Prophylactic Antimicrobial Therapy Research Articles

56-Year-Old-Man With Fever, Altered Mental Status, and Abdominal Pain

56-Year-Old-Man With Fever, Altered Mental Status, and Abdominal Pain

Preventing Infections in Children with Cancer.

1. Jennifer Lighter-Fisher, MD* 2. Kaitlin Stanley, MD* 3. Michael Phillips, MD† 4. Vinh Pham, MD, PhD† 5. Liana M. Klejmont, PharmD, BCPS‡ 1. *Department of Pediatrics, New York University Langone Medical Center, New York, NY. 2. †Department of Medicine, New York University Langone Medical Center, New York, NY. 3. ‡Department of Pharmacy, New York University Langone Medical Center, New York, NY. After completing this article, the reader should be able to: 1. Provide recommendations for bacterial prophylaxis for children experiencing severe and prolonged neutropenia. 2. Screen and recommend prophylaxis against Mycobacterium tuberculosis for children receiving immunosuppressive regimens. 3. Provide recommendations for secondary prophylaxis against Clostridium difficile infection, a common infection causing morbidity in the pediatric oncology population. 4. Recommend appropriate antifungal prophylaxis for pediatric patients who have high-risk cancers. 5. Review primary and second-line options for Pneumocystis jiroveci (carinii) pneumonia prophylaxis in children who fail trimethoprim/sulfamethoxazole therapy. 6. Prevent reactivation of viral infections in children receiving cancer treatment. 7. Screen for latent parasitic infections in newly diagnosed pediatric oncology patients. 8. Review vaccination regimens for patients receiving oncology treatment as suggested by the Infectious Diseases Society of America. Clear guidelines exist for the prevention of infections in patients undergoing hematopoietic stem cell transplantation (HSCT), (1)(2) but there is no guidance regarding prophylactic antimicrobial therapy for pediatric cancer patients receiving systemic chemotherapy. Infection, whether due to bacterial, fungal, viral, or parasitic pathogens, is a leading cause of morbidity and mortality in this patient population. (3)( 4)( 5) For example, more than 60% of children being treated for acute myeloid leukemia (AML) experienced at least 1 microbiologically documented infection during therapy, and the cumulative infectious mortality rate was 11%. (5) Therefore, infection prevention is of the utmost importance. Due to the lack of standard guidelines for infection prevention in most children being treated for cancer, current …

The role of targeted prophylactic antimicrobial therapy before transrectal ultrasonography-guided prostate biopsy in reducing infection rates: a systematic review.

To compare the incidence of infective complications after transrectal ultrasonography (TRUS)-guided biopsy with either empirical fluoroquinolone or culture-based targeted antimicrobial prophylaxis, and the prevalence of fluoroquinolone resistance (FQ-R) in men undergoing prostate biopsy. A systematic review of the literature was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included studies of patients undergoing TRUS-guided biopsy that compared infective outcomes of those who received targeted antimicrobial therapy based on the results of pre-procedural rectal swab cultures, with those receiving empiric fluoroquinolone antimicrobial prophylaxis. The prevalence of FQ-R was recorded as a secondary outcome measure. Studies with no control group were excluded. From 125 studies screened, nine studies (4 571 patients) met the inclusion criteria. All studies were of cohort design, and included a combination of retrospective and prospective data. Six studies included were undertaken in North America. The remaining studies were undertaken in Spain, Turkey and Columbia. Within these studies, 2 484 (54.3%) patients received empirical fluoroquinolone prophylaxis, whilst 2 087 (45.7%) patients had pre-biopsy rectal swabs and targeted antibiotics. The mean FQ-R was 22.8%. Post-biopsy infection and sepsis rates were significantly higher in groups given empirical prophylaxis (4.55% and 2.21%) compared with groups receiving targeted antibiotics (0.72% and 0.48%). Based on these results 27 men would need to receive targeted antibiotics to prevent one infective complication. Our systematic review suggests that targeted prophylactic antimicrobial therapy before TRUS-guided prostate biopsy is associated with lower rates of sepsis. We therefore recommend changing current pathways to adopt this measure.

The non-immunosuppressive management of childhood nephrotic syndrome.

Idiopathic nephrotic syndrome (INS) is one of the most common renal diseases found in the paediatric population and is associated with significant complications, including infection and thrombosis. A high proportion of children enter sustained remission before adulthood, and therapy must therefore mitigate the childhood complications, while minimising the long-term risk to health. Here we address the main complications of INS and summarise the available evidence and guidance to aid the clinician in determining the appropriate treatment for children with INS under their care. Additionally, we highlight areas where no consensus regarding appropriate management has been reached. In this review, we detail the reasons why routine prophylactic antimicrobial and antithrombotic therapy are not warranted in INS and emphasise the conservative management of oedema. When pharmacological intervention is required for the treatment of oedema, we provide guidance to aid the clinician in determining the appropriate therapy. Additionally, we discuss obesity and growth, fracture risk, dyslipidaemia and thyroid dysfunction associated with INS. Where appropriate, we describe how recent developments in research have identified potential novel therapeutic targets.

Peri-anaesthetic complications in an equine referral hospital: Risk factors for post anaesthetic colic.

Peri-anaesthetic complications are relatively common in equine patients and further investigations are warranted to identify manageable risk factors. To report morbidity and mortality rates and identify associated risk factors for horses undergoing general anaesthesia, within a predominantly racing Thoroughbred (TB) population. Single centre retrospective observational study. Anaesthetic and case records of all horses ≥12 months old undergoing general anaesthesia at Newmarket Equine Hospital between August 2010 and April 2012 were analysed, excluding emergency abdominal/dystocia procedures or traumatology cases with cardiovascular compromise. Mortality and morbidity rates were calculated and described. Uni- and multivariable analyses were used to investigate the relationship between the principal complication, post anaesthetic colic (PAC) and risk factors. A total of 1067 anaesthetic records of 1021 horses were included in the study; of these, 702 horses (65.8%) were TB, 169 (15.8%) developed a complication within 7 days of general anaesthesia and 10 (0.94%) died as a result. The most prevalent morbidity was PAC, 111 horses (10.5%) developed colic within 7 days of general anaesthesia. Thoroughbred horses (odds ratio [OR] 2.93, 95% confidence interval [CI] 1.73-4.96) and horses receiving sodium benzylpenicillin (NaBP) (OR 2.77, 95% CI 1.69-4.50) were at increased risk of PAC. Thoroughbred racehorses were identified as at increased risk of PAC in this study and might benefit from more critical evaluation of post anaesthetic gastrointestinal function. An alternative to the administration of NaBP for prophylactic antimicrobial therapy needs to be further investigated if its role in PAC is confirmed by other studies.

Pathogenesis of infection in surgical patients.

Purpose of reviewDespite the application of prophylactic antimicrobial therapy and advanced technologies, infection remains one of the most common causes of morbidity and mortality in surgical patients. Understanding the pathogenesis of surgical infection would offer new insights into the development of biomarkers to predict and stratify infection in patients, and to explore specific strategies to minimize this serious postoperative complication.Recent findingsThe acute nonspecific inflammatory response triggered by endogenous danger signals evoked by surgical insult is beneficial, while paradoxically associated with reduced resistance to infection. There is growing evidence indicating that primed inflammation by surgical insult exaggerates the dysregulation of the immune-inflammatory response to the invasion of pathogens postoperatively. Innate immune receptors, such as Toll-like receptors (TLRs), contribute to detecting both pathogen-associated molecular patterns and endogenous damage-associated molecular patterns, and to further amplifying inflammatory responses to infection. Current evidence shows the fascinating role of non-TLRs in the process of infection. Non-TLRs, such as membrane-associated triggering receptor expressed on myeloid cells family, cytosolic nucleotide-binding oligomerization domain-like receptors and nuclear receptor nuclear family 4 subgroup A receptors, are also crucial in triggering the immune responses and mounting an effective defense against surgical insults and the second hit of infection.SummaryUnderstanding the pivotal role of non-TLRs in sensing exogenous and endogenous molecules, and the influence of primed systemic inflammation and depressed immune status on the defense against pathogen after surgical insult, would be helpful to fully explore the relevant sophisticated phenomena of surgical infection, and to elucidate the occurrence of heterogeneous constellations of clinical signs and symptoms among this special population.

Perioperative risk factors for surgical site infection in tibial tuberosity advancement: 224 stifles.

To examine perioperative factors affecting surgical site infection (SSI) rate following tibial tuberosity advancement (TTA). Retrospective case series. 224 stifles in 186 dogs. Medical records of dogs that underwent TTA in a single institution were reviewed. Information on signalment, anaesthetic and surgical parameters, as well as occurrence of SSI was recorded. Dogs were followed for a minimum of three months postoperatively. The association between perioperative factors and SSI was assessed using Chi-squared tests and binary logistic regression. The prevalence of SSI was 5.3% (12/224 TTA). Surgical time (p = 0.02) and anaesthesia time (p = 0.03) were significantly associated with SSI. For every minute increase in surgical time and anaesthesia time, the likelihood of developing SSI increased by seven percent and four percent respectively. The use of postoperative antimicrobial therapy was not significantly associated with lower SSI (p = 0.719). Implants were removed in 1.3% of cases (3/224 TTA). The findings of this study suggest that increased surgical and anaesthesia times are significant risk factors for SSI in TTA, and that there is no evidence that postoperative prophylactic antimicrobial therapy is associated with SSI rate.

708Risk Factors for Infections after Open Fractures - Opportunities for Improving Prophylactic Antimicrobial Therapy

708Risk Factors for Infections after Open Fractures - Opportunities for Improving Prophylactic Antimicrobial Therapy

Decompensated Cirrhotics Have Slower Intestinal Transit Times as Compared With Compensated Cirrhotics and Healthy Controls

Altered small intestinal motility in cirrhotics may play a major role in the development of bacterial translocation (BT) by leading to small intestinal bacterial overgrowth. BT has been implicated in the development of several complications including spontaneous bacterial peritonitis, esophageal variceal hemorrhage, and hepatorenal syndrome. Prior studies using antroduodenal manometry to evaluate intestinal motility have shown discrepancies regarding the relationship between dysmotility and the severity of cirrhosis. (1) To characterize the frequency of small bowel motility disturbances in cirrhotic patients using a wireless motility capsule (SmartPill); (2) To assess the relationship of intestinal dysmotility with liver disease severity and cirrhosis complications; and (3) To compare intestinal transit times and motility indices among cirrhotics and healthy controls. We conducted a prospective study of 20 patients with cirrhosis (10 compensated, 10 decompensated) who were recruited from Yale New Haven Hospital and Hepatology clinics (February 2011 to July 2011). All patients underwent and completed SmartPill studies. Intestinal transit times were calculated, analyzed, and compared among compensated versus decompensated cirrhotics versus historical, healthy controls. Intestinal transit delays/motility indices were correlated with disease severity and complications. Decompensated cirrhotics had significantly longer small bowel transit times (SBTT) as compared with compensated cirrhotics (6.17 vs. 3.56 h, P=0.036). There was a significant correlation (r=0.77, P=0.0003) between SBTT and cirrhosis severity as assessed by Child-Pugh score. There were no statistical differences noted between the groups for gastric or colonic transit times, although there was a trend toward prolonged transit throughout the gut in decompensated. Cirrhotics with spontaneous bacterial peritonitis and ascites also had significantly longer SBTT as compared with those without. This study demonstrates that decompensated cirrhotics have slower intestinal transit times as compared with compensated cirrhotics and healthy controls. Additional prospective studies are needed to further characterize dysmotility in cirrhotics and its relationship to complications related to BT. This would aid in the identification of patients at risk for developing severe complications and who may benefit from prophylactic prokinetic and/or antimicrobial therapy.

Approach to prophylactic measures for central venous catheter‐related infections in hemodialysis: A critical review

Vascular access is the major risk factor for bacteremia, hospitalization, and mortality among hemodialysis (HD) patients. The type of vascular access most associated with bloodstream infection is central venous catheter (CVC). The incidence of catheter-related bacteremia ranges between 0.6 and 6.5 episodes per 1000 catheter days and increases linearly with the duration of catheter use. Given the high prevalence of CVC use and its direct association with catheter-related bacteremia, which adversely impacts morbidity and mortality rates and costs among HD patients, several prevention measures aimed at reducing the rates of CVC-related infections have been proposed and implemented. As a result, a large number of clinical trials, systematic reviews, and meta-analyses have been conducted in order to assess the effectiveness, clinical applicability, and long-term adverse effects of such measures. In the following article, prophylactic measures against CVC-related infections in HD patients and their possible advantages and limitations will be discussed, and the more recent literature on clinical experience with prophylactic antimicrobial lock therapy in HD CVCs will be reviewed.

Postoperative Septic Arthritis After Elective Equine Arthroscopy Without Antimicrobial Prophylaxis

To determine the frequency of postoperative septic arthritis after elective arthroscopy in the absence of prophylactic antimicrobial therapy and to report complication rate of 444 consecutive equine arthroscopies. Retrospective case series. Horses (n = 444). Medical records of 444 consecutive elective equine arthroscopies (2008-2010) were reviewed. Horses that had septic arthritis on admission or those admitted for tenoscopy and bursoscopy, or had arthroscopic assisted internal fracture fixation were not included. Age and sex of horse, duration of anesthesia, joint examined, number of portals, surgeon, postoperative complications, date of complication, and number of septic joints were recorded. For 444 horses, 636 joints were explored. Nineteen horses had 20 complications (fever [n = 9], surgical site infection [3], cellulitis [1], wounds associated with inappropriate bandaging [2], limb swelling postsuture removal [1], medical colic [1], septic joint [3]). Horses with septic joints did not have any other complications. The incidence of sepsis was 0.5% joints or 0.7% horses. All horses survived and returned to function. Joint infection rate in the horse population that had elective arthroscopy without antimicrobial prophylaxis compares favorably with other reports citing 0.9% sepsis in horses after arthroscopy in which horses received either no antimicrobials or were administered pre or perioperative antimicrobial therapy.

A Critical Evaluation and Comparison of Antimicrobial Prophylaxis in Elective Surgeries Across three Hospitals

1. To evaluate and compare the pattern and rationality of prophylactic antimicrobial therapy in elective surgeries. 2. To evaluate and compare the adherence of hospitals to the standard guidelines on prophylactic antimicrobial therapy. A total of 150 patients each from a government hospital (group I), medical college teaching hospital (group II), and corporate hospital attached to the institution (group III) who had undergone elective, non-complicated surgery were included. The number & types of antimicrobials used along with duration were noted. Rationality was assessed on the basis of Kunin's criteria, ASHP guidelines & SIGN guidelines. Statistical analysis was done using appropriate tests. Cephalosporins were the most commonly used antimicrobials in all three groups (52.6%,85.7% & 84.8% respectively) followed by nitroimidazoles. Antimicrobial prophylaxis was appropriate in only 14.1%, 23.3% & 32.9% cases in the three groups respectively (p<0.01).The most common problem was prolonged duration of administration in 50.3%,58% & 45% respectively. The implementation of prophylaxis with respect to regimen & duration was erroneous in 20.1%, 12.7% & 4.7% respectively (p<0.01). The rationality & regimen of antimicrobial prophylaxis was comparatively better in the corporate hospital followed by medical college hospital and the government hospital. The present study calls for an urgent review on rational use of antimicrobials for prophylaxis in all the 3 hospitals.

Assessment of antimicrobial prophylaxis to prevent perioperative infection in patients undergoing prostate brachytherapy: multicenter cohort study

To propose an appropriate prophylactic antimicrobial therapy for patients undergoing brachytherapy, we evaluated the relationships between various antimicrobial prophylaxis (AMP) protocols and the incidence of postimplant infections in a multicenter cohort study conducted in Japan. The records of 826 patients with localized prostate cancer who underwent a transperineal (125)I brachytherapy procedure between January 2009 and December 2010 were retrospectively reviewed. Perioperative infections, including surgical site and remote infections, were recorded up to postoperative day 30. A total of 6 (0.73%) patients had a perioperative infection following seed implantation, of whom all received AMP for 1 or more days. None of the patients who received a single-dose protocol of AMP using fluoroquinolone p.o. or penicillin with a beta-lactamase inhibitor i.v. developed a perioperative infection. Statistical analysis showed that a single-dose protocol was more significantly related to a lower risk of perioperative infection as compared to the other AMP protocols examined (p = 0.045). Furthermore, our results indicated that bacteriuria and preoperative hair removal were risk factors of perioperative infection with statistical significance (p = 0.007, p = 0.004). Analysis of patient clinical parameters, including age, American Society of Anesthesiologists score, diabetes mellitus, prostate volume, numbers of implanted seeds and needle punctures, operation time, and indwelling duration time of the Foley catheter, did not reveal significant differences in terms of perioperative infection. Our results indicated that a single-dose AMP protocol is sufficient to prevent perioperative infections following seed implantation. On the other hand, AMP is only one of several measures to prevent perioperative infectious complications. It is necessary to know that the patient must have no bacteriuria and that preoperative hair removal should be avoided.

Lethal small bowel necrosis due to aspergillosis during acute promyelocytic leukemia induction

Lethal small bowel necrosis due to aspergillosis during acute promyelocytic leukemia induction

Compliance with the Eastern Association for the Surgery of Trauma guidelines for prophylactic antibiotics after open extremity fracture

Context:Prophylactic antibiotics, paired with wound care and surgical intervention, is considered the standard of care for patients with open fracture. Guidelines from the Eastern Association for the Surgery of Trauma (EAST) recommend specific prophylactic antimicrobial therapy based on the type of open fracture.Aims:We quantified adherence to EAST guideline recommendations and documented the incidence of infection in patients with open fracture.Settings and Design:A retrospective, observational study of all patients with open fracture admitted to our facility from January 2004 to December 2008 was conducted.Materials and Methods:Patients were divided into compliant and noncompliant groups according to the EAST guideline recommendations. Compliance was defined as an appropriate spectrum of therapy for guideline suggested duration. We assessed for surgical and non-surgical site infections, and morbidity outcomes.Statistical Analysis:Nominal data were explored using summary measures. Continuous variables were compared using the Student t-test or the Mann–Whitney U-test. Dichotomous data were compared using χ2 statistic or Fisher's exact test.Results:The final analysis included 214 patients. Prophylactic antibiotics were guideline compliant in 28.5% of patients, and ranged from 10.0% in type 3b fractures to 52.7% in type 1 fractures. The most common reason for non-compliance was the use of guideline recommended coverage that exceeded the suggested duration (71.2%). Patients who received non-compliant therapy required prolonged hospital lengths of stay (6 vs. 3 days, P = 0.0001). The overall incidence of infection was similar regardless of guideline compliance (17.0% vs. 11.5%, P = 0.313).Conclusions:Prophylactic antibiotics for open fracture frequently exceeded guideline recommendations in duration and spectrum of coverage, especially in more severe fracture types. Non-compliance with EAST recommendations was associated with increased in-hospital morbidity.

5.56 Ofatumumab in Combination with High-Dose Methylprednisolone as a Salvage Treatment for Heavily Pretreated or Refractory Patients with Chronic Lymphocytic Leukemia

Treatment options for relapsed / refractory or heavily pretreated patients with chronic lymphocytic leukemia (CLL) are limited, and these patients typically have a poor prognosis. We conducted a study to evaluate the combination of High-dose methylprednisolone (HDMP) with ofatumumab (HDMP-O) in patients who were not considered eligible to receive chemotherapy due to the presence of comorbidities, poor performance status, severe cytopenias and / or refractory status to fludarabine or alemtuzumab. Patients received HDMP 1 g/m2 IV daily × 3 every 28 days for three consecutive cycles, and ofatumumab 300 mg (dose 1) followed by 11 doses of 2,000 mg over a 6 month period, along with prophylactic antimicrobial therapy (trimethoprim-sulfamethoxazole 160/800 mg twice a day × 3 per week, fluconazole 100 mg/day and valganciclovir 900 mg/day). Eight patients were evaluated; all of them were males with progressive and symptomatic CLL. Median age was 69 years (range 49–78 years). The mean number of prior treatment regimens was 3.75, including four patients that had previously received HDMP and rituximab and two patients that underwent matched unrelated donor stem cell transplantation. All patients had been previously treated with rituximab, 75% of the patients were refractory to fludarabine and / or aletuzumab, and 88% had high-risk disease based on the presence of unfavorable cytogenetics (17p-, 11q-), unmutated IgVH status, or ZAP-70 expression. Bulky disease and splenomegaly were present in 62.5% of patients. All patients completed the planned therapy with no major side effects or toxicities. There was no evidence of myelosupression, and even patients with pancytopenia improved their peripheral blood counts. Response assessment based on the IW-CLL 2008 criteria showed an overall response rate of 50% (4 partial responses), 25% of patients had stable disease and the remainder showed progressive disease. The median time to progression in responders was 7 months. Overall survival 6 months after treatment was 65%. This study suggests that the combination of HDMP and Ofatumumab is a safe and effective salvage regimen for high-risk CLL patients who otherwise would not be candidates for additional treatment.

Anti-lymphocyte therapy successfully controls late “cholestatic” rejection in pediatric liver transplant recipients

Rejection is independently associated with liver graft loss in children. We report the successful rescue of grafts using ATG+/-OKT3 in late rejection associated with cholestasis. Retrospective chart review was performed after IRB approval. Between 2003 and 2010, 14 pediatric liver transplant recipients received anti-lymphocyte treatment for "cholestatic" rejection. Median age at transplantation was 12.7 yr (range 0.9-23.4), eight were boys, and immunosuppression was tacrolimus based. Median time from transplantation to rejection was five yr (range 1.1-10.5). Median peak total bilirubin was 11.1 mg/dL (range 1.4-18). All showed moderate to severe acute rejection and hepatocellular cholestasis on histology. ATG/OKT3 was started as first-line therapy in six and in the remaining eight as second-line therapy after failure of pulse steroids. Thirteen responded with normalization of aminotransferases and bilirubin, median time 16 wk (range 7-112); one non-adherent recipient has still not achieved normal graft function at last follow-up. Patient survival is 100%, with no re-transplantation and no post-transplant lymphoproliferative disease, median follow-up 2.9 yr (range 1.1-7.2). Cholestasis associated with acute rejection occurring late after liver transplantation may herald steroid resistance. First-line therapy with anti-lymphocyte preparations, prophylactic anti-microbial therapy, and close monitoring allow excellent rates of patient and graft survival.

Experience with the NICE Guidelines for Imaging Studies in Children with First Pyelonephritis

This retrospective study evaluates the applicability of a selective approach for imaging in children aged 0-15 years with a first episode of pyelonephritis, based on the UTI guidelines of the National Institute for Health and Clinical Excellence (NICE). A total of 96 consecutive patients were included (age range: 0.1-14.9 years, median age: 0.7 years), treated for a first episode of confirmed culture-positive pyelonephritis. At initial hospitalization all patients underwent ultrasound examination of the kidneys and urinary tract (US) and technetium-99m mercaptoacetyltriglycine scinti- and renography ( (99m)Tc MAG3). If vesicoureteral reflux (VUR) was suspected, then prophylactic antimicrobial therapy was prescribed and the patients were referred to a surgeon for further evaluation including voiding cystoureterography (VCU). Patients with known urological anomalies including antenatally diagnosed anomalies were excluded. All patients were followed up for a median of 5.2 years (3.5-8.6 years). Initially, US findings were abnormal in 29 (30%) patients and (99m)Tc MAG3 findings were abnormal in 20 (21%) cases. At follow-up, prophylactic antimicrobial therapy was prescribed for 19 (20%), and VUR was diagnosed by VCU in 9 patients. Surgery was carried out in 7 (7%) patients, primarily for VUR. If the NICE guidelines had been initially followed, 5 of our 9 patients with VUR would not have been identified. VUR surgery was performed in 4 of these cases. Moreover, 9 cases with urological anomalies subsequently prescribed prophylactic antimicrobial therapy would have been missed. We do not recommend following the imaging strategies of the NICE guidelines for children with a first episode of pyelonephritis. Our most important argument is that at follow-up, after a minimum of 3.5 years, the initial diagnosis of VUR would have been missed in 4 out of the 5 patients who underwent VUR surgery.

Ofatumumab and High-Dose Methylprednisolone Is An Effective Salvage Treatment for Heavily Pretreated, Unfit or Refractory Patients with Chronic Lymphocytic Leukemia: Single Institution Experience

AbstractAbstract 4638High-dose methylprednisolone (HDMP) and the fully human monoclonal anti-CD 20 Ofatumumab each can produce partial responses in CLL, even though complete remissions are not often observed following treatment with either agent alone.Previously we have reported that the combination of Rituximab and HDMP is an effective non-myelosuppressive treatment combination for previously untreated CLL patients as well as in patients that are fludarabine refractory. We report here our single institution experience of treatment using the combination of HDMP and Ofatumumab in CLL patients that were not considered to be good candidates for chemotherapy treatment due to comorbidities, poor performance status, profound cytopenias or because refractory status to fludarabine and/or alemtuzumab.Eight patients with progressive, symptomatic CLL were treated with HDMP 1 g/m2 IV daily × 3 every 28 days for three consecutive cycles, and ofatumumab administered based on package insert instructions (300 mg dose # 1 followed by 11 doses of 2,000 mg over a 6 month period) along with prophylactic antimicrobial therapy. The main objectives were to determine the safety, toxicity and clinical efficacy of this regimen.All of the patients were males with a median age of 69 years (range 49–78). The median of prior treatments was 4.5 including 4 patients that have received previously HDMP and rituximab and two patients that underwent matched unrelated donor stem cell transplant. All patients have been previously treated with rituximab, 75% of the patients failed or were intolerant to fludarabine and/or aletuzumab and 88% had high-risk disease by the modified Rai classification. Most of the patients had bulky disease with median lymph node product of 42 cms2 and median splenomegaly of 6. 5 cm (range 0–17) below the left costal margin. The median lymphocyte count was 28,000 cells/mm3. 75% of the patients had high-risk prognostic markers including unfavorable cytogenetics, unmutated IgVH region genes or high expression levels of ZAP-70.All patients completed the planned therapy with no major side effects or toxicities. There was no evidence of marrow suppression and even patients with pancytopenia improved their peripheral blood counts with this salvage regimen. During treatment patients experience significant decrease in peripheral white blood cell counts, increase in hemoglobin, elevation of platelets and a dramatic reduction in lymphadenopathy and splenomegaly. Response assessment based on the IW-CLL 2008 criteria showed that the overall response rate was 50% (4 partial remissions), 25% of patients had stable disease and the remainder showed progressive disease.Overall, these data suggest that the combination of HDMP and Ofatumumab is a safe and effective salvage regimen for high-risk CLL patients that otherwise were not candidates for additional treatment. The response rates observed for the combination of HDMP and Ofatumumab in this group of patients appear to be favorable with the majority of patients achieving a response to therapy or experiencing disease stabilization. Moreover, HDMP and Ofatumumab treatment was not associated with bone marrow suppression, which is a major limiting factor for treatment administration, making this regimen a potential valid alternative for high-risk CLL patients. Additional clinical studies of this combination are warranted. Disclosures:No relevant conflicts of interest to declare.

Prophylaxis of posttraumatic endophthalmitis

AbstractInfectious endophthalmitis is a devastating complication of open globe injuries. The incidence of culture‐positive endophthalmitis after open globe injuries varies between 0.5% and 17%. Several reports have demonstrated that delayed primary repair, dirty wound, breach of lens capsule, retained intraocular foreign body (IOFB), grade 4 injury (presenting visual acuity of worse than 5/200 to light perception), placement of primary intraocular lens, and rural setting are associated with an increased risk of posttraumatic endophthalmitis. Posttraumatic endophthalmitis is associated with its own microbiologic spectrum which is distinct from other subgroups of exogenous endophthalmitis. Posttraumatic endophthalmitis still carries a poor prognosis. Reasons for guarded prognosis include polymicrobial infection and the virulence of the infecting microorganisms. In addition, concomitant injuries may directly result in ocular damage that limits ultimate visual recovery. Because of the substantial incidence of endophthalmitis after open globe injuries, careful consideration should be given to the use of prophylactic antimicrobial therapy. The purpose of prophylaxis is to provide effective antibiotic levels as rapidly as possible against a broad range of organisms. Good coverage for most organisms is obtained with intravenous vancomycin coupled with a third generation cephalosporin, such as ceftazidime, which can penetrate the vitreous cavity in effective levels in inflamed aphakic experimental eyes. Recently, the use of prophylactic intravitreal antibiotic administration in high‐risk cases was recommended.