Search

BACKGROUND Human metapneumovirus (hMPV) causes upper and lower respiratory tract infections (URIs and LRIs, respectively) in healthy and immunocompromised patients; however, its clinical burden in patients with cancer remains unknown. METHODS In a retrospective study of all laboratory-confirmed hMPV infections treated at the authors’ institution between April 2012 and May 2015, clinical characteristics, risk factors for progression to an LRI, treatment, and outcomes in patients with cancer were determined. RESULTS In total, 181 hMPV infections were identified in 90 patients (50%) with hematologic malignancies (HMs), in 57 (31%) hematopoietic cell transplantation (HCT) recipients, and in 34 patients (19%) with solid tumors. Most patients (92%) had a community-acquired infection and presented with URIs (67%), and 43% developed LRIs (59 presented with LRIs and 19 progressed from a URI to an LRI). On multivariable analysis, an underlying HM (adjusted odds ratio [aOR], 3.11; 95% confidence interval [CI], 1.12-8.64; P = .029), nosocomial infection (aOR, 26.9; 95% CI, 2.79-259.75; P = .004), and hypoxia (oxygen saturation [SpO2], ≤ 92%) at presentation (aOR, 9.61; 95% CI, 1.98-46.57; P = .005) were identified as independent factors associated with LRI. All-cause mortality at 30 days from hMPV diagnosis was low (4%), and patients with LRIs had a 10% mortality rate at day 30 from diagnosis; whereas patients with URIs had a 0% mortality rate. CONCLUSIONS hMPV infections in patients with cancer may cause significant morbidity, especially for those with underlying HM who may develop an LRI. Despite high morbidity and the lack of directed antiviral therapy for hMPV infections, mortality at day 30 from this infection remained low in this studied population. Cancer 2017;123:2329–2337. © 2017 American Cancer Society.

Background Morbidity and mortality from Mycobacterium tuberculosis (Mtb) infection remain significant in cancer patients. We evaluated clinical characteristics, management, and outcomes in patients with active Mtb infection at our institution who had cancer or suspicion of cancer. Methods We retrospectively examined medical records of all patients with laboratory-confirmed active Mtb infection diagnosed between 2006 and 2014. Results A total of 52 patients with laboratory-confirmed active Mtb infection were identified during the study period, resulting in an average rate of 6 new cases per year. Thirty-two (62%) patients had underlying cancer, while 20 (38%) patients did not have cancer but were referred to the institution because of suspicion of underlying malignancy. Among patients with cancer, 18 (56%) had solid tumors; 8 (25%) had active hematologic malignancies; and 6 (19%) had undergone hematopoietic-cell transplantation (HCT). Patients with and without cancer were overall similar with the exception of median age (61 years in cancer patients compared to 53 years in noncancer patients). Pulmonary disease was identified in 32 (62%) patients, extrapulmonary disease in 10 (19%) patients, and disseminated disease in 10 (19%) patients. Chemotherapy was delayed in 53% of patients who were to receive such treatment. Eleven patients (all of whom had cancer) died; 3 of these deaths were attributable to Mtb infection. Conclusions Although not common, tuberculosis remains an important infection in patients with cancer. Approximately one-third of patients were referred to our institution for suspicion of cancer but were ultimately diagnosed with active Mtb infection rather than malignancy.

The burden of invasive fungal infections is alarming worldwide. The aim of this paper is to review the published literature and evaluate the knowledge gap pertaining to studies on invasive fungal infections in the countries of the Arab League. Few countries from this region have published reports. The most commonly studied invasive fungal infections is invasive candidiasis. Candida albicans remains overall the most common causative pathogen (33.8–60%), however, non-albicans Candida species are increasing. Antifungal susceptibility testing is non-standardized across the published studies. Data on aspergillosis and other fungal infections is scarce. This sheds light on the need for standardized surveillance in the region encompassing more countries of the Arab League to guide diagnostic approach and empiric therapy.

Hematopoietic cell transplant (HCT) recipients have lower immune response to influenza vaccination and are susceptible to lower respiratory tract infection (LRI) and death. We determined clinical characteristics and outcomes of laboratory-confirmed influenza, including 2014/H3N2 infection, in 146 HCT recipients. An immunodeficiency scoring index (ISI) was applied to identify patients at high risk for LRI and death. Thirty three patients developed LRI (23%), and 7 died within 30 days of diagnosis (5%). Most patients received antiviral therapy (83%); however, only 18% received it within 48 hours of symptom onset. The incidence of LRI was significantly higher in the ISI high-risk group than in the low-risk group (P < 0.001). Receiving early antiviral therapy was associated with a substantial reduction in LRI for all ISI risk groups with the greatest risk reduction observed in the high-risk group. When compared to previous seasons, no significant differences in patient outcomes were observed during the 2014/H3N2 season; however, antiviral therapy was more promptly initiated in the latter season. The ISI that was originally developed for respiratory syncytial virus may help identifying HCT recipients at risk for progression to LRI and mortality following influenza infection. These patients should be monitored more closely. Early initiation of antiviral therapy for influenza in HCT recipients, irrespective of the ISI risk group, may improve morbidity as well as mortality.

Background Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is associated with high mortality in patients with hematologic malignancies (HM). We sought to determine whether allogeneic hematopoietic cell transplant (allo-HCT) recipients would be at higher risk for 60-day mortality. Methods We examined a retrospective cohort of adults with HM with or without HCT treated for RSV LRTI (n = 154) at our institution from 1996-2013. We defined possible RSV LRTI as RSV detected only in the upper respiratory tract with new radiologic infiltrates and proven RSV LRTI as RSV detected in BAL fluid with new radiologic infiltrates. Immunodeficiency Scoring Index (ISI) and Severe Immunodeficiency (SID) criteria were calculated for HCT recipients. Multivariable logistic regression analyses were performed to identify independent risk factors associated with 60-day all-cause mortality. Results Mortality was high in HM patients (25%), but there was no difference between those without HCT, autologous or allo-HCT recipients in logistic regression models. Separate multivariate models showed that at RSV diagnosis, neutropenia (OR 8.3, 95% CI 2.8-24.2, P = 0.005) and lymphopenia (OR 3.7, 95% CI 1.7-8.2, P = 0.001) were associated with 60-day mortality. Proven LRTI was associated with higher 60-day mortality (neutropenia model: OR 4.7, 95%CI 1.7-13.5; lymphopenia model: OR 3.3, 95% CI 1.2-8.8), and higher ICU admission. In HCT recipients, high ISI and very severe immunodeficiency by SID criteria were associated with higher 60-day all-cause mortality. Conclusions Mortality is similarly high among HM patients without HCT and HCT recipients. High-grade immunodeficiency and detection of RSV from BAL fluid are associated with higher 60-day mortality.

INTRODUCTION: Pulmonary impairment predicts increased mortality in many settings, and respiratory viral infection (RVI) causes considerable morbidity and mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT). We hypothesized that pulmonary impairment following respiratory viral infection, defined as a decline of forced expiratory volume in 1 second values by ≥10%, may identify allo-HCT recipients at high risk for mortality. METHODS: We studied all allo-HCT recipients at our institution who had RVI with respiratory syncytial virus, parainfluenza virus, or influenza from 2004-2013 and had pre-RVI and post-RVI pulmonary function tests. We used competing risk regression models to identify risk factors for 2-year non-relapse mortality (NRM) as the primary outcome after RVI and relapse-related mortality as a competing risk. RESULTS: From 223 eligible patients, pulmonary impairment following RVI was associated with over a 3-fold increase in 2-year NRM (pulmonary impairment: 25.3%; no impairment: 7.4%, univariate sub-hazard ratio [SHR] 3.9, 95% confidence interval [CI] 1.9-8.1, p

The emergence of resistance to glycopeptide antibiotics such as vancomycin and teicoplanin among Gram-positive bacteria has spurred the search for second-generation drugs of this class. Oritavancin, a promising novel, second-generation, semisynthetic lipoglycopeptide, is distinguished by two mechanisms of action: inhibition of cell wall synthesis and disruption of the cell membrane. This dual mechanism of action has increased the activity of oritavancin against vancomycin-resistant Gram-positive bacteria compared to other glycopeptides. Oritavancin has a concentration-dependent and rapid bactericidal activity against Gram-positive bacteria, particularly enterococci, contrary to vancomycin and teicoplanin, which exhibit bacteriostatic activity. It has a long half-life of about 195.4 hours and is slowly eliminated by the liver and kidneys, allowing once-daily dosing. Oritavancin has demonstrated preliminary safety and efficacy in Phase I and Phase II clinical trials. It was recently shown to be noninferior to vancomycin in a large Phase III randomized, double-blind clinical trial. To date, adverse events have been mild and limited, the most common being administration site complaints, headache, and nausea. Oritavancin appears to be a promising antimicrobial alternative to vancomycin with additional activity against Staphylococcus and Enterococcus isolates resistant to vancomycin and a more convenient way of administration.

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.

The treatment of infections caused by multidrug-resistant Gram-negative bacteria is challenging given the limited options for effective therapy. Combination therapy has garnered great interest recently, with the goals of ensuring appropriate therapy with at least one active agent, and achieving synergistic activity among the anti-microbials used. In this review, we evaluate the data supporting the use of combination therapy against Pseudomonas aeruginosa, carbapenem-resistant Enterobacteriaceae, Acinetobacter species and Stenotrophomonas maltophilia. Various regimens have been tried with promising results; however, the data are mostly derived from in vitro synergy studies. While these reports suggest an advantage of combination therapy over monotherapy, clinical data are scarce, and are comprised of retrospective and a few prospective observational studies. Well-designed randomized trials are needed to better elucidate the efficacy of the various combination regimens. Until then, this review offers a critical appraisal of the published literature and provides recommendations based on the available evidence.

Results: Based on the 43 patients enrolled, a comparable treatment success rates between the 3 arms was observed. Progression to pneumonia occurred in 10% (2/20) of pts in the no therapy arm, 8% (1/13) in the OR arm, and 30% (3/10) in the AR arm. A total cost-savings of $1,830,348 was estimated for this current trial alone. Conclusions: If proven non-inferior, OR is a good and costeffective alternative to AR for management of RSV infections in HCT recipients. Application of ISI-RSV may lead to significant cost-savings by avoiding antiviral therapy in low-risk patients but needs further validation in multi-center studies.

Combination therapy for infections with Gram-negative bacteria (GNB) has been the subject of debate over years, with studies leading to different and at times conflicting outcomes. Proponents of combination therapy propose several arguments: efficacy with expanded broad-spectrum coverage provided by two antimicrobial agents with different spectra of activity; prevention of the emergence of resistance; in vitro synergy between two antibiotics, and improved mortality.Most of the reviewed published data included retrospective studies, and no randomized controlled trials were found. There seems to be a consensus that in sensitive GNB, combination therapy has no added benefit in improving mortality. Hence, the widely used practice is to de-escalate the coverage as soon as the cultures grow a sensitive organism. However, in the era of multidrug resistant (MDR) bacteria and the absence of new antimicrobials in the pipeline, combination therapy should be readdressed.Most of the available data derive from studies involving Pseudomonas aeruginosa , carbapenem-resistant Enterobacteriaceae (CRE), and Acinetobacter baumannii . The results of clinical studies on combination therapy in the treatment of P. aeruginosa are conflicting and non-conclusive. One of the largest recent retrospective cohort studies found no difference in 30-day mortality between combination and monotherapy. However, the isolation of an MDR organismwas not specifically examined. In another study, in vitro activity against MDR P. aeruginosa demonstrated the effectiveness of antimicrobial agents when used in combination, and that despite documented resistance, bacterial killing may still be achieved with some combinations. As for CRE, several retrospective and prospective observational studies showed improvement inmortality with combination therapy. In vitro studies showed that the combination of colistin/tigecycline, rifampin/polymyxin, tigecycline/meropenem, and imipenem/colistin had synergistic activity and fosfomycin/carbapenems prevented the emergence of resistance. Recent studies suggested that combination therapy of 2 or more agents was associated with less mortality. Extended infusion of meropenem in combination with other drugs seemed to have the best outcome when the MIC is