Increase In Infectious Complications Research Articles

A Pilot Phase II Trial of Combining Extracorporeal Photopheresis (ECP) and Low Dose IL-2 for Treatment of Sclerodermatous Steroid Refractory Chronic Graft-Versus-Host Disease (cGvHD)

Chronic GVHD remains as the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Systemic corticosteroids are the first line of therapy, but outcomes are poor in steroid refractory (SR) patients. Previous reports show that in SR patients, IL-2 therapy results in partial response (PR) associated with increase in regulatory T cells (Tregs). ECP has been used for cGVHD with skin response rates of 40-100%. Based on non-overlapping toxicities and, we prospectively studied a combination of low dose IL-2 + ECP to treat SR-cGVHD. Patients with SR-cGVHD, were treated with low dose IL-2 (1 × 106 U/m2, daily) + ECP for 12 weeks. IL-2 was provided by Prometheus Laboratories. ECP was administered 2 times/week for 4 weeks followed by 2 treatments every 2 weeks for the next 8 weeks. The NIH consensus criteria was used to assess cGVHD severity. PBMC and plasma samples were banked at baseline and on 3-week intervals to assess regulatory T cell (Tregs) and reactive oxygen species (ROS). Of the 12 consented patients, 9 completed the study (2 were not treated due to rapid disease progression before enrollment and 1 died from sepsis at week 11). All enrolled patients (n=10) had scleroderma as the predominant cGVHD manifestation. Median age was 45.6 years (range: 23-66). Median prior lines of therapy were 4.2(range 3-6), 5 patients had prior exposure to ruxolitinib and 4 were on ECP at the enrollment. Donors were fully matched unrelated (n=8), matched sibling (n=1) or mismatched unrelated (n=1). Conditioning regimen was myeloablative (n=5) or reduced intensity (n=4). GVHD prophylaxis was tacrolimus/Sirolimus (tac/sir) (n=6), tac/methotrexate (MTX) (n=2), or Tac/sir/MTX (n=1). Of the 10 enrolled patients, 9 responded to IL-2 + ECP combination (all classified as PR). A 37% dose reduction in steroid dose was noted among 7 patients. The remaining 3 patients were on stable steroid dose at end of study. Only 1 patient had progressive cGVHD in form of scleroderma. ECP+IL-2 therapy was well tolerated with no drug related serious adverse events (SAE). Grade 3-4 AEs included grade 3 metabolic and nutrition (n=8), grade 3 anemia (n=3), and grade 4 atrial flutter (n=1). Infectious complications were noted in 3 patients (one grade 4 [sepsis]). There was a robust increase in Tregs from the baseline mean of 0.755% (range 0.08-1.88) to end of treatment 6.999% (range 0.78-17.13) [p=0.02] Fig 1. Increment in Tregs was seen in patients who were on ECP therapy prior to enrollment (n=4) and in one patient who progressed while on therapy. No correlation was found between the treatment response and ROS levels. In conclusion, the combination of ECP +IL-2 is well tolerated in patients with SR-cGVHD with no apparent increase in infectious complications or other toxicities. Clinical response correlates with a robust increase in Tregs, but no correlation was found with ROS levels.

The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey.

Infections represent a major cause of morbidity and mortality in multiple myeloma and are linked to both therapy- and disease-related factors. Although it has been suggested that the rate of infections increased since the introduction of novel agents, controversies still exist. To better assess the risk factors associated with infections in the era of novel agents, we conducted a large retrospective analysis of 479 myeloma patients treated at Jena University Hospital over a period of 12years. During their disease history, 65% of patients developed at least one infection, and 37% of therapies were associated with at least one infectious episode. The rate of infections was constant over the years, with no increase in infectious complications after the routine implementation of novel agents. Infections were mainly bacterial and strongly associated with high disease burden, relapsed disease, and treatment with high-dose chemotherapy. Varicella zoster virus (VZV) reactivations occurred late during treatment (median time between high-dose chemotherapy and VZV reactivation 6months, range 0-44months), and fewer patients developed a VZV reactivation after 2009 (p = 0.001). Infections are still one of the major causes of morbidity in myeloma patients, and prophylactic measures are urgently needed to reduce this potentially lethal complication.

Pre-operative total parenteral nutrition improves post-operative outcomes in a subset of Crohn's disease patients undergoing major abdominal surgery.

BackgroundDespite major advances in the medical management of Crohn’s disease (CD), a significant proportion of patients will require surgery within 5 years of diagnosis. Malnutrition is an independent risk factor for adverse post-operative outcomes following gastrointestinal surgery. Data on the value of pre-operative total parenteral nutrition (TPN) in CD patients are mixed and there is a paucity of data in the biologic era. We aimed to define the role of pre-operative TPN in this population.MethodsThis was a retrospective cohort study conducted at a tertiary referral center. CD patients who underwent major abdominal surgery were identified. Patients receiving pre-operative TPN were compared to controls. We compared the incidence of 30-day infectious and non-infectious post-operative complications between the two groups.ResultsA total of 144 CD patients who underwent major abdominal surgery between March 2007 and March 2017 were included. Fifty-five patients who received pre-operative TPN were compared to 89 controls. Twenty-one (14.6%) patients developed infectious complications (18.2% in TPN group vs 12.3% in non-TPN group, P = 0.34) and 23 (15.9%) developed non-infectious complications (14.5% in TPN group vs 16.9% in non-TPN group, P = 0.71). In a multivariate analysis, controlling for differences in baseline disease severity and malnutrition between groups, patients receiving pre-operative TPN for ≥60 days had significantly lower odds of developing non-infectious complications (odds ratio 0.07, 95% confidence interval: 0.01–0.80, P = 0.03). Weight loss of >10% in the past 6 months was a significant predictor of post-operative complications. ConclusionsIn a subset of malnourished CD patients, TPN is safe and allows comparable operative outcomes to controls. Pre-operative TPN for ≥60 days reduced post-operative non-infectious complications without associated increase in infectious complications.

Intraoperative hyperglycemia is independently associated with infectious complications after non-cardiac surgery

BackgroundPerioperative hyperglycemia and its associated increase in morbidity and mortality have been well studied in the critical care and cardiac surgery literature. However, there is little data regarding the impact of intraoperative hyperglycemia on post-operative infectious complications in non-cardiac surgery.MethodsAll National Surgery Quality Improvement Program patients undergoing general, vascular, and urological surgery at our tertiary care center were reviewed. After integrating intraoperative glucose measurements from our intraoperative electronic health record, we categorized patients as experiencing mild (8.3–11.0 mmol/L), moderate (11.1–16.6 mmol/L), and severe (≥ 16.7 mmol/L) intraoperative hyperglycemia. Using multiple logistic regression to adjust for patient comorbidities and surgical factors, we evaluated the association of hyperglycemia with the primary outcome of postoperative surgical site infection, pneumonia, urinary tract infection, or sepsis within 30 days.ResultsOf 13,954 patients reviewed, 3150 patients met inclusion criteria and had an intraoperative glucose measurement. 49% (n = 1531) of patients experienced hyperglycemia and 15% (n = 482) patients experienced an infectious complication. Patients with mild (adjusted odds ratio 1.30, 95% confidence interval [1.01 to 1.68], p-value = 0.04) and moderate hyperglycemia (adjusted odds ratio 1.57, 95% confidence interval [1.08–2.28], p-value = 0.02) had a statistically significant risk-adjusted increase in infectious complications. The model c-statistic was 0.72 [95% confidence interval 0.69–0.74].ConclusionsThis is one of the first studies to demonstrate an independent relationship between intraoperative hyperglycemia and postoperative infectious complications. Future studies are needed to evaluate a causal relationship and impact of treatment.

Transabdominal Versus Subcuticular Sutures to Secure a Laparoscopic Gastrostomy.

Traditional methods for securing a laparoscopic gastrostomy (LG) involve the placement of two monofilament transabdominal (TA) sutures to be removed after a short interval of 5 days. A modified technique employing an absorbable suture tunneled subcutaneously has been adopted by many surgeons. The aim of this study was to compare wound complications between these techniques. A retrospective review of patients who underwent LG placement between 2010 and 2016 was conducted, dividing patients into two cohorts by securing stitch type, TA and subcutaneous (SC), and evaluating for complications. A total of 740 children underwent laparoscopic gastrostomy tube (GT) placement, of whom 554 (75%) patients had a TA stitch and the remaining 186 (25%) had a SC stitch. Demographic data were comparable in both groups. The most common wound complication was granulation tissue (22%), dislodgement (19%), external drainage (16%), cellulitis (10%), erosion (3%), and abscess formation (2%). Seven patients required operative revision for dislodgement; TA patients comprised the majority of these patients. Operative times were significantly longer in the SC group (22 minutes versus 28 minutes, P < .05). Rates of granulation, erosion, external and internal leakage, and dislodgement were equivalent between cohorts. There were higher rates of cellulitis (7.3% versus 19%, P < .05) and abscess (0.8% versus 7.6%, P < .05) noted in the SC group. Time to external leakage was significantly earlier in the SC group (P < .05); however, all other complications occurred at comparable times following initial operation. Persistent gastrocutaneous fistula requiring surgical closure occurred at equal rates with no difference in times to closure from GT discontinuation in both groups. While both techniques are feasible, there was a significant increase in infectious complications and operative times observed in the SC stitch patients, suggesting this may not be the optimal securing method.

Three-Piece Inflatable Penile Prosthesis Placement Following Pelvic Radiation: Technical Considerations and Contemporary Outcomes

BackgroundPelvic radiation is a known risk factor for the development and progression of erectile dysfunction. When medical therapy fails, the 3-piece inflatable penile prosthesis (IPP) can offer patients a definitive treatment option. Because of radiation-induced vascular changes and tissue fibrosis, a careful surgical approach is necessary to avoid intraoperative complications and attain successful outcomes. Despite its widespread use in prostate cancer treatment, there are no contemporary studies examining the effects that pelvic radiation can have on 3-piece IPP placement and device survival. AimTo present technical considerations and contemporary outcomes of placing a 3-piece IPP for refractory erectile dysfunction in patients with a history of pelvic radiation. MethodsWe retrospectively reviewed 78 patients who underwent placement of a 3-piece IPP (AMS 700; Boston Scientific, Marlborough, MA, USA) after being treated with pelvic radiotherapy from 2003 through 2016. All patients had been treated with external beam and/or brachytherapy for treatment of prostate malignancy. An infrapubic approach was used in all patients, with reservoir placement in the space of Retzius or in the lateral retroperitoneal space. Patient demographics, perioperative data, and postoperative outcomes including prosthetic infection and mechanical failure were examined and statistical analysis was performed. OutcomesRates of device infection, revision surgery, and reservoir complications. ResultsNo intraoperative complications were observed. After a mean follow-up of 49.0 months (6.6–116.8), 2 patients developed an infection of their prosthesis that required explantation. These patients underwent successful IPP removal and immediate reimplantation. 11 patients (14.1%) required revision surgery (pump replacement, n = 4; pump relocation, n = 2; cylinder replacement, n = 4; reservoir replacement owing to leak, n = 1). No reservoir-related complications such as herniation or erosion into adjacent structures were observed. Clinical ImplicationsThe 3-piece IPP can be placed safely in a broad range of patients treated with pelvic radiotherapy. Strengths and LimitationsThis study describes contemporary long-term outcomes of the IPP in patients treated with pelvic radiation and includes patients with prior pelvic surgery and artificial urinary sphincter, which are commonly encountered in practice. It is limited by its single-center experience and lacks a comparison group of patients. Objective patient satisfaction data were not available for inclusion. ConclusionsThe 3-piece IPP can be placed successfully in patients with a history of pelvic radiation without a significant increase in infectious complications, reservoir erosion, or mechanical failure compared with the global literature.Loh-Doyle J, Patil MB, Nakhoda Z, et al. Three-Piece Inflatable Penile Prosthesis Placement Following Pelvic Radiation: Technical Considerations and Contemporary Outcomes. J Sex Med 2018;15:1049–1054.

3-Piece Inflatable Penile Prosthesis Placement Following Radical Cystoprostatectomy and Urinary Diversion: Technique and Outcomes

BackgroundAfter radical cystoprostatectomy (RC), postoperative erectile dysfunction (ED) is a common consequence with multiple contributing etiologies. The inflatable penile prosthesis (IPP) offers patients a definitive treatment option when ED is refractory to medical therapies. Because of the hostile postoperative anatomy of these patients, a careful surgical approach is necessary for successful outcomes and to avoid adjacent organ injury. To date, there is no series describing the outcomes of 3-piece IPP placement in patients with urinary diversions. AimTo present contemporary outcomes and a description of our technique in placing a 3-piece IPP for postoperative ED in patients with a history of RC with orthotopic neobladder, ileal conduit, or continent cutaneous diversion. MethodsWe retrospectively reviewed 80 patients who underwent primary placement of a 3-piece IPP (AMS 700; American Medical Systems Inc, Minnetonka, MN, USA) after RC and urinary diversion from 2003 through 2016. 79 patients underwent RC in their treatment of urologic malignancy (71 for bladder cancer, 8 for prostate cancer) and 1 underwent RC for refractory interstitial cystitis. An infrapubic approach was used in most patients, with reservoir placement in the lateral retroperitoneal space through a counterincision medial to the anterior superior iliac spine. Patient demographics, perioperative data, and postoperative outcomes including prosthetic infection and mechanical failure were examined and statistical analysis was performed. OutcomesRates of device infection, revision surgery, and reservoir complications. ResultsAfter mean follow-up of 53.9 months (6.5–150.7 months), 4 patients developed infection of the prosthesis that required explantation. 3 of those patients underwent successful IPP reimplantation. 5 patients required revision surgery (pump replacement, n = 3; pump relocation, n = 1; cylinder replacement for cylinder aneurysm, n = 1) for mechanical failure. No statistically significant associations were found between infection and comorbidities, urinary diversion, exposure to chemotherapy, radiation, or presence of an artificial urinary sphincter. Clinical ImplicationsThe 3-piece IPP is an effective treatment option for medication-refractory ED that can be placed safely in patients with all forms of urinary diversion. Strengths and LimitationsThis study represents the 1st series that describes a successful technique and long-term outcomes of patients with urinary diversion. It is limited by its single-surgeon, single-center experience and lacks validated patient satisfaction data in follow-up. ConclusionsThe 3-piece IPP, with reservoir placement in the lateral retroperitoneum, can be implanted successfully in patients with all forms of urinary diversion without a significant increase in infectious complications, reservoir erosion, or mechanical failure.Loh-Doyle J, Patil MB, Sawkar H, et al. 3-Piece Inflatable Penile Prosthesis Placement Following Radical Cystoprostatectomy and Urinary Diversion: Technique and Outcomes. J Sex Med 2018;15:907–913.

Side Effects of Long-Term Continuous Intra-arterial Nimodipine Infusion in Patients with Severe Refractory Cerebral Vasospasm after Subarachnoid Hemorrhage.

Long-term continuous intra-arterial nimodipine infusion (CIAN) is a rescue therapy option in cases of severe refractory cerebral vasospasm (CV) following acute non-traumatic subarachnoid hemorrhage (SAH). However, CIAN therapy can be associated with relevant side effects. Available studies focus on intracerebral complications, whereas extracerebral side effects are rarely examined. Aim of the present study was to generate descriptive data on the clinical course during CIAN therapy and expectable extracerebral side effects. All patients treated with CIAN therapy for at least 5days between May 2011 and December 2015 were included. We retrospectively extracted data from the patient data management system regarding the period between 2days before the beginning and 5days after the termination of CIAN therapy to analyze the course of ventilation parameters and pulmonary gas exchange, hemodynamic support, renal and liver function, integrity of the gastrointestinal tract, and the occurrence of infectious complications. In addition, we recorded the mean daily values of intracranial pressure (ICP) and intracerebral problems associated with CIAN therapy. Data from 28 patients meeting inclusion criteria were analyzed. The mean duration of long-term CIAN therapy was 10.5±4.5days. Seventeen patients (60.7%) reached a good outcome level (Glasgow Outcome Scale [GOS] 4-5) 6months after SAH. An impairment of the pulmonary gas exchange occurred only at the very beginning of CIAN therapy. The required vasopressor support with norepinephrine was significantly higher on all days during and the first day after CIAN therapy compared to the situation before starting CIAN therapy. Two patients required short-time resuscitation due to cardiac arrest during CIAN therapy. Acute kidney injury was observed in four patients, and one of them required renal replacement therapy with sustained low-efficiency daily dialysis. During CIAN therapy, 23 patients (82.1%) needed the escalation of a previous antiinfective therapy or the onset of antibiotics which was in line with a significant increase of C-reactive protein and white blood cell count. Obstipation was observed in 22 patients (78.6%). Ten patients (35.7%) even showed insufficient defecation on at least seven consecutive days. Compared to the situation before, ICP was significantly higher during the whole period of CIAN therapy. Long-term CIAN therapy is associated with diverse side effects. The leading problems are an impairment of the hemodynamic situation and cardiac problems, an increase in infectious complications, a worsening of the motility of the gastrointestinal tract, and rising ICP values. Teams on neurointensive care units must be aware of these side effects to avoid that the beneficial effects of CIAN therapy on CV reported elsewhere are foiled by the problems this technique can be associated with.

Prospective Monitoring and Adapting Strategies for Prevention of Infection Following Transrectal Prostate Procedures

IntroductionA number of strategies have been attempted to minimize the risk of infection following transrectal prostate procedures. We report our prospective efforts at augmenting our prophylaxis strategy over time. MethodsSince 2010 we have prospectively monitored infections after transrectal prostate procedures and changed our prophylaxis regimen twice in an effort to respond to increases in infectious complications. In 2011 we added a single dose of intramuscular aminoglycoside to our prophylaxis regimen of fluoroquinolones or trimethoprim-sulfamethoxazole. In 2015 we began performing formalin needle tip disinfection before each biopsy and screening high risk patients for antibiotic resistance using rectal swab cultures (targeted prophylaxis). We report our rates of infections and antibiotic resistance patterns during this period. ResultsFrom 2010 to 2016 we performed 2,398 transrectal prostate procedures. Overall there were 41 cases (1.7%) of infection related hospitalization. However, the rate differed significantly during the course of the study period. The infection related hospitalization rate declined from 3.8% to 1.1% in the first 3 years following the addition of intramuscular aminoglycoside (2011 to 2013), a decrease of 69%. In 2014 our infection rate increased to 2.6%, prompting the initiation of protocol 3, wherein the addition of target prophylaxis and formalin needle tip disinfection identified a 29.8% fluoroquinolone resistance rate and resulted in another decline in our infection rate to 1.2% (a decrease of 53%). ConclusionsWhile the initial addition of intramuscular aminoglycoside appeared to be effective in decreasing post-procedure infections, further augmentation of our prophylaxis regimen through rectal swab screening of high risk patients and formalin needle tip disinfection led to an additional decline in rates of infection related hospitalizations.

Long Term Follow up and Impact of Comorbidity Prior to Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Relapsed or Refractory AML - Lessons Learned from the Prospective Bridge Trial -

In patients with relapsed or refractory (r/r) Acute Myeloid Leukemia (AML), allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is considered to be the only treatment providing long-term disease control for fit patients. The BRIDGE trial studied the safety and efficacy of a clofarabine-based salvage therapy prior to HSCT in patients with r/r AML. Here, we report the long-term follow up of this Phase II, multi-center, Intent-To-Transplant study and the impact of comorbidity on outcome.Eighty-four patients with a median age of 61 years (range 40 - 75) were enrolled. Patients were scheduled for at least one cycle of salvage therapy with CLARA (clofarabine 30 mg/m2 and cytarabine 1 g/m2, days 1-5). Chemo-responsive patients with a donor received HSCT after first CLARA. In the event of a prolonged donor search, HSCT was performed as soon as possible. The conditioning regimen consisted of clofarabine 30 mg/m2, day -6 to -3, and melphalan 140 mg/m2 on day -2. The ECOG score, hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and Cumulative Illness Rating scale (CIRS) were obtained at study enrolment as well as prior to HSCT.Sixty-seven percent of the patients received HSCT within the trial. After a median follow up of 40months (95% CI, 38-49 months), the estimated 4-year OS (Figure 1) for all enrolled patients was 38% (95% CI, 28-50%) and Disease-Free Survival for transplanted patients was48% (95% CI, 36-64%). The CIR at four years was 30% (95% CI, 17-43%) and the NRM 22% (95% CI, 10-33%).Those patients who received an allogeneic HSCT within the trial had a median HCT-CI at the time of study enrollment of 1 (range, 0 - 6) compared to a median of 2 (range, 0 - 6) for those who did not proceed to allogeneic HSCT (p = .17). Corresponding figures for the CIRS were a median of 2 (range, 0 - 9) compared to 4 (range, 0 - 8) (p = .09). The median ECOG score was 1 (range, 0 - 3) in both groups. Compared to the time point of study enrollment, both the HCT-CI as well as the CIRS increased to a median of 2 (observed range of score, 0 - 7) and a median of 4 (observed range of score, 0 - 12), respectively, at the time of start of the conditioning regimen. This was almost exclusively due to an increase in infectious complications (Figure 2). In multivariate analysis, both the baseline HCT-CI and the ECOG score had a statistically significant impact with a HR of 1.22 (p = .025) and 1.72 (p = .001), respectively, on OS.Using a clofarabine-based salvage therapy combined with early allogeneic HSCT we were able to achieve good long-term results for patients with r/r AML. In this cohort, both the HCT-CI and the ECOG score gave prognostic information on OS, showing feasibility of comorbidity evaluation at the time of diagnose of r/r AML. [Display omitted] [Display omitted] DisclosuresMiddeke:Sanofi: Honoraria. Rösler:Janssen: Consultancy, Other: Travel/Accommodation/Expenses. Thiede:AgenDix: Employment, Other: Ownership. Schetelig:Sanofi: Honoraria.

Abstract P1-10-19: Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy

Abstract Objectives: We have maintained a local registry of skin and nail infections in patients receiving pertuzumab and trastuzumab as treatment for HER2 positive breast cancer. Over the past 16 months, we have continued to observe an increase in infectious complications in patients receiving the combination of pertuzumab and trastuzumab with or without chemotherapy. We expand a series of prospectively identified patients who developed infections while on these regimens. Methods: We became concerned about an increased incidence of infections shortly after the FDA approval of pertuzumab, and created an IRB approved registry of these patients. Results: Twenty-eight women were identified to have 32 separate infections (often at more than one site); 9 after cycle 1; 6 after cycle 2, 9 after cycle 3 and 8 after 4 or more cycles. The median age was 51 (Range 25-67); 14 received pertuzumab, trastuzumab, carboplatin, and docetaxel (PTCH), 5 pertuzumab, trastuzumab, and docetaxel, 7 pertuzumab, trastuzumab, and nab-paclitaxel, and 2 pertuzumab and trastuzumab. Folliculitis of the scalp, abdomen, and/or buttocks was observed in 19 patients, abscesses in 8 patients (4 of whom required incision and drainage) and cellulitis in 2. Severe paronychial infections involving one to 16 digits were observed in 4; 2 pt required surgical removal of 2 nails. Quantitative immunoglobulins were found to be low in 8 of 17 women tested; 2 patient had low total protein but did not have an assessment of quantitative immunoglobulins. All patients were initially treated with oral antibiotics, and 6 required hospitalization. Cultures were obtained in 10 patients; Staphylococcus aureus was identified in 4, methicillin resistant Staphylococcus aureus (MRSA) in 5, Enterococcus faecalis in 1. A 57 year old pt receiving neoadjuvant PTCH died on cycle 2 day 7. Autopsy was consistent with sepsis and gram positive cocci were identified. A 62 year old became septic and developed renal failure. Skin biopsies were performed in 3 patients and are consistent with changes associated with EGFR inhibition. Conclusions: We believe these infections are a result of combining pertuzumab with trastuzumab as 2 pts received no concurrent chemotherapy. An awareness of this complication is critical as some infections may be life-threatening. We have initiated patient education to ensure awareness of this potential complication. Citation Format: Mortimer JE, Yuan Y, Jung J, Kruper L, Stewart D, Chung S, Yu WK, Mendelsohn M, D'Apuzzo M, Tegtmeier B, Dadwal S. Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-10-19.

Improving Outpatient Antibiotic Prescribing

More than250millionoutpatient antibiotic prescriptions are written in the US each year,1 most of which are for acute respiratory tract infections.A largeproportionof theseprescriptions are unnecessary.2 Antibiotic overuse leads to unnecessary adverse drug effects and antimicrobial-resistant infections, which harm patients. To address this threat, professional organizations and regulatory agencies have called for acute care hospitals to establish antimicrobial stewardshipprograms,which are quality improvement and patientsafety initiatives tooptimize antimicrobial use.3 The vast majority of antibiotic use, however, occurs in the outpatient setting, mostly in internal medicine, familypractice, pediatric, anddental offices,1where there is virtually no formal antimicrobial stewardship. In addition, although themost resistantorganismsusually involve infections among hospitalized patients, difficult-to-treat infections such as methicillin-resistant Staphylococcus aureus and extended-spectrumbeta lactamase–producingEnterobacteriaciae arenowcommonly isolated fromcommunity-onset infections. Thus, adapting the principles of antimicrobial stewardship to the ambulatory setting should be prioritized. The appropriate use of antibiotics for the most common acute respiratory tract infections isknownbutnot followed.For example, numerous randomized trials have shown that otherwisehealthyadultsshouldnotreceiveantibiotics foracutebronchitis.However, roughly75%ofadults receiveantibiotics for this condition, a proportion that has not changed in more than 20 years.4 Even when an antibiotic is indicated, often the wrong one is chosen: roughlyhalf of antibiotics for childrenarebroadspectrum, second-line agents,5 and the most commonly prescribed antibiotic for adults is azithromycin, despite this drug being recommended as the first-line choice for relatively few conditions. So how can these issues be addressed? Changing clinician behavior is challenging. Public health campaigns help, but they are time consuming and expensive. Education is important, butwhenasked, internists andpediatricians agree that antibiotics are overused and that antibiotic resistance is a problem, but not in their practice.6 Factors other than specific medical need drive prescribing behavior. These include perceived patient (or parent) pressure,7,8 the presence of trainees,9 and even the time of day10 or the race of the patient.11 Different levers that shape clinician behavior need to be considered, especially at the point of care, when thedecision toprescribe ismade. In the acute care setting, including the ambulatory setting, behavioral determinants and social norms clearly influence antibiotic prescribing.12 For example, a simple “behavioral nudge” in the form of a signed commitment letter posted in the patient room was associatedwith a 20%reduction in inappropriate prescribing for viral acute respiratory tract infections.13 In this issue of JAMA, Meeker and colleagues14 report the results of a cluster randomized trial to reduce inappropriate antibiotic prescribing in 47 primary care practices in Boston orLosAngeles staffedby248clinicians.The investigators compared the effect of 3 different behavioral interventions that were triggered when an antibiotic was ordered for a targeted acute respiratory tract infection: suggestedalternatives,which triggeredanelectronichealth record–basedpop-upstating that “antibiotics are generally not indicated for this” and provided suggestions for nonantibiotic alternatives (eg, decongestants); accountable justification, which required the clinician to document the justification for antibiotic treatment (using free text) or, if nothing was entered, “no justification given”wouldpopulate thechart; orpeer comparison,whereby clinicianswereemailedamessagestatingthat theywerea“high performer” if their inappropriateantibioticprescribing ratewas in the topdecile and“nota topperformer” if their ratewasoutside this range. Practiceswere randomly assigned to0, 1, 2, or all 3 of the interventions and followed up for 18 months. The rate of antibiotic prescribing for upper respiratory tract infection, acute bronchitis, or influenza—all conditions for which antibiotics are not indicated—was then compared across each of the 3 intervention groups. The resultsof these simple interventionswerepromising. Over the18-month intervention, inappropriateprescribingdecreased ineachgroupsubstantially: from22%to6%withsuggestedalternatives, 23%to5%with accountable justification, and 20% to 4% with peer comparison. However, because inappropriate prescribing declined substantially in the control group (24% to 13%), the absolute between-group reductions inprescribingwereonlyapproximately5%foreachgroupand wereonly statistically significant in the accountable justificationgroup(differenceofdifferences inprescribingrates,−7.0% [95%CI,−9.1%to−2.9%];P < .001)andpeercomparisongroups (difference of differences, −5.2% [95% CI, −6.9% to −1.6%]; P < .001) but not the suggested alternative groups (difference of differences, −5.0% [95%CI, −7.8% to0.1%];P = .66). Investigatorsobservednocodeshifting fromviraldiagnoses tobacterialdiagnoses,whichcouldsimulatea reduction in inappropriate use based on the outcome definition used, and did not find a clinically significant increase in infectious complications in patients who did not receive antibiotics. Related article page 562 Opinion

Large-volume paracentesis with indwelling peritoneal catheter and albumin infusion: a community hospital study

BackgroundThe management of ascites can be problematic. This is especially true in patients with diuretic refractory ascites who develop a tense abdomen. This often results in hypotension and decreased venous return with resulting renal failure. In this paper, we further examine the risks and benefits of utilizing an indwelling peritoneal catheter to remove large-volume ascites over a 72-h period while maintaining intravascular volume and preventing renal failure.MethodsWe retrospectively reviewed charts and identified 36 consecutive patients undergoing continuous large-volume paracentesis with an indwelling peritoneal catheter. At the time of drain placement, no patients had signs or laboratory parameters suggestive of spontaneous bacterial peritonitis. The patients underwent ascitic fluid removal through an indwelling peritoneal catheter and were supported with scheduled albumin throughout the duration. The catheter was used to remove up to 3 L every 8 h for a maximum of 72 h. Regular laboratory and ascitic fluid testing was performed. All patients had a clinical follow-up within 3 months after the drain placement.ResultsAn average of 16.5 L was removed over the 72-h time frame of indwelling peritoneal catheter maintenance. The albumin infusion utilized correlated to 12 mg/L removed. The average creatinine trend improved in a statistically significant manner from 1.37 on the day of admission to 1.21 on the day of drain removal. No patients developed renal failure during the hospital course. There were no documented episodes of neutrocytic ascites or bacterial peritonitis throughout the study review.ConclusionLarge-volume peritoneal drainage with an indwelling peritoneal catheter is safe and effective for patients with tense ascites. Concomitant albumin infusion allows for maintenance of renal function, and no increase in infectious complications was noted.

Rectal swab testing before prostate biopsy: experience in a VA Medical Center urology practice.

Infectious complications following transrectal ultrasound prostate biopsy (TRUSBx) have been increasing. Pre-biopsy prophylaxis with fluoroquinolone (FQL) antibiotics is a recommended and accepted practice. Increasing emergence of FQL-resistant bacteria is believed to be related to the increase in infectious complications. We sought to determine the effect of targeted antibiotic prophylaxis (TAP) before TRUSBx on infectious complications in our practice. TAP was introduced in our practice in 2012. A retrospective analysis was performed analyzing infectious complications from TRUSBx before and after TAP was introduced. Two hundred forty-four patients underwent TRUSBx with TAP directed by bacterial antibiotic sensitivity identified on rectal swab. A group of two hundred sixty-four consecutive patients who underwent TRUSBx in our practice before introduction of TAP were chosen for comparison. Infectious complications were recorded and compared between groups. Prostate volume, PSA, number of biopsy cores, finding of prostate cancer, presence of diabetes, race and age were also compared. The infectious complication rate after TRUSBx in the pre-TAP group was 7/264 (2.65%), the rate in the TAP group was 1/244 (0.41%), a statistically significant difference (P=<0.05). There were no differences between groups in regards to prostate volume, number of prostate biopsy cores, race and presence of diabetes. The rectal swab group was younger (65.4 ± 6.0) than the non-swab group (67.9 ± 6.2), had higher PSA values, and a higher chance of prostate cancer on biopsy. The use of TAP based on rectal swab testing significantly lowered our infectious complication rate for TRUSBx. TAP is now adopted as standard practice before TRUSBx in our center. The younger age and higher chance of prostate cancer on biopsy in the rectal swab group, we believe, is due to implementation of recent guidelines directing urologists be more selective in recommending prostate biopsy to older men.

Prise en charge nutritionnelle en réanimation : choc septique

Major stress such as severe trauma, infection or postoperative state, is frequently associated with increased catabolism and energy expenditure. These contribute to fat-free mass loss. The increase of energy debt in the first week of intensive care unit (ICU) stay is associated with an increase in infectious complications and length of mechanical ventilation and ICU stay. When oral intake is insufficient to cover nutritional needs after the three first days of ICU stay, enteral nutrition (EN) is the first choice and should be started within 24hours. The volume of daily EN should be gradually increased to reach the target within 48hours (20–25kcal/kg/day). Protein provision must be 1.2–1.5g/kg/day. However, enteral feeding could be poorly tolerated by ICU patients due to impaired gastrointestinal motility. In case of gastroparesis, prokinetics can be administered according to previously established protocol. Nevertheless, the use of supplemental parenteral nutrition (PN) or jejunal EN could be necessary in case of failure or insufficient gastric EN. In the ICU, enteral immunonutrition is not indicated because of the absence of additional benefits. Undernutrition prior to admission is likely to worsen during the ICU stay. In case of preexisting undernutrition, the risk of refeeding syndrome is high. EN must be increased very cautiously under tight monitoring of plasma electrolytes, including phosphates, potassium, sodium, calcium, and magnesium. An electrolyte supplementation is warranted in case of plasma deficiencies, along with vitamins and trace elements. Nutrition support is taking part of the management of the ICU patient, as ventilation and hemodynamics. Specific nutritional monitoring is essential to prevent any risk of over- or undernutrition, and to optimize clinical outcome.

Rituximab Maintenance after Chemoimmunotherapy Induction in 1st and 2nd Line Improves Progression Free Survival: Planned Interim Analysis of the International Randomized AGMT-CLL8/a Mabtenance Trial

▪Introduction: Chemoimmunotherapy has become a standard approach in previously untreated and also in pretreated CLL. Addition of Rituximab to FC in fit patients has proven superior to chemotherapy alone and more recently aCD20 treatment was shown to improve outcomes in patients treated with Chlorambucil, suggesting that immunotherapy may be of benefit, independent of the chosen chemotherapy backbone. In follicular and mantle cell lymphoma rituximab maintenance treatment has become a clinical standard. While we and others have presented Phase II data on the feasibility of Rituximab maintenance after chemoimmunotherapy induction, there are currently no available randomized data on the efficacy of such an approach.Study design: Patients were recruited after informed consent at the end of any Rituximab-containing induction treatment in 1st or 2nd line that achieved at least a PR. Excluded were patients with uncontrolled bacterial or viral infections and conditions that might severely affect life-expectancy (such as other malignancy, heart disease etc). The trial was registered at clinicaltrials.gov with the identifier NCT01118234. Randomization was stratified by country, line of treatment, induction response and type of induction regimen. Primary endpoint was PFS and a planned sample-size of 256 patients was calculated. All patients were recruited in participating centers between September 2009 and December 2013. An interim analysis was planned to be conducted after half of the planned events (i.e. 46) were observed and is presented here.Results: The current analysis includes 263 patients enrolled into the trial. Patients had a median age of 63 years, 28.9% were female and 80.6% were enrolled after 1st induction treatment. Hierarchical FISH cytogenetic risk was available in 221 patients: del17p 3.1%, del11q 27.6%, tris 12 10.8%, del13q 36.2%, and normal FISH karyotype 21.2%. IgVH Mutation state was available in 161 patients at time of interim analysis and 67% were unmutated. The induction regimen was FCR in 73.5% and BR in 20.2%, the response to induction treatment was CR/CRi in 58% and PR in 41.8% of patients and 57% scored negative in an 8-colour MRD flowcytometric analysis after induction. Rituximab treatment was allocated to 134 patients and 129 were in the observation arm. No significant imbalances in randomization were found in the above-mentioned parameters. Median observation time is currently 17.3 months. Regarding toxicities the current state of monitoring allows an analysis on the level of SAEs only. SAE causes were well balanced between arms with the exception of infectious SAEs - 32 in the rituximab and 22 in the observation arm, 3 deaths were attributed to infections (1 in the rituximab arm and 2 in the observation arm) - and secondary malignancies (8 in the rituximab arm vs. 1 in the observation arm). Four of the neoplasms in the rituximab arm were localized non-melanoma skin cancers and the 2 deaths from malignomas occurred one in each arm. Regarding efficacy, currently 27.9% have progressed in the observation arm and 14.9% in the rituximab arm. Ten patients died in the observation arm and 7 in the rituximab arm. The primary endpoint (PFS) is significantly in favour of rituximab maintenance (see Fig) with a p-value of 0.007 and a PFS at 17.3 months of 85.1% vs.75.5% in rituximab vs. observation arms, respectively. To account for toxicities and secondary neoplasms an EFS was calculated counting secondary malignancies, termination of treatment due to toxicities, progression or death as events. In this analysis the benefit was preserved, albeit with a lower p-value of 0.03. The observed benefit seemed independent from response after induction (CR vs. PR), but associated with positive MRD state after induction. Further factors that influenced the benefit in exploratory subgroup analyses were sex, cytogenetics, IgVH and B-symptoms at diagnosis.Conclusions: Rituximab maintenance after chemoimmunotherapy induction in CLL seems feasible, although with an increase in infectious complications, and shows signs of efficacy in this interim analysis. The presented interim analysis refutes the alternative hypothesis and allows the trial to continue. Exploratory analyses suggest that with longer follow-up it may be possible to define subpopulations with larger benefit from extended immunotherapy. [Display omitted] DisclosuresGreil:Roche: Honoraria; Pfizer: Honoraria, Research Funding; Boehringer-Ingelheim: Honoraria; Astra-Zeneca: Honoraria; Novartis: Honoraria; Genentech: Honoraria, Research Funding; Janssen-Cilag: Honoraria; Merck: Honoraria; Mundipharma: Honoraria, Research Funding; Eisai: Honoraria; Amgen: Honoraria, Research Funding; Celgene: Consultancy, Research Funding; Cephalon: Consultancy, Honoraria, Research Funding; Bristol-Myers-Squibb: Consultancy, Honoraria; Sanofi Aventis: Honoraria; GSK: Research Funding; Ratiopharm: Research Funding. Off Label Use: Rituximab in Maintenace Treatment of CLL. Kozak:Roche: Honoraria, Travel grants Other. Girschikofsky:Pfizer: Honoraria, Research Funding; Mundipharm: Consultancy, Honoraria. Petzer:Celgene: Honoraria, unrestricted grant Other. Egle:Roche: Honoraria, Research Funding, Travel Grants Other.

A Systematic Review of the Use of Rituximab for Desensitization in Renal Transplantation

Rituximab is a B lymphocyte-depleting agent used to treat lymphoma and autoimmune diseases. Recently, it has been used for desensitization therapy in ABO-incompatible and highly sensitized recipients undergoing renal transplantation. A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Four databases and three trial registries were searched for studies comparing rituximab with non-rituximab desensitization protocols. A lack of randomized evidence precluded meta-analysis, and thus a narrative review was conducted. Forty-five records met the inclusion criteria, relating to 21 individual studies (two randomized controlled trials and 19 retrospective cohort studies). Ten studies investigated the use of rituximab in ABO-incompatible patients; most found no significant differences in patient and graft outcomes when compared most frequently to splenectomy-based protocols. Nine studies of limited quality focused on highly sensitized recipients (positive cross-match, donor-specific antibody, and elevated panel reactive antibody) and demonstrated some benefits in graft survival, acute and chronic rejection, and sensitization levels with rituximab. The remaining two studies combined ABO-incompatible and highly sensitized recipients and found no statistically significant increase in infectious complications with rituximab. Evidence of limited quality was identified to support the use of rituximab desensitization in highly sensitized recipients. Among ABO-incompatible recipients, rituximab was found to be equivalent to splenectomy, indicating that this invasive surgical procedure is not necessary. Further randomized controlled trials are required to better define the efficacy, long-term safety, and optimal dosing regimen of rituximab in this setting.

Which Cannulation Technique for Which Patient

Cannulation of arteriovenous (AV) access is a crucial part of vascular access management in hemodialysis patients. It can significantly affect survival of the AV access, and consequently, it probably influences patient survival. The best type of cannulation technique, rotating site versus constant site (or buttonhole), is currently debated, but the increase in infectious complications observed with the buttonhole technique suggests a prudent use of this technique, restricting it to specific patients. Even in cases with a specific indication, the balance between advantages of the constant site needling and the potentially severe consequences of access related systemic infection should be considered. Educational efforts in improving cannulation skills of dialysis staff are important for improving outcomes, as the proper use of the rotating site technique might still be the best approach to cannulation.

Effective Control of an Outbreak of Sepsis After Prostate Biopsy Using Antibiogram-Guided Antimicrobial Prophylaxis

Abstract Background: The emergence of strains of Escherichia coli (E. coli) that are resistant to fluoroquinolones (FQ) has resulted in an increase in infectious complications associated with transrectal ultrasound-guided prostate biopsy (TRUSPB). Two strategies have been proposed to deal with the increase: broadening the antimicrobial coverage and individualizing prophylaxis using transrectal swab cultures. This article describes an alternative strategy, one that adjusts TRUSPB prophylaxis, using the local antibiogram as a guide. Methods: In 2012, screening software for electronic medical records facilitated the identification of seven patients who presented with sepsis within 10 days of a TRUSPB at the Bruce W. Carter Department of Veterans Affairs Medical Center in Miami, Florida. At the time, TRUSPB antimicrobial prophylaxis consisted of oral ciprofloxacin and an intramuscular dose of gentamicin. The outbreak of TRUSPB-associated sepsis between January and June 2012 prompted a reassessment of this reg...

Successful Management Of Calcineurin Induced Thrombotic Microangiopathy(TMA) With Eculizumab After Non- Renal Solid Organ Transplantation

Thrombotic microangiopathy (TMA) is seen in up to 30% of patients receiving solid organ transplantation and almost always occurs in the setting of calcineurin inhibitor (CNI) therapy. The underlying pathophysiology of calcineurin induced TMA is poorly understood. Long term follow up in non renal transplant patients with TMA suggests that in spite of plasma exchange therapy the 1 year mortality following TMA is up to 70%.Between November 2010 and August 2012, 7 patients at our institution who underwent organ transplants ( 5 small bowel, 2 orthotopic liver) developed clinical and laboratory evidence of TMA while receiving CNI therapy. TMA was diagnosed from 3 to 13(median 11) months post transplant and none of the patients responded symptomatically or by laboratory parameters to a reduction in dose of CNI. Other unsuccessful therapies included substitution of other immunosuppressive agents (N=1) and 11 daily plasma exchanges (N=1). At the time of TMA diagnosis notable laboratory values included platelets 22-73 (median 46) K/UL, hemoglobin 4.5 to 8.1(median 6.9) GM/DL, serum creatinine 1.16-5.4 (median 2.66)MG/DL, LDH 262-2903(median 435) Units/L, and ADAMSTS13 37-137%. All patients had a negative DAT, schistocytes on peripheral smear and all but one had undetectable haptoglobin. ( Table 1 ) Clinical symptoms at diagnosis included nausea, vomiting, abdominal pain, fever, hypertension, cerebral vascular accident (N=1), acute coronary syndrome (N=1). None of the patients had evidence of graft rejection on biopsy of the transplanted organ at the time of TMA diagnosis however 2 patients with small bowel transplants had pathologic evidence of ischemic changes and vascular thrombi on biopsy of the small bowel graft.Table 1Comparison of Medians of TMA Laboratory ParametersMedian ValuesPreTransplantTMA Diagnosis4 weeks post eculizumabPlatelet count K/UL12046202Hemoglobin GM/DL11.06.99.0Serum Creatinine MG/DL0.832.661.7LDH Units/L174435322HaptoglobinNT<3190Eculizumab is a monoclonal antibody which binds with high affinity to C5 and is highly effective in disorders associated with abnormalities in the regulation of complement such as paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome (aHUS) another TMA disease. Due to the clinical and laboratory similarities of post transplant CNI associated TMA and aHUS all patients in our series were treated with the standard induction dose of eculizumab 1200mg weekly for 4 weeks and 900mg every 2 weeks thereafter. Treatment duration ranges from 4 weeks to 107 weeks. All patients were successfully maintained on adequate immunosuppression with calcineurin inhibitor (tacrolimus in all cases) to inhibit graft rejection. All patients demonstrated a rapid and complete resolution of laboratory and clinical manifestations of TMA. After the fourth dose of eculizumab platelet counts ranged from 104-291(median 202), hemoglobin 8.1-10.9(median 9.0), serum creatinine 0.70-4.08(median 1.7), LDH 157-475(median 322) and haptoglobin 23-204(median 90). Only 1 of the 4 patients requiring dialysis at TMA diagnosis remained on dialysis at 4 weeks of therapy.( Table 1) No patients show evidence of recurrent TMA or increase in infectious complications on continued eculizumab plus calcineurin inhibitor therapy at greater than 2 years of eculizumab therapy.The excellent clinical and laboratory response of our patients to eculizumab strongly suggests a central role for complement dysregulation in the pathophysiology of calcineurin induced TMA. There are multiple theories regarding the mechanism by which CNIs induce complement dysregulation including: (1) an underlying genetic predisposition to complement dysregulation worsened or exacerbated by CNI therapy, (2) CNI therapy may induce widespread and significant endothelial damage which serves as a stimulus for chronic complement activation, or (3) chronic over stimulation of complement production secondary to CNI inhibition of T-cell function .While the mechanism remains to be elucidated the clinical implications seem clear: CNI induced TMA is mediated by complement and is treated very effectively with eculizumab allowing patients to continue on graft function preserving CNI therapy. Disclosures:Broome:Alexion Pharmaceuticals: Honoraria, Speakers Bureau. Off Label Use: Eculizumab for the treatment of calcineurin induced TMA.