Days Of Intravenous Antibiotics Research Articles

Chronic sinus disease and epidural abscess: Gemella morbillorum as emerging cause of central nervous system infections

Dear Editor, There is emerging evidence of Gemella morbillorum (GM) as a pathogen capable of causing potentially lifethreatening central nervous system (CNS) infections. We document the first case of intracranial epidural abscess (EA) caused by this pathogen, and emphasize the need to consider potential neurological involvement in patients with chronic sinus disease from whom GM is isolated. A 14-year-old boy presented with a 2-week history of headache and fever. His past medical history was only significant for sinusitis 2 years earlier. He was initially treated in the community for acute sinusitis by the family physician. Upon admission, he appeared mildly distressed, with a body temperature of 38.5 °C, complained of frontal headache, and vomited twice during clinical examination. Neurological examination was unremarkable, and blood investigations documented a CRP of 260 mg/l and an ESR of 99 mm/h. He was therefore empirically administered a large-spectrum antibiotic therapy. Over the following day, he remained pyrexial and his headache and vomiting worsened: a CT head scan showed frontal and left-sided maxillary and ethmoidal sinuses opacification, with extensive epidural frontal collection. A contrast-enhanced MRI scan revealed frontal epidural empyema and superior sagittal sinus compression with no evidence of dural sinuses thrombosis (Fig. 1, top). The patient underwent an urgent frontobasal bilateral craniotomy. A bicoronal flap was raised and an initial burr hole was placed in the frontal parasagittal area, yielding copious purulent debris under pressure. After craniotomy was performed, a purulent collection extending from the frontal sinuses up to the coronaric suture was noted. The frontal sinuses were opened and drained, with subsequent cranialization and closure with a galeal flap. The post-operative course was uneventful and our patient has remained apyrexial ever since the operation, with normalization of inflammatory markers. Intraoperative cultures from purulent material grew a metronidazole-resistant strain of Gemella morbillorum. He received a total of 14 days of intravenous antibiotics and was discharged on the 15th postoperative day, in good clinical condition. Gammainterferon and IL-12 serum levels were normal. A contrastenhanced MRI head scan carried out 3 months after surgery was unremarkable (Fig. 1, bottom).

Some wounds are hard to heal: an interesting presentation of Ehlers-Danlos syndrome

A 17-year-old female patient was admitted for an elective mini laparotomy and cystectomy of the right ovary for the treatment of chronic supra-pubic abdominal pain. The procedure went without complication and she was discharged the next day. She was re-admitted a month later as an acute case with wound dehiscence. HIV serology, thyroid function, immunoglobulin, protein electrophoresis and electrolyte levels were all normal. There were no obvious signs of infection and the bacterial swabs failed to culture an organism. Despite conservative measures with regular dressing, oral antibiotics and input from the tissue viability team the wound failed to epithelialise. The wound was debrided and re-sutured a total of three times and the patient received 24 days of intravenous antibiotics. After input from various teams a diagnosis of Ehlers-Danlos syndrome was made, allowing for appropriate management and wound healing.

Submandibular Space Abscess

In this study, the authors compare the external cervical approach with their new minimally invasive technique of intraoral drainage for submandibular space abscesses. In a randomized clinical trial, 40 patients with submandibular abscess entered the study in Amiralam Hospital of Tehran. Subjects were randomly divided in 2 groups of the classic external approach with skin incision in the submandibular area and the intraoral approach for abscess drainage. The data, including demographic details, need for a repeated surgery, days of postoperative hospitalization, scar formation, and possible complications, were recorded and analyzed. The patients required an average of 5.5 and 5.4 days of postoperative intravenous (IV) antibiotics in the intraoral and external approaches, respectively, and were discharged from the hospital 1 day after the cessation of the IV antibiotics. There was no significant difference between the 2 groups in terms of postoperative hospitalization and days of intravenous antibiotics administration. No patients had weakness in their marginal mandibular nerve or skin scarring postoperatively in the intraoral approach group. This study reveals that submandibular abscess in selected cases can be successfully treated with an intraoral drainage approach, which is a better choice than the external technique in terms of better cosmetic outcome. Postoperative care in these patients is much easier because there is no need for daily irrigation and dressing of the wound. Also, there is possibly no risk for injury to surrounding nerves.

Pediatric Calcaneal Osteomyelitis

Osteomyelitis continues to be a common problem amongst the pediatric population. Osteomyelitis of the calcaneus is an uncommon problem that still poses a problem to the treating physician. The purpose of this article is to retrospectively review a large series of pediatric patients with calcaneal osteomyelitis. We compare our experience with that in the literature to determine any factors that may aid earlier diagnosis and or improve treatment outcomes. A 10-year retrospective review was performed of clinical records of all cases of pediatric calcaneal osteomyelitis managed at the 2 children's orthopaedic departments in the Auckland region. The Osteomyelitis Database was used to identify all cases between 1997 and 2007, at Starship Children's Hospital, and 1998 and 2008 at Middlemore's Kids First Hospital. Sixty patients fulfilled the inclusion criteria, and had a review of clinical notes and relevant investigations. The average duration of symptoms before presentation to hospital was 6.8 days. About 40% of patients had a recent episode of trauma. About 82% of patients could not bear weight on admission. Only 22% of patients had a temperature above 38°C. Erythrocyte sedimentation rate was elevated in 81% and the C-reactive protein was elevated in 77% of patients. About 27% of patients had positive blood cultures with Staphylococcus aureus being the most commonly cultured organism. X-rays, bone scans, and magnetic resonance imaging were all used to aid the diagnosis. About 20% of patients had surgery with an average of 1.3 surgeries for those who progressed to surgery. Treatment length was an average of 2 weeks 6 days of intravenous antibiotics followed by 3 weeks 2 days of oral treatment. There were no postsurgical complications and 10 readmissions: 3 for relapse, 3 for peripherally inserted central catheter line problems, and 4 for antibiotic-associated complications. Although sometimes more difficult to diagnose, calcaneal osteomyelitis can be diagnosed with an appropriate history, clinical examination, and investigations. Treatment with intravenous and oral antibiotics and surgical debridement if indicated can lead to a good clinical outcome with minimal complications.

A Novel High Dose Chemotherapy Strategy with Bendamustine In Adjunct to Etoposide, Cytarabine and Melphalan (BeEAM) Followed by Autologous Stem Cell Rescue Is Safe and Highly Effective for the Treatment of Resistant/Relapsed Lymphoma Patients: a Phase I-II Study on 44 Patients

AbstractAbstract 31 Background:BEAM (Carmustine, etoposide, cytarabine, and melphalan) regimen is the most used conditioning regimen before autologous stem cell transplant (ASCT) in lymphoma patients. However, patients receiving BEAM show a significant number of side effects, and relapse rate after transplant is still a matter of concern. Therefore, new regimens with a higher efficacy and a better toxicity profile in comparison to BEAM are highly needed. Aims:We designed a phase I-II study to evaluate the safety and the efficacy of increasing doses of Bendamustine for the conditioning regimen to ASCT for resistant/relapsed lymphoma patients. Methods:Forty-four patients (median age 47 years, range 18–70) with resistant/relapsed non-Hodgkin (29) or Hodgkin (15) lymphoma were consecutively enrolled in the study. The new conditioning regimen consisted of increasing doses of Bendamustine coupled with fixed doses of Etoposide (200mg/m2/day on days -5 to -2), Cytarabine (400mg/m2 on days -5 to -2) and Melphalan (140 mg/m2 on day -1) (BeEAM regimen). Three cohorts of 3 patients each were treated starting with Bendamustine 160 mg/m2/daily given on days -7 and -6. The dose of Bendamustine was then escalated according to the Fibonacci's increment rule until the onset of severe adverse events and/or the attainment of the expected MTD, but not higher than 200 mg/m2. Patients were carefully monitored for adverse events. The study was registered at EMEA with the EUDRACT no 2008–002736-15. Results:The administration of Bendamustine was safe in all the 3 cohorts of patients. The major side effect was a grade III-IV oral mucositis developed by 9 patients during neutropenia. We then fixed the dose of Bendamustine 200 mg/m2 as safe and effective for the Phase II study. A median number of 5.68×106CD34+/kg cells (range 2.4–15.5) collected from peripheral blood was reinfused to patients. All patients engrafted, with a median time to ANC>0.5×109/l of 10 days. Median times to achieve a platelet count >20×109/l and >50×109/l were 13 and 16 days respectively. Twenty-two out of 44 patients presented a fever of unknown origin (50%). The median number of days with fever was 2 (range: 0–7), with a median number of 9 days of intravenous antibiotics (range: 3–22). All patients received G-CSF after transplant for a median time of 9 days (range: 8–25). Two patients developed a viral infection (1 HSV-6, 1 CMV) early after transplant. Thirty-nine out of 44 patients are evaluable up to now for the response to treatment. All evaluable patients are alive. 32/39 are in complete remission whereas 4/39 are in partial response, after a median follow-up of 11 months from transplant. Three out of 39 patients relapsed after a median time of 3 months from transplant. It is of note that 4/39 patients achieved the first complete remission after receiving the high-dose therapy with autologous stem cell rescue. Conclusions:The new BeEAM regimen is safe and seems to have a high efficacy in heavily pretreated lymphoma patients. Basing on this experience, future studies incorporating Bendamustine in conditioning regimens pre-ASCT in lymphoma patients should use Bendamustine 200 mg/m2/day over 2 days. Acknowledgments:supported in part by AIL Pesaro Onlus. Disclosures:Malerba:celgene, Janssen-Cilag: Honoraria.

P97 Do intravenous antibiotics influence arterial stiffness in adults with cystic fibrosis?

Introduction and objectivesAdults with cystic fibrosis (CF) have evidence of increased arterial stiffness which is associated with a chronic systemic inflammatory status (1). We hypothesised that an intervention which decreased...

Physiologic predictors of postoperative abscess in children with perforated appendicitis: Subset analysis from a prospective randomized trial

Intra-abdominal abscess after appendectomy is the most common complication in patients with perforated appendicitis. There are currently little data that may forecast which patients are more likely to develop an abscess. Therefore, we performed a retrospective analysis of a prospectively collected dataset to determine whether there are predictors for developing a postoperative abscess. The dataset was collected prospectively in a randomized trial comparing antibiotic regimens in 98 pediatric patients with perforated appendicitis. All patients underwent laparoscopic appendectomy and received a minimum of 5 days of intravenous antibiotics. The Pearson correlation was used to evaluate the influence of patient, intra-operative, and early postoperative variables on the development of an abscess. Two-tailed P values were determined from the correlation coefficient, and significance was defined as P < or = .05. At presentation, a positive correlation for abscess formation was identified with increasing age (P = .003), weight (P = .001), body mass index (P = .008), and diarrhea (P = .005). Operative time had no influence on abscess development. After operation, there was progressively increasing positive correlation between abscess and the maximum temperature each successive postoperative day. This relationship became significant at day 3. An increased white blood cell count on day 5 was highly predictive of abscess (P < .001). In children presenting with perforated appendicitis, increasing age, weight, and/or body mass index correlated with the development of a postoperative abscess. Diarrhea on presentation also poses an increased risk of abscess. Postoperatively, each successive day with a fever is incrementally more predictive of an abscess formation.

Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients with Renal Insufficiency: a Single Centre Experience.

Abstract 4362 BACKGROUND AND AIMSMultiple myeloma (MM) might be a cause a of the malignancy-related renal insufficiency, often present at diagnosis. Severity of it implicates further therapy. Patients with severe renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy regimens. The goal of this study was to evaluate the eligibility and efficacy of autologous hematopoietic stem cell transplantation (AHCT) in MM patients with concomitant renal insufficiency. 239 MM patients were treated in our department with high-dose chemotherapy followed by AHCT between 1993 and 2009. Twenty of them (8%) were also diagnosed with renal impairment. PATIENTS AND METHODS20 patients (8 women, 12 men), age 40-65 years (median 51) were enrolled. MM subtype at diagnosis was: IgG, n=14 (kappa-9, lambda-5); IgA kappa, n=1; light chain disease (LCD), n=4 (kappa-3, lambda-1); non-secretory, n=1. Chronic kidney disease (CKD) stage at MM diagnosis was 2-5 (median 3). One pt. was on chronic hemodialysis, two required plasmapheresis. Before AHCT pts. were treated with 1-4 (1) regimens, mainly VAD and CTD. 8/20 pts. received radiotherapy.Mobilization regimen was high-dose cyclophosphamide in 8 and IVE (iphosphamide, etoposide, epirubicin) in 12 cases. Stem cell collection yield was effective in all pts. (median 17.6 (1.9 - 44.7) x 10e6 CD34+ cells/kg). Disease stage at AHSCT: CR n=6, VGPR n=2, PR n=12. RESULTSRenal function measured before transplantation significantly improved due to MM treatment compared to that at diagnosis, p=0.008. CKD stage before transplantation equaled 1-4 (median 2). The only one patient who initially required hemodialysis became dialysis independent before AHCT.Conditioning regimen with melphalan (range 75-200mg/m2) was generally well tolerated. The median numbers of transplanted cells were following: NC 2.5 (1-7.6) x10e8/kg; CD34+ 7.9 (0.8-21.7) x 10e6/kg. All patients engrafted. Median regeneration time of granulocytes up to >0.5 G/l and of platelets to >50 G/l equaled 14 (12-19) and 14 (12-101) days, respectively. Transplant related mortality at day 100 was 0%. Mucositis, diarrhoea, bacterial and HSV infections were main complications after AHCT. Regeneration time, hospital stay, days of intravenous antibiotics or antifungal drugs administration and number of transfusion were comparable to pts. transplanted without renal impairment. No renal complications were observed. On the contrary creatinine clearance after transplantation showed trend towards further improvement compared to that before AHCT, p=0.07. The probability of overall (OS) and progression free (PFS) survival for studied group of pts. were 84% and 63%, respectively. Median observation time 2.3 years (0.1-12.5). CONCLUSIONSOur observation demonstrates that AHCT is an effective and well tolerated option for MM patients with mild or moderate renal insufficiency. Treatment before transplantation and also high-dose chemotherapy followed by AHCT may even improve renal function. No relationship between CKD and stem cell collection yield, engraftment or severity of post-transplant complications was observed in this group of patients. Disclosures:No relevant conflicts of interest to declare.

A novel High dose chemotherapy strategy with Bendamustine in Adjunct to Etoposide, Aracytin and Melphalan (BeEAM) Followed by Autologous Stem cell rescue in Resistant/Relapsed Hodgkin and Non-Hodgkin Lymphoma Patients: a Phase I Study.

Abstract 4351We designed a phase I study to evaluate the safety and the efficacy of increasing doses of Bendamustine, coupled with fixed doses of Etoposide, Cytarabine and Melphalan in the conditioning regimen to autologous stem cell transplant for resistant/relapsed lymphoma patients. Nine patients (median age 54 years, range 18-70) with resistant/relapsed non-Hodgkin's (6) or Hodgkin's (3) lymphoma were consecutive enrolled in the study, starting from August, 1st 2008. The new conditioning regimen (BeEAM) consisted of increasing doses of Bendamustine coupled with fixed doses of Etoposide (200mg/m2/day on days -5 to -2), Cytarabine (400mg/m2 on days -5 to -2) and Melphalan (140 mg/m2 on day -1) (BeEAM regimen). Three cohorts of three patients each were treated starting with Bendamustine 160 mg/m2 given on days -7 and -6. The dose of Bendamustine was then escalated according to the Fibonacci's increment rule until the onset of severe adverse events and/or the attainment of the expected maximum tolerated dose, but not higher than 200 mg/m2. Patients were carefully monitored for any adverse event, particularly for cardiotoxicity. Electrocardiography and troponin monitoring was performed at baseline and thereafter at 24, 72 and 96 hours after the two-days Bendamustine administration.The administration of Bendamustine was safe in all the three cohorts of patients. No grade III or IV non hematological toxicities were observed at any dose of the drug. In particular, we did not observe any grade III-IV cardiotoxicity. All patients engrafted, with a median time to ANC>0.5×109/l of 11 days (range: 11-27). Median times to achieve a platelet count >20×109/l and >50×109/l were 13 and 15 days respectively. Six out of 9 patients experienced an episode of FUO (66%), whereas 1/9 (11%) presented a bacteriemia. However, the median number of days with fever was 2 (range: 0-5), with a median number of 9 days of intravenous antibiotics (range: 3-22). All patients received G-CSF after transplant for a median time of 8 days (range: 8-24).At the time of writing all patients are alive and in complete remission, after a median follow-up of 5 months from transplant. It is of note that 2/9 patients achieved the first complete remission after receiving the high-dose therapy with autologous stem cell rescue. However, the small number of the patients and the short duration of follow-up might be taken in account when analyzing these preliminary data.In conclusion, the new BeEAM regimen is safe and seems to have a high efficacy in heavily pretreated lymphoma patients. Further studies are warranted to compare the efficacy of this new regimen with the conventional BEAM regimen for resistant/relapsed lymphoma patients submitted to ASCT. All the future studies who want to incorporate Bendamustine on such conditioning regimens for ASCT in lymphoma patients should use Bendamustine at a dose of 200 mg/m2 daily given overt 2 days.The study was conducted in accordance with the principles of the Helsinki Declaration, Good Clinical Practices and the current National Rules for conducting clinical studies. The study was registered at European Medicines Agency (EMEA) with the EUDRACT no 2008-002736-15. AcknowledgmentsWe kindly acknowledge Mundipharma Italy and Mundipharma Europe for providing us the drug for the study free of charge. The study was supported in part by AIL Pesaro Onlus, Disclosures:Off Label Use: Bendamustine is used in adjunct to etoposide, cytarabine and melphalan in a novel strategy of high-dose therapy followed by autologous stem cell rescue.

Assessing response to treatment of exacerbations of bronchiectasis in adults

The present study aimed to assess the effect of intravenous antibiotic therapy on clinical and laboratory end-points in exacerbations of noncystic fibrosis bronchiectasis and to determine whether the outcomes were influenced by the pathogenic organism isolated. A prospective cohort study was conducted from November 2006 to March 2008 of exacerbations requiring intravenous antibiotics. End-points included 24-h sputum volume, forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), incremental shuttle walk test, qualitative sputum microbiology, white cell count, erythrocyte sedimentation rate, C-reactive protein (CRP) and St George's Respiratory Questionnaire (SGRQ). Exacerbations due to Pseudomonas aeruginosa were compared with exacerbations due to other potential pathogenic organisms. In total, 32 exacerbations were studied. Following 14 days of intravenous antibiotics, all outcomes significantly improved independent of a pathogenic organism, except FEV(1) and FVC. The most responsive markers were: 24-h sputum volume (reduced in all patients and 80% had >/=50% reduction); sputum bacterial clearance (78.1%); CRP (>/=75% reduction in 62.5%) and SGRQ (>/=4 unit improvement in 89.7%). CRP, 24-h sputum volume and SGRQ improved independent of microbial clearance. In the current study, 24-h sputum volume, microbial clearance, C-reactive protein and St George's Respiratory Questionnaire were the most useful parameters to assess response to treatment of exacerbations of bronchiectasis. Outcomes were similar independent of the pathogenic organism with the exception of forced expiratory volume in one second and forced vital capacity.

Delayed Femoral Shaft Fracture Secondary to Nail Gun Injury: A Case Report

Nail gun injuries are common workplace occurrences among construction workers; however, delayed fractures of the femur after a nail gun injury are not found in the medical literature. We report the case of a patient who presented with such a fracture 3 days after accidentally firing a nail into his thigh. The patient was taken to the operating room for intramedullary nailing, irrigation and debridement, and antibiotic beads. Standard postoperative hospital care was provided, and after 2 days of intravenous antibiotics, the patient was returned to the operating room for removal of the antibiotic beads and a delayed primary closure. At the most recent follow-up, over 1 year postinjury, he had radiographic healing and was asymptomatic. Although it is difficult to predict whether the stress riser created by a nail gun injury will lead to a fracture, weight-bearing status and the aggressiveness of treatment to prevent infection are factors that need to be carefully considered in patients with this type of injury.

Tratamiento intravenoso inicial abreviado en 70 pacientes pediátricos con infecciones osteo-articulares

Osteoarticular infections (OAI) are infrequent in pediatrics and there is controversy on the need for prolonged use of intravenous antimicrobials.To characterize and describe evolution and complications of a regimen of 7 days initial intravenous antibiotic treatment for OAI in children, completing 4-6 weeks of total treatment.In a large pediatric hospital, 70 children younger than 15 years of age were diagnosed with OAI between March 2003 and December 2004. Children received 7 days of intravenous antibiotics followed by 3 to 5 weeks of oral treatment.Incidence of OAI in this hospital was 1.8:10000. Patients mean age was 6.4 +/-4.4 years and 60% presented with septic arthritis, 36% osteomyelitis and 4% osteoarthritis. In 80% of cases, the infection was located in the lower extremity. Positive cultures were obtained in 59% predominating Staphylococcus aureus (46.5%). Seven patients had prolonged pain or persistently high or increasing serum C reactive protein levels and were maintained on prolonged intravenous therapy. None of the 63 children with 7 day intravenous antimicrobials nor the 7 children with prolonged intravenous use developed a complication in the short-term follow up.Seven days of intravenous antibiotic for the initial phase of OAI treatment was effective in a majority of children and may be recommended.

Short duration of initial intravenous treatment in 70 pediatric patients with osteoarticular infections

Osteoarticular infections (OAI) are infrequent in pediatrics and there is controversy on the need for prolonged use of intravenous antimicrobials. To characterize and describe evolution and complications of a regimen of 7 days initial intravenous antibiotic treatment for OAI in children, completing 4-6 weeks of total treatment. In a large pediatric hospital, 70 children younger than 15 years of age were diagnosed with OAI between March 2003 and December 2004. Children received 7 days of intravenous antibiotics followed by 3 to 5 weeks of oral treatment. Incidence of OAI in this hospital was 1.8:10000. Patients mean age was 6.4 +/-4.4 years and 60% presented with septic arthritis, 36% osteomyelitis and 4% osteoarthritis. In 80% of cases, the infection was located in the lower extremity. Positive cultures were obtained in 59% predominating Staphylococcus aureus (46.5%). Seven patients had prolonged pain or persistently high or increasing serum C reactive protein levels and were maintained on prolonged intravenous therapy. None of the 63 children with 7 day intravenous antimicrobials nor the 7 children with prolonged intravenous use developed a complication in the short-term follow up. Seven days of intravenous antibiotic for the initial phase of OAI treatment was effective in a majority of children and may be recommended.

Un torticolis fébrile

Pediatric deep neck space infection (DNI) is a relatively rare but potentially life-threatening condition and requires prompt and accurate management. This study retrospectively reviews our experience in a tertiary referral hospital from 2004 to 2019.Systematic data collection from medical records using ICD10 codes between 2004 and 2019.age ≤16 years, DNI requiring hospitalization and/or surgery.peritonsillar abscess without complications.We identified 42 patients, 21 boys and 21 girls, with a median age of 4.9 years. Most of the patients had severe symptoms, the most common of which were neck swelling (n = 39; 92.9%), neck pain (n = 39; 92.9%) and fever (n = 32; 76.2%). Twenty-two (52.4%) had torticollis, and the mean duration of symptoms before hospitalization was 4.95 days. Diagnosis was confirmed by MRI (n = 24), contrast-enhanced CT (n = 11) or ultrasonography (n = 6), except in one case. Twenty-three (54.8%) required an open neck incision, ten (23.8%) patients had intraoral surgery and nine were treated conservatively. Twelve (28.6%) patients were admitted to the pediatric ICU. Median hospitalization duration was six days. The infection most commonly had tonsillopharyngeal etiology (n = 18) and a retropharyngeal location (n = 17). Staphylococcus Aureus (n = 7) and Streptococcus pyogenes (n = 7) were the most frequent pathogens. We compared the early surgical intervention group (<2 days of intravenous antibiotics; n = 18; 42.9%) to the late surgery group (n = 15; 35.7%) and the conservatively treated groups (n = 9; 21.4%). The overall length of stay (LOS) was lower in the shorter preoperative medication group (mean 4.4 vs. 7.2; p = 0.009). The size of the abscess did not differ between the groups (mean 28 mm; 30 mm; 21 mm; p = 0.075) and the neck incision rate was similar in the operated groups.Early surgical intervention is associated with decreased LOS among severe pediatric DNI patients.

Effectiveness of early switch from intravenous to oral antibiotics in severe community acquired pneumonia: multicentre randomised trial

Objectives To compare the effectiveness of an early switch to oral antibiotics with the standard 7 day course of intravenous antibiotics in severe community acquired pneumonia. Design Multicentre randomised controlled...

Measurement of urinary N-acetyl- b- d-glucosaminidase in adult patients with cystic fibrosis: Before, during and after treatment with intravenous antibiotics

Background Patients with cystic fibrosis (CF) are at high risk from the nephrotoxic effects of intravenous antibiotics due to repeated and prolonged courses of therapy. Routine methods of monitoring renal injury are insensitive. N-acetyl- b- d-glucosaminidase (NAG) is a lysosomal enzyme present in the renal proximal tubular cells, with increased excretion an indicator of renal tubular dysfunction. Methods Urinary NAG, creatinine, serum creatinine, electrolytes and BUN were measured on days 1, 14 and at the first out-patient visit following treatment with tobramycin or colistin. Urinary NAG levels were corrected for urinary creatinine and expressed as a NAG ratio. Patients who received > 1 course of intravenous antibiotics during the study period were included in a separate analysis of the cumulative effect of treatment. Results 88 patients (44 female, 31 with CFRD) completed a single course of intravenous antibiotics. 71 patients had urinary NAG levels at follow-up. The median time to follow-up was 50 days. Serum electrolytes, creatinine and BUN were normal throughout. A 3.5-fold increase in urinary NAG excretion was observed between day 1 and 14 and 46% of patients had an elevated NAG level at follow-up. A highly significant difference in NAG excretion was observed on day 14 for tobramycin vs. colistin (median 2.24 vs. 0.98, p < 0.001). A significant difference in NAG excretion was seen in patients with CFRD at all measured time points. Patients with CFRD had a significantly worse clinical status and had received more days of intravenous antibiotics over the previous 6 years. In 20 (80%) of 25 patients who received > 1 course of treatment during the study period, baseline NAG levels were significantly higher in subsequent courses ( p < 0.001). There was a significant correlation between previous exposure to colistin and baseline NAG levels ( r = 0.389, p < 0.001). Conclusions Both tobramycin and colistin cause acute renal tubular injury with a significant rise in urinary NAG excretion. Patients with CFRD seem to be at greatest risk of renal tubular damage. Cumulative damage is evident with repeated dosing. Previous exposure to nephrotoxic antibiotics, especially colistin, is associated with elevated baseline NAG levels. We recommend that colistin is reserved for patients with resistant Pseudomonas aeruginosa or those who are intolerant to tobramycin. Serial longitudinal NAG measurements may be useful in patients with CF, especially those with CFRD, to identify patients at risk of developing renal disease.

Treatment of pediatric suppurative mastoiditis: Is peripherally inserted central catheter (PICC) antibiotic therapy necessary?

A review of the treatment of pediatric acute mastoiditis requiring surgical intervention managed with and without PICC therapy postoperatively. Retrospective study of 42 cases from 1989 to 2004 treated at a regional children's hospital. Sixteen patients received postoperative PICC therapy and 26 received a course of oral antibiotics. The PICC group received on average 12.12 days of intravenous antibiotics compared to only 3.53 days for the non-PICC group (P < 0.001). No differences were observed between the two groups in treatment outcomes. One patient from each group required rehospitalization. One minor complication was experienced in a patient in the PICC group. There were no surgical complications. The total cost for outpatient PICC therapy increased treatment costs by approximately $1500 to $2500. Oral antibiotic therapy is sufficient after surgical intervention for acute pediatric suppurative mastoiditis without intracranial complications and does not result in adverse treatment outcome. Use of PICC therapy after surgical intervention for mastoiditis should be limited. B-3b.

Endoscopic Submucosal Dissection for Early Esophageal Cancer

Introduction: The Japanese Esophageal Association recommended endoscopic mucosal resection (EMR) as a treatment of choice for these cancers. However, these lesions often spread laterally exceeding the limitation of en-block respectability with conventional EMR methods. The lesions resected in piece-meal manner with conventional EMR methods are prone to recur locally. Therefore, we developed a new endoluminal surgery method. Patients and Methods: One hundred and thirty cases of superficial esophageal SCC were resected with ESD using hook knife from Jan. 2000 to Apr. 2005. Resected size, complete resection rate, complications and local recurrence were investigated in this study. Complete resection was defined as follows; enbloc resection, lateral margin was negative and vertical margin was negative. Results: The median size of the resected specimen was 32 mm (8-76 mm) and that of cancer was 28 mm (4-64 mm), respectively. 2. Complete resection: Complete resection rate was 93.8% (122/130). The hook knife could not be rotated in the early stage, therefore submucosal dissection was difficult. However, submucosal dissection became easier after the direction of hook could be controlled. The incidence of lymph nodal metastasis has correlate with invasion depth, historical type and duct involvement. Therefore, precise pathological examination with enbloc resected specimen is necessary to decide the additional treatment should be done or not. Because, the specimens resected in piecemeal were damaged and precise pathological diagnosis was often impossible. 3. Complications: The major complications were perforation, bleeding and stenosis. There were no perforations in our experience. The most important point to avoid perforation is to keep the visual field of the submucosal layer clear and to control the direction of the hook knife parallel with the proper muscle. Ten cases of mediastinal emphysema (7.7%) were observed. Two days of intravenous antibiotics (Flomoxef 2 gr/day) and fasting with intravenous infusion were instituted to treat the patients. 3. Local recurrence: the local recurrent rate was 0% (0/130) and mean period of follow-up was 28months (3 - 61 months). The lateral extension of the esophageal SCC could be diagnosed easy with lugol staining. And precise resection, two or three mm out of the cancer, could be able to performed with ESD using hook knife. Therefore, local recurrence will never occur after ESD. Conclusion: The complete resection rate with ESD is 93.8%, there has been no severe complication and no local recurrence. ESD with hook knife is a novel endoluminal surgery method for early esophageal cancer.

Outcomes of Adults with Cystic Fibrosis Infected with Antibiotic-Resistant Pseudomonas aeruginosa

Background: Although Pseudomonas aeruginosa is the most common bacterial infection in adults with cystic fibrosis and frequently develops resistance to multiple classes of antibiotics, it has not been determined whether patients with multiple antibiotic-resistant Pseudomonas aeruginosa have worse clinical outcomes than patients with more susceptible strains. Objectives: This study assessed the impact of multiply-resistant P. aeruginosa on lung function, hospitalizations, antibiotic use, lung transplantation and survival in adults with cystic fibrosis. Methods: In a cohort study at a university-based adult cystic fibrosis program, 75 consecutive adult cystic fibrosis patients who had P. aeruginosa isolated from sputum cultures were studied over a 4-year period. Outcomes included decline in FEV₁, clinic visits, hospitalizations, courses and days of intravenous antibiotics, and lung transplantation. Multiple linear and Poisson regression for repeated measures were used to assess the outcomes. Results: In comparison to patients with susceptible strains, patients with resistant P. aeruginosa had more severe baseline lung disease, more rapid decline in FEV₁ (160 ml/year, p = 0.003) and were significantly more likely to undergo lung transplantation (17.6 vs. 0%, p = 0.005). Conclusions: Infection with multiple-antibiotic-resistant P. aeruginosa is associated with accelerated progression of cystic fibrosis, and has important implications for infection control strategies, antibiotic use and lung transplantation.

Granulocyte–colony‐stimulating factor–mobilized prophylactic granulocyte transfusions given after allogeneic peripheral blood progenitor cell transplantation result in a modest reduction of febrile days and intravenous antibiotic usage

It was hypothesized that transfusion of two granulocyte-colony-stimulating factor (G-CSF)-mobilized prophylactic granulocyte components into allogeneic peripheral blood progenitor cell (PBPC) transplant patients during the regimen-related neutropenic interval would result in clinical benefit. HLA-matched sibling PBPC donors (n=151) were biologically randomized based on ABO mismatch to donate granulocyte components (Cohort G) or not donate granulocytes (control group, Cohort C). ABO-matched donors who did not meet other study-specific criteria were reassigned to Cohort C. Feasibility, defined as the proportion of ABO-matched donors who underwent granulocyte collections, was 42 percent (53 of 125). The percentage of patients who developed fever during the initial hospitalization was greater in Cohort C versus Cohort G (82.7% vs. 64.2%; p=0.03). In the interval from when granulocyte transfusions were initially given in Cohort G (Day +3 or Day +5) until neutrophil engraftment, the number of febrile days was less in Cohort G versus Cohort C (median, 0 vs. 1; Mann-Whitney p=0.003). The median number of days of intravenous antibiotics given during the initial hospitalization was less in Cohort G versus Cohort C (9 vs. 11; Mann-Whitney p=0.03), a difference accounted for in the interval from Day +3 or Day +5 to neutrophil recovery. There was no significant difference in length of the initial hospital stay, acute graft-versus-host disease rates, or 100-day survival between the two cohorts. This prospective study demonstrates a modest, but significant, benefit of G-CSF-mobilized HLA-matched prophylactic granulocyte transfusions in neutropenic allogeneic PBPC recipients.