Antimicrobial Activity of Doripenem Tested Against Leading Bacterial Pathogens: Results from a Latin American Surveillance Study (2003-2006)
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2008-10-01
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Gales, Ana Cristina [UNIFESP]
Jones, Ronald N.
Sader, Helio Silva [UNIFESP]
Fritsche, Thomas R.
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Carbapenems have been the therapeutic choice for empirical treatment of serious infections when multidrug-resistant Gram-negative organisms are suspected. Doripenem is a parenteral 1-beta-methyl-carbapenem that was recently approved in the USA for complicated urinary tract and intra-abdominal infections. We performed a longitudinal surveillance study on the in vitro activity of doripenem and comparator agents against patient isolates from Latin America. Consecutive, non-duplicate bacterial isolates (13,809) were collected from patients in 10 medical centers in Brazil (45.2%), Chile (21.1%), Argentina (17.9%), Mexico (12.9%) and Venezuela (2.9%). Isolate identifications were confirmed and susceptibility testing was performed using reference methods at a central laboratory (JMI Laboratories, North Liberty, IA). Doripenem and meropenem were the most active compounds tested against E. coli and Klebsiella spp. (MIC(90) values, <= 0.12 mu g/mL), including against those strains with ESBL phenotypes (15.2% of E. coli and 44.9% of Klebsiella spp.). All Enterobacter spp. strains were inhibited at <= 4 mu g/mL of doripenem, meropenem or imipenem; only ertapenem was less active (94.8% susceptible). Furthermore, only 86.6 and 77.0% of Enterobacter spp. strains were susceptible to amikacin and polymyxin B, respectively. Doripenem and meropenem were equally potent against R aeruginosa (MIC(50) 1 mu g/mL) and Acinetobacter spp. (MIC(50) 2 mu g/mL); however, doripenem inhibited a greater number of R aeruginosa (78.1%) at MIC values of <= 4 mu g/mL compared to meropenem (70.9%) or imipenem (67.9%). Moreover, doripenem inhibited 34.0% of imipenem-non-susceptible P aertiginosa isolates at MIC values <= 4 mu g/mL. Doripenem inhibited all oxacillin-susceptible staphylococci and S. pneumoniae, including penicillin-resistant strains, at <= 2 mu g/mL. In summary, doripenem showed potent activity against Enterobacteriaceae (including ESBL- and/or AmpC-producing strains), oxacillin-susceptible staphylococci and streptococci isolated in Latin American hospitals participating in the international doripenem surveillance program. Doripenem activity was also comparable to that of other carbapenems against P aeruginosa and Acinetobacter spp. Given limited therapeutic choices available, doripenem shows a promising broad-spectrum that should prove useful in geographic regions with problematic emerging resistances.
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Brazilian Journal Of Infectious Diseases. Salvador: Contexto, v. 12, p. 59-66, 2008.