Administration Of Antibiotic Therapy Research Articles

Retrospective analysis of molecular characteristics, risk factors, and outcomes in carbapenem-resistant Klebsiella pneumoniae bloodstream infections

BackgroundKlebsiella pneumoniae (KP) is the second most prevalent Gram-negative bacterium causing bloodstream infections (BSIs). In recent years, the management of BSIs caused by KP has become increasingly complex due to the emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although numerous studies have explored the risk factors for the development of CRKP-BSIs, the mortality of patients with KP-BSIs, and the molecular epidemiological characteristics of CRKP, the variability in data across different populations, countries, and hospitals has led to inconsistent conclusions. In this single-center retrospective observational study, we utilized logistic regression analyses to identify independent risk factors for CRKP-BSIs and factors associated with mortality in KP-BSI patients. Furthermore, a risk factor-based prediction model was developed. CRKP isolates underwent whole-genome sequencing (WGS), followed by an evaluation of microbiological characteristics, including antimicrobial resistance and virulence genes, as well as epidemiological characteristics and phylogenetic analysis.ResultsOur study included a total of 134 patients with KP-BSIs, comprising 50 individuals infected with CRKP and 84 with carbapenem-susceptible Klebsiella pneumoniae (CSKP). The independent risk factors for CRKP-BSIs were identified as gastric catheterization (OR = 9.143; CI = 1.357–61.618; P = 0.023), prior ICU hospitalization (OR = 4.642; CI = 1.312–16.422; P = 0.017), and detection of CRKP in non-blood sites (OR = 8.112; CI = 2.130-30.894; P = 0.002). Multivariate analysis revealed that microbiologic eradication after 6 days (OR = 3.569; CI = 1.119–11.387; P = 0.032), high Pitt bacteremia score (OR = 1.609; CI = 1.226–2.111; P = 0.001), and inappropriate empirical treatment after BSIs (OR = 6.756; CI = 1.922–23.753; P = 0.003) were independent risk factors for the 28-day mortality in KP-BSIs. The prediction model confirmed that microbiologic eradication after 6.5 days and a Pitt bacteremia score of 4.5 or higher were significant predictors of the 28-day mortality. Bioinformatics analysis identified ST11 as the predominant CRKP sequence type, with blaKPC−2 as the most prevalent gene variant. CRKP stains carried multiple plasmid-mediated resistance genes along with some virulence genes. Phylogenetic analysis indicated the presence of nosocomial transmission of ST11 CRKP within the ICU.ConclusionsThe analysis of risk factors for developing CRKP-BSIs and the association between KP-BSIs and 28-day mortality, along with the development of a risk factor-based prediction model and the characterization of CRKP strains, enhances clinicians’ understanding of the pathogens responsible for BSIs. This understanding may help in the timely administration of antibiotic therapy for patients with suspected KP-BSIs, potentially improving outcomes.

Case Report: Severe Community-Acquired Pneumonia in Réunion Island due to Acinetobacter baumannii.

Acinetobacter baumannii (Ab) is a well-known nosocomial pathogen that has emerged as a cause of community-acquired pneumonia (CAP) in tropical regions. Few global epidemiological studies of CAP-Ab have been published to date, and no data are available on this disease in France. We conducted a retrospective chart review of severe cases of CAP-Ab admitted to intensive care units in Réunion University Hospital between October 2014 and October 2022. Eight severe CAP-Ab cases were reviewed. Median patient age was 56.5 years. Sex ratio (male-to-female) was 3:1. Six cases (75.0%) occurred during the rainy season. Chronic alcohol use and smoking were found in 75.0% and 87.5% of cases, respectively. All patients presented in septic shock and with severe acute respiratory distress syndrome. Seven patients (87.5%) presented in cardiogenic shock, and renal replacement therapy was required for six patients (75.0%). Five cases (62.5%) presented with bacteremic pneumonia. The mortality rate was 62.5%. The median time from hospital admission to death was 3 days. All patients received inappropriate initial antibiotic therapy. Acinetobacter baumannii isolates were all susceptible to ceftazidime, cefepime, piperacillin-tazobactam, ciprofloxacin, gentamicin, and imipenem. Six isolates (75%) were also susceptible to ticarcillin, piperacillin, and cotrimoxazole. Severe CAP-Ab has a fulminant course and high mortality. A typical case is a middle-aged man with smoking and chronic alcohol use living in a tropical region and developing severe CAP during the rainy season. This clinical presentation should prompt administration of antibiotic therapy targeting Ab.

Primary Ciliary Dyskinesia Associated with Rheumatoid Lung at The Koulikoro Reference Health Center, Mali

Primary ciliary dyskinesia is a cause of bronchial dilatation, associated with rheumatoid lung is rare. This is why we report a case with the aim of discussing the clinical, diagnostic characteristics and therapeutic possibilities of ciliary pathology and showing the link between it and rheumatoid arthritis. Observation: This is a 40-year-old African patient, married without children, from a consanguineous couple, with a family history of a brother who died in adulthood in a picture of respiratory failure and productive cough. She presented with recurrent rhinorrhea since childhood and bronchorrhea in a picture of progressively worsening dyspnea and clubbing. During the evolution of the disease, inflammatory polyarthralgia was associated. The ultrastructural ciliary study by electron microscopy and the measurement of nasal nitrogen oxide are the confirmatory examinations of primary ciliary dyskinesia. They are not achievable in our practice. However, based on the history and clinical findings, the patient presented several elements in favor of this pathology. additional investigations, notably the rheumatoid factor and the chest CT scan, allowed us to suggest rheumatoid lung. Our therapeutic conduct was the administration of antibiotic therapy, oxygen therapy, immunosuppressant, anti-inflammatory and the practice of respiratory physiotherapy. Conclusion: Primary ciliary dyskinesia associated with pulmonary involvement in rheumatoid arthritis increases the risk of developing respiratory failure.

Chronic endometritis - a constantly discussed issue in infertile women.

A review of current knowledge on the pathophysiology, diagnostic and treatment options for chronic endometritis in infertile women. One of the major causes of failed in vitro fertilization (IVF) is undiagnosed intrauterine pathologies, including chronic inflammation of the uterine mucosa - chronic endometritis. However, some authors relativize the negative impact of chronic endometritis on reproductive outcomes. The etiopathogenesis of chronic endometritis is due to qualitative and quantitative changes in the endometrial microbiome with abnormal multiplication of microorganisms naturally occurring in the uterine cavity or vagina. There is no uniform consensus on the most common pathogen causing chronic endometritis. It is characterized by infiltration of plasma cells into the endometrial stroma outside the menstrual cycle, accompanied by hyperaemia and endometrial oedema. Clinical symptoms are very mild or absent. The diagnosis of chronic endometritis is often difficult because there is no specific clinical or laboratory diagnostic method. The following investigative options are commonly used for the diagnosis of chronic endometritis: diagnostic hysteroscopy, histopathological examination of the endometrium including CD 138 immunohistochemistry and culture from the uterine cavity. However, standardised international hysteroscopic and histopathological criteria for accurate diagnosis of chronic endometritis are still lacking. Empirically administered antibiotic therapy improves the success rate of pregnancy and delivery of a viable foetus in infertile patients with proven chronic endometritis. In addition to reviewing the current knowledge of chronic endometritis, this article discusses the importance of hysteroscopy in the diagnostic process. Chronic endometritis is often a clinically silent disease with negative impact on reproduction in infertile women. Although there are still many unresolved issues, the introduction of hysteroscopy into the diagnostic process is important for clinical practice; however, hysteroscopy even in combination with histological examination of the endometrium, often does not allow an unequivocal diagnosis of chronic endometritis. Further prospective randomised studies in a selected group of women with proven chronic endometritis and repeated failure to implant proven euploid embryos should refine this knowledge.

The Jarisch-Herxheimer Reaction on Secondary Syphilis Patient with Roseola Syphilitica and Human Immunodeficiency Virus Co-Infection: A Case Report

Background: The Jarisch-Herxheimer reaction is an inflammatory reaction that occurs within 12 hours after administration of antibiotic therapy for spirochaeta species like Treponema pallidum. The reaction includes fever, headache, reappearing or worsening of skin lesions, lymphadenopathy, pharyngitis, malaise, and myalgias.
 Case presentation: We present a 27-year-old man complaining of high fever 4 hours after the injection of benzathine penicillin. The patient also complained of headaches, body aches and aches. There were no complaints of shortness of breath, itching, skin blisters, red eyes, or sores on the genitals. History of take any medication was denial by the patient. After treatment by giving antipyretics and corticosteroids and getting enough rest, in the 24 hours, the patient was improved.
 Conclusion: The Jarisch-Herxheimer reaction is an inflammatory reaction that occurs after the administration of antibiotic therapy for spirochaeta species like Treponema pallidum.

Influence of antibiotic therapy with hemodynamic optimization on 30-day mortality among septic shock patients cared for in the prehospital setting

BackgroundIn order to reduce septic shock mortality, international guidelines recommend early treatment implementation, antibiotic therapy (ABT) and hemodynamic optimisation, within 1-h.This retrospective multicentric study aims to investigate the relationship between prehospital ABT delivered within 1st hour and mean blood pressure (MAP) ≥ 65 mmHg at the end of the prehospital stage, and 30-day mortality among patients with septic shock. MethodsFrom May 2016 to December 2021, patients with septic shock requiring pre-hospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To assess the relationship between 30-day mortality and prehospital ABT delivered within 1st hour and/or MAP ≥ 65 mmHg at the end of the prehospital stage, Inverse Probability Treatment Weighting (IPTW) propensity score method was performed. ResultsAmong the 530 patients included, 341 were male gender (64%) with a mean age of 69 ± 15 years. One-hundred and thirty-two patients (25%) patients received prehospital ABT, among which 98 patients (74%) were treated with 3rd generation cephalosporin.Suspected pulmonary, urinary and digestive infections were the cause of sepsis in respectively 43%, 25% and 17%. The 30-day overall mortality was 31%.A significant association was observed between 30-day mortality rate and (i) ABT administration within the first hour: RRa = 0.14 [0.04–0.55], (ii) ABT administration within the first hour associated with a MAP ≥ 65 mmHg: RRa = 0.08 [0.02–0.37] and (iii) ABT administration within the first hour in the prehospital setting associated with a MAP < 65 mmHg at the end of the prehospital stage: RRa = 0.75 [0.45–0.85]. Patients who received prehospital ABT after the first hour have also a 30-day mortality rate decrease: RRa = 0.87 [0.57–0.99], whereas patients who did not received ABT had an increased 30-day mortality rate: RRa = 2.36 [1.89–2.95]. ConclusionIn this study, we showed that pre-hospital ABT within the first hour and MAP≥65 mmHg at the end of prehospital stage are both associated with 30-day mortality decrease among patients suffering from septic shock cared for by a MICU. Further prospective studies are needed to confirm these preliminary results.

Investigation of the effects of clinical parameters on mortality in patients with necrotizing fasciitis.

Necrotizing fasciitis is a rapidly progressing, potentially fatal soft-tissue infection that spreads through the fascia. Due to the late onset of diagnostic signs during the disease's advanced stage and its rapid progression, it can be challenging to make a prompt diagnosis. However, with a rapid and accurate diagnosis, the progression of the disease can be halted through appropriate early surgical intervention. Even with correct and timely treatment, the mortality rate for necrotizing fasciitis is higher compared to other soft-tissue infections. This study aims to investigate the effects of clinical parameters in patients with necrotizing fasciitis on mortality. The study included 37 patients with a necrotizing fasciitis diagnosis between 2009 and 2018. Demographic characteristics of the patients (age, gender, comorbid conditions), duration from diabetes diagnosis if present, blood glucose level at the time of diagnosis, microorganisms isolated from wound cultures, presence of positive blood cultures, administered antibiotic therapy, laboratory risk indicator for necrotizing fasciitis (LRINEC) score at presentation, number and types of surgical procedures performed, length of hospital stay, and mortality rates were retrospectively recorded. Statistical analysis of dependent and independent variables was conducted using t-tests, Mann-Whitney U test, Chi-square test, and Fisher's exact test. Age was found to be an average of 70 in the mortality group, and it is significantly higher compared to the non-mortality group. A high LRINEC score, the presence of comorbidity, and a positive blood culture were also found to be significant in the mortal-ity group. The low number of surgical procedures performed is significantly lower in the mortality group. This study highlights the conditions associated with high mortality in patients with necrotizing fasciitis, which is a treatable disease through timely and accurate diagnosis followed by appropriate antibiotic therapy and surgical intervention. It emphasizes the importance of updating the approach for high-risk group patients and aims to provide information that will help lower the threshold for diagnosing necrotizing fasciitis.

The effectiveness comparison of appendectomy action through the antibiotic therapy administration in acute appendicitis patients

The purpose of this research to compare the effectiveness of appendectomy by administering non-operative management in the form of antibiotics in acute appendicitis patients. The research method used descriptive qualitative through the Literature Review (LR) approach. The data source used a secondary source. Data analysis technique selects literature based on title, year, and indexed articles, then reviews articles that match the subject matter. the articles from those journals are compared to find the differences and similarities. A literature review of four PubMed, DOAJ, Cochrane, and Google Scholar databases published in the last five years, i.e. from 2018-2022. Twelve pieces of literature were obtained and reported the advantages and disadvantages of each procedure. Apshortextomy keeps the gold standard with a lower risk of recurrence and severity and a higher treatment success rate. Appendectomy is also required for appendicitis cases with complications. However, antibiotic therapy has advantages with lower levels of complications, fewer costs, and fewer hospital stays. The success rate of non-operative therapy in the form of antibiotics can reach 65-75%, while it can reach 67,1% in children. There are differences in research results related to the effectiveness of appendectomy and antibiotic therapy in acute appendicitis patients. Each of these therapeutic procedures has its advantages and disadvantages. It is very important to be concerned about the urgency and expectations of the patient in selecting this therapy.

Calcaneal V-shaped osteotomy combined with subtalar arthrodesis for Stephens Ⅱ and Ⅲ calcaneal fractures malunion

To investigate the effectiveness of calcaneal V-shaped osteotomy combined with subtalar arthrodesis in the treatment of Stephens Ⅱand Ⅲ calcaneal fracture malunion. The clinical data of 24 patients with severe calcaneal fracture malunion treated by calcaneal V-shaped osteotomy combined with subtalar arthrodesis between January 2017 and December 2021 were retrospectively analyzed. There were 20 males and 4 females with an average age of 42.8 years (range, 33-60 years). Conservative treatment of calcaneal fracture failed in 19 cases and operation failed in 5 cases. Stephens classification of calcaneal fracture malunion was type Ⅱ in 14 cases, and type Ⅲ in 10 cases. Preoperative Böhler angle of calcaneus was 4.0°-13.5° (mean, 8.6°), Gissane angle was 100°-152° (mean, 119.3°). The time from injury to operation was 6-14 months (mean, 9.7 months). American Orthopedic Foot and Ankle Society (AOFAS) ankle and hindfoot score and visual analogue scale (VAS) score were used to evaluate the effectiveness before operation and at last follow-up. Bone healing was observed and the healing time was recorded. The talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were measured. Necrosis of the cuticle edge of the incision occurred in 3 cases, which were cured by dressing change and oral administration of antibiotic therapy. The other incisions healed by first intention. All the 24 patients were followed up 12-23 months, with an average of 17.1 months. The foot shape of the patients recovered well, the shoes were restored to the size before injury, and there was no anterior ankle impingement. Bone union was achieved in all patients, and the healing time ranged from 12 to 18 weeks, with an average of 14.1 weeks. At last follow-up, no adjacent joint degeneration occurred in all patients; 5 patients had mild foot pain during walking, which had no significant impact on daily life and work; no patient needed revision surgery. The AOFAS ankle and hindfoot score was significantly higher than that before operation ( P<0.001), the results were excellent in 16 cases, good in 4 cases, and poor in 4 cases, and the excellent and good rate was 83.3%. The VAS score, talocalcaneal height, talus inclination angle, Pitch angle, calcaneal width, and hindfoot alignment angle were significantly improved after operation ( P<0.001). Calcaneal V-shaped osteotomy combined with subtalar arthrodesis can effectively relieve hindfoot pain, correct talocalcaneal height, restore talus inclination angle, and reduce the risk of nonunion after subtalar arthrodesis.

Nurse-led study on treatment delay and streamlining antibiotic therapy among haematology patients with febrile neutropenia post chemotherapy

Objective: The aim of the study is to identify gaps that exist among health professionals that may impact practices in caring effectively for patients with febrile neutropenia (FN). Background: Haematology patients with FN following chemotherapy frequently experience delays in antibiotic administration that may be linked to poorer clinical outcomes. To aid timely review and treatment, FN care pathways have been developed. However, observations of clinical practice and patient anecdotal reports have highlighted that the care pathways may not be adhered to. The impact on patient care outcomes due to treatment delays and the rate of protocol adherence to the FN management pathway is unknown due to insufficient evidence. Methods: Using the Clinical Records Integrated System (CRIS), data were collected by auditing patients’ electronic health records (EHR) from November 2017 through to November 2018. Information retrieved were screened using the inclusion and exclusion criteria. Inclusion criteria: Haematology patients with FN (temperature ≥ 38° and neutrophil count < 1.0 x109/L) post chemotherapy, and 18 years or older. Exclusion criteria: Medical oncology patients and patients who were under 17 years old. Results: The mean time for antibiotic administration from first temperature spike was 90±15 minutes for inpatients (n=48). The mean time for antibiotic administration from medical officer review was significantly lower at 48±5 minutes for outpatients (n=31). Inpatients who were given antibiotics within 60 minutes or less of their first temperature spike, their mean length of total stay in the ward was 17±1 whilst inpatients who were given antibiotics 60 minutes after their first temperature spike, the mean length of their hospital stay was slightly greater at 21±3 days. Outpatients who were given antibiotics within 60 minutes or less of their first temperature spike, their mean length of stay was 12±2 days. For outpatients given antibiotics 60 minutes after their first temperature spike, their mean length of hospital stay was slightly shorter at 9±3 days. Conclusion: The study identified antibiotic delays among inpatient population, and with correlation to increased length of hospital stay and mortality. Another key factor identified in the study was delayed medical officer review although reasons for delays are outside of the scope this study to report. What is already known: Febrile neutropenia is a serious and life-threatening illness. Delays in antibiotic administration exists among healthcare facilities. Adherence to FN treatment guidelines among healthcare settings are challenging. What this review adds: Standardised orders to allow timely administration of antibiotic therapy that may reduce morbidity and mortality. Increased education on the seriousness and outcome from delayed antibiotics to patients, families, and healthcare staff. Further studies are required to standardise the clinical pathway and make antibiotics accessible for prompt delivery.

Oral vs. parenteral antibiotic therapy in adult patients with community-acquired pneumonia: a systematic review and meta-analysis of randomized controlled trials

Antibiotic therapy is widely used for patients with community-acquired pneumonia (CAP), and yet whether the efficacy of antibiotics differs based on the treatment mode remains unclear. This study aimed to summarize the evidence regarding the efficacy and safety of oral vs. parenteral administration of antibiotic therapy for the treatment of patients with CAP. The databases of PubMed, EmBase, and the Cochrane Central Register of Controlled Trials were systematically searched for eligible randomized controlled trials (RCTs) from inception until 11 December 2021. The effectiveness of oral vs. parenteral administration of antibiotic therapy was estimated using a random-effects model. Additional sensitivity, subgroup, and publication bias analyses were performed. Of 912 identified articles, 12 RCTs involving 2158 patients with CAP were included in our pooled analysis. This mostly included trials with low certainty and some concerns regarding risk of bias, including lack of allocation concealment and blinding of participants and personnel. Overall, oral antibiotic therapy did not affect the incidence of clinical success at the end of treatment (relative risk [RR], 1.01; 95% confidence interval [CI], 0.98-1.05; P=0.417), clinical success at follow-up (RR, 1.02; 95% CI, 0.98-1.06; P=0.301), or adverse events (RR, 0.87; 95% CI, 0.56-1.35; P=0.527). Moreover, oral antibiotic therapy had a beneficial effect on the risk of all-cause mortality (RR, 0.58; 95% CI, 0.35-0.96; P=0.034). Oral administration of antibiotics is associated with a reduced risk of all-cause mortality compared with parenteral therapy based on RCTs with low to moderate quality. This finding should be verified in further large-scale RCTs.

QSOFA does not predict bacteremia in patients with severe manifestations of sepsis.

Bloodstream infections in septic patients may be missed due to preceding antibiotic therapy prior to obtaining blood cultures. We leveraged the FABLED cohort study to determine if the quick Sequential Organ Failure Assessment (qSOFA) score could reliably identify patients at higher risk of bacteremia in patients who may have false negative blood cultures due to previously administered antibiotic therapy. We conducted a multi-centre diagnostic study among adult patients with severe manifestations of sepsis. Patients were enrolled in one of seven participating centres between November 2013 and September 2018. All patients from the FABLED cohort had two sets of blood cultures drawn prior to the administration of antimicrobial therapy, as well as additional blood cultures within 4 hours of treatment initiation. Participants were categorized according to qSOFA score, with a score ≥2 being considered positive. Among 325 patients with severe manifestations of sepsis, a positive qSOFA score (defined as a score ≥2) on admission was 58% sensitive (95% CI 48% to 67%) and 41% specific (95% CI 34% to 48%) for predicting bacteremia. Among patients with negative post-antimicrobial blood cultures, a positive qSOFA score was 57% sensitive (95% CI 42% to 70%) and 42% specific (95% CI 35% to 49%) to detect patients who were originally bacteremic prior to the initiation of therapy. Our results suggest that the qSOFA score cannot be used to identify patients at risk for occult bacteremia due to the administration of antibiotics pre-blood culture.

Prehospital Bundle of Care Based on Antibiotic Therapy and Hemodynamic Optimization Is Associated With a 30-Day Mortality Decrease in Patients With Septic Shock.

This study aims to investigate the association between the 30-day mortality in patients with septic shock (SS) and a prehospital bundle of care completion, antibiotic therapy administration, and hemodynamic optimization defined as a fluid expansion of at least 10 mL.kg -1 .hr -1 . To assess the association between prehospital BUndle of Care (BUC) completion and 30-day mortality, the inverse probability treatment weighting (IPTW) propensity method was performed. International guidelines recommend early treatment implementation in order to reduce SS mortality. More than one single treatment, a bundle of care, including antibiotic therapy and hemodynamic optimization, is more efficient. From May 2016 to March 2021, patients with SS requiring prehospital mobile ICU (mICU) intervention were retrospectively analyzed. None. Among the 529 patients with SS requiring action by the mICU enrolled in this study, 354 (67%) were analyzed. Presumed pulmonary, digestive, and urinary infections were the cause of the SS in 49%, 25%, and 13% of the cases, respectively. The overall 30-day mortality was 32%. Seventy-one patients (20%) received prehospital antibiotic therapy and fluid expansion. Log binomial regression weighted with IPTW resulted in a significant association between 30-day mortality and prehospital BUC completion (respiratory rate [RR] of 0.56 [0.33-0.89]; p = 0.02 and adjusted RR 0.52 [0.27-0.93]; p = 0.03). A prehospital bundle of care, based on antibiotic therapy and hemodynamic optimization, is associated with a 30-day mortality decrease among patients suffering from SS cared for by an mICU.

Association of antibiotic therapy and treatment efficacy in patients with renal cell carcinoma receiving immune checkpoint inhibitors.

4556 Background: There is growing evidence indicating that gut microbiome content is associated with the effectiveness of immune checkpoint inhibitory (ICI) therapy in various cancer types. Antibiotic therapy (ABT) induces significant changes in gut microbiota; however, the effects of ABT on oncologic outcomes with ICI therapy has only been explored in small, single-institution studies. We aimed to investigate the relationship between ABT on overall survival (OS) and real-world progression free survival (rwPFS) in subjects with advanced renal cell carcinoma (RCC) treated with ICI utilizing a national database. Methods: We queried the nationwide electronic health record (EHR)-derived de-identified FlatIron Health (FIH) database after Institutional Review Board approval was obtained and included a waiver of informed consent to select 1809 subjects who received ICI therapy. Patient characteristics were described and compared between those with known ABT use and without known ABT use (in the 3 months pre/post ICI initiation) using ANOVA and Chi-square tests. rwPFS and OS were calculated from date of initiation of ICI to date of real-world progression/date of death. Three-month landmark Kaplan Meier and log-rank tests were used to compare rwPFS and OS between groups defined by ABT use (any ABT, and ABT in 3 months pre-ICI vs 3 months post-ICI initiation). Cox proportional models were used to investigate the association between rwPFS, OS, and antibiotic use, adjusting for patient characteristics. Results: Patients receiving ABT group were younger (p = 0.007) and more likely female (p = 0.024) but similar in other measured demographic variables. rwPFS (median: 9.03 vs 11.6 months; p = 0.015) and OS (median: 23.7 vs 31.8 months; p = 0.019) were significantly shorter in the with-ABT group than in the without-ABT group. When assessing ABT use 3 months prior to initiation of ICI (vs ABT during/no known ABT use), neither rwPFS (median: 9.53 vs 11.66, p = 0.38) nor OS (median: 23.7 vs 22.6 months; p = 0.38) were significantly different. However, rwPFS (median: 23.5 vs 14.0 months vs not reached; p = 0.004) and OS (median: 36.2 vs 22.5 vs 31.8; p = 0.007) were statistically significantly different when stratifying based on exposure and timing of ABT amongst pre-ICI initiation ABT, post-ICI initiation ABT and no ABT groups, respectively. Multivariable analysis identified as a significant predictor of rwPFS (HR = 0.725, CI = 0.579-0.908; p =.005) and OS (HR = 0.722, CI = 0.573-0.911; p = 0.006). Conclusions: This study identifies a significant negative prognostic association of ABT administration on survival in advanced RCC treated by ICI in the first line setting. These results are consistent with the growing body of evidence suggesting that alterations in gut microbiome secondary to antibiotics appear to blunt efficacy of ICI treatment and emphasize the importance of antibiotic stewardship.

Kingella kingae Spinal Infections in Children.

Nowadays, Kingella kingae is considered an important cause of primary spinal infections in children aged between 6 and 48 months. The presentation of the disease is often characterized by mild clinical features and a moderate biological inflammatory response, requiring a high index of suspicion. Performing magnetic resonance imaging (MRI) and obtaining an oropharyngeal specimen and subjecting it to a K. kingae-specific nucleic acid amplification test are recommended for its diagnosis. Most patients respond promptly to conservative treatment after administration of antibiotic therapy, which is prolonged for up to 3 months according to the individual clinical and biological response. Invasive surgical procedures are not required except for children who do not improve with antibiotic treatment, develop signs of cord compression, or if the presence of atypical microorganisms is suspected. Kingella kingae spinal infections usually run an indolent and benign clinical course, living no permanent sequelae.

Exercise Capacity Mediated by the Gut Microbiome

Female C57BL/6J wild‐type (WT) mice (5 months old) exhibited greater maximal exercise capacity for running distance (489 ± 15 meters; n=6, p&lt;0.05) than age‐matched male WT mice (307 ± 17 m; n=8), as well as a 21% greater capacity for work to exhaustion. We hypothesized that these observed differences may be mediated by gut microbiota, as the sexes are known to have distinctly different microbiota. Predominant species in the male mice were found to be Faecalibacterium prausnitzii, Roseburia intestinalis and Allobaculum spp. while female mice had predominantly Parabacteroides goldstenii and Eubacterium coprostanoligenes. To determine if microbiota contribute to exercise tolerance, we administered antibiotic therapy (ABX) in drinking water to eliminate gut microbes. ABX eliminated the enhanced exercise tolerance of WT females. We then examined a model of enhanced exercise capacity ‐‐ Regulator of G Protein Signaling 14 (RGS14) knockout (KO) mice ‐‐ which exhibit greater maximal running distance (648 ± 38 m vs. 405 ± 21 m; p&lt;0.05) than age matched WT mice, as well as a 53% increase in work to exhaustion (n=10/group). There is no difference in the enhanced exercise capacity of RGS14 KO mice between males and females. The greater exercise capacity in the RGS14 KO mice was also abolished by ABX. In conclusion, the gut microbiome appears to be a key factor in mediating exercise performance, since eliminating its action with chronic antibiotic therapy also eliminates the enhanced exercise performance in female vs male WT mice and in RGS14 KO mice of either sex.

Adequacy of probabilistic prehospital antibiotic therapy for septic shock.

Guidelines on sepsis management recommend early recognition, diagnosis and treatment, especially early antibiotic therapy (ABT) administration in order to reduce septic shock (SS) mortality. However, the adequacy of probabilistic prehospital ABT remains unknown. From May 2016 to March 2021, all consecutive patients with SS cared for by a prehospital mICU intervention were retrospectively analyzed. Among 386 patients retrospectively analyzed, 119 (33%) received probabilistic prehospital ABT, among which 74% received a 3rd generation cephalosporin: 31% cefotaxime and 42% ceftriaxone. No patient had a serious adverse effect related to ABT administration. Overall mortality rate on day-30 was 29%. Among the 119 patients with prehospital ABT, bacteriological identification was obtained for 81 (68%) patients with adequate prehospital ABT for 65 patients (80%) of which 10 (15%) deceased on day-30. Conversely, among the 16 (20%) patients with inadequate prehospital ABT, 9 patients (56%) were deceased on day-30. Prehospital adequate ABT was significantly different between alive and deceased patients on day-30 (p=4.10-3). After propensity score matching, a significant association between adequate prehospital ABT administration and day-30 mortality was observed (aOR=0.09 [0.01-0.47]). Inverse probability treatment weighting with multivariable logistic regression reported a day-30 mortality decrease in the adequate prehospital ABT group: aOR=0.70 [0.53-0.93]. Among SS cared for by a mICU, probabilistic prehospital ABT is adequate most of the time and associated with a day-30 mortality decrease. Further prospective studies are needed to confirm these results and the weight of prehospital ABT in the prehospital bundle of care for SS.

Pharmacokinetic/Pharmacodynamic Optimization of Hospital-Acquired and Ventilator-Associated Pneumonia: Challenges and Strategies.

Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are correlated with high mortality rates worldwide. Thus, the administration of antibiotic therapy with appropriate dosing regimen is critical. An efficient antibiotic is needed to maintain an adequate concentration at the infection site, for a sufficient period of time, to achieve the best therapeutic outcome. It can, however, be challenging for antibiotics to penetrate the pulmonary system due to the complexity of its structure. Crossing the blood alveolar barrier is a difficult process determined by multiple factors that are either drug related or infection related. Thus, the understanding of pharmacokinetics/pharmacodynamics (PK/PD) of antibiotics identifies the optimum dosing regimens to achieve drug penetration into the epithelial lining fluid at adequate therapeutic concentrations. Critically ill patients in the ICU can express augmented renal clearance (ARC), characterized by enhanced renal function, or may have renal dysfunction necessitating supportive care such as continuous renal replacement therapy (CRRT). Both ARC and CRRT can alter drug elimination, thus affecting drug concentrations. PK of critically ill patients is less clear due to the multiple variabilities associated with their condition. Therefore, conventional dosing regimens often lead to therapeutic failure. Another major hurdle faced in optimizing treatment for HAP/VAP is the reduction of the in vitro potency. Therapeutic drug monitoring (TDM), if available, may allow health care providers to personalize treatment to maximize efficacy of the drug exposures while minimizing toxicity. TDM can be of significant importance in populations whom PK are less defined and for resistant infections to achieve the best therapeutic outcome.

SURGICAL TREATMENT OF AN UNUSUALLY LARGE MANDIBULAR RESIDUAL CYST: A CASE REPORT

Residual cysts are common after the extraction of a third impacted molar. Many of them are usually asymptomatic and can be detected incidentally on routine radiography before symptoms appear. Lately, 3D CBCT is the most common diagnostic method for detecting them. We present a case of a residual cyst that exists 20 years after extraction of the right lower third molar. Cysts can vary in size, and over the years can grow and disrupt bone continuity. In this case, a 53-year-old patient has painless swelling that manifests extra-orally in the buccal and masseteric regions. It has been recurring in recent years but the condition was improving with the administration of antibiotic therapy. Surgical treatment is the method of choice. Diagnosis and management of the patient are discussed. Keywords: odontogenic cyst, residual cyst, operative extraction, third lower molar.

The efficacy of systemic antibiotics as an adjunct to surgical treatment of peri-implantitis: a systematic review

BackgroundMicrobial biofilm accumulation is the main cause of peri-implantitis. The majority of surgical peri-implantitis treatment protocols suggests adjunctive use of systemic antibiotics to target specific putative bacteria. The aim of this systematic review was to critically evaluate the adjunctive use of systemically administered antibiotics in surgical treatment of peri-implantitis by reviewing previously published systematic reviews and primary studies.MethodsA systematic literature search was conducted in four electronic databases (MEDLINE, The Cochrane Library, EMBASE, and Web of Science) for randomised controlled trials, cohort studies, case–control studies, and systematic reviews reporting surgical treatment of peri-implantitis with and without adjunctive systemically administered antibiotic therapy. The included systematic reviews and primary studies were qualitatively assessed using AMSTAR and GRADE, respectively. No restrictions were set for date of publication, journal, or language.ResultsThe literature search identified 681 papers. Only seven systematic reviews and two primary studies met the inclusion criteria. Four out of seven included systematic reviews concluded that no evidence exists for use of systemic antibiotics to improve the clinical outcomes in surgical treatment of peri-implantitis. One review did not estimate the level of evidence, one did not clearly state any beneficial effect, whereas one reported a limited adjunctive effect. Further, the two included primary studies did not show a long-term significant benefit of adjunctive use of systemically administrated antibiotics. However, one study reported a short-term adjunctive effect in patients with modified surface implants. Due to heterogeneity in study design, low number of included primary studies, and grade of bias, no meta-analysis was performed.ConclusionThe use of systemically administered antibiotics as an adjunct to surgical interventions of peri-implantitis cannot be justified as a part of a standard treatment protocol. A pervasive problem is the lack of uniform diagnosis criteria for peri-implantitis, deficient information about patient characteristics, absence of high quality long-term randomised controlled trials, and authors’ declaration on conflict of interest.