Course Of Parenteral Antibiotics Research Articles

Short duration of parenteral antibiotics in infants with urinary tract infections.

Current guidelines by the Canadian Paediatric Society on treating urinary tract infections (UTIs) exclude infants ≤ 60 days old. There is considerable practice variability in this age group, especially around the optimal duration of parenteral antibiotics. The study aimed to assess local practice patterns, and the safety of a short course (≤3 days) of parenteral antibiotics in young infants. In this retrospective cohort study, 95 infants (≤60 days) with confirmed UTIs were identified at British Columbia Children's Hospital. Patients receiving short (≤3 days) and long (>3 days) duration of parenteral antibiotics were compared. Outcomes of interest included urinary tract infection recurrence within 30 days, hospital length of stay (LOS), representation, and readmission. Twenty infants (21%) received a short course of parenteral antibiotics. These infants were older (median 47 days versus 28 days) and non-bacteremic. Urinary tract infection recurrence was identified in 8 patients (8%), of which 7 were treated with a long duration (P = 1.0). Patients treated with a short duration had a significantly shorter LOS, with a mean difference of 4.21 days [95% CI: 3.37 to 5.05] (P < 0.001). All five (5%) bacteremic patients were treated exclusively with parenteral antibiotics. In a Canadian setting, a short course of parenteral antibiotics is safe in young, non-bacteremic infants with UTIs. Despite substantial evidence, local practice patterns suggest a tendency towards prescription of long courses, providing an opportunity for quality improvement.

Carpal tunnel syndrome secondary to splinter injury: a case report

Carpal tunnel syndrome is a mononeuropathy arising as a result of compression of the median nerve as it travels through the carpal tunnel at the level of the wrist. The symptoms of this disabling condition include pain or paresthesia in the palmar aspect of the radial 3 and half digits of the hand. This is the case of a 30-year-old man who sustained a penetrating injury to his left wrist following a fall from a height. He presented with pain in his hand and a chronic discharging sinus from a puncture wound on the volar aspect of his left wrist. Wound debridement, extraction of the foreign body and a course of parenteral antibiotics led to resolution of his symptoms.

194. The fate of patients with early postoperative surgical site infections following instrumented lumbar fusion

BACKGROUND CONTEXT Acute postoperative surgical site infections (SSI) following instrumented lumbar fusions are a relatively infrequent occurrence. Treatment with aggressive surgical debridement and parenteral antibiotics are generally effective in leading to eradication of infection and maintenance of the instrumentation. However, it is not clear what the long-term effect may be on clinical outcome or more specifically the potential for development of a non-union or instrumentation loosening. PURPOSE To evaluate the long term clinical and radiographic outcomes of patients who underwent an instrumented lumbar fusion which was complicated by an acute postoperative surgical site infection that necessitated a surgical debridement and a prolonged course of parenteral antibiotics. STUDY DESIGN/SETTING A retrospective review of a cohort of consecutive patients treated a single institution. PATIENT SAMPLE A consecutive cohort of patients who underwent an elective lumbar decompression and instrumented fusion for lumbar stenosis complicated by an acute surgical site infection within the first 4 weeks postoperatively that required additional surgery to debride the wound and maintain the instrumentation. Patients underwent surgery over a 12-year period (2007-2016) at a tertiary spine referral center. Follow-up was a minimum of 2 years and a mean of 6.2 years. OUTCOME MEASURES Hospital length of stay, need for further surgery, clinical outcome measures: ODI, VAS (back), VAS (leg), patient-reported satisfaction, willingness to repeat index surgery and radiographic fusion rates. METHODS The clinical data base at our medical center was queried to identify acute surgical site infections occurring within 4 weeks following a posterior lumbar decompression and instrumented fusion. RESULTS A total of 1,602 patients underwent an instrumented lumbar fusion: 604 (38%) L4-5, 623 L3-5 (39%), 375 L2-5 (23%). An acute surgical site infection occurred in 39 patients (.024%). Significant risk factors (p 80, BMI > 30, Diabetes, osteoporosis and prior decompressive surgery. Notable nonsignificant risk factors included length of surgery, preoperative diagnosis (degenerative spondylolisthesis or degenerative scoliosis), use of iliac crest autograft or allograft, duration of postoperative suction drain, or occurrence of an incidental durotomy requiring repair. Mean length of hospital stay was significantly longer in patients with an SSI, 3.2 days vs 7.2 days (p=.02). Longer term follow-up revealed revision surgery to address symptomatic non-union was slightly greater in the SSI cohort, 6 patients (15%) vs 15 patients (12%) in the noninfected cohort, but this did not reach significance (p>.05). Radiographic evidence of non-union or loose instrumentation was not significantly different between the two cohorts. At 6-month follow-up, clinical outcomes were consistently better in the noninfected cohort: VAS back (p=.04), VAS leg (p=.03) and ODI (p=.04), as were patient reported satisfaction (p=.04) and willingness to repeat the index procedure (p=.04). By 1 year postoperatively and onward thereafter to the latest follow-up, no significant difference was noted in clinic outcomes, patient satisfaction, or willingness to repeat the index surgery. CONCLUSIONS In a single center study of 1,602 patients undergoing a posterior decompression and instrumented fusion for degenerative lumbar disease, acute postoperative surgical site infection occurred in 2% of cases. Older, obese, diabetic patients were more prone to an SSI and the initial 6-month clinical outcomes were inferior to patients without an infection. However, long-term clinical and radiographic follow-up showed no significant differences between those with and without an infection. As well, late revision rates were not greater in patients with history of an SSI. Recognition of a postoperative infection, especially in high risk patients, followed by prompt surgical intervention and appropriate parenteral antibiotics allows for maintenance of instrumentation and favorable clinical outcomes. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

27-Year-Old Woman With Fever, Headache, and Anemia

27-Year-Old Woman With Fever, Headache, and Anemia

Cavitary Pneumonia: A Complication of Antibiotic Noncompliance

In this report, we present a complicated case of community-acquired pneumonia in a 5-year-old boy. The patient first presented to the pulmonology clinic with the diagnosis of asthma and a recent history of recurrent pneumonia. Poor compliance to two courses of outpatient oral antibiotics resulted in persistent pneumonia symptoms with unresolved radiographic findings warranting parenteral antibiotics. Despite 2 symptom-free weeks, the patient returned to the emergency department with recurrence of symptoms where imaging revealed a cavitary lesion requiring a prolonged course of parenteral antibiotics. This report further supports the detrimental impact of partially treated infections related to poor compliance to antibiotic regimens.

1428. Comparing Outcomes of Diabetic Foot Infections Requiring Amputation, Negative vs. Positive Margins

BackgroundThis was a retrospective, observational cohort study of patients with diabetes and lower extremity osteomyelitis requiring amputation. Patients were categorized as having negative margins (without residual osteomyelitis or with joint disarticulation), or positive margins (with residual osteomyelitis). Health outcomes were compared between groups. The primary outcomes were relapse of infection at one year and reintervention at one year. Secondary outcomes include mortality at 30 days, 90 days, and 1 year; treatment failure at one year; and a composite of relapse of infection at one year, reintervention at 1 year, and death at 1 year.MethodsCPRS ICD-10 codes were reviewed from patients at Audie L. Murphy VA with amputation for osteomyelitis between July 2, 2015 and July 13, 2017. Pathology reports were reviewed for the presence or absence of residual osteomyelitis, and outcomes were determined by chart review. Patient characteristics were recorded, such as age, serum albumin, presence of diabetes, hemoglobin A1c, organism on culture, peripheral vascular disease, and occurrence of a peripheral vascular intervention.ResultsThe ALMVA is a 500-bed medical center with an active BMT program. Clinical data from 146 patients were obtained and analyzed. There were no significant differences in primary or secondary outcomes relative to patients with positive margins or negative margins. A lack of consistency in margin reporting by Pathology was seen. Albumin level and number of patients with residual osteomyelitis were significantly different between the two groups (table).ConclusionThere were no significant differences in outcomes between amputations with positive margins and those with negative margins. Based on current IDSA guidelines, treatment varies significantly for patients with positive or negative margins, with the former requiring 6 weeks of parenteral antibiotic therapy. Extended courses of parenteral antibiotics increase risk for treatment-associated morbidity, and more evidence is needed to support these recommended durations. A quality improvement project is underway with the ID, Podiatry and Pathology departments to resolve issues related to obtaining and processing surgical samples, as well as interpreting and reporting margin results. Disclosures All authors: No reported disclosures.

An End in Sight: Shorter Duration of Parenteral Antibiotics in Neonates.

* Abbreviations: GBS — : Group B Streptococcus UTI — : urinary tract infection Prescribing the appropriate duration of antibiotic therapy is at the top of mind for the Centers for Disease Control and Prevention, hospital systems, and individual providers alike because it has a resounding impact on antimicrobial resistance.1 In this month’s issue of Pediatrics , Desai et al2 have taken on the duration of parenteral antibiotics for infants ≤60 days old with bacteremic urinary tract infection (UTI). This is a critical piece of a complicated puzzle that not only includes minimum duration of parenteral antibiotic treatment but also involves bioavailability of antimicrobial agents in infants and total treatment duration, which includes parenteral and oral antibiotic therapy. They have written a methodologically sound multicenter study and propose that a short course of parenteral antibiotics is no less effective than a long course in infants ≤60 days old with bacteremic UTIs. This study uniquely affords granularity with respect to the patient population, including a physician’s documented clinical assessment providing information such as temperature, ill appearance, or presence of a known genitourinary condition, which allowed for ascertainment of critical clinical information that influenced management decisions. Ultimately, … Address correspondence to Hillary L. Copp, MD, MS, Department of Pediatric Urology, University of California, San Francisco, Mission Hall Global Health Sciences Building, 550 16th St, 6th Floor, Box 1695, San Francisco, CA 94143. E-mail: hillary.copp{at}ucsf.edu

Intravenous Cyclophosphamide Therapy for Anti-IFN-Gamma Autoantibody-Associated Mycobacterium abscessus Infection.

Introduction Anti-interferon-gamma (IFN-γ) autoantibodies are increasingly recognized as a cause of adult-onset immunodeficiency (AOID) worldwide. These patients are susceptible to various intracellular pathogens especially nontuberculous mycobacteria. Most of the patients have a refractory clinical course. Herein, we report the use of immunotherapy with pulse intravenous cyclophosphamide (IVCY) in patients who had progressive, refractory Mycobacterium abscessus infection. Method We included patients, seen at Srinagarind Hospital, Thailand, infected with M. abscessus, who had received ≥3 courses of parenteral antibiotics within the last 12 months and who received pulse IVCY with a tapering dose of prednisolone. Results There were 8 AOID patients who met the criteria and received pulse IVCY between January 2011 and December 2015. One patient was lost to follow-up after 5 courses of IVCY: he had died at home 3 months later. Five patients had favorable outcomes: 2 were able to discontinue NTM therapy, and 3 had stable disease and were on NTM treatment without hospitalization for parenteral antibiotics. Two patients relapsed and needed hospitalization. The IFN-γ Ab titers among the 7 patients were significantly decreased during treatment, and the median initial antibody titer started at 200,000 and then decreased to 5,000 after 2 years of treatment (P < 0.0001). The antibody titer reduction among responsive vs. nonresponsive patient was significantly different after 6 months of treatment: the median antibody titer was 5,000 and 100,000, respectively (P = 0.0467). Conclusion IVCY therapy might be an alternative treatment for AOID patients infected with M. abscessus and refractory to antimycobacterial therapy.

MP36-02 MICROBIOLOGICAL PROFILE AND DRUG SUSCEPTIBILITY PATTERNS OF PUBIC SYMPHYSIS OSTEOMYELITIS IN THE PROSTATE CANCER SURVIVOR

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia II1 Apr 2016MP36-02 MICROBIOLOGICAL PROFILE AND DRUG SUSCEPTIBILITY PATTERNS OF PUBIC SYMPHYSIS OSTEOMYELITIS IN THE PROSTATE CANCER SURVIVOR Garjae Lavien, Uwais Zaid, and Andrew Peterson Garjae LavienGarjae Lavien More articles by this author , Uwais ZaidUwais Zaid More articles by this author , and Andrew PetersonAndrew Peterson More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1636AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pubic symphysis osteomyelitis is seen in patients who have undergone prior radiation or other ablative therapy for treatment of their prostate cancer and presents up to 7 to 10 years later with pelvic pain. In this review we sought to delineate the microbiological features and antibiotic susceptibility patterns of pubic symphysis osteomyelitis in the prostate cancer survivor. METHODS We conducted a review from January 2011 to August 2015 of an IRB approved database to identify prostate cancer survivors who underwent multidisciplinary treatment for pubic symphysis osteomyelitis. Demographic and microbiological data were extracted. The diagnosis of pubic symphysis osteomyelitis was established with magnetic resonance imaging and confirmed by tissue culture of pubic symphysectomy specimens at the time of resection. Antimicrobial susceptibility testing was performed using the Clinical and Laboratory Standards Institute criteria. RESULTS We identified 17 patients with a median age of 71 years of age (range 64-84). Surgical debridement is pending in 4. Thirteen have undergone pubic symphysectomy with or without pubic rami debridement, along with concomitant urinary and/or fecal diversion. All patients received a course of parenteral antibiotics for 6 weeks or longer prior to surgical management which was stopped 2 weeks prior to surgery. We identified 26 cultured isolates from 13 tissue specimens. Positive isolates were cultured in 92% of patients, with polymicrobial infections noted in 62%. Enterococcus was the most predominant isolate identified representing 27% of all cultured organisms, followed by Escherichia coli at 19%. The antibiotic resistance rates are noted in Table 1. The most commonly used classes of antibiotics that were administered based on these cultures included carbapenems (35%) and glycopeptides (16%). CONCLUSIONS Upon resection, the majority of prostate cancer survivors with pubic symphysis osteomyelitis will have a dominant organism identified. Enterococcus and Escherichia coli account for the majority of the offending pathogens. Clinicians should consider the empiric use of carbapenems and glycopeptides in patients prior to definitive surgical management. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e489 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Garjae Lavien More articles by this author Uwais Zaid More articles by this author Andrew Peterson More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Recent lessons for the management of bone and joint infections

The epidemiology and clinical manifestations of osteoarticular infections are changing primarily as a result of the emergence of community-acquired methicillin-resistant Staphylococcus aureus infections. Multifocal disease, venous thrombosis and pathologic fractures are manifestations of CA-MRSA osteomyelitis. MRI is the diagnostic imaging modality of choice for musculoskeletal infections. Nafcillin/oxacillin or cefazolin remains the antibiotic of choice for treating infections caused by MSSA. A β-lactam antibiotic is recommended for Kingella kingae. Vancomycin and clindamycin are the first line agents for treating osteomyelitis caused by CA-MRSA. A short course of parenteral antibiotics followed by appropriate oral antibiotics is equivalent to total course of parenteral antibiotics for most patients and avoids the risks associated with PICCs. Surgical drainage of subperiosteal abscesses and surrounding pyomyositis is common with S. aureus clones currently circulating. Collaboration with hematologists for managing patients with venous thromboses is recommended.

Safety and Efficacy of Simplified Antibiotic Regimens for Outpatient Treatment of Serious Infection in Neonates and Young Infants 0–59 Days of Age in Bangladesh

Background:Because access to care is limited in settings with high mortality, exclusive reliance on the current recommendation of 7–10 days of parenteral antibiotic treatment is a barrier to provision of adequate treatment of newborn infections.Methods:We are conducting a trial to determine if simplified antibiotic regimens with fewer injections are as efficacious as the standard course of parenteral antibiotics for empiric treatment of young infants with clinical signs suggestive of severe infection in 4 urban hospitals and in a rural surveillance site in Bangladesh. The reference regimen of intramuscular procaine-benzyl penicillin and gentamicin given once daily for 7 days is being compared with (1) intramuscular gentamicin once daily and oral amoxicillin twice daily for 7 days and (2) intramuscular penicillin and gentamicin once daily for 2 days followed by oral amoxicillin twice daily for additional 5 days. All regimens are provided in the infant’s home. The primary outcome is treatment failure (death or lack of clinical improvement) within 7 days of enrolment. The sample size is 750 evaluable infants enrolled per treatment group, and results will be reported at the end of 2013.Discussion:The trial builds upon previous studies of community case management of clinical severe infections in young infants conducted by our research team in Bangladesh. The approach although effective was not widely accepted in part because of feasibility concerns about the large number of injections. The proposed research that includes fewer doses of parenteral antibiotics if shown efficacious will address this concern.

Spontaneous Perforation of the Tympanic Membrane in the First 10 Days of Life

Twelve cases of neonates admitted to the neonatal unit of our hospital, between January 1, 2000, and December 31, 2005, because of otorrhea due to spontaneous perforation of the tympanic membrane within the first 10 days of life are presented. Data were collected retrospectively from medical records. Cultures of the middle ear exudate grew PSEUDOMONAS AERUGINOSA in 10, SERRATIA MARCENSCENS in 1, and STAPHYLOCOCCUS AUREUS in 1 neonate. Cultures of nasopharyngeal secretions grew P. AERUGINOSA in nine, S. MARCENSCENS in one, S. AUREUS in one, and STREPTOCOCCUS VIRIDANS in one neonate. Middle ear versus nasopharyngeal secretions cultures grew the same organism in 11 neonates. A 10-day course of parenteral antibiotics was administered (ampicillin-ceftazidime for all neonates except for the one neonate with the S. AUREUS otitis who received netilmicin-cloxacillin). All neonates had uneventful course and were discharged home in good clinical condition. Our findings suggest that neonates with eardrum perforation should receive antibiotics parenterally, as the most common pathogens is P. AERUGINOSA, for which there are no satisfactory antibiotics for oral use.

Outcomes of treatment for hematogenous Staphylococcus aureus vertebral osteomyelitis in the MRSA ERA

Hematogenous vertebral osteomyelitis is caused predominantly by Staphylococcus aureus. The rise in incidence of methicillin-resistant S. aureus (MRSA) has complicated the treatment of this infection. Our objective was to evaluate therapeutic outcomes for S. aureus vertebral osteomyelitis in a setting of high MRSA prevalence. We conducted a retrospective chart review of all patients who presented with S. aureus vertebral osteomyelitis over a 7-year period at 2 tertiary care hospitals in Houston, TX, USA. Thirty-five patients were identified who received > or =2-week course of parenteral antibiotics and had a follow-up period of at least 12 months post-therapy. MRSA was responsible for 20 (57%) cases. Mean duration of total antibiotic therapy was 61.4 days. The overall relapse rate was 14%. At 12 months post-therapy, 86% patients were cured. The one factor significantly associated with relapse was presence of undrained abscesses (p=0.04). When the mean duration of effective antibiotic therapy was 60 days, cure rates for S. aureus vertebral osteomyelitis exceeded 80%. Drainage of all associated abscesses correlated with a significantly higher rate of cure.

Test Characteristics and Interpretation of Cerebrospinal Fluid Gram Stain in Children

Few data exist regarding the test characteristics of cerebrospinal fluid (CSF) Gram stain among children at risk for bacterial meningitis, especially the rate of false positive Gram stain. We conducted a retrospective cohort study of children seen in the emergency department of Children's Hospital Boston who had CSF obtained between December 1992 and September 2005. Patients who had ventricular shunts, as well as those who received antibiotics before CSF was obtained were excluded. Test characteristics of CSF Gram stain were assessed using CSF culture as the criterion standard. Patients were considered to have bacterial meningitis if there was either: (1) growth of a pathogen, or (2) growth of a possible pathogen noted on the final CSF culture report and the patient was treated with a course of parenteral antibiotics for 7 days or more without other indication. A total of 17,569 eligible CSF specimens were collected among 16,036 patients during the 13-year study period. The median age of study subjects was 74 days. Seventy CSF specimens (0.4%) had organisms detected on Gram stain. The overall sensitivity of Gram stain to detect bacterial meningitis was 67% [42 of 63; 95% confidence interval (CI): 54-78] with a positive predictive value of 60% (42 of 70; 95% CI: 48-71). Most patients without bacterial meningitis have negative Gram stain [specificity 99.9% (17,478 of 17,506; 95% CI: 99.8-99.9)] with a negative predictive value of 99.9 (17,478 of 17,499; 95% CI: 99.8-99.9). CSF Gram stain is appropriately used by physicians in risk stratification for the diagnosis and empiric treatment of bacterial meningitis in children. Although a positive Gram stain result greatly increases the likelihood of bacterial meningitis; the result may be because of contamination or misinterpretation in 40% of cases and should not, by itself, result in a full treatment course for bacterial meningitis.

Ohpat for complicated and high-risk endocarditis cases: the sheffield experience

Outpatient and Home Parenteral Antibiotic Therapy (OHPAT) has provided health providers in secondary care with an alternative to prolonged hospitalization in conditions requiring lengthy courses of parenteral antibiotics. There is growing international experience of OHPAT in the treatment of infective endocarditis, but to date, there is still only limited published criteria/guidance on patients suitable for this approach. One recent publication1, has however, recommended routinely excluding patients in a number of high-risk groups, including Staphylococcus aureus infections, prosthetic valve infections and aortic valve involvement.

Epidural Abscess as a Delayed Complication of Spinal Instrumentation in Scoliosis Surgery

A case report of late-onset paraplegia from an epidural abscess in a patient years after her instrumentation and fusion for scoliosis. To present a case of delayed complication of progressive paraplegia from an epidural abscess after spinal instrumentation in scoliosis surgery and to highlight an effective surgical intervention that resulted in complete resolution of symptoms. Spinal epidural abscess is a rare but devastating disorder that has previously been reported to have a mean incidence during sixth or seventh decade. It is exceedingly uncommon in the pediatric population. Deep wound infection after adolescent idiopathic scoliosis surgery is a well-known entity that has been reported in several studies; however, we could find no documented incidences of epidural abscess resulting from adolescent idiopathic scoliosis surgery in the pediatric population. To our knowledge there has been no report of a management algorithm for such a complication. A 15-year-old female with progressive thoracic and lumbar curves underwent posterior spinal fusion from T5 to L3 with instrumentation. Her postoperative course was complicated by acute wound infection that underwent irrigation and debridement with retention of implants. The patient did well for 9 months, after which she presented with recurrent back pain and elevated inflammatory markers. She had her implants removed and another course of parenteral antibiotics. After an uneventful course for 2 years, the patient presented with a 2-week history of progressive bilateral lower extremity incomplete paralysis. After magnetic resonance imaging confirmation of a T5 to T10 epidural mass, the patient underwent debridement through her fusion mass from T5 to L1. No supplemental instrumentation was required, but the patient was placed in a thoracolumbosacral orthosis brace after surgery. She was treated with a total of 12 weeks of antibiotics. Within days of her procedure, her motor paralysis improved. By discharge, she had regained the majority of her lower extremity function. During the subsequent year, her motor and sensory function completely normalized and she has had no sequelae with over 2 years' follow-up. This case reports a delayed spinal epidural abscess years after removal of her implants for infection. This demonstrates that our patients remain at risk for reactivation of spinal infections even though they may be healthy hosts and may have had all foreign bodies removed as part of their treatment for deep postoperative infections. This case suggests that extensive unilateral decompression and debridement through a fusion mass is a viable treatment method in patients with fused spine.

Success of Short-Course Parenteral AntibioticTherapy for Acute Osteomyelitis of Childhood

The outcome of acute osteomyelitis treated with sequential therapy consisting of a short course of parenteral antibiotics, followed by oral antibiotics, was studied. To be considered acute osteomyelitis, related symptoms must have been present for less than 2 weeks before diagnosis. Short-course parenteral antibiotics (therapy for 7 days or less) and then oral antibiotics were used to treat 29 patients (median age, 6.3 years). Pathogens were identified from blood cultures and bone aspirates. Staphylococcus aureus was isolated in 59%. Median duration of parenteral antibiotics and oral antibiotics was 4 days (range, 0-7 days) and 28 days (range, 14-42 days), respectively. Median duration of combined (parenteral and oral) therapy was 32 days (range, 20-49 days). No failures or complications were noted at the 6-month follow-up, which was available for 27 patients. Short-course parenteral antibiotic therapy followed by oral therapy appears to be effective for treatment of acute, uncomplicated osteomyelitis.

The management of peri-prosthetic infection in total joint arthroplasty

Deep peri-prosthetic infection following total joint arthroplasty is a major complication. Although it only occurs in a small percentage of patients it results in substantial morbidity and a decline in functional outcome. The risk of infection is generally quoted as being 1%. The lowest reported

Non-Myeloablative Conditioning with Busulfan Prior to Allogeneic Hematopoietic Stem Cell Transplant Results in Mixed Chimerism and Reversal of the Phenotype in Canine Leukocyte Adhesion Deficiency with Minimal Regimen Related Toxicity and without Graft-vs.-Host Disease.

Leukocyte adhesion deficiency (LAD), a genetic disease caused by defects in the integrin CD18, results in a clinical syndrome in which the affected children suffer severe recurrent infections due to the inability of their leukocytes to adhere to endothelium and migrate to sites of infection. Approximately 75% of children with the severe deficiency phenotype of LAD die by two years of age. Allogeneic hematopoietic stem cell transplant (HSCT) preceded by a myeloablative conditioning regimen corrects the LAD phenotype, however this treatment carries significant regimen-related toxicity and mortality. Full donor chimerism after myeloablation is commonly accompanied by graft-vs.-host disease (GvHD). We utilized an animal model of LAD, canine leukocyte adhesion deficiency (CLAD), to test new transplant regimens for LAD. CLAD is due to a point mutation in canine CD18, and the phenotype closely resembles the severe deficiency phenotype of LAD. We have previously shown that treatment with 200 cGy total body irradiation (TBI), matched sibling HSCT, and immunosuppression with cyclosporine A (CsA) and mycophenolate mofetil (MMF) corrects the CLAD phenotype. Because TBI in children is associated with growth suppression, sterility and increased risk of cancer, translation of this approach to humans will be limited by concern for toxicity. To develop a non-TBI conditioning regimen for LAD transplants, we tested single-agent busulfan. CLAD pups were identified by absence of CD18 on leukocytes by fluorescence-activated cell sorting (FACS). Three dogs that lacked a DLA-matched littermate donor died at 2, 4 and 6 months of age, respectively. Three CLAD pups were given 10 mg/kg busulfan IV followed 2 days later by 6-17x10^6 CD34+ cells/kg from matched sibling donors and immunosuppression with CsA/MMF. Chimerism was assessed by CD18 FACS. Dogs were observed for evidence of infection, regimen-related toxicity, graft-versus-host disease and overall health. All three dogs engrafted, and two animals maintained CD18+ leukocyte levels of 17.0% and 19.0% at 16 and 4 months post-transplant respectively. In both dogs, blood counts are normal with no signs of CLAD. These dogs are clinically and behaviorally indistinguishable from their healthy littermates. The third dog has had decreasing CD18+ cells and at 12 months post-transplant has 0.2% CD18+ donor leukocytes. Despite requiring two courses of parenteral antibiotics since stopping immunosuppression, this dog has considerably exceeded the life expectancy of non-transplanted CLAD pups. Thus, two CLAD dogs have had complete correction of the phenotype, and the third has had partial correction. There has been no need for transfusion and no other regimen-related toxicity. Post-transplant fevers were easily managed with no cases of refractory infection. There has been no GvHD. Our data show that a regimen using a single, non-myeloablative dose of busulfan can lead to long-term engraftment, stable mixed chimerism and reversal of CLAD phenotype with minimal toxicity. This treatment may provide LAD patients with matched sibling donors with an alternative to either myeloablation with full donor chimerism and risk of GvHD or non-myeloabaltive transplant using TBI with its attendant complications.

Parenteral antibiotics in a palliative care unit: prospective analysis of current practice.

All patients receiving parenteral antibiotics in a palliative care unit were prospectively monitored over a 13-month period. Of 913 consecutive admissions, 41 patients received 43 courses of parenteral antibiotics. On 27 of 43 occasions, the use of parenteral antibiotics was considered helpful (62%), in eight cases it was considered unhelpful (19%) and in a further eight cases the outcome could not be assessed (19%). The sites of infection for which parenteral antibiotics were prescribed included urinary tract infections (37%), lower respiratory tract infections (26%), soft tissue/skin or wound infections (16%), purulent terminal respiratory secretions (5%) and other (16%). In this sample, urinary tract infections were more commonly associated with a positive outcome than other indications combined (88% versus 48%, respectively). There appeared to be no association between outcome of use and age of the patient (median age 70, range 37-90), underlying diagnosis (HIV versus advanced malignancy) and reason for admission (symptom control versus respite care versus terminal care). However, outcomes appeared to vary in this sample according to the palliative care phase of the patient at the time parenteral antibiotics were administered. Positive outcomes were more common in terminal- (83%) and stable-phase (71 %) patients than deteriorating- (58%) or acute-phase (38%) patients. This survey demonstrates that in specific circumstances a beneficial role exists for the use of parenteral antibiotics in a palliative care setting. The establishment of appropriate guidelines is recommended.