Categories: ReAct Spotlight Date: Feb 29, 2012 Title: ReAct SPOTLIGHT - FOCUS ON "OLD" ANTIBIOTICSThis issue of ReAct Spotlight focuses on the antibiotics that currently exist on the market. Unfortunately, all antibiotics are not always available as is highlighted in the first article in this issue, “Forgotten Antibiotics: An Inventory in Europe, the United States, Canada, and Australia”. A short summary by Ingrid Trolin, ReAct accompanies this paper.
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This issue of ReAct Spotlight focuses on the antibiotics that currently exist on the market. Unfortunately, all antibiotics are not always available as is highlighted in the first article in this issue, “Forgotten Antibiotics: An Inventory in Europe, the United States, Canada, and Australia”. A short summary by Ingrid Trolin, ReAct accompanies this paper. Thus physicians in many countries cannot always follow treatment guidelines, which might lead to sub-optimal therapy for patients. This is especially worrisome as we do not have a vibrant pipeline of novel antibiotics and we should make the most of the antibiotics we already have. Possible consequences of these drug shortages are brought up in the article “The Impact of Anti-infective Drug Shortages on Hospitals in the United States: Trends and Causes”. In addition, this Spotlight issue brings up the importance of some “old” and sometimes last-line antibiotics such as fosfomycin, colistin and the carbapenems.
Jan. 2012 | Reviews of anti-infective agents
In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better availability of these antibiotics on a global scale.
Summary by Ingrid Trolin, ReAct:
Antibiotic resistance is an alarming and increasing problem around the world. As few new antibiotics are entering the drug development pipe-line, an international expert panel has collected information on the availability of potentially useful older products in 38 countries in Europe, United States, Canada, and Australia.
Older drugs are disappearing from the market or are temporarily unavailable in many countries due to lack of profit or other reasons like new demands from regulatory authorities.
In the overview, the experts selected a number of bacteria, which often cause blood-stream infections and old antibiotics, where actual data on effectiveness against such infections could be found. From this review, 31 of 33 selected substances were found to be active against resistant bacteria or having a unique value.
To great astonishment among the reviewers, the number of antibiotics available per country varied considerably. Twenty-two of the selected antibiotics were available in less than 20 of the 38 countries surveyed. Nafcillin was available in only one country whereas Benzylpenicillin (Penicillin G) could be found in 35 countries. The authors find that it would be interesting to extend the inventory to other regions such as Asia, South America, and Africa and call upon regulatory bodies to develop new and “perhaps less burdensome” procedures so that the old medicines could be used globally in a timely manner when needed.
Jan. 2012 | Clinical Infectious Diseases
Anti-infective shortages pose significant logistical and clinical challenges to hospitals and may be considered a public health emergency. Anti-infectives often represent irreplaceable life-saving treatments. Furthermore, few new agents are available to treat increasingly prevalent multidrug-resistant pathogens. Frequent anti- infective shortages have substantially altered patient care and may lead to inferior patient outcomes. Because many of the shortages stem from problems with manufacturing and distribution, federal legislation has been introduced but not yet enacted to provide oversight for the adequate supply of critical medications. At the local level, hospitals should develop strategies to anticipate the impact and extent of shortages, to identify therapeutic alternatives, and to mitigate potential adverse outcomes. Here we describe the scope of recent anti- infective shortages in the United States and explore the reasons for inadequate drug supply.
Jan. 2012 | Clin Microbiol Infect
Can we survive with only a few old antibiotics? In this issue of Clinical Microbiology and Infection, three antibiotics are re-visited: colistin, co-trimoxazole and fosfomycin. The review by Raz underlines the increased role of fosfomycin as a therapeutic option against multidrug-resistant pathogens, particularly those responsible for urinary tract infections. For co-trimoxazole, Goldberg and Bishara summarize the accumulated evidence in the literature on the new, ‘unconventional’ clinical use of co-trimoxazole during the last three decades. Obviously, those compounds are still effective against both Gram-positive and Gram-negative organisms. Colistin remains efficient even for Gram-negative bacteria that harbour carbapenemases, or complex associated mechanisms, such as Pseudomonas aeruginosa. It is less toxic than anticipated. However, more strains are becoming resistant to colistin. Yahav et al. in their review summarize the results of studies on the clinical use of colistin administered intravenously or as an aerosol. The article of Couet et al. conducts a critical review with prospective thoughts and focuses on the most recent pharmacokinetic studies on colistin, published during the last few years or months, or not yet published but only presented at international meetings. Combination therapy (mandatory for fosfomycin administered intravenously) is often used to increase the efficiency of these three drugs, and limit the occurrence of resistance. However, the best partner remains to be determined even if aminoglycosides are often used when a combination of colistin and fosfomycin would be a reasonable therapy for infections caused by resistant Gram-negative bacteria.
Nov. 2011 | Antimicrobial Agents and Chemotherapy
In this review, we summarize the current “state of the art” of carbapenem antibiotics and their role in our antimicrobial armamentarium. Among the b-lactams currently available, carbapenems are unique because they are relatively resistant to hydrolysis by most b-lactamases, in some cases act as “slow substrates” or inhibitors of b-lactamases, and still target penicillin binding proteins. This “value-added feature” of inhibiting b-lactamases serves as a major rationale for expansion of this class of b-lactams. We describe the initial discovery and development of the carbapenem family of b-lactams. Of the early carbapenems evaluated, thienamycin demonstrated the greatest antimicrobial activity and became the parent compound for all subsequent carbapenems. To date, more than 80 compounds with mostly improved antimicrobial properties, compared to those of thienamycin, are described in the literature. We also highlight important features of the carbapenems that are presently in clinical use: imipenem-cilastatin, meropenem, ertapenem, doripenem, panipenem-betamipron, and biapenem. In closing, we emphasize some major challenges and urge the medicinal chemist to continue development of these versatile and potent compounds, as they have served us well for more than 3 decades.
Jan. 2012 | Clin Microbiol Infect
Colistin has been re-introduced into clinical practice for the treatment of carbapenem-resistant Gram-negative bacteria. Studies in the last decade attempted to reconstruct the path that present-day medications undergo prior to clinical use. In this review, we summarize the results of recent clinical studies. Colistin was associated with lower mortality than no effective treatment and higher unadjusted mortality than b-lactams in non-randomized clinical studies. However, it was administered to sicker patients with carabapenem-resistant bacteria. Overall, nephrotoxicity rates were not higher with colistin in these studies, and colistin-induced nephrotoxicity is reversible in most patients. The emergence of colistin resistance has been described in high-use settings. Synergy with carbapenem, rifampin and other antibiotics has been reported in vitro. Randomized controlled trials are ongoing or in planning to assess this and other aspects of colistin use in clinical practice.
Jan. 2012 | Clin Microbiol Infect
Fosfomycin is a broad-spectrum antibiotic discovered in Spain in 1969. It has bactericidal activity against a wide range of bacteria, includ- ing gram-negative micro-organisms and some gram-positive bacteria, such as staphylococci. Initially fosfomycin was administered paren- terally and only to patients with severe infections. Today it is often dispensed as fosfomycin–trometamol, an oral formula recommended in the treatment of urinary tract infections. Fosfomycin–trometamol in a single dose is indicated for the treatment of women with uncomplicated urinary tract infections.
Aug. 2011 | Scandinavian Journal of Infectious Diseases
Objective: To analyze the indications for and the efficacy of parenteral fosfomycin, especially against multidrug-resistant (MDR) and pan-resistant bacterial infections. Patients and methods: During a unique crisis in fosfomycin production, the supply of this antibiotic had to be carefully monitored in France over a 10-week period. One hundred and sixteen assessable patients were included in a prospective cohort study.
Results: The main indications for use were osteoarthritis, lung infection, urinary tract infection, and bacteraemia. The 2 bacteria most frequently involved were Pseudomonas aeruginosa and methicillin-resistant Staphylococcus. MDR bacteria were seen in 71.5% (83/116) of cases, especially MDR P. aeruginosa (n=28). Critical situations were common, with 44.0% (51/116) of hospitalizations occurring in an intensive care unit and 22.4% (26/116) of patients with septic shock. The overall outcome was favourable in 76.8% of cases (76/99 assessable patients).
Conclusion: This study provided a unique opportunity to describe the use of fosfomycin and assess its efficacy, especially against MDR bacterial infections, even in critical situations.