocellular damage. Urgent thoracic CT revealed no signs of pneumonia while echocardiography demonstrated severe biventricular dysfunction with 25% left ventricular ejection fraction and severe functional mitral regurgitation. Due to worsening tachypnea and desaturation the patient was intubated and transferred to our Intensive Cardiac Care Unit where urgent instatement of circulatory support with iv fluids, blood transfusions, adrenaline and intra-aortic balloon pump were performed and empirical broad-spectrum antibiotic therapy was started after performing blood cultures from peripheral and central veins. Concurrent right ventricular catheterisation demonstrated high-output cardiac failure (Qs Fick 7.89 Qp/m2, Qs thermodilution 8.0 Qp/m2) with mild increase in biventricular filling pressures and post-capillary pulmonary hypertension. Endomyocardial biopsy in turn revealed only mild subendocardial fibrosis and oedema thus excluding myocarditis as a potential cause for the severe biventricular dysfunction. Due to worsening of renal function with persistent anuria despite circulatory support the patient required continuous veno-venous haemofiltration. Notably, over the coming days no pathogen was isolated from any of the cultures with haemodynamic and respiratory parameters gradually improving, allowing for weaning from circulatory and respiratory support. On further examination of blood tests on admission, hypertriglyceridemia, raised ferritin levels and thrombin consumption were noted. These biochemical features, together with the history of Hodgkin's lymphoma relapse, recent chemotherapy, pancytopenia and splenomegaly, suggestive of natural killer cell dysfunction-related haemophagocytosis, pointed to reactive haemophagocytic syndrome as a potential aetiology of the severe distributive shock (&amp;gt; 99% probability on recently published “HS Score” for Reactive Haemophagocytic Syndrome). This hypothesis was further corroborated by the gradual albeit not complete regression of the severe biventricular dysfunction after haemodynamic support suggesting that this may have represented a byproduct of the patient's high-output state. Unfortunately, due to lymphoma progression with severe multiorgan involvement the patient was admitted shortly after discharge and deceased thereafter. This case provides an example of the diversity of potential disease mechanisms underlying distributive shock where biventricular dysfunction may represent a reversible albeit severe bystander rather than the true driving factor of its life-threatening haemodynamic compromise.

Non-Coding RNA Networks as Potential Novel Biomarker and Therapeutic Target for Sepsis and Sepsis-Related Multi-Organ Failure.

According to “Sepsis-3” consensus, sepsis is a life-threatening clinical syndrome caused by a dysregulated inflammatory host response to infection. A rapid identification of sepsis is mandatory, as the extent of the organ damage triggered by both the pathogen itself and the host’s immune response could abruptly evolve to multiple organ failure and ultimately lead to the death of the patient. The most commonly used therapeutic strategy is to provide hemodynamic and global support to the patient and to rapidly initiate broad-spectrum empiric antibiotic therapy. To date, there is no gold standard diagnostic test that can ascertain the diagnosis of sepsis. Therefore, once sepsis is suspected, the presence of organ dysfunction can be assessed using the Sepsis-related Organ Failure Assessment (SOFA) score, although the diagnosis continues to depend primarily on clinical judgment. Clinicians can now rely on several serum biomarkers for the diagnosis of sepsis (e.g., procalcitonin), and promising new biomarkers have been evaluated, e.g., presepsin and adrenomedullin, although their clinical relevance in the hospital setting is still under discussion. Non-codingRNA, including long non-codingRNAs (lncRNAs), circularRNAs (circRNAs) and microRNAs (miRNAs), take part in a complex chain of events playing a pivotal role in several important regulatory processes in humans. In this narrative review we summarize and then analyze the function of circRNAs-miRNA-mRNA networks as putative novel biomarkers and therapeutic targets for sepsis, focusing only on data collected in clinical settings in humans.

Positivity Trends of Bacterial Cultures from Cases of Acute and Chronic Periprosthetic Joint Infections.

Background: There is no clear distinction in the literature regarding the positivity trends of bacterial cultures in acute and chronic prosthetic joint infections. Methods: We prospectively included in this study all consecutive patients, aged over 18 years, that were hospitalized from September 2016 through December 2019, that underwent a joint arthroplasty revision surgery. Results: Forty patients were included in our analysis, 11 acute/acute hematogenous and 29 chronic PJIs. We were able to identify all strains of acute/acute hematogenous PJIs within 3 days, whereas this took 8 days for chronic PJIs. Sonication fluid cultures increased the positivity rate and helped in identifying rare pathogens such as Ralstonia pickettii from chronic PJIs, but also increased the number of identified strains from acute PJIs. Culturing synovial fluid in our study did not seem to have a clear benefit compared to sonication fluid and periprosthetic tissue cultures. Conclusion: There was a different positivity trend in bacterial cultures. Empiric broad-spectrum antibiotic therapy can be re-evaluated after 3 days for acute PJIs. A prolonged incubation time, especially in the case of chronic PJIs, is mandatory; however, extending the incubation period beyond 14 days would not further improve the ability to identify microorganisms.

Necrotizing fasciitis of the neck: A rare diagnostic emergency

A 76-year-old male, with no prior medical history, was referred to our hospital due to odynophagia and fever with 3 days, sudden worsening with dyspnea, drooling, edema and anterior neck pain. Physical examination revealed tachypnea, trismus, halitosis, bulging of the pharyngeal lateral walls and salivary stasis. No evidence of peritonsillar abscess or tonsil exudate was observed. Contrast-enhanced computed tomography (CT) of the neck revealed an organized collection involving both parapharyngeal and retropharyngeal with air bubbles and edema of the surrounding tissues (Figure 1). The patient was immediately admitted, started empiric broad-spectrum antibiotic therapy and submitted to an emergent surgical drainage. After securing the airway with tracheotomy, a trans-cervical drainage was performed. The drained pus had a grayish color and a foul smell. Necrotic tissue of fascia and sternocleidomastoid muscle were removed, as much as possible, without compromising vital structures. The cervical spaces were irrigated with a diluted solution of povidone-iodine and hydrogen peroxide. Penrose drains were placed and the skin was “loosely” approximated with minimal sutures. (Figure 2). Microbiology of the pus culture revealed the presence of Streptococcus constellatus, Eikenella corrodens, Prevotella buccae and Parvimonas micra.