Bruno Granwehr

Perils of quinolone exposure in cancer patients: Breakthrough bacteremia with multidrug-resistant organisms

The objective of this study was to determine the effect of antibiotic use (including prophylaxis) on the emergence of multidrug‐resistant (MDR) breakthrough bacteremia in cancer patients.

A multicenter study of pandemic influenza A (H1N1) infection in patients with solid tumors in 3 countries: early therapy improves outcomes.

Pandemic influenza A (hereafter 2009/H1N1) caused significant morbidity and mortality during the 2009 pandemia. Patients with chronic medical conditions and immunosuppressive diseases had a greater risk of complications. However, data regarding the characteristics and outcome of 2009/H1N1 infection in patients with solid tumors are nonexistent. Herein, the authors describe a series of influenza 2009/H1N1 in patients with solid malignancies at 3 major cancer hospitals worldwide.

Characteristics and outcomes of pandemic 2009/H1N1 versus seasonal influenza in children with cancer.

Background: Novel 2009/H1N1 influenza has significant impact on immunocompromised children with cancer; however, it is uncertain how it compares with seasonal influenza (SFlu) in this vulnerable population. We compared clinical characteristics and outcomes for these 2 infections in children with cancer and identified risk factors for progression to lower respiratory infection (LRI) and/or death. Methods: Influenza infections confirmed by positive viral culture and/or fluorescence antigen test between January 1998 and February 2010 were identified from microbiology databases at a comprehensive cancer center. Characteristics and outcomes were compared for the 2 groups. Kaplan-Meier survival curves and Cox proportional hazards model were generated to identify risk factors for LRI and/or death. Results: When compared with SFlu, 2009/H1N1 cases had significantly lower acute physiology and chronic health evaluation II score (median: 9 versus 14), fewer comorbidities (15% versus 46%), fewer hematopoietic stem-cell transplantation (5% versus 16%), more solid tumors (45% versus 16%), higher LRI at presentation (20% versus 4%), higher rates of antiviral therapy (90% versus 48%) and higher mortality (10% versus 0%). Male gender (hazard ratio [HR]: 8.4, 95% confidence interval [CI]: 1.08–65.2, P = 0.042), acute physiology and chronic health evaluation II score > 15 (HR: 3.29, 95% CI: 1.04–10.39, P = 0.027) and a 24-hour delay in initiation of antiviral treatment (HR: 1.12, 95% CI: 1.02–1.23, P = 0.015) were the most significant predictors of progression to LRI and mortality, regardless of virus strain. Conclusions: Significant differences between 2009/H1N1 and SFlu with respect to clinical presentation, management and associated outcomes were identified. Early diagnosis and prompt initiation of antiviral therapy may prevent serious complications of influenza in children with cancer.

Antiviral therapy improves overall survival in hepatitis C virus-infected patients who develop diffuse large B-cell lymphoma

Chronic Hepatitis C virus (HCV) infection is associated with increased incidence of non‐Hodgkin lymphoma. Several studies have demonstrated regression of indolent lymphoma with antiviral therapy (AVT) alone. However, the role of AVT in HCV‐infected patients with diffuse large B‐cell lymphoma (DLBCL) is unclear. We therefore analyzed AVTs impact on oncologic outcomes of HCV‐infected patients (cases) who developed DLBCL. Cases seen at our institution (June 2004–May 2014) were matched with uninfected counterparts (controls) and then divided according to prior AVT consisting of interferon‐based regimens. We studied 304 patients (76 cases and 228 controls). More cases than controls had extranodal (79% vs. 72%; p = 0.07) and upper gastrointestinal (GI; 42% vs. 24%; p = 0.004) involvement. Cases never given AVT had DLBCL more refractory to first‐line chemotherapy than that in the controls (33% vs. 17%; p = 0.05) and exhibited a trend toward more progressive lymphoma at last examination compared to controls (50% vs. 32%; p = 0.09) or cases given AVT (50% vs. 27%; p = 0.06). Cases never given AVT had worse 5‐year overall survival (OS) rates than did the controls (HR, 2.3 [95% CI, 1.01–5.3]; p = 0.04). Furthermore, AVT improved 5‐year OS rates among cases in both univariate (median [Interquartile range]: 39 [26–56] vs. 16 [6–41] months, p = 0.02) and multivariate analyses (HR = 0.21 [95% CI, 0.06–0.69]; p = 0.01). This study highlights the negative impact of chronic HCV on survival of DLBCL patients and shows that treatment of HCV infection is associated with a better cancer response to chemotherapy and improves 5‐year OS.

The impact of infectious diseases consultation on oncology practice

Purpose of review Traditional utilization of infectious diseases consultants by oncologists ranges from inpatient management of a variety of acute infectious syndromes to management of ambulatory patients with acute or chronic infections; however, there is a paucity of data to evaluate in which circumstances the impact of infectious diseases input may be most valuable. Recent findings Data derived from the general population of patients emphasize the value of infectious diseases consultation in specific infections, such as Staphylococcus aureus bacteremia, candidemia, and hepatitis C virus infection. In addition, infectious diseases involvement has been associated with greater adherence to guidelines (up to 34% increase), more appropriate antibiotic utilization (up to 52% increase in appropriate duration), decreased cost and complications of care, and lower mortality (up to 17% decrease). Recent studies suggest that bedside, formal infectious diseases consultation is more optimal than informal interactions (e.g., e-mail, telephone, other). Furthermore, infectious diseases consultants play central roles in antibiotic stewardship, infection control, and quality improvement, particularly in oncology centers. Summary Infectious diseases consultants contribute value in various inpatient and outpatient infections, decreasing mortality, cost, and complications.

Real-life assessment of the safety and effectiveness of the new tablet and intravenous formulations of posaconazole in the prophylaxis of invasive fungal infections via analysis of 343 courses

ABSTRACT Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infections (IFIs) in patients with hematological malignancy. Delayed-release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis for patients with hematological malignancy. A retrospective cohort of all consecutive adult inpatients with hematological malignancy who received ≥3 days of tablet or intravenous posaconazole therapy for primary IFI prophylaxis at the M. D. Anderson Cancer Center between 1 December 2013 and 31 December 2015 was established. Clinical information was collected and correlated with low posaconazole serum levels (<700 ng/ml). Rates of IFIs and safety events were assessed. A total of 1,321 courses of posaconazole were administered at the M. D. Anderson Cancer Center during the study period, of which 343 courses were assessed for prophylactic safety and effectiveness. Seventy-nine patients (23%) had posaconazole serum level measurements available for interpretation. Acute myeloid leukemia was the primary malignancy (62%), with 20% of all patients having previously received a stem cell transplant. The median posaconazole level was 1,380 ng/ml (interquartile range, 864 to 1,860 ng/ml). Low posaconazole levels (<700 ng/ml) were observed for 14 patients (18%). Proven or probable breakthrough IFIs occurred in 8 patients (2%); posaconazole therapeutic drug monitoring (TDM) was performed for 6 of those patients, all with levels above 700 ng/ml. Overall, 19% of patients experienced grade 3 or 4 liver injury, manifesting primarily as hyperbilirubinemia and being correlated with serum levels of >1,830 ng/ml. Although hepatotoxicity in a small percentage of patients is of concern, posaconazole tablets appeared to be generally safe and effective. As all breakthrough IFIs for which TDM was performed occurred in patients with levels of >700 ng/ml, and a posaconazole level of >1,830 ng/ml was correlated with grade 3 or 4 liver toxicity, further studies are needed to assess the role of TDM.

Comparing quantitative culture of a blood sample obtained through the catheter with differential time to positivity in establishing a diagnosis of catheter-related bloodstream infection

Differential Time to Positivity in Establishing a Diagnosis of Catheter‐Related Bloodstream Infection • Author(s): Iba Al Wohoush, MD; Javier Cairo, MD; Gopikishan Rangaraj, MD; Bruno Granwehr, MD; Ray Hachem, MD; Issam Raad, MD, FACP Source: Infection Control and Hospital Epidemiology, Vol. 31, No. 10 (October 2010), pp. 10891091 Published by: The University of Chicago Press on behalf of The Society for Healthcare Epidemiology of America Stable URL: http://www.jstor.org/stable/10.1086/656381 . Accessed: 21/05/2014 14:49

Case-Control Study of Telavancin as an Alternative Treatment for Gram-Positive Bloodstream Infections in Patients with Cancer

ABSTRACT Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.)

HIV testing in patients with cancer at the initiation of therapy at a large US Comprehensive Cancer Center

PURPOSE To determine the rates of HIV testing and infection among patients with cancer at initiation of systemic cancer therapy. METHODS We conducted a retrospective cohort study of adults with cancer who registered at a comprehensive cancer center from January 2004 through April 2011 and received systemic cancer therapy. We determined rates of HIV-1/2 and/or Western blot testing and HIV positivity at initiation of systemic cancer therapy. Multivariable logistic regression was used to determine predictors of HIV testing. RESULTS Of 18,874 patients with cancer who received systemic cancer therapy during the study period, 3,514 (18.6%) were tested for HIV at initiation of cancer therapy. The prevalence of positive HIV test results was 1.2% (41 of 3,514), and the prevalence of newly diagnosed HIV was 0.3% (12 of 3,514). The HIV testing rate was lower in black than in white patients (13.7% v 19.2%), but the prevalence of positive test results was higher in black patients (4.5%) than in any other racial/ethnic group. Among patients with AIDS-defining cancers (eg, non-Hodgkin lymphoma and cervical cancer), predictors of HIV testing were history of non-Hodgkin lymphoma, younger age, and registration after 2006. Among patients with non-AIDS-defining cancers, predictors of HIV testing were younger age, registration after 2006, male sex, history of illicit drug use or sexually transmitted disease, having a hematologic malignancy, and black race. CONCLUSION The prevalence of HIV infection among patients with cancer was 1.2%, higher than the 0.1% prevalence threshold above which national guidelines recommend routine opt-out testing; however, the overall HIV testing rate was low.

Development of non-Hodgkin lymphoma as a second primary cancer in hepatitis C virus-infected patients with a different primary malignancy

This study will be presented in part at the 52nd Annual Meeting of American Society of Clinical Oncology (ASCO), 3–7 June 2016, Chicago, IL. Chronic hepatitis C virus (HCV) infection affects more than four million people in U.S.A. (1.6% of the population).[1] The carcinogenic effect of HCV is well documented, with hepatocellular carcinoma (HCC) and non-Hodgkin lymphoma (NHL) the most common cancers associated with chronic infection.[2] HCC may develop as a second primary cancer (SPC) in up to 7% of HCVinfected patients with a nonliver first primary cancer (FPC).[3] However, reports of the development of NHL as a SPC in patients with a different FPC are lacking. In the present study, we sought to describe the characteristics of NHL in chronically HCV-infected patients with a different FPC and identify predictors for its development. In this case–control study, we identified patients with chronic HCV infection (positive anti-HCV and detectable HCV RNA in the serum) in whom NHL developed as a SPC in the setting of a different FPC and were seen at our institution from January 2008 through December 2015. The process followed to select patients for the study is depicted in Figure 1. The study was approved by the MD Anderson Institutional Review Board. We extracted data on NHL characteristics at the time of cancer diagnosis and characteristics of FPCs. Additionally, we analyzed data on virologic parameters such as viral genotype and duration of viremia. Non-Hodgkin lymphoma was diagnosed using computed tomography and/or biopsy. NHL was classified according to the 2008 World Health Organization guidelines and HCV-associated NHL was identified as previously described.[4] The Ann Arbor staging system was used to determine the stage and prognosis of NHL. Sustained virological response (SVR) was defined as an absence of HCV RNA in the serum 24 weeks after completion of antiviral treatment (AVT), the treatment endpoint used with interferon-based regimens (the most common therapy used in our study patients).[5] The duration of HCV infection was measured with a starting point of diagnosis of FPC. Endpoints included dates of SVR, death and last follow-up. Descriptive statistics were used to characterize the study population. Chronically HCV-infected patients with a FPC in whom NHL developed as a SPC (cases) were matched at a 1:3 ratio with HCV-infected cancer patients who did not develop any SPC (controls), based on their FPC. Matched analysis was conducted and p values <0.05 were considered statistically significant. One hundred seventeen patients with HCV-associated NHL were seen at MD Anderson during the study period. Among them, 21 (18%) developed NHL as a SPC (cases) and underwent further analysis. The median patient age at the time of diagnosis of SPC was 63 years (interquartile range: 52–88 years). Eleven patients (52%) had a family history of cancer, but only one patient (5%) had a family history of lymphoma in particular. The types of NHL were diffuse large B cell lymphoma (57%), marginal zone B cell lymphoma (24%), mantle cell lymphoma (14%) and lymphoplasmacytic lymphoma (5%). The distribution of Ann Arbor stage was almost even among cases: stage 2 (38%), stage 3 (33%) and stage 4 (29%). NHL was diagnosed at a median of 6 years (interquartile range, 3–11 years) after the FPC diagnosis. NHL as a SPC was diagnosed as an incidental finding in 11 cases (52%). First primary cancers were mainly solid tumors (81%), mostly involving the genitourinary (38%) or respiratory (19%) tracts (Table 1). Four cases (19%) had a hematologic malignancy as FPC: three of them (3/4; 75%) with Hodgkin disease and one (1/4; 25%) with chronic lymphocytic leukemia. At the time of diagnosis of NHL, 11 cases (52%) had their FPC in complete remission and 9 (43%) had progressive disease. The most common chemotherapeutic agents administered were mitotic inhibitors [paclitaxel (3/9; 33%)], antimetabolites [5-flurouracil, gemcitabine (3/9; 33%)] and alkylating agents