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We analyzed the clinical factors associated with late cytomegalovirus (CMV) reactivation in a group of 269 consecutive recipients of allogeneic stem cell transplant (SCT) for hematological malignancies. Eighty-four subjects (31%) experienced late CMV reactivation, including 64 with prior early reactivation and 20 with isolated late reactivation. Multivariate analyses were conducted in patients with early CMV reactivation to identify factors associated with late recurrence. Important risk factors included lymphoid diagnosis, occurrence of graft-versus-host disease (GVHD), greater number of episodes of early reactivation, persistent day 100 lymphopenia and the use of a CMV-seronegative donor graft. We combined these risk factors in a predictive model to identify those at relatively low, intermediate and high risk. The low-risk group (15% cumulative incidence, CI) encompassed patients without early CMV reactivation, and subjects transplanted for a myeloid malignancy from a matched-related (MR) donor without subsequent acute GVHD. The high-risk patients (73% CI) met all of the following criteria: (1) received an MR graft but developed GVHD, or received a non-MR graft irrespective of GVHD; (2) had more than two episodes of early reactivation; and (3) received a CMV-seronegative graft and/or remained persistently lymphopenic at day 100 after SCT. The remaining patients had an intermediate incidence of 32%.

Disseminated adenoviral infection (AI) is associated with profound immunosuppression and poor outcome after allogeneic hematopoietic SCT (allo-HSCT). A better understanding of AI in allo-HSCT recipients can serve as a basis to develop more effective management strategies. We evaluated all adult patients who received allo-HSCT at MD Anderson Cancer Center between 1999 and 2008. Among the 2879 allo-HSCT patients, 73 (2.5%) were diagnosed with AI. Enteritis (26%) and pneumonia (24%) were the most common clinical manifestations; pneumonia was the most common cause of adenovirus-associated death. A multivariable Bayesian logistic regression showed that when the joint effects of all covariates were accounted for, cord blood transplant, absolute lymphocyte count (ALC) ⩽200/mm 3 and male gender were associated with a higher probability of disseminated AI. The OS was significantly worse for patients with AI that was disseminated rather than localized (median of 5 months vs median of 28 months, P <0.001) and for patients with ALC ⩽200/mm 3 ( P <0.001). Disseminated AI, in patients who received allo-HSCT, is a significant cause of morbidity and mortality. Strategies for early diagnosis and intervention are essential, especially for high-risk patients.

CMV infection is a common complication in patients undergoing hematopoietic-cell transplantation. The incidence of CMV infection was 23 percentage points lower with prophylactic letermovir, a CMV–terminase complex inhibitor, than with placebo, with only low-level toxic effects.

Simultaneously drawn quantitative blood cultures are used to diagnose catheter-related bloodstream infections. We conducted this study to determine the frequency with which central venous catheters were the source of bloodstream infections detected through paired positive blood cultures drawn from cancer patients and the potential for quantitative blood cultures to help predict outcome in neutropenic and non-neutropenic patients. From September 1999 to November 2000, we identified 169 patients with bloodstream infections. Of all bloodstream infections, 56% were catheter-related bloodstream infections. Gram-positive bacteremia was found to be catheter-related in 55% and 69% of patients with hematologic malignancy and solid tumors, respectively, whereas gram-negative bacteremia was catheter-related in only 19% of patients with underlying hematologic malignancy and in 60% of patients with solid tumor (P = 0.01). By multivariate analysis, poor response was associated with critical illness and persistent neutropenia (P < 0.01). In neutropenic patients with catheter-related bloodstream infections, peripheral quantitative blood cultures of >or=100 CFU/mL was also associated with poor response (P = 0.05). Central venous catheters were the major source of bloodstream infection, particularly in patients with solid tumors. In addition to critical illness and persistent neutropenia, quantitative blood cultures might be useful in predicting outcomes for neutropenic patients with catheter-related bloodstream infections.

Few data exist on the etiology, presentation, prognosis, and management of fungal endophthalmitis (FE) in cancer patients. FE cases were identified by reviewing the ophthalmology reports and microbiology cultures of patients at The University of Texas M. D. Anderson Cancer Center. We retrospectively reviewed the medical records and obtained information related to malignancy, fungal infection and its management, visual outcome, and mortality. We compared FE caused by Candida spp. (CE) to FE caused by molds (ME). Of the 102 cancer patients with a fungal infection for whom an ophthalmology consult was requested, 23 met the criteria for definite ( N  = 6) or probable ( N  = 17) FE (8 with CE, 15 with ME). All of the patients with ME had hematologic malignancies, whereas half of the patients with CE had solid tumor ( P  = .008). Only patients with CE had a history of surgery within 30 days of FE diagnosis (38%, P  = .03). Fungal pneumonia [17 (74%)] and disseminated infection [14, (61%)] were common. The most common presenting symptoms were decreased vision [16 (70%)] and ocular pain [14 (61%)]. All treated patients received systemic antifungals (combination therapy in 72% of the cases). Seven patients (30%) underwent vitrectomy. Only one patient received intraocular injection of amphotericin B along with systemic antifungals. Four-week mortality was high [13 (57%)], especially in ME (73%, P  = .04). Among the eight surviving patients where visual acuity could be assessed, visual outcome improved or remained stable in five (63%). FE in cancer patients occurs in the setting of severe, frequently disseminated opportunistic mycoses, is caused predominantly by hyalohyphomycetes, and is a marker for high 4-week mortality.

Pneumocystis jiroveci pneumonia is a common infection in patients with AIDS but an infrequent cause of pneumonia in cancer patients. Little is known about the impact of cancer type and hematopoietic stem cell transplantation on the presentation and outcome of P. jiroveci pneumonia in cancer patients. A retrospective cohort study of all patients with cancer and P. jiroveci pneumonia cared for at The M.D. Anderson Cancer Center during 1990-2003 was conducted. Eighty episodes of P. jiroveci pneumonia in 79 patients were identified. In most (67%) episodes, patients had a hematologic malignancy. In 23 (29%) episodes, patients had undergone hematopoietic stem cell transplantation. Twenty-seven percent of patients with histopathologically confirmed P. jiroveci pneumonia had nodular infiltrates on the radiographic study. Pleural effusion and pneumothorax were more common in patients with hematopoietic stem cell transplantation than in those with solid tumors. Clinical suspicion of P. jiroveci pneumonia was less common in patients with nodular infiltrates than in those without such a radiographic finding (7 vs. 39%; p=0.002). Twenty-six of 76 (34%) patients with data available died of P. jiroveci pneumonia. Predictors of death by univariate analysis included older age, tachypnea, high APACHE II score, use of mechanical ventilation or vasopressors, lower arterial pH level, absence of interstitial component, pneumothorax, and comorbid conditions (all p<0.05). Multivariate analysis identified the use of mechanical ventilation as an independent predictor of death. Death attributable to P. jiroveci pneumonia appeared to be higher in patients with hematopoietic stem cell transplantation. The clinical presentation of P. jiroveci pneumonia in cancer patients may be affected by the category of cancer and the history of hematopoietic stem cell transplantation. P. jiroveci pneumonia remains a rare yet severe infection in cancer patients.

The overall risk of infections is lower in patients undergoing non-myeloablative allogeneic stem cell transplantation (NST) than in conventional stem cell transplant recipients. We sought to evaluate conditions associated with increased risk of infections after NST. In 81 patients, 187 infection episodes were noted; chronic lymphocytic leukemia (138 episodes/100 person-years) and recipients of matched unrelated donor graft (128 episodes/100 person-years) had higher risk of infection. Only half of the cytomegalovirus (CMV) infections occurred 31–100 days after transplantation. Most patients with CMV infection were non-neutropenic (100%), had lymphoma (76%), were younger (<55 years; 72%) and had received matched related donor (MRD) graft (72%). However, graft-versus-host disease (GVHD) was present in only 15% of these patients. Seven (78%) of nine invasive fungal infections (IFI) were diagnosed >100 days after NST and were associated with high mortality (78%). Most patients with IFI were also not neutropenic (100%), had received MRD graft (100%), had lymphoma (78%) and were given systemic steroids (78%); unlike CMV infection, 67% of these patients also had GVHD. On the basis of our results, we propose that NST recipients with lymphoma treated with high-dose corticosteroids for GVHD be considered for antifungal prophylaxis or pre-emptive antifungal therapy.

We reviewed the records of 33 patients with leukemia who experienced influenza during the period from October 2000 to March 2004. Three (38%) of the 8 patients who did not receive neuraminidase inhibitor therapy and none of the 25 patients who received it died of influenza pneumonia (P = .001). The use of neuraminidase inhibitor therapy seems to improve the outcome of influenza in patients with leukemia.

Purpose Ertapenem is being increasingly utilized in cancer patients, but published data regarding its usage are limited. Our objective was to describe the various indications for ertapenem therapy and its safety and efficacy in cancer patients. Methods We conducted a retrospective cohort study of cancer patients who received monotherapy with ertapenem for at least 72 h, between January 2007 and February 2013. Results Among 97 unique patients who received ertapenem monotherapy, the most common indications were: (1) To facilitate discharge from the hospital of stable patients still requiring antimicrobial therapy (46 %). (2) Primary therapy of various documented infections (bacteremia, pneumonia, urinary tract infection, skin and skin structure infection) with ertapenem (28 %). (3) De-escalation from a different broad-spectrum agent or regimen to ertapenem within the hospital setting in patients not ready for discharge (25 %). The median age of the 97 patients studied was 59 years (range 9–87 years) with 52 % being men. Most patients had underlying hematologic malignancies (54 %), and 7 % were recipients of hematopoietic stem cell transplantation. Twenty-nine patients (30 %) were neutropenic, 26 % were diabetic, and 6 % had chronic lung disease. Primary ertapenem monotherapy was successful in all patients, de-escalation in 95.8 % of patients, and the strategy of discharge on outpatient therapy with ertapenem in 95.6 % of patients. Patients failing de-escalation or early discharge responded to alternative regimens. We documented no significant ertapenem associated toxicity or adverse events. Conclusions Ertapenem appears to be safe and effective for several indications in cancer patients.

Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32 Gut bacteria influence patient response to cancer therapy. Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti–programmed cell death 1 protein (PD-1) immunotherapy ( n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples ( n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity ( P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family ( P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.