In vitro activity of cefepime/taniborbactam and comparator agents against Gram-negative bacterial bloodstream pathogens recovered from patients with cancer.

Background: Taniborbactam is a ß-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. MIC50, 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 ß-lactam/ß-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.

Comparing Molnupiravir to Nirmatrelvir/Ritonavir (Paxlovid) in the Treatment of Mild-to-Moderate COVID-19 in Immunocompromised Cancer Patients.

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.

In vitro activity of tebipenem and comparator agents against bacterial pathogens isolated from patients with cancer.

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. MIC50, 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.

Long COVID in cancer patients: preponderance of symptoms in majority of patients over long time period.

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.

Prevention of device-related infections in patients with cancer: Current practice and future horizons.

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.

Procalcitonin for antimicrobial stewardship among cancer patients admitted with COVID-19.

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.

A Prospective Randomized Study Comparing Ceftolozane/Tazobactam to Standard of Care in the Management of Neutropenia and Fever in Patients With Hematological Malignancies.

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/ß-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.

Real-World Use of Isavuconazole as Primary Therapy for Invasive Fungal Infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant.

(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.

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.

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.

Prognostic Value of Procalcitonin, C-Reactive Protein, and Lactate Levels in Emergency Evaluation of Cancer Patients with Suspected Infection.

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.

Management of enterococcal central line-associated bloodstream infections in patients with cancer.

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.

Novel antimicrobial ointment for infected wound healing in an in vitro and in vivo porcine model.

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.

Impact of Checkpoint Inhibitor Immunotherapy, Primarily Pembrolizumab, on Infection Risk in Patients With Advanced Lung Cancer: A Comparative Retrospective Cohort Study.

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.

Correction to: Impact of antibiotic therapy on the development and response to treatment of immune checkpoint inhibitor-mediated diarrhea and colitis.

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.

Impact of Catheter Management on Clinical Outcome in Adult Cancer Patients With Gram-Negative Bacteremia.

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.

Advances in the prevention and management of central-line-associated bloodstream infections: The role of chelator-based catheter locks.

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.

Epidemiology of Infectious and Noninfectious Catheter Complications in Patients Receiving Home Parenteral Nutrition: A Systematic Review and Meta-Analysis.

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.

Nitroglycerin-Citrate-Ethanol Catheter Lock Solution Is Highly Effective for In Vitro Eradication of Candida auris Biofilm.

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.

International Multicenter Experience in the Treatment Outcome of Invasive Aspergillosis in Immunocompromised Cancer Patients.

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.