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      Antibacterial prophylaxis in pediatric patients with leukemia

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          Abstract

          Background

          Bacterial infections in pediatric patients with leukemia are associated with increased risks for morbidity and mortality. Few Recommendations have been made on the use of antibacterial prophylaxis in pediatrics with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML).

          Objectives

          To determine the role of antibacterial prophylaxis in pediatric patients with leukemia and the most appropriate regimen that can be safely and effectively used.

          Methods

          Literature search was conducted independently by 3 reviewers to find studies on the safety and effectiveness of antibacterial prophylactic regimens.

          Results

          The search strategy resulted in 13 studies; most of them were observational studies. The available evidence recommends use of antibiotics with Gram-positive bacterial coverage in AML patients. In ALL patients, prophylaxis was used during the intensive phases of chemotherapy with ciprofloxacin being recommended most commonly.

          Conclusion

          Antibacterial prophylaxis mainly with coverage against Gram-positive bacteria is recommended in pediatric patients with AML. For ALL patients, prophylaxis may be considered for patients who are undergoing intensive chemotherapy phases and are at high risk for infections with ciprofloxacin being the most commonly used agent. In general more studies are needed to determine the role of antibacterial prophylaxis in pediatric patients with leukemia.

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          Most cited references29

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          Pediatric AML: From Biology to Clinical Management

          Pediatric acute myeloid leukemia (AML) represents 15%–20% of all pediatric acute leukemias. Survival rates have increased over the past few decades to ~70%, due to improved supportive care, optimized risk stratification and intensified chemotherapy. In most children, AML presents as a de novo entity, but in a minority, it is a secondary malignancy. The diagnostic classification of pediatric AML includes a combination of morphology, cytochemistry, immunophenotyping and molecular genetics. Outcome is mainly dependent on the initial response to treatment and molecular and cytogenetic aberrations. Treatment consists of a combination of intensive anthracycline- and cytarabine-containing chemotherapy and stem cell transplantation in selected genetic high-risk cases or slow responders. In general, ~30% of all pediatric AML patients will suffer from relapse, whereas 5%–10% of the patients will die due to disease complications or the side-effects of the treatment. Targeted therapy may enhance anti-leukemic efficacy and minimize treatment-related morbidity and mortality, but requires detailed knowledge of the genetic abnormalities and aberrant pathways involved in leukemogenesis. These efforts towards future personalized therapy in a rare disease, such as pediatric AML, require intensive international collaboration in order to enhance the survival rates of pediatric AML, while aiming to reduce long-term toxicity.
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            Comparative efficacy and safety of vancomycin versus teicoplanin: systematic review and meta-analysis.

            Vancomycin and teicoplanin are the glycopeptides currently in use for the treatment of infections caused by invasive beta-lactam-resistant gram-positive organisms. We conducted a systematic review and meta-analysis of randomized controlled trials that have compared vancomycin and teicoplanin administered systemically for the treatment of suspected or proven infections. A comprehensive search of trials without year, language, or publication status restrictions was performed. The primary outcome was all-cause mortality. Two reviewers independently extracted the data. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled by using the fixed-effect model (RRs of >1 favor vancomycin). Twenty-four trials were included. All-cause mortality was similar overall (RR, 0.95; 95% CI, 0.74 to 1.21), and there was no significant heterogeneity. In trials that used adequate allocation concealment, the results favored teicoplanin (RR, 0.82; 95% CI, 0.63 to 1.06), while in trials with unknown methods or inadequate concealment, the results favored vancomycin (RR, 3.61; 95% CI, 1.27 to 10.30). The latter trials might have recruited more severely ill patients. No other variable affected the RRs for mortality, including the assessment of glycopeptides administered empirically or for proven infections, neutropenia, the participant's age, and drug dosing. There were no significant differences between teicoplanin and vancomycin with regard to clinical failure (RR, 0.92; 95% CI, 0.81 to 1.05), microbiological failure (RR, 1.24; 95% CI, 0.93 to 1.65), and other efficacy outcomes. Lower RRs (in favor of teicoplanin) for clinical failure were observed with a lower risk of bias and when treatment was initiated for infections caused by gram-positive organisms rather than empirically. Total adverse events (RR, 0.61; 95% CI, 0.50 to 0.74), nephrotoxicity (RR, 0.44; 95% CI, 0.32 to 0.61), and red man syndrome were significantly less frequent with teicoplanin. Teicoplanin is not inferior to vancomycin with regard to efficacy and is associated with a lower adverse event rate than vancomycin.
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              Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials.

              Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow transplant (allo-BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the relapse risk (RR), this did not translate into a significant improvement in overall survival (OS). A risk group stratification based on cytogenetics and response to the first course of chemotherapy derived from MRC AML 10 was used to deliver risk-directed therapy in MRC AML 12. Allo-BMT was limited to standard and poor risk patients and A-BMT was not employed. Instead, the benefit of an additional block of treatment was tested by randomising children to receive either four or five blocks of treatment in total. While the results of MRC AML 12 remain immature, there appears to be no survival advantage for a fifth course of treatment. The 5 year OS, disease-free survival (DFS), event-free survival (EFS) and RR in MRC AML 12 are 66, 61, 56 and 35%, respectively; at present superior to MRC AML 10, which had a 5-year OS, DFS, EFS and RR of 58, 53, 49 and 42%, respectively. MRC AML trials employ a short course of triple intrathecal chemotherapy alone for CNS-directed treatment and CNS relapse is uncommon. Improvements in supportive care have contributed to improved outcomes and the number of deaths in remission fell between trials. Anthracycline-related cardiotoxicity remains a concern and the current MRC AML 15 trial tests the feasibility of reducing anthracycline dosage without compromising outcome by comparing standard MRC anthracycline-based consolidation with high-dose ara-C. MRC studies suggest that the role of allo-BMT is limited in 1st CR and that there may be a ceiling of benefit from current or conventional chemotherapy.
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                Author and article information

                Contributors
                Journal
                Saudi Pharm J
                Saudi Pharm J
                Saudi Pharmaceutical Journal : SPJ
                Elsevier
                1319-0164
                2213-7475
                03 April 2018
                September 2018
                03 April 2018
                : 26
                : 6
                : 810-816
                Affiliations
                [a ]Department of Clinical Pharmacy, King Hussain Cancer Center, Amman, Jordan
                [b ]Department of Pediatric Oncology, Pediatric Bone Marrow and Stem Cell Transplantation, King Hussain Cancer Center, Amman, Jordan
                Author notes
                [* ]Corresponding author. suha_mao@ 123456hotmail.com
                Article
                S1319-0164(18)30082-3
                10.1016/j.jsps.2018.04.002
                6128709
                30202221
                e346dc74-2b4f-474c-890f-95483251a350
                © 2018 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 18 November 2017
                : 1 April 2018
                Categories
                Article

                antibiotics,prophylaxis,leukemia,pediatrics,infection
                antibiotics, prophylaxis, leukemia, pediatrics, infection

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