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.

Disseminated cryptococcosis and anti-granulocyte-macrophage colony-stimulating factor autoantibodies: An underappreciated association.

The development of disseminated cryptococcosis has historically occurred in patients living with advanced human immunodeficiency virus or other immunosuppressive conditions affecting T-cell function. Recently, patients with anti-cytokine neutralising autoantibodies have been recognised to be at risk for disseminated infections by opportunistic intracellular pathogens, including Cryptococcus species. Herein, we present a previously healthy 26-year-old man who was evaluated with disseminated cryptococcosis involving the bone, lung, mediastinum and brain. The patient's serum cryptococcal antigen titres were >1:1,100,000, and evaluation for an underlying immunodeficiency revealed high titres for anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies. We also review the literature of all published cases of disseminated cryptococcosis associated with the presence of anti-GM-CSF autoantibodies. Clinicians should have a heightened awareness of anti-cytokine autoantibodies in patients without a known immunodeficiency and development disseminated infections by opportunistic intracellular pathogens.

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.

Graft loss attributed to possible transfusion-transmitted ehrlichiosis following cord blood stem cell transplant.

We present a case of possible transfusion-transmitted Ehrlichia chaffeensis infection in a heavily transfused cord blood transplant recipient, resulting in severe infection and graft loss. Transfusion-transmitted, vector-borne infections in immunocompromised individuals can have severe consequences, and should be considered in hospitalized patients receiving blood products with unexplained fever or sepsis.

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.).

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.).

Reconstructive breast implant-related infections: Prevention, diagnosis, treatment, and pearls of wisdom.

Implant-based reconstructions are increasingly utilized following mastectomy in the prevention and treatment of breast cancer. However, these implants are associated with a high rate of infection, which is a major complication that can lead to implant removal, delay in adjuvant radiation and chemotherapy, and increase in health care costs. Early clinical signs and symptoms of infection, such as erythema, warmth, and tenderness, are challenging to discern from expected postsurgical responses. Furthermore, when atypical features are present or the patient's condition does not improve on adequate antimicrobials, the clinician should be prompted to consider an alternative noninfectious etiology. Herein we highlight the key elements of the preventive, diagnostic, and multidisciplinary therapeutic approach to salvaging the infected breast implant; review several infectious disease mimickers; and provide many pearls of wisdom that the practicing clinician must be familiar with and be able to manage in an effective and successful manner.

Effect of local prolonged-release incisional doxycycline on surgical site infection prophylaxis in abdominal colorectal surgery: The SHIELD 1 randomized clinical trial.

INTRODUCTION: Despite advanced infection control practices including preoperative antibiotic prophylaxis, surgical site infection (SSI) remains a challenge. This study aimed to test whether local administration of a novel prolonged-release Doxycycline-Polymer-Lipid Encapsulation matriX (D-PLEX) before wound closure, concomitantly with standard of care (SOC), reduces the incidence of incisional SSI after elective abdominal colorectal surgery. MATERIALS AND METHODS: This was a phase 3 randomized, controlled, double-blind, multinational study (SHIELD 1) between June 2020 to June 2022. Patients with at least one abdominal incision length >10 cm were randomized 1:1 to the investigational arm (D-PLEX+SOC) or control (SOC) arm . The primary outcome was a composite of incisional SSI, incisional reintervention, and all-cause mortality. RESULTS: A total of 974 patients were analyzed, of whom 579 (59.4%) were male. The mean age (±SD) was 64.2±13.0 years. The primary outcome occurred in 9.3% of D-PLEX patients versus 12.1% (SOC) (risk difference estimate [RDE], -2.8%; 95% CI [-6.7%, 1.0%], P=0.1520). In a pre-specified analysis by incision length, a reduction in the primary outcome was observed in the >20 cm subpopulation: 8% (D-PLEX) versus 17.5% (SOC) (RDE, -9.4%; 95% CI [-15.5%, -3.2%], P=0.0032). In the >10 to ≤20 cm subgroup, no reduction was observed: 9.9% versus 7.9% (RDE, 2.0%; 95% CI [-2.8%, 6.7%], P=0.4133). Exploratory post-hoc analyses of patients with increased SSI risk (≥1 patient-specific comorbidity) indicated a reduction in the incidence of the primary outcome: 9.0% (D-PLEX) versus 13.7% (SOC) (RDE, -4.8%; 95% CI [-9.5%, -0.1%], P=0.0472). The D-PLEX safety profile was good (no difference in treatment-emergent adverse events between the groups). CONCLUSIONS: The SHIELD-1 study did not meet its primary outcome of reduced incisional SSI, incisional reinterventions, or all-cause mortality. Pre-specified and post-hoc analyses suggested that D-PLEX may reduce the incidence of the primary outcome event in patients with increased SSI risk, including lengthy incisions.

Management of rapidly growing mycobacterial bacteremia in cancer patients.

Rapidly growing mycobacteria (RGM) are environmental organisms capable of causing a wide spectrum of diseases. We identified 116 cancer patients with RGM. Mycobacterium mucogenicum was the leading cause of disease. Removal of the catheter correlated with significant decrease in the bacteremia relapse rate (P = .007). A median duration of 4 weeks of therapy produced a good outcome.

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.

Nonstaphylococcal infections of cardiac implantable electronic devices.

BACKGROUND: Along with the rising use of cardiac implantable electronic devices (CIEDs), there has been a disproportional increase in the number of infections of such devices. Little is known about nonstaphylococcal CIED-related infections, which make up approximately 10% to 30% of all CIED infections. METHODS AND RESULTS: A retrospective review of hospital records of patients admitted with a CIED-related infection was conducted in 4 academic hospitals in Houston, Tex, between 2002 and 2009. Of the 504 identified patients with CIED-related infection, 80 (16%) had a nonstaphylococcal infection and were the focus of this study. The mean duration of CIED placement before infection was 109+/-27 weeks, whereas 44% had their device previously manipulated within a mean of 29.5+/-6 weeks. The mean duration of clinical symptoms before admission was 48+/-12.8 days. Furthermore, 13 patients (16%) presented with CIED-related endocarditis. Although not described in prior reports, we identified 3 definite and 2 suspected cases of secondary Gram-negative bacteria seeding of the CIED. Inappropriate antimicrobial coverage was provided in approximately 50% of the cases with a mean period of 2.1 days. The overall mortality rate was 4%. CONCLUSIONS: Nonstaphylococcal CIED-related infections are prevalent and diverse with a relatively low virulence and mortality rate. Because nonstaphylococcal organisms are capable of secondarily seeding the CIED, a high suspicion for CIED-related infection is warranted in patients with bloodstream infection. In patients with suspected CIED infection, adequate Gram-positive and Gram-negative antibacterial coverage should be administered until microbiological data become available.

Cardiovascular implantable device infections.

As life expectancy continues to increase and biotechnology advances, the use of cardiovascular implantable devices will continue to rise. Unfortunately, despite modern medical advances, the infection and mortality rates remain excessively elevated. This article reviews the pathophysiology and general concepts of cardiac device-related infections, including the physical and chemical characteristics of the medical device, host response to the medical device, and the microbiologic virulence factors. Infections of the most commonly utilized cardiovascular implantable devices, including cardiovascular implantable electronic devices, bioprosthetic and mechanical valves, ventricular assist devices, total artificial hearts, and coronary artery stents, are reviewed in detail.

Characteristics of infective endocarditis in a cancer population.

BACKGROUND: Infective endocarditis (IE) is more common in patients with cancer as compared with the general population. Due to an immunocompromised state, the need for invasive procedures, hypercoagulability and the presence of indwelling catheters, patients with cancer are particularly predisposed to the development of IE. OBJECTIVES: Limited information exists about IE in patients with cancer. We aimed to evaluate the characteristics of patients with cancer and IE at our tertiary care centre, including a comparison of the microorganisms implicated and their association with mortality. METHODS: A retrospective chart review of patients with cancer who had echocardiography for suspicion of endocarditis was conducted. A total of 56 patients with a confirmed diagnosis of cancer and endocarditis, based on the modified Duke criteria, were included in the study. Baseline demographics, risk factors for developing IE, echocardiography findings, microbiology and mortality data were analysed. RESULTS: Following the findings of vegetations by echocardiography, the median survival time was 8.5 months. Staphylococcus aureus was the most common organism identified as causing endocarditis. The mitral and aortic valves were the most commonly involved sites of endocarditis. Patients with S. aureus endocarditis (SAE) had a significantly poorer survival when compared with patients without SAE (p=0.0217) over the 12-month period from diagnosis of endocarditis. CONCLUSIONS: Overall survival of patients with cancer and endocarditis is poor, with a worse outcome in patients with SAE.

Prevention of Cardiac Implantable Electronic Device-Related Infection in Patients With Cancer: The Role of a Comprehensive Prophylactic Bundle Approach That Includes the Antimicrobial Mesh.

BACKGROUND: Oncological patients have several additional risk factors for developing a cardiac implantable electronic device (CIED)-related infection. Therefore, we evaluated the clinical impact of our comprehensive bundle approach that includes the novel minocycline and rifampin antimicrobial mesh (TYRX) for the prevention of CIED infections in patients living with cancer. METHODS: We retrospectively reviewed all consecutive patients who had a CIED placement at our institution during 2012-2017 who received preoperative vancomycin, intraoperative pocket irrigation with bacitracin and polymyxin B, plus TYRX antimicrobial mesh, followed by postoperative oral minocycline. RESULTS: A total of 154 patients had a CIED, with 97 permanent pacemakers (PPMs), 23 implantable cardioverter defibrillators (ICDs), and 34 cardiac resynchronization therapy (CRT) devices. An underlying solid cancer was present in 62% of patients, while 38% had a hematologic malignancy. Apart from a higher proportion of surgical interventions in the PPM group than in the ICD and CRT groups (P = .007), no other oncologic variables were statistically significantly different between groups. Despite an extensive median follow-up period (interquartile range) of 21.9 (6.7-33.8) months, 16 patients (10%) had a mechanical complication, while only 2 patients (1.3%) developed a CIED infection, requiring the device to be explanted. CONCLUSIONS: Our comprehensive prophylactic bundle approach using TYRX antimicrobial mesh in an oncologic population at high risk for infections was revealed upon extensive follow-up to be both safe and effective in maintaining the rate of CIED infection at 1.3%, well within published averages in the broader population of CIED recipients.

Incubation alone is adequate as a culturing technique for cardiac rhythm management devices.

There exist no standardized methods for culturing cardiac rhythm management devices. To identify the most optimal culturing method, we compared various techniques that comprise vortex, sonication, and incubation or combinations thereof. Incubation alone yielded bacterial colony counts similar to those of other culturing combinations and is the least labor-intensive.

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.

Evaluation of Current Perioperative Antimicrobial Regimens for the Prevention of Surgical Site Infections in Breast Implant-based Reconstructive Surgeries.

Several steps to reduce the rate of postoperative surgical site infections (SSIs) have been implemented. The use of prophylactic antimicrobials targeting patient's microbial flora has been associated with a decrease in postoperative infections. We evaluated the relationship between perioperative antimicrobials, baseline microbial flora, and occurrence of SSIs. METHODS: We prospectively enrolled 241 patients scheduled to receive a postmastectomy implant-based reconstructive procedure between September 2015 and January 2018. Axillary swab cultures were obtained preoperatively, and all recovered bacteria were identified. Surgeons were blinded to these results. The use of prophylactic perioperative antimicrobials was defined as concordant if the baseline axillary flora were susceptible to the given antibiotic and discordant if not. As Staphylococcus species are the most common pathogen causative for breast implant-related infections, patients colonized with these organisms were analyzed in detail. All patients were followed up for at least 6 months postoperatively and evaluated for SSIs. RESULTS: A total of 238 patients (99%) received both perioperative and postoperative oral antimicrobials. The most common preoperative staphylococci axillary flora recovered were methicillin-sensitive coagulase-negative Staphylococcus (67%), methicillin-resistant coagulase-negative Staphylococcus (35%), with only 1 case of methicillin-sensitive Staphylococcus aureus (0.4%). Thirty-three patients (14%) developed an SSI. Of those with a positive Staphylococcus culture, only 54% received a concordant antimicrobial regimen, but this was not associated with an increased risk for infection (P > 0.72). CONCLUSIONS: The use of perioperative antimicrobials whether concordant or discordant with the preoperative axillary microbial flora, specifically Staphylococci species, did not provide a significant impact on the risk of SSI.