Days Of Antibiotic Treatment Research Articles

Efficacy of seven and fourteen days of antibiotic treatment in uncomplicated Staphylococcus aureus bacteremia (SAB7): study protocol for a randomized controlled trial

BackgroundStaphylococcus aureus bacteremia (SAB) is frequently encountered in the hospital setting, and current guidelines recommend at least 14 days of antibiotic treatment for SAB in order to minimize risks of secondary deep infections and relapse. However, evidence to support these treatment recommendations remains scarce. Patients with uncomplicated SAB are known to have a low of risk of recurrence and death. Reducing treatment length in uncomplicated SAB would reduce the total consumption of antibiotics, duration of hospital admission, and potentially the risk of adverse events. With SAB7 we seek to determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is non-inferior to 14 days of treatment.Methods/designThe study is designed as a randomized, non-blinded, non-inferiority, multicenter interventional study. Primary measure of outcome will be 90-day survival without clinical or microbiological failure to treatment or relapse. Secondary outcomes include the prevalence of severe adverse effects, in particular secondary infection with Clostridium difficile, all-cause mortality, as well as public health related costs. Patients identified with uncomplicated SAB who have received 7 days of protocol-approved antibiotics will be eligible for inclusion and randomized 1:1 in two parallel arms to either (i) discontinue antibiotic treatment at day 7 or (ii) to continue antibiotic treatment for a total of 14 days. Main exclusion criteria include signs of complicated SAB, such as the presence of secondary deep infections, persistent bacteremia, and implantable devices. Patients are followed for 6 months with clinical examinations, consecutive blood tests, and registration of adverse events. A total of 284 patients are to be included at ten centers across Denmark. The primary endpoint will be tested with a statistical non-inferiority margin of 10 percentage points.DiscussionSAB 7 will determine if 7 days of antibiotic treatment in patients with uncomplicated SAB is sufficient and safe. Results of the study will provide important knowledge on optimized SAB management and could potentially modify the current treatment recommendations.Trial registrationClinicalTrails.gov, H-17027414. Registered on May 2, 2018. The Danish Medicines Agency (EudraCT), 2017–003529-13. Registered on October 30, 2017.

Impact of antibiotic treatment duration on outcomes in older men with suspected urinary tract infection: Retrospective cohort study

Clinical guidelines recommend at least 7days of antibiotic treatment for older men with urinary tract infection (UTI). There may be potential benefits for patients, health services, and antimicrobial stewardship if shorter antibiotic treatment resulted in similar outcomes. We aimed to determine if treatment duration could be reduced by estimating risk of adverse outcomes according to different prescription durations. This retrospective cohort study included men aged greater than or equal to 65years old with a suspected UTI. We compared outcomes in men prescribed 3, 5, 7, and 8 to 14days of antibiotic treatment in a multivariable logistic regression analysis and 3 versus 7days in a propensity-score matched analysis. Our outcomes were reconsultation and represcription (proxy for treatment failure), hospitalisation for UTI, sepsis, or acute kidney injury (AKI), and death. Of 360640 men aged greater than or equal to 65years, 33745 (9.4%) had a UTI. Compared with 7days, men prescribed 3-day treatment had greater odds of reconsultation and represcription (adjusted OR 1.48; 95% CI, 1.25-1.74) but lower odds of AKI hospitalisation (adjusted OR 0.66; 95% CI, 0.45-0.97). We estimated that treating 150 older men with 3days instead of 7days of antibiotics could result in four extra reconsultation and represcriptions and one less AKI hospitalisation. We estimated annual prescription cost savings at around £2.2 million. Antibiotic treatment for older men with suspected UTI could be reduced to 3days, albeit with a small increase in risk of treatment failure. A definitive randomised trial is urgently needed.

A tale of four valves: outcome of Brucella endocarditis: a case series.

BackgroundBrucellosis is a zoonotic infection. Humans contract brucellosis through inhalation of aerosolized infected particles, or when they come in direct contact with infected animal parts, or on consuming unpasteurised dairy products. It can affect multiple organs and systems. Endocarditis is diagnosed late in the course of the disease with mostly aortic valve involvement with serious morbidity and mortality.Case summaryWe report a case series of four patients with Brucella endocarditis. The first patient presented with fever, malaise, and exertional breathlessness. He underwent aortic valve replacement for refractory heart failure and bulky vegetations after failed medical therapy. The second patient presented with fever, breathlessness New York Heart Association (NYHA) III, with arthralgia, myalgia, anorexia, and weight loss. In view of aortic abscess with impending rupture and compression of left main coronary artery, aortic valve replacement was performed on the 4th day of antibiotic treatment. The third patient presented with fever, fatigue, NYHA II, and developed peripheral embolization but responded to medical treatment alone. The fourth patient presented with intermittent fever for 7 months. During hospitalization, he suffered acute limb ischaemia and stroke with absence of left dorsalis pedis and posterior tibial pulsation. Brucella IgG ELISA was positive. Mitral valve replacement was done subsequently with unremarkable hospital course.DiscussionBrucellosis is a challenging diagnosis to make. The diagnosis and treatment is often delayed as it presents with non-specific symptoms and signs. Cardiac involvement occurs in only 2% of the cases, but accounts for 80% of the mortality due to brucellosis. Brucella endocarditis should be suspected in cases of endocarditis with negative blood cultures and a risk of exposure. The most accepted treatment for Brucella endocarditis is a combination of antimicrobial therapy with surgery.

Management of Emphysematous Pyelonephritis and Subsequent Renal Functional Outcome

Background & objective: Emphysematous pyelonephritis (EPN) is an acute severe necrotizing infection of the renal parenchyma and its surrounding tissues that is caused by the presence of gas in the renal parenchyma, collecting system or perinephric tissue.The present study was intended to assess the functional status of the emphysematous kidney recovered from infection after treatment.
 Methods: This prospective study was conducted on 50 consecutive cases of emphysematous pyelonephritis, who were admitted in BIRDEM General Hospital from January 2011 to June 2012. Patients with EPN were selected after taking history, clinical examination and radiological image findings. Based on clinical parameter and radiological grading, patients were categorized for medical or surgical intervention. The forms of surgeries were open drainage or nephrectomy. Renal parenchymal destruction more than 50% on CT required nephrectomy.
 Results: The mean age of the patients at diagnosis was 47.5 ± 11.8 years (range: 26-70 years). The patients were predominantly female (82%), invariably diabetic and primarily presented with fever (88%) and loin pain (82%) followed by dysuria (60%). Over three-quarters (78%) of the patients had poor glycemic control (HbA1c >7%) and over half (54%) were classified as having class 1 or 2 disease and the rest had class 3 and 4 diseases. Escherichia coli was the commonest pathogen found in urine cultures (70%). Over half (56%) received medical treatment alone. In the surgical intervention group, patients were mostly toxic with spreading or severe localized infection, fever and were deteriorating or static even after three days of aggressive intravenous antibiotic treatment. Of the 22 patients who underwent surgery, nephrectomy was performed in 8(16%) and open drainage in 14(28%) cases. The overall survival rate was 94%. Average serum creatinine level was found to decrease gradually during follow up. The function of the preserved kidney was found to improve in the subsequent follow up.
 Conclusion: Emphysematous pyelonephritis predominantly affects diabetic females. Kidney preservation should be the primary target in treating EPN. Adequate resuscitation, diabetic control and parenteral antibiotic are the treatment of choice. Rapid drainage and nephrectomy should be performed in advanced stages. The focus of management of patients with emphysematous pyelonephritis should not only to improve survival but also salvage of the renal unit, for the affected kidney may still function once the infection is eradicated.
 Ibrahim Card Med J 2017; 7 (1&2): 57-63

405 - Fever in patients with upper ureteral stone: How many days of antibiotic treatment are sufficient to proceed with URSL?

405 - Fever in patients with upper ureteral stone: How many days of antibiotic treatment are sufficient to proceed with URSL?

Association of a blood culture utilization intervention on antibiotic use in a pediatric intensive care unit

Blood cultures are essential for the evaluation of sepsis. However, they may sometimes be obtained inappropriately, leading to high false-positive rates, largely due to contamination.1 As a quality improvement project, clinician decision-support tools for evaluating patients with fever or signs and symptoms of sepsis were implemented in April 2014 in our pediatric intensive care unit (PICU). This initiative resulted in a 46% decrease in blood culture obtainment2 and has been replicated in other institutions.3 It is important to evaluate antibiotic use as a balancing measure because a reduction in blood cultures could lead to an increase in antibiotic treatment days if clinicians continued empiric treatment in scenarios when blood culture results were not available. The objective of this study was to evaluate whether antibiotic use in the PICU changed in association with a reduction in blood culture utilization.

FDG-PET/CT for Detecting an Infection Focus in Patients With Bloodstream Infection: Factors Affecting Diagnostic Yield.

To investigate the diagnostic performance of F-fluoro-2-deoxy-D-glucose (FDG) PET/ CT for the detection of an infection focus in patients with a bloodstream infection (BSI) and to identify factors influencing the diagnostic yield of FDG-PET/CT. This retrospective single-center study included 185 consecutive patients with a BSI who underwent an FDG-PET/CT scan for the detection of an infection focus between 2010 and 2017. The final diagnosis at hospital discharge was used as reference standard. Diagnostic performance of FDG-PET/CT for the detection of an infection focus was assessed, and logistic regression analyses were performed to identify factors associated with FDG-PET/CT yield. An infection focus was identified on FDG-PET/CT in 120 (64.8%) of 185 patients. FDG-PET/CT achieved a sensitivity of 80.2%, specificity of 79.6%, positive predictive value of 90.8%, and a negative predictive value of 61.4% for detecting an infection focus in patients with a BSI. Blood cultures positive for enterococci (odds ratio, 0.14; P = 0.019) and days of antibiotic treatment before FDG-PET/CT (odds ratio, 0.94 per day increase; P = 0.014) were statistically significant independent predictors of a lower odds of detecting an infection focus on FDG-PET/CT. In patients who received antibiotics for less than 7 days before FDG-PET/CT, an infection focus was found in 71% (56/79). In patients who received antibiotics for 8 to 14 days before FDG-PET/CT, an infection focus was found in 52% (22/42). After 15 to 21 days of antibiotic treatment, an infection focus was found in 61% (8/13), and for 22 days or more, this declined to 38% (5/13). FDG-PET/CT is a useful method for detecting an infection focus in patients with BSI. However, longer duration of antibiotic treatment before FDG-PET/CT and bacteremia with enterococci reduce the diagnostic yield of FDG-PET/CT. These factors should be taken into account when considering an FDG-PET/CT scan for this indication.

Reconstruction of a Calvarial Wound Complicated by Infection: Comparing the Effects of Biopatterned Bone Morphogenetic Protein 2 and Vascular Endothelial Growth Factor.

Bone morphogenetic protein 2 (BMP2) bioprinted on biological matrix induces osseous regeneration in large calvarial defects in rabbits, both uncomplicated and scarred. Healing in unfavorable defects scarred from previous infection is decreased due in part to the lack of vascularity. This impedes the access of mesenchymal stem cells, key to osseous regeneration and the efficacy of BMP2, to the wound bed. The authors hypothesized that bioprinted vascular endothelial growth factor (VEGF) would augment the osseous regeneration achieved with low dose biopatterned BMP2 alone. Thirteen New Zealand white rabbits underwent subtotal calvariectomy using a dental cutting burr. Care was taken to preserve the underlying dura. A 15 mm × 15 mm flap of bone was cut away and incubated in a 1 × 108 cfu/mL planktonic solution of S aureus before reimplantation. After 2 weeks of subsequent infection the flap was removed and the surgical wound debrided followed by 10 days of antibiotic treatment. On postoperative day 42 the calvarial defects were treated with acellular dermal matrix bioprinted with nothing (control), VEGF, BMP2, BMP2/VEGF combined. Bone growth was analyzed with serial CT and postmortem histology. Defects treated with BMP2 (BMP2 alone and BMP2/VEGF combination) showed significantly greater healing than control and VEGF treated defect (P < 0.5). Vascular endothelial growth factor treated defect demonstrated less healing than control and VEGF/BMP2 combination treatments achieved less healing than BMP2 alone though these differences were nonsignificant. Low dose BMP2-patterned acellular dermal matrix improves healing of scarred calvarial defects. Vascular endothelial growth factor at the doses applied in this study failed to increase healing.

Study of clinical profile and antibiotic response in typhoid fever: A study in a Dhaka shishu (children) hospital, Dhaka, Bangladesh

The objectives of this Crosse sectional e analysis study is to gauge the clinical profile and pattern of varied medication employed in the treatment of infectious disease. A retrospective analysis of medicine patients littered with infectious disease was done at Department of Pediatric, Dhaka Shishu (Children) Hospital, and Dhaka throughout the year 2017-2018. Designation of patients was supported clinical options, agglutination test and blood culture. The mode of presentation, clinical course, treatment history, and laboratory investigations reports, antibiotic administered, response to medical care and also the complications were recorded. Total variety of 50 cases of infectious disease were studied. Out of those 23 (46%) were males and 27 (54%) were females. Average age of presentation was 8.2 years. Average length of hospital keep was 10.8 days. Fever was gift altogether patients. Resistance of S. typhi to ceftriaxone, Cipro, Azithromycin were considerably high. Antibiotic drug conjointly showed resistance in 21.4% of cases. Sensitivity to antibiotic was 100 percent in our study. Antibiotic drug was the foremost normally used antibiotic in our study (26 patients). Chloromycetin alone was employed in 2 patients and in 3 patients it had been given once 6 days of antibiotic drug treatment. Third generation antibiotic (ceftriaxone) alone were employed in ten patients. Indiscriminate use of medication in infectious disease ought to be discouraged. Acceptable antibiotic as indicated by sensitivity tests ought to use to forestall the event of resistant strains of S. typhi.

Early ureteroscopic treatment in patients with urosepsis associated with ureteral calculi is a safe approach. A pilot study.

IntroductionEmergency drainage of the urinary tract is the first necessary approach in patients with urosepsis secondary to obstructive ureteral calculi. The appropriate waiting time before definitive treatment has not been determined. We hypothesized that early ureteroscopic treatment after the patient has been stabilized is as safe as deferred treatment.Material and methodsA pilot study was developed between November 2013 and September 2017. Patients with urosepsis associated with ureteral calculi were included. All the patients were initially decompressed with a ureteral stent. Patients were randomized to early ureteroscopic treatment (EUT), who received definitive treatment during the initial hospitalization, or deferred ureteroscopic treatment (DUT), that received definitive treatment in a second hospitalization. The stone location and size, sex distribution, age, APACHE II score, length of hospital stay, days with ureteral catheter and complications were registered. Statistical analysis was performed using Stata 12.0.ResultsA total of 13 patients were included in the EUT group and 13 in the DUT group. No differences in sex distribution, stone location, APACHE II score, age, stone size and time between admission and urinary drainage were found. Total length of hospital stay and complications were also similar between both groups. A statistically significant difference was found in terms of duration of antibiotic treatment (p = 0.04) and total days with double J catheter (p = 0.0009).ConclusionsEUT for ureteral stone is as safe as DUT in patients admitted with urosepsis secondary to ureterolithiasis. EUT is associated with a shorter period of ureteral stent and it is not associated with an increase in complications.

Compassionate Use of Lumacaftor/Ivacaftor in Cystic Fibrosis: Spanish Experience

BackgroundThe most common cystic fibrosis (CF)-causing mutation is deltaF508 (F508del), which is present in 28% of CF Spanish patients. While the literature based on real-life studies on CF patients homozygous F508del treated with lumacaftor/ivacaftor is limited, it demonstrates the need for better strategies to prevent related adverse events (AEs) as well as the development of newer drugs. MethodsWe conducted a multicenter, retrospective, observational study to describe the effects of lumacaftor/ivacaftor treatment in real-life in Spain. 20 CF patients were included, all aged 6 and upwards and presented with ppFEV1<40%, chosen from CF units country-wide. For the purposes of the study, they were treated with lumacaftor/ivacaftor 200/125mg two tablets twice a day on a compassionate use programme throughout 2016. The primary endpoint was measured in all of the sample patients. Data were analysed from ppFEV1 at baseline and was measured every 6 months. ResultsThe mean age was 26.65 (range of 10–45), while the mean ppFEV1 before the treatment was 32.4% and mean BMI was 19.9kg/m2. We analysed the changes in ppFEV1 and BMI from baseline during the treatment with lumacaftor/ivacaftor, but no differences were found. However, a moderate association between days of intravenous antibiotic needed and the use of lumacaftor/ivacaftor (p=0.001) was established. Indeed, under the lumacaftor/ivacaftor, patients required 5.8 days of intravenous antibiotic treatment compared to 14.9 days prior to study. Also, severe pulmonary exacerbations requiring hospitalisation were statistically fewer under lumacaftor/ivacaftor treatment (p=0.003). Finally, 75% of the sample presented with AEs, which led 35% of the subjects to discontinue the treatment. ConclusionsWhile treatment with lumacaftor/ivacaftor resulted in an improvement in the number of pulmonary severe exacerbations, no improvement in ppFEV1 or BMI was found.

291. Effect of Previous Antibiotic Exposure on the Yield of Bone Biopsy Culture in Patients With Osteomyelitis

BackgroundBone biopsy and culture are gold standards for the diagnosis of osteomyelitis and are key factors in defining the etiology and treatment of osteomyelitis. There is concern that recent antibiotic exposure will decrease the sensitivity of microbiologic cultures.MethodsA retrospective analysis was performed of patients who underwent bone biopsy for evaluation of osteomyelitis at the University of Nebraska Medical Center from 2014 to 2017. Microbiological culture data were compared with the number of days of antibiotic treatment the patient received prior to biopsy. Days of antibiotic use was divided into quartiles and the Cochran-Armitage test was used to test whether antibiotic exposure was associated with culture yield. Fisher’s exact test and the Mann–Whitney test were used to compare anatomic location, diagnostic method, tobacco use, median WBC, ESR, CRP with culture positivity. Multivariable logistic regression was used to determine independent predictors of culture positivity.ResultsA total of 211 patients were studied. Descriptive statistics: 63% male, 85% Caucasian, median age: 55 years, duration of osteomyelitis prior to biopsy: median 39 days (mean 139 days). Location of osteomyelitis: lower extremity 48%, sacral/pelvic 19%, skull/facial 12%, spine 11%, upper extremity/chest 9%. Within 2 weeks prior to biopsy, the median value of the maximum WBC count, ESR, and CRP was 10.5, 66, and 5.7, respectively. A significant negative linear trend between culture positivity and days of antibiotic exposure (P < 0.0001) was observed (Figure 1). The rate of culture positivity was 85.07% for patients diagnosed with osteomyelitis who did not receive antibiotics and dropped to 78.57%, 73.08%, and 50% for patients who received 1–3 days, 4–14 days, and >14 days of antibiotics, respectively. Other independent predictors of culture positivity included elevated CRP (P = 0.0017) and clinical diagnosis of osteomyelitis (vs. histologic or radiographic) (P = 0.0042). ConclusionThere is a clear negative linear correlation between pre-bone biopsy antibiotic exposure and culture positivity in patients diagnosed with osteomyelitis. In addition, elevated CRP and method of osteomyelitis diagnosis independently correlate with culture positivity.Disclosures All authors: No reported disclosures.

319. Is Chronic Vertebral Disk Infection With Low Virulence Bacteria a Common Cause of Back Pain?

BackgroundIn 1998 Modic described changes in vertebral body marrow with magnetic resonance imaging, and related those changes to pathological findings in the adjacent disc that were similar to those seen in bacterial discitis. As early as 2001 Stirling noted a relationship between sciatica and Propionibacterium acnes cultured from disc space material obtained at discectomy. In 2013 Albert demonstrated that Modic type I changes, strongly associated with low back pain, responded to 100 days of antibiotic treatment in a large randomized controlled trial. The findings were controversial, and we proposed that modern microdiscectomy techniques would minimize the potential for contamination with the common skin bacteria reported most often in previous studies.MethodsWe performed a prospective uncontrolled case series of patients undergoing microdiscectomy for symptomatic disc degeneration or herniation. Subjects were greater than 18 years old, nonpregnant, with chronic low back pain, and meeting standard criteria for microdiscectomy. After giving informed consent, data were extracted from existing medical records and cultures of disc material were obtained at discectomy prior to perioperative prophylactic antibiotics, and were processed by standard methodology for aerobic, anaerobic and acid-fast bacterial growth.ResultsThirty-three patients were included in the study, mean age 52.6 (SE 3.1), 19 females and 14 males. The study was terminated after these 33 cases when only one aerobic culture was positive from one male subject, and this for a minimal growth of Staphylococcus epidermidis.ConclusionIf a significant fraction of chronic low back pain is indeed caused by chronic infection with low-virulence bacteria, this would be a paradigm shift in the evaluation and management of a common and often debilitating condition. In our study of patients with chronic low back pain undergoing microdiscectomy, we did not find evidence of chronic low-virulence bacterial infection.Disclosures All authors: No reported disclosures.

2333. Practice of Endotracheal Tube Suction Catheter Flushes With Polymyxin in Extremely Low Birthweight Neonates

BackgroundAerosolized or powdered forms of polymyxin have been used as prophylaxis for ventilator associated infections in adults. In 2015, Children’s National Medical Center neonatal intensive care unit (NICU) protocol recommended that neonates <1,000 g receive polymyxin endotracheal tube suction catheter flushes with the goal to reduce acquired respiratory infection. The objective of this study was to describe the clinical characteristics and outcomes of patients who received polymyxin endotracheal tube flushes compared with those who received saline.MethodsA retrospective cohort study of infants weighing <1,000 g ventilated for >48 hours in the NICU, January 1, 2015–June 30, 2016 was performed. Data were collected from an internal NICU database, medication billing data, and through chart review of the electronic health record. Demographics, antibiotic treatment days, ventilator days, length of stay, mortality, and microbiologic culture data were compared between patients receiving polymyxin and saline using chi-squared for binary and t-test for continuous variables.ResultsOf the 71 patients included, 38 received polymyxin and 33 received saline. Mean gestational age at birth was 24.1 weeks (23.9 polymyxin vs. 24.2 saline, P = 0.06); median age on admission 4 days (3 vs 12, P = 0.019); median admission weight 700 g (640 vs. 800, P = 0.002); 52% were male (58% vs. 45% group). Median antibiotic days was 52 (77 vs. 41, P = 0.056), median ventilator days 39 (43.5 vs. 33, P = 0.06). Pathogenic bacteria was cultured in 38% of patients in whom at least one lower respiratory tract (LRT) culture was obtained (62.5% vs. 38.1% P = 0.24). Pathogenic bacteria resistant to at least one antibiotic class to which is normally susceptible was found in 10% (13% vs. 6%, P = 0.32). No differences were seen in mortality (16% vs. 15%, P = 0.94) or median length of stay (101 vs. 92, P = 0.41).ConclusionAn NICU protocol recommending prophylactic polymyxin use for ELBW infants was implemented more frequently in younger and more premature neonates. Mortality and length of stay did not differ among babies who received polymyxin. Patients who received polymyxin did not grow a statistically significant higher proportion of pathogenic or resistant bacteria from LRT cultures compared with those receiving saline.Disclosures All authors: No reported disclosures.

Faecal microbiota transplantation shortens the colonisation period and allows re-entry of patients carrying carbapenamase-producing bacteria into medical care facilities

BackgroundColonisation with carbapenemase-producing Enterobacteriaceae or Acinetobacter (CPE/A) is associated with complex medical care requiring implementation of specific isolation policies and limitation of patient discharge to other medical facilities. Faecal microbiota transplantation (FMT) has been proposed in order to reduce the duration of gut colonisation. ObjectivesThis study investigated whether a dedicated protocol of FMT could reduce the negativation time of CPE/A intestinal carriage in patients whose medical care has been delayed due to such colonisation. MethodA matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A-colonised patients addressed for initial clustering at the current institute. The study adjusted two controls per case based on sex, age, bacterial species, and carbapenemase type. The primary outcome was delay in negativation of rectal-swab cultures. ResultsAt day 14 post FMT, 8/10 (80%) treated patients were cleared for intestinal CPE/A carriage. In the control group, 2/20 (10%) had spontaneous clearance at day 14 after CPE/A diagnosis. Faecal microbiota transplantation led patients to reduce the delay in decolonisation (median 3 days post FMT for treated patients vs. 50.5 days after the first documentation of digestive carriage for control patients) and discharge from hospital (median 19.5 days post FMT for treated patients vs. 41 for control patients). ConclusionFaecal microbiota transplantation is a safe and time-saving procedure to discharge CPE/A-colonised patients from the hospital. A standardised protocol, including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal, should improve protocol effectiveness.

Corticosteroids for septic arthritis in children.

Septic arthritis is an acute infection of the joints characterised by erosive disruption of the articular space. It is the most common non-degenerative articular disease in developing countries. The most vulnerable population for septic arthritis includes infants and preschoolers, especially boys. Septic arthritis disproportionately affects populations of low socioeconomic status. Systemic corticosteroids and antibiotic therapy may be beneficial for treatment of septic arthritis. Even if the joint infection is eradicated by antibiotic treatment, the inflammatory process may produceresidual joint damage and sequelae. To determine the benefits and harms of corticosteroids as adjunctive therapy in children with a diagnosis of septic arthritis. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library, Latin American Caribbean Health Sciences Literature (LILACS), the World Health Organization (WHO) trials portal (www.who.int/ictrp/en/), ClinicalTrials.gov (www.ClinicalTrials.gov), and Google Scholar. We searched all databases from their inception to 17 April 2018, with no restrictions on language of publication. We included randomised controlled trials (RCTs) with patients from two months to 18 years of age with a diagnosis of septic arthritis who were receiving corticosteroids in addition to antibiotic therapy or as an adjuvant to other therapies such as surgical drainage, intra-articular puncture, arthroscopic irrigation, or debridement. Two review authors independently assessed eligibility, data extraction, and evaluation of risk of bias. We considered as major outcomes the presence of pain, activities of daily living, normal physical joint function, days of antibiotic treatment, length of hospital stay, and numbers of total and serious adverse events. We used standard methodological procedures expected by Cochrane. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table. We included two RCTs involving a total of 149 children between three months and 18 years of age who were receiving antibiotics for septic arthritis. The most commonly affected joints were hips and knees. These studies were performed in Costa Rica and Israel. In both studies, dexamethasone administered intravenously (ranging from 0.15 to 0.2 mg/kg/dose every six to eight hours) during four days was the corticosteroid, and the comparator was placebo. Trials excluded patients with any degree of immunodeficiency or immunosuppression. The longest follow-up was one year. Trials did not report activities of daily living nor length of hospital stay. Both studies used adequate processes for randomisation, allocation concealment, and blinding, and review authors judged them to have low risk of selection and performance bias. Losses to follow-up were substantive in both studies, and we judged them to have high risk of attrition bias and of selective outcome reporting. We graded all outcomes as low quality due to concerns about study limitations and imprecision.The risk ratio (RR) for absence of pain at 12 months of follow-up was 1.33, favouring corticosteroids (95% confidence interval (CI) 1.03 to 1.72; P = 0.03; number needed to treat for an additional beneficial outcome (NNTB) = 13, 95% CI 6 to 139; absolute risk difference 24%, 95% CI 5% to 43%).The RR for normal function of the affected joint at 12 months of follow-up was 1.32, favouring corticosteroids (95% CI 1.12 to 1.57; P = 0.001; NNTB = 13, 95% CI 7 to 33; absolute risk difference 24%, 95% CI 11% to 37%).We found a reduction in the number of days of intravenous antibiotic treatment favouring corticosteroids (mean difference (MD) -2.77, 95% CI -4.16 to -1.39) based on two trials with 149 participants.Researchers did not report length of hospital stay. One trial (49 participants) reported that treatment with dexamethasone was associated with a shorter duration of IV antibiotic treatment, leading to a shorter hospital stay, and although duration of hospitalisation was a primary outcome of the study, study authors did not provide data on the duration of hospitalisation. We downgraded the quality by one level for concerns about study limitations (high risk of attrition bias and selective reporting), and by another level for imprecision.In one trial of 49 participants, researchers followed 29 children for 12 months, and parents reported that no children demonstrated adverse effects of the intervention. Evidence for corticosteroids as adjunctive therapy in children witha diagnosisof septic arthritis is of low quality and is derived from the findings of two trials (N = 149). Corticosteroids may increase the proportion of patients without pain andthe proportionof patients withnormalfunction of the affected joint at 12 months, and may also reduce the number of days of antibiotic treatment. However, we cannot draw strong conclusions based upon these trial results. Additional randomised clinical trials in children with relevant outcomes are needed.

Serum Interleukin-33 as a Biomarker in Predicting Neonatal Sepsis in Premature Infants.

Neonatal sepsis is considered as the most frequent cause of death in newborns. Early diagnosis is important to reduce mortality and morbidity. The rapid progression of the disease requires proper use of biomarkers specific for prompt diagnosis and intervention. We aimed to evaluate the benefit of interleukin-33 serum levels in the diagnosis and treatment of neonatal sepsis. We included 51 infants with neonatal sepsis as the main study group and 50 neonates without sepsis as the control group. Serum levels of interleukin-6, interleukin-33 and C-reactive protein were measured on the 1st, 3rd and 7th days of sepsis in the study group and on the 3rd postpartum day in the control group, respectively. Serum levels of interleukin-6, interleukin-33 and C-reactive protein were significantly higher in the first day of sepsis. Serum levels of interleukin-6, interleukin-33 and C-reactive protein decreased significantly on the 3rd and the 7th days of antibiotic treatment. We found a significant relationship between interleukin-33 and C-reactive protein and between interleukin-6 and C-reactive protein on the first day of sepsis. Serum interleukin-33 level is up-regulated in neonatal sepsis, which might be used as a novel diagnostic marker and also a useful tool to predict prognosis in early neonatal sepsis.

Alterations of serum vitamin K levels and prothrombin time-international normalized ratio during tooth extractions among patients receiving warfarin

ObjectiveThe British guideline described that antibiotic treatment during tooth extraction kills bacteria in the intestine, which reduces their production of vitamin K and leads to an increased prothrombin time-international normalized ratio (PT-INR). In this study, we attempted to clarify the influence of antibiotics on serum vitamin K levels and alteration of PT-INR in patients receiving warfarin. MethodsWe measured PT-INR and serum vitamin K levels (K1 from diet and K2 from intestinal bacteria) among 11 patients receiving warfarin during tooth extractions (on days 0, 1, 3, and 5) at Dokkyo Medical University Hospital, Sano Kosei General Hospital and Kamma Memorial Hospital from 2008 to 2018. All patients received 5 days of oral antibiotic treatment after the tooth extractions. ResultsThere were no significant changes in PT-INR between days 0 and 5. Serum vitamin K1 levels on day 0 were varied. Most patients had decreased serum vitamin K1 levels on days 1 and 3. Mean serum vitamin K1 levels on day 3 were significantly lower than those on day 0 (p = 0.04) in patients who were admitted to Dokkyo Medical University Hospital. Most patients still had low serum vitamin K1 levels between days 3 and 5. Serum vitamin K2 levels in most patients examined were below the detection limit (0.05 ng/ml) except two patients (0.24 ng/ml, 0.06 ng/ml at day 0). ConclusionIt appears that antibiotic treatment during tooth extractions might not affect PT-INR among patients receiving warfarin through the alteration of serum vitamin K2 production by intestinal bacteria.

Compassionate Use of Lumacaftor/Ivacaftor in Cystic Fibrosis: Spanish Experience

BackgroundThe most common cystic fibrosis (CF)-causing mutation is deltaF508 (F508del), which is present in 28% of CF Spanish patients. While the literature based on real-life studies on CF patients homozygous F508del treated with lumacaftor/ivacaftor is limited, it demonstrates the need for better strategies to prevent related adverse events (AEs) as well as the development of newer drugs. MethodsWe conducted a multicenter, retrospective, observational study to describe the effects of lumacaftor/ivacaftor treatment in real-life in Spain. 20 CF patients were included, all aged 6 and upwards and presented with ppFEV1<40%, chosen from CF units country-wide. For the purposes of the study, they were treated with lumacaftor/ivacaftor 200/125mg two tablets twice a day on a compassionate use programme throughout 2016. The primary endpoint was measured in all of the sample patients. Data were analysed from ppFEV1 at baseline and was measured every 6 months. ResultsThe mean age was 26.65 (range of 10–45), while the mean ppFEV1 before the treatment was 32.4% and mean BMI was 19.9kg/m2. We analysed the changes in ppFEV1 and BMI from baseline during the treatment with lumacaftor/ivacaftor, but no differences were found. However, a moderate association between days of intravenous antibiotic needed and the use of lumacaftor/ivacaftor (p=0.001) was established. Indeed, under the lumacaftor/ivacaftor, patients required 5.8 days of intravenous antibiotic treatment compared to 14.9 days prior to study. Also, severe pulmonary exacerbations requiring hospitalisation were statistically fewer under lumacaftor/ivacaftor treatment (p=0.003). Finally, 75% of the sample presented with AEs, which led 35% of the subjects to discontinue the treatment. ConclusionsWhile treatment with lumacaftor/ivacaftor resulted in an improvement in the number of pulmonary severe exacerbations, no improvement in ppFEV1 or BMI was found.

Prolonged use of antibiotics after birth is associated with increased morbidity in preterm infants with negative cultures

Background: Most preterm infants are exposed to a variable duration of antibiotic therapy after birth despite negative cultures. Data is emerging about the risks of prolonged antibiotics. We sought to assess the association between length of initial antibiotic course and neonatal outcomes in a cohort from a single large perinatal center. Methods: Retrospective cohort study of prospectively collected data on all infants with a birth weight of less than 1250 g hospitalized in our NICU in a 4 year window and who had negative blood and CSF cultures in the first 2 days of life. The primary outcome is a composite of necrotizing enterocolitis (NEC), late onset sepsis (LOS) and death evaluated using multivariable regression analysis. Results: A total of 620 infants less than 1250 g with negative cultures were eligible for study over a 4 year period. The 238 infants with more than 5 days initial antibiotic use were significantly smaller and of lower gestational age than the 382 infants who received up to 5 days of antibiotics. Their mothers had more clinical chorioamnionitis, less maternal hypertension and greater perinatal use of antibiotics. On multivariate analysis, infants who received empiric antibiotics for longer than 5 days had higher rates of neonatal morbidities after adjusting for gestational age, SNAP II, small-for-gestational age status, gender, maternal hypertension, prenatal steroid treatment, clinical chorioamnionitis, intrapartum antibiotic treatment, and multiple births. Composite outcome OR: 1.83 (1.15 to 2.92), LOS OR: 2.02 (1.20 to 3.39), bronchopulmonary dysplasia OR: 1.58 (1.04 to 2.29). Mortality and NEC were not significantly different. Conclusion: More than 5 days of antibiotic treatment in very preterm infants with negative cultures was associated with increased morbidity in our population, and that included BPD. It is of note that patterns of increased morbidity and/or mortality differ between studies. Prospective trials of clinical protocols for starting and stopping antibiotics in the very preterm infants are required.