Time-kill studies of linezolid, piperacillin-tazobactam, imipenem, amikacin, trimethoprim-sulfametoxazole and moxifloxacin alone or in combination against Nocardia spp.
Abstract number: 1134_03_206
Tripodi M.F., Fortunato R., Ruggiero G., Cuccurullo S., Utili R.
Nocardia may cause severe infections in immunocompromised hosts. Treatment has been largely based on sulfonamide agents. The aim of the study was to evaluate the in-vitro bactericidal activity of several antibiotic combinations against Nocardia spp.
Seven Nocardia strains (N. asteroides, 3; N. brasiliensis, 2; N. farcinica 1, N. spp. 1) were isolated from pulmonary lesions in heart-transplant patients. In vitro activity of antibiotic combinations was evaluated by time-kill method on Mueller Hinton broth II (MHBII) using the following antibiotics alone or in combination with each other at the following peak-serum concentrations (mg/l): LZD, 20; piperacillin-tazobactam (TZP), 200; imipenem (IMP), 43; trimethoprim-sulphametoxazole (SXT), 3.4/17; amikacin (AN), 38; moxifloxacin (MFX), 4.3. Time-kill studies were performed in MHBII using an inoculum of 1 × 106 cfu/ml, incubated at 37°C for 72 h. Viability counts were performed at 0,24, and 72 h, by plating 10 fold dilutions onto blood agar plates (BioMèrieux, France). The bactericidal activity was defined as a decrease major or equal to 3 log10cfu/ml in the viable count at 24, 72 h compared with the initial inoculum. Synergism or antagonism were defined as a decrease or increase major or equal to 2 log10 cfu/ml in the viable count with the combination at 24, 72 h compared with the most active agent alone.
Only AN, IMP, MFX, as single drug, showed a bactericidal activity in 7, 4 and 2 strains respectively, all other agents were bacteriostatic. For antibiotic combinations, high rate of bactericidal activity was observed with: IMP + AN and IMP + MFX in all seven strains; TZP + MFX, TZP + AN and MFX + AN in 6 strains; AN + SXT in 5. Among the bactericidal combinations, synergism was observed for TZP with MFX or SXT in 2 and 1 strain respectively. For the other combinations, synergism was not evaluable due to high bactericidal activity of AN, IMP and MFX. Linezolid behaved always as bacteriostatic agent and was bactericidal only in one case with AN and MFX, respectively, but was antagonistic with AN and IMP in 7 and 2 strains, respectively. All the other antibiotic combinations were bacteriostatic.
To date there is no standardized treatment for nocardosis. Based on these data the combinations of IMP and AN or MFX appears suitable as initial treatment of invasive nocardiosis. LZD, MFX and SXT may represent a choice for sequential oral therapy as single drugs.
|Session name:||XXIst ISTH Congress|
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