Before implementing a therapeutic interchange, P&T committee members must invest time and resources to research and analyze the various agents under consideration. Formulary decisions are normally based on information collected from a variety of sources, including in-hospital data, published literature, and discussions with colleagues. Important considerations include current disease-management guidelines, the complexity of the treatment regimen, the adverse-event profile, the pharmacokinetic (PK) profile, and cost-savings data.
To ensure greater acceptance of a formulary decision, it is important to take a holistic approach that incorporates the needs of all departments in the hospital. To evaluate options about, a multidisciplinary team should be formed that includes clinical pharmacists, nurses, infectious-disease specialists, internal medicine physicians, urologists, pulmonologists, microbiologists, and other specialists who commonly use these agents.
Implementing a therapeutic interchange by the hospital staff can be challenging. It can involve multiple steps, with each step requiring a number of actions (Table 2). A first step is to educate and train the staff both before and during the initial process.
Table 2 Actions Required after Implementing a Therapeutic Interchange Program with Fluoro-quinolones
• Staff education and training
• Computer software upgrades
• Efficacy and adverse events monitoring
• Monitoring of physician acceptance
• Follow-up discussions with physicians
• Changes in hospital antibiogram (for antimicrobials)
Another critical step is upgrading computer software so that it “recognizes” the formulary change. Continued monitoring may be needed to gauge physicians’ acceptance of the switch and to detect any changes in clinical outcomes or frequency of adverse events directly associated with the formulary switch.
A more difficult task may be changing ingrained habits. Pharmacists may need to persuade physicians who continue to prescribe nonpreferred agents by following up with letters to them and by scheduling one-on-one discussions with them.
With antibiotic interchanges in particular, the hospital’s antibiogram may need to be updated, followed by careful monitoring to detect any changes in susceptibility to infection after a formulary substitution.
THE FLUOROQUINOLONE CLASS
When a therapeutic interchange involving the fluoro-quinolone class of drugs is being considered, these specific aspects should be kept in mind (Table 3):
Streptococcus pneumoniae is a major cause of community-acquired respiratory tract infections, such as community-acquired pneumonia (CAP), acute bacterial sinusitis, and acute exacerbations of chronic bronchitis (AECB). In contrast to the respiratory fluoroquinolones, ciprofloxacin has limited activity against S. pneumoniae (86.7% susceptibility vs. more than 99% for the respiratory fluoroquinolones from 2001 to 2004). It is not indicated for treatment of these infections, primarily because of the treatment failures and cases of breakthrough bacteremias that were reported shortly after this agent was introduced in the clinic.
Efflux mechanisms can also play an important part in initiating resistance to ciprofloxacin. In one study, approximately one-third of ciprofloxacin-resistant S. pneumoniae clinical isolates were efflux-positive, although none of these isolates was resistant to respiratory fluoroquinolones.
In addition to ciprofloxacin, a respiratory fluoroquinolone such as canadian levofloxacin (Levaquin drug) or moxifloxacin, would be needed on the formulary to treat community-acquired respiratory infections. However, the presence of multiple fluoroquinolones on a formulary can raise the risk of inappropriate use of these agents for unapproved indications. Although moxi-floxacin is effective for most community-acquired respiratory tract infections, it is not approved for genitourinary tract infections, in which gram-negative pathogens predominate, because of limited concentrations attained in the urine. In addition, there are no Clinical and Laboratory Standards Institute interpretive standards for any gram-negative bacteria.
Table 3 Drug Characteristics to Consider before Implementing a Potential Therapeutic Interchange with Fluoroquinolones
• Pathogen coverage
• Safety profile
• Drug interactions
• Drug acquisition costs
• Dosing frequency
• Ease of intravenous-to-oral switch
• Local and national susceptibility profiles
Levofloxacin offers the possibility of coverage for nosoco-mial and community-acquired respiratory tract infections, including S. pneumoniae and genitourinary tract infections. Having one broad-spectrum agent on the formulary, in contrast to two agents with more limited spectra, may reduce the need for antibiotic switching after the pathogen has been identified.
Among the gram-negative bacteria, results from the Tracking Resistance in the U.S. Today (TRUST) surveillance program have shown that susceptibility rates are generally comparable between levofloxacin and ciprofloxacin canadian. Susceptibility rates to some key pathogens, such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae, are typically about 90% or higher for both agents, whereas susceptibility rates to Pseudomonas aeruginosa are approximately 65%.
In vitro and animal studies have shown that once-daily ciprofloxacin 400 mg, administered three times daily, are equally likely to achieve PK and pharmaco-dynamic (PD) targets for effective eradication of gram-negative pathogens and have the potential to prevent resistance development by P. aeruginosa.
Because the fluoroquinolones exhibit concentration-dependent bactericidal activity, the 750-mg dose of levofloxacin optimizes PK/PD parameters for more complete bacterial eradication and has the potential to reduce the risk of antimicrobial resistance.