Optimizing Therapy for Stenotrophomonas maltophilia.
Semin Respir Crit Care Med. 2007 Dec
Muder RR.
Infectious Disease Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.
STENOTROPHOMONAS (XANTHOMONAS) MALTOPHILIA is a nonfermentative, gram-negative bacillus that is widely distributed in natural and humanmade environments. In the nonhospital setting it is an uncommon pathogen, typically causing soft tissue infection of contaminated wounds. In the hospital setting, particularly among critical care and oncology patients, S. MALTOPHILIA may cause catheter-related bacteremia, pneumonia, soft tissue infection, meningitis, prosthetic valve endocarditis, and ocular infections. S. MALTOPHILIA is usually resistant to multiple antimicrobials, including expanded-spectrum penicillins, third-generation cephalosporins, carbapenems, aminoglycosides, and quinolones. Trimethoprim-sulfamethoxazole is the antimicrobial agent of choice for this pathogen but is bacteriostatic. Further, resistance to this agent is increasing. Certain combinations of antibiotics are synergistic and may be appropriate for patients harboring resistant organisms or with life-threatening infections.
Thieme Connect
Monday, December 24, 2007
Optimizing Use of beta-Lactam Antibiotics in the Critically Ill.
Optimizing Use of beta-Lactam Antibiotics in the Critically Ill.
Semin Respir Crit Care Med. 2007 Dec
Roberts JA, Lipman J.
Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia.
The escalation of serious infections in critically ill patients over the past 25 years has continued despite advances in contemporary medicine. Ongoing research to reduce the high morbidity and mortality rates is mandated. beta-lactam antibiotics are often used empirically in serious infections. The efficacy of these time-dependent antibiotics is correlated with the time that concentrations are maintained above the minimum inhibitory concentration of the infective pathogen. In critically ill patients, pathophysiological changes can reduce antibiotic concentrations and thus alternative modes of administration such as continuous infusion have been studied and shown to standardize beta-lactam pharmacokinetics and meet pharmacodynamic targets. Clinical data supporting the efficacy of continuous infusion are currently scarce, but data continue to grow. Likewise antibiotic resistance continues to grow. Recent data suggest that poor dosing strategies may be contributing to this problem, which is exacerbated by a lack of development of alternate antibiotics. Suffice to say clinicians must use antibiotic regimens that optimally treat the individual patient and reduce the development of antibiotic resistance.
Thieme Connect
Semin Respir Crit Care Med. 2007 Dec
Roberts JA, Lipman J.
Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia.
The escalation of serious infections in critically ill patients over the past 25 years has continued despite advances in contemporary medicine. Ongoing research to reduce the high morbidity and mortality rates is mandated. beta-lactam antibiotics are often used empirically in serious infections. The efficacy of these time-dependent antibiotics is correlated with the time that concentrations are maintained above the minimum inhibitory concentration of the infective pathogen. In critically ill patients, pathophysiological changes can reduce antibiotic concentrations and thus alternative modes of administration such as continuous infusion have been studied and shown to standardize beta-lactam pharmacokinetics and meet pharmacodynamic targets. Clinical data supporting the efficacy of continuous infusion are currently scarce, but data continue to grow. Likewise antibiotic resistance continues to grow. Recent data suggest that poor dosing strategies may be contributing to this problem, which is exacerbated by a lack of development of alternate antibiotics. Suffice to say clinicians must use antibiotic regimens that optimally treat the individual patient and reduce the development of antibiotic resistance.
Thieme Connect
Optimizing Therapy for Infections Caused by Enterobacteriaceae Producing Extended-Spectrum beta-Lactamases.
Optimizing Therapy for Infections Caused by Enterobacteriaceae Producing Extended-Spectrum beta-Lactamases.
Semin Respir Crit Care Med. 2007 Dec
Endimiani A, Paterson DL.
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Semin Respir Crit Care Med. 2007 Dec
Endimiani A, Paterson DL.
Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
The spread of multidrug-resistant Enterobacteriaceae is complicating the treatment of nosocomial infections. In many parts of the world, resistance to third-generation cephalosporins exceeds 10% of total nosocomial isolates and 30% of isolates detected in the intensive care unit. This resistance is frequently due to the acquisition of plasmids containing genes encoding for extended-spectrum beta-lactamases (ESBLs). Furthermore, these mobile elements often carry genes encoding resistance to other drugs such as aminoglycosides. A high risk of poor clinical outcome has been observed in patients infected with ESBL producers receiving third-generation cephalosporins, even if the organism appears susceptible to the antibiotic. For this reason, clinical microbiology laboratories are advised to incorporate specific ESBL detection methodology into routine clinical practice. This should prevent erroneous use of cephalosporins for these infections. Most ESBL producers remain susceptible to carbapenems, and these agents are considered the drugs of choice against ESBL-producing organisms. Unfortunately, there is now an increasing occurrence of carbapenem resistance in the Enterobacteriaceae. In this context, clinical response to new antibiotics (e.g., tigecycline) and old antibiotics (e.g., colistin) with good in vitro activity against ESBL producers needs to be evaluated.
Thieme Connect
Optimizing use of colistin and polymyxin B in the critically ill.
Optimizing use of colistin and polymyxin B in the critically ill.
Semin Respir Crit Care Med. 2007 Dec
Nation RL, Li J.
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
Semin Respir Crit Care Med. 2007 Dec
Nation RL, Li J.
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.
Polymyxin B and colistin are being used increasingly for the treatment of infections caused by gram-negative bacteria that are resistant to all other currently available antibiotics. Although the polymyxins have been available in the clinic for around 50 years, they have never been subjected to the drug development procedures required of modern pharmaceuticals. As a result, the available knowledge on the pharmacokinetics (PK), pharmacodynamics (PD), and toxicodynamics (TD) of the polymyxins is limited. Although significant advances have been made in the last 5 years or so, there are still large gaps in our understanding of the PK, PD, and TD, and of the PK/PD and PK/TD relationships. This information is required to generate recommendations on dosage regimens for various categories of critically ill patients. This paper reviews the growing understanding of the pharmacology of the polymyxins and factors that may impact on the optimization of the dose of these antibiotics in critically ill patients.
Thieme Connect
Optimizing antipseudomonal therapy in critical care
Optimizing antipseudomonal therapy in critical care
Iredell JR.
Centre for Infectious Diseases and Microbiology, University of Sydney/Westmead Hospital, Westmead, Australia.
PSEUDOMONAS AERUGINOSA is a common and important pathogen in the critically ill. It combines environmental hardiness with genomic plasticity and is well adapted to the various niches available in the intensive care unit (ICU). Unresolved arguments over the value of dual versus monotherapy relate primarily to rapidity of killing and to the avoidance of therapeutic failure due to antibiotic resistance. Increasing resistance to conventional antibiotics means that we need to be aware of the factors that promote the success of this pathogen in the ICU, and of emerging alternative strategies. This review focuses on an understanding of the underlying issues and on the practical aspects of prescribing, particularly in the ICU.
Thieme Connect
Iredell JR.
Centre for Infectious Diseases and Microbiology, University of Sydney/Westmead Hospital, Westmead, Australia.
PSEUDOMONAS AERUGINOSA is a common and important pathogen in the critically ill. It combines environmental hardiness with genomic plasticity and is well adapted to the various niches available in the intensive care unit (ICU). Unresolved arguments over the value of dual versus monotherapy relate primarily to rapidity of killing and to the avoidance of therapeutic failure due to antibiotic resistance. Increasing resistance to conventional antibiotics means that we need to be aware of the factors that promote the success of this pathogen in the ICU, and of emerging alternative strategies. This review focuses on an understanding of the underlying issues and on the practical aspects of prescribing, particularly in the ICU.
Thieme Connect
Friday, December 21, 2007
Optimizing Therapy for Vancomycin-Resistant Enterococci (VRE).
Optimizing Therapy for Vancomycin-Resistant Enterococci (VRE).
Semin Respir Crit Care Med. 2007 Dec
Linden PK.
Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Enterococci are gram-positive, facultative bacteria with low intrinsic virulence but capable of causing a diverse variety of infections such as bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection. During the past 2 decades the incidence of hospital-acquired enterococcal infection has significantly risen and is increasingly due to multidrug-resistant strains, primarily to the coacquisition of genetic determinants that encode for the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide resistance. Because enterococci constitute part of the normal colonizing flora, careful clinical interpretation of cultures that grow enterococci is paramount to avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based regimen, or vancomycin in a penicillin-intolerant individual. The need for a bactericidal combination with a cell-wall active agent combined with an aminoglycoside is most supported for native- or prosthetic valve endocarditis but is unproven for the majority of infections due to enterococci. The emergence of vancomycin-resistant enterococci prompted the clinical development of several novel and modified antimicrobial compounds approved for VRE infection (quinupristin-dalfopristin, linezolid) and several approved for non-VRE indications (daptomycin, tigecycline). There is a paucity of comparative clinical trial data with these new agents, although linezolid, based upon its efficacy and tolerability, appears to be the cornerstone of current treatment approaches. Despite a relatively short period of clinical use, enterococcal resistance has now been described for quinupristin-dalfopristin and linezolid and more recently even for daptomycin and tigecycline. Moreover, the optimal treatment of endocarditis due to VRE strains is unknown because, with the exception of daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial measures to treat VRE infection, such as foreign body removal and percutaneous or surgical drainage of close-spaced infection, reduce both the need for and the duration of anti-enterococcal treatment and the emergence of resistance to the newer antimicrobials.
PMID: 18095227 [PubMed - in process]
Semin Respir Crit Care Med. 2007 Dec
Linden PK.
Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Enterococci are gram-positive, facultative bacteria with low intrinsic virulence but capable of causing a diverse variety of infections such as bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection. During the past 2 decades the incidence of hospital-acquired enterococcal infection has significantly risen and is increasingly due to multidrug-resistant strains, primarily to the coacquisition of genetic determinants that encode for the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide resistance. Because enterococci constitute part of the normal colonizing flora, careful clinical interpretation of cultures that grow enterococci is paramount to avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based regimen, or vancomycin in a penicillin-intolerant individual. The need for a bactericidal combination with a cell-wall active agent combined with an aminoglycoside is most supported for native- or prosthetic valve endocarditis but is unproven for the majority of infections due to enterococci. The emergence of vancomycin-resistant enterococci prompted the clinical development of several novel and modified antimicrobial compounds approved for VRE infection (quinupristin-dalfopristin, linezolid) and several approved for non-VRE indications (daptomycin, tigecycline). There is a paucity of comparative clinical trial data with these new agents, although linezolid, based upon its efficacy and tolerability, appears to be the cornerstone of current treatment approaches. Despite a relatively short period of clinical use, enterococcal resistance has now been described for quinupristin-dalfopristin and linezolid and more recently even for daptomycin and tigecycline. Moreover, the optimal treatment of endocarditis due to VRE strains is unknown because, with the exception of daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial measures to treat VRE infection, such as foreign body removal and percutaneous or surgical drainage of close-spaced infection, reduce both the need for and the duration of anti-enterococcal treatment and the emergence of resistance to the newer antimicrobials.
PMID: 18095227 [PubMed - in process]
Perioperative antibiotics and anti-inflammatory agents in cataract surgery.
Perioperative antibiotics and anti-inflammatory agents in cataract surgery.
Curr Opin Ophthalmol. 2008 Jan
Decroos FC, Afshari NA.
Duke University Eye Center, Duke University Medical Center, Durham, North Carolina, USA.
PURPOSE OF REVIEW: Cataract surgery has benefited from great technical advances but no consensus exists as regards optimal perioperative medical management of inflammation and infection prophylaxis.
RECENT FINDINGS: The present article primarily reviews recent evidence about the most advantageous antibiotic regimen to minimize endophthalmitis, and the utility of steroids or nonsteroidal anti-inflammatory drugs (NSAIDs) in management of both postoperative inflammation and cystoid macular edema. Prospective data from Europe supports the efficacy of intracameral cephalosporins in reducing the incidence of endophthalmitis. We compare this with retrospective data from the United States describing a low incidence of endophthalmitis when using fourth-generation fluoroquinolones as chemoprophylaxis. Other studies demonstrate the anti-inflammatory effect of multiple perioperative topical NSAIDs. Further important questions remain, however, including whether NSAIDs exhibit a superior side-effect profile relative to corticosteroids, whether benefit exists to combination NSAID/corticosteroid therapy, as well as whether NSAIDS can reduce the incidence of cystoid macular edema.
SUMMARY: New evidence clarifies the use of intracameral antibiotics, and other studies support a niche anti-inflammatory role for NSAIDs.
PMID: 18090893 [PubMed - in process]
The role of NSAIDs in the management of postoperative ophthalmic inflammation.
Curr Opin Ophthalmol. 2008 Jan
Decroos FC, Afshari NA.
Duke University Eye Center, Duke University Medical Center, Durham, North Carolina, USA.
PURPOSE OF REVIEW: Cataract surgery has benefited from great technical advances but no consensus exists as regards optimal perioperative medical management of inflammation and infection prophylaxis.
RECENT FINDINGS: The present article primarily reviews recent evidence about the most advantageous antibiotic regimen to minimize endophthalmitis, and the utility of steroids or nonsteroidal anti-inflammatory drugs (NSAIDs) in management of both postoperative inflammation and cystoid macular edema. Prospective data from Europe supports the efficacy of intracameral cephalosporins in reducing the incidence of endophthalmitis. We compare this with retrospective data from the United States describing a low incidence of endophthalmitis when using fourth-generation fluoroquinolones as chemoprophylaxis. Other studies demonstrate the anti-inflammatory effect of multiple perioperative topical NSAIDs. Further important questions remain, however, including whether NSAIDs exhibit a superior side-effect profile relative to corticosteroids, whether benefit exists to combination NSAID/corticosteroid therapy, as well as whether NSAIDS can reduce the incidence of cystoid macular edema.
SUMMARY: New evidence clarifies the use of intracameral antibiotics, and other studies support a niche anti-inflammatory role for NSAIDs.
PMID: 18090893 [PubMed - in process]
The role of NSAIDs in the management of postoperative ophthalmic inflammation.
Drugs. 2007
University Hospital Complex of Bordeaux, Peflegrin Hospital, Bordeaux, France. joseph.colin@chu-bordeaux.fr
Recent advances in cataract surgery, such as phacoemulsification, small-incision surgery and advances in foldable intraocular lenses, have resulted in the decrease of physical trauma associated with cataract surgery. The decrease in the physical surgical trauma decreases the release of prostaglandins, which are the main players in postoperative ocular inflammation. However, postoperative inflammation continues to be a cause of patient discomfort, delayed recovery and, in some cases, suboptimal visual results. Left untreated, this inflammation might interfere with patients' rehabilitation and/or contribute to the development of other complications, such as cystoid macular oedema.NSAIDs are commercially available, in topical or systemic formulations, for the prophylaxis and treatment of ocular conditions. Topically applied NSAIDs are commonly used in the management and prevention of non-infectious ocular inflammation and cystoid macular oedema following cataract surgery. They are also used in the management of pain following refractive surgery and in the treatment of allergic conjunctivitis. Despite their chemical heterogeneity, all NSAIDs share the similar therapeutic property of inhibiting the cyclo-oxygenase enzyme. The appeal of using NSAIDs in the treatment of ocular inflammation hinges on the complications associated with corticosteroids, the other commonly used therapy for ophthalmic inflammation.
PMID: 17547472 [PubMed - indexed for MEDLINE]
Saturday, December 15, 2007
Carbapenems: a potent class of antibiotics.
Carbapenems: a potent class of antibiotics.
Expert Opin Pharmacother. 2008 Jan
Nicolau DP.
Hartford Hospital, Center for Anti-Infective Research and Development, 80 Seymour Street, Hartford, Connecticut 06102-5037, USA +1 860 545 3941 ; +1 860 545 3992 ; dnicola@harthosp.org.
The purpose of this review is to assess the relative strengths and weaknesses of individual members of the carbapenem class of antibiotics. Clinical trials and review articles were identified from a Medline search (1979 - July 2006), in addition to, reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and the 12th International Congress on Infectious Disease, and package inserts. Articles in English were reviewed, with emphasis on those containing efficacy or safety data. Carbapenems bind to critical penicillin-binding proteins, disrupting the growth and structural integrity of bacterial cell walls. They provide enhanced anaerobic and Gram-negative coverage as compared with other beta-lactams and their stability against extended-spectrum beta-lactamases (ESBLs) makes them an effective treatment option. The most common adverse effects are infusion-site complications and gastrointestinal distress.
Ertapenem has limited efficacy against non-fermenting, Gram-negative bacteria, restricting its use to community-acquired infections. Imipenem is slightly more effective against Gram-positive organisms and meropenem slightly more effective against Gram-negative organisms. However, both have broad-spectrum activity, including non-fermenting, Gram-negative bacteria. Among non-fermenting, Gram-negatives, resistance to imipenem in particular is increasing. Doripenem is in late-stage clinical development and combines the broad-spectrum coverage of imipenem and meropenem, and more potent activity against Pseudomonas aeruginosa. Due to the increasing challenges represented by ESBLs and multi-drug resistant organisms, the carbapenems are assuming a greater role in the treatment of serious infections.
Imipenem and meropenem are presently available and have been shown to be effective against nosocomial infections.
Doripenem is an investigational carbapenem that has completed Phase III clinical trials and that has the potential to improve on this efficacy and minimize the emergence of resistance to the carbapenem class.
PMID: 18076336 [PubMed - in process]
Expert Opin Pharmacother. 2008 Jan
Nicolau DP.
Hartford Hospital, Center for Anti-Infective Research and Development, 80 Seymour Street, Hartford, Connecticut 06102-5037, USA +1 860 545 3941 ; +1 860 545 3992 ; dnicola@harthosp.org.
The purpose of this review is to assess the relative strengths and weaknesses of individual members of the carbapenem class of antibiotics. Clinical trials and review articles were identified from a Medline search (1979 - July 2006), in addition to, reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and the 12th International Congress on Infectious Disease, and package inserts. Articles in English were reviewed, with emphasis on those containing efficacy or safety data. Carbapenems bind to critical penicillin-binding proteins, disrupting the growth and structural integrity of bacterial cell walls. They provide enhanced anaerobic and Gram-negative coverage as compared with other beta-lactams and their stability against extended-spectrum beta-lactamases (ESBLs) makes them an effective treatment option. The most common adverse effects are infusion-site complications and gastrointestinal distress.
Ertapenem has limited efficacy against non-fermenting, Gram-negative bacteria, restricting its use to community-acquired infections. Imipenem is slightly more effective against Gram-positive organisms and meropenem slightly more effective against Gram-negative organisms. However, both have broad-spectrum activity, including non-fermenting, Gram-negative bacteria. Among non-fermenting, Gram-negatives, resistance to imipenem in particular is increasing. Doripenem is in late-stage clinical development and combines the broad-spectrum coverage of imipenem and meropenem, and more potent activity against Pseudomonas aeruginosa. Due to the increasing challenges represented by ESBLs and multi-drug resistant organisms, the carbapenems are assuming a greater role in the treatment of serious infections.
Imipenem and meropenem are presently available and have been shown to be effective against nosocomial infections.
Doripenem is an investigational carbapenem that has completed Phase III clinical trials and that has the potential to improve on this efficacy and minimize the emergence of resistance to the carbapenem class.
PMID: 18076336 [PubMed - in process]
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