Effectiveness and antimicrobial susceptibility profiles during primary antimicrobial prophylaxis for pediatric acute myeloid leukemia

Abstract

Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0–18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.

Effect of Antibacterial Prophylaxis on Febrile Neutropenic Episodes and Bacterial Bloodstream Infections in Dutch Pediatric Patients with Acute Myeloid Leukemia: A Two-Center Retrospective Study

“…In our study, musculoskeletal toxicities were not reported in any patient receiving ciprofloxacin prophylaxis, which was in agreement with two other studies on the efficacy of ciprofloxacin prophylaxis in childhood AML [16,18]. A few other retrospective studies among pediatric AML patients have shown that cefepime monotherapy [14] or vancomycin combined with an agent with Gram-negative coverage are highly effective in reducing bacterial BSIs [14,15,17,20,23]. However, vancomycin is associated with dosing difficulties and infusion-related side effects and requires administration (at least) every 12 h with therapeutic drug monitoring.…”

“…Compared to daily dosing, such an alternate dosing schedule not only improves the quality of life but also minimizes the antibiotic exposure and handling of central venous lines. These advantages are of major interest as a decreased susceptibility to vancomycin and teicoplanin of Enterococcus species [23] and an increase in VRE strains in rectal cultures [15] have been observed with the use of vancomycin prophylaxis. One study also observed VRE BSIs with the use of vancomycin prophylaxis [15], whereas others did not [14,23].…”

“…These advantages are of major interest as a decreased susceptibility to vancomycin and teicoplanin of Enterococcus species [23] and an increase in VRE strains in rectal cultures [15] have been observed with the use of vancomycin prophylaxis. One study also observed VRE BSIs with the use of vancomycin prophylaxis [15], whereas others did not [14,23]. Some patients in the study of Boztug, et al [13] received prophylactic vancomycin monotherapy, but no VRE BSIs occurred and there was no increase in VRE in surveillance stool cultures.…”

“…The few available studies evaluating the efficacy of antibacterial prophylaxis regimens in pediatric AML are mainly single-centered with small sample sizes and are often limited by their retrospective design and the comparison of only two regimens [13][14][15][16][17][18][19][20][21][22]. The most effective prophylactic antibacterial agents seem those with Gram-positive coverage, such as vancomycin or teicoplanin [13,22], or a combination of an agent with Gram-positive coverage and an agent with Gram-negative coverage [15,17,23]. In a randomized clinical trial, the effect of the fluoroquinolone levofloxacin, which has activity against both Gram-positive and Gram-negative bacteria, has been compared with no prophylaxis [24].…”

Effectiveness of Quinolone Prophylaxis in Pediatric Acute Leukemia and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-analysis

“…Among the 9 studies selected for the meta-analysis, 6 were retrospective single-center studies [ 33–38 ] and 3 were prospective studies [ 39–41 ], 2 of which were randomized [ 40 , 41 ]; 1 was also multicentric [ 41 ]. Two studies included only patients with acute lymphoblastic leukemia (ALL) [ 39 , 40 ], 1 only patients with acute myeloid leukemia (AML) [ 37 ], 2 both ALL and AML patients [ 33 , 42 ], 1 only patients undergoing autologous HSCT (auto-HSCT) [ 35 ], 2 both auto- and allogenic HSCT (allo-HSCT) [ 34 , 36 ], and 1 all groups of patients [ 41 ]. Two of the 6 studies on ALL patients studied relapsed ALL (rALL) [ 33 , 41 ].…”