![]() ![]() ![]() Every effort needs to be made to carefully select antibiotics, balancing the need for a broad spectrum of empiric coverage of potential microorganisms with the need to preserve available antibiotics for when they are absolutely necessary. A reduction in inappropriate utilization of broad-spectrum antibiotics is clearly important to minimize the emergence of MDRGNs. The emergence and proliferation of these highly resistant Gram-negative organisms are particularly concerning given the limited number of antimicrobial agents that are currently available or in the drug development pipelines of the pharmaceutical industry to combat these organisms ( 35). A vicious cycle is created as MDRGN infections force us to rely on additional broad-spectrum antibiotics to treat these infections, leading to yet more resistance ( 208, 241). The abundant and often inappropriate use of broad-spectrum antibiotics contributes to the emergence of MDRGNs ( 208). Multidrug-resistant Gram-negative organisms (MDRGNs) have emerged as a major threat to hospitalized patients and have been associated with mortality rates ranging from 30 to 70% ( 30, 33, 89, 102, 153, 177, 203). ![]() In this review, we summarize the available data comparing monotherapy versus combination antimicrobial therapy for the treatment of infections with Gram-negative bacteria. The available evidence suggests that the greatest benefit of combination antibiotic therapy stems from the increased likelihood of choosing an effective agent during empiric therapy, rather than exploitation of in vitro synergy or the prevention of resistance during definitive treatment. ![]() The wisdom of continued combination therapy after an organism is isolated and antimicrobial susceptibility data are known, however, is more controversial. An argument can be made for empiric combination therapy, as we are witnessing a rise in infections caused by multidrug-resistant Gram-negative organisms. In summary, ceftriaxone has retained its potent activity against the most commonly encountered Gram-positive and Gram-negative human pathogens despite widespread and ongoing clinical use for more than 15 years.Summary: Combination antibiotic therapy for invasive infections with Gram-negative bacteria is employed in many health care facilities, especially for certain subgroups of patients, including those with neutropenia, those with infections caused by Pseudomonas aeruginosa, those with ventilator-associated pneumonia, and the severely ill. All Haemophilus influenzae (n=7911) and Neisseria gonorrhoeae (n=218) were susceptible to ceftriaxone, as were 99.7% of Moraxella catarrhalis (n=312) tested in 19. Rates of resistance to ceftriaxone among Acinetobacter spp. Resistance to ceftriaxone among Enterobacter cloacae (n=48114 range, 21.7-23.9%) was relatively high, compared with other Enterobacteriaceae, but unchanged from 1996 to 2000. Among methicillin-susceptible Staphylococcus aureus (n=39 284) ceftriaxone resistance was 0.1-0.3% per year from 1996 to 2000. Beta-lactam-resistant Streptococcus pyogenes (n=935) and group B beta-haemolytic streptococci (n=2267) were not identified in any year. Ceftriaxone resistance (range, 5.1-6.9%) among viridans group streptococci (n=6621) varied by <2% from 1997 to 2000. Ceftriaxone resistance among isolates of Streptococcus pneumoniae (n=17219) remained essentially unchanged over the 5 years studied and in fact was lower from 1998 to 2000 (5.0-5.1%) than in 1996 (6.3%) and 1997 (6.6%). All MIC results were interpreted using NCCLS breakpoint criteria. We reviewed the activity of ceftriaxone and relevant comparative agents against five Gram-positive and 11 Gram-negative species for a 5-year period, 1996-2000, using data from The Surveillance Network (TSN) Database-USA. Review of ceftriaxone activity is important given its continued use since the mid-1980s and reports of emerging resistance among all antimicrobial agent classes. Ceftriaxone was introduced into clinical practice in the USA in 1985 and was the first extended-spectrum (third-generation) cephalosporin approved for once-daily treatment of patients with Gram-positive or Gram-negative infections. ![]()
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