In Vitro and In Vivo Evaluation of Antibiotic Combinations against Multidrug Resistant Proteus Mirabilis Isolated from Admitted Patients of Dhaka Medical College Hospital, Dhaka

Author(s): Rizwana Zaman, S.M. Shamsuzzaman

Emergence of MDR P. mirabilis is a threat for high morbidity and mortality with catheter-associated urinary tract infections leading to urolithiasis and permanent renal damage, bacteremia and sepsis. Global shortage of new effective antibiotic with reduced susceptibility of P. mirabilis to imipenem, tigecycline and resistance to colistin needs antimicrobial combinations. So, different antimicrobial combinations were used to see their efficacy both in vitro and in vivo with their resistance in Bangladesh.

MIC of antibiotics alone and in combination and efficacies of different antibiotic combinations in vivo (mice model) were evaluated. PCR and sequencing of resistance genes were done.

Among the 500 samples, 70% were culture positive and out of these, 10.57% were P. mirabilis. Among isolated P. mirabilis, 24.32%, 21.62%, 27.03% and 78.38% were resistant to fosfomycin, imipenem, tigecycline and amikacin respectively and 75.68%, 13.51% and 10.81% were MDR, XDR and PDR respectively. Among fosfomycin resistant P. mirabilis, 77.78%, 44.44% and 22.22% were positive for fosA, fosA3 and fosA4 respectively. Among imipenem resistant P. mirabilis, 62.50% were positive for NDM-1 and OXA-10, 50% for NDM-2, OXA-23 and OXA-48, 25% for OXA-58.

In vitro combination of imipenem-amikacin and imipenem-fosfomycin showed 100%, and 75% synergism respectively. The best in vivo results appeared in the group treated with imipenem-amikacin and imipenem-fosfomycin combinations where 100% bacterial clearance was observed.

As P. mirabilis showed high level resistance towards commonly used antimicrobial agents, it is very difficult to treat by a single agent. So, emphasis should be given on using antibiotic combinations.

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