Bacterial Infections in Children With Acute Myeloid Leukemia Receiving Ciprofloxacin Prophylaxis

Abstract Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.

Download Full-text

Intensified induction therapy with reduced total anthracycline exposure in pediatric low-risk acute myeloid leukemia.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.10533 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 10533-10533

Author(s):

Katherine Ashley Minson ◽

Caitlin Herring ◽

Jonathan Metts ◽

Himalee Sabnis ◽

Todd Michael Cooper ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Induction Therapy ◽

Myeloid Leukemia ◽

Bacterial Infections ◽

Viral Infections ◽

De Novo ◽

Disease Free Survival ◽

Low Risk ◽

Current Therapy ◽

Acute Myeloid

10533 Background: Despite advances in risk stratification and therapy, the post-induction disease free survival (DFS) and overall survival (OS) for children with low-risk acute myeloid leukemia (LR-AML) remain low with DFS and OS of 50% and 68%, respectively, on the standard arm of the recent Children’s Oncology Group (COG) trial, AAML1031. Additionally, current therapy for pediatric LR-AML contains anthracycline doses exceeding thresholds known to increase the risk of adverse cardiac effects. In an effort to decrease exposure to cardiotoxic therapy, the Aflac Cancer and Blood Disorders Center adopted an institutional practice to treat LR-AML patients with a regimen of intensified induction therapy with decreased anthracycline exposure (Aflac-AML consisting of ADE10, Mitox/HiDAC, HiDAC/VP, Capizzi II). The aim of this study is to describe the associated toxicities and outcomes of this regimen in pediatric LR-AML. Methods: We retrospectively reviewed medical records of patients diagnosed with de novo LR-AML and treated per the Aflac-AML regimen from 2011-2014. Charts were reviewed for cardiac outcomes, ICU admissions, and the rate of infectious toxicities. DFS and OS were determined using Kaplan-Meier survival analysis. Results: We identified 11 LR-AML patients treated with Aflac-AML therapy. Patients received a planned 317 mg/m2 cumulative anthracycline dose vs 442 mg/m2for those treated on AAML1031. There was no decrease in LVEF with a mean change of +2.17% for Aflac-AML patients from the time of diagnosis to therapy completion (p = 0.23). The primary infectious toxicities observed were febrile neutropenia and bacterial infections with a median of 36.4±6% documented bacterial infections per cycle. Fungal and viral infections were rare as were ICU admissions – median 4.5±4% per cycle – and there were no toxic mortalities. The 3-year DFS and OS from end of induction I for Aflac-AML patients were 72.7% and 90.9%, respectively. Conclusions: The Aflac-AML regimen resulted in short-term toxicities and outcomes comparable to current chemotherapy regimens for pediatric LR-AML but with reduced anthracycline exposure. These data support use of this regimen for pediatric LR-AML patients.

Download Full-text

The Value of Adding Surveillance Cultures to Fluoroquinolone Prophylaxis in the Management of Multiresistant Gram Negative Bacterial Infections in Acute Myeloid Leukemia

Journal of Clinical Medicine ◽

10.3390/jcm8111985 ◽

2019 ◽

Vol 8 (11) ◽

pp. 1985 ◽

Cited By ~ 1

Author(s):

Christelle Castañón ◽

Ahinoa Fernández Moreno ◽

Ana María Fernández Verdugo ◽

Javier Fernández ◽

Carmen Martínez Ortega ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bacterial Infections ◽

Multidrug Resistant ◽

Induction Phase ◽

Gram Negative ◽

Risk Of Death ◽

Surveillance Cultures ◽

Fluoroquinolone Prophylaxis ◽

Acute Myeloid

Multidrug resistant Gram-Negative Bacterial Infections (MR-GNBI) are an increasing cause of mortality in acute myeloid leukemia (AML), compromising the success of antineoplastic therapy. We prospectively explored a novel strategy, including mandatory fluoroquinolone prophylaxis, weekly surveillance cultures (SC) and targeted antimicrobial therapy for febrile neutropenia, aimed to reduce infectious mortality due to MR-GNBI. Over 146 cycles of chemotherapy, cumulative incidence of colonization was 50%. Half of the colonizations occurred in the consolidation phase of treatment. Application of this strategy led to a significant reduction in the incidence of GNB and carbapenemase-producing Klebisella pneumoniae (cpKp) species, resulting in a reduction of infectious mortality (HR 0.35 [95%, CI 0.13–0.96], p = 0.042). In multivariate analysis, fluroquinolone prophylaxis in addition to SC was associated with improved survival (OR 0.55 [95% CI 0.38–0.79], p = 0.001). Targeted therapy for colonized patients did not overcome the risk of death once cpKp or XDR Pseudomonas aeruginosa infections were developed. Mortality rate after transplant was similar between colonized and not colonized patients. However only 9% of transplanted patients were colonized by cpkp. In conclusion, colonization is a common phenomenon, not limited to the induction phase. This strategy reduces infectious mortality by lowering the global incidence of GN infections and the spread of resistant species.

Download Full-text

Cancrum Oris-associated with Acute Myeloid Leukemia: A Forgotten Disease

International Journal of Head and Neck Surgery ◽

10.5005/jp-journals-10001-1032 ◽

2010 ◽

Vol 1 (3) ◽

pp. 167-169

Author(s):

Arvind Krishnamurthy ◽

Shirley Sundersingh ◽

Satish Srinivas ◽

Anita Vaidhyanathan ◽

Krishnarathinam LNU

Keyword(s):

Acute Myeloid Leukemia ◽

Mortality Rate ◽

Oral Hygiene ◽

Myeloid Leukemia ◽

Bacterial Infections ◽

Poor Oral Hygiene ◽

Faecal Contamination ◽

Cancrum Oris ◽

The Face ◽

Acute Myeloid

Abstract Cancrum oris is an orofacial gangrene, which during its fulminating course causes, progressive and mutilating destruction of the infected tissues with a consortium of microorganisms. This condition is considered to represent the “face of poverty” because factors connected with poverty, such as chronic malnutrition, poor oral hygiene and sanitation, faecal contamination, and exposure to viral and bacterial infections in an immunosupressed host contribute to disease progression. This condition is seen almost exclusively among the young children and carries a high mortality rate. We present a case of cancrum oris in a 45 years old lady being treated for acute myeloid leukemia with chemotherapy, who in addition to a polymicrobial bacterial infection had superinfection with Mucormycosis.

Download Full-text

Dynamics of Procalcitonin and Bacteremia In Adult Acute Myeloid Leukemia with Chemotherapy-Induced Neutropenia

Blood ◽

10.1182/blood.v116.21.4378.4378 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4378-4378

Author(s):

Anne-Claire Gac ◽

Jean-Jacques Parienti ◽

Sylvain Chantepie ◽

Roland Leclercq ◽

Oumedaly Reman

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bacterial Infections ◽

Conflicts Of Interest ◽

Fungal Infections ◽

Short Term ◽

Neutropenic Patients ◽

Chemotherapy Induced Neutropenia ◽

Sensitive Marker ◽

Acute Myeloid

Abstract Abstract 4378 Sensitive markers of infection are rare or of limited validity in neutropenic patients. Procalcitonin (PCT), a precursor protein of calcitonin, is a specific and sensitive marker of severe bacterial infections during short-term neutropenia. Because the value of PCT measurements among patients undergoing long periods of neutropenia remains uncertain and because several mechanisms, such as bacterial or fungal infections, reactions to drugs or blood products or tumor-associated events, can cause fever, we described the dynamics of PCT in 29 acute myeloid leukemia (AML) patients with 39 instances of chemotherapy-induced neutropenia. Plasma levels of PCT were determined prospectively by an immunoluminometric assay every four days starting at the onset of chemotherapy and continuing until the resolution of fever. We found that bacteremia did increase PCT levels above 0.5 ng/mL and these levels predicted bacteremia at day 15 of chemotherapy. This finding may be relevant in the decision to alter antibiotic regimens to decrease toxicity and cost when patients remain febrile at day 15. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Adverse Effects of Intravenous Vancomycin-Based Prophylaxis during Therapy for Pediatric Acute Myeloid Leukemia

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01838-17 ◽

2017 ◽

Vol 62 (3) ◽

Author(s):

Yilun Sun ◽

Rachael L. Huskey ◽

Li Tang ◽

Hiroto Inaba ◽

Aditya H. Gaur ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bacterial Infections ◽

Liver Toxicity ◽

Antibacterial Prophylaxis ◽

Content Type ◽

Life Threatening ◽

Stage Renal Disease ◽

End Stage ◽

Acute Myeloid

ABSTRACT Children and adolescents with acute myeloid leukemia (AML) are at risk of life-threatening bacterial infections, especially with viridans group streptococci. Primary antibacterial prophylaxis with vancomycin-based regimens reduces this risk but might increase the risks of renal or liver toxicity or Clostridium difficile infection (CDI). A retrospective review of data for patients treated for newly diagnosed AML at St. Jude Children's Research Hospital between 2002 and 2008 was conducted. Nephrotoxicity was classified according to pediatric risk, injury, failure, loss, and end-stage renal disease (pRIFLE) criteria and hepatotoxicity according to Common Terminology Criteria for Adverse Events (CTCAE) criteria. The risks of nephrotoxicity, hepatotoxicity, and CDI were compared between patients receiving vancomycin-based prophylaxis, no intravenous prophylaxis, or other prophylaxis. Generalized linear mixed models were used to address potential confounding. A total of 392 chemotherapy courses (108 with no intravenous prophylaxis, 218 with vancomycin-based prophylaxis, and 66 with other prophylaxis) for 111 patients were included. Development of pRIFLE risk, injury, and failure occurred in 190, 44, and 2 courses, respectively. Increases of at least one, two, and three grades for hepatotoxicity occurred in 189, 52, and 19 courses, respectively. After adjustment for confounders, vancomycin-based prophylaxis was not associated with nephrotoxicity or hepatotoxicity and reduced the risk of CDI, compared to no intravenous prophylaxis (0.9% versus 6.5%; P = 0.007) or other prophylactic regimens (0.9% versus 3.0%; P = 0.23). Despite concerns about vancomycin toxicity, vancomycin-based prophylaxis in pediatric patients with AML did not increase the risk of nephrotoxicity or hepatotoxicity and reduced the risk of CDI. Caution is advised to avoid contributing to antibiotic resistance.

Download Full-text

Fungal and Bacterial Infections in Acute Myeloid Leukemia Patients Treated with Induction Regimens Including Fludarabine: A Retrospective Analysis of 224 Cases.

Blood ◽

10.1182/blood.v110.11.4351.4351 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4351-4351

Author(s):

Michele Malagola ◽

Annalisa Peli ◽

Daniela Damiani ◽

Anna Candoni ◽

Mario Tiribelli ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bacterial Infections ◽

Fungal Infections ◽

High Dose ◽

Induction Phase ◽

Consolidation Chemotherapy ◽

Gram Negative ◽

Induction Regimen ◽

Acute Myeloid

Abstract Infections are the major cause of morbidity and mortality of acute myeloid leukemia (AML). Invasive Fungal Infections (IFIs) occur in at least 10 to 20% of the patients submitted to induction and consolidation treatments, are responsible for death during induction in up to the 5% of the cases and may cause a delay in consolidation and intensification therapy. Among the risk factors for IFIs it has been included the use of Fludarabine (Fluda), which can induce severe and prolonged immunosuppression. In this study we retrospectively analyzed the infections occurred in 224 newly diagnosed AML patients, aged at least 65 years, consecutively treated with an induction regimen including Fluda, Ara-C and idarubicine with or without etoposide (FLAI/FLAIE). During induction phase, 181/224 (81%) patients experienced a fever of undetermined origin (FUO), the incidence of Gram negative and positive sepsis was 16% (37/224) and 29% (65/224) respectively and 7/224 (3%) patients developed a possible/probable IFI. In 6/224 patients (3%) a proven IFI was found (4 aspergillosis and 2 candidiasis). We then collected the data of the incidence of infections during the first consolidation course (FLAI: n=70; high-dose Ara-C [HD-AC]: n=65; idarubicine and HD-AC: n=89). The overall incidence of FUO was 34% (76/224), the number of Gram negative and positive sepsis was 52/224 (23%) and 49/224 (22%), respectively and 2/224 (1%) patients developed a proven IFI (3 aspergillosis and 1 candidiasis). We subsequently evaluated the incidence of infections in the three different consolidation groups. No significant differences were observed in terms of FUO, Gram positive and negative bacteraemia/sepsis and possible, probable and proven IFIs, during consolidation with Fluda-based regimen and with HD-AC-based regimens. Interestingly, the overall incidence of IFIs during consolidation with FLAI was significantly lower than during consolidation with HD-AC-based treatment program (0% vs 9%; p=0.02). These data, even though retrospectively collected, suggest that Fluda-based chemotherapy is not followed by increased incidence of infections, in particular IFIs, in comparison with conventional non-Fluda based regimens commonly used for AML induction. In our series, Fluda-based consolidation chemotherapy caused a significantly lower incidence of IFIs compared to HD-AC-based consolidation. This may be related to the lower duration of neutropoenia in patients treated with FLAI with respect to those treated with HD-AC/HD-AC + idarubicine.

Download Full-text