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Background With increased use of antibiotics in high-risk patients, the investigation of new antibiotics to cover potentially resistant pathogens is warranted. In this prospective randomized trial, we compared ceftolozane/tazobactam (C/T), a new cephalosporin/β-lactamase inhibitor, to the standard of care (SOC) for the empiric treatment of neutropenia and fever in patients with hematological malignancies. Methods We enrolled 100 patients to receive intravenous (IV) C/T or SOC antibiotics (cefepime, piperacillin/tazobactam, or meropenem) in combination with gram-positive antibacterial agents. We evaluated responses at the end of IV therapy (EOIV), test of cure (TOC; days 21–28), and late follow-up (LFU; days 35–42). Results We analyzed 47 C/T patients and 50 SOC patients. C/T patients had a higher rate of favorable clinical response at EOIV (87% vs 72%). A 1-sided noninferiority analysis indicated that C/T was at least not inferior to the SOC for favorable clinical response at EOIV (P = .002), TOC (P = .004), and LFU (P = .002). Superiority tests showed that C/T led to significantly lower rates of clinical failure at TOC (6% vs 30%; P = .003) and LFU (9% vs 30%; P = .008). C/T and SOC patients with documented infections had similar rates of favorable microbiological response. Serious adverse events leading to drug discontinuation (2% vs 0%; P = .48) and overall mortality (6% vs 4%; P = .67) were similar in both groups. Conclusions The empiric use of C/T in high-risk patients with hematological malignancies and febrile neutropenia is safe and associated with better clinical outcomes than SOC antimicrobial agents. Clinical Trials Registration NCT03485950.

Background Fiberoptic bronchoscopy with BAL (FOB) remains the cornerstone in the diagnosis of pneumonia in immunocompromised patients; however, there is no uniform agreement on the best timing for FOB, and its impact on microbiological diagnostic rate and clinical outcome has not been established. Methods Retrospective study (October 2017–December 2017, July 2018–January 2019) at MD Anderson Cancer Center. The medical records of adult patients with AML, MDS or ALL who developed pneumonia (CAP, HCAP, HAP excluding VAP) and underwent FOB were reviewed. By definition, patients who underwent FOB within 48 hours after the diagnosis of pneumonia were categorized as early FOB group. We compared demographic, clinical, microbiological data, and outcomes between two groups. Data were analyzed via χ 2, Fisher’s exact and Wilcoxon rank-sum test and logistic regression. Results Of 140 patients included, 33 patients (24%) had early FOB and 107 patients (76%) had late FOB. There was no significant difference between two groups in demographic features, radiological findings, ANC and pneumonia severity index. Microbiological diagnostic rate of FOB did not differ between early FOB and late FOB: identification of pathogenic microorganisms (33.3% vs. 36.5%, p = 0.837), bacteria (6.1% vs. 13.1%, P = 0.36), fungi (18.2% vs. 12.2%, P = 0.39) and respiratory virus (12.1% vs. 16.8%, P = 0.6), respectively (Figures 1 and 2). On univariate analysis, the duration of intravenous antibacterial therapy was shorter in early FOB, with a median duration of 8.5 days (IQR 6.5–12) in early FOB and 11 days (IQR 8–18) in late FOB (P = 0.0047) (Figure 3). Multivariable logistic regression analysis showed that late FOB (OR 3.26, 95% CI 1.41 to 7.53, P = 0.0057) and negative bacterial culture on FOB (OR 3.06, 95% CI 1.01 to 9.22, P = 0.048) were significantly associated with longer duration of intravenous antibacterial therapy (≥10 days). There was no significant difference in ICU admission, 30-day and 60-day mortality and re-admission rate. Conclusion Early FOB was associated with shorter duration of intravenous antibacterial therapy for pneumonia in acute leukemia patients, which has an important impact on both optimization of antimicrobial therapy for patients and improvement of antimicrobial stewardship. Disclosures All authors: No reported disclosures.

Herbaspirillum species are gram-negative, flagellate members of the Betaproteobacteria class of bacteria, which includes Burkholderia, Ralstonia, and other plant-associated bacteria. Most species of Herbaspirillum are nitrogen-fixing bacteria that are commonly found in the rhizosphere and colonize plants endophytically. They are found in the roots and stems of maize, rice, beans, bananas, sugar cane, pineapple, and other plants [1, 2] and they have been recovered from groundwater [3] and drinking water distribution systems [4] as well. In the published literature, Herbaspirillum species have been recovered from respiratory secretions of patients with cystic fibrosis (CF) [5, 6] and described in case reports of 4 patients with bacteremia, 2 of whom had an underlying malignancy [6–9]. Its close phylogenetic and phenotypic resemblance to Burkholderia cepacia complex led to initial misidentification in 2 of the 4 reported cases [6, 9]. To our knowledge, no outbreaks or clusters of cases have been previously reported in the literature. Between June and August 2011, we identified an initial cluster of 5 patients with bloodstream infection caused by a gram-negative bacillus, initially identified as B. cepacia complex. The isolates were susceptible to all antibiotics tested, whereas over the years, previous B. cepacia isolates recovered in our institution were resistant to at least 1 and up to 4 of the antibiotics tested. These isolates were submitted to the Cystic Fibrosis Foundation Burkholderia cepacia Research Laboratory and Repository at the University of Michigan and were subsequently reidentified as Herbaspirillum species. We conducted a joint investigation with the Texas Department of State Health Services (TDSHS) and the Centers for Disease Control and Prevention (CDC) to determine the nature and extent of the cluster of Herbaspirillum species infections. This report describes the clinical and epidemiologic findings from our investigation and provides a review of the literature.

The optimal antiretroviral therapy (ART) regimen for human immunodeficiency virus (HIV)-infected patients with cancer remains unknown, as clinical trials are lacking and published data are insufficient to guide recommendations. When concomitant use of chemotherapy and ART is anticipated, overlap of toxic effects and drug-drug interactions between chemotherapy and ART may alter the optimal choice of ART. Prospective studies are urgently needed to further define the toxic effects of combined chemotherapy and ART in HIV-positive cancer patients. Such studies should aid the development of guidelines for treatment of this population. For now, clinicians should individualize decisions regarding treatment of HIV according to clinical and laboratory findings, cancer treatment plan (chemotherapy, radiotherapy, or surgery), liver or renal disease, potential adverse drug effects (eg, rash, gastrointestinal intolerance, bone marrow suppression), and patient preference. This review focuses on what infectious disease specialists need to know to select the most appropriate ART regimens for patients receiving chemotherapy.

Background Pneumonia is one of the main causes of morbi-mortality in acute leukemia (AL) patients. The positive yield of microbiology diagnosis is still significantly low. The aim of the study was to evaluate the possible impact of use of diagnostic methods (within first 48 hours of diagnosis) in AL patients with pneumonia during chemotherapy. Methods Retrospective study (January 2017–December 2017) at MD Anderson Cancer Center. The medical records of adult patients with AML, MDS, or ALL who developed CT-confirmed pneumonia after induction or second-line chemotherapy were reviewed, including demographic, clinical, microbiology data, and outcomes. Results During 2017, 174 patients with AL developed pneumonia confirmed by CT chest. Fifty (29%) of them during induction/second-line chemotherapy: 42 (84%) AML, five (10%) MDS, and three (6%) ALL. Thirty-one (62%) showed consolidation in CT, 14 (28%) nodules, and five (10%) both findings. Mean age was 65 (SD: 11.5, range: 24–87) years with 46% males. Thirty-three (66%) patients had neutropenia (ANC48 hours after diagnosis). The patients with early bronch were sicker, with higher rate of ICU admission (42% vs. 0% in late group) and in-hospital mortality (25% vs. 8% in late group). However, those patients who underwent bronch later had a higher rate of 30-day re-admission (33% vs. 22% in early group). Conclusion Bronchoscopy/BAL was the best diagnostic test in patients with AL and CT-confirmed pneumonia, even though it was only performed in 48% of patients. Early bronchoscopy (first 48 hs) has better diagnostic yield than late bronchoscopy (>48 hs), directing the antimicrobial therapy on these patients (based on the identification of bacteria, fungus or viruses), and decreasing the 30-day re-admission rate. Disclosures J. Adachi, Merck: Grant Investigator, Research grant.

Background Resistant or refractory CMV infections are not well defined and may be associated with high morbidity and mortality in allogeneic hematopoietic cell transplant (allo-HCT) recipients. Suspicion of resistant CMV infections is usually based on suboptimal responses to antiviral agents. Methods We performed a single-center retrospective chart review (January 2010 to September 2017) of Allo-HCT recipients who had CMV genotypic testing performed for suspected antiviral resistance. Based on the results, we categorized patients as either having refractory CMV (defined as CMV viremia that fails to decrease after at least 2 weeks of appropriately dosed and delivered antiviral therapy; and in the absence of known genetic mutations to the available antiviral agents) or resistant CMV infection (defined as refractory infection with identification of genetic mutations in the UL97 and/or UL54 genes correlating with in vitro antiviral resistance). Primary outcome was all-cause mortality. Results CMV genotypic resistance analysis was performed in 97 patients. Of those, 23 had resistant (11 had UL54 gene, 10 had UL97 gene, and two had both UL54 and 97) and 74 had refractory CMV infections. The majority of patients had AML (53%), underwent matched unrelated donor transplantation (43%), and received ATG during conditioning (64%). Patients with resistant CMV infections had a greater number of prior episodes when compared with those with refractory infections and had a longer time from transplant to suspicion of resistance (P < 0.01; each). Overall, the incidence of CMV disease was 41% (25% vs. 58% affecting the lungs and 56% vs. 17% the GI tract, in resistant vs. refractory infections, respectively). All-cause mortality was 57% (61% resistant vs. 55% refractory) and CMV-attributable mortality was 11% (9% resistant vs. 12% refractory). Conclusion Our data showed that resistant CMV infections are associated with a higher rate of CMV disease. However, both resistant and refractory CMV infections had increased all-cause mortality and similar CMV-attributable mortality. There was no difference in outcomes between allo-HCT recipients who had resistant or refractory CMV infections. New treatment strategies for resistant or refractory CMV infections are needed. Disclosures S. L. Aitken, Merck: Speaker’s Bureau, Consulting fee. E. Ariza-Heredia, Oxford Immunotec: Grant Investigator, Research grant. R. Chemaly, Merck: Consultant, Research grant; Chimerix: Consultant, Research grant; Novartis: Investigator, Research grant; Oxford Immunotec: Consultant, Research grant.

Background Patients with certain types of cancer are at increased risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (ATB) because of immunosuppression. The purpose of this study was to compare the utility of the two commonly used IGRAs, QuantiFERON-TB Gold® (QFT) and T-spot.TB® (T-spot.TB), for diagnosis of LTBI or ATB in cancer patients. Methods We identified patients who had an initial IGRA during 2013 and 2014 at our institution. Along with demographic information, collected clinical data included type of underlying cancer or other condition, reason for testing, diagnosis of ATB following testing, and absolute lymphocyte count (ALC) at the time of testing. IGRA results (positive, negative, borderline, or indeterminate/invalid) were compared between patients who underwent testing with either QFT or T-spot.TB. Results A total of 356 patients had 411 QFT tests done, while 737 patients had 853 T-spot.TB tests performed. The most common underlying malignancies in the QFT and T-spot.TB groups were acute myeloid leukemia (30% and 25%, respectively) and solid tumors (28% vs. 30%, respectively). The most common reasons for testing were pre-hematopoietic-cell transplantation (HCT) screening (42% with QFT and 31% with T spot.TB) or suspected pulmonary ATB (34% with QFT and 42% with T spot.TB). In the QFT group, 145/411 (35%) tests were indeterminate, while only 96/853 (11%) tests in the T-spot.TB group were invalid (P Conclusion The frequency of an inconclusive test result is significantly higher with QFT as compared with T-spot.TB for diagnosis of LTBI or ATB in cancer patients. A low ALC is likely a contributing factor in indeterminate QFT and invalid T spot.TBresults. Disclosures E. Ariza-Heredia, Oxford Immunotec: Grant Investigator, Research grant. R. F. Chemaly, Oxford Immunotec: Consultant and Grant Investigator, Research grant.

A 28-year-old male infected with the human immunodeficiency virus (HIV) developed a pleural empyema caused by Cryptococcus neoformans. He responded well to chest-tube drainage and antifungal therapy; he received fluconazole as maintenance therapy for 1 year and has not relapsed. We reviewed the English-language literature on cryptococcal pleural effusions in patients with and without AIDS. Only three other cases of empyema, one of them in an HIV-infected patient, have been reported. A pleural-fluid cryptococcal antigen test was diagnostic in our case and should be included in the diagnostic evaluation of unexplained pleural empyema/effusion in immunocompromised patients.