Yazan Numan

Comparing the safety and efficacy of voriconazole versus posaconazole in the prevention of invasive fungal infections in high-risk patients with hematological malignancies

Invasive fungal infection (IFI) is a leading cause of morbidity and mortality in immunocompromised cancer patients. New triazole-based antifungal agents have been recommended for IFI prophylaxis in these patients. This retrospective study compared the safety and efficacy of voriconazole and posaconazole as prophylaxis in patients with hematological malignancies (HM), who were admitted to The University of Texas MD Anderson Cancer Center between January 2014 and August 2015, and who were started on single antifungal prophylaxis consisting of either voriconazole or posaconazole. A total of 200 patients with hematological malignancy were evaluated, the majority of whom had acute myeloid leukemia (AML) (67%). Baseline characteristics, including malignancy status and neutropenia status, were comparable in the two groups. The duration of prophylaxis was similar in the two groups, with medians of 46 days for voriconazole and 48 days for posaconazole. There was no significant difference in breakthrough IFIs between the two groups (3% vs. 0%, P = 0.25). Adverse events occurred in 65% of the voriconazole group vs. 78% of the posaconazole group (P = 0.08). Symptomatic adverse events were more common for voriconazole than for posaconazole (6% vs. 0%, P = 0.03). Eleven patients discontinued voriconazole and seven patients discontinued posaconazole due to adverse events. All-cause mortality was similar in the two groups. Both agents were effective in preventing IFI in hematological malignancy, with comparable all-cause mortality rates. Symptomatic adverse events were significantly more common in the voriconazole group, whereas liver function test abnormality was more common in the posaconazole group.

Clonal Emergence of Invasive Multidrug-Resistant Staphylococcus epidermidis Deconvoluted via a Combination of Whole-Genome Sequencing and Microbiome Analyses

Background Pathobionts, bacteria that are typically human commensals but can cause disease, contribute significantly to antimicrobial resistance. Staphylococcus epidermidis is a prototypical pathobiont as it is a ubiquitous human commensal but also a leading cause of healthcare-associated bacteremia. We sought to determine the etiology of a recent increase in invasive S. epidermidis isolates resistant to linezolid. Methods Whole-genome sequencing (WGS) was performed on 176 S. epidermidis bloodstream isolates collected at the MD Anderson Cancer Center in Houston, Texas, between 2013 and 2016. Molecular relationships were assessed via complementary phylogenomic approaches. Abundance of the linezolid resistance determinant cfr was determined in stool samples via reverse-transcription quantitative polymerase chain reaction. Results Thirty-nine of the 176 strains were linezolid resistant (22%). Thirty-one of the 39 linezolid-resistant S. epidermidis infections were caused by a particular clone resistant to multiple antimicrobials that spread among leukemia patients and carried cfr on a 49-kb plasmid (herein called pMB151a). The 6 kb of pMB151a surrounding the cfr gene was nearly 100% identical to a cfr-containing plasmid isolated from livestock-associated staphylococci in China. Analysis of serial stool samples from leukemia patients revealed progressive staphylococcal domination of the intestinal microflora and an increase in cfr abundance following linezolid use. Conclusions The combination of linezolid use plus transmission of a multidrug-resistant clone drove expansion of invasive, linezolid-resistant S. epidermidis. Our results lend support to the notion that a combination of antibiotic stewardship plus infection control measures may help to control the spread of a multidrug-resistant pathobiont.

A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients

ABSTRACT For long-term central lines (CL), the lumen is the major source of central line-associated bloodstream infections (CLABSI). The current standard of care for maintaining catheter patency includes flushing the CL with saline or heparin. Neither agent has any antimicrobial activity. Furthermore, heparin may enhance staphylococcal biofilm formation. We evaluated the safety and efficacy of a novel nonantibiotic catheter lock solution for the prevention of CLABSI. Between November 2015 and February 2016, we enrolled 60 patients with hematologic malignancies who had peripherally inserted central catheters (PICC) to receive the study lock solution. The study lock consisted of 15 or 30 μg/ml of nitroglycerin in combination with 4% sodium citrate and 22% ethanol. Each lumen was locked for at least 2 h once daily prior to being flushed. After enrollment of 10 patients at the lower nitroglycerin dose without evidence of toxicity, the dose was escalated to the higher dose (30 μg/ml). There were no serious related adverse events or episodes of hypotension with lock administration. Two patients experienced mild transient adverse events (one headache and one rash) possibly related to the lock and that resolved without residual effect. The CLABSI rate was 0 on lock days versus 1.6/1,000 catheter days (CD) off lock prophylaxis, compared with a rate of 1.9/1,000 CD at the institution in the same patient population. In conclusion, the nitroglycerin-based lock prophylaxis is safe and well tolerated. It may prevent CLABSI when given daily to cancer patients. Large, prospective, randomized clinical trials are needed to validate these findings. (This study has been registered at ClinicalTrials.gov under identifier NCT02577718.)

Ammonia vs. Lactic Acid in Predicting Positivity of Microbial Culture in Sepsis: The ALPS Pilot Study

Objective: The use of serum ammonia as a novel marker for sepsis compared to lactic acid levels in intensive care unit (ICU) patients. Design and Interventions: Single arm, prospective clinical trial to collect arterial blood samples from patients with sepsis. Serial ammonia and lactic acid levels were sent every six hours for a total of three days. Measurements and results: Compare mean levels of ammonia and lactic acid in terms of diagnosing sepsis and patient outcome, including length of stay and mortality. A total of 30 patients were enrolled in the pilot study. On admission, mean ammonia level was 35.7 μmol/L and lactic acid was 3.06 mmole/L. Ammonia levels checked at the end of day 2 (ammonia 2-4) and the beginning of day 3 (ammonia 3-1) were higher in patients who had a microbial culture-proven sepsis (p-values 0.029 and 0.002, respectively) compared to those without culture-positive sepsis. Ammonia levels did predict a longer hospital stay; ammonia level of more than 40 μmol/L had a mean hospital stay of 17.6 days vs. patients with normal levels who had a mean hospital stay of 9.62 days (p-value 0.0082). Conclusion: Elevated ammonia level can be a novel biomarker for sepsis, comparable to conventional markers. Ammonia levels have a prognostic utility as elevated levels were associated with longer hospital stay.

Correction for Chaftari et al., “A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients”

Volume 61, no. 7, e00091-17, 2017, https://doi.org/10.1128/AAC.00091-17. Page 1: the 7th author’s name should be Sapna Amin rather than Amin Sapna. The corrected author list appears above. Citation Chaftari A-M, Hachem R, Szvalb A, Taremi M, Granwehr B, Viola GM, Amin S, Assaf A, Numan Y, Shah P, Gasitashvili K, Natividad E, Jiang Y, Slack R, Reitzel R, Rosenblatt J, Mouhayar E, Raad I. 2017. Correction for Chaftari et al., “A novel nonantibiotic nitroglycerin-based catheter lock solution for prevention of intraluminal central venous catheter infections in cancer patients.” Antimicrob Agents Chemother 61:e01324-17. https://doi.org/10.1128/AAC.01324-17. Copyright