85 results on '"Chaftari AM"'
Search Results
2. A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia.
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Chaftari AM, Dagher H, Hachem R, Jiang Y, Lamie P, Wilson Dib R, John T, Haddad A, Philip A, Alii S, Mulanovich P, Yuan Y, Chaftari P, and Raad I
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- Humans, Male, Female, Middle Aged, Aged, Adult, Treatment Outcome, Imipenem therapeutic use, Imipenem adverse effects, Imipenem administration & dosage, Standard of Care, Gram-Negative Bacteria drug effects, Cilastatin therapeutic use, Cilastatin adverse effects, Cilastatin administration & dosage, Aged, 80 and over, Febrile Neutropenia drug therapy, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents adverse effects, Anti-Bacterial Agents administration & dosage, Neoplasms complications, Neoplasms drug therapy, Gram-Negative Bacterial Infections drug therapy, Cilastatin, Imipenem Drug Combination therapeutic use, Azabicyclo Compounds therapeutic use, Azabicyclo Compounds adverse effects, Azabicyclo Compounds administration & dosage
- Abstract
Background: Antibiotic overuse leads to the emergence of antibiotic resistance that threatens immunocompromised cancer patients. Infections caused by MDR Gram-negative pathogens are difficult to treat and associated with high mortality. Hence, empirical therapy with standard-of-care (SOC) antibiotics could be suboptimal in these vulnerable patients. New antibiotics covering potential resistant pathogens may be considered., Methods: We conducted a randomized non-inferiority study comparing safety and efficacy of imipenem/cilastatin/relebactam (IPM/REL), a β-lactam/β-lactamase inhibitor combination, with SOC antibiotics (cefepime, piperacillin/tazobactam or meropenem) in cancer patients with febrile neutropenia. Patients received at least 48 h of IV antibiotics and were assessed at end-of-IV (EOIV) therapy, test of cure (TOC; Days 21-28), and late follow-up (LFU; Days 35-42)., Results: A total of 100 patients were enrolled (49 IPM/REL and 50 SOC). Demographics and rates of documented microbiological infections were similar in both groups. In the SOC arm, 86% of antibiotics consisted of cefepime. Patients on IPM/REL had a higher favourable clinical response at EOIV than those on SOC (90% versus 74%; P = 0.042); however, responses were similar at TOC and LFU. Microbiological eradication was comparable at all three timepoints. Study drug-related adverse events and adverse events leading to drug discontinuation were similar in both groups, with no study drug-related mortality., Conclusions: Our results suggest that compared with SOC antibiotics, predominantly cefepime, IPM/REL for empirical coverage of febrile neutropenia in cancer patients is generally safe and could be associated with a better clinical outcome at EOIV. The current SOC consisting mainly of agents that do not cover for ESBL-producing and carbapenem-resistant Enterobacterales bacteria should be reconsidered., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
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- 2024
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3. In vitro activity of cefepime/taniborbactam and comparator agents against Gram-negative bacterial bloodstream pathogens recovered from patients with cancer.
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Gerges B, Rosenblatt J, Truong YL, Jiang Y, Shelburne SA Sr, Chaftari AM, Hachem R, and Raad I Sr
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Background: Taniborbactam is a β-lactamase inhibitor that, when combined with cefepime, may offer a potential treatment option for patients with serious and resistant Gram-negative bacterial (GNB) pathogens., Objectives: This study evaluated in vitro activity of cefepime/taniborbactam and comparator agents against GNB pathogens isolated from patients with cancer at our institution., Methods: A total of 270 GNB pathogens (2019-23) isolated from patients with cancer were tested against cefepime/taniborbactam and comparator agents commonly used for these patients. CLSI-approved broth microdilution methods were used. MIC
50 , MIC90 , MIC range and percentage of susceptibility calculations were made using FDA breakpoints when available., Results: Cefepime/taniborbactam showed highly potent activity against tested Enterobacterales, including isolates producing ESBLs and carbapenem-resistant Enterobacterales. At a provisional breakpoint of ≤16/4 mg/L, cefepime/taniborbactam inhibited most tested species of GNB pathogens, with overall 98.9% susceptibility, which was significantly ( P < 0.0001) higher than the susceptibility of the GNB isolates to all other tested comparator agents, ranging from 39.6% for cefepime to 86.3% for ceftazidime/avibactam., Conclusions: Our results showed that taniborbactam in combination with cefepime improved in vitro activity against GNB pathogens isolated from patients with cancer, including MDR Pseudomonas aeruginosa , carbapenem-resistant Enterobacterales, ESBL-producing Enterobacterales and Stenotrophomonas maltophilia isolates, with highest activity compared with all tested comparator agents, including other β-lactam/β-lactamase inhibitor combinations. Further studies are warranted to explore the efficacy of cefepime/taniborbactam for empirical initial treatment of GNB infections in cancer patients with high rates of febrile neutropenia requiring hospitalization., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)- Published
- 2024
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4. Comparing Molnupiravir to Nirmatrelvir/Ritonavir (Paxlovid) in the Treatment of Mild-to-Moderate COVID-19 in Immunocompromised Cancer Patients.
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Haddad AJ, Hachem RY, Moussa M, Jiang Y, Dagher HR, Chaftari P, Chaftari AM, and Raad II
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Background: Nirmatrelvir/Ritonavir has been shown to reduce the risk of COVID-19 progression by 88% compared to placebo, while Molnupiravir reduced it by 31%. However, these two agents have not been compared head-to-head. We therefore compared the safety and efficacy of both agents for the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients., Methods: We identified 240 cancer patients diagnosed with COVID-19 and treated with Molnupiravir or Nirmatrelvir/Ritonavir. Patients were matched using a 1:2 ratio based on age group (18-64 years vs. ≥65) and type of cancer. The collected data included demographics, comorbidities, and treatment outcome., Results: Both groups had comparable characteristics and presenting symptoms. However, dyspnea was more prevalent in the Molnupiravir group, while sore throat was more prevalent in the Nirmatrelvir/Ritonavir group. The rate of disease progression was comparable in both groups by univariate and multivariable analysis. Treatment with Molnupiravir versus Nirmatrelvir/Ritonavir revealed no significant difference in disease progression by multivariable analysis (adjusted OR = 1.31, 95% CI: 0.56-3.14, p = 0.70). Patients who received Nirmatrelvir/Ritonavir, however, were significantly more prone to having drug-drug interactions/adverse events (30% vs. 0%, p < 0.0001)., Conclusions: In the treatment of mild-to-moderate COVID-19 in cancer patients, Molnupiravir was comparable to Nirmatrelvir/Ritonavir in preventing progression to severe disease/death and rebound events, and it had a superior safety profile.
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- 2024
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5. In vitro activity of tebipenem and comparator agents against bacterial pathogens isolated from patients with cancer.
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Gerges B, Rosenblatt J, Shellburne SA, Chaftari AM, Hachem R, and Raad I
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Background: Tebipenem is a broad-spectrum orally administered carbapenem antibiotic that could be an alternative to IV carbapenems. The current study evaluated in vitro activity of tebipenem against bacterial isolates recovered from patients with cancer., Methods: A total of 611 bacterial pathogens recently isolated from patients with cancer were tested for susceptibility to tebipenem and comparators. CLSI-approved broth microdilution methods were used. MIC
50 , MIC90 , MIC range and percentage susceptibility calculations were made using FDA breakpoints when available., Results: Tebipenem had a low MIC90 for most Gram-positive and Enterobacterales isolates. Tebipenem MIC90 ranged from 0.06 to 0.25 mg/L for all tested Enterobacterales., Conclusions: Oral tebipenem has promising activity against clinically significant bacterial pathogens isolated from patients with cancer. Further clinical evaluation of tebipenem for the treatment of bacterial infections in patients with cancer is warranted., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)- Published
- 2023
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6. Prevention of device-related infections in patients with cancer: Current practice and future horizons.
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Viola GM, Szvalb AD, Malek AE, Chaftari AM, Hachem R, and Raad II
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- Humans, Medical Oncology, Health Personnel, Quality of Life, Neoplasms
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Over the past several years, multifaceted advances in the management of cancer have led to a significant improvement in survival rates. Throughout patients' oncological journeys, they will likely receive one or more implantable devices for the administration of fluids and medications as well as management of various comorbidities and complications related to cancer therapy. Infections associated with these devices are frequent and complex, often necessitating device removal, increasing health care costs, negatively affecting quality of life, and complicating oncological care, usually leading to delays in further life-saving cancer therapy. Herein, the authors comprehensively review multiple evidence-based recommendations along with best practices, expert opinions, and novel approaches for the prevention of diverse device-related infections. The authors present many general principles for the prevention of these infections followed by specific device-related recommendations in a systematic manner. The continuous involvement and meaningful cooperation between regulatory entities, industry, specialty medical societies, hospitals, and infection control-targeted interventions, along with primary care and consulting health care providers, are all vital for the sustained reduction in the incidence of these preventable infections., (© 2022 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)
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- 2023
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7. Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.
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Dagher H, Chaftari AM, Subbiah IM, Malek AE, Jiang Y, Lamie P, Granwehr B, John T, Yepez E, Borjan J, Reyes-Gibby C, Flores M, Khawaja F, Pande M, Ali N, Rojo R, Karp DD, Chaftari P, Hachem R, and Raad II
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- United States, Female, Male, Humans, Adolescent, Young Adult, Adult, Middle Aged, Aged, Aged, 80 and over, Post-Acute COVID-19 Syndrome, COVID-19 Testing, SARS-CoV-2, Fatigue, COVID-19, Neoplasms
- Abstract
Background: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery., Methods: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020, and September 1, 2020, and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months., Results: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%), and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%), and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs. 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were re-admitted for COVID-related reasons., Conclusions: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even 1 year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia, and gastrointestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8.5% requiring a COVID-19-related re-admission., Funding: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication., Competing Interests: HD, AC, IS, AM, YJ, PL, BG, TJ, EY, JB, CR, MF, FK, MP, NA, RR, DK, PC, RH, IR No competing interests declared, (© 2023, Dagher et al.)
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- 2023
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8. International multicenter study comparing COVID-19 in patients with cancer to patients without cancer: Impact of risk factors and treatment modalities on survivorship.
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Raad II, Hachem R, Masayuki N, Datoguia T, Dagher H, Jiang Y, Subbiah V, Siddiqui B, Bayle A, Somer R, Fernández Cruz A, Gorak E, Bhinder A, Mori N, Hamerschlak N, Shelanski S, Dragovich T, Vong Kiat YE, Fakhreddine S, Pierre AH, Chemaly RF, Mulanovich V, Adachi J, Borjan J, Khawaja F, Granwehr B, John T, Yepez EY, Torres HA, Ammakkanavar NR, Yibirin M, Reyes-Gibby CC, Pande M, Ali N, Rojo RD, Ali SM, Deeba RE, Chaftari P, Matsuo T, Ishikawa K, Hasegawa R, Aguado-Noya R, García AG, Puchol CT, Lee DG, Slavin M, Teh B, Arias CA, Kontoyiannis DP, Malek AE, and Chaftari AM
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- Humans, Retrospective Studies, SARS-CoV-2, Survivorship, Risk Factors, Oxygen, COVID-19 complications, COVID-19 therapy, Neoplasms complications, Neoplasms epidemiology, Lymphopenia
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Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries., Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers., Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03)., Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality., Funding: National Cancer Institute and National Institutes of Health., Competing Interests: IR, RH, NM, TD, HD, YJ, VS, BS, AB, RS, AF, EG, AB, NM, NH, SS, TD, YV, SF, AP, RC, VM, JA, JB, FK, BG, TJ, EY, HT, NA, MY, CR, MP, NA, RR, SA, RD, PC, TM, KI, RH, RA, AG, CP, DL, MS, BT, CA, DK, AM, AC No competing interests declared, (© 2023, Raad, Hachem et al.)
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- 2023
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9. Procalcitonin for antimicrobial stewardship among cancer patients admitted with COVID-19.
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Dagher H, Chaftari AM, Mulanovich P, Jiang Y, Hachem R, Malek AE, Borjan J, Viola GM, and Raad I
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- Humans, Middle Aged, Procalcitonin therapeutic use, Retrospective Studies, Biomarkers, Anti-Bacterial Agents therapeutic use, Antimicrobial Stewardship, COVID-19, Bacterial Infections drug therapy, Neoplasms complications, Neoplasms drug therapy
- Abstract
Background: Procalcitonin (PCT) has been used to guide antibiotic therapy in bacterial infections. We aimed to determine the role of PCT in decreasing the duration of empiric antibiotic therapy among cancer patients admitted with COVID-19., Methods: This retrospective study included cancer patients admitted to our institution for COVID-19 between March 1, 2020, and June 28, 2021, with a PCT test done within 72 hr after admission. Patients were divided into two groups: PCT <0.25 ng/ml and PCT ≥0.25 ng/ml. We assessed pertinent cultures, antibacterial use, and duration of empiric antibacterial therapy., Results: The study included 530 patients (median age, 62 years [range, 13-91]). All the patients had ≥1 culture test within 7 days following admission. Patients with PCT <0.25 ng/ml were less likely to have a positive culture than were those with PCT ≥0.25 ng/ml (6% [20/358] vs. 17% [30/172]; p<0.0001). PCT <0.25 ng/ml had a high negative predictive value for bacteremia and 30 day mortality. Patients with PCT <0.25 ng/ml were less likely to receive intravenous (IV) antibiotics for >72 hr than were patients with PCT ≥0.25 ng/ml (45% [162/358] vs. 69% [119/172]; p<0.0001). Among patients with PCT <0.25 ng/ml and negative cultures, 30 day mortality was similar between those who received IV antibiotics for ≥72 hr and those who received IV antibiotics for shorter durations (2% [2/111] vs. 3% [5/176], p=0.71)., Conclusions: Among cancer patients with COVID-19, PCT level <0.25 ng/ml is associated with lower likelihood of bacterial co-infection and greater likelihood of a shorter antibiotic course. In patients with PCT level <0.25 ng/ml and negative cultures, an antibiotic course of >72 hr may not be necessary. PCT could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19., Funding: This research was supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports MD Anderson Cancer Center's Clinical Trials Office., Competing Interests: HD, AC, PM, YJ, RH, AM, JB, GV, IR No competing interests declared, (© 2022, Dagher et al.)
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- 2022
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10. International Multicenter Study Comparing Cancer to Non-Cancer Patients with COVID-19: Impact of Risk Factors and Treatment Modalities on Survivorship.
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Raad I, Hachem R, Masayuki N, Datoguia T, Dagher H, Jiang Y, Subbiah V, Siddiqui B, Bayle A, Somer R, Cruz AF, Gorak E, Bhinder A, Mori N, Hamerschlak N, Shelanski S, Dragivich T, Kiat YEV, Fakhreddine S, Hanna PA, Chemaly RF, Mulanovich V, Adachi J, Borjan J, Khawaja F, Granwehr B, John T, Guevara EY, Torres H, Ammakkanavar NR, Yibirin M, Reyes-Gibby CC, Pande M, Ali N, Rojo RD, Ali SM, Deeba RE, Chaftari P, Matsuo T, Ishikawa K, Hasegawa R, Aguado-Noya R, García-García Á, Puchol CT, Lee DG, Slavin M, Teh B, Arias CA, Kontoyiannis DP, Malek AE, and Chaftari AM
- Abstract
Background: In this international multicenter study we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries., Methods: We retrospectively collected de-identified data on a cohort of cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, from 16 international centers., Results: We analyzed 3966 COVID-19 confirmed patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were more likely to be pancytopenic, and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding two weeks (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms (p≤0.01). By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who did not (5.9% vs 17.6%; p=0.03)., Conclusions: Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality., Condensed Abstract: In this large multicenter worldwide study of 4015 patients with COVID-19 that included 1115 patients with cancer, we found that cancer is an independent risk factor for increased 30-day all-cause mortality. Remdesivir is a promising treatment modality to reduce 30-day all-cause mortality.
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- 2022
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11. A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients With Hematological Malignancies.
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Chaftari AM, Hachem R, Malek AE, Mulanovich VE, Szvalb AD, Jiang Y, Yuan Y, Ali S, Deeba R, Chaftari P, and Raad I
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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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2022
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12. Real-World Use of Isavuconazole as Primary Therapy for Invasive Fungal Infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant.
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Dagher H, Hachem R, Chaftari AM, Jiang Y, Ali S, Deeba R, Shah S, and Raad I
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(1) Introduction: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with hematologic malignancies (HM) and stem cell transplants (SCT). Isavuconazole was approved by FDA as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. The aim of this study is to look at the real-world use of Isavuconazole in patients with HM and evaluate their clinical outcomes and safety. (2) Methods: We conducted a retrospective study of HM patients at MD Anderson Cancer Center who had definite, probable or possible mold infections between 1 April 2016 and 31 January 2020 and were treated with Isavuconazole for a period of at least 7 days. Clinical and radiological findings were assessed at baseline and at 6 and 12 weeks of follow up. (3) Results: We included 200 HM patients with IFIs that were classified as definite (11), probable (63) and possible (126). Aspergillus spp was the most commonly isolated pathogen. The majority of patients (59%) received prophylaxis with anti-mold therapy and Isavuconazole was used as a primary therapy in 43% of patients, and as salvage therapy in 58%. The switch to Isavuconazole was driven by the failure of the primary therapy in 66% of the cases and by adverse effects in 29%. Isavuconazole was used as monotherapy in 30% of the cases and in combination in 70%. Adverse events possibly related to Isavuconazole were reported in eight patients (4%) leading to drug discontinuation. Moreover, a favorable response with Isavuconazole was observed in 40% at 6 weeks and in 60% at 12 weeks. There was no significant difference between isavuconazole monotherapy and combination therapy ( p = 0.16 at 6 weeks and p = 0.06 at 12 weeks). Finally, there was no significant difference in outcome when Isavuconazole was used after failure of other anti-mold prophylaxis or treatment versus when used de novo as an anti-mold therapy ( p = 0.68 at 6 weeks and p = 0.25 at 12 weeks). (4) Conclusions: Whether used as first-line therapy or after the failure of other azole and non-azole prophylaxis or therapies, isavuconazole seems to have a promising clinical response and a good safety profile as an antifungal therapy in high-risk cancer patients with hematologic malignancies. Moreover, combination therapy did not improve the outcome compared to Isavuconazole therapy.
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- 2022
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13. The role of procalcitonin in identifying high-risk cancer patients with febrile neutropenia: A useful alternative to the multinational association for supportive care in cancer score.
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Chaftari P, Chaftari AM, Hachem R, Yeung SJ, Dagher H, Jiang Y, Malek AE, Dailey Garnes N, Mulanovich VE, and Raad I
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- Adult, Aged, Female, Humans, Lactates blood, Male, Middle Aged, Neoplasms mortality, Predictive Value of Tests, Retrospective Studies, Risk Assessment, Sensitivity and Specificity, Biomarkers, Tumor blood, Febrile Neutropenia blood, Neoplasms blood, Procalcitonin blood
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Background: The Multinational Association for Supportive Care in Cancer (MASCC) risk index has been utilized to determine the risk for poor clinical outcomes in patients with febrile neutropenia (FN) in an emergency center (EC). However, this index comprises subjective elements and elaborated metrics limiting its use in ECs. We sought to determine whether procalcitonin (PCT) level (biomarker of bacterial infection) with or without lactate level (marker of inadequate tissue perfusion) offers a potential alternative to MASSC score in predicting the outcomes of patients with FN presenting to an EC., Methods: We retrospectively identified 550 cancer patients with FN who presented to our EC between April 2018, and April 2019, and had serum PCT and lactate levels measured., Results: Compared with patients with PCT levels <0.25 ng/ml, those with levels ≥0.25 ng/ml had a significantly higher 14-day mortality rate (5.2% vs. 0.7%; p = 0.002), a higher bloodstream infection (BSI) rate, and a longer hospital length of stay (LOS). Logistic regression analysis showed that patients with PCT levels ≥0.25 ng/ml and lactate levels >2.2 mmol/L were more likely to be admitted and have an LOS >7 days, BSI, and 14-day mortality than patients with lower levels. PCT level was a significantly better predictor of BSI than MASSC score (p = 0.003) or lactate level (p < 0.0001)., Conclusions: Procalcitonin level is superior to MASCC index in predicting BSI. The combination of PCT and lactate levels is a good predictor of BSI, hospital admission, and 14-day mortality and could be useful in identifying high-risk FN patients who require hospital admission., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2021
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14. Impact of Checkpoint Inhibitor Immunotherapy, Primarily Pembrolizumab, on Infection Risk in Patients With Advanced Lung Cancer: A Comparative Retrospective Cohort Study.
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Malek AE, Khalil M, Hachem R, Chaftari AM, Fares J, Jiang Y, Kontoyiannis DP, Fossella F, Chaftari P, Mulanovich VE, Viola GM, and Raad II
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- Antibodies, Monoclonal, Humanized, Humans, Immunotherapy, Retrospective Studies, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy
- Abstract
Background: Checkpoint inhibitor (CPI) immunotherapy has revolutionized cancer treatment. However, immune-related adverse events and the risk of infections are not well studied. To assess the infectious risk of CPIs, we evaluated the incidence of infections in lung cancer patients treated with CPIs plus conventional chemotherapy (CC) vs CC alone., Methods: We performed a retrospective comparative study of patients with advanced non-small cell lung cancer who received CPIs combined with CC and those treated with CC alone at our institution during January 2016 to February 2019. We compared clinical characteristics, treatments, and outcomes including infection rate and mortality between the groups., Results: We identified 123 patients for the CPI group and 147 patients for the control (CC) group. Eighteen patients (15%) in the CPI group and 33 patients (22%) in the control group developed infections (P = .1). Pneumonia was the most common infection encountered in both groups. Urinary tract infection was higher in the CC group (40%) than in the CPI group (9%) (P = .01). On multivariable analysis, chronic obstructive pulmonary disease (P = .024), prior use of corticosteroids (P = .021), and neutropenia (P < .001) were independent risk factors for infection and severe infection requiring hospital admission. Chronic kidney disease (P = .02), prior cancer treatment (P = .023), and neutropenia (P < .0001) were identified as independent risk factors for all-cause mortality., Conclusions: Lung cancer patients treated with CPIs combined with CC have a comparable risk of infection to those treated with CC alone, although there is a trend towards fewer infections in those given CPIs, particularly when it comes to urinary tract infections., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)
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- 2021
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15. Novel antimicrobial ointment for infected wound healing in an in vitro and in vivo porcine model.
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Hachem R, Parikh UM, Reitzel R, Rosenblatt J, Kaul A, Vargas-Cruz N, Hill L, Moore L, Meyer J, Chaftari AM, Gagea M, Balaji S, and Raad II
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- Animals, Anti-Bacterial Agents pharmacology, Ointments, Swine, Wound Healing, Anti-Infective Agents pharmacology, Wound Infection drug therapy
- Abstract
Microbial contamination of wounds is a significant problem that delays healing, particularly when bacterial biofilms are present. A novel combination of pectinic acid (PG) + caprylic acid (CAP) was previously found in vitro to be highly effective in eradicating various pathogens in biofilms with minimal cytotoxicity. In this study, a novel wound ointment was formulated with PG + CAP and first assessed in vitro using a well-established biofilm eradication model. In vitro, the PG + CAP ointment was shown to be efficacious in reducing the microbial biofilms. This ointment was then tested in vivo in two pilot porcine wound healing models, with and without Staphylococcus aureus microbial challenge. Ointments were applied to each wound daily, and healing by wound closure area measurement was assessed weekly over 4 weeks. After 4 weeks, pigs were sacrificed and wounds were scored for reepithelialization, inflammation, granulation tissue, and collagen deposition. We compared PG + CAP to hydroxyethylcellulose + glycerol ointment base (control) and MediHoney (comparator). In the porcine microbial challenge model, the novel antimicrobial PG + CAP wound ointment rapidly eradicated bacterial organisms embedded in wounds, was safe and well-tolerated, and was associated with enhanced healing compared to ointment base and MediHoney. Specifically, the cumulative histopathology, reepithelialization of epidermis, and mature granulation tissue in the wound bed was significantly better with PG + CAP than with control and MediHoney treatments. This ointment warrants further study as a non-antibiotic ointment for use in treating a wide array of infected wounds., (© 2021 The Wound Healing Society.)
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- 2021
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16. Prognostic Value of Procalcitonin, C-Reactive Protein, and Lactate Levels in Emergency Evaluation of Cancer Patients with Suspected Infection.
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Chaftari P, Qdaisat A, Chaftari AM, Maamari J, Li Z, Lupu F, Raad I, Hachem R, Calin G, and Yeung SJ
- Abstract
Cancer patients have increased risk of infections, and often present to emergency departments with infection-related problems where physicians must make decisions based on a snapshot of the patient's condition. Although C-reactive protein, procalcitonin, and lactate are popular biomarkers of sepsis, their use in guiding emergency care of cancer patients with infections is unclear. Using these biomarkers, we created a prediction model for short-term mortality in cancer patients with suspected infection. We retrospectively analyzed all consecutive patients who visited the emergency department of MD Anderson Cancer Center between 1 April 2018 and 30 April 2019. A clinical decision model was developed using multiple logistic regression for various clinical and laboratory biomarkers; coefficients were used to generate a prediction score stratifying patients into four groups according to their 14-day mortality risk. The prediction score had an area under the receiver operating characteristic curve value of 0.88 (95% confidence interval 0.85-0.91) in predicting 14-day mortality. The prediction score also accurately predicted intensive care unit admission and 30-day mortality. Our simple new scoring system for mortality prediction, based on readily available clinical and laboratory data, including procalcitonin, C-reactive protein, and lactate, can be used in emergency departments for cancer patients with suspected infection.
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- 2021
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17. Management of enterococcal central line-associated bloodstream infections in patients with cancer.
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Awadh H, Chaftari AM, Khalil M, Fares J, Jiang Y, Deeba R, Ali S, Hachem R, and Raad II
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Device Removal, Female, Humans, Male, Middle Aged, Retrospective Studies, Young Adult, Bacteremia therapy, Catheter-Related Infections therapy, Central Venous Catheters adverse effects, Enterococcus, Neoplasms complications
- Abstract
Objective: Enterococcus species are the third most common organisms causing central line-associated bloodstream infections (CLABSIs). The management of enterococcal CLABSI, including the need for and timing of catheter removal, is not well defined. We therefore conducted this study to determine the optimal management of enterococcal CLABSI in cancer patients., Methods: We reviewed data for 542 patients diagnosed with Enterococcus bacteremia between September 2011 to December 2018. After excluding patients without an indwelling central venous catheter (CVC), polymicrobial bacteremia or with CVC placement less than 48 h from bacteremia onset we classified the remaining 397 patients into 3 groups: Group 1 (G1) consisted of patients with CLABSI with mucosal barrier injury (MBI), Group 2 (G2) included patients with either catheter-related bloodstream infection (CRBSI) as defined in 2009 Clinical Practice Guidelines for the Diagnosis and Management of Intravascular Catheter-Related Infection by the Infectious Diseases Society of America (IDSA) or CLABSI without MBI, and Group 3 (G3) consisted of patients who did not meet the CDC criteria for CLABSI. The impact of early (< 3 days after bacteremia onset) and late (3-7 days) CVC removal was compared. The composite primary outcome included absence of microbiologic recurrence, 90-day infection-related mortality, and 90-day infection-related complications., Results: Among patients in G2, CVC removal within 3 days of bacteremia onset was associated with a trend towards a better overall outcome than those whose CVCs were removed later between days 3 to 7 (success rate 88% vs 63%). However, those who had CVCs retained beyond 7 days had a similar successful outcome than those who had CVC removal < 3 days (92% vs. 88%). In G1, catheter retention (removal > 7 days) was associated with a better success rates than catheter removal between 3 and 7 days (93% vs. 67%, p = 0.003). In non-CLABSI cases (G3), CVC retention (withdrawal > 7 days) was significantly associated with a higher success rates compared to early CVC removal (< 3 days) (90% vs. 64%, p = 0.006)., Conclusion: Catheter management in patients with enterococcal bacteremia is challenging. When CVC removal is clinically indicated in patients with enterococcal CLABSI, earlier removal in less than 3 days may be associated with better outcomes. Based on our data, we cannot make firm conclusions about whether earlier removal (< 3 days) could be associated with better outcomes in patients with Enterococcal CLABSI whose CVC withdrawal is clinically indicated. In contrast, it seemed that catheter retention was associated to higher success outcome rates. Therefore, future studies are needed to clearly assess this aspect.
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- 2021
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18. Is a single dose of mRNA vaccine sufficient for COVID-19 survivors?
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Malek AE, Dagher H, Hachem R, Chaftari AM, and Raad II
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- 2019-nCoV Vaccine mRNA-1273, Adult, BNT162 Vaccine, Humans, Immunity, Immunization Schedule, Reinfection prevention & control, mRNA Vaccines, COVID-19 immunology, COVID-19 prevention & control, COVID-19 Vaccines administration & dosage, Vaccines, Synthetic administration & dosage
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- 2021
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19. Whole-genome sequencing of Staphylococcus epidermidis bloodstream isolates from a prospective clinical trial reveals that complicated bacteraemia is caused by a limited number of closely related sequence types.
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Shelburne SA, Dib RW, Endres BT, Reitzel R, Li X, Kalia A, Sahasrabhojane P, Chaftari AM, Hachem R, Vargas-Cruz NS, Jiang Y, Garey K, Fowler VG Jr, Holland TL, Gu J, Miller W, Sakurai A, Arias CA, Aitken SL, Greenberg DE, Kim J, Flores AR, and Raad I
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- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Clinical Trials as Topic, Drug Resistance, Bacterial drug effects, Drug Resistance, Bacterial genetics, Female, Genome, Bacterial genetics, Genotype, Humans, Male, Microbial Sensitivity Tests, Multicenter Studies as Topic, Phenotype, Phylogeny, Staphylococcal Infections drug therapy, Staphylococcus epidermidis classification, Staphylococcus epidermidis drug effects, Staphylococcus epidermidis isolation & purification, Bacteremia microbiology, Bacteremia pathology, Staphylococcal Infections microbiology, Staphylococcal Infections pathology, Staphylococcus epidermidis genetics
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Objectives: The significance of isolating Staphylococus epidermidis from a blood culture is highly heterogeneous, ranging from contamination to an indication of a serious infection. Herein we sought to determine whether there is a relationship between S. epidermidis genotype and clinical severity of bacteraemia., Methods: S. epidermidis bacteraemias from a prospective, multicentre trial at 15 centres in the United States and one in Spain were classified as simple (including possible contamination), uncomplicated, and complicated. Whole-genome sequencing (WGS) was performed on 161 S. epidermidis isolates, and clinical outcomes were correlated with genotypic information., Results: A total of 49 S. epidermidis sequence types (STs) were identified. Although strains of all 49 STs were isolated from patients with either simple or uncomplicated infection, all strains causing complicated infections were derived from five STs: ST2, ST5, ST7, ST16, and ST32. ST2 and ST5 isolates were significantly more likely to cause uncomplicated and complicated bloodstream infections compared to simple bacteraemia (odds ratio 2.0, 95%CI 1.1-3.9, p 0.04). By multivariate regression analysis, having an ST2 or ST5 S. epidermidis bacteraemia was an independent predictor of complicated bloodstream infection (odds ratio 3.7, 95%CI 1.2-11.0, p 0.02). ST2/ST5 strains carried larger numbers of antimicrobial resistance determinants compared to non-ST2/ST5 isolates (6.34 ± 1.5 versus 4.4 ± 2.5, p < 0.001)., Conclusion: S. epidermidis bacteraemia was caused by a genetically heterogeneous group of organisms, but only a limited number of STs-particularly multidrug-resistant ST2 and ST5 strains-caused complicated infections., (Copyright © 2019 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)
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- 2020
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20. Invasive pulmonary aspergillosis: comparative analysis in cancer patients with underlying haematologic malignancies versus solid tumours.
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Dib RW, Khalil M, Fares J, Hachem RY, Jiang Y, Dandachi D, Chaftari AM, and Raad II
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- Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Retrospective Studies, Risk Factors, Treatment Outcome, Young Adult, Antifungal Agents therapeutic use, Aspergillus fumigatus, Hematologic Neoplasms epidemiology, Invasive Pulmonary Aspergillosis epidemiology, Neoplasms epidemiology
- Abstract
Background: Invasive pulmonary aspergillosis (IPA) is commonly associated with haematologic malignancies but also occurs with solid tumours., Aim: To compare the diagnostic approaches and therapeutic outcomes for IPA between patients with haematologic malignancies and solid cancers., Methods: A retrospective study was conducted evaluating consecutive cases of proven and probable IPA from 2004 to 2016. Patients >18 years of age with an underlying solid tumour, haematologic malignancy, or haematopoietic cell transplantation (HCT) within one year of IPA diagnosis were included., Findings: Of the 311 patients analysed, 225 had haematologic malignancies and 86 had solid tumours. Patients with solid tumours were more likely to have had chronic obstructive pulmonary disease (COPD) or other pulmonary diseases, have Aspergillus fumigatus infections, and have received radiotherapy before IPA occurrence than were those with haematologic malignancies (all P<0.01). Antifungal monotherapy and voriconazole-based therapy were more often prescribed in the solid group (87% vs 56%, P<0.0001, and 77% vs 53%, P=0.0002, respectively). The median duration of primary antifungal therapy was longer in the solid group (64 days vs 20 days, P<0.0001). Complete or partial response to antifungal therapy was recorded in 66% of the solid group and 40% of the haematologic group (P=0.0001). At 12 weeks, overall mortality was similar in both groups, but IPA-attributable mortality was higher in the haematologic group (30% vs 18%, P=0.04)., Conclusions: Monotherapy was more often prescribed in patients with solid tumours than in patients with haematologic malignancies. Patients with solid tumours had better antifungal therapy response and lower 12-week IPA-attributable mortality than did those with haematologic malignancies., (Copyright © 2019 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)
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- 2020
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21. Pilot Ex Vivo and In Vitro Evaluation of a Novel Foley Catheter with Antimicrobial Periurethral Irrigation for Prevention of Extraluminal Biofilm Colonization Leading to Catheter-Associated Urinary Tract Infections (CAUTIs).
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Vargas-Cruz N, Rosenblatt J, Reitzel RA, Chaftari AM, Hachem R, and Raad I
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- Animals, Candida albicans drug effects, Catheter-Related Infections microbiology, Catheters, Indwelling, Drug Resistance, Multiple, Bacterial drug effects, Enterococcus faecalis drug effects, Escherichia coli drug effects, Female, Humans, In Vitro Techniques, Infection Control methods, Klebsiella pneumoniae drug effects, Models, Animal, Proteus mirabilis drug effects, Pseudomonas aeruginosa drug effects, Swine, Urinary Catheterization instrumentation, Urinary Tract Infections microbiology, Anti-Infective Agents pharmacology, Bacteria drug effects, Biofilms drug effects, Catheter-Related Infections prevention & control, Urinary Catheterization methods, Urinary Tract Infections prevention & control
- Abstract
CAUTI remains a serious healthcare issue for incontinent patients whose urine drainage is managed by catheters. A novel double-balloon Foley catheter was developed which was capable of irrigating the extraluminal catheter surfaces within the periurethral space between the urethral-bladder junction and meatus. The catheter has a retention cuff that is inflated to secure the catheter in the bladder and a novel irrigation cuff proximal to the urethral-bladder junction capable of providing periurethral irrigation from the urethral-bladder junction to the meatus. Uniform periurethral irrigation was demonstrated in an ex vivo porcine model by adding a dye to the antimicrobial urethral irrigation solution. An in vitro biofilm colonization model was adapted to study the ability of periurethral irrigation with a newly developed antimicrobial combination consisting of polygalacturonic acid + caprylic acid (PG + CAP) to prevent axial colonization of the extraluminal urethral indwelling catheter shaft by common uropathogens. The extraluminal surface of control catheters that were not irrigated formed biofilms along the entire axial urethral tract after 24 hours. Significant ( p < 0.001) inhibition of colonization was seen against multidrug-resistant Pseudomonas aeruginosa (PA), carbapenem-resistant Escherichia coli (EC), and carbapenem-resistant Klebsiella pneumoniae (KB). For other common uropathogens including Candida albicans (CA), Proteus mirabilis (PR), and Enterococcus faecalis (EF), a first irrigation treatment completely inhibited colonization of half of the indwelling catheter closest to the bladder and a second treatment largely disinfected the remaining intraurethral portion of the catheter towards the meatus. The novel Foley catheter and PG + CAP antimicrobial irrigant prevented biofilm colonization in an in vitro CAUTI model and merits further testing in an in vivo CAUTI prevention model., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Nylev Vargas-Cruz et al.)
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- 2019
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22. Correction to: Impact of antibiotic therapy on the development and response to treatment of immune checkpoint inhibitor-mediated diarrhea and colitis.
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Abu-Sbeih H, Herrera LN, Tang T, Altan M, Chaftari AM, Okhuysen PC, Jenq RR, and Wang Y
- Abstract
Following publication of the original article [1], the authors have reported that an author's name has been incorrectly spelled: the correct given name is Anne-Marie (instead of Anne-Maria P) and family name is Chaftari.
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- 2019
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23. Impact of Catheter Management on Clinical Outcome in Adult Cancer Patients With Gram-Negative Bacteremia.
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Fares J, Khalil M, Chaftari AM, Hachem R, Jiang Y, Kantarjian HM, and Raad II
- Abstract
Objective: Gram-negative organisms have become a major etiology of bloodstream infections. We evaluated the effect of central venous catheter management on cancer patients with gram-negative bloodstream infections., Method: We retrospectively identified patients older than 14 years with central venous catheters who were diagnosed with gram-negative bloodstream infections to determine the effect of catheter management on outcome. Patients were divided into 3 groups: Group 1 included patients with central line-associated bloodstream infections (CLABSI) without mucosal barrier injury and those whose infection met the criteria for catheter-related bloodstream infection; group 2 included patients with CLABSI with mucosal barrier injury who did not meet the criteria for catheter-related bloodstream infection; and group 3 included patients with non-CLABSI., Results: The study included 300 patients, with 100 patients in each group. Only in group 1 was central venous catheter removal within 2 days of bloodstream infection significantly associated with a higher rate of microbiologic resolution at 4 days compared to delayed central venous catheter removal (3-5 days) or retention (98% vs 82%, P = .006) and a lower overall mortality rate at 3-month follow-up (3% vs 19%, P = .01). Both associations persisted in multivariate analyses ( P = .018 and P = .016, respectively)., Conclusions: Central venous catheter removal within 2 days of the onset of gram-negative bloodstream infections significantly improved the infectious outcome and overall mortality of adult cancer patients with catheter-related bloodstream infections and CLABSI without mucosal barrier injury., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
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- 2019
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24. Advances in the prevention and management of central-line-associated bloodstream infections: The role of chelator-based catheter locks.
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Chaftari AM, Viola GM, Rosenblatt J, Hachem R, and Raad I
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- Catheterization, Central Venous, Humans, Anti-Infective Agents therapeutic use, Bacteremia prevention & control, Catheter-Related Infections prevention & control, Catheters, Indwelling microbiology, Central Venous Catheters microbiology, Chelating Agents therapeutic use
- Abstract
The proper functioning of central lines is imperative for the management of patients with cancer or on hemodialysis. However, these lifelines can become infected and can malfunction.Chelators such as citrate and EDTA have been widely studied alone or in combination with other antimicrobial agents in catheter lock solutions to prevent catheter-related bloodstream infections and to maintain catheter patency. Given their anticoagulation, antiplatelet aggregation, antibiofilm, antimicrobial activity, safety profile, as well as their low cost, chelators have long been considered alternatives to heparin and a vital component of catheter lock solutions. In this review, we present a detailed summary of the properties of chelators and in vitro and in vivo studies of chelator-containing lock solutions.
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- 2019
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25. Epidemiology of Infectious and Noninfectious Catheter Complications in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Meta-Analysis.
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Reitzel RA, Rosenblatt J, Chaftari AM, and Raad II
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- Adolescent, Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents, Bacteremia, Catheter-Related Infections microbiology, Catheter-Related Infections prevention & control, Child, Equipment Failure, Ethanol, Female, Humans, Male, Middle Aged, Taurine analogs & derivatives, Thiadiazines, Venous Thrombosis epidemiology, Venous Thrombosis etiology, Young Adult, Catheter-Related Infections epidemiology, Catheterization, Central Venous adverse effects, Central Venous Catheters adverse effects, Parenteral Nutrition, Home adverse effects
- Abstract
Patients receiving parenteral nutrition (PN) as their primary source of nutrition are at high risk for both infectious and noninfectious catheter complications (catheter-related infections, catheter occlusion, and venous thrombosis). The aim of this review was to synthesize and evaluate what is known about catheter complications and prevention strategies in the PN population. Three electronic databases (Medline, Embase, and CINAHL) were screened for studies published between January 2012 and February 2019 regarding infectious and noninfectious catheter complications in patients receiving PN. Rates of infectious and noninfectious catheter complications, prevalence of causative pathogens, potential risk factors, and prevention strategies via the use of antimicrobial lock therapy (ALT) were assessed. Fifty-three catheter complication studies and 12 ALT studies were included. Studies were grouped by definition of complication: catheter-related bloodstream infections (CRBSI) or central line-associated bloodstream infections (CLABSI). Random effects summary rates per 1000 catheter days were 0.85 CRBSI episodes (95% CI 0.27-2.64) and 1.65 CLABSI episodes (95% CI 1.09-2.48). Use of taurolidine or ethanol ALT was efficacious in reducing infectious catheter complications; however, several studies had concerns for adverse mechanical complications. Potential risk factors for catheter complications were highly varied and often contradictory between studies. The rates of catheter complications were higher among catheterized patients receiving PN compared with nationally reported rates of complications in all catheterized patients. Risk factors for catheter complications need to be better understood for targeted prophylactic use of ALT. Future studies are warranted; however, they should be conducted using more standardized definitions and criteria., (© 2019 American Society for Parenteral and Enteral Nutrition.)
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- 2019
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26. Nitroglycerin-Citrate-Ethanol Catheter Lock Solution Is Highly Effective for In Vitro Eradication of Candida auris Biofilm.
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Vargas-Cruz N, Reitzel RA, Rosenblatt J, Chaftari AM, Wilson Dib R, Hachem R, Kontoyiannis DP, and Raad II
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- Amphotericin B pharmacology, Anidulafungin pharmacology, Biofilms, Caspofungin pharmacology, Catheter-Related Infections prevention & control, Ethanol pharmacology, Fluconazole pharmacology, Micafungin pharmacology, Pharmaceutical Solutions, Voriconazole pharmacology, Antifungal Agents pharmacology, Candida drug effects, Catheters microbiology, Citric Acid pharmacology, Nitroglycerin pharmacology
- Abstract
Candida auris poses emerging risks for causing severe central line-associated bloodstream infections. We tested in vitro the ability of antifungal lock solutions to rapidly eradicate C. auris biofilms. Liposomal amphotericin B, amphotericin B deoxycholate, fluconazole, voriconazole, micafungin, caspofungin, and anidulafungin failed to completely eradicate all 10 tested C. auris biofilms. Conversely, nitroglycerin-citrate-ethanol (NiCE) catheter lock solution completely eradicated all replicates for all of C. auris biofilms tested., (Copyright © 2019 American Society for Microbiology.)
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- 2019
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27. Corrigendum to "Can procalcitonin differentiate Staphylococcus aureus from coagulase-negative staphylococci in clustered gram-positive bacteremia?" [Diagn Microbiol Infect Dis 2019;76(2):158-161].
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Shomali W, Hachem R, Chaftari AM, Bahu R, El Helou G, Jiang Y, Hanania AN, Reitzel R, and Raad I
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- 2019
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28. International Multicenter Experience in the Treatment Outcome of Invasive Aspergillosis in Immunocompromised Cancer Patients.
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Hachem R, Batista MV, Kanj SS, El Zein S, Haddad S, Jiang Y, Mori N, Vanderson R, Chaftari AM, and Raad I
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Background: Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised patients. In this study, we compared the efficacy of voriconazole containing regimen vs non-voriconazole containing regimen in patients with IA., Methods: In this retrospective study, we reviewed the medical records of all immunocompromised cancer patients diagnosed with proven or probable IA between February 2012 and March 2018. This trial included 26 patients from the American University of Beirut, Lebanon, 20 patients from Hospital das Clinicas da Faculdade de Medicina, Universidade de São Paulo, Brazil, and 10 patients from St. Luke's International Hospital Tokyo, Japan., Results: A total of 56 patients were analyzed. They were divided into 2 groups voriconazole containing regimen and non-voriconazole containing regimen (90% Amphotericin B based regimen). Both groups had similar characteristic, age, gender, and immunocompromised status. The majority of patients had underlying leukemia (63%), followed by lymphoma (20%), myeloma (16%) and other hematologic malignancy (1%). Antifungal primary therapy with voriconazole-containing regimen was associated with better response to treatment ( p = 0.003). Survival analysis showed that primary therapy with a voriconazole containing regimen was significantly associated with improved survival ( p =0.006). By multivariate logistic regression analysis, mechanical ventilation was a predictor of worse outcomes (poor response to therapy and increased mortality within 6 months), whereas primary treatment with voriconazole containing regimen was associated with improved outcomes including response to primary therapy (OR=18.1, p =0.002) and 6-month mortality (OR=0.14, p =0.011)., Conclusions: Based on international experience in immunocompromised cancer patients with IA, primary therapy with voriconazole-containing regimen is associated with improved response and survival compared with non-voriconazole amphotericin B based regimen., Competing Interests: Competing interests: The authors have declared that no competing interests exist.
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- 2019
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29. Treating invasive aspergillosis in patients with hematologic malignancy: diagnostic-driven approach versus empiric therapies.
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Dib RW, Hachem RY, Chaftari AM, Ghaly F, Jiang Y, and Raad I
- Subjects
- Adult, Aged, Aged, 80 and over, Aspergillosis complications, Aspergillosis diagnosis, Aspergillosis drug therapy, Aspergillosis mortality, Empiricism, Female, Hematologic Neoplasms complications, Hematologic Neoplasms diagnosis, Hematologic Neoplasms mortality, Humans, Invasive Pulmonary Aspergillosis complications, Invasive Pulmonary Aspergillosis diagnosis, Invasive Pulmonary Aspergillosis mortality, Male, Middle Aged, Precision Medicine methods, Precision Medicine statistics & numerical data, Prognosis, Retrospective Studies, Standard of Care statistics & numerical data, Survival Analysis, Treatment Outcome, Voriconazole therapeutic use, Young Adult, Antifungal Agents therapeutic use, Hematologic Neoplasms drug therapy, Invasive Pulmonary Aspergillosis drug therapy
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Background: Early antifungal therapy for invasive aspergillosis (IA) has been associated with improved outcome. Traditionally, of empiric antifungal therapy has been used for clinically suspected IA. We compared outcomes of patients with hematologic malignancy and IA who were treated with voriconazole using the diagnostic driven DDA (DDA-Vori) that includes galactomannan testing vs. empiric therapy with a non-voriconazole-containing regimen (EMP-non-Vori) or empiric therapy with voriconazole (EMP-Vori)., Methods: We retrospectively reviewed the medical records of 342 hematologic malignancy patients diagnosed with proven, or probable IA between July 1993 and February 2016 at our medical center who received at least 7 days of DDA-Vori, EMP-Vori, or EMP-non-Vori. Outcome assessment included response to therapy (clinical and radiographic), all-cause mortality, and IA-attributable mortality., Results: By multivariate analysis, factors predictive of a favorable response included localized/sinus IA vs. disseminated/pulmonary IA (p < 0.0001), not receiving white blood cell transfusion (p < 0.01), and DDA-Vori vs. EMP-non-Vori (p < 0.0001). In contrast, predictors of mortality within 6 weeks of initiating IA therapy included disseminated/pulmonary infection vs. localized/sinus IA (p < 0.01), not undergoing stem cell transplantation within 1 year before IA (p = 0.01), and EMP-non-Vori vs. DDA-Vori (p < 0.001)., Conclusions: DDA-Vori was associated with better outcome (response and survival) compared with EMP-non-Vori and with equivalent outcome to EMP-Vori in hematologic malignancy patients. These outcomes associated with the implementation of DDA could lead to a reduction in the unnecessary costs and adverse events associated with the widespread use of empiric therapy.
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- 2018
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30. Invasive pulmonary aspergillosis in patients with solid tumours: risk factors and predictors of clinical outcomes.
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Dandachi D, Wilson Dib R, Fernández-Cruz A, Jiang Y, Chaftari AM, Hachem R, and Raad I
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- Aged, Female, Follow-Up Studies, Humans, Immunocompromised Host, Incidence, Invasive Pulmonary Aspergillosis drug therapy, Invasive Pulmonary Aspergillosis immunology, Invasive Pulmonary Aspergillosis microbiology, Lung diagnostic imaging, Lung microbiology, Male, Middle Aged, Neoplasms diagnosis, Neoplasms immunology, Prognosis, Retrospective Studies, Risk Factors, Survival Analysis, Tomography, X-Ray Computed, Treatment Outcome, Voriconazole therapeutic use, Antifungal Agents therapeutic use, Aspergillus isolation & purification, Invasive Pulmonary Aspergillosis mortality, Neoplasms epidemiology
- Abstract
Background: The characteristics and management of invasive pulmonary aspergillosis (IPA) in patients with hematologic malignancies are well known, but IPA in patients with solid tumours is not well described., Methods: We retrospectively reviewed all Aspergillus-positive cultures at a tertiary cancer center during 2004-2017. We identified 101 patients with IPA and solid tumours. We analyzed the association between clinical features and treatment and 12-week mortality and response to antifungal therapy., Results: Fifty-one patients had lung cancer, 77 had underlying lung disease, 47 received chest radiation and 33 had chronic obstructive pulmonary disease. Aspergillus fumigatus was the most common type isolated (71%); 68 patients (70%) were treated with voriconazole monotherapy. Independent risk factors for 12-week mortality included receiving steroids within 30 days of diagnosis (hazard ratio 2.2, 95% confidence interval [CI]: 1.1-4.6; p = .03) and chest radiotherapy (hazard ratio 2.6, 95% CI: 1.2-5.5; p = .01). In multivariate analysis, a positive fungal stain was associated with lower odds of a successful response (odds ratio 0.2; 95% CI: 0.05-0.75; p = .02), whereas voriconazole treatment was associated with higher odds (odds ratio 10.1; 95% CI: 2.1-48.5; p < .01)., Conclusions: IPA should be considered in patients with solid tumours, particularly those with underlying lung disease. Key messages Invasive pulmonary aspergillosis should be considered in patients with solid tumours, particularly those with underlying lung disease, lung cancer and those who received chest radiotherapy. Most of the patients with invasive pulmonary aspergillosis and solid tumours presented with nonspecific symptoms and signs as well as nonspecific CT findings. Unlike patients with hematologic malignancies, fever and hemoptysis were not predominant symptoms and the classical halo sign and the air-crescent sign were not described. Independent risk factors for 12-week mortality included receiving steroids within 30 days of diagnosis and chest radiotherapy. In multivariate analysis, a positive fungal stain was associated with lower odds of a successful response to antifungal therapy, whereas voriconazole treatment was associated with higher odds.
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- 2018
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31. Catheter-Related Staphylococcus aureus Bacteremia and Septic Thrombosis: The Role of Anticoagulation Therapy and Duration of Intravenous Antibiotic Therapy.
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Wilson Dib R, Chaftari AM, Hachem RY, Yuan Y, Dandachi D, and Raad II
- Abstract
Background: Catheter-related septic thrombosis is suspected in patients with persistent central line-associated bloodstream infection (CLABSI) after 72 hours of appropriate antimicrobial therapy. The clinical diagnosis and management of this entity can be challenging as limited data are available. We retrospectively studied the clinical characteristics of patients with Staphylococcus aureus catheter-related septic thrombosis and the outcomes related to different management strategies., Methods: This retrospective study included patients with CLABSI due to S. aureus who had concomitant radiographic evidence of catheter site thrombosis treated at our institution between the years 2005 and 2016. We collected data pertaining to patients' medical history, clinical presentation, management, and outcome within 3 months of bacteremia onset., Results: A total of 128 patients were included. We found no significant difference in overall outcome between patients who had deep vs superficial thrombosis. Patients with superficial thrombosis were found to have a higher rate of pulmonary complications (25% vs 6%; P = .01) compared with those with deep thrombosis. Patients who received less than 28 days of intravascular antibiotic therapy had higher all-cause mortality (31 vs 5%; P = .001). A multivariate logistic regression analysis identified 2 predictors of treatment failure: ICU admission during their illness (odds ratio [OR], 2.74; 95% confidence interval [CI], 1.08-6.99; P = .034) and not receiving anticoagulation therapy (OR, 0.24; 95% CI, 0.11-0.54; P < .001)., Conclusions: Our findings suggest that the presence of S. aureus CLABSI in the setting of catheter-related thrombosis may warrant prolonged intravascular antimicrobial therapy and administration of anticoagulation therapy in critically ill cancer patients.
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- 2018
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32. Emerging outbreaks associated with conflict and failing healthcare systems in the Middle East.
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Raad II, Chaftari AM, Dib RW, Graviss EA, and Hachem R
- Subjects
- Communicable Diseases, Emerging diagnosis, Communicable Diseases, Emerging therapy, Health Services trends, Humans, Incidence, Middle East epidemiology, Communicable Diseases, Emerging epidemiology, Health Services supply & distribution, Refugees statistics & numerical data, War Exposure adverse effects
- Abstract
The escalating conflicts in the Middle East have been associated with the rapid collapse of the existing healthcare systems in affected countries. As millions of refugees flee their countries, they become vulnerable and exposed to communicable diseases that easily grow into epidemic crises. Here, we describe infectious disease epidemics that have been associated with conflicts in the Middle East, including cholera, poliomyelitis, measles, cutaneous leishmaniasis, and diphtheria, that call for appropriate preventive measures. Local ongoing wars and failing healthcare systems have resulted in regional and global health threats that warrant international medical interventions.
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- 2018
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33. Challenge of hepatitis C in Egypt and hepatitis B in Mauritania.
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Raad II, Chaftari AM, Torres HA, Ayoub EM, Narouz LI, Bartek J, and Hachem R
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Egypt has one of the highest prevalence rates of hepatitis C virus (HCV) in the world, mostly with genotype 4 that is highly associated with severe fibrosis. As a consequence, hepatocellular carcinoma has become the leading cause of cancer in this country. Mauritania is a highly endemic area for hepatitis B virus (HBV). HBV and HCV could both be iatrogenically transmitted through infected blood products, infected needles, and medical equipment improperly sterilized. Adequate and efficient healthcare and public health measures with good surveillance programs, access for screening, prevention strategies, and successful treatment are needed to halt the spread of these diseases. Herein, we have reviewed the epidemiology, modes of transmission, predisposing factors, and novel treatment modalities of these viruses. We have proposed practices and interventions to decrease the risk of transmission of HCV and HBV in the affected countries, including strict adherence to standard precautions in the healthcare setting, rigorous education and training of patients and healthcare providers, universal screening of blood donors, use of safety-engineered devices, proper sterilization of medical equipment, hepatitis B vaccination, as well as effective direct-acting antiviral agents for the treatment of HCV., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest. No financial support.
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- 2018
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34. Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.
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Holland TL, Raad I, Boucher HW, Anderson DJ, Cosgrove SE, Aycock PS, Baddley JW, Chaftari AM, Chow SC, Chu VH, Carugati M, Cook P, Corey GR, Crowley AL, Daly J, Gu J, Hachem R, Horton J, Jenkins TC, Levine D, Miro JM, Pericas JM, Riska P, Rubin Z, Rupp ME, Schrank J Jr, Sims M, Wray D, Zervos M, and Fowler VG Jr
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- Adult, Aged, Aged, 80 and over, Anti-Bacterial Agents adverse effects, Coagulase, Confidence Intervals, Drug Administration Schedule, Female, Humans, Intention to Treat Analysis, Male, Middle Aged, Single-Blind Method, Staphylococcus isolation & purification, Algorithms, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Staphylococcal Infections drug therapy, Staphylococcus aureus isolation & purification
- Abstract
Importance: The appropriate duration of antibiotics for staphylococcal bacteremia is unknown., Objective: To test whether an algorithm that defines treatment duration for staphylococcal bacteremia vs standard of care provides noninferior efficacy without increasing severe adverse events., Design, Setting, and Participants: A randomized trial involving adults with staphylococcal bacteremia was conducted at 16 academic medical centers in the United States (n = 15) and Spain (n = 1) from April 2011 to March 2017. Patients were followed up for 42 days beyond end of therapy for those with Staphylococcus aureus and 28 days for those with coagulase-negative staphylococcal bacteremia. Eligible patients were 18 years or older and had 1 or more blood cultures positive for S aureus or coagulase-negative staphylococci. Patients were excluded if they had known or suspected complicated infection at the time of randomization., Interventions: Patients were randomized to algorithm-based therapy (n = 255) or usual practice (n = 254). Diagnostic evaluation, antibiotic selection, and duration of therapy were predefined for the algorithm group, whereas clinicians caring for patients in the usual practice group had unrestricted choice of antibiotics, duration, and other aspects of clinical care., Main Outcomes and Measures: Coprimary outcomes were (1) clinical success, as determined by a blinded adjudication committee and tested for noninferiority within a 15% margin; and (2) serious adverse event rates in the intention-to-treat population, tested for superiority. The prespecified secondary outcome measure, tested for superiority, was antibiotic days among per-protocol patients with simple or uncomplicated bacteremia., Results: Among the 509 patients randomized (mean age, 56.6 [SD, 16.8] years; 226 [44.4%] women), 480 (94.3%) completed the trial. Clinical success was documented in 209 of 255 patients assigned to algorithm-based therapy and 207 of 254 randomized to usual practice (82.0% vs 81.5%; difference, 0.5% [1-sided 97.5% CI, -6.2% to ∞]). Serious adverse events were reported in 32.5% of algorithm-based therapy patients and 28.3% of usual practice patients (difference, 4.2% [95% CI, -3.8% to 12.2%]). Among per-protocol patients with simple or uncomplicated bacteremia, mean duration of therapy was 4.4 days for algorithm-based therapy vs 6.2 days for usual practice (difference, -1.8 days [95% CI, -3.1 to -0.6])., Conclusions and Relevance: Among patients with staphylococcal bacteremia, the use of an algorithm to guide testing and treatment compared with usual care resulted in a noninferior rate of clinical success. Rates of serious adverse events were not significantly different, but interpretation is limited by wide confidence intervals. Further research is needed to assess the utility of the algorithm., Trial Registration: ClinicalTrials.gov Identifier: NCT01191840.
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- 2018
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35. Biomarkers of Sepsis and Bloodstream Infections: The Role of Procalcitonin and Proadrenomedullin With Emphasis in Patients With Cancer.
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El Haddad H, Chaftari AM, Hachem R, Chaftari P, and Raad II
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- Biomarkers blood, Critical Illness, Fever etiology, Humans, Immunocompromised Host, Neoplasms microbiology, Randomized Controlled Trials as Topic, Adrenomedullin blood, Bacteremia diagnosis, Neoplasms complications, Procalcitonin blood, Protein Precursors blood, Sepsis diagnosis
- Abstract
Sepsis and bloodstream infections remain a leading cause of death in immunocompromised patients with cancer. The management of these serious infections consist of empiric use of antimicrobial agents which are often overused. Procalcitonin and proadrenomedullin are biomarkers that have been extensively evaluated in the general populations but with little emphasis in the population immunocompromised patients with cancer, where they may have promising roles in the management of febrile patients. In this review, we summarize the available evidence of the potential role of these available biomarkers in guiding antimicrobial therapy to optimize the use of resources in the general patient population. Special emphasis is given to the role of these 2 biomarkers in the immunocompromised and critically ill patients with cancer, highlighting the distinctive utility of each.
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- 2018
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36. Removal and insertion of central venous catheters in cancer patients is associated with high symptom burden.
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Raad S, Chaftari AM, Hachem RY, Shah P, Natividad E, Cleeland CS, and Rosenblatt J
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- Factor Analysis, Statistical, Humans, Catheterization, Central Venous, Central Venous Catheters, Device Removal, Neoplasms pathology
- Abstract
Objectives: To assess the symptom burden associated with CVC removal and insertion in cancer patients., Methods: We collected patient-reported symptom-burden outcomes for 60 consecutive cancer patients: 30 undergoing CVC removal and 30 undergoing CVC insertion. Cancer patients self-administered the MD Anderson Symptom Inventory to rate the severity of 21 different symptoms immediately after the procedure Results: Symptoms were present in up to 57% to 67% of patients undergoing CVC insertion and removal respectively. Nineteen patients (32%) were moderately symptomatic with a symptom burden of four or more: ten insertion and nine removal patients. Symptoms with a score of 4 or more clustered around physical symptoms (pain, pressure or burning) or more generalized symptoms (fatigue, sleep, distress, dry mouth, and drowsiness). Nine (15%) patients rated at least one symptom as eight or more, five (17%) being insertion patients., Conclusions: CVCs are essential for the management of cancer patients. However, they can become infected and may need to be removed. Catheter removal and insertion produced moderate to severe symptom burden in cancer patients. Safe interventions that would salvage the vascular access without worsening the infectious outcome should be explored to alleviate morbidity associated with the symptom burden of removal and re-insertion.
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- 2018
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37. International experience with minocycline, EDTA and ethanol lock for salvaging of central line associated bloodstream infections.
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Hachem R, Kanj S, Hamerschlak N, Saad H, Assir FF, Mori N, Jiang Y, Ghaly F, Chaftari AM, and Raad II
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- Bacteremia microbiology, Female, Humans, Male, Middle Aged, Salvage Therapy, Bacteremia drug therapy, Edetic Acid therapeutic use, Ethanol therapeutic use, Minocycline therapeutic use
- Abstract
Background: The use of long-term central venous catheters (CVCs) could lead to serious bloodstream infections. Removal of the infected CVC and reinsertion of a new CVC are not always feasible and alternative lock therapy may be considered. We conducted a multicenter trial to assess the efficacy and safety of the lock therapy., Methods: Between October 2013 and August 2014, we prospectively enrolled 20 patients with catheter-related bloodstream infections (CRBSIs) or central line-associated bloodstream infections (CLABSIs) in our sister institutions in three countries including Brazil, Lebanon, and Japan. The 20 patients who received M-EDTA-EtOH lock therapy were compared to 24 control patients who had their CVCs removed and a new CVC inserted., Results: Both groups had comparable clinical characteristics. In the lock therapy group, 95% of the patients had microbiological eradication within 96 h after starting lock therapy versus 83% of the patients in the control group (p = .36). In the lock group, the CVC was salvaged and retained for a median of 21 days (range 7-51) from the onset of bacteremia., Conclusion: Our study suggests that M-EDTA-EtOH lock therapy may be an effective intervention to salvage long-term CVCs in the setting of CLABSI/CRBSI and hemodialysis cancer patients with limited vascular access.
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- 2018
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38. Changing Epidemiology of Catheter-Related Bloodstream Infections in Cancer Patients.
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Chaftari AM, Hachem R, Jiang Y, Shah P, Hussain A, Hamal ZA, Yousif A, Jordan M, Michael M, and Raad I
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- Adolescent, Adult, Aged, Aged, 80 and over, Catheterization, Central Venous adverse effects, Central Venous Catheters adverse effects, Child, Child, Preschool, Cohort Studies, Cross Infection epidemiology, Cross Infection microbiology, Databases, Factual, Female, Humans, Male, Middle Aged, Neoplasms, Risk Factors, Texas epidemiology, Young Adult, Bacteremia epidemiology, Catheter-Related Infections epidemiology, Catheter-Related Infections microbiology, Gram-Negative Bacterial Infections epidemiology, Gram-Positive Bacterial Infections epidemiology
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We compared the etiologic organisms of bloodstream infections (BSIs) in cancer patients with central venous catheters (CVCs) between 2 cohorts separated by more than a decade.Gram-negative organisms have become the predominant etiologic organisms of BSIs (52%); they now contribute to 41% of catheter-related BSIs (CRBSIs).Infect Control Hosp Epidemiol 2018;39:727-729.
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- 2018
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39. Appropriate Duration of Intravenous Treatment of Candidemia and Timing of Step Down to Oral Therapy in Non-neutropenic Patients.
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Dib RW, Hachem R, Chaftari AM, and Raad I
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In this review, we have analyzed the available literature pertaining to the total duration of intravenous (IV) therapy and the appropriate timing of step down to oral therapy in the management of candidemia. Overview of the guidelines and literature seem to indicate that a minimum of 14 days of antifungal therapy is required in the treatment of candidemia without deeply seated infection. However, this was never based on evidence. Furthermore, step down to oral therapy seems to be dependent on the clinical stability criteria of the patient with candidemia after 4 to 7 days of IV therapy. Further studies are required to evaluate the appropriate total duration of IV therapy, appropriate timing of step down to oral therapy and to validate the clinical criteria that would allow the switch to happen., Competing Interests: Competing interests: The authors have declared that no competing interests exist.
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- 2018
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40. Author Correction: Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients with Documented Infection or Neutropenia.
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El Haddad H, Chaftari AM, Hachem R, Michael M, Jiang Y, Yousif A, Raad S, Jordan M, Chaftari P, and Raad I
- Abstract
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
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- 2018
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41. Unnecessary Removal of Central Venous Catheters in Cancer Patients with Bloodstream Infections.
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Chaftari AM, Hachem R, Raad S, Jiang Y, Natividad E, Chaftari P, and Raad I
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- Adolescent, Adult, Aged, Aged, 80 and over, Bacteremia epidemiology, Catheter-Related Infections epidemiology, Child, Child, Preschool, Cross Infection microbiology, Databases, Factual, Equipment Contamination, Female, Gram-Negative Bacteria isolation & purification, Gram-Negative Bacterial Infections epidemiology, Gram-Positive Bacteria isolation & purification, Gram-Positive Bacterial Infections epidemiology, Humans, Male, Middle Aged, Neoplasms, Retrospective Studies, Texas epidemiology, Young Adult, Bacteremia etiology, Catheter-Related Infections microbiology, Catheterization, Central Venous adverse effects, Central Venous Catheters microbiology, Gram-Negative Bacterial Infections etiology, Gram-Positive Bacterial Infections etiology
- Abstract
We evaluated the rate of central venous catheter (CVC) removal in 283 cancer patients with bloodstream infections (BSIs). Removal of CVCs occurred unnecessarily in 57% of patients with non-central-line-associated BSI (non-CLABSI), which was equivalent to the rate of CVC removal in patients with CLABSIs. Physician education and safe interventions to salvage the vascular access are warranted. Infect Control Hosp Epidemiol 2018;39:222-225.
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- 2018
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42. Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients with Documented Infection or Neutropenia.
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Haddad HE, Chaftari AM, Hachem R, Michael M, Jiang Y, Yousif A, Raad S, Jordan M, Chaftari P, and Raad I
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In this analysis, we identified febrile cancer patients with documented infections or neutropenia, whose procalcitonin levels are low at baseline or decrease on antibiotics. These patients had similar outcomes in terms of mortality and relapse of infection regardless of the duration of antimicrobial therapy (less or more than 7 days).
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- 2018
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43. Caprylic and Polygalacturonic Acid Combinations for Eradication of Microbial Organisms Embedded in Biofilm.
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Rosenblatt J, Reitzel RA, Vargas-Cruz N, Chaftari AM, Hachem R, and Raad I
- Abstract
There is a need for non-antibiotic, antimicrobial compositions with low toxicity capable of broad-spectrum eradication of pathogenic biofilms in food preparation and healthcare settings. In this study we demonstrated complete biofilm eradication within 60 min with synergistic combinations of caprylic and polygalacturonic (PG) acids in an in vitro biofilm eradication model against representative hospital and foodborne infectious pathogen biofilms (methicillin-resistant Staphylococcus aureus , multidrug-resistant Pseudomonas aeruginosa , Candida albicans , Escherichia coli , and Salmonella enteritidis ). Antimicrobial synergy against biofilms was demonstrated by quantifying viable organisms remaining in biofilms exposed to caprylic acid alone, PG acid alone, or combinations of the two. The combinations also synergistically inhibited growth of planktonic organisms. Toxicity of the combination was assessed in vitro on L929 fibroblasts incubated with extracts of caprylic and PG acid combinations using the Alamar Blue metabolic activity assay and the Trypan Blue exclusion cell viability assay. The extracts did not produce cytotoxic responses relative to untreated control fibroblasts.
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- 2017
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44. Comparing catheter-related bloodstream infections in pediatric and adult cancer patients.
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Zakhour R, Hachem R, Alawami HM, Jiang Y, Michael M, Chaftari AM, and Raad I
- Subjects
- Adolescent, Adult, Age Factors, Child, Child, Preschool, Female, Humans, Infant, Male, Catheter-Related Infections blood, Catheter-Related Infections diagnosis, Catheter-Related Infections epidemiology, Electronic Health Records, Gram-Negative Bacterial Infections blood, Gram-Negative Bacterial Infections diagnosis, Gram-Negative Bacterial Infections epidemiology, Hematologic Neoplasms blood, Hematologic Neoplasms epidemiology, Hematologic Neoplasms microbiology, Hematologic Neoplasms therapy
- Abstract
Objective: Central venous catheters (CVCs) are essential to treatment of children with cancer. There are no studies comparing catheter-related bloodstream infections (CRBSIs) in pediatric cancer patients to those in adults, although current guidelines for management of CRBSI do not give separate guidelines for the pediatric population. In this study, we compared CRBSIs in both the pediatric and adult cancer population., Methods: We retrospectively reviewed the electronic medical records of 92 pediatric and 156 adult patients with CRBSI cared for at MD Anderson Cancer Center between September 2005 and March 2014., Results: We evaluated 248 patients with CRBSI. There was a significant difference in etiology of CRBSI between pediatric and adult patients (P = 0.002), with the former having less Gram-negative organisms (27 vs. 46%) and more polymicrobial infections (10 vs. 1%, P = 0.003). Pediatric patients had less hematologic malignancies (58 vs. 74%) and less neutropenia at presentation (40 vs. 54%) when compared with adult patients. Peripheral blood cultures were available in only 43% of pediatric cases. CVC was removed in 64% of pediatric cases versus 88% of adult cases (P < 0.0001)., Conclusion: We found higher rates of Gram-negative organisms in adults and higher rates of polymicrobial in children. Because of the low rates of peripheral blood cultures and the low rates of CVC removal, CRBSI diagnosis could be challenging in pediatrics. A modified CRBSI definition relying more on clinical criteria may be warranted., (© 2017 Wiley Periodicals, Inc.)
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- 2017
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45. Comparing the safety and efficacy of voriconazole versus posaconazole in the prevention of invasive fungal infections in high-risk patients with hematological malignancies.
- Author
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Hachem R, Assaf A, Numan Y, Shah P, Jiang Y, Chaftari AM, and Raad II
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Chemoprevention methods, Drug-Related Side Effects and Adverse Reactions epidemiology, Drug-Related Side Effects and Adverse Reactions pathology, Female, Hematologic Neoplasms complications, Hospitals, University, Humans, Invasive Fungal Infections drug therapy, Male, Middle Aged, Retrospective Studies, Survival Analysis, Texas, Treatment Outcome, Young Adult, Antifungal Agents administration & dosage, Antifungal Agents adverse effects, Invasive Fungal Infections prevention & control, Triazoles administration & dosage, Triazoles adverse effects, Voriconazole administration & dosage, Voriconazole adverse effects
- Abstract
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., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)
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- 2017
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46. Correction for Chaftari et al., "A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients".
- Author
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Chaftari AM, 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, and Raad I
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- 2017
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47. A Novel Nonantibiotic Nitroglycerin-Based Catheter Lock Solution for Prevention of Intraluminal Central Venous Catheter Infections in Cancer Patients.
- Author
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Chaftari AM, 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, and Raad I
- Subjects
- Adult, Aged, Aged, 80 and over, Catheter-Related Infections prevention & control, Catheterization, Central Venous adverse effects, Female, Humans, Male, Middle Aged, Prospective Studies, Central Venous Catheters microbiology, Neoplasms drug therapy, Neoplasms microbiology, Nitroglycerin therapeutic use
- 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.)., (Copyright © 2017 American Society for Microbiology.)
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- 2017
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48. In Vitro Study of Antimicrobial Percutaneous Nephrostomy Catheters for Prevention of Renal Infections.
- Author
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Vargas-Cruz N, Reitzel RA, Rosenblatt J, Jamal M, Szvalb AD, Chaftari AM, Hachem R, and Raad I
- Subjects
- Anti-Infective Agents therapeutic use, Biofilms drug effects, Candida albicans drug effects, Candida albicans pathogenicity, Candida glabrata drug effects, Candida glabrata pathogenicity, Enterobacter drug effects, Enterobacter pathogenicity, Escherichia coli drug effects, Escherichia coli pathogenicity, Methicillin-Resistant Staphylococcus aureus drug effects, Methicillin-Resistant Staphylococcus aureus pathogenicity, Nephrotomy, Vancomycin-Resistant Enterococci drug effects, Vancomycin-Resistant Enterococci pathogenicity, Anti-Bacterial Agents therapeutic use, Kidney Diseases drug therapy, Kidney Diseases microbiology
- Abstract
Percutaneous nephrostomy (PCN) catheters are the primary method for draining ureters obstructed by malignancy and preventing a decline of renal function. However, PCN catheter-related infections, such as pyelonephritis and urosepsis, remain a significant concern. Currently, no antimicrobial PCN catheters are available for preventing infection complications. Vascular catheters impregnated with minocycline-rifampin (M/R) and M/R with chlorhexidine coating (M/R plus CHD) have previously demonstrated antimicrobial activity. Therefore, in this study, we examined whether these combinations could be applied to PCN catheters and effectively inhibit biofilm formation by common uropathogens. An in vitro biofilm colonization model was used to assess the antimicrobial efficacy of M/R and M/R-plus-CHD PCN catheters against nine common multidrug-resistant Gram-positive and Gram-negative uropathogens as well as Candida glabrata and Candida albicans Experimental catheters were also assessed for durability of antimicrobial activity for up 3 weeks. PCN catheters coated with M/R plus CHD completely inhibited biofilm formation for up to 3 weeks for all the organisms tested. The reduction in colonization compared to uncoated PCN catheters was significant for all Gram-positive, Gram-negative, and fungal organisms ( P < 0.05). M/R-plus-CHD PCN catheters also produced significant reductions in biofilm colonization relative to M/R PCN catheters for Enterobacter spp., Escherichia coli , Pseudomonas aeruginosa , methicillin-resistant Staphylococcus aureus , vancomycin-resistant enterococci, C. glabrata , and C. albicans ( P < 0.05). M/R-plus-CHD PCN catheters proved to be highly efficacious in preventing biofilm colonization when exposed to multidrug-resistant pathogens common in PCN catheter-associated pyelonephritis. M/R-plus-CHD PCN catheters warrant evaluation in a clinical setting to assess their ability to prevent clinically relevant nephrostomy infections., (Copyright © 2017 American Society for Microbiology.)
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- 2017
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49. Novel plasma telomerase detection method to improve cancer diagnostic assessment.
- Author
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Hilal G, Reitzel R, Al Hamal Z, Chaftari AM, Al Wohoush I, Jiang Y, Hachem R, and Raad II
- Subjects
- Animals, Carcinoma, Pancreatic Ductal enzymology, Case-Control Studies, Humans, Mice, Pancreatic Neoplasms enzymology, Real-Time Polymerase Chain Reaction, Sensitivity and Specificity, Carcinoma, Pancreatic Ductal diagnosis, Pancreatic Neoplasms diagnosis, Telomerase blood
- Abstract
Background: The activity levels of telomerase and its mRNA have been found to be more diagnostically sensitive than cytological results in many cancerous tissues and correlate well with the clinical disease stage. Currently, there are several methods of detecting telomerase in tissues and in blood. The most commonly used method is a conventional quantitative real-time polymerase chain reaction (PCR) which is time and labor exhausting., Methods: We have developed a simple and innovative blood test method that allows us to diagnose cancer and relapsed cancer in a cost- and time -effective manner. We had evaluated our novel method in two populations: 1) in vivo in three mice with pancreatic ductal adenocarcinoma (PDAC) versus one control mouse and 2) clinically in 30 cancer patients versus 10 individuals without cancer. We compared our novel method with the old conventional method. At least one sample was obtained from each patient included in the study., Results: The novel method substantially increased the sensitivity (from 37% to 77%, p<0.001) and negative predictive value (from 32% to 56%, p = 0.005) of the telomerase test for all cancer patients (those who were substantially treated and those who were not). There was no significant difference in telomerase activity between cancer patients and healthy volunteers using the conventional method (p = 0.13), whereas there was a significant difference using the novel method (p = 0.001)., Conclusion: Conventional method shows no significant difference in telomerase activity between cancer patients and healthy volunteers (p = 0.13), whereas there was a significant difference using the novel method (p = 0.001).
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- 2017
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50. Antimicrobial Activities of Ceftazidime-Avibactam and Comparator Agents against Clinical Bacteria Isolated from Patients with Cancer.
- Author
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Hachem R, Reitzel R, Rolston K, Chaftari AM, and Raad I
- Subjects
- Cefepime, Cephalosporins pharmacology, Drug Combinations, Enterobacteriaceae growth & development, Enterobacteriaceae isolation & purification, Enterobacteriaceae Infections complications, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections microbiology, Humans, Meropenem, Microbial Sensitivity Tests, Neoplasms complications, Neoplasms drug therapy, Neoplasms microbiology, Opportunistic Infections complications, Opportunistic Infections drug therapy, Opportunistic Infections microbiology, Penicillanic Acid analogs & derivatives, Penicillanic Acid pharmacology, Piperacillin pharmacology, Piperacillin, Tazobactam Drug Combination, Pseudomonas Infections complications, Pseudomonas Infections drug therapy, Pseudomonas Infections microbiology, Pseudomonas aeruginosa growth & development, Pseudomonas aeruginosa isolation & purification, Thienamycins pharmacology, Anti-Bacterial Agents pharmacology, Azabicyclo Compounds pharmacology, Ceftazidime pharmacology, Drug Resistance, Multiple, Bacterial, Enterobacteriaceae drug effects, Pseudomonas aeruginosa drug effects
- Abstract
A total of 521 unique clinical isolates from cancer patients with primarily (>90%) bloodstream infections were tested for susceptibility to ceftazidime-avibactam and comparators using broth microdilution methods. Ceftazidime-avibactam inhibited 97.8% of all Enterobacteriaceae ( n = 321) at the susceptibility breakpoint of ≤8/4 μg/ml (there were 7 nonsusceptible strains). It was also active against Pseudomonas aeruginosa (91.7% isolates susceptible, n = 121), including many isolates not susceptible to meropenem, cefepime, ceftazidime, piperacillin-tazobactam, or other comparators., (Copyright © 2017 American Society for Microbiology.)
- Published
- 2017
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