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.

A randomized non-inferiority study comparing imipenem/cilastatin/relebactam with standard-of-care Gram-negative coverage in cancer patients with febrile neutropenia.

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 ß-lactam/ß-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.

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.

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.

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.

Neutropenic Enterocolitis: Clinical Features and Outcomes.

BACKGROUND: Patients undergoing chemotherapy are at risk for mucosal injury and neutropenia, which facilitate colonic mucosal invasion by the bowel flora and subsequent neutropenic enterocolitis, which has a poor prognosis. OBJECTIVE: This study aimed to assess the clinical features and outcomes of neutropenic enterocolitis in patients at a comprehensive cancer center. DESIGN: This is a retrospective cohort study. SETTING: The study was conducted at the University of Texas MD Anderson Cancer Center. PATIENTS: Neutropenic enterocolitis was defined by the presence of an absolute neutrophil count <1000/mm, compatible abdominal symptoms, and either mucosal thickening on abdominal imaging or mucosal injury on colon biopsy. Patients who had been diagnosed between 2010 and 2018 were included. MAIN OUTCOMES: Complication and survival rates were analyzed using logistic regression and Cox regression analyses, respectively. RESULTS: Of the 49,244 patients who had neutropenia during the study period, 134 (2.7%) were included. The median time from neutropenia onset to neutropenic enterocolitis was 2 days (interquartile range, 1-10 days). Neutropenic enterocolitis symptoms lasted for a median of 11 days (interquartile range, 6-22 days). Most patients received antibiotics (88%) and granulocyte colony-stimulating factor (68%). Complications included sepsis (11%), colonic perforation (2%), pneumatosis intestinalis (2%), and abscess formation (2%). The risks associated with complications included immunosuppressive therapy use within 1 month before neutropenic enterocolitis onset (OR, 3.92; 95% CI, 1.04-14.76) and delayed imaging (OR, 1.10; 95% CI, 1.03-1.17). Older age, severe neutropenia, prolonged neutropenia before and after neutropenic enterocolitis diagnosis, and other concomitant systemic infections were associated with lower survival rates. LIMITATIONS: The performance of this study at a single center and its retrospective nature are limitations of the study. CONCLUSION: The prompt diagnosis and management of neutropenic enterocolitis are critical to prevent complications. The use of granulocyte colony-stimulating factor can be beneficial to shorten the duration of neutropenia. See Video Abstract at http://links.lww.com/DCR/B116. ENTEROCOLITIS NEUTROPÉNICA: CARACTERÍSTICAS CLÍNICAS Y RESULTADOS: Los pacientes sometidos a quimioterapia, están en riesgo de lesión de la mucosa y neutropenia, lo que facilita la invasión de la mucosa colónica por la flora intestinal y la subsecuente enterocolitis neutropénica, con un mal pronóstico.Evaluar las características clínicas y los resultados de la enterocolitis neutropénica de pacientes en un centro integral de cáncer.Estudio de cohorte retrospectivo.El estudio se realizó en el MD Anderson Cancer Center de la Universidad de Texas.Se definió la enterocolitis neutropénica, como la presencia de un recuento absoluto de neutrófilos <1000 / mm3, con síntomas compatibles abdominales y engrosamiento de la mucosa en imagen abdominal o lesión de la mucosa en biopsia de colon. Se incluyeron pacientes diagnosticados entre 2010 y 2018.Se analizaron las tasas de complicaciones y supervivencia mediante análisis de regresión logística y regresión de Cox.De 49,244 pacientes que tuvieron neutropenia durante el período de estudio, 134 (2.7%) fueron incluidos. La media del tiempo desde el inicio de la neutropenia hasta la enterocolitis neutropénica, fue de 2 días (RIC, 1-10 días). Los síntomas de enterocolitis neutropénica duraron una media de 11 días (RIC, 6-22 días). La mayoría de los pacientes recibieron antibióticos (88%) y factor estimulante de colonias de granulocitos (68%). Las complicaciones incluyeron sepsis (11%), perforación colónica (2%), neumatosis intestinal (2%) y formación de abscesos (2%). Los riesgos asociados con las complicaciones incluyeron, uso de terapia inmunosupresora dentro de 1 mes antes del inicio de la enterocolitis neutropénica (razón de probabilidades 3.92; intervalo de confianza del 95% 1.04-14.76) y demora en la obtención de imágenes (razón de probabilidades 1.10; intervalo de confianza del 95% 1.03-1.17), edad avanzada, neutropenia grave, neutropenia prolongada antes y después del diagnóstico de enterocolitis neutropénica y de otras infecciones sistémicas concomitantes, se asociaron con bajas tasas de supervivencia.Centro único y estudio retrospectivo.El rápidodiagnóstico y manejo de la enterocolitis neutropénica, es crítico para prevenir complicaciones. El uso del factor estimulante de colonias de granulocitos puede ser beneficioso para acortar la duración de la neutropenia. Consulte Video Resumen en http://links.lww.com/DCR/B116.

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.

Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines.

Aerobic glycolysis, known as the "Warburg effect", is one of several hallmarks of cancer cells. The conversion of phosphoenolpyruvate (PEP) to pyruvate can be down regulated by the re-expression of the embryonic isoform 2 of pyruvate kinase (PKM2). This mechanism allows the accumulation of glycolytic intermediates for the biosynthesis of macromolecules, such as proteins, lipids and nucleic acids. PKM2 is favored by the well-known PI3K/Akt/mTOR proliferative pathway. This pathway is induced by high glucose levels, and the mTOR kinase is the central activator of the Warburg effect. In this study, we investigated the role of glucose restriction (GR) and mTOR inhibition  in reversing the Warburg effect in MDA-MB 231 and MCF-7 breast cancer cell lines. PKM2 expression was measured by western blot. Lactate production by cells was determined by a colorimetric assay. The concentration of glucose in the supernatant of cells was measured using the Trinder method. ATP level  was evaluated by using a Colorimetric/Fluorometric ATP Assay Kit. Our results showed that MDA-MB 231 cells increased glucose consumption when the glucose concentration was 0 g/L (P <0.01). In MCF-7 cells, glucose deprivation reduced lactate secretion by 80% (P =0.0001) but tripled glucose consumption (P = 0.0041). ATP concentration increased approximately when MCF-7 cells were deprived of glucose (P = 0.02). GSK1059615 does not significantly modulate lactate secretion and glucose uptake in both cell lines. Glucose restriction contribute to the reduction of the Warburg effect through mTOR inhibition and regulation of PKM2 kinases.

Biomarkers of Sepsis and Bloodstream Infections: The Role of Procalcitonin and Proadrenomedullin With Emphasis in Patients With Cancer.

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.

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

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

Treating invasive aspergillosis in patients with hematologic malignancy: diagnostic-driven approach versus empiric therapies.

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.

Effect of Algorithm-Based Therapy vs Usual Care on Clinical Success and Serious Adverse Events in Patients with Staphylococcal Bacteremia: A Randomized Clinical Trial.

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.

Antimicrobial Activities of Ceftazidime-Avibactam and Comparator Agents against Clinical Bacteria Isolated from Patients with Cancer.

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.

In Vitro Study of Antimicrobial Percutaneous Nephrostomy Catheters for Prevention of Renal Infections.

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.

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

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.).

Comparing catheter-related bloodstream infections in pediatric and adult cancer patients.

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.

In Vitro Assessment of the Antimicrobial Efficacy of Optimized Nitroglycerin-Citrate-Ethanol as a Nonantibiotic, Antimicrobial Catheter Lock Solution for Prevention of Central Line-Associated Bloodstream Infections.

The rapid, broad-spectrum, biofilm-eradicating activity of the combination of 0.01% nitroglycerin, 7% citrate, and 20% ethanol and its potential as a nonantibiotic, antimicrobial catheter lock solution (ACLS) were previously reported. Here, a nitroglycerin-citrate-ethanol (NiCE) ACLS optimized for clinical assessment was developed by reducing the nitroglycerin and citrate concentrations and increasing the ethanol concentration. Biofilm-eradicating activity was sustained when the ethanol concentration was increased from 20 to 22% which fully compensated for reducing the citrate concentration from 7% to 4% as well as the nitroglycerin concentration from 0.01% to 0.0015% or 0.003%. The optimized formulations demonstrated complete and rapid (2 h) eradication of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate Staphylococcus aureus (VISA), methicillin-resistant Staphylococcus epidermidis (MRSE), vancomycin-resistant enterococci (VRE), multidrug-resistant (MDR) Pseudomonas aeruginosa, MDR Klebsiella pneumoniae, MDR Enterobacter cloacae, MDR Acinetobacter baumannii, MDR Escherichia coli, MDR Stenotrophomonas maltophilia, Candida albicans, and Candida glabrata biofilms. The optimized NiCE lock solutions demonstrated anticoagulant activities comparable to those of heparin lock solutions. NiCE lock solution was significantly more effective than taurolidine-citrate-heparin lock solution in eradicating biofilms of Staphylococcus aureus and Candida glabrata The optimized, nonantibiotic, heparin-free NiCE lock solution demonstrates rapid broad-spectrum biofilm eradication as well as effective anticoagulant activity, making NiCE a high-quality ACLS candidate for clinical assessment.

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

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

Successful Salvage of Central Venous Catheters in Patients with Catheter-Related or Central Line-Associated Bloodstream Infections by Using a Catheter Lock Solution Consisting of Minocycline, EDTA, and 25% Ethanol.

In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter in situ Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.).