Efficacy of Combinations of Piperacilline/Tazobactam, Ceftazidime, Amikacin and Bacteriophage against Enterobacteriaceae Sepsis in Neonates: In Vitro Study

Abstract

Huda Husham Abdul-Jabar, AbdulKareem Hameed Abd, Ahmed Sahib Abdulamir

Background neonatal sepsis is considered as one of the main causes of morbidity and mortality in preterm and full-term neonates. It is a clinical disorder caused by bacterial infections of blood stream. Enterobacteriaceae group (including Klebsiella Pneumonia and Escherichia coli) is a gram-negative (G-ve) bacteria which is one of the most serious causative organisms of neonatal sepsis. Klebsiella Pneumonia and Escherichia coli phages are bacterial viruses that infect bacteria and pursue in two possible ways: lytic and lysogenic life cycle. The risk of neonatal sepsis increase with multi drug resistant organisms which make the treatment of their infections difficult. Therefore, antibiotics and phage combinations are possible choices to solve this problem.
Aims of the study: this study aims to evaluate the antibacterial activity of bacteriophages alone and in combination with certain antibiotics against most common Enterobacteriaceae that cause neonatal sepsis and to obtain desired antibacterial combinations for the treatment of most common Enterobacteriaceae in neonatal sepsis with synergistic effects.
Materials and methods: thirty isolated bacterial cultures from blood samples of neonates with sepsis were collected from the laboratories of Al-Kadimia pediatric hospital and Central teaching hospital of pediatric from December 2019 to March 2020. They were identified using morphological characteristics, Api20E test and by Vitek2 compact system. Fourteen isolates among them (46.67%) were Klebsiella Pneumonia and eleven isolates (36.67%) were Escherichia Coli. Results: The bacterial profile of the collected isolates was found as follows: Klebsiella Pneumonia (46.67%), E. Coli(36.67%), Enterobacter(13.33%) and Serratia (3.33%). The percentages of resistance to the tested antibiotics were as follows: of Klebsiella Pneumonia isolates amikacin14.28%, aztreonam ,cefepime and ceftazidime 71.43% for each, ciprofloxacin 7.14%, piperacillin/tazobactam, gentamicin, tobramycin, imipenem and meropenem 21.43% for each, minocycline 0%, piperacillin 78.57%, ticarcillin 100%, ticarcillin/clavulanic acid 50%, and trimethoprim-sulfamethoxazole 28.57%. For Escherichia Coli isolates amikacin 0%, aztreonam , ticarcillin, piperacillin, cefepime and ceftazidime 72.73% for each, piperacillin/tazobactam, ticarcillin/clavulanic acid, ciprofloxacin and trimethoprim-sulfamethoxazole 27.27% for each, gentamicin, tobramycin and minocycline 9.09% for each, imipenem and meropenem 18.18%. (64.29%) of Klebsiella Pneumonia isolates and (45.45%) of E. coli were MDR. Antibiotic-antibiotic combinations of piperacillin/tazobactam or ceftazidime with amikacin for isolate 11, piperacillin/tazobactam or amikacin with ceftazidime for isolate 12 were resulted in synergistic effects. Also, antibiotic-antibiotic combinations of piperacillin/tazobactam or ceftazidime with amikacin for isolates 4 and 6 resulted in synergistic effects. Combinations of phage with each of 1/4and 1/2 MIC piperacillin/tazobactam or ceftazidime for tested isolates (4and6 which were E. coli and Klebsiella Pneumoia respectively) and phage with 1/4 and 1/2 MIC amikacin for E. coli isolate 4 showed synergistic effects to the antibiotics.
Conclusions: all combinations of piperacillin/tazobactam, ceftazidime with amikacin and phage- antibiotic combinations with piperacillin/tazobactam, ceftazidime or amikacin showed highly synergistic effects against resistant and MDR Klebsiella Pneumonia and E. coli strains that cause neonatal sepsis.