Early Antibiotic Research Articles

Invasive Meningococcal Disease due to group C N. meningitidis ST11 (cc11): The Tuscany cluster 2015–2016

ObjectivesTo describe the cluster of MenC ST11 Invasive Meningococcal Disease (IMD) occurred in Tuscany in the years 2015–2016. MethodsA retrospective charts analysis of clinical, epidemiological and microbiological aspects of documented IMD was performed. Prognostic factors for death were evaluated. ResultsSixty-one patients with IMD in the 2015–2016 period were documented: 28 had meningococcemia, 24 meningitis plus meningococcemia and 9 meningitis. MenC ST11 (cc11) was identified in 48/54 (89%) of the tested strains. All patients, with the exception of three very early death, received timely and appropriate antibiotic therapy and, in selected case, adjunctive therapy with steroids and Pentaglobin®. Forty-one patients recovered (67.3%, mean age: 26 years), 7 had permanent sequelae (11.3%, mean age 31 years) and 13 died (21.3%; mean age: 46 years). In a multivariate analysis, septic shock, purpura fulminans and advanced age were negative prognostic factors, while emergency admittance to a tertiary-care, university hospital, positively influenced the survival rate. The epidemiological analysis of the cluster identified close contacts and recreational environments such as discos as hotspot for MenC transmission. After a massive vaccination campaign, the number of MenC cases reported in Tuscany in 2017 decreased to 10, with no death. ConclusionsVaccination campaign of key populations together with the need for rapid and qualified emergency care of the affected patients seems to be the main lesson learned by the MenC ST11 Tuscany epidemic.

Sepsis bei Kindern – alles anders?

Background: A child with sepsis represents a great challenge for all healthcare workers involved in the rescue services and the emergency room, especially those not regularly confronted by pediatric emergencies. Method: Narrative review focused on diagnosis, epidemiology and management of neonatal and pediatric sepsis in the emergency department. Articles published in English or German within the last 5 years were eligible. Presentation of age-specific case vignettes and tables including clinical signs, risk factors, and management in the first hour during transport and in the emergency department. Results: The highest incidence of bacterial sepsis in children is reported within the first few years of life. Clinical signs, site of infection and management of sepsis are age specific. The most frequently reported organ dysfunctions in pediatric sepsis are respiratory dysfunction and circulatory depression but arterial hypotension is a late sign of circulatory insufficiency. Vasoconstriction with a cold periphery and tachycardia is typical in infants but the recognition is often not simple. Immediate administration of 20 ml/kg body weight of balanced crystalloid fluid is mandatory in a state of shock. Diagnosis of sepsis remains challenging, yet outcomes are directly related to time to recognition and treatment. Initially, laboratory markers may be normal or slightly abnormal and are thus not sufficiently predictive to rule out sepsis. Early empiric antibiotic treatment is mandatory for every clinically suspected case of pediatric sepsis. Every child with suspected sepsis has to be admitted to a children’s hospital as soon as possible. Conclusion: The early recognition of signs of sepsis, the prompt initiation of fluid replacement and an adequate antibiotic therapy remain the most important factors to improve the prognosis of pediatric sepsis.

Fever within 48 h after Melody implantation is a risk factor of late infective endocarditis

Fever following pulmonary valve implantation is known but its frequency and impact have been poorly described. The aim of this study was to analyze clinical and biological parameters of inflammation just after the Melody valve implantation, and to see if early onset of inflammation can predict the risk of late infective endocarditis (IE). We performed a retrospective study on patients with Melody valve implanted for dysfunctional RVOT in our unit between January 2008 and December 2016. All clinical and biological inflammatory parameters following Melody implantation were recorded. In total, 198 patients were included (median age = 22.8 [Q1–Q3: 15.4–31.5] years). Before the procedure, the RVOT statute of patients was: 74 (37.4%) pulmonary valved conduits, 57 (28.8%) natives (with or without valve), 50 (25.2%) homografts, and 17 (8.6%) valveless conduits. Within 48 h post procedure, 58 patients (29.3%) had fever [T > 37.9 °C] and 140 patients (70.7%) had no fever, 98 patients (49.5%) had a CRP >5 mg/L, and 61 patients (30.8%) had white blood cells (WBC) >10G/L. Fifty-five patients received large spectral antibiotic regimen waiting for results of blood culture. No patients were found to have early IE and antibiotics were stopped after a median duration of 2 [1–2] days. Length of stay was longer in patients with fever compared to those without fever ( P < 0.001). The median follow-up was 3.3 [1.3–5.3] years. Twenty-one patients developed IE (10.6%), with a median at 1.8 [0.3–3.5] years. At 5 years, freedom from IE was 87.2%. Fever within 48 h post procedure was a significative risk factor (HR = 6.1, IC95%[2.5–15.1], P < 0.001). At 5 years, freedom from IE was 88.5% for patients without fever and 67.7% patients with fever within 48 h post-procedure ( P < 0.001). Elevated post-procedural WBC ( P = 0.62), CRP level ( P = 0.90), and initial RVOT statute of patients ( P = 0.70) were not a risk factor for IE. Patients with fever within 48 hours after Melody valve implantation are at particular risk of IE in their life. The reasons might be related to a specific genetic profile. Further studies are needed to understand the causes behind.

Calcium Phosphate Cement loaded with 10% vancomycin delivering high early and late local antibiotic concentration in vitro

BackgroundAntibiotics impregnated calcium phosphate cement (CPC) has emerged as a local treatment of osteomyelitis. However, there is no study investigating the optimal concentrations of vancomycin (VCM) included in CPC to obtain prolonged drug release (≥8 weeks) and also with enough compressive strength (>the normal cancellous bone, 11MPa) for osteomyelitis therapy. Therefore, we bring forward two questions: 1) Was antibiotic activity of the eluates correlated to the load of antibiotics within the cement? 2) Were the mechanical properties of CPC affected by VCM-loading? HypothesizedThere was an optimal concentrations of vancomycin (VCM) loaded in CPC which could provide sufficient effective antibacterial time (≥8 weeks) and enough compressive strength (>11MPa). Materials and methodsCPC specimens were obtained by incorporating different doses (weigh ratios of 0%, 5%, 10%, 15%, 20%, 25 and 30%) of injectable VCM into CPC. The antibacterial effect of released VCM solution against Staphylococcus aureus was assessed by inhibition ring assays. The physicochemical properties such as compressive strengths were characterized and compared among these specimens. ResultsDrug release profiles showed only 5 and 10% VCM-loaded CPC displayed a long enough drug release time (at least 8 weeks) and maintained the eluate concentrations (>4μg/mL) with effective antibacterial ability. The concentration of VCM in 10% group at 8th week was twice higher than 5% group. Compressive strength test showed that the proportional increase of VCM/CPC ratios resulted in a significant decrease of compressive strength (r=−0.906, p<0.001). Conclusion10% VCM-loaded CPC offered the optimal physicochemical properties and drug releasing profile and appears as the most suitable concentration for clinical use. Level of evidenceIII.

Early childhood antibiotics use and autism spectrum disorders: a population-based cohort study.

Changes in microbiota composition as a result of antibiotics use in early life has been proposed as a possible contributor in the aetiology of autism spectrum disorders (ASD). We aimed to examine the association between early life antibiotic exposure and risk of ASD. This was a population-based cohort study which included all live births in Manitoba, Canada, between 1 April 1998 and 31 March 2016. We used administrative health data from the Manitoba Population Research Data Repository. Exposure was defined as having filled one or more antibiotic prescription during the first year of life. The main outcome was ASD diagnosis. Cox proportional hazards regression models were used to estimate the risk of developing ASD in the overall population and in a sibling cohort. Of all subjects in the cohort (n = 214834), 94024 (43.8%) filled an antibiotic prescription during the first year of life. During follow-up, 2965 children received an ASD diagnosis. Compared with children who did not use antibiotics during the first year of life, those who received antibiotics had a reduced risk of ASD [adjusted hazardz ratio (HR) 0.91, 95% confidence interval (CI) 0.84-0.99). Number of treatment courses and cumulative duration of antibiotic exposure were not associated with ASD. In the sibling-controlled analysis, early life antibiotic exposure was not associated with ASD (adjusted HR 1.03, 95% CI 0.86-1.23). Our findings suggested no clinically significant association between early life antibiotics exposure and risk of autism spectrum disorders, and should provide reassurance to concerned prescribers and parents.

Nosocomial Pneumonia in Patients Admitted to the Intensive Care Unit of a Tertiary Care Center in Mashhad, Northeast of Iran; an Etiologic Survey

Background: Hospital-acquired pneumonia (HAP) prevalence is related to patients’ population and diagnostic methods. HAP incidence is reported in different studies from 9% to 46%. The current study aimed at evaluating the etiology of HAP in patients admitted to intensive care units (ICUs). Methods: The patients admitted to ICU of Imam Reza hospital (a tertiary care and teaching hospital in Mashhad, Northeast of Iran) were evaluated for HAP based on the following criteria: fever, leukocytosis, purulent discharge, new radiologic findings, changes in O2 saturation, and ventilator setting. Blood and endotracheal aspirates cultures were performed for all patients. Demographic characteristics were recorded in a checklist. Results: Among the 88 adult patients enrolled in the current study, the most frequent radiologic finding was patchy infiltration in chest X-ray (71.6%). Mean age of the patients was 58 ± 20.1 years; mean hospital stay was 63 ± 40.8 days; mean interval between hospitalization and pneumonia development was 20.9 ± 16.8 days; and 41 patients (46.6%) died. Acinetobacter spp. were the most frequent microorganisms in purulent discharge and methicillin-resistant Staphylococcus aureus (MRSA) were the main bacteria isolated from blood culture. Conclusions: Early diagnosis and appropriate antibiotic therapy can decrease HAP mortality and morbidity. The current study findings revealed that Acinetobacter app. were the most frequent cause of HAP in ICU patients in the studied center, which should be considered at the time of diagnosis and empirical antibiotics administration. Appropriate infection control and preventive measures should also be taken in ICUs to prevent HAP, especially against those caused by Acinetobacter spp.

Combat Soft Tissue Injuries

The soft tissue injuries encountered in combat are generally orders of magnitude more dramatic that those seen in civilian practice. The goal of this chapter is to help shorten the learning curve to care for the extensive soft tissue wounds of war by reviewing the limited research available on the subject and sharing lessons learned from the battlefield. Data from recent conflicts in Iraq, Afghanistan, and Syria demonstrate that the soft tissue injuries sustained in a warzone are unique compared to the types of injuries seen in civilian practice. These injuries have high infection rates, result in extensive tissue loss, and require special strategies to optimize outcomes. Devastating soft tissue injuries in combat are often accompanied by multiple life-threatening injuries and one must have a systematic approach to evaluation and treatment. War wounds are highly contaminated. Early antibiotics, thorough exploration, serial debridement, and irrigation are the mainstays of therapy. While plans for wound closure must start with the first operation, all combat wounds should initially be left open.

A prospective study on quality of life in patients with pulmonary tuberculosis at a tertiary care hospital in Kashmir, Northern India

BackgroundPulmonary Tuberculosis (PTB) is a contagious, airborne infection that destroys when M. tuberculosis primarily attacks the lungs. PTB is curable with an early diagnosis and antibiotic treatment. Stigmatization and negative emotions resulting from the illness could result in long term impairment of patients psychological well being which may result in work absenteeism resulting in loss of productivity and reduced monthly income. MethodsThis was a prospective study which was conducted over a period of one and half year. A total of 198 patients were recruited for the study. Quality Of Life (QOL) was assessed at baseline and at the end of intensive phase. For QOL WHO based QOLBREF was used. ResultsIn the present study patients scored lowest in the baseline physical (8.36 ± 1.60) followed by the psychological domain (10.40 ± 1.72) however at the end of intensive phase both physical (11.98 ± 1.70) and psychological (12.75 ± 1.) domains improved very much and the difference was statistically significant. ConclusionWe conclude that HRQOL is significantly reduced in patients with PTB, and that it improves rapidly and significantly with DOTS-based intensive phase of treatment. Special focus on reduction of stigmatization should be given in the management of TB to reduce the psychological distress.

Risk factors for hospitalized patients with resistant or multidrug-resistant Pseudomonas aeruginosa infections: a systematic review and meta-analysis

BackgroundIdentifying risk factors predicting acquisition of resistant Pseudomonas aeruginosa will aid surveillance and diagnostic initiatives and can be crucial in early and appropriate antibiotic therapy. We conducted a systematic review examining risk factors of acquisition of resistant P. aeruginosa among hospitalized patients.MethodsMEDLINE®, EMBASE®, and Cochrane Central were searched between 2000 and 2016 for studies examining independent risk factors associated with acquisition of resistant P. aeruginosa, among hospitalized patients. Random effects model meta-analysis was conducted when at least three or more studies were sufficiently similar.ResultsOf the 54 eligible articles, 28 publications (31studies) examined multi-drug resistant (MDR) or extensively drug resistant (XDR) P. aeruginosa and 26 publications (29 studies) examined resistant P. aeruginosa. The acquisition of MDR P. aeruginosa, as compared with non-MDR P. aeruginosa, was significantly associated with intensive care unit (ICU) admission (3 studies: summary adjusted odds ratio [OR] 2.2) or use of quinolones (4 studies: summary adjusted OR 3.59). Acquisition of MDR or XDR compared with susceptible P. aeruginosa was significantly associated with prior hospital stay (4 studies: summary adjusted OR 1.90), use of quinolones (3 studies: summary adjusted OR 4.34), or use of carbapenems (3 studies: summary adjusted OR 13.68). The acquisition of MDR P. aeruginosa compared with non-P. aeruginosa was significantly associated with prior use of cephalosporins (3 studies: summary adjusted OR 3.96), quinolones (4 studies: summary adjusted OR 2.96), carbapenems (6 studies: summary adjusted OR 2.61), and prior hospital stay (4 studies: summary adjusted OR 1.74). The acquisition of carbapenem-resistant P. aeruginosa compared with susceptible P. aeruginosa, was statistically significantly associated with prior use of piperacillin-tazobactam (3 studies: summary adjusted OR 2.64), vancomycin (3 studies: summary adjusted OR 1.76), and carbapenems (7 studies: summary adjusted OR 4.36).ConclusionsPrior use of antibiotics and prior hospital or ICU stay was the most significant risk factors for acquisition of resistant P. aeruginosa. These findings provide guidance in identifying patients that may be at an elevated risk for a resistant infection and emphasize the importance of antimicrobial stewardship and infection control in hospitals.

Impact on the intestinal microbiota of early antibiotic treatment in preterm neonates

Objective: To investigate the impact of early antibiotics treatment on intestinal microbiota in preterm infants. Methods: The cohort study was performed from January 2015 to June 2015 in Neonatal Intensive Care Unit of Peking University Third Hospital. A total of 33 preterm infants were enrolled, among whom 25 were antibiotics-exposure group, and 8 were non-exposure group. Serial stool samples were collected on the first day, 14th and 30th days of life and analyzed by high-throughput sequencing. In exposure group, intestinal microbiota was also analyzed at 8 months to 1 year of age. Categorical variables were analyzed with χ(2) test, and continuous variables were analyzed with t test or non-parametric test. Results:Proteobacteria was the most prominent flora after birth in all cases (exposure group 69.6%, non-exposure group 83.7%) . In exposure group, at the phylum level, Proteobacteria was the dominant bacteria within the first 30 days, followed by Firmicutes after 30 days of life. At the genus level, Escherichia was the most abundant genera within 30 days after birth, while Veillonella became dominant after 8 months to 1 year of life. In non-exposure group, at the phylum level, Proteobacteria was the dominant phylum within the first 30 days. At the genus level, Actinobacteria (37.5%) was the dominant genus after birth, followed by Escherichia within the first month. Intestinal bacterial abundance and diversity were lower in exposure group, which was most significant on 30th day of life (shannon index 2.6 vs.3.4, ACE index 563.9 vs.591.6) . The influence of single antibiotics was less significant than combined treatment (shannon index 2.7 vs.2.5, ACE index 727.3 vs.492.9) . At the genus level, compared to non-exposure group, there were significant decrease of Escherichia (9.3% vs. 54.3%, Z=-2.830, P=0.005), Klebsiella (0.03% vs.12.4%,Z=-2.240, P=0.025), and Clostridium (0.2% vs. 4.8%, Z=-2.979, P=0.003) in exposure group on 14 days of life. Bifidobacterium (0.1% vs.2.0%, Z=-2.349, P=0.019) in cases treated with combined antibiotics was lower than that treated with antibiotic monotherapy on 30 days of life. Conclusions: Early application of combined antibiotics impacts on the intestinal microbiome of preterm infants significantly. The infants who have received antibiotic after birth have lower quantity and diversity of Clostridium, Lactobacillus, Bacteroides and Bifidobacterium.

Incidence and Risk Factors for Complications of Exposed Kirschner Wires Following Elective Forefoot Surgery

Category: Midfoot/Forefoot Introduction/Purpose: Kirschner wires (K-wires) are commonly utilized for temporary metatarsal and phalangeal fixation following forefoot corrective osteotomies. K-wires can remain in place for up to 6 weeks postoperatively and are at risk for wound complications. Their exposure to the outside environment and direct osseous communication makes infection an important concern for the clinician. Early removal, prophylactic antibiotics, and re-operation are potential sequelae of infected K-wires and can affect outcomes. The purpose of this study is to evaluate the incidence of complications of exposed K-wires after forefoot surgery and identify patient or perioperative risk factors for these complications. Methods: A single surgeon retrospective chart review of forefoot surgeries over the past 10 years was undertaken. Inclusion criteria were any adult undergoing elective forefoot surgery with the use of exposed K-wires. Incidence of wound complication defined as cellulitis, pin site drainage, or migration/loosening of the pin requiring prophylactic antibiotics or early removal was noted. Patient demographic data such as age, BMI, comorbidities, and smoking status were recorded. Perioperative data such as tourniquet time, type of anesthesia, and perioperative antibiotics was also recorded. Univariate analysis was performed via Mann-Whitney test for continuous variables and Chi square test for categorical variables. Multivariate analysis was performed for statistically significant risk factors. Results: 1,217 Patients (2,018 K-wires) were analyzed. There was a 10% complication rate requiring prophylactic antibiotics or early removal (N=123). 40 patients required early pin removal, 54 patients were given oral antibiotics, and 29 patients required both. Female gender (p&lt;0.001), BMI over 28 (p&lt;0.001), general anesthesia (p=0.025), increased tourniquet time (p=0.003) and history of rheumatoid arthritis (p=0.047) were significantly associated with complications. Both male gender [OR 2.62] and tourniquet time [OR 1.01] remained significant on multivariate regression analysis. There was no increased risk of complications with a history of smoking or diabetes. Conclusion: The K-wire is an important modality for providing temporary immobilization of the smaller bones of the forefoot following deformity correction. Male gender, elevated BMI, history of rheumatoid arthritis, general anesthesia, and longer tourniquet time are associated with increased risk of pin infection requiring early removal and/or antibiotics. Further study is needed to determine whether optimizing inflammatory disease, using efficient perioperative technique, and utilizing local anesthesia may limit the risk of wound complications with K-wires in forefoot surgery.

Current perspectives on diagnosis and management of sternal wound infections.

Deep sternal wound infection (DSWI), also known as mediastinitis, is a serious and potentially fatal condition. The diagnosis and treatment of DSWI are challenging. In this current narrative review, the epidemiology, risk factors, diagnosis, and surgical and antimicrobial management of DSWI are discussed. Ideally, the management of DSWI requires early and sufficient surgical debridement and appropriate antibiotic therapy. When foreign material is present, biofilm-active antibiotic therapy is also needed. Because DSWI is often complex, the management requires the involvement of a multidisciplinary team consisting of cardiothoracic surgeons, plastic surgeons, intensivists, infectious disease specialists, and clinical microbiologists.

Early Prediction of Sepsis in EMR Records Using Traditional ML Techniques and Deep Learning LSTM Networks.

Sepsis is a life-threatening condition caused by infection and subsequent overreaction by the immune system. Physicians effectively treat sepsis with early administration of antibiotics. However, excessive use of antibiotics on false positive cases cultivates antibiotic resistant bacterial strains and can waste resources while false negative cases result in unacceptable mortality rates. Accurate early prediction ensures correct, early antibiotic treatment; unfortunately, prediction remains daunting due to error-ridden electronic medical records (EMRs) and the inherent complexity of sepsis. We aimed to predict sepsis using only the first 24 and 36 hours of lab results and vital signs for a patient. We used the Medical Information Mart for Intensive Care III (MIMIC3) dataset to test machine learning (ML) techniques including traditional methods (i.e., random forest (RF) and logistic regression (LR)) as well as deep learning techniques (i.e., long short-term memory (LSTM) neural networks). We successfully created a data pipeline to process and clean data, identified important predictive features using RF and LR techniques, and trained LSTM networks. We found that our best performing traditional classifier, RF, had an Area Under the Curve (AUC-ROC) score of 0.696, and our LSTM networks did not outperform RF.

Impact of printed antimicrobial stewardship recommendations on early intravenous to oral antibiotics switch practice in district hospitals.

Background:Early intravenous to oral (IV-PO) antibiotics switch, which is one of the important elements in antimicrobial stewardship (AMS) is not well implemented in Malaysian district hospitals. A systematic interventional strategy is required to facilitate IV-PO antibiotic switch.Objective:This study aimed to evaluate the impact of printed AMS recommendations on early IV-PO antibiotics switch practice in district hospitals.Methods:This study was an interventional study conducted in medical wards of eight Sarawak district hospitals from May to August 2015. In pre-intervention phase, pharmacists performed the conventional practice of reviewing medication charts and verbally informed the prescribers on eligible IV-PO switches. In post-intervention phase, pharmacists attached printed checklist which contained IV-PO switch criteria to patients’ medical notes on the day patients were eligible for the switch. Stickers of IV-PO switch were applied to the antibiotic prescription to serve as reminders.Results:79 and 77 courses of antibiotics were studied in the pre-intervention phase and post-intervention phase respectively. Timeliness of switch was improved by 1.63 days in the post-intervention phase (95%CI 1.26:2.00 days, p<0.001). Mean duration of IV antibiotics in the post-intervention phase was shorter than pre-intervention phase (2.81 days (SD=1.77) vs 4.05 days (SD=2.81), p<0.001). The proportion of IV-PO switches that were only performed upon discharge reduced significantly in the post-intervention phase (31.2% vs 82.3%, p<0.001). Length of hospital stay in the post-intervention phase was shortened by 1.44 days (p<0.001). Median antibiotic cost savings increased significantly in the post-intervention phase compared to the pre-intervention phase [MYR21.96 (IQR=23.23) vs MYR13.10 (IQR=53.76); p=0.025)].Conclusions:Pharmacist initiated printed AMS recommendations are successful in improving the timeliness of IV-PO switch, reducing the duration of IV, reducing the length of hospitalisation, and increasing antibiotic cost savings.

Efficacy of Preoperative Antibiotic Therapy for the Treatment of Vascular Graft Infection

Objective: We aimed to assess the efficacy of preoperative antibiotic therapy for the treatment of prosthetic graft infection.Materials and Methods: We retrospectively analyzed the treatment strategies used for managing patients with prosthetic vascular graft infections between 2000 and 2016. The patients were divided into two groups: early antibiotic (EA) group, those who were administered with antibiotics ≥2 weeks preoperatively and late antibiotic (LA) group, those who were administered with antibiotics <2 weeks preoperatively. We evaluated the outcomes including surgical procedures, length of hospital stay, and surgical revision.Results: All the surgical procedures performed in the EA group were elective surgeries. Three of the 11 surgeries performed in the LA group were emergency surgeries (P=0.16). No significant differences were observed in the operative procedure (P=0.64), operation time (P=0.37), and blood loss (P=0.63) of the two groups. Although the length of postoperative hospital stay did not significantly differ (P=0.61), the total length of hospital stay was longer in the EA group (P=0.02). Surgical revisions were performed for five patients in the LA group and for none in the EA group (P=0.04).Conclusion: Preoperative antibiotic therapy provided excellent outcomes in terms of avoiding surgical revisions in the treatment of vascular graft infection.

Early Life Exposure to Antibiotic Alters Energy Balance during Chronic High-Fat Feeding in Adult Male and Female Mice

Gut microbiota are affected by antibiotics and may modulate host energy metabolism. Male and female C57BL/6J mice (n=5∼11/group) were exposed to low-dose penicillin (LDP) via maternal drinking water from birth to 4 weeks (w) of age, and chronic changes in energy balance were examined using metabolic cages. Through 8w of age (Chow), LDP and Control mice had comparable fat mass, but male and female LDP mice showed significantly increased O2 consumption rates without changes in food intake and activity (Figure). At 9w of age, mice were given a high-fat diet (HFD; 45% fat by calories), and they began gaining adiposity with female LDP mice showing ∼40% lower fat mass than Controls. After 8w of HFD, male LDP group showed significantly elevated O2 consumption rates compared to Controls. Male LDP mice also showed marked reductions in food intake and activity, but these effects were no longer observed after 12w of HFD. In contrast, female LDP group had reduced O2 consumption rates compared to Controls after 4 and 8w of HFD without changes in food intake and activity. In conclusion, these results indicate that early life exposure to penicillin modulates energy balance in young and mature mice, suggesting an important role of altered populations of gut microbiota in diet-induced obesity. Our findings also identify important gender-selective effects of early life antibiotic exposure on energy balance in mature mice. Disclosure H. Noh: None. S. Suk: None. R.H. Friedline: None. K. Inashima: None. D.A. Tran: None. A.M. Kim: None. S. Kim: None. S. Jeong: None. C. Uong: None. B.A. Ozkan: None. V. Kasina: None. K.P. Knowles: None. G. Perez-Perez: None. K. Lee: None. M.J. Blaser: None. J.K. Kim: None.

Early prophylactic antibiotics for severe acute pancreatitis: A population-based cohort study using a nationwide database in Japan.

Previous studies evaluating the clinical benefits of prophylactic antibiotics for severe acute pancreatitis (SAP) have generated inconsistent results due to heterogeneities among the study settings. We determined if early prophylactic antibiotics improved the outcomes of SAP patients using a study designed to overcome these previous methodological weaknesses. We conducted a retrospective cohort study of SAP patients discharged between July 2010 and March 2016, using a Japanese nationwide inpatient database. We divided patients into those with early prophylactic carbapenem use (prophylaxis group) and those without prophylaxis (control group). The primary outcome was in-hospital mortality and the secondary outcomes included oral vancomycin use and others. We identified a total of 3354 eligible patients, including 2493 in the prophylaxis group and 861 in the control group. The overall in-hospital mortality was 12.8%. Prophylactic antibiotics were not significantly associated reduced in-hospital mortality according to Cox regression analysis (hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.62-1.23) or instrumental variable analysis (risk difference,-1.2%; 95% CI,-9.8%-7.4%). However, prophylactic antibiotic use was significantly associated with oral vancomycin use during hospitalization in a competing-risk model (subdistribution HR, 1.91; 95% CI, 1.02-3.56). The present study suggests that routine early prophylactic antibiotic use have no significant clinical benefit in SAP patients but may increase the risk of hospital-acquired infections.

Postoperative Spinal Implant Infections in Children: Risk Factors, Characteristics and Outcome.

Postoperative infection is a major complication of spinal surgery with implants. We aimed to identify risk factors for, and characteristics of, postoperative spinal infections in children. We performed a retrospective observational study of all children who underwent posterior spinal fusion with instrumentation in 2 referral hospitals in 2008-2013. Spinal infections were defined as local and/or general signs of infection that required surgical treatment in the early postoperative phase (ie, within 30 days). Data were collected on a standardized questionnaire from medical charts. Of the 450 children who underwent spinal surgery, 26 (5.8%) were diagnosed with early postoperative spinal implant infection, with a median age of 14 years (interquartile range, 13-17) and a median delay of 13 days postsurgery (interquartile range, 7-18). Postoperative infection was more common in children with neurologic scoliosis as compared with idiopathic scoliosis (12.2% [15/123] versus 2.4% [5/211]; P < 0.01). Neurologic scoliosis was an independent predictor of spinal implant infections (hazard ratio, 3.87 [1.72-8.69]; P < 0.001). Main pathogens were Staphylococcus aureus (n = 14) and Enterobacteriaceae (n = 8). All children underwent early surgery (wound exploration, debridement and lavage) and antibiotics for a median duration of 19 weeks [interquartile range, 12-26]. Two children (7.7%) required a second surgery. Spinal implants could be retained in all, and no relapse occurred with a follow-up of ≥24 months after antibiotic discontinuation. Postoperative spinal implant infection is not rare in pediatric patients, especially with neurologic scoliosis. Most children may be cured with implant retention if managed with early surgery followed by a 3-month course of appropriate antibacterial agents.

Marked Response in Microbial Community and Metabolism in the Ileum and Cecum of Suckling Piglets After Early Antibiotics Exposure.

In modern swine husbandry systems, antibiotics have been used as growth promoters for piglets during suckling or weaning period. However, while early colonization of intestinal microbiota has been regarded crucial for the host’s later life performance and well-being, little is known about the impact of antibiotics on intestinal microbiota in suckling piglets. The present study aimed to investigate the effects of early antibiotics exposure on gut microbiota and microbial metabolism of suckling piglets. Sixteen litters of suckling piglets were fed a creep feed diet with (Antibiotic) or without (Control) antibiotics from postnatal days 7–23 (n = 8). The ileal and cecal digesta were obtained for microbial composition and microbial metabolites analysis. The results showed that the antibiotics significantly altered the bacterial community composition by decreasing (P < 0.05) the diversity and richness in the ileum. The antibiotics significantly reduced the abundance of Lactobacillus in both the ileum and cecum, increased the abundance of Streptococcus, unclassified Enterococcaceae, unclassified Fusobacteriales, and Corynebacterium in the ileum, and the abundance of unclassified Ruminococcaceae and unclassified Erysipelotrichaceae in the cecum. The antibiotics decreased (P < 0.05) ileal lactate concentration and cecal concentration of total short-chain fatty acids (SCFAs). But the antibiotics enhanced protein fermentation (P < 0.05) in the ileum and cecum, as ileal concentrations of putrescine and cadaverine, and cecal concentrations of isobutyrate, isovalerate, putrescine, cadaverine, spermine, and spermidine were significantly increased (P < 0.05). These results indicated that early antibiotics exposure significantly altered the microbial composition of suckling piglets toward a vulnerable and unhealthy gut environment. The findings provide a new insight on the antibiotics impact on neonates and may provide new framework for designing alternatives to the antibiotics toward a healthy practice for suckling piglets.

Temporal Trends and Center Variation in Early Antibiotic Use Among Premature Infants

Premature infants are frequently administered empirical antibiotic therapy at birth. Early and prolonged antibiotic exposures among infants without culture-confirmed infection have been associated with increased risk of adverse outcomes. To examine early antibiotic use among premature infants over time and across hospitals in the United States. This retrospective cohort study used a comprehensive administrative database of inpatient encounters from 297 academic and community hospitals across the United States to examine data concerning very low-birth-weight (VLBW) infants (<1500 g), including extremely low-birth-weight (ELBW) infants (<1000 g), who were admitted to the neonatal intensive care unit and survived for at least 1 day. Data collection took place in November 2015 and analysis took place from February 2016 to November 2016. Antibiotic initiation within the first 3 days of age and subsequent antibiotic administration for more than 5 days. Temporal trends in early antibiotic initiation and duration from 2009 to 2015, and center variation in early antibiotic use from 2014 to 2015. We identified 40 364 VLBW infants (20 447 female [50.7%]) who survived for at least 1 day, including 12 947 ELBW infants, from 297 centers. The majority of premature infants had early antibiotic initiation (31 715 VLBW infants [78.6%] and 11 264 ELBW infants [87.0%]), and no differences were observed over time in temporal trend analyses (P = .12 for VLBW and P = .52 for ELBW). The annual risk difference in the proportion of VLBW infants administered early antibiotic therapy ranged from -0.75% (95% CI, -1.61% to 0.11%) to -0.87% (95% CI, -2.04% to 0.30%); in ELBW infants the annual risk difference ranged from -0.34% (95% CI, -1.28% to 0.61%) to -0.38% (95% CI, -1.61% to 0.85%). There was a small but significant decrease over time in the rate of prolonged antibiotic duration for VLBW infants (P = .02), but not for ELBW infants (P = .22). The annual risk difference in the proportion of VLBW infants with prolonged antibiotic duration ranged from -0.94% (95% CI, -1.65% to -0.23%) to -1.08% (95% CI, -2.00% to -0.16%); in ELBW infants the annual risk difference ranged from -0.72% (95% CI, -1.83% to 0.39%) to -0.75% (95% CI, -1.96% to 0.46%). We also observed variation in early antibiotic exposures across centers. Sixty-nine of 113 centers (61.1%) started antibiotic therapy for more than 75% of VLBW infants, and 56 of 66 centers (84.8%) started antibiotic therapy for more than 75% of ELBW infants. The proportion of VLBW and ELBW infants administered prolonged antibiotics ranged from 0% to 80.4% and 0% to 92.0% across centers, respectively. Most premature infants in this study received empirical early antibiotic therapy with little change over a recent 7-year period. The variability in exposure rates across centers, however, suggests that neonatal antimicrobial stewardship efforts are warranted to optimize antibiotic use for VLBW and ELBW infants.