Topical antibacterial agents

Decreased systemic toxicity, ease of application, and increased concentration at the target site are some of the important advantages topical antibacterial agents offer. This article reviews the literature on selected indications of these agents and provides in-depth examination of specific agents for the prophylaxis and treatment of skin and wound infections.     

Topical antibacterial agents

Topical antibacterial agents occupy an important niche of antimicrobial therapy for both inpatients and outpatients. These agents, including antiseptic and antibiotic preparations, are used for prophylaxis and treatment of infection. Prophylactic uses include application for traumatic and surgical wounds, burns, intravascular catheters, and eradication of S. aureus nasal carriage. Topical antibacterial agents are also used for treatment of primary and secondary pyodermas. Individual antibacterial agents have been reviewed. Of note, despite the widespread use of topical antibacterial agents, further data on which to guide therapy are needed in many instances.     

Principles of use of antibacterial agents

The selection of an antimicrobial regimen is based on a number of factors, including the nature of the infection, the identity and susceptibility of the pathogens, host characteristics, and the pharmacokinetics and pharmacodynamics of antimicrobial agents. This article provides a comprehensive overview of these factors, with particular attention to pharmacokinetics and monitoring for efficacy and toxicity. A brief summary is also provided of some other topics discussed in detail elsewhere in this issue, such as susceptibility testing, pharmacodynamics, and pharmacokinetics-pharmacodynamics parameters.     

Long-circulating bacteriophage as antibacterial agents.

The increased prevalence of multidrug-resistant bacterial pathogens motivated us to attempt to enhance the therapeutic efficacy of bacteriophages. The therapeutic application of phages as antibacterial agents was impeded by several factors: (i) the failure to recognize the relatively narrow host range of phages; (ii) the presence of toxins in crude phage lysates; and (iii) a lack of appreciation for the capacity of mammalian host defense systems, particularly the organs of the reticuloendothelial system, to remove phage particles from the circulatory system. In our studies involving bacteremic mice, the problem of the narrow host range of phage was dealt with by using selected bacterial strains and virulent phage specific for them. Toxin levels were diminished by purifying phage preparations. To reduce phage elimination by the host defense system, we developed a serial-passage technique in mice to select for phage mutants able to remain in the circulatory system for longer periods of time. By this approach we isolated long-circulating mutants of Escherichia coli phage lambda and of Salmonella typhimurium phage P22. We demonstrated that the long-circulating lambda mutants also have greater capability as antibacterial agents than the corresponding parental strain in animals infected with lethal doses of bacteria. Comparison of the parental and mutant lambda capsid proteins revealed that the relevant mutation altered the major phage head protein E. The use of toxin-free, bacteria-specific phage strains, combined with the serial-passage technique, may provide insights for developing phage into therapeutically effective antibacterial agents.     

Assessment of the efficacy of antibacterial agents

Assessment of the efficacy of antibacterial agents
The committee for The Japanese Respiratory Society guidelines in management of respiratory infections. Respirology 2004; 9: S40–S42     

The tissue cage model in the distribution of antibacterial agents.

Developments in the measurement of interstitial tissue fluid using the tissue cage model are described. The design and physical characteristics of tissue cages are examined and evidence is presented to show that the fluid contained within these cages is representative of interstitial tissue fluid. The distribution of a variety of antibacterial agents into tissue cage fluid is examined and shows that this technique is a reliable experimental model for the study of drug distribution. The results also show that some antibacterial agents may never, normally, distribute into the tissue fluid and that the use of tissue homogenates, especially the kidney, is unreliable as a guide to the tissue concentration of a drug.     

Use of antibacterial agents in renal failure

This article provides information on the pharmacokinetics of antibacterial agents in patients with normal renal function and those with impaired renal function. Specific discussion includes the use of serum levels, dosage adjustments in dialysis, new strategies for cefazolin dosages in dialysis patients, and antibiotic toxicity in renal failure, and tabular data is presented for determining appropriate dosages for varying degrees of renal failure.     

Use of antibacterial agents in renal failure

This article provides background information on the pharmacokinetics of antibacterial agents in patients with normal and impaired renal function. Tables are provided to allow quick determination of appropriate dosages for varying degrees of renal failure. The use of serum levels, newer strategies for cefazolin, vancomycin, and aminoglycoside dosing, methods of dialysis and associated antibiotics dosage adjustments, and antibiotic toxicity in renal failure are reviewed.     

Use of antibacterial agents in renal failure

This article reviews the pharmacokinetics of antibacterial agents in patients with normal and decreased renal function. The concepts of volume and distribution, rate of elimination, loading and maintenance doses, and therapeutic drug monitoring are delineated. Special reference is made to the intermittent dosing of cefazolin with hemodialysis. Newer, as well as traditional methods of extracorporeal circulation and the resultant changes in antibacterial agent pharmacodynamics are discussed.     

Principles of selection and use of antibacterial agents

The selection of an antimicrobial treatment regimen is based on many factors, including the nature of the infection, the identity and susceptibility pattern of the infecting organism, and the pharmacokinetics and pharmacodynamics of the drug(s). Principles of susceptibility testing, pharmacology, and monitoring of therapy are discussed in this article.     

Basic approach for the selection of antibacterial agents

• In these guidelines, antimicrobials are selected according to the severity ranking and in conformance with the health insurance system in Japan and the prevailing situation with regard to hospital-acquired pneumonia. Reference was made to the 2005 ATS/IDSA guidelines as precedents for guidelines regarding hospital-acquired pneumonia. After examining these guidelines, the need to consider the medical system and particularities of infectious disease treatment in each country was identified. Preparation of these guidelines was thus necessary to take into consideration special conditions in Japan, including the long period of hospitalization, large number of patients with mild pneumonia, and large differences in test methods and antimicrobial doses.
• In the selection of specific antimicrobials, the mild group (A) corresponds to the early-onset group or the group with no risk factors for drug-resistant strains of bacteria in the ATS/IDSA guidelines, and the severe group (C) corresponds to the late group or group with risk of drug-resistant bacteria. Antimicrobial selection for the moderate group (B) between these two groups is carried out with consideration of drug-resistant bacteria, including Pseudomonas aeruginosa . In cases when MRSA is suspected, administration of anti-MRSA agents is recommended in addition to the antimicrobial for the respective group. Moreover, according to pharmacokinetic/pharmacodynamic theory, a sufficient antimicrobial dose needs to be administered in the early stage. As the efficacy of aminoglycoside drugs may be low using the doses and administration methods applied in Japan, administration using therapeutic drug monitoring is emphasized.     

Intrapulmonary pharmacokinetics of antibacterial agents: implications for therapeutics

The idea of studying the pharmacokinetics and pharmacodynamics of antibacterials in order to predict their efficacy has long been of interest. Traditionally, serum drug concentrations have been evaluated against the minimum inhibitory concentration (MIC) of a given pathogen; however, infection site-specific data continue to gain interest from clinicians. Despite methodological limitations, progress in techniques has improved the clinical significance of data generated. Rather than using tissue homogenates which fail to differentiate between interstitial and intracellular concentrations, newer collection techniques focus on sampling of matrices that allow for this differentiation. These collection techniques now allow one to accurately describe beta-lactam and aminoglycoside interstitial penetrations, as well as, the interstitial and phagocytic concentrations of macrolides and fluoroquinolones. By using these specific data and the MICs of infecting pathogens, it is hoped that conclusions can be drawn by a clinician as to the appropriateness of the choice of an antibacterial.     

New synthetic quinolone antibacterial agents and serum concentration of theophylline

The effect of pipemidic acid and five new synthetic antibacterial agents--norfloxacin, enoxacin, ofloxacin, ciprofloxacin, and pefloxacin--on the serum level of theophylline was studied in healthy male adult volunteers after concomitant oral administration of these agents with a slow release preparation of theophylline. The results indicated that enoxacin, ciprofloxacin, and pipemidic acid might decrease the clearance of theophylline in the liver, and the attention should be paid in clinical use when enoxacin or pipemidic acid is coadministered with theophylline.