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

Formulary Optimization

Restricting antibiotic use and using rotational antimicrobial strategies are among the methods employed to control the development of antibiotic resistance. In light of the Armageddon that we are now facing, the solution to resistance prevention has not been clearly established. In large part, the solution will employ vigilant infection control measures in concert with effective antimicrobial management strategies to relieve selective pressure. What has been demonstrated is that by removing known offending agents from use within the institutional environment, particular outbreaks of resistant pathogens can be eliminated. What to replace these offending agents with is the difficult question. Compounds with intense gram-negative potency are the logical choice; however, the ß-lactamase induction potential possessed by the agent is also an important consideration. For instance, during the ESBL-producing K. pneumoniae outbreak, imipenem replaced ceftazidime, subsequently leading to an increase in P. aeruginosa resistance.

Optimizing the antimicrobial Formulary has been recently shown to have a favorable impact on the susceptibilities of problematic gram-negative bacilli in several institutions. Restricting the use of ceftazidime in a pediatric intensive care unit resulted in a small but not significant reduction in ceftazidime- resistant gram-negative bacteria. When the data were further analyzed, however, the number of known class C ß-lactamase-producing organisms substantially decreased from 68.2% to 45.9%, p ß 0.05.[82] Improved susceptibilities appear to be even greater when ceftazidime has been replaced by a fourth-generation cephalosporin. Goldman and colleagues 83 showed a dramatic increase in E. cloacae susceptibilites to a variety of antibiotic classes following a Formulary conversion from ceftazidime to cefepime in six CCUs at the Cleveland Clinic Foundation. Mebis and colleagues[84] replaced ceftazidime-based combination regimens with cefepime-based combination therapy in the treatment of fever and neutropenia. This conversion was in response to E. cloacae resistance rates of 75% (ceftazidime), 52.5% (ciprofloxacin), and 36% (amikacin). Ten months following a single antibiotic change, resistance rates decreased to 35% (ceftazidime), 24% (cipro-floxacin), and 18% (amikacin). Similar results were observed in the oncology units when our institution converted from ceftazidime to cefepime as the preferred monotherapeutic regimen.[85] Although these situations occurred in oncology units, they provided meaningful data. Because the antibiotic regimens used in the oncology unit tend to be monopolistic, with preference given to a select few choices, the outcome of a single regimen substitution can be quantified with less confounding variables. Information from such studies can be useful to study the impact of regimen selection in other infectious diseases, including respiratory tract infections.

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