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.

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.

Immune reconstitution and severity of COVID-19 among hematopoietic cell transplant recipients.

Severe acute respiratory syndrome coronavirus 2 can lead to life-threatening coronavirus disease 2019 (COVID-19) infections in patients with hematologic malignancies, particularly among hematopoietic cell transplant (HCT) recipients. We describe two patients with COVID-19 during the pre-engraftment period after HCT and review previous reports of COVID-19 in HCT recipients. Because of significant mortality from COVID-19, primarily after allogeneic HCT, early, preemptive, and optimal directed therapy may improve outcomes and reduce the mortality rate but still needs to be established in clinical trials.

Minocycline-EDTA-Ethanol Antimicrobial Catheter Lock Solution Is Highly Effective In Vitro for Eradication of Candida auris Biofilms.

Candida auris is an emerging pathogen that can cause virulent central-line-associated bloodstream infections. Catheter salvage through the eradication of biofilms is a desirable therapeutic option. We compared taurolidine and minocycline-EDTA-ethanol (MEE) catheter lock solutions in vitro for the eradication of biofilms of 10 C. auris strains. MEE fully eradicated all C. auris biofilms, while taurolidine lock partially eradicated all of the C. auris biofilms. The superiority was significant for all C. auris strains tested (P = 0.002).

Assessment of the Potential for Inducing Resistance in Multidrug-Resistant Organisms from Exposure to Minocycline, Rifampin, and Chlorhexidine Used To Treat Intravascular Devices.

To assess the potential for the induction of antimicrobial resistance following repeated subinhibitory exposures to the combination minocycline (MIN), rifampin (RIF), and chlorhexidine (CHX), a total of 29 clinical microbial pathogenic isolates were repeatedly exposed to subinhibitory concentrations of MIN, RIF, and CHX for 20 passages. MICs of the MIN, RIF, and CHX combination were assessed at each passage to evaluate the potential for resistance to have been induced. The combination of MIN, RIF, and CHX showed significant antimicrobial efficacy and synergy against organisms resistant to all 3 individual components (MIC of ≥16 µg/ml for MIN or MIC of ≥4 µg/ml for RIF or CHX). Among the organisms originally resistant to 2 or more individual components and the organisms originally susceptible to 2 or more individual components, there was no evidence that organisms became resistant following 20 repeated subinhibitory exposure cycles to the triple combination. The risk of resistance developing to the triple combination is extremely low because microbes are inhibited or killed before resistance can simultaneously emerge to all three agents. Surveillance studies monitoring the development of resistance should be conducted in a clinical setting.

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.

Sofosbuvir-Based Therapy in Hepatitis C Virus-Infected Cancer Patients: A Prospective Observational Study.

BACKGROUND: Data are sparse on treatment of chronic hepatitis C virus (HCV) in cancer patients. We evaluated the efficacy and safety of sofosbuvir-based therapy (SOFBT) in cancer patients. METHODS: Patients treated with SOFBT at our center during 2014-2017 were included in a prospective observational study. Efficacy [sustained virologic response at 12 weeks after the end of treatment (SVR12)], cancer-related outcomes and adverse events (AEs) were assessed. RESULTS: We included 153 patients. Most were men (109; 71%), white (92; 60%), non-cirrhotic (105; 69%), and with HCV genotype 1 (110; 72%). The most common cancers were hepatocellular carcinoma (HCC) (27; 18%) and multiple myeloma (14; 9%). The overall SVR12 rate was 91% (128/141). SVR12 was 100% in patients treated with ledipasvir/sofosbuvir for 8 weeks. Of the 32 patients initially excluded from cancer clinical trials because of HCV, 27 (84%) were granted cancer therapy access after starting SOFBT. Six patients with indolent non-Hodgkin's lymphoma (NHL) received SOFBT without cancer treatment. Two achieved complete remission, one had partial remission, and two had stable cancer. Within 6 months after SOFBT, 5% (6/121) of patients in remission or with stable cancer, had progression or recurrence (two with HCC and one each with esophageal cancer, cholangiocarcinoma, NHL, and tonsillar cancer). No de novo HCCs occurred. AEs were most commonly grade 1-2 (90%). CONCLUSIONS: SOFBT in HCV-infected cancer patients is effective and safe, may permit access to investigational cancer therapy expanding treatment options, may induce remission of NHL, and may be used for 8 weeks.

Risk factors for recurrent percutaneous nephrostomy catheter-related infections.

PURPOSE: Percutaneous nephrostomy (PCN) catheters are mainly indicated for urinary tract obstructions. Unfortunately, the rate for infection and recurrence remains elevated. Our objective was to identify the risk factors leading to recurrent PCN-related infections (PCNI) in cancer patients. METHODS: We retrospectively reviewed 571 patients who underwent initial PCN catheter placement at our institution. Of these, we identified patients with a definite PCNI and catheter exchange, with a minimum 30-day follow-up. We defined PCNI as presence of a urine culture positive for bacteria (≥ 104 CFU/mL) plus symptoms of urinary tract infection. A PCNI was considered recurrent if the same organism was isolated. Antibiotics were considered concordant if they were active against all identified organisms. RESULTS: A total of 81 patients (14%) developed an initial PCNI. Of 47 patients with 30-day follow-up, 10 patients (21%) were identified as having a recurrent PCNI. In terms of demographic characteristics, clinical manifestations, and microbiological data, there was no statistically significant difference between the recurrent and non-recurrent groups. However, in multivariate logistic regression analysis, two factors were independently associated with a decrease in recurrent PCNI: concordant antibiotic use (OR 0.04; p = 0.008) and PCN catheter exchange within 4 days of infection (OR 0.1; p = 0.048). CONCLUSIONS: To decrease the high rate of recurrent infections, associated costs, and potential delay in further chemotherapy, we recommend that once antimicrobial susceptibility test results are available and the patient is known to be receiving concordant antimicrobials, clinicians proceed with immediate PCN catheter exchange, ideally within the first 4 days of the infection.

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.

Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.

BACKGROUND: Isavuconazole is a novel triazole with broad-spectrum antifungal activity. The SECURE trial assessed efficacy and safety of isavuconazole versus voriconazole in patients with invasive mould disease. METHODS: This was a phase 3, double-blind, global multicentre, comparative-group study. Patients with suspected invasive mould disease were randomised in a 1:1 ratio using an interactive voice-web response system, stratified by geographical region, allogeneic haemopoietic stem cell transplantation, and active malignant disease at baseline, to receive isavuconazonium sulfate 372 mg (prodrug; equivalent to 200 mg isavuconazole; intravenously three times a day on days 1 and 2, then either intravenously or orally once daily) or voriconazole (6 mg/kg intravenously twice daily on day 1, 4 mg/kg intravenously twice daily on day 2, then intravenously 4 mg/kg twice daily or orally 200 mg twice daily from day 3 onwards). We tested non-inferiority of the primary efficacy endpoint of all-cause mortality from first dose of study drug to day 42 in patients who received at least one dose of the study drug (intention-to-treat [ITT] population) using a 10% non-inferiority margin. Safety was assessed in patients who received the first dose of study drug. This study is registered with ClinicalTrials.gov, number NCT00412893. FINDINGS: 527 adult patients were randomly assigned (258 received study medication per group) between March 7, 2007, and March 28, 2013. All-cause mortality from first dose of study drug to day 42 for the ITT population was 19% with isavuconazole (48 patients) and 20% with voriconazole (52 patients), with an adjusted treatment difference of -1·0% (95% CI -7·8 to 5·7). Because the upper bound of the 95% CI (5·7%) did not exceed 10%, non-inferiority was shown. Most patients (247 [96%] receiving isavuconazole and 255 [98%] receiving voriconazole) had treatment-emergent adverse events (p=0·122); the most common were gastrointestinal disorders (174 [68%] vs 180 [69%]) and infections and infestations (152 [59%] vs 158 [61%]). Proportions of patients with treatment-emergent adverse events by system organ class were similar overall. However, isavuconazole-treated patients had a lower frequency of hepatobiliary disorders (23 [9%] vs 42 [16%]; p=0·016), eye disorders (39 [15%] vs 69 [27%]; p=0·002), and skin or subcutaneous tissue disorders (86 [33%] vs 110 [42%]; p=0·037). Drug-related adverse events were reported in 109 (42%) patients receiving isavuconazole and 155 (60%) receiving voriconazole (p<0·001). INTERPRETATION: Isavuconazole was non-inferior to voriconazole for the primary treatment of suspected invasive mould disease. Isavuconazole was well tolerated compared with voriconazole, with fewer study-drug-related adverse events. Our results support the use of isavuconazole for the primary treatment of patients with invasive mould disease. FUNDING: Astellas Pharma Global Development, Basilea Pharmaceutica International.

Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use.

Continuous subcutaneous insulin infusion (CSII) using pumps is a widely used method for insulin therapy in patients with diabetes mellitus. Among the major factors that usually lead to the discontinuation of CSII are CSII set-related issues, including infection at the infusion site. The American Diabetic Association currently recommends rotating sites every 2 to 3 days. This recommendation adds cost and creates inconvenience. Therefore, in order to prevent infections and extend the duration between insertion site changes, we developed a Teflon cannula coated with a combination of gentian violet and chlorhexidine (gendine) and tested its antimicrobial efficacy against different pathogens. The cannulas were coated with gendine on the exterior surface and dried. The efficacy and durability of gendine-coated cannulas were determined against methicillin-resistant Staphylococcus aureus, Staphylococcus epidermidis, methicillin-susceptible S. aureus, Streptococcus pyogenes, vancomycin-resistant enterococci, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, and Candida glabrata using a biofilm colonization method. The cytotoxicity of gendine was assessed against mouse fibroblast cell lines. The gendine-coated cannulas showed complete prevention of biofilm colonization of all organisms tested for up to 2 weeks (P < 0.0001) compared to that with the uncoated control. A gendine-coated catheter against mouse fibroblast cells was shown to be noncytotoxic. Our in vitro results show that a novel gendine cannula is highly effective in completely inhibiting the biofilm of multidrug-resistant pathogens for up to 2 weeks and may have potential clinical applications, such as prolonged use, cost reduction, and lower infection rate.

Effect of hepatitis C virus infection in patients with cancer: addressing a neglected population.

BACKGROUND: Hepatitis C virus (HCV) infection is a neglected disease in patients with cancer. Therefore, this study examined the impact of HCV infections in these patients. METHODS: The records of HCV-infected patients with cancer seen at The University of Texas MD Anderson Cancer Center (2008-2011) were reviewed. The outcomes of those who underwent HCV treatment were analyzed. RESULTS: Of 1291 patients who had positive test results for an antibody to HCV (anti-HCV), 744 (58%) were tested for HCV-RNA; 642 (86%) of which had chronic HCV infections. Most had solid tumors (72%) and genotype-1 (G-1) infections (66%). HCV therapy was administered in 348 patients (98 of them after cancer diagnosis). Sustained virologic response (SVR) occurred in 27 (35%) of the 78 patients treated for whom outcome data were available. Compared with patients who experienced an SVR, more patients who did not were black (29% vs 4%; P=.007), had G-1 infections (72% vs 6%; P<.0001), and had higher baseline aspartate aminotransferase (78 vs 47 IU/L; P=.006) and alanine aminotransferase levels (71.1 vs 43.3 IU/L; P=.009). Overall, progression to cirrhosis (hazard ratio [HR], 0.38; P=.03) and portal hypertension (HR, 0.19; P=.009) was less common in those treated, irrespective of the treatment outcome (SVR or non-SVR). Hepatocellular carcinoma (HCC) developed as a second primary malignancy in 7% of patients with non-HCC cancer. CONCLUSIONS: This is the largest series to analyze HCV infections in patients with cancer. HCV therapy is feasible and prevents liver disease progression in this forgotten population. A treatment algorithm is provided.

Prevention of transmission of multidrug-resistant organisms during catheter exchange using antimicrobial catheters.

Exchanging a central venous catheter (CVC) over a guide wire for a fresh uncoated CVC in the presence of bacteremia can result in cross-infection of the newly exchanged CVC. A recent retrospective clinical study showed that exchanging a catheter over a guide wire in the presence of bacteremia using an antimicrobial minocycline-rifampin (M/R) catheter may improve outcomes. To expand on this, we developed an in vitro cross-contamination model of exchange to evaluate the efficacy of different antimicrobial CVCs in preventing cross-contamination of multidrug-resistant organisms during exchange. Uncoated CVCs were allowed to form biofilm by methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. After 24 h, the biofilm-colonized CVCs were placed in a glass tube containing bovine calf serum plus Mueller-Hinton broth, and each catheter was exchanged over a guide wire for a fresh uncoated or an M/R-, chlorhexidine-silver sulfadiazine (CHX/SS)-, or chlorhexidine-M/R (CHX-M/R)-coated CVC. Cross-contamination of exchanged catheters was enumerated by sonication and quantitative plating methods. The exchange of M/R CVCs completely prevented cross-contamination by MRSA biofilms compared to control exchanged CVCs (P<0.0001). Exchange with CHX/SS CVCs reduced but did not completely prevent cross-contamination by MRSA (P=0.005). Exchange with CHX-M/R CVCs completely prevented cross-contamination by MRSA, P. aeruginosa, and C. albicans biofilms (P<0.0001). Furthermore, CHX-M/R CVCs were superior to M/R CVCs against P. aeruginosa and C. albicans (P=0.003) and were superior to CHX/SS CVCs against MRSA and P. aeruginosa (P=0.01). In conclusion, exchange with the novel CHX-M/R CVC was the only exchange effective in completely and concurrently preventing cross-contamination from bacteria and Candida.

Prevention of biofilm colonization by Gram-negative bacteria on minocycline-rifampin-impregnated catheters sequentially coated with chlorhexidine.

Resistant Gram-negative bacteria are increasing central-line-associated bloodstream infection threats. To better combat this, chlorhexidine (CHX) was added to minocycline-rifampin (M/R) catheters. The in vitro antimicrobial activity of CHX-M/R catheters against multidrug resistant, Gram-negative Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia was tested. M/R and CHX-silver sulfadiazine (CHX/SS) catheters were used as comparators. The novel CHX-M/R catheters were significantly more effective (P < 0.0001) than CHX/SS or M/R catheters in preventing biofilm colonization and showed better antimicrobial durability.