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

This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates of Streptococcus 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 against H. influenzae, respectively.

Telithromycin: an oral ketolide for respiratory infections.

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.

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 agent's 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.

In vitro activities of a new ketolide, ABT-773, alone and in combination with amoxicillin, metronidazole, or tetracycline against Helicobacter pylori.

The in vitro activity of ABT-773, a new ketolide, was compared with those of clarithromycin, amoxicillin, metronidazole, and tetracycline against 15 strains of Helicobacter pylori. The MIC of ABT-773 at which 90% of isolates were inhibited was 0.25 microg/ml, which was 3 dilutions higher than that of the most active agent, clarithromycin. Synergy and antagonism were not seen with any combinations. Additive activity was seen with tetracycline, metronidazole, and amoxicillin in 100, 60, and 40% of the combinations, respectively.

Pharmacokinetics and pharmacodynamics of ceftizoxime in patients with dosages adjusted for renal function.

STUDY OBJECTIVE: Our institution developed dosing guidelines for patients with renal impairment based on pharmacokinetic data and class-specific pharmacodynamics. Ceftizoxime was chosen as a model agent to evaluate if the modified guidelines achieved similar minimal plasma concentration (Cp(min)) and time above the minimum inhibitory concentration of the infecting organism (T>MIC) in patients with renal impairment versus those with normal renal function. DESIGN: Prospective pharmacokinetic and pharmacodynamic evaluation of ceftizoxime dosages. SETTING: University-affiliated hospital. PATIENTS: Forty-three patients with suspected or documented infection were enrolled and classified into four groups based on creatinine clearance (Cl(cr); ml/min): group 1, above 100; group 2, 61-99; group 3, 31-60; and group 4, 15-30. INTERVENTIONS: Ceftizoxime serum concentrations were obtained at steady state. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic and pharmacodynamic parameters were calculated. As expected, clearance and elimination rate constant were reduced, and half-life tended to be greater in patients with renal impairment. The Cp(min) and area under the concentration-time curve over 24 hours were similar between groups (p=0.39, p=0.42). The T>MIC was 100% for all patient isolates, and 90% or more versus our clinical strain for all groups. Clinical outcomes were similar among all groups. CONCLUSION: Our dosing guidelines achieved similar Cp(min) among all groups of patients. Our results support that recommendations for dosing adjustments should be based on pharmacokinetic data and must also consider pharmacodynamic parameters.

Efficacy and cost of ampicillin-sulbactam and ticarcillin-clavulanate in the treatment of hospitalized patients with bacterial infections.

STUDY OBJECTIVE: To evaluate the efficacy and cost of treatment with two beta-lactam/beta-lactamase-inhibitor combinations. DESIGN: Retrospective, open-label multicenter study. SETTING: Fifty-four hospitals across the United States. PATIENTS: Eight hundred ninety patients with skin and soft tissue, intraabdominal, gynecologic, respiratory, urinary tract, or other infections that required parenteral antibiotic therapy. INTERVENTION: Patients were administered either ampicillin-sulbactam 1.5 or 3.0 g every 6 hours or ticarcillin-clavulanate 3.1 g every 6 hours. MEASUREMENTS AND MAIN RESULTS: The agents did not differ significantly in efficacy for most infections; although, ampicillin-sulbactam was bacteriologically superior to ticarcillin-clavulanate in the treatment of intraabdominal infections (p=0.0011). Costs of ampicillin-sulbactam, particularly the 1.5-g dose, were lower than those of ticarcillin-clavulanate for skin and soft tissue (p<0.001), intraabdominal (p=0.005), and respiratory tract (p<0.001) infections. CONCLUSION: Ampicillin-sulbactam provides effective coverage for patients with the above infections and is as effective as the broader-spectrum agent.

Outcome assessment of minimizing vancomycin monitoring and dosing adjustments.

An approach to minimize monitoring of vancomycin therapy was evaluated in 120 patients, and results were compared with data from 120 patients in whom vancomycin therapy was monitored and adjusted based on serum peak and trough concentrations and traditional pharmacokinetic methods. Patients dosed by the nomogram (NM) had regimens adjusted based on actual body weight, estimated creatinine clearance, and a targeted trough concentration of 5-20 microg/ml. A single trough serum concentration was drawn only after 5 or more days of therapy. Overall, the average length of therapy was similar between groups (9.9 +/- 9.4 days NM and 8.6 +/- 7.2 days pharmacokinetic). The most common regimen for both groups was 1 g every 12 hours, although NM patients received significantly fewer grams/day (1.9 +/- 0.7 g/day) than the pharmacokinetic group (2.2 +/- 1.0 g/day, p<0.04). Patients dosed by NM also had significantly fewer regimen changes (0.63 +/- 0.96 vs pharmacokinetic 0.92 +/- 0.97, p=0.02) as well as significantly fewer serum concentrations measured/patient (1.08 +/- 1.9 vs 1.96 +/- 2.0, p=0.001). In addition, serum concentrations for NM patients were drawn later in therapy (5.4 +/- 2.5 vs 3.8 +/- 3.4 days, p=0.004). Of patients dosed by NM guidelines, 77 had trough concentrations drawn; these data were used to validate the nomogram. Seventy-two patients (94%) had trough concentrations in the target range of 5-20 microg/ml. No differences were found between groups with respect to cure, improvement, failure, or days to eradication, or with respect to nephrotoxicity. Finally, total drug cost/patient was not different between groups. A considerable cost savings to our institution was noted for patients dosed by NM compared with pharmacokinetics ($232.5 +/- 50.74 vs $403.75 +/- 70.97/mo, p=0.009) based on levels saved. Caution should be applied when generalizing our results to other patient populations.