New Antibiotics in Pulmonary and Critical Care Medicine

†, * University of the Pacific, School of Pharmacy Stockton, California, and Kendle International, Inc.;   †Maine Medical Center, Portland, Maine, and University of Vermont, College of Medicine, Burlington, Vermont

Semin Respir Crit Care Med. 2000;21(1) 

In This Article

Clinical Importance Of Bacterial Resistance

Recent epidemiological data from an extensive global effort documenting geographic bacterial susceptibilities have been useful in identifying emerging resistance trends.[57,58,59,60] Among the problematic organisms identified that are capable of causing nosocomial respiratory tract infections are Enterobacter spp., Citrobacter spp., indole-positive Proteeae, Klebsiella spp, E. coli, and S. aureus. Nearly one quarter and one third of K. pneumoniae and Enter-obacter cloacae isolates, respectively, demonstrated resistance to ceftazidime. Now that clinicians are faced with this type of data, specific antimicrobial management and infection control countermeasures must be employed to steer away from the current predicament.

Clinical failures to third-generation cephalosporins have been reported, further substantiating the in vitro descriptive data being generated.[61,62,63,64,65,66,67,68] Clinical failures are important for several reasons. The most compelling, perhaps, is that organisms such as E. cloacae have been associated with a high mortality rate specifically attributable to infection. [63,69] A prospective study evaluated Enterobacter bacteremias and demonstrated a strong association between third-generation cephalosporin use and the emergence of resistant Enterobacter spp. during therapy.[68] In this study, multidrug resistant Enter-obacter strains were associated with significantly higher mortality rates than were their susceptible counterparts, an association that was confirmed via multivariate regression analysis. In addition, combination therapy failed to prevent the emergence of resistance. Johnson and Ramphal[61] also reported substantial mortality associated with ceftazidime-resistant Enterobacter infections compared with infection due to susceptible strains in neutropenic patients.

In addition to the assessment of the clinical impact of such failures, the costs associated with these treatment failures due to resistant bacteria have been evaluated.[67,70] Although difficult to quantify, costs associated with bacterial resistance are significant. In fact, it has been shown that, for community-and hospital-acquired infections caused by drug-resistant organisms, mortality, likelihood for hospital admission, and length of hospital stay were commonly twice as great compared with infection caused by the same, but drug-susceptible, bacteria.[70] Ambrose and colleagues[67] evaluated the efficacy of cefepime compared with ceftazidime for the treatment of nosocomial pneumonia. A cost-effectiveness analysis demonstrated a reduction in total costs (e.g., drug acquisition, supplies, additional antibiotics required for treatment failures, and hospitalization costs) when cefepime was utilized (cefepime cost/cure = $235.89 and cost/failure = $375.44 versus ceftazidime cost/cure = $319.81 and cost/failure = $520.11). Significantly more treatment failures occurred in patients receiving ceftazidime (40%) compared with those patients that received cefepime (20%) (p = 0.04).

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