Antibiotics In Cancer Patients Research Articles

The utility of procalcitonin in febrile neutropenia.

12040 Background: The utility of procalcitonin (PCT) in febrile neutropenia (FN) in oncology patients on active therapy has not been well validated. FN constitutes a critical oncologic emergency, often characterized by subtle manifestations of infection, and timely diagnosis and treatment is vital. Although a potential harbinger of dangerous infection, FN can also occur without an identifiable infection, in which case hospitalization and antibiotics may be unnecessary. PCT, an amino acid, is elevated specifically during bacterial infections in the non-cancer population and correlates with infection severity. Clinicians employ PCT levels as a diagnostic adjunct, discerning bacterial from viral infections and analyzing PCT changes to guide treatment decisions. We examined oncology patients presenting with FN to correlate PCT levels and trends with confirmed infections. Methods: We identified patients with neutropenic fever, cancer, and a PCT result seen at our institution from 12/1/2017-12/1/2022. Patients were determined to have a confirmed infection if they had a positive bacterial blood culture. Demographics and clinical characteristics were compared between infection status and induction chemotherapy or transplant status using a Wilcoxon Rank Sum test for continuous variables and a Chi-Square or Fisher’s Exact test for categorical variables. Baseline (at time of initial FN) and highest PCT levels were compared by patient and disease characteristics and proven infection using Wilcoxon Rank Sum test. Logistic regression was used to determine the association of log-transformed PCT (baseline and highest) with proven infection (yes/no) while adjusting for covariates. All tests were two-tailed with p< 0.05 considered statistically significant. Results: Of 365 patients, 61 (16.7%) had an identified infection. Median baseline and peak PCT of 1.26 and 1.51 ng/mL, respectively, were significantly greater for these patients as compared to those with negative cultures at 0.54 and 0.65 ng/mL, respectively (P= 0.01 and <0.01). For every unit increase in the log transformed baseline PCT, the odds of having a proven infection increased by 23%. There were no significant differences in patient or clinical characteristics between those with and without infection. Of those admitted for induction chemotherapy and transplant who developed FN, PCT at time of initial fever was higher at 0.97 vs 0.56 ng/mL (p=0.02). Interestingly, median baseline and median peak PCT differed between gender with females 0.51 and males 0.72 ng/mL (p=0.02) at baseline, and 0.63 vs 0.83 ng/mL (p=0.04), respectively, at peak. Conclusions: PCT levels in cancer patients with FN are significantly associated with culture positive infection. This data can help guide treatment and de-escalation of antibiotics in cancer patients admitted with FN. Further evaluation should be taken to determine how to best use PCT to determine the need for admission and antibiotic prescription.

Antibiotics use patterns in end-of-life cancer patients and medical staff's perception of antimicrobial stewardship programs.

While most cancer patients with end-of-life (EOL) care receive antibiotic treatments, antibiotic use should be decided appropriately considering the benefits, side effects, resistance, and cost effects. Antimicrobial stewardship programs (ASP) are important for patients with EOL care, but there is limited study analyzing actual antibiotic use in EOL care and the perceptions of Korean medical staff. Electronic medical records of 149 deceased cancer patients hospitalized in the medical hospitalist units at Asan Medical Center in Seoul from May 2019 to September 2021 were reviewed. Basic information, antibiotic use, duration, and changes were investigated. We surveyed medical staff's perceptions of antibiotics in cancer patients with EOL. Of the 149 cancer patients with EOL care, 146 (98.0%) agreed with physician orders for life-sustaining treatment (POLST). In total, 143 (95.9%) received antibiotics, 110 (76.9%) received combination antibiotic treatment, and 116 (81.1%) were given antibiotics until the day of death. In a survey of 60 medical staff, 42 (70.0%) did not know about ASP, and 24 (40.0%) thought ASP was important in EOL care. Nineteen doctors (31.7%) discussed the use or discontinuation of antibiotics with patients or caregivers when writing POLST, but only 8 patients (5.6%) stopped antibiotics after POLST. Most cancer patients with EOL care continue to receive antibiotics until just before their death. A careful approach is needed, considering the benefits and side effects of antibiotic use, and the patient's right to self-decision. It is necessary to actively improve awareness of ASP and its importance for medical staff.

A case-control study of Clostridioides difficile symptomatic infections in a pediatric cancer hospital.

The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer. This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016-2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors. We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3-12.5); for meropenem, 4.41 (95%CI 2.1-9.2); and for cefepime, 2.6 (95%CI 1.3-5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2-6.2), melphalan 9.04 (95%CI 1.9-42.3), busulfan 16.7 (95%CI 2.1-134.9), and asparaginase 8.97 (95%CI 1.9-42.9). C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors.

Broad-spectrum antibiotics associated gut microbiome disturbance impairs T cell immunity and promotes lung cancer metastasis: a retrospective study

BackgroundGut microbiome has been linked to a regulatory role in cancer progression. However, whether broad-spectrum antibiotics (ATB) associated gut microbiome dysbiosis contributes to an impaired T cell immune function, and ultimately promotes lung cancer metastasis is not well known.MethodsIn this study, a retrospective analysis was performed in a cohort of 263 patients initially diagnosed with non-small cell lung cancer (NSCLC) patients, including the ATB group (patients with broad-spectrum antibiotics treatment) (n = 124), and non-ATB group (n = 139) as control. ATB patients were prescribed ATB for over 5 days within 30 days prior to the collection of blood and fecal specimens and followed surgical treatment or first-line therapy. T cell immune function and metastasis-free survival (MFS) were evaluated between the two groups. Gut microbiota was evaluated by 16S rDNA sequencing. The predictive value of T cell immunity for MFS was evaluated by ROC analysis and Cox regression analysis.ResultsOur results suggest that broad-spectrum antibiotics (ATB) impair T cell immune function in patients with either early-stage or advanced NSCLC, which likely contribute to the promotion of lung cancer metastasis. Results of the survival analysis show that metastasis-free survival (MFS) is significantly shorter in the ATB patients than that in the non-ATB patients with stage III NSCLC. The 16S rDNA sequencing shows that ATB administration contributes to a significant dysbiosis of the composition and diversity of gut microbiota. Moreover, ROC analysis results of CD4 (AUC 0.642, p = 0.011), CD8 (AUC was 0.729, p < 0.001), CD16 + 56 + (AUC 0.643, p = 0.003), and the combination of CD4, CD8 and CD16 + 56+ (AUC 0.810, p < 0.001), or Cox regression analysis results of CD4 (HR 0.206, p < 0.001), CD8 (HR 0.555, p = 0.009), which is likely regulated by ATB administration, have significantly predictive values for MFS.ConclusionThese results provide evidence of gut microbiome disturbance due to ATB administration is involved in the regulation of T cell immunity, and their predictive value for the tumor metastasis in lung cancer patients. Thus, gut microbiota may serve as a therapeutic target for lung cancer. Consequently, caution should be exercised before the long-term administration of broad-spectrum antibiotics in cancer patients.

356. The Role of Procalcitonin in Antimicrobial Stewardship Among Cancer Patients Admitted with COVID-19

BackgroundProcalcitonin (PCT) has been used to guide antimicrobial therapy in bacterial infections. With the wide spread use of empiric use of antibiotics in cancer patients admitted with COVID-19 disease, we aimed to evaluate the role of PCT in decreasing the duration of empiric antimicrobial therapy among cancer patients admitted with COVID-19. MethodsWe conducted a retrospective study of cancer patients admitted to MD Anderson Cancer Center who had a PCT test done within 72 hours of admission following their COVID-19 diagnosis between March 1, 2020 and June 6, 2021. Patients were divided into 2 groups of PCT < 0.25 ng/mL and PCT >=0.25 ng/mL. We assessed pertinent cultures including blood and respiratory, as well as antibacterial use and duration of empiric antibacterial therapy.ResultsWe identified 544 patients with a median age of 62 years (range, 14-93). There were 312 (57%) patients that had at least one culture obtained from a sterile or infected site within 7 days following admission. None of the patients who had PCT< 0.25 had a positive culture whereas 41/111 (37%) patients with PCT >= 0.25 had at least one positive culture [P< 0.0001]. Among the 373 patients who had a PCT < 0.25, 129 (35%) patients received more than 72 hours of IV antibiotics compared to 87/171 (51%) among patients with PCT >=0.25 [P= 0.0003].ConclusionThese results confirm the correlation between a PCT level greater than 0.25 and a documented bacterial infection. Furthermore, procalcitonin could be useful in enhancing antimicrobial stewardship in cancer patients with COVID-19 by reducing the duration of antimicrobial therapy beyond the initial empiric 72 hours until PCT results become available.Disclosures Natalie J Dailey Garnes, MD, MPH, AlloVir (Other Financial or Material Support, collaborator on research protocol)

Early switch from intravenous to oral antibiotic therapy in patients with cancer who have low-risk neutropenic sepsis (the EASI-SWITCH trial): study protocol for a randomised controlled trial

BackgroundNeutropenic sepsis remains a common treatment complication for patients receiving systemic anti-cancer treatment. The UK National Institute for Health and Care Excellence have not recommended switching from empirical intravenous antibiotics to oral antibiotics within 48 h for patients assessed as low risk for septic complications because of uncertainty about whether this would achieve comparable outcomes to using intravenous antibiotics for longer. The UK National Institute for Health Research funded the EASI-SWITCH trial to tackle this uncertainty.MethodsThe trial is a pragmatic, randomised, non-inferiority trial that aims to establish the clinical and cost-effectiveness of early switching from intravenous to oral antibiotics in cancer patients with low-risk neutropenic sepsis. Patients ≥ 16 years, receiving systemic anti-cancer treatment (acute leukaemics/stem cell transplants excluded), with a temperature of > 38 °C, neutrophil count ≤ 1.0 × 109/L, MASCC (Multinational Association of Supportive Care in Cancer) score ≥ 21 and receiving IV piperacillin/tazobactam or meropenem for less than 24 h are eligible to participate. Patients are randomised 1:1 either (i) to switch to oral ciprofloxacin and co-amoxiclav within 12–24 h of commencing intravenous antibiotics, completing at least 5 days total antibiotics (intervention), or (ii) to continue intravenous antibiotics for at least 48 h, with ongoing antibiotics being continued at the physician’s discretion (control). Patients are discharged home when their physician deems it appropriate. The primary outcome measure is a composite of treatment failures as assessed at day 14. The criteria for treatment failure include fever persistence or recurrence 72 h after starting intravenous antibiotics, escalation from protocolised antibiotics, hospital readmission related to infection/antibiotics, critical care support or death. Based on a 15% treatment failure rate in the control group and a 15% non-inferiority margin, the recruitment target is 230 patients.DiscussionIf the trial demonstrates non-inferiority of early switching to oral antibiotics, with potential benefits for patient quality of life and resource savings, this finding will have significant implications for the routine clinical management of those with low-risk neutropenic sepsis.Trial registrationISRCTN: 84288963. Registered on the 1 July 2015. https://doi.org/10.1186/ISRCTN84288963.EudraCT: 2015-002830-35.

Antibiotics in cancer patients: is the verdict still out?

Immune checkpoint inhibitors (ICI) have shown tremendous successes on treatment of multiple tumor malignancies, offering a valuable but rare commodity to both patients and researchers (1-3). As an important part of tumor immunotherapies, ICIs inspire the once-questioned idea that although inhibited our immune system is able to eliminate tumor cells in a similar way that it does to infectious microorganisms. ICIs can release the brakes imposed by the tumor on this fabulous capability, which then heightens the immune response against tumor cells.

The impact of antibiotic usage on the efficacy of chemoimmunotherapy is contingent on the source of tumor-reactive T cells.

In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies. We investigated the impact of antibiotics on the therapeutic outcomes of cyclophosphamide (CTX) chemotherapy and adoptive T-cell therapy (ACT) where CTX was used as the host-conditioning regimen in mice. We show that antibiotic prophylaxis dampened the endogenous T cell responses elicited by CTX, and reduced the efficacy of CTX against B-cell lymphoma. In the ACT setting, antibiotics administration impaired the therapeutic effects of adoptively transferred tumor-specific CD4+ T cells in mice with implanted colorectal tumors. In contrast, long-term antibiotic exposure did not affect the efficacy of ACT using CD19-targeting chimeric antigen receptor (CAR) T cells in mice with systemic B-cell lymphoma, although it correlated with prolonged CAR expression and sustained B-cell aplasia. Our study demonstrates that chemoimmunotherapies may have variable reliance on intestinal microbiota for T cell activation and function, and thus have different sensitivities to antibiotic prophylaxis. These findings may have implications for the judicial use of antibiotics in cancer patients receiving chemoimmunotherapies.

The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients.

Cancer remains a leading cause of mortality and morbidity worldwide. In addition to organ failure, the most frequent reasons for admission of cancer patients to intensive care units (ICU) are: infections and sepsis. As critically ill, the complexity of the health situation of cancer patients renders the standard antimicrobial regimen more complex and even inadequate which results in increased mortality rates. This is due to pathophysiological changes in the volume of distribution, increased clearance, as well as to organ dysfunction. While in the former cases a decrease in drug efficacy is observed, the hallmark of the latter one is overdosing leading to increased toxicity at the expense of efficacy. Furthermore, an additional risk factor is the potential drug-drug interaction between antibiotics and antineoplastic agents. Therefore, therapeutic drug monitoring (TDM) is a necessity to improve the clinical outcome of antimicrobial therapy in cancer patients. To be applied in routine analysis the method used for TDM should be cheap, fast and highly accurate/sensitive. Furthermore, as ICU patients are treated with a cocktail of antibiotics the method has to cover the simultaneous analysis of antibiotics used as a first/second line of treatment. The aim of the current review is to briefly survey the pitfalls in the current antimicrobial therapy and the central role of TDM in dose adjustment and drug-drug interaction's evaluation. A major section is dedicated to summarize the currently published analytical methods and to shed light on the difficulties and potential problems that can be encountered during method development.

Prophylactic antibiotics or G(M)-CSF for the prevention of infections and improvement of survival in cancer patients receiving myelotoxic chemotherapy.

Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (macrophage) colony-stimulating factors (G(M)-CSF) and antibiotics, frequently quinolones or cotrimoxazole. Current guidelines recommend the use of colony-stimulating factors when the risk of febrile neutropenia is above 20%, but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. To compare the efficacy and safety of G(M)-CSF compared to antibiotics in cancer patients receiving myelotoxic chemotherapy. We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to December 2015). We planned to include both full-text and abstract publications. Two review authors independently screened search results. We included randomised controlled trials (RCTs) comparing prophylaxis with G(M)-CSF versus antibiotics for the prevention of infection in cancer patients of all ages receiving chemotherapy. All study arms had to receive identical chemotherapy regimes and other supportive care. We included full-text, abstracts, and unpublished data if sufficient information on study design, participant characteristics, interventions and outcomes was available. We excluded cross-over trials, quasi-randomised trials and post-hoc retrospective trials. Two review authors independently screened the results of the search strategies, extracted data, assessed risk of bias, and analysed data according to standard Cochrane methods. We did final interpretation together with an experienced clinician. In this updated review, we included no new randomised controlled trials. We included two trials in the review, one with 40 breast cancer patients receiving high-dose chemotherapy and G-CSF compared to antibiotics, a second one evaluating 155 patients with small-cell lung cancer receiving GM-CSF or antibiotics.We judge the overall risk of bias as high in the G-CSF trial, as neither patients nor physicians were blinded and not all included patients were analysed as randomised (7 out of 40 patients). We considered the overall risk of bias in the GM-CSF to be moderate, because of the risk of performance bias (neither patients nor personnel were blinded), but low risk of selection and attrition bias.For the trial comparing G-CSF to antibiotics, all cause mortality was not reported. There was no evidence of a difference for infection-related mortality, with zero events in each arm. Microbiologically or clinically documented infections, severe infections, quality of life, and adverse events were not reported. There was no evidence of a difference in frequency of febrile neutropenia (risk ratio (RR) 1.22; 95% confidence interval (CI) 0.53 to 2.84). The quality of the evidence for the two reported outcomes, infection-related mortality and frequency of febrile neutropenia, was very low, due to the low number of patients evaluated (high imprecision) and the high risk of bias.There was no evidence of a difference in terms of median survival time in the trial comparing GM-CSF and antibiotics. Two-year survival times were 6% (0 to 12%) in both arms (high imprecision, low quality of evidence). There were four toxic deaths in the GM-CSF arm and three in the antibiotics arm (3.8%), without evidence of a difference (RR 1.32; 95% CI 0.30 to 5.69; P = 0.71; low quality of evidence). There were 28% grade III or IV infections in the GM-CSF arm and 18% in the antibiotics arm, without any evidence of a difference (RR 1.55; 95% CI 0.86 to 2.80; P = 0.15, low quality of evidence). There were 5 episodes out of 360 cycles of grade IV infections in the GM-CSF arm and 3 episodes out of 334 cycles in the cotrimoxazole arm (0.8%), with no evidence of a difference (RR 1.55; 95% CI 0.37 to 6.42; P = 0.55; low quality of evidence). There was no significant difference between the two arms for non-haematological toxicities like diarrhoea, stomatitis, infections, neurologic, respiratory, or cardiac adverse events. Grade III and IV thrombopenia occurred significantly more frequently in the GM-CSF arm (60.8%) compared to the antibiotics arm (28.9%); (RR 2.10; 95% CI 1.41 to 3.12; P = 0.0002; low quality of evidence). Neither infection-related mortality, incidence of febrile neutropenia, nor quality of life were reported in this trial. As we only found two small trials with 195 patients altogether, no conclusion for clinical practice is possible. More trials are necessary to assess the benefits and harms of G(M)-CSF compared to antibiotics for infection prevention in cancer patients receiving chemotherapy.

Beating Cancer with a Gut Feeling.

Blockade of immune checkpoint molecules, a group of molecules normally involved in maintaining self-tolerance and limiting T cell responses, has emerged as a breakthrough in cancer therapy. Two recent studies published in Science show that, in mice, gut commensal microbes promote antitumor immunity and may determine therapy efficacy.

Effectiveness of early antibiotic administration in septic patients with cancer

Introduction: First dose intravenous antimicrobial therapy should be administered within 1 hour of admission but this is achieved in a minority of patients.. Methods: We performed a retrospective analysis at the largest Oncology hospital in Europe. Nurse-led administration of initial antibiotic therapy was introduced to the admissions unit. Results: The nurse led protocol increased compliance with the 1 hour target from 40% to 88.6%. There was a statistically significant decrease in the mean length of stay (p=0.045) which was more pronounced in the neutropenic population (p=0.006). There was a trend to improved 30 day mortality. Conclusions: A nurse led protocol can be effective in improving compliance with the 1 hour target. Early administration of intravenous antibiotics in cancer patients with sepsis is associated with a shorter length of inpatient stay and a trend to decreased mortality.

Trough serum concentrations of β-lactam antibiotics in cancer patients: inappropriateness of conventional schedules to pharmacokinetic/pharmacodynamic properties of β-lactams

Serum concentrations of β-lactams that continuously exceed the minimum inhibitory concentration may improve therapeutic outcomes for immunosuppressed patients. The trough serum levels of ceftazidime (CAZ), cefepime (FEP) or imipenem (IMP) were prospectively determined on days 1 and 3 of treatment in cancer patients. Seventy-eight episodes of suspected infection were analysed. Trough serum levels were higher than 4 mg/L in 62%, 24% and 0% of cases in the CAZ, FEP and IMP groups, respectively, and were higher than 20 mg/L in 24% of cases in the CAZ group compared with 0% both in the FEP and IMP groups. For suspected infectious episodes in cancer patients, the traditional intermittent regimen of β-lactams does not appear to be appropriate for the pharmacokinetic/pharmacodynamic properties of these antibiotics.

Management of infection in cancer patients: studies of the EORTC International Antimicrobial Therapy Group (IATG)

Infection remains an important cause of morbidity and mortality in cancer patients, especially those undergoing chemotherapy for haematological malignancies. The practice of instituting an empirical broad-spectrum antibiotic therapy as soon as possible after the onset of fever has substantially reduced the clinical impact of this complication. In the last 25 years, the International Antimicrobial Therapy Group of the European Organisation for Research and Treatment of Cancer (EORTC-IATG) have published nearly 30 articles and a number of abstracts on several facets of the epidemiology and management of infection in cancer patients. With a progressive methodological refinement, the EORTC-IATG trials have established the standard for the management of febrile neutropenia, both by setting methodologies and definitions and by testing several antibiotic regimens that are active and effective for this indication. With the aim of supporting a more rational use of antibiotics in cancer patients, the most recent trials have dealt with the management of low risk patients, showing the safety and feasibility of oral therapy.

Implantable subcutaneous infusion ports.

Limited vascular access hinders administration of chemotherapy, blood products and antibiotics in cancer patients. Repeated venous cannulation is often psychologically traumatic to patients. The use of a subcutaneous infusion port allows convenient vascular access. Twenty-two cancer patients had ports implanted for venous access (17 patients) and administration of regional chemotherapy (5 patients). The period of indwelling ranged from 70 to 470 days (median 270 days). Two patients (9%) had wound dehiscence that required port revision. Despite this, the wound did not heal in 1 patient and the port had to be removed. Other complications included venous thrombosis (5%) and subcutaneous haematoma (5%). There was no catheter-related bacteraemia. The subcutaneous infusion port provides a suitable vascular access in cancer patients.

Coagulation abnormalities induced by beta-lactam antibiotics in cancer patients.

The records of 714 neutropenic cancer patients who were treated with high doses of a combination of beta-lactam antibiotics were analyzed. In 268 patients, coagulation parameters were measured at least once before, during, and after therapy. Alterations on the prothrombin time, activated partial thromboplastin time, and thrombin time were found in those regimens containing a semisynthetic penicillin, cefamandole, and moxalactam. Mild and severe hemorrhage was observed in some patients receiving these regimens. After prophylactic administration of vitamin K to all patients treated with moxalactam, no further hemorrhage was noted. Alteration of the prothrombin time, with preservation of other parameters, was found in patients receiving antibiotic regimens containing semisynthetic penicillin and cefoxitin. No evidence of hemorrhage was found in this group of patients. In neutropenic cancer patients, the occurrence of another impairment in the clotting process, in addition to thrombocytopenia, greatly increases the risk of serious hemorrhage. Coagulation parameters must be routinely monitored when these patients receive antibiotics known to cause coagulation abnormalities.