Dose Of Intravenous Antibiotics Research Articles

Association of Timing With Postoperative Complications in the Management of Open Distal Radius Fractures

Background: This study investigates whether open distal radius fractures (ODRFs) treated after 24 hours from time of injury have an increased risk of infection or overall complication profile compared with those treated within 24 hours. Methods: Retrospective review was performed of all patients treated for ODRF over a 6-year period at a single large academic institution. Postoperative complications included surgical site infections, need for revision irrigation and debridement, delayed soft tissue healing, loss of reduction, nonunion, and malunion. Results: One-hundred twenty patients were treated for ODRF. Mean (SD) age at time of injury was 59.92 (17.68) years. Twenty patients (16.7%) had postoperative complications. Regarding mechanism of injury, 78 (65.0%) had a low-energy and 42 (35.0%) had a high-energy injury. Age and fracture grade were not significant factors. Mean (SD) open wound size was 1.18 (1.57) cm. Mean (SD) time from injury presentation to the emergency department (ED) and first dose of intravenous antibiotics was 3.07 (4.05) hours and mean (SD) time from presentation to the ED and operative treatment was 11.90 (6.59) hours, which did not show a significant association with postoperative complications. Twenty-four patients (20.0%) were treated greater than 24 hours after presentation to the ED, which was not significantly distinct from those treated within 24 hours. Conclusion: Patients with ODRFs treated after 24 hours were not associated with a greater risk of postoperative complications. Factors including age, energy and mechanism of injury, and fracture grade did not alter outcome in any statistically significant manner. Level of Evidence: Level IV

Timing of antibiotics in febrile children meeting sepsis criteria at a paediatric emergency department.

Delay in antibiotic administration in paediatric sepsis is associated with increased mortality and prolonged organ dysfunction. This pre-intervention study evaluated performance in paediatric sepsis management. Retrospective cohort study of febrile children admitted through the ED at The Children's Hospital at Westmead, Sydney, between 1 May and 31 July 2017. Participants were children aged 29 days to 60 months excluding children with simple febrile seizures, neonates and children who had received intravenous antibiotics elsewhere. We assessed the timing of antibiotic administration in children meeting local sepsis guidelines. We conducted a survey of clinicians in ED in 2018 to describe contributing factors. There were 160 febrile children admitted and 144 presentations were included in the analysis. Male 53% (n = 76); median age 20.1 months (interquartile range [IQR] 3.9-37 months). Thirty-seven (26%) febrile children met local sepsis criteria. The median time from triage to first dose of intravenous antibiotic was 109 min (IQR 62-183 min). Delay (>60 min) occurred in 26 (76%) children. Reported reasons contributing to delay included high patient load, long waiting times, difficult intravenous access, delayed prescribing, inadequate staffing and difficulty distinguishing between a viral infection and serious bacterial infection. There was frequent delay in administering antibiotics in children meeting local sepsis criteria, more commonly in young infants. Reasons contributing to delay were specific to young children along with departmental factors that will require addressing through targeted quality improvement interventions.

Reversible Bilateral Basal Ganglia and Brainstem Lesions in Neuropsychiatric Systemic Lupus Erythematosus: A Case Report

<p>The pathophysiology behind neuropsychiatric SLE (NPSLE) remains poorly understood and its clinical and radiological manifestations are highly varied. In this report, we present a complex case of an adolescent female patient with a three-week history of systemic symptoms (fever, nausea, vomiting, weight-loss, polyarticular joint pain), progressive motor weakness, tremor, and altered mental status. Physical examination was significant for oromandibular and cervical dystonia rigidity, and general weakness with imposed right-sided hemiparesis. A head MRI demonstrated bilateral hyperintense lesions of the basal ganglia and brainstem, SS without restricted diffusion. The patient was diagnosed with NPSLE, lupus nephritis, electrolyte imbalance, severe hypoalbuminemia, lupus cardiomyopathy, autoimmune hemolytic anemia, pulmonary tuberculosis, and sepsis. The patient was given treatment in the ICU with pulse dose corticosteroids, intravenous antibiotics, intravenous immunoglobulins (IVIg), and supportive treatment with correction of hematologic and electrolyte abnormalities. Her condition improved rapidly. Full alertness was regained, and symptoms of oromandibular dystonia, tremor, and weakness diminished significantly. A follow-up MRI three weeks later revealed complete disappearance of lesions, which we attribute to resolution of the inflammatory process in the brain.</p>

One week pre-operative oral antibiotics for percutaneous nephrolithotomy reduce risk of infection: a systematic review and meta-analysis.

The aim of this meta-analysis is to assess the efficacy of extended dose of preoperative antibiotics to reduce infectious risk in patients undergoing percutaneous nephrolithotomy (PCNL). A literature search for prospective case-control studies or randomized controlled trials was done. PICO framework was used. adult patients that underwent to PCNL; Intervention: extended dose preoperative antibiotic prophylaxis before PCNL; Control: short dose preoperative antibiotic prophylaxis before PCNL; and Outcome: systemic inflammatory response syndrome (SIRS) or sepsis, fever after PCNL and positive intraoperative urine and stone culture. This meta-analysis was registered in PROSPERO database under the number: CRD42022359589. Three RCT and two prospective studies (475 patients) were included. SIRS/sepsis outcome was retrieved from all studies included. Seven days preoperative oral antibiotics for PCNL was a protective factor for developing SIRS/sepsis (OR 0.366, 95% CI 0.234 - 0.527, p < 0.001). There was no statistical association between seven-day use of antibiotics and fever (OR 0.592, 95% CI 0.147 - 2.388, p = 0.462). Patients who received seven days preoperative antibiotics had lower positive intraoperative urine culture (OR 0.284, 95% CI 0.120 - 0.674, p = 0.004) and stone culture (OR 0.351, 95% CI 0.185 - 0.663, p = 0.001) than the control group. one week of prophylactic oral antibiotics based on local bacterial sensitivity pattern plus a dose of intravenous antibiotics at the time of surgery in patients undergoing PCNL reduces the risk of infection.

Time to first dose of antibiotics in febrile neonates.

To assess whether febrile neonates from the community received their first dose of intravenous antibiotics within 1 h from time of arrival, as per the regional paediatric sepsis pathway, at a tertiary combined adult/child emergency department in New Zealand. Retrospective data were collected from January 2018 to December 2019 with 28 patients included. Mean time to first antibiotic dose for all neonates and those with serious bacterial infection was 3h 20 min and 2h 53 min respectively. No case used the paediatric sepsis pathway. A pathogen was identified in 19/28 (67%) neonates and 16/28 (57%) had clinical signs of shock. This study adds to Australasian data on community neonatal sepsis. Antibiotic administration was delayed for neonates with serious bacterial infection, clinical signs of shock and raised lactate. The reasons for delay are examined, with a number of potential areas for improvement identified.

Is Time Truly of the Essence? Outcomes of Open Distal Radius Fracture Management

BACKGROUND: The standard of care of open distal radius fractures is urgent irrigation and debridement along with operative fixation. Herein, we investigate if open distal radius fractures (ODRF) treated after 24 hours from time of injury have an increased risk of infection or overall complication profile compared to open distal radius fractures treated urgently. METHODS: An IRB-approved retrospective chart review was performed of all patients treated for ODRF over a 6-year period at an academic institution in a large metropolitan city. Post-operative complications included: surgical site infections, need for revision irrigation and debridement, delayed soft tissue healing, loss of reduction, non-union, and malunion. For statistical analyses, nominal data were compared for distributional equality between complication dichotomy via Pearson chi-square or Fisher’s exact test depending on sample size distribution. Ordinal data were tested for ordinal association via exact Kendall’s tau test. Rank equivalency between complication dichotomy was determined for numeric data via Mann-Whitney U tests. All statistical tests were two-sided with p<0.05 considered statistically significant. RESULTS: Ninety-four patients were treated for ODRF with 62% female and 38% male patients included in the cohort. The mean (SD) age at time of injury was 58.6 (17.41) years. Notably, 28% of patients had a history of smoking. Overall, there were 16 patients (16.8%) with post-operative complications: 2 infections, 8 re-operations, 4 wound healing complications, 2 loss of reductions, 7 non-unions, and 1 malunion. Regarding energy and mechanism of injury, 74.4% had a low energy injury and 26.6% had a high energy injury, and this was not statistically significant for any post-operative complications (0.352). Likewise, age (p = 0.197) and fracture grade (p = 0.068) were not statistically significant factors for any surgical complications. The overwhelming majority of patients were treated with irrigation, debridement, and ORIF with volar locking plates. The mean (SD) open wound size was 1.6 (1.66) cm, ulnar sided, and did not correlate with any post-operative complications (p = 0.093). The mean (SD) time from injury presentation to the ER to the first dose of intravenous antibiotics was 4.7 (14.88) hours, and was not statistically significant for any post-operative complications (p = 0.186). The mean (SD) time from presentation to the ER to operative treatment was 19.1 (30.57) hours, and was not statistically significant for the presence of any post-operative complications (p = 0.092). There were 11 patients (11.7%) treated greater than 24 hours after presentation to the ER, which was not significantly distinct from those treated prior to 24 hours (p=1.000). CONCLUSION: Patients with open distal radius fractures treated after 24 hours did not have a greater risk of post-operative complications, including surgical site infections and non-union. Regarding factors that may influence urgent treatment, age, energy and mechanism of injury, and fracture grade were all not statistically significant for any post-operative complications in ODRF management.

A case-control study evaluating the unnecessary use of intravenous broad-spectrum antibiotics in presumed sepsis and septic-shock patients in the emergency department.

Recognition of sepsis frequently occurs in emergency departments. To evaluate the appropriateness of empiric antibiotic use in the setting of suspected sepsis in emergency department, the percentages of bacterial infection and antibiotic-related adverse drug effects were quantified in an emergency department at an academic medical center. We retrospectively reviewed electronic medical records of adults who presented to the emergency department between January 2018 and June 2018 with suspected sepsis (defined as having ≥2 systemic inflammatory response syndrome [SIRS] criteria) and received ≥1 dose of intravenous broad-spectrum antibiotic. In total, 218 patients were included in the final analysis. Moreover, 19.3% of these patients had confirmed bacterial infections; 44.5% had suspected bacterial infections; and 35.9% did not have bacterial infection. Elevated SIRS score (ie, ≥2) and Quick Sequential Organ Failure Assessment (qSOFA) score (ie, ≥2) were not associated with the presence of bacterial infections. We identified 90-day Clostridioides difficile infections in 7 patients and drug-resistant organism infections in 6 patients, regardless of the presence of bacterial infections. A high number of patients received intravenous broad-spectrum antibiotics in the emergency department without confirmed or suspected bacterial infections that were supported by microbiologic cultures, radiographic imaging, or other symptoms of infections. Most patients who were initially admitted to the emergency department with suspected sepsis were discharged home after receiving 1 dose of intravenous antibiotic. Patients who were initially screened using SIRS score and who received broad-spectrum antibiotics in the emergency department were without confirmed or suspected bacterial infection.

Management of sacrococcygeal pilonidal sinus disease in children: A survey study in Turkey.

Sacrococcygeal pilonidal sinus disease is common in children. The disease reduces the quality of life of patients with symptoms such as pain and chronic discharge. Variable surgical techniques have been described for the treatment of pilonidal sinus disease. This study aims to evaluate clinical approach of Turkish pediatric surgeons to children with pilonidal sinus disease. Survey questions were prepared through a literature review for controversial issues. The participants were asked pre-selected and checkbox questions. The survey was sent to 450 pediatric surgeons, members of the Association of Turkey Pediatric Surgery via a link to Google Forms. Nineteen percent (88) of the members responded. Seventy five (85.2%) of the pediatric surgeons stated that they did not perform additional preoperative imaging. Surgical excision methods were preferred more than minimally invasive procedures (102 to 46). Sixty (68.2%) of the participants preferred preoperative prophylactic single dose intravenous antibiotics and postoperative oral antibiotics. Regarding the participants' practices, poor local hygiene, overweight, wide or deep sinus pit were stated as the most common causes of recurrence. Vast majority of the pediatric surgeons recommended laser epilation (%85.2) and slimming (59.1%) to patients. Various studies have been published from Turkey for pilonidal sinus disease. As seen in the current study, Turkish pediatric surgeons do not have a common opinion in pilonidal sinus disease and prefer surgical excision methods more frequently. Prospective randomized studies with bigger number of patients are required to establish common guidelines in disease management.

The effect of delays in second-dose antibiotics on patients with severe sepsis and septic shock.

Early antibiotics are fundamental to sepsis management. Second-dose antibiotic delays were associated with increased mortality in a recent study. Study objectives include: 1) determine factors associated with delays in second-dose antibiotic administration; 2) evaluate if delays influence clinical outcomes. ED-treated adults (≥18 years; n = 1075) with severe sepsis or septic shock receiving ≥2 doses of intravenous antibiotics were assessed, retrospectively, for second-dose antibiotic delays (dose time > 25% of recommended interval). Predictors of delay and impact on outcomes were determined, controlling for MEDS score, 30 mL/kg fluids and antibiotics within three hours of sepsis onset, lactate, and renal failure, among others. In total, 335 (31.2%) patients had delayed second-dose antibiotics. A total of 1864 second-dose antibiotics were included, with 354 (19.0%) delays identified by interval (delayed/total doses): 6-h (36/67) = 53.7%; 8-h (165/544) = 30.3%; 12-h (114/436) = 26.1%; 24-h (21/190) = 8.2%; 48-h (0/16) = 0%. In-hospital mortality in the timely group was 15.5% (shock-17.6%) and 13.7% in the delayed group (shock-16.9%). Increased odds of delay were observed for ED boarding (OR 2.54, 95% 1.81-3.55), shorter dosing intervals (6/8-h- OR 2.99, 95% CI 1.95-4.57; 12-h- OR 2.46, 95% CI 1.72-3.51), receiving 30 mL/kg fluids by three hours (OR 1.42, 95% CI 1.06-1.90), and renal failure (OR 2.57, 95% CI 1.50-4.39). Delays were not associated with increased mortality (OR 0.87, 95% CI 0.58-1.29) or other outcomes. Factors associated with delayed second-dose antibiotics include ED boarding, antibiotics requiring more frequent dosing, receiving 30 mL/kg fluid, and renal failure. Delays in second-dose administration were not associated with mortality or other outcomes.

Open Supracondylar Humerus Fractures in Children.

Purpose: Supracondylar humerus (SCH) fractures are the most common elbow fracture in children; however, they rarely occur as open injuries. Open fractures are associated with higher rates of infection, neurovascular injury, compartment syndrome, and nonunion. The purpose of this study was to evaluate the treatment and outcomes of open SCH fractures in children.Methods: Between 2008 and 2015, four children (1%) had open injuries among 420 treated for SCH fractures at a single center. The mean patient age was six years (range, four to eight years). Two patients had Gustilo-Anderson grade 1 open fractures and two had grade 2 fractures. Tetanus immunization was up-to-date in all. First dose of intravenous antibiotics was given on average 3hr 7min after onset of injury (range, 1hr 38min to 8hr 15min). Time from injury to irrigation and debridement (I&D) and closed reduction and percutaneous pinning (CRPP) was on average 8hr 16min (range, 4hr 19min to 13hr 15min). All patients received 24-hour intravenous antibiotics. Pins were removed at four weeks and bony union occurred by six weeks.Results: After an average follow-up period of 12 months (range, 6 to 22 months), there were no infections, neurovascular deficits, compartment syndromes, cubitus varus deformities, or range of motion losses. All outcomes were excellent according to the Flynn criteria. Due to the unstable nature of open SCH fractures, a medial pin was used in all four cases. No loss of reduction or ulnar nerve injury occurred.Conclusion: Open injuries occur in approximately 1% of all SCH fractures in children. The authors recommend urgent intravenous antibiotics, I&D, and CRPP involving a medial pin to treat open SCH fractures. Excellent outcomes based on the Flynn criteria were obtained in four cases.

Nurse-initiated pre-prescribed antibiotic orders to facilitate prompt and appropriate antibiotic administration in febrile neutropenia.

To assess the impact of a pathway allowing nurse initiation of first dose intravenous (IV) antibiotics on time to antibiotic administration (TTA) in adult inpatients with febrile neutropenia (FN). This study evaluated the impact on TTA of a clinical pathway (November 2017 to April 2018) allowing nurse initiation of pre-prescribed antibiotics in adult haematology patients with FN, compared with a prior cohort (November 2016 to April 2017) in which antibiotics were only prescribed and administered after medical review. The primary endpoint for comparison was TTA, calculated as the time between the first recorded fever and IV antibiotic administration. Secondary endpoints included appropriateness of initial antibiotic choice, 30-day all-cause mortality and admission to intensive care unit (ICU). Forty-seven eligible FN episodes in 40 patients and 61 episodes in 52 patients were evaluated in the pre- and post-implementation groups, respectively. Baseline characteristics were comparable between groups. Median (IQR) TTA, in the pre-implementation group [66min (40-100min)] was significantly prolonged versus post-implementation group [29min (20-41min); p < 0.001]. A significantly higher proportion of episodes were administered appropriate initial antibiotics in the post-versus pre-implementation groups (100% vs. 89%, p = 0.03). There was no significant change in 30-day all-cause mortality (0% vs. 5%, p = 0.3) or ICU admission within 48h of fever (0% vs. 2%, p > 0.99) between pre- and post-implementation groups, respectively. A pathway allowing nurse initiation of pre-prescribed antibiotic orders for FN significantly reduced TTA from first recorded fever and increased the proportion of appropriate initial antibiotic choices without significantly impacting on patient outcomes.

Time is of the essence: evaluation of emergency department triage and time performance in the preoperative management of acute abdomen.

Acute abdomen is a time-critical condition, which requires prompt diagnosis, initiation of first-line preoperative therapy and expedient surgical intervention. The earliest opportunity to intervene occurs at presentation to the emergency department triage. The aim of this audit was to evaluate the relationship between emergency triage and time performance measures in the preoperative management of abdominal emergencies. Retrospective audit of time performance measures of key clinical events from emergency triage. Patient characteristics, elapsed time from triage to commencement of fluid resuscitation, intravenous antibiotics and emergency surgery and post-operative outcomes were obtained from review of operative medical records data over a 1-year duration. There was variability in triage allocation of patients with acute abdomen requiring urgent surgery. Category 3 was the most commonly assigned triage category (65.6%). The majority of patients (94.8%) had initial clinical assessment within the National Emergency Access Target '4-hour' rule, and 41.7% seen within 1-h from triage. Despite this, in cases of intra-abdominal sepsis, there was nearly a fourfold elapsed time for first dose intravenous antibiotics, beyond the 1-h recommendation in the Sepsis Kills pathway. There was non-significant trend in faster overall time performances with successive higher triage category allocation. This study highlights an opportunity to consider alternative triage methods or fast-track of patients with acute abdomen to promote early surgical assessment, resuscitation, antibiotic therapy and definitive intervention.

Does delay in initiation of intravenous antibiotics correlate with wound infections in children with open fractures?

Introduction: One of the common complications of open fractures is an infection which may be dependent on the time of administration of antibiotics. The study aimed to determine the prevalence of wound infection due to the delay in the interval between the initiation of intravenous (IV) antibiotics and time of paediatrics open injury. Materials and Methods: Retrospective observational study included paediatrics patients (0 to 16 years) with open fractures. A retrospective chart review was performed to identify patients with open fracture, who were treated between May 2012 and October 2013 at the tertiary care centre. The time between the injury and the first dose of intravenous antibiotic was calculated from transfer and hospital records. Fracture groups were stratified according to the severity of soft-tissue damage as determined with use of the Gustilo- Anderson system for the classification of open fractures. Results: Sixty patients with 84 open fractures were included in this study. Majority of 31.58% of participants had type III B Gustilo - Anderson fracture type. The proportion of grade IIIA, I, III C and II fracture was 29.82%, 21.05%, 14.04% and 3.51% respectively. 43 (71.6%) received IV antibiotics within 6 hours of injury of which eight had documented wound infections. Of the 17 (28%) patients who received IV antibiotics after 6 hours, 7 (41%) were diagnosed with wound infections. The incidence of infection was high in higher grades of Gustilo- Anderson opens injuries. Conclusion: The immediate administration of appropriate antibiotics on presentation is crucial to minimise the risk of infection in children.

Life-Threatening paediatric odontogenic cellulitis secondary to a partially erupted primary molar

Abstract: A 15-month-old male was admitted to hospital with a facial swelling of unknown origin which was of rapid onset over three hours, resulting in airway occlusion and septic shock. Ultimately, the swelling was found to be of odontogenic origin and was managed with high dose intra-venous antibiotics. Cellulitis of the face can be life-threatening and it is important to be aware of the clinical signs and ensure that the patient receives appropriate care to prevent deterioration. CPD/Clinical Relevance: It is essential for dentists in primary and secondary care to recognize and understand how to manage or refer a patient with facial cellulitis, and also for medical teams to seek prompt dental input in cases of facial swelling with a possible dental cause.

Patient preferences for treatment of acute bacterial skin and skin structure infections in the emergency department

BackgroundLimited research has assessed patient preferences for treatment disposition and antibiotic therapy of acute bacterial skin and skin structure infection (ABSSSI) in the emergency department (ED). Understanding patient preference for the treatment of ABSSSI may influence treatment selection and improve satisfaction.MethodsA survey was conducted across 6 US hospital EDs. Patients with ABSSSI completed a baseline survey assessing preferences for antibiotic therapy (intravenous versus oral) and treatment location. A follow-up survey was conducted within 30–40 days after ED discharge to reassess preferences and determine satisfaction with care.ResultsA total of 94 patients completed both baseline and follow-up surveys. Sixty (63.8%) participants had a history of ABSSSI, and 69 (73.4%) were admitted to the hospital. Treatment at home was the most common preference reported on baseline and follow-up surveys. Patients with higher education were 82.2% less likely to prefer treatment in the hospital. Single dose intravenous therapy was the most commonly preferred antibiotic regimen on baseline and follow-up surveys (39.8 and 19.1%, respectively). Median satisfaction scores for care in the ED, hospital, home, and with overall antibiotic therapy were all 8 out of a maximum of 10.ConclusionsIn these patients, the most common preference was for outpatient care and single dose intravenous antibiotics. Patient characteristics including higher education, younger age, and current employment were associated with these preferences. Opportunities exist for improving ABSSSI care and satisfaction rates by engaging patients and offering multiple treatment choices.

First dose of intravenous antibiotics in Outpatient Parenteral Antimicrobial Therapy/Hospital in the Home – criteria for administration at home

First dose of intravenous antibiotics in Outpatient Parenteral Antimicrobial Therapy/Hospital in the Home – criteria for administration at home

A nurse-led protocol improves the time to first dose intravenous antibiotics in septic patients post chemotherapy.

Neutropenic sepsis is a time-dependent emergency with early interventions shown to improve outcomes. Broad spectrum intravenous antibiotic administration is the initial therapy in patients with suspected neutropenic sepsis. Compliance with early antibiotic administration in febrile neutropenia patients is poor. Innovations have been trialled to improve the time to first dose intravenous antibiotics in patients with suspected neutropenic sepsis. Consideration of extending first dose intravenous antibiotic prescribing to trained nursing staff may improve performance in this key standard. A retrospective analysis was performed at a specialist oncology hospital in the North West of England from January 1st 2015 to January 31st 2016. The nurses on the Medical Admissions Unit (MAU) have been given the responsibility of assessing patients presenting with fever post chemotherapy including prescribing and administering the first dose of intravenous antibiotics with the aim of improving the speed of this intervention. During the study period, 697 patients presented to the MAU with suspected sepsis post chemotherapy. Six hundred seventy-two (96.4%) patients received their first dose of intravenous antibiotics within 60min of presentation to the MAU. Of this group, 323 (48.1%) were administered antibiotics within 15min of arrival. Of the 25 (3.6%) patients who did not receive antibiotics within 1h, root cause analysis revealed the reason in 23 (92%) patients was an inability to ascertain intravenous access. Nurse-led protocols are an effective, safe, and sustainable method for achieving early antibiotic administration in patients with suspected febrile neutropenia. This is a key component of ensuring improved outcomes for this cohort of patients.

A simple intervention to improve antibiotic treatment times for neutropenic sepsis

Objectives: Patients with suspected Neutropenic sepsis require rapid antibiotic administration, but despite extensive education, only 67% of patients received antibiotics within 60 minutes. Methods: A Neutropenic Sepsis Alert Card was created, as a Patient Specific Directive – this allows nurses to administer antibiotics to specific patients without prior medical review. Results: Since the intervention, 301 patients presented with suspected neutropenic sepsis. 277 patients (92%) received their first dose of intravenous antibiotics within 1 hour of arrival into hospital, compared to 95 out of 143 patients (67%) presenting between January and June of 2014 (p=0.036). Conclusion: The Neutropenic Sepsis Alert Card can significantly improve door to antibiotic needle time for chemotherapy patients with suspected neutropenic sepsis. This intervention is inexpensive and easily replicable in other health care organisations.

Characterization of anti‐drug antibodies and drug‐responsive B‐lymphocytes in piperacillin hypersensitive patients with cystic fibrosis

Cystic fibrosis is the most common autosomal recessive condition in Caucasians and recurrent infections lead to a plethora of complications. Repeated courses of high dose intravenous β-lactam antibiotics, such as piperacillin, are employed for the treatment of respiratory exacerbations. Unfortunately, delayed-type hypersensitivity reactions develop in between 26-50% of treated patients. We have recently described the cellular immunological processes that underlie drug-specific response in hypersensitive patients; however, the involvement of the humoral immune system has not been studied. The aim of this study was to quantify piperacillin-specific antibodies in plasma of hypersensitive and tolerant patients and investigate whether B-cells can be stimulated to secrete antibodies in vitro following drug stimulation. Drug-specific antibodies were quantified by ELISA using piperacillin-modified BSA as an antigen. Adducts generated using different drug-protein ratios were used to measure the degree of conjugation that elicits an antibody response. BSA was modified with different β-lactam antibiotics to define structural specificity. Specificity for the piperacillin BSA adduct was confirmed by hapten inhibition. Mass spectrometry was used to characterize the Lys residues modified with piperacillin. B-cells isolated from PBMC were cultured with piperacillin for 5 days and IgG secretion and B-cell activation was measured using ELISpot and flow cytometry (CD19, CD27), respectively. A significantly higher level of anti-piperacillin IgG antibody was detected in plasma of hypersensitive patients when hypersensitive and tolerant patients were compared. Hapten inhibition ELISA confirmed specificity for the piperacillin antigenic determinant. Antibody binding was detected with adducts generated at piperacillin:BSA ratios between 1:1 and 100:1. In contrast, antibody binding was not detectable with penicillin G, amoxicillin or aztreonam BSA conjugates. IgG antibody secretion was also detected from purified B-cells from hypersensitive patients cultured with soluble piperacillin. Drug treatment was associated with increased expression of the B-cell activation marker CD27. These data begin to describe the drug-specific humoral immune response in piperacillin hypersensitive patients with cystic fibrosis. Further work is needed to define the role different antibody subtypes play in the disease pathogenesis.

The effect of intrapartum antibiotics on early-onset neonatal sepsis in Dhaka, Bangladesh: a propensity score matched analysis.

BackgroundWe estimate the effect of antibiotics given in the intrapartum period on early-onset neonatal sepsis in Dhaka, Bangladesh using propensity score techniques.MethodsWe followed 600 mother-newborn pairs as part of a cohort study at a maternity center in Dhaka. Some pregnant women received one dose of intravenous antibiotics during labor based on clinician discretion. Newborns were followed over the first seven days of life for early-onset neonatal sepsis defined by a modified version of the World Health Organization Young Infants Integrated Management of Childhood Illnesses criteria.Using propensity scores we matched women who received antibiotics with similar women who did not. A final logistic regression model predicting sepsis was run in the matched sample controlling for additional potential confounders.ResultsOf the 600 mother-newborn pairs, 48 mothers (8.0%) received antibiotics during the intrapartum period. Seventy-seven newborns (12.8%) were classified with early-onset neonatal sepsis. Antibiotics appeared to be protective (odds ratio 0.381, 95% confidence interval 0.115–1.258), however this was not statistically significant. The results were similar after adjusting for prematurity, wealth status, and maternal colonization status (odds ratio 0.361, 95% confidence interval 0.106–1.225).ConclusionsAntibiotics administered during the intrapartum period may reduce the risk of early-onset neonatal sepsis in high neonatal mortality settings like Dhaka.