Sickle cell disease children’s gut colonization by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales: an antibiotic prophylaxis effect?

Abstract

Introduction: Sickle cell disease (SCD) children have a high susceptibility to pneumococcal infection. For this reason, they are routinely immunized with pneumococcal vaccines and use antibiotic prophylaxis (AP). Hypothesis/Gap Statement: Yet, little is known about SCD children’s gut microbiota. If antibiotic-resistant Enterobacterales may colonize people on AP, we hypothesized that SCD children on AP are colonized by resistant enterobacteria species. Objective: To evaluate the effect of continuous AP on Enterobacterales gut colonization from children with SCD. Methodology: We analysed 30 faecal swabs from SCD children on AP and 21 swabs from children without the same condition. Enterobacterales was isolated on MacConkey agar plates and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (bioMérieux, Marcy l'Etoile, France). We performed the antibiogram by Vitek 2 system (bioMérieux, Marcy l'Etoile, France), and the resistance genes were identified by multiplex PCR. Results: We found four different species with resistance to one or more different antibiotic types in the AP-SCD children’s group: Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, and Citrobacter farmeri. Colonization by resistant E. coli was associated with AP (prevalence ratio 2.69, 95% confidence interval [CI], 1.98–3.67, P<0.001). Strains producing extended-spectrum β-lactamases (ESBL) were identified only in SCD children, E. coli, 4/30 (13%), and K. pneumoniae, 2/30 (7%). The ESBL-producing Enterobacterales were associated with penicillin G benzathine use (95 % CI, 22.91–86.71, P<0.001). CTX-M-1 was the most prevalent among ESBL-producers (3/6, 50%), followed by CTX-M-9 (2/6, 33%), and CTX-M-2 (1/6, 17%). Conclusion: Resistant enterobacteria colonize SCD children on AP, and this therapy raises the chance of ESBL-producing Enterobacterales colonization. Future studies should focus on prophylactic vaccines as exclusive therapy against pneumococcal infections.