CID2008年9月增刊：美罗培南治疗严重细菌性感染进展

David

15 September 2008 Supplement
Introduction
Update on the Appropriate Use of Meropenem for the Treatment of Serious Bacterial Infections
美罗培南治疗严重细菌性感染进展
Clinical Infectious Diseases 2008;47:S3–S13

SUPPLEMENT ARTICLE
Broad-Spectrum Antimicrobials and the Treatment of Serious Bacterial Infections: Getting It Right Up Front
广谱抗生素和重症细菌性感染的治疗
Marin H. Kollef

Washington University School of Medicine and Barnes-Jewish Hospital, St. Louis, Missouri

The treatment of serious bacterial infections is complicated by the fact that time to initiation of effective antimicrobial therapy is a strong predictor of mortality. Therefore, therapy must be initiated before the causative pathogen is identified. However, inappropriate or inadequate initial empirical therapy is associated with increased mortality, morbidity, and length of hospital stay. Initial empirical therapy with broad-spectrum antimicrobials attempts to address this dilemma by “getting it right up front.” The goal is to provide treatment active against the most likely pathogens until culture/susceptibility test results are obtained. After the causative pathogen is identified, streamlining to more-precise therapy of the shortest acceptable duration is implemented. In this way, the risks of death, morbid complications, increased duration of hospital stay (as a result of ineffective initial treatment), and emergence of resistance (due to extended treatment with broad-spectrum agents) are lowered. Improved clinical and economic outcomes after such an approach have been demonstrated.

Clinical Infectious Diseases 2008;47:S14–S20

SUPPLEMENT ARTICLE
Impact of Antibiotic Resistance in Gram-Negative Bacilli on Empirical and Definitive Antibiotic Therapy
革兰阴性杆菌的耐药性对经验和对症抗生素治疗的影响
David L. Paterson

University of Queensland, Clinical Research Centre, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia; and Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Serious infections with gram-negative pathogens continue to be associated with considerable mortality. Increasing antibiotic resistance in organisms such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae is contributing to difficulties with choosing antibiotics to prescribe for these infections. Optimization of therapy against these organisms starts with the initial empirical antibiotic choice. Surveillance data and hospital or unit antibiograms may inform this decision, although individualization of the initial regimen on the basis of prior antibiotic use and prior isolation of resistant pathogens may be more important. Combinations of antibiotics are often required empirically, and “combination antibiograms” may need to be developed for this purpose. Preliminary data suggest that extending the time over which a dose of antipseudomonal β-lactam antibiotics is infused may improve clinical outcomes; however, this idea remains to be confirmed in randomized trials. The role of direct susceptibility testing in aiding more-rapid initiation of appropriate antibiotic therapy is also being studied. When identification and susceptibility testing is complete, the antibiotic regimen for infections due to gram-negative pathogens can be “fine tuned.” On some occasions, this fine tuning necessitates the introduction of “salvage” antibiotics, such as colistin or tigecycline; on others, it necessitates de-escalation and early termination of therapy. The lack of new antibiotic options against gram-negative pathogens underscores the need for optimization of current therapies and prevention of the spread of these organisms.

Clinical Infectious Diseases 2008;47:S21–S31

SUPPLEMENT ARTICLE
The Importance and Future of Antimicrobial Surveillance Studies
抗生素监测研究的重要性和未来发展
Robert Masterton

Ayrshire and Arran National Health Service Board, The Ayr Hospital, Ayr, United Kingdom

Surveillance studies provide important information that allows for the identification of trends in pathogen incidence and antimicrobial resistance, including identification of emerging pathogens at national and global levels. Routine surveillance is critical for creating and refining approaches to controlling antimicrobial resistance and for guiding clinician decisions regarding appropriate treatment. The traditional approach has been to monitor pathogen antimicrobial susceptibility; numerous large studies have been performed, and their designs have evolved over time. Longitudinal studies are particularly useful because important information can be obtained by comparing data over time. Another approach to surveillance, that of monitoring antimicrobial use, can help to identify trends in dosing, to prevent the development of resistance. Several studies have incorporated this approach into their methods, and both large and small studies have attempted to correlate antimicrobial use data with antimicrobial resistance data. Overall, care must be taken to coordinate programs for optimal utilization of resources, to avoid duplication of effort.

Clinical Infectious Diseases 2008;47:S32–S40

SUPPLEMENT ARTICLE
Pharmacokinetic and Pharmacodynamic Properties of Meropenem
美罗培南的药代动力和药效特性
David P. Nicolau

Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut

Pharmacokinetic and pharmacodynamic profiles of antibiotics are important in determining effective dosing regimens. Although minimum inhibitory concentration (MIC) data reflect microbial susceptibility to an antibiotic, they do not provide dosing information. The integration of pharmacokinetic and microbiological data, however, can be used to design rational dosing strategies. Meropenem is a broad-spectrum β-lactam antibiotic that penetrates most body fluids and tissues rapidly after intravenous administration. Meropenem undergoes primarily renal elimination; therefore, dosage adjustment is required for patients with renal impairment. Meropenem is indicated for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and bacterial meningitis. Meropenem has time-dependent bactericidal activity; thus, the percentage of time that free-drug concentrations are higher than the MIC ( ) best characterizes the drug's pharmacodynamic profile (bactericidal target of  ). Pharmacodynamic modeling can identify regimens with the greatest probability of attaining this target, and probabilities can be compared with clinical and microbiological responses in patients.

Clinical Infectious Diseases 2008;47:S41–S51

SUPPLEMENT ARTICLE
Update on the Efficacy and Tolerability of Meropenem in the Treatment of Serious Bacterial Infections
美罗培南在治疗重症细菌性感染方面的效用和患者耐受性进展
John F. Mohr IIIa

University of Texas Health Science Center, Houston

Meropenem is a carbapenem antibiotic approved by the US Food and Drug Administration for the treatment of complicated skin and skin-structure infections, complicated intra-abdominal infections, and pediatric bacterial meningitis (in patients 3 months of age). In clinical trials, it also has shown efficacy as initial empirical therapy for the treatment of nosocomial pneumonia. Unlike other β-lactam antibiotics, including third-generation cephalosporins, carbapenems have shown activity against extended-spectrum β-lactamase–producing and AmpC chromosomal β-lactamase–producing bacteria. Compared with imipenem, meropenem is more active against gram-negative pathogens and somewhat less active against gram-positive pathogens, and it does not require coadministration of a renal dehydropeptidase inhibitor. In most comparative trials, clinical and bacteriological response rates with imipenem and meropenem were similar. Compared with clindamycin/tobramycin, meropenem is associated with a reduced length of hospital stay and a shorter duration of therapy among patients with complicated intra-abdominal infections. Meropenem is well tolerated by children and adults and has an acceptable safety profile. Alternative meropenem dosing strategies for the optimization of outcomes are under investigation.

[ 本帖最后由 David 于 2008-8-25 11:51 编辑 ]