Antibiotics for the treatment of hepatic encephalopathy.

Feb 2013

Patidar KR, Bajaj JS.

Source

Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University and McGuire VA Medical Center, 1201 Broad Rock Boulevard, Richmond, VA, USA.

Abstract

The treatment of hepatic encephalopathy (HE) is complex and therapeutic regimens vary according to the acuity of presentation and the goals of therapy. Most treatments for HE rely on manipulating the intestinal milieu and therefore antibiotics that act on the gut form a key treatment strategy. Prominent antibiotics studied in HE are neomycin, metronidazole, vancomycin and rifaximin. For the management of the acute episode, all antibiotics have been tested. However the limited numbers studied, adverse effects (neomycin oto- and nephrotoxicity, metronidazole neurotoxicity) and potential for resistance emergence (vancomycin-resistant enterococcus) has limited the use of most antibiotics, apart from rifaximin which has the greatest evidence base. Rifaximin has also demonstrated, in conjunction with lactulose, to prevent overt HE recurrence in a multi-center, randomized trial. Despite its cost in the US, rifaximin may prove cost-saving by preventing hospitalizations for overt HE. In minimal/covert HE, rifaximin is the only systematically studied antibiotic. Rifaximin showed improvement in cognition, inflammation, quality-of-life and driving simulator performance but cost-analysis does not favor its use at the current time. Antibiotics, especially rifaximin, have a definite role in the management across the spectrum of HE.

PubMed

Perioperative Antibiotic Use for Spinal Surgeries in US Children's Hospitals.

Jan 2013 

McLeod LM, Keren R, Gerber J, French B, Song L, Sampson NR, Flynn J, Dormans JP.

Source

1Department of General Pediatrics, Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, PA 2Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 3Division of Pediatric Infectious Diseases, Children's Hospital of Philadelphia, Philadelphia, PA 4Division of Orthopaedic Surgery, Children's Hospital of Philadelphia, Philadelphia, PA.

Abstract

ABSTRACT: Study Design: Retrospective cohort study using the Pediatric Health Information Systems (PHIS) database.

Objective: To describe longitudinal patterns of prophylactic antibiotic use and determinants of antibiotic choice for spinal fusion surgeries performed at US children's hospitals.Summary of Background Data: Surgical Site Infections (SSIs) account for a significant proportion of post-spinal surgery complications, particularly among children with complex conditions such as neuromuscular disease. Antimicrobial prophylaxis with intravenous (IV) cefazolin or cefuroxime has been a standard practice, but postoperative infections caused by organisms resistant to these antibiotics are increasing in prevalence. Studies describing the choice of antibiotic prophylaxis for pediatric spinal surgery are lacking.

Methods: We included children 6 months to 18 years of age discharged from 37 US children's hospitals between January 1, 2006 - June 30, 2009 with 1) an ICD9-CM procedure code indicating a spinal fusion and 2) combinations of diagnosis codes indicating adolescent idiopathic scoliosis (AIS, n = 5,617) or neuromuscular scoliosis (NMS, n = 3,633). After identifying antibiotics ordered on the operative day, we described variation in broad-spectrum antibiotic use over time, and measured associations between patient/surgery characteristics and antibiotic choice.

Results: Prophylactic antibiotic choice varied across hospitals and over time. Broad-spectrum antibiotics were used in 37% of AIS and 52% of NMS operations. Seven (19%) hospitals used broad spectrum coverage for greater than 80% of all cases. For NMS procedures, broad-spectrum antibiotic use was associated with patient characteristics known to be associated with high SSI risk. Use of vancomycin and broad gram-negative agents increased over time.

Conclusion: Broad-spectrum antimicrobial prophylaxis varied across hospitals, and was often associated with known risk factors for SSI. These results highlight the need for future studies comparing the effectiveness of various prophylaxis strategies, particularly in high risk subgroups. This research can inform the development of best practice for SSI prevention in spinal fusion procedures.

PubMed

Use of antibacterial agents in the neonate: 50 years of experience with vancomycin administration.

Nov 2012

Jacqz-Aigrain E, Zhao W, Sharland M, van den Anker JN.

Source

Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Department of Paediatric Pharmacology and Pharmacogenetics, Hôpital Robert Debré, AP-HP, Paris, France; Clinical Investigation Center CIC9202, INSERM, Paris, France. Electronic address: evelyne.jacqz-aigrain@rdb.aphp.fr.

Abstract

Neonatal sepsis, classified as either early or late onset, has specific pathogen distribution and infection rates in the different neonatal age groups. It is a major cause of mortality and morbidity and administration of antibiotics is urgently required for suspected or proven infection. Vancomycin is the first choice treatment of late onset sepsis due to resistant staphylococci. 

Although it has been used for more than 50 years, prescription remains a challenge in neonatal intensive care units for many reasons, including: high pharmacokinetic variability, numerous presentations, lack of consensus on dosing regimen and therapeutic drug monitoring. In addition, recent concerns about the increase in minimal inhibition concentration and other more generic problems have prompted reappraisal of the rational use of vancomycin. 

This article highlights the goal of optimising vancomycin therapy in the neonate and discusses future research directions. Specific attention is given to dosing optimisation of vancomycin to avoid resistance and maximise the likelihood of achieving the therapeutic target. Modelling and simulation approaches have clear advantages in dosing optimisation of antimicrobial agents in the neonate. Neonatologists and paediatric pharmacologists should work closely together to achieve this goal.

PubMed

Electrical signals guided entrapment and controlled release of antibiotics on titanium surface.

Oct 2012

Shi X, Wu H, Li Y, Wei X, Du Y.

Source

Department of Environmental Science, School of Resource and Environmental Science, Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key Laboratory, Wuhan University, Wuhan 430079, China. shixwwhu@163.com.

Abstract

Electrical signals are used to trigger the entrapment and release of antibiotics on the surface of titanium plate. The entrapment of antibiotics relies on the electrochemically induced pH gradient generated at the titanium surface that allows the gelation of an aminopolysaccharide chitosan and codeposition of vancomycin, a common antibiotic, within chitosan gel. The release of vancomycin is controlled by an anodic signal imposed to the titanium plate that causes a pH decrease and erosion of chitosan gel. We show that the on demand entrapment and release of vancomycin at the surface of titanium plate is fundamentally altered and controlled by voltage. We expect that this rapid, mild and facile electrochemical process forantibiotics loading and release will find applications in controlled drug release from titanium implants.

PubMed

Assessment of antibiotic resistance in probiotic strain Lactobacillus brevis KB290.

Assessment of antibiotic resistance in probiotic strain Lactobacillus brevis KB290.

J Food Prot. 2009 Sep

Fukao M, Tomita H, Yakabe T, Nomura T, Ike Y, Yajima N.

Probiotics Research Department, Research Institute, Kagome Company, Limited, 17 Nishitomiyama, Nasushiobara, Tochigi, 329-2762, Japan. Masanori_Fukao@kagome.co.jp

Our purpose was to investigate the safety of the probiotic strain Lactobacillus brevis KB290. The European Qualified Presumption of Safety (QPS) evaluation approach was applied to the strain. We determined the strain's antibiotic resistance, verified it at the genetic level, and determined whether it could be transferred to intestinal microflora. Of 14 antibiotics tested, 11 showed MICs within the limits of the QPS criteria. However, the L. brevis KB290 MICs of ciprofloxacin (a fluoroquinolone), tetracycline, and vancomycin were two, four, and eight times, respectively, the breakpoint MICs suggested by the European Scientific Committee on Animal Nutrition, and the MIC of tetracycline was eight times the breakpoint MIC suggested by the European Scientific Panel on Additives and Products or Substances Used in Animal Feed. Using analysis of gapped-genome sequences, we found no known transferable determinants for tetracycline or vancomycin resistance, and we found no mutations in the quinolone resistance-determining regions of the genes encoding GyrA or ParC for ciprofloxacin resistance associated with insertion sequences, integrons, or transposons. These data were confirmed by using PCR primers specific for the respective genes. We assessed the transferability of the resistance traits in conjugation experiments with enterococci and obtained no transconjugants, strongly suggesting that the resistance traits were not transferable. This study demonstrated that the antibiotic resistance observed in L. brevis KB290 was due not to dedicated mechanisms but to intrinsic resistance. According to the QPS criteria, these results provide safety assurance for the ongoing use of L. brevis KB290 as a probiotic.

PMID: 19777895 [PubMed - in process]

Comparative antibacterial effects of daptomycin, vancomycin and teicoplanin studied in an in vitro pharmacokinetic model of infection.

Comparative antibacterial effects of daptomycin, vancomycin and teicoplanin studied in an in vitro pharmacokinetic model of infection
J Antimicrob Chemother. 2009 Sep 16

Bowker KE, Noel AR, Macgowan AP.
Bristol Centre for Antimicrobial Research and Evaluation (BCARE), Department of Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.

* Corresponding author. Tel: +44-(0)1179-9595654; Fax: +44-(0)117-9593217; E-mail: karen.bowker@nbt.nhs.uk

Objectives
To compare the antibacterial effects (ABEs) of the free (f) drugs daptomycin, vancomycin and teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), using high and low inocula in a pharmacokinetic in vitro model. To determine the daptomycin fAUC/MIC ratio for a static effect and 3 log reduction in viable count and relate this target to the clinical breakpoint.

Methods
Five clinical MRSA isolates held at Southmead Hospital were used (SMH 15841, SMH 40289, SMH 40275, SMH 33922 and SMH 33024) together with a VRSA isolate (SMH 19898); inocula of 10(6) and 10(8) cfu/mL were used. Daptomycin (6 mg/kg once daily), vancomycin (1 g twice daily) and teicoplanin (400 mg once daily) regimens were simulated. ABEs were measured using the 24 h area-under-the-bacterial kill curve (AUBKC) and log change in viable count at 24 h (Delta24). For daptomycin, dose escalation was used to determine the relationship between ABE and AUC/MIC.

Results
Daptomycin was bactericidal against the MRSA strains. Daptomycin and vancomycin were active against the VRSA strain; teicoplanin had a static effect. The higher inoculum reduced the ABEs. Analysis of variance (ANOVA) indicated that daptomycin had a superior ABE to teicoplanin and vancomycin. Daptomycin fAUC/MIC was related to AUBKC and Delta24; the fAUC/MIC ratios for a static effect and 1 log and 3 log drop were 37.2 +/- 16.5, 40.6 +/- 17.8 and 49.8 +/- 19.2, respectively.

Conclusions
These data define the fAUC/MIC sizes for daptomycin for bacteriostatic and bactericidal ABEs and indicate that a 6 mg/kg dose of daptomycin is superior to vancomycin and teicoplanin against MRSA and VRSA strains.

Antimicrobial Chemotherapy

Daptomycin in bone and joint infections: a review of the literature.

Daptomycin in bone and joint infections: a review of the literature.

Arch Orthop Trauma Surg. 2008 Nov 7

Rice DA, Mendez-Vigo L.
St. Joseph's/Candler Health System, Savannah, GA, USA.

INTRODUCTION: To review the pharmacology, pharmacokinetics, efficacy, and safety of daptomycin, a novel antibiotic for the treatment of bone and joint infections, a literature search of relevant articles was conducted.

MATERIALS AND METHODS: A PubMed/MEDLINE search (1990-April 2008) to identify relevant English-language literature was conducted. Search terms included bone and joint infection, osteomyelitis, daptomycin, and methicillin-resistant Staphylococcus aureus (MRSA). Additional articles were identified by reviewing the bibliographies of articles cited. Programs and abstracts from infectious disease meetings were searched, and prescribing information of antibiotics indicated for bone and joint infections consulted. All articles identified from data sources published in English were evaluated.

RESULTS: Caused primarily by Gram-positive pathogens such as S. aureus and, to a lesser extent, Enterococcus faecalis, bone and joint infections are difficult to treat successfully. Surgical intervention and prolonged courses of antibiotics are frequently required, and failure of first-line antibiotic therapy is common. The emergence of S. aureus strains with reduced susceptibility to vancomycin, the longstanding gold standard for bone and joint infections, has complicated the clinical scenario. Few randomized trials comparing the efficacy of different antibiotics for bone and joint infections exist. Daptomycin, a novel intravenous lipopeptide antibiotic, has shown potent in vitro activity against a broad spectrum of Gram-positive bacteria, including many resistant pathogens commonly associated with bone and joint infections such as MRSA and vancomycin-resistant E. faecalis. Early clinical investigation of daptomycin in bone and joint infections unresponsive to antibiotics, such as vancomycin, has found a cure rate of approximately 80%, with a low incidence of adverse events and drug resistance.

CONCLUSION: Further studies are warranted to determine if limited clinical evidence, described in individual case reports and a daptomycin-specific retrospective registry, suggests daptomycin is a promising option for patients with bone and joint infections such as MRSA osteomyelitis.

Springerlink

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

Int J Artif Organs. 2007 Sep

Presterl E, Lassnigg A, Eder M, Reichmann S, Hirschl AM, Graninger W.
Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna - Austria and Institute of Hygiene and Medical Microbiology, Division of Clinical Microbiology, Medical University of Vienna, Vienna - Austria.

Background: Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis.

Methods and Results: Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05).>

Conclusions: In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.

PMID: 17918125 [PubMed - as supplied by publisher]