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Beta-lactams and aminoglycosides in combination for pneumonia by carbapenem-resistant Acinetobacter baumannii in a mice model

Abstract number: 902_p908

Montero A.

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Infections by Acinetobacter baumannii (Ab) with high-degree resistance (HDR) to carbapenems have recently increased. Only colistin seems to keep its in vitro efficacy, but clinical practice is scarce. To our knowledge, no clinical data are currently available to evaluate the systematic use of the beta-lactam (BL)–aminoglycoside (AG) combination to treat serious Ab infections in a way similar to that in other infections by Gram-negative bacteria.

Objective:

To analyse the efficacy of the combination of two BL (imipenem [I] or sulbactam [S]) and one AG (tobramycin [T]) in an experimental model of pneumonia by Ab in mice.

Methods:

We used immunocompetent C57BL/6 mice and three strains of Ab with susceptibility, moderate-degree resistance and HDR to carbapenems (A, D and E respectively). MICs (mg/L) were (strains A, D, E): I: 1, 8, 512; S: 2, 4, 128; and T: 128, 8, 8. The in vivo activity was examined by quantitative evaluation of the lung homogenate cultures after 48 h of induction of pneumonia.

Results:

In control (CON) animals (n = 45), the bacterial counts in lungs at 48 h were (mean ± SD): 10.66 ± 0.37, 10.83 ± 0.32 and 10.77 ± 0.35 log 10 CFU/g of tissue for strains A, D and E, respectively (P = NS between strains). Results of antibiotic activity were expressed as differences between treated (n = 4 in each therapy) and CON groups (delta log 10 CFU/g) (see Table).

Conclusions:

In this mice pneumonia model, I or S kept his efficacy for Ab with moderate resistance to carbapenems. In infections caused by this strain D, T in combination conferred a possible greater efficacy on these BLs. In infections by Ab with HDR to carbapenems, T alone was also effective. Interestingly the combination BL + AG also showed a higher effect on the infection by this HDR strain E, against which monotherapy with I or S were totally ineffective. Although the pharmacodynamics of T in this model may have been overestimated, because of the peak levels achieved are not usually found in humans at the recommended doses (Cmax 32.87 ± 5.45 mg/L), these results are promising to treat multiresistant Ab infections.

Table.  

Therapy (dose)Strain AStrain DStrain E
I (200 mg/kg/day)-5.38a-4.48a0.24a
S (120 mg/kg/day)-4.64a-3.67a-0.04a
T (60mg/kg/day)0.02-3.45a-4.16a
I+T-4.54a-5.37a,b-5.59a,b
S+T-3.83a-4.62a,b-4.95a,b
aP < 0.05 vs. CON (t-student).
bP < 0.05 vs. monotherapies (ANOVA).
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Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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