Efficacy of imipenem, sulbactam and rifampin in an experimental meningitis model caused by multiresistant Acinetobacter baumannii

Abstract number: 1134_04_19

Docobo-Pérez F., Pachón-Ibáñez M.E., Fatela-Cantillo D., Jiménez-Mejías M.E., Pichardo C., García-Curiel A., Pachón J.

Objectives:  

Postsurgical meningitis due to multiresistant (resistant to all clinically used antibiotics except colistin) Acinetobacter baumannii (MrAb) is an important therapeutical problem. It is necessary to know the antimicrobials or synergistic active-combinations against MrAb in this clinical process. The aim of this study was to evaluate the efficacy of rifampin (RF), sulbactam (SB), and imipenem (IMP) in monotherapy and in combinations in an experimental meningitis model due to MrAb.

Methods:  

A multiresistant bacteremic strain was used. In vitro studies: MIC and MBC; bactericidal activity and synergy of the combinations (time-killing curves). PK parameters (Cmax, AUC, t_1/2) were measured after administration of a single dose of each antimicrobial. In vivo studies: 1st phase, characterization of a meningitis experimental model due to MrAb in New Zealand rabbits (2–3 Kg), with an intracisternal inoculum of 6–7 log cfu/ml. 2nd phase: Rabbits were grouped as CON (controls, without treatment), IMP (120 mg/Kg/d), SB (240 mg/Kg/d), RF (100 mg/Kg/d), IMP + SB, IMP + RF and SB + RF; animals received a single dose of treatment. Measures: bacterial clearance in CSF; WBC, brain edema, and lactate concentration in CSF. Statistical tests: Friedman and Kruskal-Wallis.

Results:  

MIC/MBC (mg/l): SB 32/32, IMP 32/32, RF 4/8. IMP (MIC) showed bactericidal in vitro activity; no synergies were found. The PK parameters were: Cmax (mg/l), 16.62, 75.33, 25.35; AUC (mg·h/l), 40.28, 57.07, 50.45; t_1/2(h), 3.38, 0.54, 1.74; for RF, SB and IMP respectively. All of the rabbits presented high levels of lactate, WBC and an increased brain weight due to the infection and brain edema. The treatments that showed a reduction of the bacterial concentration in CSF were: RF (p < 0.001), RF + IMP (p < 0.01), RF + SB (p < 0.05) and IMP + SB (p < 0.05).

Conclusions:  

In the experimental meningitis caused by multiresistant A. baumannii, rifampin in monotherapy and the combinations of rifampin plus sulbactam or imipenem, and imipenem plus sulbactam were effective in the clearance of bacteria from CSF.