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Imipenem, doxycycline and amikacin in monotherapy and in combination in Acinetobacter baumannii experimental
M J Rodríguez-Hernández1, J Pachón, C Pichardo
1Service of Infectious Diseases and Service of Microbiology, Hospital Universitario Virgen del Rocio, Avenida Manuel Siurot s/n, 41013 Seville, Spain. rodher@cica.es
Abstract:
Acinetobacter baumannii is a common cause of nosocomial pneumonia and other nosocomial infections. Multiresistant A. baumannii has also a high prevalence, which can make effective treatment difficult. We designed a new model of A. baumannii experimental pneumonia using C57BL/6 immunocompetent mice. This model was used to compare the efficacy of imipenem, doxycycline and amikacin in monotherapy, and the combination of imipenem plus amikacin and doxycycline plus amikacin. Doxycycline plus amikacin were synergic in vitro after 24 h incubation, whereas imipenem plus amikacin showed no in vitro synergy. The number of sterile lungs and the lung clearance of A. baumannii were greater in the group treated with imipenem than in those treated with amikacin or doxycycline in monotherapy (P < 0.05). The combination of imipenem plus amikacin and doxycycline plus amikacin was no more effective than imipenem alone in the clearance of organisms from lungs (2.42 +/- 1.46 cfu/g versus 2.7 +/- 1.5 cfu/g versus 1.23 +/- 1.02 cfu/g). These results suggest that the addition of amikacin does not improve the results obtained by imipenem monotherapy. Doxycycline plus amikacin is an alternative to imipenem in the therapy of A. baumannii pneumonia.
Insights
Multiresistant Acinetobacter baumannii pneumonia is challenging to treat. Doxycycline plus amikacin showed promise as an alternative therapy, demonstrating efficacy comparable to imipenem monotherapy in a mouse model.
Area of Science:
- Infectious Diseases
- Microbiology
- Pharmacology
Background:
- Acinetobacter baumannii is a significant cause of hospital-acquired infections, including pneumonia.
- The rise of multidrug-resistant strains complicates treatment options.
- Effective therapeutic strategies for A. baumannii infections are urgently needed.
Purpose of the Study:
- To evaluate the efficacy of imipenem, doxycycline, and amikacin as monotherapies and in combination for experimental Acinetobacter baumannii pneumonia.
- To compare the effectiveness of different antibiotic regimens in clearing A. baumannii from the lungs in a murine model.
Main Methods:
- Development of a novel mouse model of Acinetobacter baumannii pneumonia using C57BL/6 mice.
- In vitro synergy testing of antibiotic combinations (imipenem plus amikacin, doxycycline plus amikacin).
- In vivo efficacy assessment through monotherapy and combination therapy, measuring lung bacterial burden and sterile lung counts.
Main Results:
- Doxycycline plus amikacin demonstrated in vitro synergy after 24 hours; imipenem plus amikacin did not.
- Imipenem monotherapy resulted in greater lung bacterial clearance and more sterile lungs compared to amikacin or doxycycline monotherapy (P < 0.05).
- Combination therapies (imipenem plus amikacin, doxycycline plus amikacin) were not superior to imipenem monotherapy in lung clearance.
Conclusions:
- Adding amikacin to imipenem does not enhance the efficacy of imipenem monotherapy for A. baumannii pneumonia.
- Doxycycline plus amikacin represents a viable alternative therapeutic option for treating Acinetobacter baumannii pneumonia.