Search

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.

Peritoneal histoplasmosis is a rare entity with few cases reported in the literature. We present a case of isolated acute peritoneal histoplasmosis that mimicked an advanced ovarian malignancy in a patient undergoing antitumor necrosis factor therapy for rheumatoid arthritis. We also reviewed the literature on Histoplasma peritonitis.

Background Percutaneous nephrostomy tube infections (PCNIs) are complex, affect quality of life, necessitate implant exchanges, and increase health care costs. Here, we analyzed risk factors for recurrent PCNIs in patients treated with our standardized institutional algorithm. Methods At our institution, we prospectively evaluated consecutive patients with gynecological malignancies who developed PCNIs between July 2019 to September 2021. All patients were treated using our institutional algorithm for PCNI, which consists of obtaining blood cultures plus urine analyses and cultures from each percutaneous nephrostomy tube (PCN); utilizing ultrasound or abdominal pelvic computed tomography scans to rule out obstructive hydronephrosis, pyelonephritis, or renal abscess; exchanging the PCN once patients are receiving concordant antimicrobial therapy; and having patients complete an adequate course of targeted antimicrobials. Thereafter, patients were followed up until reinfection, routine PCN exchange at 3 months, being lost to follow-up, or death. Results We treated 100 patients. Their median age was 54 years; 53% were White. The most common malignancies were cervical (61%), ovarian (23%), and endometrial (13%), with 60% being metastatic. To analyze the risk factors for developing a recurrent PCNI, patients were placed in 3 different groups: those reinfected with the same organism (19%), reinfected with a different organism (17%), and not reinfected (64%). Overall, there were no differences among the patient groups regarding demographics, comorbidities, clinical presentation, infection timing, PCN exchange (Table 1) or microorganisms encountered (Table 2). However, patients with prior radiation therapy or pelvic fistulas (urinary-vaginal-rectal or their permutations) had higher rates for developing a recurrent PCNIs with the same organism (P< .002). Conclusion Patients with prior radiation therapy and underlying pelvic fistulas have an increased risk for reinfection with the same pathogen. Therefore, further studies should be performed to mitigate this increased risk of recurrent infections with more frequent PCN exchanges or, more invasive procedure such as ureteral embolization, sclerosis, or ligation to dissociate the upper and lower urinary tracts. Disclosures All Authors: No reported disclosures.

Bruton’s tyrosine kinase (BTK) plays a pivotal role in B-cell proliferation and survival of leukemic cells. Ibrutinib, a molecule targeting BTK, was approved by the U.S. Food and Drug Administration in 2013 for treatment of mantle cell lymphoma and has since been approved for treatment of several other hematologic malignancies, including chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia, and marginal zone lymphoma (MZL) (1). Recently, Ibrutinib plus venetoclax have been found to be effective as first line treatment for high risk and older patients with CLL (2). Patients receiving ibrutinib are at increased risk for serious bacterial, fungal, and viral reactivation (3). In this report, we describe the first case, to our knowledge, of HBV-associated liver failure after ibrutinib therapy in a patient with B-cell non-Hodgkin lymphoma. Additionally, we review the previously reported cases of HBV reactivation after ibrutinib therapy (3–7). We analyzed our patient reported below together with 5 of the 6 previously described patients for whom sufficient data about HBV reactivation were available. HBV-related outcomes were defined according to the American Association for the Study of Liver Diseases (AASLD) 2018 hepatitis B guidance (8), and included past or chronic HBV infection, HBV reactivation, HBV-associated hepatitis, and HBV-associated liver failure

Background With increased use of antibiotics in high-risk patients, the investigation of new antibiotics to cover potentially resistant pathogens is warranted. In this prospective randomized trial, we compared ceftolozane/tazobactam (C/T), a new cephalosporin/β-lactamase inhibitor, to the standard of care (SOC) for the empiric treatment of neutropenia and fever in patients with hematological malignancies. Methods We enrolled 100 patients to receive intravenous (IV) C/T or SOC antibiotics (cefepime, piperacillin/tazobactam, or meropenem) in combination with gram-positive antibacterial agents. We evaluated responses at the end of IV therapy (EOIV), test of cure (TOC; days 21–28), and late follow-up (LFU; days 35–42). Results We analyzed 47 C/T patients and 50 SOC patients. C/T patients had a higher rate of favorable clinical response at EOIV (87% vs 72%). A 1-sided noninferiority analysis indicated that C/T was at least not inferior to the SOC for favorable clinical response at EOIV (P = .002), TOC (P = .004), and LFU (P = .002). Superiority tests showed that C/T led to significantly lower rates of clinical failure at TOC (6% vs 30%; P = .003) and LFU (9% vs 30%; P = .008). C/T and SOC patients with documented infections had similar rates of favorable microbiological response. Serious adverse events leading to drug discontinuation (2% vs 0%; P = .48) and overall mortality (6% vs 4%; P = .67) were similar in both groups. Conclusions The empiric use of C/T in high-risk patients with hematological malignancies and febrile neutropenia is safe and associated with better clinical outcomes than SOC antimicrobial agents. Clinical Trials Registration NCT03485950.

Background Non-typhoidal Salmonella (NTS) infection is thought to be more severe in cancer patients, but this has not been studied since the development of new cancer therapies, increasing antibiotic resistance and the introduction of new antibiotics. We sought to describe the demographic characteristics, microbiological findings, clinical manifestations, and outcomes of NTS infections in cancer patients at our institution. Methods We reviewed microbiology laboratory records and identified patients who had cancer and from whom NTS organisms were recovered between January 1, 2000 and December 31, 2013, at a comprehensive cancer center in Houston, Texas. Descriptive statistics were used to summarize patient characteristics, clinical presentation and outcomes. Results We identified 110 isolates from 82 patients with 88 episodes of NTS infection (including five relapses [6%] in four patients, and two consecutive episodes in one patient). Fifty-five patients (67%) had hematologic malignancies. Most NTS isolates were susceptible to the commonly prescribed antimicrobials. Sixty-nine percent of patients had sepsis and one-third had severe sepsis or septic shock. Gastroenteritis, bacteremia, or both were present in 69% of patients, and the rest had focal infection. Mortality at 30 days was low (8%). Relapses occurred only in patients receiving ≤ 10 days of antibiotic therapy. Conclusions NTS affects predominantly patients with hematologic malignancies, followed by gastrointestinal and genitourinary cancers. Invasive disease, sepsis, and septic shock are common presentations among admitted patients. Antimicrobial prophylaxis may not prevent NTS infection. Thirty-day mortality and attributable mortality rates were low in our series compared to older case series. Early appropriate antibiotic therapy may have had a role in decreasing mortality. Relapses occurred in patients receiving ≤ 10 days of therapy, suggesting the need for longer duration of antibiotic therapy in cancer patients with uncomplicated NTS infections.

Fungal cholecystitis is an uncommon entity, and no cases of cholecystitis associated with mould infection have been reported. We present a case of acute Fusarium cholecystitis in a cytopenic patient with leukaemia who had disseminated fusariosis. We also review the published cases of fungal cholecystitis, which is most often caused by Candida species. Although it is rare, fungal cholecystitis should be part of the differential diagnosis of acute cholecystitis in high-risk patients with predisposing factors for opportunistic fungal infections.

Background Despite the implementation of successful antibiotic stewardship programs, antibiotic resistance continue to emerge particularly against gram-negative bacteria. With the increase use of antibiotics in high risk patients with hematological malignancies, the empiric therapy with standard antibiotic could be inappropriate. New antibiotics may be useful to cover potential resistant pathogens. We evaluated the role of a new cephalosporin /β-lactamase inhibitor ceftolozane-tazobactam (C/T) in comparison to standard of care (SOC) antibiotics in the empiric treatment of febrile neutropenic cancer patients with hematological malignancies. Methods We conducted a prospective randomized open label comparative study to evaluate the safety and efficacy of C/T vs SOC antibiotics consisting of cefepime, piperacillin-tazobactam or meropenem when used in combination with gram positive antibacterial agents. Between May 2018 and March 2020, we enrolled 88 febrile neutropenic patients with hematological malignancies who presented to our emergency center. Patients received at least 72 hours of intravenous study drugs and were followed through end of IV therapy and for up to 42 days. Results A total of 88 patients were analyzed of whom 42 received C/T and 46 SOC antimicrobial agents. The rate of documented bloodstream infections was similar in both groups (CE-TZ 21% vs SOC 26%, p=0.61). Favorable clinical response at end of IV therapy was significantly better in the C/T arm compared to SOC therapy (88% vs 72%, p=0.039), at test of cure (21 days), and last follow-up (42 days). In patients with documented infections, the rate of microbiological eradication was similar in both groups. Drug-related adverse events that led to drug discontinuation was similar in both groups (7%). Similarly overall mortality was similar in both groups. Conclusion The empiric use of C/T to cover gram negative organisms in high risk febrile neutropenic patients with hematological malignancies is safe and associated with better clinical outcome than SOC antimicrobial agents. The emergence of resistant pathogens should be further evaluated. Disclosures Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

Summary Objective To investigate the clinical manifestations, microbiological data, and outcomes of Bordetella bronchiseptica (Bb) infections in patients with cancer. Methods Review of electronic medical records of 24 patients with Bb infection, from 2000 to 2013. An infection was considered to be associated with Bb if both clinical manifestations plus microbial growth from infected sites were present. Results Ten patients (42%) had a monomicrobial infection, whereas multiple pathogens in addition to Bb were isolated from the rest (14 patients, 58%). The most frequent sites of infection were the respiratory tract (18 patients, 75 %) and bloodstream (17%). The most frequently associated conditions were lymphopenia (71%), tobacco use (42%), and chemotherapeutic or immunosuppressive agents (33% each). Animal exposure was established in four patients. Overall, the response rate to treatment was 100% for monomicrobial and 79% for polymicrobial infections, respectively. Conclusions Bb is an uncommon pathogen even in immunosuppressed patients. Predominant sites of infection are the respiratory tract and bloodstream. Bb should be considered pathogenic in immunocompromised hosts, particularly with history of zoonotic exposure, even if accompanied by co-pathogens. Therefore, contact with potential animal sources should be minimized. The infection ranges from mild to severe and has no specific clinical or radiographic manifestations.

Background Several cases of severe bacterial, fungal, and viral infections have been reported following ibrutinib therapy. Here, we report a case of a patient with non-Hodgkin lymphoma who developed hepatitis B virus (HBV)–associated liver failure after anti-cancer treatment most recently with ibrutinib. We also review reported cases of HBV reactivation (HBVr) after ibrutinib. Methods We searched the Medline and Embase databases and identified 5 patients with HBVr related to ibrutinib for a total of 6 study patients, including our case (figure). HBV-related outcomes were defined according to the 2018 AASLD HBV guidance document. Results All 6 patients were men and most (5 or 83%) had chronic lymphocytic leukemia and past HBV infection (table). Three patients (50%) developed HBV-related hepatitis and 2 of them progressed to liver failure. Four patients (67%) had a remote history (≥24 months) of other potential risk factors besides ibrutinib that could contribute to HBVr, including the use of direct-acting antivirals for hepatitis C co-infection (1 pt), hematopoietic cell transplant (HCT) (1 pt) and rituximab use (4 patients). HBVr occurred at least 6 months after initiation of ibrutinib in most patients (4 or 67%), with a median of 9.7 months (range, 1.5–42). In all 4 patients pretreated with rituximab, that treatment was completed at least 24 months before HBVr. Two of these patients received anti-HBV prophylaxis that was stopped 12 months after the completion of rituximab; the other 2 patients were only monitored without antivirals. The HCT recipient received anti-HBV prophylaxis per guidelines. None of the 6 patients treated with ibrutinib were receiving anti-HBV prophylaxis at the time of HBVr, but 5 patients were started on anti-HBV drugs at the first sign of HBVr. Four received entecavir and 1, tenofovir. All treated patients recovered from HBVr. No pt died of HBVr. Conclusion Life-threatening HBVr can occur following ibrutinib therapy in patients with past or chronic HBV infection. The temporal association between ibrutinib therapy and reactivation indicates that ibrutinib is the likely cause of the HBVr, and clinicians should be aware of the risk of HBVr in these patients. A provisional approach could be HBV monitoring at regular intervals with initiation of antiviral therapy at the earliest sign of HBV reactivation. Disclosures All authors: No reported disclosures.

Chronic diarrhea, defined as symptoms ongoing for two or more weeks, in patients with chronic lymphocytic leukemia (CLL), has various causes, including medications, infections, autoimmunity, and ga...

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.)

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.

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.)

Summary Objectives As infection is a severe complication of Ommaya reservoirs (OR), and existing data is limited, herein we describe the largest study of the clinical manifestations and treatment outcomes of Ommaya reservoir-related infections (ORRI). Methods We retrospectively reviewed the records of all patients at our institution who had an OR placed, and developed a definite device-related infection between 2001 and 2011. Results Among 501 OR placements, 40 patients (8%) developed an ORRI. These presented with meningitis and/or meningoencephalitis (60%), cellulitis (20%), or a combination thereof (20%). Approximately 40% occurred ≤30 days of OR placement, while 60% occurred ≤10 days after the device was last accessed. Only 20% presented with leukocytosis, while another 18% had a normal cerebrospinal fluid (CSF). Gram-positive skin flora accounted >80% of the pathogens. The median hospital stay and duration of antibiotics were 13 and 24 days, respectively. Although mortality rates (≈10%) were similar among all treatment groups ( p > 0.99), shorter hospitalization and antimicrobial treatment durations were obtained with early versus late device removal ( p Conclusions As clinical symptoms can be non-specific and CSF parameters may be within normal limits, a high suspicion for infection is required. The shortest hospitalization and treatment course was achieved with early device removal.

Background Percutaneous nephrostomy tubes (PCN) are indicated for relief of urinary tract obstruction. These devices are prone to mechanical and infectious complications. The infection rate at 90 days is ±20%. Our objective was to determine whether discordant antimicrobial coverage provided prior to PCN exchange was associated with a higher rate of recurrent infection compared with those who received concordant therapy. Methods We retrospectively reviewed 780 patients that had undergone initial PCN placement at our institution between July 2014 and February 2017. We only included patients that had developed a definite PCN infection, subsequent PCN exchange, with a minimum 30 day post-PCN exchange follow up. We defined PCN infection as the presence of a positive urine culture (≥104 cfu/mL) plus symptoms consistent with a urinary tract infection. Recurrence was defined as a new PCN infection with the isolation of the same organism to the initial episode. Antibiotics were defined as concordant if they had activity against all organisms’ isolated based on antimicrobial susceptibilities. Results A total of 47 patients met our inclusion criteria. The median age of patients was 59, with 49% being male. The most common underlying tumors were urothelial (45%), cervical (17%) and prostate cancer (15%). Clinical characteristics included ureteral stents (17%), diabetes (19%), history of GU surgery (38%), and active chemotherapy at the time of PCN insertion (70%). The median time to onset of infection was 42 days. Infections were polymicrobial in 50% of the cases. The most common organisms encountered were Pseudomonas spp. (36%), Enterococcus spp. (23%) and Escherichia coli (18%). The median length of follow up of PCN tubes after exchange was 55 days. There were 12 (26%) recurrences occurring at a median time of 27 days. The provision of discordant antibiotics preceding PCN exchange was significantly associated with recurrence of infection (66.7% vs. 12.8%; P < 0.002). Conclusion Discordant antimicrobial therapy provided during PCN exchange, in the setting of a PCN infection is associated with a higher rate of relapse. Therefore, to decrease the high rate for PCN reinfection, we propose that prior to PCN exchange secondary to infection, patients should be receiving concordant antimicrobial therapy. Disclosures All authors: No reported disclosures.

Species of Clostridium bacteria are notable for their ability to lyse tumor cells growing in hypoxic environments. We show that an attenuated strain of Clostridium novyi (C. novyi-NT) induces a microscopically precise, tumor-localized response in a rat orthotopic brain tumor model after intratumoral injection. It is well known, however, that experimental models often do not reliably predict the responses of human patients to therapeutic agents. We therefore used naturally occurring canine tumors as a translational bridge to human trials. Canine tumors are more like those of humans because they occur in animals with heterogeneous genetic backgrounds, are of host origin, and are due to spontaneous rather than engineered mutations. We found that intratumoral injection of C. novyi-NT spores was well tolerated in companion dogs bearing spontaneous solid tumors, with the most common toxicities being the expected symptoms associated with bacterial infections. Objective responses were observed in 6 of 16 dogs (37.5%), with three complete and three partial responses. On the basis of these encouraging results, we treated a human patient who had an advanced leiomyosarcoma with an intratumoral injection of C. novyi-NT spores. This treatment reduced the tumor within and surrounding the bone. Together, these results show that C. novyi-NT can precisely eradicate neoplastic tissues and suggest that further clinical trials of this agent in selected patients are warranted.