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The treatment of patients with infection secondary to carbapenem-resistant Acinetobacter baumannii with emerging cefiderocol resistance remains challenging and unclear. We present a case of in vivo emergence of pandrug-resistant A baumannii that was successfully treated with the compassionate use of investigational sulbactam-durlobactam-based antibiotic regimen. We also performed a longitudinal genomic analysis of the bacterial isolates and showed the development of resistance and genetic mutations over time., Competing Interests: Potential conflicts of interest. S. L. A. serves on the advisory boards for Entasis, GSK, Basilea, bioMérieux, AstraZeneca, Melinta, Shionogi, Ferring, and F2G. S. H. M. is a current employee of Innoviva Specialty Therapeutics, Inc. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

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., (© 2022 The Authors. CA: A Cancer Journal for Clinicians published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: An increasing number of observational studies have reported the persistence of symptoms following recovery from acute COVID-19 disease in non-cancer patients. The long-term consequences of COVID-19 are not fully understood particularly in the cancer patient population. The purpose of this study is to assess post-acute sequelae of SARS-CoV-2 infection (PASC) in cancer patients following acute COVID-19 recovery., Methods: We identified cancer patients at MD Anderson Cancer Center who were diagnosed with COVID-19 disease between March 1, 2020, and September 1, 2020, and followed them till May 2021. To assess PASC, we collected patients reported outcomes through questionnaires that were sent to patients daily for 14 days after COVID-19 diagnosis then weekly for 3 months, and then monthly thereafter. We also reviewed patients' electronic medical records to capture the persistence or emergence of new COVID19-related symptoms reported during any clinic or hospital encounter beyond 30 days of the acute illness and up to 14 months., Results: We included 312 cancer patients with a median age of 57 years (18-86). The majority of patients had solid tumors (75%). Of the 312 patients, 188 (60%) reported long COVID-19 symptoms with a median duration of 7 months and up to 14 months after COVID-19 diagnosis. The most common symptoms reported included fatigue (82%), sleep disturbances (78%), myalgias (67%), and gastrointestinal symptoms (61%), followed by headache, altered smell or taste, dyspnea (47%), and cough (46%). A higher number of females reported a persistence of symptoms compared to males (63% vs. 37%; p=0.036). Cancer type, neutropenia, lymphocytopenia, and hospital admission during acute COVID-19 disease were comparable in both groups. Among the 188 patients with PASC, only 16 (8.5%) were re-admitted for COVID-related reasons., Conclusions: More than one out of two cancer patients, and more likely females, report PASC that may persist beyond 6 months and even 1 year. The most common symptoms are non-respiratory and consist of fatigue, sleep disturbance, myalgia, and gastrointestinal symptoms. Most of the cancer patients with PASC were managed on outpatient basis with only 8.5% requiring a COVID-19-related re-admission., Funding: This research is supported by the National Institutes of Health/National Cancer Institute under award number P30CA016672, which supports the MD Anderson Cancer Center Clinical Trials Office. The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication., Competing Interests: HD, AC, IS, AM, YJ, PL, BG, TJ, EY, JB, CR, MF, FK, MP, NA, RR, DK, PC, RH, IR No competing interests declared, (© 2023, Dagher et al.)

Background: In this international multicenter study, we aimed to determine the independent risk factors associated with increased 30 day mortality and the impact of cancer and novel treatment modalities in a large group of patients with and without cancer with COVID-19 from multiple countries., Methods: We retrospectively collected de-identified data on a cohort of patients with and without cancer diagnosed with COVID-19 between January and November 2020 from 16 international centers., Results: We analyzed 3966 COVID-19 confirmed patients, 1115 with cancer and 2851 without cancer patients. Patients with cancer were more likely to be pancytopenic and have a smoking history, pulmonary disorders, hypertension, diabetes mellitus, and corticosteroid use in the preceding 2 wk (p≤0.01). In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin, and procalcitonin) but were less likely to present with clinical symptoms (p≤0.01). By country-adjusted multivariable logistic regression analyses, cancer was not found to be an independent risk factor for 30 day mortality (p=0.18), whereas lymphopenia was independently associated with increased mortality in all patients and in patients with cancer. Older age (≥65y) was the strongest predictor of 30 day mortality in all patients (OR = 4.47, p<0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30 day mortality (OR = 0.64, p=0.036). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30 day mortality rate than those who did not (5.9 vs 17.6%; p=0.03)., Conclusions: Increased 30 day all-cause mortality from COVID-19 was not independently associated with cancer but was independently associated with lymphopenia often observed in hematolgic malignancy. Remdesivir, particularly in patients with cancer receiving low-flow oxygen, can reduce 30 day all-cause mortality., Funding: National Cancer Institute and National Institutes of Health., Competing Interests: IR, RH, NM, TD, HD, YJ, VS, BS, AB, RS, AF, EG, AB, NM, NH, SS, TD, YV, SF, AP, RC, VM, JA, JB, FK, BG, TJ, EY, HT, NA, MY, CR, MP, NA, RR, SA, RD, PC, TM, KI, RH, RA, AG, CP, DL, MS, BT, CA, DK, AM, AC No competing interests declared, (© 2023, Raad, Hachem et al.)

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., Competing Interests: HD, AC, PM, YJ, RH, AM, JB, GV, IR No competing interests declared, (© 2022, Dagher et al.)

Use of immune checkpoint inhibitors (ICIs), a revolutionary treatment in modern oncology, is frequently complicated by immune-related adverse events (irAEs), which can be confused with infections, and vice versa, thus complicating management decisions. In this study, we review the published cases of infections as simulators of irAEs in cancer patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Cryptococcal infection has been increasingly reported in patients with COVID-19 infection, but the epidemiological factors, presentation, diagnostic certainty, and outcome have not been well-described., Methods: We reviewed the published cases of COVID-19-associated Cryptococcus infections (CACI) to shed the light on the burden of this infection., Results: We identified 13 patients with confirmed cryptococcal infection. Cryptococcus infection was primarily seen in patients with severe COVID-19 disease who received corticosteroids therapy and admitted to the intensive care unit. Pulmonary CACI was the most common reported infection followed by cryptococcal meningitis., Conclusion: In light of the high mortality rate, clinicians should maintain a high clinical suspicion of CACI in critically ill patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The Multinational Association for Supportive Care in Cancer (MASCC) risk index has been utilized to determine the risk for poor clinical outcomes in patients with febrile neutropenia (FN) in an emergency center (EC). However, this index comprises subjective elements and elaborated metrics limiting its use in ECs. We sought to determine whether procalcitonin (PCT) level (biomarker of bacterial infection) with or without lactate level (marker of inadequate tissue perfusion) offers a potential alternative to MASSC score in predicting the outcomes of patients with FN presenting to an EC., Methods: We retrospectively identified 550 cancer patients with FN who presented to our EC between April 2018, and April 2019, and had serum PCT and lactate levels measured., Results: Compared with patients with PCT levels <0.25 ng/ml, those with levels ≥0.25 ng/ml had a significantly higher 14-day mortality rate (5.2% vs. 0.7%; p = 0.002), a higher bloodstream infection (BSI) rate, and a longer hospital length of stay (LOS). Logistic regression analysis showed that patients with PCT levels ≥0.25 ng/ml and lactate levels >2.2 mmol/L were more likely to be admitted and have an LOS >7 days, BSI, and 14-day mortality than patients with lower levels. PCT level was a significantly better predictor of BSI than MASSC score (p = 0.003) or lactate level (p < 0.0001)., Conclusions: Procalcitonin level is superior to MASCC index in predicting BSI. The combination of PCT and lactate levels is a good predictor of BSI, hospital admission, and 14-day mortality and could be useful in identifying high-risk FN patients who require hospital admission., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Arcanobacterium haemolyticum causes pharyngotonsillitis in children and young adults. It is rarely isolated in pharyngeal swabs as testing for it is not routine. Data on complications, management, and antibiotic susceptibility testing is limited. We sought to review the available literature on the presentation and management of A. haemolyticum pharyngotonsillitis in this age group., Methods: A systematic review of eligible studies reporting pharyngotonsillitis and related complications in children and young adults caused by A. haemolyticum was conducted. Literature from case reports, case series, and available cohorts was compiled. Data were analyzed using descriptive statistics., Results: The initial database search yielded 63 articles, after applying exclusion criteria 17 studies were included. 191 patients were identified with a median age of 16.5 years. The most common presentation was throat pain reported in 93.7% of patients. Tonsillar exudates, fever at presentation and rash were present in more than half of the reviewed cases. The diagnosis was established by a positive culture on a pharyngeal swab in 98.8% of swabs collected. Complications described included peritonsillar abscesses, Lemierre's syndrome, pneumonia, and sepsis. Penicillin was the first line antibiotic in 81% of patients followed by macrolides in 19 patients (18%)., Conclusions: A. haemolyticum occurs in children and young adults and may result in complications. Our review supports its susceptibility to penicillin. We suggest a diagnostic and management algorithm to guide clinicians in targeted testing and aid with decision making regarding timely and appropriate antibiotic therapy, in an effort to reduce the burden of its complications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (© 2021 Wiley-VCH GmbH.)

Cutaneous tuberculosis secondary to skin inoculation of Mycobacterium tuberculosis is uncommon but it can occur in the health care settings. Herein, we report an unusual case of primary cutaneous tuberculosis of the thumb following a needlestick injury. The infection progressed with a necrotic granuloma, lymphatic dysfunction as visualized by near-infrared fluorescence lymphatic imaging, and the development of an axillary web syndrome., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The novel coronavirus disease 2019 (COVID-19) pandemic has led to an unprecedented threat to the international community and raised major concerns in terms of public health safety. Although our current understanding of the complexity of COVID-19 pathogenesis remains limited, the infection is largely mediated by the interaction of viral spike protein and angiotensin-converting enzyme 2 (ACE2). The functional importance of ACE2 in different demographic and comorbid conditions may explain the significant variation in incidence and mortality of COVID-19 in vulnerable groups, and highlights its candidacy as a potential therapeutic target. We provide evidence supporting the idea that differences in incidence and severity of COVID-19 infection may be related to ACE2. Emerging data based on the prevalence and severity of COVID-19 among those with established high levels of ACE2 expression strongly support our hypothesis. Considering the burden of COVID-19 infection in these vulnerable groups and the impact of the potential therapeutic and preventive measures that would result from adopting ACE2-driven anti-viral strategies, our hypothesis may expedite global efforts to control the current COVID-19 pandemic.

The use of granulocyte colony-stimulating factor (G-CSF) in patients with haematological malignancies is associated with less febrile neutropenia episodes. But in the presence of COVID-19 infection, the administration of G-CSF is challenging as it may trigger a robust inflammatory reaction resulting in cytokine storm, respiratory failure and severe outcomes.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: Non-HIV immunocompromised patients with Pneumocystis jirovecii pneumonia (PCP) have lower fungal load than those with AIDS, potentially affecting the accuracy of diagnostic biomarkers. Therefore, we investigated the performance of serum (1,3)-Beta-d-Glucan (BDG) in conjunction with quantitative Pneumocystis jirovecii PCR (qPCR) in non-HIV cancer patients., Methods: We reviewed records of non-HIV cancer patients and classified them as definite, probable, or possible PCP cases, according to clinicoradiological features, microscopy findings, and qPCR results in bronchoscopy specimens. We evaluated the diagnostic performance of serum BDG and its correlation with qPCR results., Results: We identified 101 PCP patients (73 definite/probable, 28 possible) and 74 controls. Correlation of BDG and qPCR was low among all 101 qPCR-positive patients (Spearman's = 0.38) and in definite/probable PCP cases (Spearman's = 0.18). Considering all qPCR-positive patients, BDG showed consistently low sensitivity at different cutoffs. Among definite/probable cases, the diagnostic accuracy of BDG remained poor, yet slightly improved with high qPCR thresholds (AUC = 0.86 at ≥2000 DNA copies/mL). BDG had a low PPV but excellent NPV across different qPCR and BDG cutoffs., Conclusions: BDG and qPCR levels correlate poorly in non-HIV cancer patients with PCP. BDG diagnostic performance is suboptimal but a negative test may be useful to rule out PCP in this population., (Copyright © 2020 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Mass-like lesions are an uncommon presentation of cytomegalovirus (CMV) disease., Case: We report on a case of disseminated CMV disease with bilateral adrenal pseudotumors in a patient with a history of acute leukemia in remission., Conclusion: In the settings of advanced cancer therapy and organ transplantation, a high index of suspicion for CMV should be maintained for mass-like disease.

Introduction : Central line-associated bloodstream infections (CLABSI) are a frequent cause of healthcare-associated infections, increasing healthcare costs and decreasing the quality of life for critically and chronically ill patients such as those with cancer. These infections are largely preventable and have been significantly reduced throughout the United States. However, further reduction of CLABSI requires continued innovation in preventive strategies. Areas covered : We provide an overview of the recent medical literature on catheter-related infections among cancer patients, discussing epidemiology, risk factors, and pathogenesis of CLABSI with a focus on the newest and current preventive measures. The data discussed here were retrieved mainly from clinical trials, meta-analyses, and systematic reviews published in the English language using a MEDLINE database search from 1 January 1990 until the end of December 2019. Expert opinion : The growing impact of CLABSI on the healthcare setting and mortality and morbidity rates in cancer patients calls for novel technologies for preventing central line-related infections. Advances in antimicrobial lock therapy are not limited to salvage therapy but have also provided a novel and promising prophylactic approach to CLABSI. Also, the use of antimicrobial-coated catheters with chlorhexidine-impregnated dressings, along with the application of insertion and maintenance bundles, is an effective and cost-effective approach for preventing central line-related infections.

Background: Nontuberculous mycobacterium (NTM) infection following cosmetic procedures usually results from inadequate sterile techniques and contamination from nonsterile water. These infections are difficult to diagnose and treat., Objective: This study aimed to describe the characteristics of NTM infections acquired after an aesthetic procedure, identify high-risk patients and high-risk cosmetic procedures, and provide a diagnostic and management algorithm for NTM infections occurring after cosmetic procedures., Methods: On December 20, 2017 an online search of the Medline database was done. All articles describing NTM infection in cosmetic procedures were included in this review., Results: In total, 92 patients with a mean age of 38.35 years were included in this review. Cosmetic procedures performed in the Dominican Republic were the most common source of infection and were noted in 33 patients. The procedure that resulted in the highest proportion of the infections was mesotherapy (34%). In most of the cases, the diagnosis was missed at the initial presentation and a short course of inadequate antibiotics was unsuccessful., Conclusion: Nontuberculous mycobacterium infections are hard to diagnose and difficult to treat, sometimes leading to severe irreversible sequalae. Aesthetic practitioners should know when to suspect and how to prevent, diagnose, and treat NTM infections.