Empirical Antibiotic Treatment Research Articles

Antibiotic and Surgical Treatment of Diabetic Foot Osteomyelitis: The Histopathological Evidence

Background: Osteomyelitis is one of the most frequent infections of the diabetic foot, accounting for 20–70% of foot infections. The treatment of osteomyelitis continues to be debated, and the possibility of performing conservative surgery associated with targeted antibiotic treatment allows for reductions in the amount of bone removed, the resolution of osteomyelitis, and a reduction in the changes in the biomechanics of the foot. The objective of this study was to evaluate the outcomes of osteomyelitis treatment with a combination of antibiotic and surgical procedures based on a histopathological analysis of the infected bone and margins. Materials and Methods: We analyzed 25 diabetic patients with osteomyelitis. We treated each patient with empiric antibiotic treatment, surgical removal of the infected bone, and targeted antibiotic treatment. During the surgical procedure, we collected infected bone samples and margins for microbiological and histopathological analyses. Results: All the patients had type 2 diabetes, with a mean age of 71 ± 10 years. Antibiotic therapy was administered orally for an average duration of 21 ± 9 days, aimed at improving the microbiological outcome. Histological examinations of the resected infected bone revealed the presence of osteomyelitis in 23 (92%) patients. The healthy margin sample, surgically assessed as non-infected, was confirmed negative in 80% of cases. At a follow-up of 18 ± 7 months, we achieved complete healing in twenty patients (80%), with an average healing time of 70 ± 41 days. No recurrence of osteomyelitis was observed. Conclusions: The data from this study demonstrate that the combination of targeted antibiotic therapy and conservative surgical treatment is effective in resolving osteomyelitis without recurrence with a very long follow-up. Histological analyses allowed us to confirm the actual presence of osteomyelitis and demonstrate that clinical differentiation during surgery is effective in identifying a healthy margin.

Current knowledge of vertebral osteomyelitis: a review.

As life expectancy increases worldwide, the elderly population in every country is growing in both the size and proportion. This review aims to provide a comprehensive overview of the microbiology, clinical presentation, diagnostic strategies, and therapeutic approaches to vertebral osteomyelitis, summarizing the latest evidence to guide effective treatment. A comprehensive literature search was conducted using the Medline and Embase databases to identify relevant studies on vertebral osteomyelitis. The search included the following keywords: "vertebral osteomyelitis," "spinal infection," "discitis," "spondylitis," " spondylodiscitis," and "spinal epidural abscess." Both retrospective and prospective studies, case series, and reviews were considered. This condition is commonly caused by bacteria such as Staphylococcus aureus or gram-negative bacilli, but can also be caused by other pathogens like fungi and parasites. The onset of vertebral osteomyelitis is insidious, with low specificity in clinical manifestations, often making early diagnosis difficult. Delayed or inadequate treatment may lead to sepsis, permanent neurological damage, or even death. Treatment strategies emphasize the importance of identifying the causative pathogen to guide effective antimicrobial therapy. Current consensus does not advocate for empirical antibiotic treatment unless patients exhibit signs of neurological impairment or severe sepsis. Severe cases involving neurological paralysis, spinal instability, or sepsis may require surgical intervention. Vertebral osteomyelitis requires prompt diagnosis and treatment for a good prognosis. Delayed diagnosis and treatment can lead to permanent neurological deficits or death. Identifying the causative organism is crucial for guiding appropriate antimicrobial therapy. In addition to conservative and surgical treatments, local drug delivery systems offer new approaches to managing spinal osteomyelitis.

Skin and Soft Tissue Nontuberculous Mycobacteria Infection: A Retrospective Case Series of 49 Patients.

The incidence of skin and soft tissue nontuberculous mycobacteria infection (SSTNI) is increasing. But it may be challenging to diagnose and treat SSTNI. To summarize course, clinical features, diagnosis and treatment of SSTNI and discuss the association between SSTNI and procedures. A retrospective case series study was conducted among patients diagnosed with SSTNI after surgical procedures. Medical history was collected, disease course and characteristics were analyzed. 49 patients were collected. Among them, 39 (80%) patients were infected with Mycobacterium abscesses. 40 (82%) patients had a history of fat-related procedures. The median and interquartile range of onset time were 15 and 43 days (1-100). Time from first visit to diagnosis was 82±57 days (23-308). Wound healing time was 161±92 days (30-545). The most common symptom were redness (96%), followed by swelling (96%), abscess (84%), pain (80%) and induration (76%). The most common infected site were head and neck (56%), followed by breasts (20%). 6 (12.5%) patients were diagnosed clearly before admission to our department. 10 (28%) patients showed positive acid-fast bacilli (AFB) smears among 36 patients. Treatment included debridement surgeries, drainage and antibiotics. Patient with the above symptoms should be considered as SSTNI. Results of AFB smears are frequently negative after empirical antibiotic treatment so that molecular diagnostic techniques are required for rapid and accurate identification. Debridement surgeries, drainage and sensitive antibiotics are effective. Drug safety and psychological status should be paid attention. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Testing and Treatment Thresholds for Pediatric Pneumonia in the Emergency Department.

Clinical prediction models for pediatric community-acquired pneumonia (CAP) may standardize management. Understanding physician risk thresholds is important for model implementation. We aimed to elucidate physician-derived thresholds for chest radiograph performance and empirical antibiotic treatment of CAP among children presenting to the emergency department with respiratory illness before and after knowledge of results of a validated clinical prediction model. Pediatric emergency physicians were surveyed through the American Academy of Pediatrics Pediatric Emergency Medicine Collaborative Research Committee and provided 8 clinical vignettes for children with respiratory symptoms. Respondents were asked to indicate their probability of radiographic CAP and choose whether they would obtain a chest radiograph or give empirical antibiotics before and after being provided with the probability of radiographic CAP based on a validated prediction model. We used logistic regression to establish testing and treatment thresholds, defined as the disease probability at which half of physicians acted. Two-hundred and eight (44.3%) of 469 physicians completed the survey. Most were attending physicians (96.0%) practicing in a freestanding children's hospital (76.8%). Testing and treatment thresholds for CAP were 17.6% (95% confidence interval [CI] 16.4% to 18.8%) and 66.1% (95% CI 60.1% to 72.5%), respectively, before knowledge of the model-estimated probability. With knowledge of the prediction model, testing and treatment thresholds were 13.5% (95% CI 12.3% to 14.7%) and 58.0% (95% CI 53.2-62.8). We elucidated physician thresholds for testing and treatment of CAP, which may be integrated into future pneumonia risk models to improve acceptability and incorporation into practice.

Burden and Risk Factors for Coinfections in Patients with a Viral Respiratory Tract Infection.

Which patients should be monitored for coinfections or should receive empirical antibiotic treatment, in patients with an acute viral respiratory infection, is largely unknown. We evaluated the prevalence, characteristics, outcomes of coinfected patients, and risk factors associated with a coinfection among patients with an acute viral infection. A retrospective, single-center study recruited consecutive patients from October 2022 to March 2023 presenting to the emergency department with signs of a respiratory tract infection. Patients were screened for respiratory viruses and bacterial/fungal secondary infections according to local standard procedures. Outcomes included severe disease, in-hospital complications, all-cause in-hospital and ICU-related mortality, time to death, time to discharge, and time to coinfection. The analysis included 652 patients. A viral infection and a secondary bacterial/fungal infection were detected in 39.1% and 40% of cases. Compared with the rest of the cohort, coinfected patients had more frequently severe disease (88.3%, p < 0.001; 51% in patients with SARS-CoV-2) and higher in-hospital mortality (16.5%, p = 0.010). Nephropathy (OR 3.649, p = 0.007), absence of COVID-19 vaccination (OR 0.160, p < 0.001), SARS-CoV-2 infection (OR 2.390, p = 0.017), and lower blood pressure at admission (OR 0.980, p = 0.007) were independent risk factors for coinfection. Multidrug-resistant pathogens were detected in 30.8% of all coinfections. Patients with a viral infection are at high risk of bacterial coinfections, which carry a significant morbidity and mortality burden.

Gram-Negative Bloodstream Infections in a Medical Intensive Care Unit: Epidemiology, Antibiotic Susceptibilities, and Risk Factors for in-Hospital Death.

Gram-negative bloodstream infection (GNBI) poses a serious threat to critically ill patients. This retrospective study aimed to uncover drug resistance of pathogens and the GNBI effect on in-hospital death and distinguish death risk factors in a medical intensive care unit (ICU). A retrospective study of all GNBI patients in the medical ICU of the Third Xiangya Hospital over 9 nine years was conducted. Blood samples were performed by a BACTEC 9240 system, MALDI-TOF MS, Bruker and Vitek-2 system. Logistic regression was used for analyzing risk factors for death. Seventy-five episodes of GNBI developed in 68 (1.4%) out of 4954 patients over a span of 9 years. The most frequently isolated bacterium was Klebsiella pneumoniae, with the lungs as the predominant source of GNBI. The resistance rate of Gram-negative bacteria to polymyxin B was 11.6% after excluding those intrinsically resistant non-fermentativebacteria. All Enterobacter spp. were susceptible to ceftazidime/avibactam. Thirty-three (48.5%) patients underwent inappropriate empirical antibiotic treatment and 48 (70.6%) patients died during the hospitalization. Multivariate logistic regression analysis identified that lymphocyte count at GNBI onset ≤0.5×109/L, invasive mechanical ventilation, and septic shock were related to in-hospital death. Body mass index ≥23 and appropriate empirical antibiotic use after GNBI were negatively associated with in-hospital death. GNBI was a frequent complication among patients in the medical ICU. This study underscored the presence of diverse factors that either heightened or attenuated the risk of in-hospital death.

Timely empirical antibiotic therapy against sepsis in a rural Norwegian ambulance service: a prospective cohort study

BackgroundEarly diagnosis and antibiotic therapy in patients with sepsis reduce morbidity and mortality, thus pre-hospital management is likely to affect patient outcomes. Pre-hospital administration may increase the risk of unnecessary use of broad-spectrum antibiotics, but identification of an infectious focus enables more targeted antibiotic therapy. The aim of this study was to investigate how paramedics, with or without the assistance of general practitioners, can administer empiric intravenous antibiotic treatment against sepsis in a timely manner.MethodsCohort study of patients with suspected sepsis that received pre-hospital intravenous antibiotics and were transported to hospital. The setting was mainly rural with long average distance to hospital. Patients received targeted antibiotic treatment after an assessment based on clinical work-up supported by scoring systems. Patients were prospectively included from May 2018 to August 2022. Results are presented as median or absolute values, and chi-square tests were used to compare categorical data.ResultsWe included 328 patients. Median age was 76 years (IQR 64, 83) and 48.5% of patients were female. 30-days all-cause mortality was 10.4%. In cases where a suspected infectious focus was determined, the hospital discharge papers confirmed the pre-hospital diagnosis focus in 195 cases (79.3%). The presence of a general practitioner during the pre-hospital assessment increased the rate of correctly identified infectious focus from 72.6% to 86.1% (p = 0.009). Concordance between pre-hospital identification of a tentative focus and discharge diagnosis was highest for lower respiratory tract (p = 0.02) and urinary tract infections (p = 0.03). Antibiotic treatment was initiated 44 min (median) after arrival of ambulance, and median transportation time to hospital was 69 min. Antibiotic therapy was started 76 min (median) before arrival at hospital.ConclusionsPre-hospital identification of infectious focus in suspected sepsis was feasible, and collaboration with primary care physicians increased level of diagnostic accuracy. This allowed initiation of intravenous focus-directed antibiotics more than one hour before arrival in hospital in a rural setting. The effect of pre-hospital therapy on timing was much stronger than in previous studies from more urban areas.

Benefits and Safety of Empiric Antibiotic Treatment Active Against KPC-Producing Klebsiella pneumoniae for Febrile Neutropenic Episodes in Colonized Children with Acute Leukemia-An 8-Year Retrospective Observational Study.

In children with acute leukemia (AL), the mortality rate from Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae bloodstream infection (KPC-KpBSI) exceeds 50%, highest when active treatment is delayed. Neutropenic KPC-K. pneumoniae carriers are at high risk of KPC-KpBSI, and preemptive empiric antibiotic treatment (EAT) of febrile neutropenic episodes (FNEs) active against KPC-K. pneumoniae may reduce this mortality. We conducted an 8-year (2014-2021) retrospective observational study of 112 febrile neutropenic episodes (FNEs) in 32 children with AL who were KPC-K. pneumoniae carriers: standard EAT for 39 FNEs and active EAT for 73 FNEs (52 ceftazidime/avibactam (CAZAVI)-based and 21 colistin-based combinations, and 5 CAZAVI monotherapy). Successful outcomes (survival from FNE) were observed in 94%; seven were fatal, with four due to infectious causes. KPC-KpBSIs caused 10/112 FNEs, 10/20 g-negative BSIs, and 3 deaths. The mortality rate of KPC-KpBSI was 30%. Active EAT was successful in 97% of the FNEs, compared to 87% with standard EAT. All deaths from KPC-KpBSI occurred in patients who received standard EAT, while none occurred with active EAT. KPC-KpBSI mortality rate with initial inactive treatment was 60%. CAZAVI-based EAT was successful in all FNEs, with a higher success rate without any modification compared to colistin-based EAT, where nephrotoxicity occurred in 14%. Therefore, active EAT, mainly a CAZAVI-based combination, was effective, safe, and associated with low overall and KPC-KpBSI-related mortality.

Spinal subdural empyema in an immunocompetent patient: illustrative case.

Spinal subdural empyemas are a rare presentation of rapid neurological decline, progressing from radiculopathy to complete paralysis and sensory loss. Although pathogenic mechanisms have been hypothesized, their occurrence in this population of patients remains unclear. The authors present the third documented case of an isolated spinal subdural empyema of unclear etiology in an immunocompetent patient with no established risk factors. Successful treatment requires prompt clinical suspicion, radiological diagnosis, and surgical evacuation along with empirical antibiotic treatment. Radiological clarification of the subdural versus the epidural location of the empyema is difficult, while intraoperative durotomy for exploration risks subdural dissemination. In these cases, intraoperative ultrasonography would be a useful adjunct and decision aid. https://thejns.org/doi/10.3171/CASE24464.

Microbiology of periprosthetic infections following implant-based breast reconstruction surgery: a multicentric retrospective study.

Implant-based breast reconstruction (IBR) is the predominant breast reconstruction technique post-mastectomy, with bacterial infections being a significant complication affecting patient recovery and quality of life. The following study aimed to determine the microbiological features of the causative agents responsible for breast implant infections, with more attention paid to the comparative analysis of Gram-positive and Gram-negative bacteria and their presentation. We conducted a retrospective analysis of 214 patients who presented with periprosthetic infection and underwent implant removal following implant-based breast reconstruction at Humanitas Research Hospital and Istituto Europeo di Oncologia between January 2018 and March 2024. The study revealed that Gram-positive bacteria were more prevalent, with Staphylococcus species, particularly Staphylococcus aureus, being the most isolated pathogen in both institutions (∼39.96%). In contrast, Gram-negative bacteria were less frequent, with a higher proportion of these pathogens being multi-resistant strains. A significant difference was observed (p = 0.007), indicating that individuals with normal BMI have a higher prevalence of Gram-positive infections (88.46%), whereas obese and overweight patients had higher proportions of Gram-negative infections (23.53% and 28.89%, respectively). In addition, smoking status was also significantly associated with pathogen distribution (p = 0.032), with active and past smokers being related to higher percentages of polymicrobial infections. Furthermore, positive prophylactic MSSA/MRSA swabs were significantly more associated with Staphylococcus aureus infections compared to those with negative results (p = <0.001). Gram-positive bacteria, especially Staphylococcus species, dominate the microbiological landscape of implant-based breast reconstruction (IBR) infections. Our findings provide insights into this critical issue, facilitating a more precise choice of empiric antibiotic treatment and prevention strategies. This analysis underscores the necessity for prophylactic protocols and therapeutic approaches tailored to the predominant bacterial groups. Further research is needed to explore long-term trends and resistance mechanisms to improve patient management.

Bacteremias in Hemato-Oncological Pediatric Patients: Clinical and Microbiological Characteristics

Abstract Background In haemato-oncologic patients bacteremia is frequent increasing mortality rates, therefore surveillance and close follow up is essential to optimize treatment. The use of invasive devices used frequently in this population increases the incidence of infections by gram-positive microorganisms (currently gram-negative bacilli have been added). Therefore, we propose the characterization the microorganisms to identify the epidemiologic conditions, and the areas of improvement to establish improvement care strategies for this population. Methods We conducted a retrospective study at the haemato-oncologic diseases service at the National Medical Center “20 de Noviembre”. Prevalence of bacteremia in pediatric patients with cancer and neutropenia in Mexican population, which ranges from 8% to 36%, assuming that our results could be similar to higher percentage, employing a proportion formula with a study population of 65 patients. Results It was demonstrated in our population studied that in all cases of bacteremia, patients were in depth neutropenia at diagnosis. The most prevalence phase of chemotherapy was Induction phase (69.2%), with Total XV ST Jude protocol. The clinical data revealed the following frequencies in 100% of the patients: Fever (92%), Tachycardia (72%), Shivering and piloerection (65%), Elevated acute-phase reactants PCT (51%), CPR (32%), and Tachypnea (28%). Cases of Central Line-associated Bloodstream Infection (CLABSI) was reported in 86.2%, affecting individuals with vascular devices. The predominant microbiological isolate in our patients was Escherichia coli ESBL (31%), followed by Klebsiella pneumoniae (18%), and Pseudomonas aeruginosa (13.8%), Staphylococcus epidermidis (11%). Other bacteria were identified at even lower frequencies, such as Stenotrophomonas maltophilia (5%), Klebsiella oxytoca (5%), Staphylococcus aureus (3%), Serratia marcescens (3%), Enterococcus faecalis (3%), and Enterobacter cloacae (3%). The least observed in our population was the identification of Acinetobacter baumannii (2%). The different outcomes recorded in our sample were highly consistent, with a resolution rate of infection in 97% of cases and 3% of cases resulting in death attributable to bacteremia (Table 1). Conclusion The low mortality found in this study may be due to the early initiation of empirical antibiotic treatment in “golden hour”, a protocol carried out in our Center, as well as the identification of severity scales.

Clinical and epidemiological characterization of infections in pediatric hemato-oncology patients with febrile neutropenia in the North of Mexico

Abstract Background Neutropenic fever is the most common complication in patients undergoing chemotherapy, where the choice of empirical antibiotic treatment should be based on the probable focus of infection, the predominant causative microorganisms, and the sensitivity of those organisms to antibiotics, which varies between each hospital and region. Over time, the spectrum of isolated microorganisms in different clinical syndromes of patients presenting during their infectious episode has changed. Our objective is to describe the prevalence of infectious etiology in pediatric patients with neutropenic fever, as well as the clinical characteristics of patients with documented infection. Methods The study design is ambispective, observational, and descriptive of a cohort type. Patients between 0 and 18 years old from the pediatric department of the “Dr. José E. González” University Hospital will be included from May 2019 to June 2023, with hematological-oncological disease during their febrile neutropenia infectious process with a complete medical record. Results A total of 326 episodes of febrile neutropenia were included, of which 15% had microbiological isolation (49 patients). The etiological classification during the events was as follows: bacteria 81%, viruses 14%, and fungi 4%. Five different infection sites were identified. Among these, bacteremia were the most frequent site of infection (10%), followed by gastrointestinal infections (2.4%), respiratory infections (1.5%), skin and soft tissue infections (1.2%), and lastly, urinary tract infections (1%). A total of 45 microorganisms were isolated from different infection sites. Among these, gram-negative bacteria (28 isolates, 62%) were more common and outnumbered gram-positive bacteria (14 isolates, 31%). Among gram-negatives, Escherichia coli (42%) was the most common isolate, followed by Pseudomonas aeruginosa (17%), and Klebsiella pneumoniae (14%). Among gram-positives, Streptococcus mitis (28%), Coagulase-negative Staphylococcus (21%), and Rothia mucilaginosa (14%) were identified. Conclusion Febrile neutropenia at the Hospital Universitario primarily affects 6-year-old males with ALL. The microbiological characterization suggests the intentional search for gram-negative bacteremia, allowing us to direct timely and targeted antibiotic therapy to influence clinical prognosis. It is worthwhile to continue the research line that allows us to identify susceptibility and resistance profiles to address these patients more effectively.

Gas gangrene with Clostridium septicum in a neutropenic patient.

Gas gangrene is a rare presentation of a necrotizing fasciitis, caused by Clostridium perfringens, C. septicum and other clostridial species. With its rapid progression it is a potentially life-threatening infection, that poses as a challenge in the clinical management requiring an interdisciplinary approach.Here we present a 62-year-old woman, who developed neutropenic fever while undergoing chemotherapy for triple negative breast cancer. She presented with a high fever, reporting little pain in her left thigh accompanied by redness and induration locally. Subsequently the patient developed pain and redness of the back of the left hand. The initial findings suggested cellulitis and immediate empiric treatment with intravenous meropenem was started. Despite the antibiotic treatment the patient rapidly developed septic shock along with progression of the local infection. Emergency surgical debridement revealed extensive necrosis of the soft tissues including extensive myonecrosis of the thigh. On the left hand an extensive debridement was performed, the left lower limb could not be preserved and exarticulation of the left hip was required. Microbiologically C. septicum was isolated in different samples, confirming gas gangrene. As there was no local entry portal on the skin, hematogenous seeding from intestinal translocation in this neutropenic patient was suspected. The empiric antibiotic treatment was tailored to intravenous penicillin and complemented with clindamycin for toxin inhibition. Following radical debridement and antibiotic treatment, the patient could be stabilized. After repetitive debridement wound closure was achieved and the patient was discharged for rehabilitation. Antibiotic treatment was continued for four weeks.This rare case of gas gangrene in a neutropenic patient shows the complexity in the diagnostic and therapeutic management of necrotizing soft tissue infections in immunocompromised patients. It particularly highlights the importance of an interdisciplinary management with fast recognition of the disease and rapid, if needed radical, surgical debridement as well as tailored antibiotic treatment for a successful outcome.

Early treatment for Clostridioides difficile infection: retrospective cohort study.

Clostridioides difficile (CDI) is a common cause of infectious diarrhea. The current recommendation is to initiate empirical antibiotic treatment for suspected CDI who have an anticipated delay of confirmatory results or fulminant colitis. This is based on limited clinical trials. The study aims to examine the impact of early treatment on mortality and clinical outcomes. This retrospective cohort study included adult patients with CDI. Early treatment was defined as the initiation of an anti-Clostridioides medication within the first 24h following stool sampling. Outcomes were 30 and 90day mortality, length of hospital stay (LOS), recurrence, and colectomy rate. To address potential bias, propensity score matching followed by logistic regression was performed, P value less than 5% was considered statistically significant. Study cohort consisted of 796 patients; clinical characteristics were balanced following matching. There was no difference, in favor of early treatment, between the groups regarding 30day mortality and 90day mortality with HR of 0.91 (95% CI 0.56-1.47) and 0.7 (95% CI 0.45-1.08), respectively. No statistically significant difference in recurrence rate, ICU admission or colectomy rate was observed. The LOS was shorter in the early-treatment group with 6days vs. 8days. Early treatment for CDI had shortened hospital stay. However, it did not affect clinical outcomes in adult patients.

Clinical Application of Metagenomic Next-Generation Sequencing in Sepsis Patients with Early Antibiotic Treatment.

This study aimed to evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) in sepsis patients who received early empirical antibiotic treatment. A retrospective analysis was conducted on clinical data from sepsis patients diagnosed in the Emergency Intensive Care Unit (EICU) between April 2019 and May 2023. All patients underwent standard conventional microbiological testing. Patients were categorized into either the mNGS group or the control group based on whether they underwent mNGS tests. Baseline variables were matched using propensity scores. Out of 461 sepsis patients screened, 130 were included after propensity matching, with 65 patients in each group. Despite prior antibiotic treatment, 57 cases (87.69%) in the mNGS group had positive mNGS results, exceeding the culture detection rate (52.31%). Besides, a higher proportion of patients in the mNGS group experienced antibiotic adjustments compared to the control group (72.31% vs 53.85%). Mortality rates were also compared based on the duration of antibiotic exposure before mNGS sampling. Patients exposed to antibiotics for less than 24hours had a lower mortality rate compared to those exposed for over 8 days (22.22% vs 42.86%). COX multivariate analysis identified mNGS testing, underlying diseases, lymphocyte percentage, infection site (respiratory and bloodstream) as independent risk factors for mortality in sepsis patients. With increased antibiotic exposure time, the positive rate of culture testing significantly decreased (44.44% vs 59.52% vs 35.71%, P = 0.031), whereas the positive rate of mNGS remained stable (77.78% vs 88.10% vs 92.86%, P = 0.557). mNGS demonstrated less susceptibility to antibiotic exposure. Early mNGS detection positively impacted the prognosis of sepsis patients.

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients (BEATLE): a randomized, multicentre, open-label, superiority clinical trial

ObjectivesThe efficacy of extended infusions (EI) of β-lactam antibiotics for optimising outcomes in febrile neutropenia is unclear. We assessed whether the administration of β-lactams was more effective in EI than in intermittent infusion (II) for the treatment of febrile neutropenia. MethodsWe performed a randomized, open-label, superiority clinical trial of patients with febrile neutropenia at four Spanish university hospitals. Patients undergoing haematopoietic stem cell transplantation or with acute leukaemia receiving chemotherapy who required empirical antibiotic treatment for febrile neutropenia were randomly assigned (1:1) to receive EI of β-lactam or II after a first dose in bolus. The choice of antipseudomonal β-lactam was left to the discretion of the attending physician. The primary endpoint was treatment success at day 5, defined as defervescence without modifying the antibiotic treatment. Secondary endpoints included adverse events, attainment of the pharmacokinetic/pharmacodynamic target of 50%, 75%, and 100%ƒuT > MIC, and 30-day mortality. ResultsFrom November 19, 2019 to June 22, 2022, 295 patients were screened for eligibility, of whom 150 were randomly assigned to receive EI (n = 77) or II (n = 73) of the antipseudomonal β-lactam of choice. In the intention-to-treat analysis, treatment success at day 5 was achieved in 39/77 patients (50.6%) receiving EI versus 46/73 patients (63.0%) receiving II (risk difference, −12.4%; 95% CI, −29.4 to 4.7; p 0.17). The pharmacokinetic/pharmacodynamic targets of 75% and 100% ƒuT > MIC for empirical treatment were achieved more frequently in the EI group. No statistically significant differences were found between groups in terms of adverse events or 30-day mortality. DiscussionOur findings do not support the routine use of empirical EI of β-lactams in febrile neutropenia. Further studies should consider the clinical heterogeneity of febrile neutropenia and focus on patients with sepsis or septic shock and microbiologically documented infections, particularly those with infections caused by microorganisms less susceptible to β-lactams.

Incidence of Multidrug Resistant Organisms and Adequacy of Empiric Antibiotic Treatment in Hospitalized Patients with Sepsis at Ain Shams University Hospital

Abstract Background Bloodstream infections (BSIs) are the most severe infections that cause the highest mortality rate, especially in patients admitted to the intensive care unit (ICU). The nightmare of the rising numbers of multidrug-resistant organisms (MDROs) requires the implementation of effective Antibiotic stewardship programs (ASPs). However, this should be preceded by making available evidence-based knowledge regarding the local antimicrobial resistance pattern, which is fundamental. Objective Is to determine the prevalence of MDROs and to measure the adequacy of the empirical Anti-Microbial Therapy (EAMT) in adult patients with sepsis hospitalized at Ain Shams University Hospitals (ASUHs) ICUs. Patients &amp; Methods This was a prospective cohort study carried out on hospitalized adult patients with evidence of BSI admitted at ICUs of ASUH by +ve blood culture and sensitivity results. 276 patients were included in the study during the period from December 1st 2022 till may 30th 2023. Results In 276 patients, our study showed male to female ratio 1:1.1, Community acquired infections account for 34.8%, while healthcare associated infections account for 65.2% of total cases. The primary source of BSI was identified in only 62% of cases; the most prevalent cause was UTI in 29.1%, and pneumonia in 16.6% of total cases with identified source. Prevalence of MDROs was 88.8% among all the studied patients, Klebsiella spp. was the most prevalent among isolated organisms in 30.8% of total cases, and adequacy of EAMT was achieved in only 40.9% of total cases. Mortality rate within 2 weeks was 23.2%, and long hospital stay &amp;gt; 2weeks noticed in 54.3% of the studied patients and only 22.5% of patients improved and discharged from ICU. Conclusion MDROs are a public health threat and their prevalence is rising over the past few years, effective ASPs are mandatory to combat that threat and improve the adequacy of EAMT.

Clinical and biochemical factors for bacteria in bile among patients with acute cholangitis.

Acute cholangitis is a clinical syndrome caused by a bacterial infection in the biliary system. The bacteria could exist in the bile before bile drainage despite empirical antibiotic treatment. Patients with acute cholangitis admitted to a tertiary hospital in Southeastern China from August 2011 to September 2021 were involved when bile cultures were performed. Patient information before bile cultures and during hospitalization was extracted from the clinical record database. The risk factors related to bacteria in bile were assessed by univariable and multivairable logistic regression analysis, respectively. A total of 533 patients (66.05%) had bacterial growth in bile. Alanine aminotransferase concentration [odds ratio (OR) = 0.998, P < 0.001], absolute monocyte count (OR = 0.335, P = 0.001), and duration of antibiotic use (OR = 0.933, P = 0.026) were negatively correlated with bacteria in bile. In contrast, C-reactive protein (OR = 1.006, P = 0.003), thrombin time (OR = 1.213, P = 0.033), prothrombin time (OR = 1.210, P = 0.011), and age (OR = 1.025, P < 0.001) were positively correlated with bacteria in bile. Based on an area under the receiver operating characteristic curve of 0.737 (95% CI, 0.697-0.776, P < 0.001), combining these seven variables could efficiently predict the presence of bacteria in bile among patients with acute cholangitis. The combination of clinical indicators before bile drainage could predict the risk of bacteria in bile for patients with acute cholangitis.

Impact of adequate empirical combination therapy on mortality in septic shock due to Pseudomonas aeruginosa bloodstream infections: a multicentre retrospective cohort study.

To determine the association of adequate empirical combination therapy (AECT) with 30-day all-cause mortality in patients with septic shock due to Pseudomonas aeruginosa bloodstream infections (BSI). This multicentre, retrospective cohort study analysed data from 14 public hospitals in Italy, including all consecutive adult patients admitted during 2021-2022 with septic shock due to P. aeruginosa BSI. We compared the outcomes of patients receiving AECT to those on adequate empirical monotherapy (AEMT) using Cox regression analyses. Of the 98 patients who received adequate empirical antibiotic treatment for septic shock due to P. aeruginosa BSI, 24 underwent AECT and 74 were given AEMT. AECT was associated with a lower 30-day all-cause mortality (25%, six out of 24) compared to AEMT (56.8%, 42 out of 74; P = 0.007). Multivariate Cox regression analysis indicated AECT as the only factor significantly associated with improved survival (aHR 0.30; 95% CI 0.12-0.71; P = 0.006). By contrast, the use of monotherapy or combination therapy in the definitive regimen did not influence mortality (aHR 0.73; 95% CI 0.25-2.14; P = 0.568). AECT may be associated with reduced mortality compared to monotherapy in septic shock patients due to P. aeruginosa BSI. However, the administration of definitive adequate monotherapy or combination therapy yields similar outcomes, suggesting that once susceptibility is documented, switching to a single active in vitro drug is safe and feasible. Further studies are recommended to validate these findings.

Assessing Diagnostic Performance of Molecular Culture for Neonatal Sepsis: Protocol of the CHAMPIONS Study.

Managing neonatal sepsis is challenging due to nonspecific clinical signs, hematological markers with poor accuracy, and a lengthy turnaround time for the identification of microorganisms. Delaying the initiation of antibiotics in truly infected infants can lead to severe morbidity and mortality. Therefore, decisions regarding empiric antibiotic treatment are risk stratified, which exposes many uninfected infants to antibiotics. This causes gut microbiota perturbation, unnecessary hospital admissions, and the generation of multi-resistant organisms. High-speed diagnostic assays could expedite discontinuation or avert the initiation of antibiotics in uninfected infants. This study will evaluate the diagnostic performance of molecular culture (MC), a rapid broad-range PCR-based bacterial profiling technique, for diagnosing neonatal sepsis in infants below 90 days old. A multi-center prospective observational cohort study will include infants evaluated for early and late-onset sepsis. Routine evaluation for suspected sepsis includes microbiological cultures of blood. Additionally, blood for MC will be collected. For early-onset sepsis, umbilical cord blood may be used alternatively. Primary outcome is the agreement between MC and conventional blood culture results. Secondary outcome is the agreement of both assays with clinical sepsis using four different, commonly used definitions. Faster diagnostic pathways for sepsis may reduce antibiotic exposure time. Broad-range molecular assays may identify pathogens undetectable by conventional methods. Employment of umbilical cord blood samples for early-onset sepsis diagnosis can resolve challenges in collecting adequate blood volume and could further expedite treatment decisions.