The penetration characteristics of cefazolin and cephradine in human bone were determined in 35 patients undergoing total knee replacement. The results were compared to previously reported data on patients undergoing total hip replacement. The time required to achieve peak bone levels in total knee replacement was less than in total hip replacement. Importantly, peak bone levels in total knee replacement (cefazolin: 11 mg/kg; cephradine: 7 mg/kg) were significantly less (less than or equal to 50%) than bone levels in total hip replacement (cefazolin: 30 mg/kg; cephradine: 23 mg/kg). The bone half-lives (t 1/2) of cephalosporins were prolonged in total knee replacement compared to total hip replacement because of the tourniquet effect. The reduction in peak bone levels and the bone t 1/2 of cephalosporins should be taken into account in patients receiving prophylaxis for total knee replacement. Therefore, patients undergoing total knee replacement should receive 2 g of a parenteral cephalosporin 30 min prior to surgery in order to achieve the same degree of protection, i. e., peak bone levels, as is achieved with 1 g of a cephalosporin administered prophylactically to patients undergoing total hip replacement. If the critical effect of the tourniquet is not taken into account in antibiotic prophylaxis for patients undergoing total knee replacement, then suboptimal bone cephalosporin levels may result.

Absorption↗

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Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition.

The absorption of ciprofloxacin was higher when administered through a nasoduodenal tube than through a nasogastric tube, indicating that even though acidic gastric pH is needed for rapid disintegration, dissolved ciprofloxacin might not be stable in the gastric environment. If the length of exposure or the different gastric environment in each individual affects the overall absorption of ciprofloxacin, this could explain the reported variability in ciprofloxacin absorption and suggests the need for the development of an enteric-coated tablet. Further studies are needed to fully characterize the absorption of ciprofloxacin in patients with different illnesses, gastric transit times, gastrointestinal environments and of different ages.

Absorption↗

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Pharmacokinetics of cefotaxime in healthy volunteers and patients.

Cefotaxime is a third-generation cephalosporin that has maintained good susceptibility pattern despite its extensive use. It is available for intravenous and intramuscular administration. Its pharmacokinetic property includes a small volume of distribution with low protein binding. Cefotaxime's half-life is approximately 1.1 h, and it is primarily eliminated by the kidney. It has an active metabolite desacetyl-cefotaxime that displays pharmacokinetic properties similar to cefotaxime. Desacetyl-cefotaxime has a half-life of 1.5 h and also is eliminated by the kidneys by both glomerular filtration and active secretion. The half-life of cefotaxime and its metabolite is altered in patients with severe renal dysfunction requiring dosage adjustment. Despite its relatively short half-life, cefotaxime may be dosed every 12 h based on its pharmacokinetic and pharmacodynamic properties.

Cefotaxime↗

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Cephalosporin-metronidazole combinations in the management of intra-abdominal infections.

With our current understanding of antimicrobial pharmacokinetics and pharmacodynamics, optimal antimicrobial dosing strategies can be developed for a variety infectious processes. Herein, we discuss the clinical utility of a combination containing a third-generation cephalosporin plus metronidazole as compared to conventional single agents (cefoxitin and ampicillin-sulbactam) for the management intra-abdominal infections. At present, several studies have been performed that compare the bactericidal activity of such combinations to that of single agents for organisms commonly isolated from these intra-abdominal process. From these studies it appears that the use of a third-generation cephalosporin with strong activity against common aerobic organisms associated with intra-abdominal infections in combination with a potent anaerobic drug such as metronidazole provides improved antibacterial activity and optimizes the pharmacodynamic profile of the agents over the dosing interval compared to conventional single agents. As a result of the pharmacokinetic and pharmaco-dynamic superiority of the combination regimen, considerable pharmacoeconomic advantages may be realized with the clinical implementation of a third-generation cephalosporin plus metronidazole regimen. This approach should result in maximal clinical efficacy and is important not only for individual patient therapy, but also for formulary management decisions.

Abdomen↗

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Cefixime in the treatment of patients with lower respiratory tract infections: results of US clinical trials.

Community-acquired acute lower respiratory tract infections are a common cause of illness, accounting for millions of physician visits and prescriptions each year. Cefixime is an extended-spectrum oral cephalosporin with activity against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the most commonly isolated bacterial pathogens. This review presents the results of eight US studies comparing the efficacy and safety of cefixime with those of amoxicillin, amoxicillin/clavulanate, cefaclor, cephalexin, and cefuroxime axetil in the treatment of patients with acute lower respiratory tract infections. Data for 211 cefixime-treated patients and a range of 19 to 49 patients in the comparator treatment groups were included in the efficacy analysis. Clinical success (cure or improvement) was observed in 94% of cefixime-treated patients; clinical success rates in the comparator treatment groups ranged from 97% for cefuroxime axetil and cefaclor to 79% for amoxicillin/clavulanate. At the end of treatment, the overall eradication rate in the cefixime treatment group was 92% and ranged from 76% (cefaclor) to 98% (cefuroxime axetil) in the comparator treatment groups. The percentage of persistent organisms was highest in the cefaclor (24%) and cephalexin (21%) treatment groups. With the exception of the cephalexin group (4%), the incidence of patients who reported adverse experiences was similar across treatment groups (34% to 50%). Those involving the gastrointestinal tract were by far the most common, and most adverse experiences were rated as mild or moderate in severity.

Adult↗

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Strategic antibiotic decision-making at the formulary level.

The proliferation of antimicrobial agents introduced for the treatment of increasingly complex infectious diseases, coupled with the obligation to provide the best possible medical care in keeping with hospital fiscal constraints, has created a need for strategic decision-making about antibiotics at the formulary level. The following experience at the Hartford Hospital, a 1,000-bed tertiary-care facility, represents an example of an antibiotic management system based on a multidisciplinary approach that utilizes infectious disease physicians, clinical microbiologists, hospital epidemiologists, and pharmacists.

Anti-Bacterial Agents↗

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Tissue penetration and half-life of cefonicid.

The pharmacokinetics of cefonicid in the serum and tissues of patients undergoing open heart surgery, vaginal hysterectomy, and hip replacement was studied and compared with that of cefazolin and cefoxitin. Cefonicid achieved serum and tissue concentrations that were higher and more prolonged than those of cefazolin and cefoxitin. For cefonicid parallelism was observed between the serum and tissue concentration-time curves. Correlations of these properties to clinical efficacy were not attempted.

Adult↗