BackgroundWe report a case of prosthetic hip joint infection in a heart transplant recipient due to Anaerobiospirillum succiniciproducens, a genus of spiral-shaped curved anaerobic gram-negative rod which colonizes the gastrointestinal tract of cats and dogs. Invasive infections in humans are rare and typically occur in immunocompromised hosts.Case presentationA 65-year-old male dog breeder with a history of rheumatoid arthritis, bilateral hip arthroplasties, and non-ischemic cardiomyopathy with a heart transplant 10years ago presented with a three month history of progressive left hip pain and frank purulence on hip aspiration. He underwent irrigation and debridement of the left hip and one-stage revision with hardware exchange. Although gram stain and culture from synovial fluid and intraoperative cultures were initially negative, anaerobic cultures from tissue specimens later grew a spiral-shaped gram-negative rod, identified as Anaerobiospirillum spp. by 16S rRNA gene sequencing. The patient was treated with ceftriaxone 2g daily for 6weeks with a good response to treatment. A similar organism was unable to be isolated from culture of 2 of the patient's dogs, however, they were thought to be the most likely source of his infection.ConclusionAnaerobiospirillum spp. should be considered in immunocompromised patients with exposure to dogs or cats who present with bacteremia, gastrointestinal infection, pyomyositis, or prosthetic joint infections, especially in cases of culture-negative or with anaerobic culture growth.

Abstract Introduction Clostridium difficile infection (CDI) is a major cause of morbidity and mortality in hospitalized patients. In autologous stem cell transplant (ASCT) recipients the national estimated incidence is approximately 5% to 10%. The use of antibacterial agents, such as ciprofloxacin, which historically has been used as a prophylactic agent in our autologous stem cell transplant population, is considered to be a risk factor for developing CDI. However, there have been few studies that have investigated the relationship of prophylactic antibiotics in the ASCT population and the development of CDI. One study, Satlin et al, found fluoroquinolone prophylaxis in ASCT patients decreased the rate of febrile neutropenia and blood stream infections and also a possible increase in the rate of CDI. Methods To attempt to decrease the incidence of CDI, our institution made a change to our standard of practice and suspended the utilization of CIP (500 mg twice daily beginning on the day zero and continued until engraftment or antibiotic escalation) for antibacterial prophylaxis in our ASCT population. All patients received antiviral and antifungal prophylaxis at baseline and broad-spectrum anti-pseudomonal antibacterial agents at the first recorded febrile event or as clinically necessary. CDI testing was completed when patients had three or more liquid stools in a 24-hour period along with other symptoms (i.e., fever, abdominal pain). Patients were found to have a CDI when the stool sample resulted positive while experiencing correlative symptoms. Stool samples were assessed for Clostridium difficile with the Cepheid GeneXpert NAAT. We retrospectively collected data on patients who received CIP prophylaxis from June 2016 - June 2017 and compared it to patients who did not receive CIP prophylaxis from July 2017 - June 2018. Data were analyzed using Chi-squared and T-tests were used to assess for significance and logistic regression was utilized to assess for possible associations between patient characteristics (age, race, sex, diagnosis, and conditioning regimen) and CDI. Results A total of 116 ASCT patients were analyzed; the median age was 57 years old and the most common diagnoses were multiple myeloma, non-Hodgkin's lymphoma, and Hodgkin's lymphoma; 57 patients received CIP antibacterial prophylaxis and 59 patients received no antibacterial prophylaxis. The most common conditioning regimens include melphalan (60%) and BEAM with or without rituximab (22%). CDI occurred in 15% of patients who did not receive CIP prophylaxis and 18% of patients who received prophylaxis (p=0.739). Of note, 88% of patients in both groups were tested for CDI. Neutropenic fever occurred significantly more often in patients who did not receive prophylaxis, 64% vs 35% (p=0.003). The rates of bacteremia were also found to be significantly higher in the non-CIP group, 32% vs. 12% (p=0.01). Gram-negative bacteria blood isolates were increased in patients not receiving CIP prophylaxis, 19% vs. 7% (p=0.062). Interestingly, there was also an increase in the occurrence of gram-positive bacteremia isolates, 19% vs. 5% (p=0.03). The average length of hospital stay was 19 days for both groups and intensive care unit admissions were similar between the two groups, 14% vs. 11% (p=0.616). Conclusion The lack of CIP prophylaxis in ASCT did not significantly decrease the rate of CDIs. With the removal of antibacterial prophylaxis, there was a significant increase in the rate of neutropenic fever and bacteremia, specifically gram-positive bacteremia. Hospital length of stay and admissions to the intensive care unit were similar between the groups. No additional risk factors were determined to be associated with the development in CDI in the patient population. Based on the results of this study, our institution reinstituted the utilization of CIP prophylaxis. Future studies include the utilization of antibody prophylaxis for CDI and also assessing Clostridium difficile colonization and its effect on developing an active clinical infection. Disclosures No relevant conflicts of interest to declare.

Cryptococcus neoformansis an opportunistic yeast present in the environment. Practitioners are familiar with the presentation and management of the most common manifestation of cryptococcal infection, meningoencephalitis, in patients with AIDS or other conditions of immunocompromise. There is less awareness, however, of uncommon presentations where experience rather than evidence guides therapy. We report a case of primary cutaneous cryptococcosis (PCC) in a patient who had been immunosuppressed by chronic high-dose corticosteroid for the treatment of severe asthma. This case highlights the importance of early recognition of aggressive cellulitis that fails standard empiric antibiotic treatment in an immunocompromised patient. It also demonstrates successful treatment of PCC with a multispecialty approach including local debridement and fluconazole monotherapy.

Pneumonia remains one of the major disease entities practicing physicians must manage. It is a leading cause of infection-related morbidity and mortality in all age groups, and a leading cause of death in those older than 65 years of age. Despite its frequency and importance, clinical questions have remained in the therapy of community-acquired pneumonia including when to start antibiotics, when to stop them, who to treat, and what agents to use. Answers to these questions have involved historical practice, mythology, and science-sometimes good science, and sometimes better science. How clinical decisions are made for patients with community-acquired pneumonia serves as an illustrative model for other problem areas of medicine and allows for insight as to how clinical decisions have been made and clinical practice established.

Abstract 3797 Introduction and Goals. Clostridium difficile infection (CDI) is increasing in frequency and severity. Risk factors for severity of illness and treatment recommendations for patients with concurrent aggressive hematologic malignancies have not been investigated, despite data showing that this population experiences a high rate of CDI. The goal of this study was to assess mortality associated from CDI as well as risk factors for severe CDI in a population of patients with acute hematologic malignancies. Methods. Ninety-three cases of CDI among 78 patients with active acute leukemia or aggressive lymphoma at the University of Virginia (UVa) Health System from 2004–2009 were studied retrospectively. Rates of all-cause mortality, attributable mortality secondary to CDI (defined as CDI with at least one of the following: active diarrhea, toxic megacolon, or pseudomembranes on colonoscopy at time of death), and a composite outcome (defined as at least one of the following: attributable mortality, ICU stay from CDI, pseudomembranous colitis, toxic megacolon, or colectomy) were assessed as adverse outcomes. The following potential risk factors for severe CDI were investigated, adjusting for age: onset and duration of neutropenia, exposure to high dose cytarabine, number of antimicrobials given, exposure to fluoroquinolone prophylaxis for neutropenic fever, and a designation of severe CDI as previously described (at least two of the following: white blood count >15,000 cells/mL, age >60 years, albumin 38.3° C, or one of the following: ICU stay or pseudomembranous colitis). Results. All-cause mortality was 21.7%. CDI-attributable mortality was 14.1%. The rate of the composite outcome was 20.3%. All-cause mortality was higher in patients with leukemia and lymphoma than for all other patients hospitalized at this institution with CDI in 2008 (12.5% all-cause mortality, 76/610, p=0.015, 95% CI [13.2, 32.6]). Duration of neutropenic episode >14 days and neutropenia at diagnosis of CDI were associated with increased risk of attributable mortality (OR 3.12, 95% CI [0.82, 11.92], p=0.09; OR 3.39, 95% CI [0.57, 20.05], p=0.11). Cumulative duration of neutropenia >21 days was not associated with increased risk in adverse outcomes. Designation of severe CDI predicted an increase in all-cause mortality (OR 6.7, 95% CI [2.1, 21.5], p Discussion. Patients with acute hematologic malignancies and concurrent CDI were at increased risk of all-cause and CDI-attributable mortality compared with similar data from UVa of all hospitalized patients. Prolonged neutropenia at time of CDI diagnosis was associated with an increased risk of CDI-attributable mortality, although this result was not statistically significant. Established criteria for diagnosing severe CDI were helpful at predicting poor outcomes in this population. Seven of the 10 neutropenic patients who died in this study did not receive oral vancomycin. Neutropenic patients with CDI may benefit from initial treatment with oral vancomycin instead of metronidazole, especially if other criteria for severe illness are present. Future research may assess effectiveness of oral vancomycin as initial treatment for CDI in neutropenic patients. Disclosures: No relevant conflicts of interest to declare.

Pneumonia in the elderly remains a major source of morbidity and mortality in an age group that is growing in numbers. It remains unclear whether the propensity of older adults to develop community-acquired pneumonia represents an aging of host defenses, secondary effects of comorbid disease, or both. The signs and symptoms of pneumonia in the elderly are more subtle than in younger populations, which may lead to a delay in diagnosis. Although therapy for community-acquired pneumonia in the elderly is the same as for younger populations, mortality is higher, leading to an important role for prevention.

BACKGROUND Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. METHODS We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. RESULTS Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04; P=.006). The differences in response between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment (patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. CONCLUSIONS Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy.

Received 6 September 2006; accepted 6 September 2006;electronically published 13 September 2006.Author affiliations are listed at the end of the text.Reprints or correspondence: Dr. Elias J. Anaissie, MyelomaInstitute for Research and Therapy, University of Arkansasfor Medical Sciences, 4301 W. Markham, Slot 816, LittleRock, AR 72205 (anaissieeliasj@uams.edu).

remains high at 12%, and even higher rates are observed in the elderly, patients debilitated by comorbid disease, and those requiring intensive care. The clinical challenge in caring for patients with pneumonia involves the lack of definitive tests to establish a cause; signs, symptoms, and physical findings that do not differentiate bacterial pneumonia from pneumonia caused by "atypical agents"; and the fact that therapy must be started before a cause can be identified. New agents that cause pneumonia continue to be found. In addition, more diverse patient groups are being appreciated, each with its own demographic and epidemiologic characteristics, means of presentation, and likely etiologic agents. (See article on CAP in the elderly, page 18.) While Streptococcus pneumoniae remains the most likely cause of CAP, both the debate on the importance of penicillin resistance (and coresistance to other

We investigated the clinical characteristics and treatment of patients with a distinctive triad of acute infusion-related reactions (AIRRs) to liposomal amphotericin B (L-AMB) via single-center and multicenter analyses. AIRRs occurred alone or in combination within 1 of 3 symptom complexes: (1) chest pain, dyspnea, and hypoxia; (2) severe abdomen, flank, or leg pain; and (3) flushing and urticaria. The frequency of AIRRs in the single-center analysis increased over time. Most AIRRs (86%) occurred within the first 5 min of infusion. All patients experienced rapid resolution of symptoms after intravenous diphenhydramine was administered. The multicenter analysis demonstrated a mean overall frequency of 20% (range, 0%-100%) of AIRRs among 64 centers. A triad of severe AIRRs to L-AMB may occur in some centers; most of these reactions may be effectively managed by diphenhydramine administration and interruption of L-AMB infusion.

Infection in the neutropenic patient has remained a major clinical challenge for over three decades. While diagnostic and therapeutic interventions have improved greatly during this period, increases in the number of patients with neutropenia, changes in the etiologic agents involved, and growing antibiotic resistance have continued to be problematic. The evolving etiology of infections in this patient population is reviewed by Dr. Donowitz. Presently accepted antibiotic regimens and practices are discussed, along with ongoing controversies. In Section II, Drs. Maki and Crnich discuss line-related infection, which is a major infectious source in the neutropenic. Defining true line-related bloodstream infection remains a challenge despite the fact that various methods to do so exist. Means of prevention of line related infection, diagnosis, and therapy are reviewed. Fungal infection continues to perplex the infectious disease clinician and hematologist/oncologist. Diagnosis is difficult, and many fungal infections will lead to increased mortality even with rapid diagnosis and therapy. In Section III, Dr. Pappas reviews the major fungal etiologies of infection in the neutropenic patient and the new anti-fungals that are available to treat them. Finally, Dr. Rolston reviews the possibility of outpatient management of neutropenic fever. Recognizing that neutropenics represent a heterogeneous group of patients, identification of who can be treated as an outpatient and with what antibiotics are discussed.