Bacterial Infections in Children With Acute Myeloid Leukemia Receiving Ciprofloxacin Prophylaxis

Omar, Suha Al; Anabtawi, Nadeen; Qasem, Wiam Al; Rihani, Rawad

doi:10.1097/mph.0000000000000792

Cited by 11 publications

(18 citation statements)

References 30 publications

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“…Antibiotic prophylaxis in children with newly diagnosed ALL was investigated in 10 of the final studies 11,41,43,48,49,51‐53,56,57 . Patients with AML or relapsed ALL were included in 11 of the final articles 10,12,40,42,45,46,48,50,52,54,55 . Of these, seven reported observational cohort studies, 12,42,45,46,48,52,54 two reported retrospective case studies, 40,55 and one was a cross‐sectional survey study 50 .…”

Section: Resultsmentioning

confidence: 99%

Levofloxacin prophylaxis in hospitalized children with leukemia: A cost‐utility analysis

Maser

Pelland‐Marcotte

Alexander

et al. 2020

Pediatric Blood & Cancer

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Background Infections are common and are a major cause of morbidity and mortality during treatment of childhood leukemia. We evaluated the cost effectiveness of levofloxacin antibiotic prophylaxis, compared to no prophylaxis, in children receiving chemotherapy for acute myeloid leukemia (AML) or relapsed acute lymphoblastic leukemia (ALL). Procedures A cost‐utility analysis was conducted from the perspective of the single‐payer health care system using a lifetime horizon. A comprehensive literature review identified available evidence for effectiveness, safety, costs of antibiotic prophylaxis in children with leukemia, and health utilities associated with the relevant health states. The effects of levofloxacin prophylaxis on health outcomes, quality‐adjusted life‐years (QALY), and direct health costs were derived from a combined decision tree and state‐transition model. One‐way deterministic and probabilistic sensitivity analyses were performed to test the sensitivity of results to parameter uncertainty. Results The literature review revealed one randomized controlled trial on levofloxacin prophylaxis in childhood AML and relapsed ALL, by Alexander et al, that showed a significant reduction in rates of fever and neutropenia (71.2% vs 82.1%) and bacteremia (21.9% vs 43.4%) with levofloxacin compared to no prophylaxis. In our cost‐utility analysis, levofloxacin prophylaxis was dominant over no prophylaxis, resulting in cost savings of $542.44 and increased survival of 0.13 QALY. In probabilistic sensitivity analysis, levofloxacin prophylaxis was dominant in 98.8% of iterations. Conclusions The present analysis suggests that levofloxacin prophylaxis, compared to no prophylaxis, is cost saving in children receiving intensive chemotherapy for AML or relapsed ALL.

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Section: Resultsmentioning

confidence: 99%

Levofloxacin prophylaxis in hospitalized children with leukemia: A cost‐utility analysis

Maser

Pelland‐Marcotte

Alexander

et al. 2020

Pediatric Blood & Cancer

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“…with AML during periods of neutropenia (1,2,(9)(10)(11)(12)(13)(14)(15)(16). Prophylactic regimens that have been explored include oral prophylaxis with cephalosporins (1,13) or fluoroquinolones (9,11,14,16); intravenous prophylaxis with cefepime (1,13,15), teicoplanin (10), or piperacillin-tazobactam (12); and (to address specifically the risk of Gram-positive infections) intravenous administration of vancomycin plus oral or intravenous administration of a cephalosporin or fluoroquinolone (1,12,13).…”

mentioning

confidence: 99%

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

Sun

Huskey

et al. 2018

Antimicrob Agents Chemother

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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 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%; = 0.007) or other prophylactic regimens (0.9% versus 3.0%; = 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.

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“…We used the results of observational studies and randomized controlled trials studying levofloxacin prophylaxis in adult and pediatric patients in this setting to establish the risks of febrile neutropenia and bacteremia with and without prophylaxis 1,2,4,7,11‐17 . Published literature was used to estimate the probability of ICU admission or death, with or without bacteremia 4,5,11,15,18‐32 . The probability of levofloxacin‐related adverse events was estimated using the FDA‐approved package insert 33 .…”

Section: Methodsmentioning

confidence: 99%

Cost‐effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia

McCormick

Friehling

Kalpatthi

et al. 2020

Pediatric Blood & Cancer

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Background Infections are the leading cause of therapy‐related mortality in pediatric patients with acute myeloid leukemia (AML). Although effectiveness of levofloxacin antibacterial prophylaxis in oncology patients is recognized, its cost‐effectiveness is unknown. This study evaluated epidemiologic data regarding levofloxacin use and the cost‐effectiveness of this strategy as the cost per bacteremia episode, intensive care unit (ICU) admission, and death avoided in children with AML. Procedure A retrospective cohort study using the Pediatric Health Information System (PHIS) database compared demographic and clinical characteristics and receipt of levofloxacin prophylaxis in children with AML admitted for chemotherapy from January 1, 2014, through December 31, 2018. We then developed a decision analysis model in this population that compared costs associated with bacteremia, ICU admission, or death secondary to bacteremia to levofloxacin prophylaxis cost from a healthcare perspective. Time horizon is one chemotherapy cycle. Probabilistic and one‐way sensitivity analyses evaluated model uncertainty. Results Prophylaxis cost $8491 per bacteremia episode prevented compared with an average added hospital cost of $119 478. Prophylaxis cost $81 609 per ICU admission avoided, compared with an average added hospital cost of $94 181. Prophylaxis cost $220 457 per death avoided. In sensitivity analysis, at a willingness‐to‐pay threshold of $100 000 per bacteremia episode avoided, prophylaxis remained cost‐effective in 94.6% of simulations. Prophylaxis use was more common in recent years in patients with relapsed disease and with chemotherapy regimens considered more intensive. Conclusion Prophylaxis is cost‐effective in preventing bacterial infections in patients with AML. Findings support increased use in patients considered at high risk of bacterial infection secondary to myelosuppression.

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Bacterial Infections in Children With Acute Myeloid Leukemia Receiving Ciprofloxacin Prophylaxis

Abstract: A high rate of bacterial infection was detected in patients who received the AML02 protocol, mainly gram-positive bacterial infections. The prophylactic regimen should be reconsidered for its efficacy, and other antibacterial prophylaxis may be used.

Cited by 11 publications

References 30 publications

Levofloxacin prophylaxis in hospitalized children with leukemia: A cost‐utility analysis

Levofloxacin prophylaxis in hospitalized children with leukemia: A cost‐utility analysis

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

Cost‐effectiveness of levofloxacin prophylaxis against bacterial infection in pediatric patients with acute myeloid leukemia

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