Melinda M. Neuhauser

Pharmacokinetics and Pharmacodynamics of Fluoroquinolones

The pharmacokinetic characteristics of levofloxacin, moxifloxacin, and gatifloxacin include excellent oral bioavailability (90–99%), extensive penetration into tissues and body fluids, and an elimination half‐life (6–12 hrs) that allows for once‐daily dosing in patients with normal renal function. Levofloxacin and gatifloxacin primarily are excreted unchanged in the urine, whereas moxifloxacin undergoes hepatic metabolism. The pharmacodynamic values that correlate with successful clinical and microbiologic outcomes, as well as prevent emergence of bacterial resistance, are ratios of maximum or peak unbound drug concentration (Cmax) to minimum inhibitory concentration (MIC), and 24‐hour unbound area under the concentration curve (AUC0‐24hr) to MIC. For gram‐negative infections, a Cmax:MIC greater than or equal to 10 and AUC0‐24hr:MIC greater than or equal to 125 are associated with increased probability of a successful outcome. For infections caused by Streptococcus pneumoniae, an AUC0‐24hr:MIC of 30 or more is suggested for favorable clinical outcomes. Pharmacokinetic and pharmacodynamic values influence rational therapeutic decisions in the selection and dosages of these drugs.

Consensus summary of aerosolized antimicrobial agents: application of guideline criteria. Insights from the Society of Infectious Diseases Pharmacists.

Aerosolized delivery of antimicrobial agents is an attractive option for management of pulmonary infections, as this is an ideal method of providing high local drug concentrations while minimizing systemic exposure. With the paucity of consensus regarding the safety, efficacy, and means with which to use aerosolized antimicrobials, a task force was created by the Society of Infectious Diseases Pharmacists to critically review and evaluate the literature on the use of aerosolized antiinfective agents. This article summarizes key findings and statements for preventing or treating a variety of infectious diseases, including cystic fibrosis, bronchiecstasis, hospital acquired pneumonia, fungal infections, nontuberculosis mycobacterial infection, and Pneumocystis jiroveci pneumonia. Our intention was to provide guidance for clinicians on the use of aerosolized antibiotics through evidence based pharmacotherapy. Further research with well designed clinical trials is necessary to elucidate the optimal dosage and duration of therapy and, of equal importance, to appreciate the true risks associated with the use of aerosolized delivery systems.

Quinupristin-dalfopristin: an overview.

Synercid (RP 59500), the first injectable streptogramin antibiotic, is composed of two semisynthetic pristinamycin derivatives, quinupristin and dalfopristin. Individually, each component has bacteriostatic activity against staphylococci and streptococci, but together, the agents exhibit synergy, leading to bactericidal activity. The combination drug, however, is bacteriostatic against Enterococcus faecium and has poor activity against Enterococcus faecalis. Despite a short half‐life, an extended postantibiotic effect allows the agent to be dosed every 8–12 hours. Both drugs are largely hepatically metabolized and excreted in bile. Although not metabolized by cytochrome P450 3A4, quinupristin‐dalfopristin can inhibit agents that are metabolized through this pathway. Dosage adjustments may be necessary in patients with hepatic dysfunction. Alterations in renal function have minimal effects on the agents pharmacokinetics. Adverse events include arthralgia, myalgias, and infusion‐related pain. Based on available data, quinupristin‐dalfopristin appears to have a role in treating severely ill patients with infections due to multiresistant gram‐positive pathogens.

Extended-spectrum β-lactamases: Frequency, risk factors, and outcomes

Study Objective. To determine epidemiologic factors of extended‐spectrum β‐lactamase (ESBL)‐producing Escherichia coli or Klebsiella pneumoniae in a nonoutbreak setting.

Economic Consequences of Unused Medications in Houston, Texas

BACKGROUND: It is likely that a large amount of unused and outdated medications exists in households throughout the US; however, the amount and potential costs of these medications are unknown. OBJECTIVE: To determine the amount, types, and costs of unused medications present in a neighborhood surrounding a community pharmacy in Houston, Texas. METHODS: A community trial was conducted between April and September 2002. This pilot study investigated the quantity and types of drugs returned to a community pharmacy over a 6-month period. RESULTS: During the study period, approximately 17 000 oral pills worth over

Evaluation of antifungals in the surgical intensive care unit: a multi-institutional study

26 000 were collected in 1315 medication containers. Medications collected were from all drug classes and types (pharmaceutical samples, over-the-counter and prescription drugs). CONCLUSIONS: This study demonstrated that an enormous amount of unused medications were present in a community in the US. Community pharmacies may be an ideal venue to collect and destroy these unused drugs.

Telithromycin: An Oral Ketolide for Respiratory Infections

In the USA, >50% of candidemia episodes occur in medical or surgical intensive care units (SICU). However, studies focused on patterns and rationale for antifungal use are lacking. The objective of this study was to evaluate systemic antifungal usage in SICU patients. Retrospective audit of SICU patients receiving antifungal therapy from four American hospitals. Medical records were reviewed for demographics, hospital variables, microbiology results, antifungal regimens and indications for therapy. A total of 2411 patient‐days of antifungal use were evaluated in 225 patients. Fluconazole was the most frequently prescribed antifungal (1846 patient‐days) followed by amphotericin B deoxycholate (251 patient‐days), lipid formulations of amphotericin B (201 patient‐days), itraconazole (71 patient‐days), and caspofungin (42 patient‐days). Antifungals were prescribed empirically (44%), for preemptive therapy in critically ill patients colonised with Candida (43%), or for candidiasis (12%). Candida species were recovered from 98% of patients with positive fungal cultures most commonly from pulmonary (53%) or urinary sources (17%). Fluconazole is the most frequently prescribed antifungal agent in SICUs and is most often prescribed for empiric or preemptive indications. Research efforts to identify patients who warrant preemptive antifungal therapy for invasive candidiasis could dramatically change antifungal prescribing patterns in the SICU.

Involvement of Immunization-Certified Pharmacists with Immunization Activities

The ketolides represent a new subclass of antibiotics among the macrolide‐lincosamide‐streptogramin group. Telithromycin, the first ketolide to be awarded approvable status for clinical use, demonstrates in vitro activity against community‐acquired respiratory pathogens including penicillin‐ and erythromycin‐resistant Streptococcus pneumoniae. An extended half‐life permits once‐daily oral administration. Telithromycin is a substrate for cytochrome P450 (CYP) 3A4 and also inhibits drugs metabolized by CYP3A4. A relatively high frequency of mild‐to‐moderate gastrointestinal adverse effects has been reported. Similar clinical and microbiologic efficacy has been demonstrated with oral dosing in comparative clinical trials for community‐acquired pneumonia, acute sinusitis, acute exacerbations of chronic bronchitis, and pharyngitis. Although limited data on penicillin‐resistant S. pneumoniae and erythromycin‐resistant Streptococcus pyogenes are available from clinical trials, this drug appears promising for respiratory infections caused by these pathogens.

Postantibiotic effects of ABT-773 and amoxicillin-clavulanate against Streptococcus pneumoniae and Haemophilus influenzae

BACKGROUND Immunization certification courses allow pharmacists to directly administer vaccines to their patients. However, the demographics and level of immunization involvement of immunization-certified pharmacists compared with those noncertified are unknown. OBJECTIVE To document the demographics, professional activities, and job satisfaction of immunization-certified pharmacists compared with pharmacists not certified for immunization. METHODS In a cross-sectional pilot study, immunization-certified pharmacists were compared with noncertified pharmacists via a postal-mailed questionnaire. The questionnaire consisted of demographic and practice site characteristics, involvement in immunization services, and a job satisfaction survey. RESULTS Response rates were 48% (n = 101) and 36% (n = 158) for immunization-certified and noncertified pharmacists, respectively. Significantly more certified pharmacists were involved in immunizations (99% vs 24%; p < 0.001). Desire to improve the health care of the public and personal satisfaction were important factors that encouraged pharmacists to become certified to administer vaccines. Seventy-four percent of immunization-certified pharmacists directly administered the vaccines, primarily influenza (96%), pneumococcal (77%), hepatitis (55%), and diphtheria, pertussis, tetanus (19%). Adequate training, time, support from management and staff, and liability coverage were important factors that allowed pharmacists to incorporate immunizations into their practice. No significant differences in job satisfaction were observed between immunization-certified and noncertified pharmacists. CONCLUSIONS Immunization-certified pharmacists are using their skills to administer vaccines to patients within their communities. Efforts to increase the number of these pharmacists throughout the US should be undertaken.

In Vitro Activities of a New Ketolide, ABT-773, Alone and in Combination with Amoxicillin, Metronidazole, or Tetracycline against Helicobacter pylori

ABSTRACT This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates ofStreptococcus pneumoniae and Haemophilus influenzae. The PAEs of ABT-773 and amoxicillin-clavulanate ranged from 2.3 to 6.0 h and 0 to 2.2 h against S. pneumoniae and from 2.7 to 9.1 h and 0 to 0.8 h againstH. influenzae, respectively.