Evaluation Of The In Vitro Activity Of Cefepime Compared To Other Broad- Spectrum Cephalosporins Against Clinical Isolates From Eighteen Brazilian Hospitals By Using The Etest

The in vitro activity of cefepime was compared to that of ceftazidime, ceftriaxone, and cefotaxime in a multicenter study involving 10 clinical microbiology laboratories and clinical isolates from 18 Brazilian hospitals from 7 cities (4 states). A total of 982 isolates consecutively collected between December 1995 and March 1996 were susceptibility tested by using Etest and following the NCCLS procedures for agar diffusion tests. The cefepime spectrum was broader than that of the other broad-spectrum cephalosporins against both Gram-negative rods and Gram-positive cocci. Cefepime was particularly more active against Enterobacter sp. (MIC90, 2 μg/ml), Serratia sp. (MIC90, 2 μg/ml) and oxacillin-susceptible Staphylococcus aureus (MIC90, 3 μg/ml). Against Pseudomonas aeruginosa, cefepime (MIC90, 16 μg/ml) was slightly more active than ceftazidime (MIC90, 32 μg/ml) and 8- to 16-fold more active than ceftriaxone or cefotaxime (MIC90, >256 μg/ml). Our results show that nosocomial bacteria, especially Gram-negative rods, have a high rate of cephalosporin resistance in Brazil. However, part of these resistant bacteria remains susceptible to cefepime. The Etest was shown to be an excellent method for multicenter studies of the in vitro evaluation of new antimicrobial agents.2828792Barradell, L.B., Bryson, H.M., Cefepime. A review of its antibacterial activity, pharmacokinetic properties, and therapeutic use (1994) Drugs, 47, pp. 471-505Frei, R., Jones, R.N., Pignatari, A.C., Yamane, N., Marco, F., Hoban, D.J., Antimicrobial activity of FK-037: A new broad-spectrum cephalosporin. International in vitro comparison with cefepime and ceftazidime (1994) Diagn Microbiol Infect Dis, 18, pp. 167-173Fuchs, P.C., Jones, R.N., Barry, A.L., Thornsberry, C., Evaluation of the in vitro activity of BMY-28142: A new broad-spectrum cephalosporin (1985) Antimicrob Agents Chemother, 27, pp. 679-682Gales, A.C., Sader, H.S., Machado, A.M.O., Jones, R.N., Pignatari, A.C., Comparação das atividades antimicrobianas da cefepime e da ceftazidima em 1015 amostras bacterianas isoladas em São Paulo (1995) J Bras Patol, 31, pp. 55-60Jacoby, G.A., Han, P., Detection of extended-spectrum β-lactamases in clinical isolates of Klebsiella pneumoniae-and Escherichia coli (1996) J Clin Microbiol, 34, pp. 908-911Jones, R.N., Kerhberg, E.N., Erwin, M.E., Anderson, S.C., The prevalence of important pathogens and the antimicrobial activity of parenteral drugs at numerous medical centers in the United States: Study on the threat of emerging resistance, real or perceived? (1994) Diag Microbiol Infect Dis, 19, pp. 203-215Martínez-Martínez, L., Hernández-Alléz, S., Albertí, S., Tomás, J.M., Benedi, V.J., Jacoby, G.A., In vivo selection of porin-deficient mutants of Klebsiella pneumoniae with increased resistance to cefoxitin and extended-spectrum cephalosporins (1996) Antimicrob Agents Chemother, 40, pp. 342-348(1993) Performance Standards for Antimicrobial Disk Susceptibility Tests: Approved Standard M2-A5. 5th Edition, , Villanova, PA: NCCLSNovak, S.M., Etest susceptibility testing (1994) Clinical Microbiology Procedures Handbook, (SUPPL. 1), pp. 5a1-17. , Ed D Isenberg. Washington, DC: American Society for MicrobiologyPhelps, D.J., Carlton, D.D., Farrel, C.A., Kessler, R.E., Affinity of cephalosporins for β-lactamases as a factor in antibacterial efficacy (1986) Antimicrob Agents Chemother, 29, pp. 845-848Sader, H.S., Jones, R.N., Historical overview of the cephalosporin spectrum: Four generations of structural evolution (1992) Antimicrob Newslett, 8, pp. 75-82Sanchez, M.L., Jones, R.N., Etest, an antimicrobial susceptibility testing method with broad clinical and epidemiology application (1993) Antimicrob Newslett, 8, pp. 1-5Sanders, C.C., Cefepime: The next generation? (1993) Clin Infect Dis, 17, pp. 369-379Sanders W.E., Jr., Tenney, J.H., Kessler, R.E., Efficacy of cefepime in the treatment of infections due to multiply resistant Enterobacter species (1996) Clin Infect Dis, 23, pp. 454-461Washington, J.A., Jones, R.N., Gerlach, E.H., Murray, P.R., Allen, S.D., Knapp, C.C., Multicenter comparison of in vitro activities of FK-037, cefepime, ceftriaxone, ceftazidime, and cefuroxime (1993) Antimicrob Agents Chemother, 37, pp. 1696-170

Antibacterial resistance of community-acquired respiratory tract pathogens recovered from patients in Latin America: results from the PROTEKT surveillance study (1999-2000)

PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) is a global surveillance study established in 1999 to monitor antibacterial resistance of respiratory tract organisms. Thirteen centers from Argentina, Brazil and Mexico participat ed during 1999-2000; they collected 1,806 isolates (Streptococcus pneumoniae 518, Haemophilus influenzae 520, Moraxella catarrhalis 140, Staphylococcus aureus 351, S. pyogenes 277). Overall, 218 (42.1%) of the S. pneumoniae isolates had reduced susceptibility to penicillin, 79 (15.3%) were penicillin-resistant and 79 (15.3%) were erythromycin-resistant. Mexico had the highest prevalence of penicillin (76.5%) and erythromycin (31.2%) resistance. Of 77 erythromycin-resistant S. pneumoniae tested for resistance genotype, 43 possessed mef(A), 33 possessed erm(B) and 1 possessed both erm(B) and mef(A) mechanism. All S. pneumoniae isolates were fully susceptible to telithromycin, linezolid, teicoplanin and vancomycin. Among H. influenzae isolates, 88 (16.9%) produced b-lactamase, ranging from 11% (Brazil) to 24.5% (Mexico). Among M. catarrhalis isolates, 138 (98.6%) produced b-lactamase. Twenty-four (8.7%) of the S. pyogenes isolates were erythromycin-resistant; resistance being attributable to mefA (n=18), ermTR (n=5) and ermB (n=1). All H. influenzae, M. catarrhalis and S. pyogenes were fully susceptible to telithromycin. Methicillin resistance was found in 26.5% of the S. aureus isolates (Argentina 15%; Mexico 20%; Brazil 31.3%). Telithromycin was effective against 97.7% of methicillin-susceptible isolates. PROTEKT confirms that antibacterial resistance is an emerging problem in Latin America. The previously reported high levels of pneumococcal resistance to the b-lactam and macrolides were exceeded. New agents that do not induce resistance or that exert low selective pressure, e.g. telithromycin, are essential to safeguard future antibacterial efficacy