Tuesday, September 29, 2009
Retapamulin: a review of its use in the management of impetigo and other uncomplicated superficial skin infections.
Monday, September 28, 2009
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]
Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston.
Bacterial infection is the most common complication of chemotherapy-induced neutropenia particularly in patients with hematologic malignancies. Bacterial infections predominate during the initial phases of neutropenic episodes. The spectrum of bacterial infection continues to evolve globally and locally at the institutional level, as do patterns of antimicrobial susceptibility/resistance. These trends are often associated with local treatment practices (eg, use of antimicrobial prophylaxis, open versus restricted formularies, clinical pathways and/or guidelines) and have a significant effect on the nature of empiric antimicrobial therapy. Increasing rates of resistance among gram-positive and gram-negative bacteria are posing new therapeutic challenges. These challenges can to some extent be overcome by new drug development. Many novel agents for the treatment of resistant gram-positive infections have been developed and are being evaluated in clinical trials. Newer agents for the treatment of Clostridium difficile associated diarrhea are also in the pipeline. Far fewer options to treat multi-drug resistant gram-negative infections exist, and new drug development is lagging behind. Consequently, the judicious use of currently available agents is essential. This is best achieved by the development of multidisciplinary antibiotic stewardship teams that gather baseline data, make recommendations for appropriate antimicrobial usage, and provide monitoring and feedback services to clinical care providers. Along with strict adherence to infection control policies, antimicrobial stewardship provides the best strategies for the management of infectious complications in patients with hematologic malignancies and other high-risk settings.
Monday, September 21, 2009
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: firstname.lastname@example.org
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.
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.
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.
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.
Sunday, September 20, 2009
J Infect Dev Ctries. 2009 Mar
Tunger O, Karakaya Y, Cetin CB, Dinc G, Borand H.
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey. email@example.com
BACKGROUND: Development of resistance to antimicrobial agents and increase of cost as the result of unnecessary and inappropriate use of antibiotics has become a global health problem. Therefore many strategies, which are aimed at optimizing antibiotic therapy, have been developed until now. In Turkey, an antibiotic restriction policy as a governmental solution was applied to decrease the antibiotic use and especially costs by Ministry of Health in 2003. The aim of this study is to evaluate the rational antibiotic use and the impact of the implementation of new restriction policy, with their reinforcement by infectious disease specialist, on the hospital wide use of antibiotics.
METHODOLOGY: The data of the inpatients received antibiotics (n=495) during January-June 2006 were compared with our previous study performed by the same methodology before the restriction policy in 1998. In both studies, prospective active daily surveillance of patients was performed by three infectious disease specialists. The appropriateness of antibiotic therapy was determined using the criteria described by Kunin and Jones. The data were analyzed by using SPSS for Windows.
RESULTS: Thirty-seven patients were treated for burn cellulitis, 26 (70%) of whom were treated initially with continuous-infusion oxacillin. Other initial antibiotics were chosen because of concomitant infections, penicillin allergy, or development of cellulitis during treatment with a beta-lactam antibiotic. Oxacillin treatment was successful in 19 patients (73%). Success required an average of 5.16 days, with 1.53 days required for fever resolution and 0.89 days for resolution of leukocytosis. Seven patients who did not respond rapidly were switched to intravenous vancomycin an average of 2.4 days after starting oxacillin, leading to a 100% success rate. There were no deaths, and only one suspected case of allergic reaction to oxacillin. In eleven patients treated with other antibiotics, the success rate was 75%. Success with these drugs required a longer treatment course of 6.45 days. Leukocytosis resolved significantly more slowly at 4.45 days -p equals 0.02-, and fever resolution was also slower at 3.18 days.
CONCLUSIONS: Continuous-infusion oxacillin was successful in the treatment of 73% of patients, a success rate that might have been higher with clinical patience, and leukocytosis resolved faster than with other antibiotics. Failure of continuous-infusion oxacillin can be managed without clinical consequence by conversion to intravenous vancomycin.
Thursday, September 17, 2009
Mol Biosyst. 2009 Oct;
Lopez AI, Reins RY, McDermott AM, Trautner BW, Cai C.
Department of Chemistry, University of Houston, Houston, TX, USA. firstname.lastname@example.org.
We have investigated the antibacterial activity and cytotoxicity of a series of amino-terminated poly(amidoamine) (PAMAM) dendrimers modified with poly(ethylene glycol) (PEG) groups. The antibacterial activity of the PAMAM dendrimers and their derivatives against the common ocular pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, was evaluated by their minimum inhibitory concentrations (MICs). For the unmodified third and fifth generation (G3 and G5) amino-terminated dendrimers, the MICs against both P. aeruginosa and S. aureus were in the range of 6.3-12.5 mug mL(-1), comparable to that of the antimicrobial peptide LL-37 (1.3-12.5 mug mL(-1)) and within the wide range of 0.047-128 mug mL(-1) for the fluoroquinolone antibiotics. PEGylation of the dendrimers decreased their antibacterial activities, especially for the Gram-positive bacteria (S. aureus). The reduction in potency is likely due to the decrease in the number of protonated amino groups and shielding of the positive charges by the PEG chains, thus decreasing the electrostatic interactions of the dendrimers with the negatively-charged bacterial surface. Interestingly, localization of a greater number of amino groups on G5 vs. G3 dendrimers did not improve the potency. Significantly, even a low degree of PEGylation, e.g. 6% with EG(11) on G3 dendrimer, greatly reduced the cytotoxicity towards human corneal epithelial cells while maintaining a high potency against P. aeruginosa. The cytotoxicity of the PEGylated dendrimers to host cells is much lower than that reported for antimicrobial peptides. Furthermore, the MICs of these dendrimers against P. aeruginosa are more than two orders of magnitude lower than other antimicrobial polymers reported to date. These results motivate further exploration of the potential of cationic dendrimers as a new class of antimicrobial agents that may be less likely to induce bacterial resistance than standard antibiotics.