Comparative activities of antibiotics against intracellular non-typeable Haemophilus influenzae.

Comparative activities of antibiotics against intracellular non-typeable Haemophilus influenzae.
Wien Klin Wochenschr. 2007 Jun

Kratzer C, Graninger W, Macfelda K, Buxbaum A, Georgopoulos A.
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Diseases, Medical University of Vienna, Vienna, Austria, apostolos.georgopoulos@meduniwien.ac.at.

INTRODUCTION: Non-typeable Haemophilus influenzae (NTHi) is a major bacterial pathogen of community-acquired respiratory tract infection and is usually found extracellularly, although studies have revealed that NTHi may possess the ability to invade human epithelial cells where it is then protected against attack by the local immune system and partly against the effect of antibiotics. The aim of the present study was to assess the ability of ampicillin, azithromycin, telithromycin, ciprofloxacin and moxifloxacin, five antibiotics in common clinical use, to kill NTHi within bronchial epithelial cells.

METHODS: Confluent human bronchial epithelial cells were infected with NTHi 77, a particularly invasive clinical strain. Extracellular bacterial cells were killed with gentamicin and the intracellular bacteria were incubated with antibiotics at concentrations of 1 mg/l or 10 mg/l for 4 h or 8 h. Viable intracellular bacteria were counted after lysis of the epithelial cells.

RESULTS: With the exception of ampicillin, all the antibiotics caused significant reduction of intracellular bacteria at concentrations of 10 mg/l and exposure for 4 h or at 1 mg/l for 8 h. At 1 mg/l, moxifloxacin eliminated 94% of intracellular NTHi after 4 h and 98% after 8 h; ciprofloxacin, azithromycin and telithromycin only achieved killing indices below 75 after 4 h but 86-90% killing after 8 h. At 10 mg/l, moxifloxacin, ciprofloxacin, telithromycin and azithromycin were able to achieve 99.7%, 96.3%, 86.7% and 74.7% eradication of intracellular bacteria, respectively, after exposure for 4 h.

CONCLUSION: These results demonstrate the rapid antibacterial efficacy of moxifloxacin against intracellular NTHi in vitro. Moxifloxacin, which combines high extracellular and intracellular activities, could be an important tool in the treatment of recurrent respiratory tract infections.

PMID: 17571234 [PubMed - as supplied by publisher]

Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies.

Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies.

J Antimicrob Chemother. 2007 Jun 7

Vickers AA, O'neill AJ, Chopra I.
Antimicrobial Research Centre and Research Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.

Objectives: Fluoroquinolones and coumarins interfere with the activity of bacterial type II topoisomerase enzymes. We examined the development of resistance to these agents in Staphylococcus aureus and determined the effect of simultaneous topoisomerase IV and DNA gyrase mutations on the biological fitness of the organism.

This work aimed to gain insight into how such mutants might arise and survive in the clinical environment. Methods Spontaneous mutants resistant to fluoroquinolones and coumarins were selected in S. aureus. Resistance mutations were identified by DNA sequencing of PCR amplicons corresponding to the genes encoding topoisomerase IV and DNA gyrase. In vitro fitness of resistant mutants was compared with the antibiotic-susceptible progenitor strain using pair-wise competition assays.

Results: Mutants simultaneously resistant to both a fluoroquinolone and either of the coumarins, novobiocin or coumermycin A1, could not be recovered following a single-step selection. However, mutants concurrently resistant to both classes of antimicrobial could be generated by step-wise selections. These mutants demonstrated reductions in competitive fitness of up to 36%.

Conclusions: Dual-targeting of topoisomerase IV and DNA gyrase enzymes, for example with the combination of a fluoroquinolone and a coumarin agent, could minimize the emergence of resistance to these drugs in S. aureus. However, resistance-associated fitness costs may not be sufficient to limit the survival of mutants with dual resistance, if they arose in the clinical setting.

Antimicrobial Chemotherapy

Antibiotics, Physician outcome judgements, inappropriate treatment

Do physician outcome judgments and judgment biases contribute to inappropriate use of treatments? Study Protocol.

Implement Sci. 2007 Jun 7

Brehaut JC, Poses R, Shojania KG, Lott A, Man-Son-Hing M, Bassin E, Grimshaw J.

ABSTRACT: BACKGROUND: There are many examples of physicians using treatments inappropriately, despite clear evidence about the circumstances under which the benefits of such treatments outweigh their harms. When such over- or under- use of treatments occurs for common diseases, the burden to the healthcare system and risks to patients can be substantial. We propose that a major contributor to inappropriate treatment may be how clinicians judge the likelihood of important treatment outcomes, and how these judgments influence their treatment decisions. The current study will examine the role of judged outcome probabilities and other cognitive factors in the context of two clinical treatment decisions: 1) prescription of antibiotics for sore throat, where we hypothesize overestimation of benefit and underestimation of harm leads to over-prescription of antibiotics; and 2) initiation of anticoagulation for patients with atrial fibrillation (AF), where we hypothesize that underestimation of benefit and overestimation of harm leads to under-prescription of warfarin.

METHODS: For each of the two conditions, we will administer surveys of two types (Type 1 and Type 2) to different samples of Canadian physicians. The primary goal of the Type 1 survey is to assess physicians' perceived outcome probabilities (both good and bad outcomes) for the target treatment. Type 1 surveys will assess judged outcome probabilities in the context of a representative patient, and include questions about how physicians currently treat such cases, the recollection of rare or vivid outcomes, as well as practice and demographic details. The primary goal of the Type 2 surveys is to measure the specific factors that drive individual clinical judgments and treatment decisions, using a 'clinical judgment analysis' or 'lens modeling' approach. This survey will manipulate eight clinical variables across a series of sixteen realistic case vignettes. Based on the survey responses, we will be able to identify which variables have the greatest effect on physician judgments, and whether judgments are affected by inappropriate cues or incorrect weighting of appropriate cues. We will send antibiotics surveys to family physicians (300 per survey), and warfarin surveys to both family physicians and internal medicine specialists (300 per group per survey), for a total of 1,800 physicians. Each Type 1 survey will be two to four pages in length and take about fifteen minutes to complete, while each Type 2 survey will be eight to ten pages in length and take about thirty minutes to complete.

DISCUSSION: This work will provide insight into the extent to which clinicians' judgments about the likelihood of important treatment outcomes explain inappropriate treatment decisions. This work will also provide information necessary for the development of an individualized feedback tool designed to improve treatment decisions. The techniques developed here have the potential to be applicable to a wide range of clinical areas where inappropriate utilization stems from biased judgments.

PMID: 17555586 [PubMed - as supplied by publisher]

Appropriate usage of antibiotics by therapeutic drug monitoring

Appropriate usage of antibiotics by therapeutic drug monitoring

Yakugaku Zasshi. 2007 Jun

Kokubun H, Kimura T, Yago K.
Department of Pharmacy, Kitasato University Hospital.

Aminoglycosides are mainly distributed in the extracellular fluid, so when they are given to neonates who have a large amount of extracellular fluid, their distribution is increased. In our data, the volume of distribution (Vd) of Arbekacin in the neonates was twice that of the adults, 0.54 l/kg. Therefore, the dose per weight of aminoglycosides to the neonates should be increased more than to the adults. In the renal function of the neonates, differentiation of the nephron is completed within 36 weeks after conception, but it is functionally immature. In our data, renal drug excretion increased rapidly in the post-conceptional ages (PCAs) of 34-35 weeks. Consequently, we based the Arbekacin administration schedule for the neonates on the PCAs. There is excellent correlation between serum level of vancomicin (VCM) and dosexserum creatinine (Scr)/weight in the haemodialysis patients, suggesting that we can use weight and Scr to set the VCM administration schedule for these patients. We also established on administration schedule of Teicoplanin for the haemodialysis patients. In this article, we present the TDM analysis result of the antibiotics in our hospital.

PMID: 17541241

[PubMed - in process]

Zymar (Gatifloxacin 0.3%) Shows Excellent Gram-Negative Activity Against Serratia marcescens and Pseudomonas aeruginosa

Zymar (Gatifloxacin 0.3%) Shows Excellent Gram-Negative Activity Against Serratia marcescens and Pseudomonas aeruginosa in a New Zealand White Rabbit Keratitis Model.

Cornea. 2007 Jun

Mah FS,
Romanowski EG,
Kowalski RP,
Yates KA,
Gordon YJ.

From the Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

PURPOSE: Whereas gatifloxacin, a newer fluoroquinolone, was engineered to increase its Gram-positive potency, we assessed whether it still retained significant Gram-negative activity in vivo. Specifically, we compared the efficacy of Zymar (gatifloxacin 0.3%), Ciloxan (ciprofloxacin 0.3%), and fortified tobramycin (14 mg/mL) in the treatment of experimental Gram-negative bacterial infections of Serratia marcescens (SM) and Pseudomonas aeruginosa (PA) in the New Zealand White (NZW) rabbit keratitis model.

METHODS: A total of 30 NZW rabbits each were intrastromally inoculated in both eyes with approximately 1000 CFU of SM and PA. By E-test, the minimum inhibitory concentrations (MICs; mug/mL) for SM were gatifloxacin (0.125), ciprofloxacin (0.047), and tobramycin (1.5), and for PA were gatifloxacin (0.125), ciprofloxacin (0.19), and tobramycin (0.5). After 16 hours, the rabbits were divided into 4 treatment groups: (1) Zymar, (2) Ciloxan, (3) fortified tobramycin, and (4) saline control. One drop was instilled in both eyes every 15 minutes for 5 doses and then every 30 minutes for 14 doses. One hour after the final treatment, the animals were euthanized, and bacterial colony counts from the corneas were determined.

RESULTS: For SM, Zymar and Ciloxan significantly reduced the colony counts compared with tobramycin and saline control. Zymar was more effective than Ciloxan.For PA, all antibiotics reduced equivalently the colony counts compared with the saline control

CONCLUSIONS: The enhanced Gram-positive activity of gatifloxacin is not associated with any decreased Gram-negative activity in vivo. Zymar may prove useful for SM and PA keratitis.

PMID: 17525656 [PubMed - in process]

Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome.

Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome.

Aliment Pharmacol Ther. 2007 Jun

Frissora CL,
Cash BD.
Division of Gastroenterology and Hepatology, Weill Cornell Medical College of Cornell University, New York, NY, USA.

Background

The concept of augmenting the management of irritable bowel syndrome with antibiotics is evolving, and many questions remain regarding this therapy relative to known and hypothesized irritable bowel syndrome pathophysiology. The clinical evidence of small intestinal bacterial overgrowth as an important aetiology of irritable bowel syndrome continues to accumulate. Clinical symptoms of bacterial overgrowth and irritable bowel syndrome are similar; however, a definitive cause-and-effect relationship remains unproven. It is unclear whether motility dysfunction causes bacterial overgrowth or gas products of enteric bacteria affect intestinal motility in irritable bowel syndrome.

Aim

To discusses the efficacy and tolerability of current symptom-directed pharmacotherapies and of antibiotics in the treatment of irritable bowel syndrome. Methods A computerized search of PubMed was performed with search terms 'IBS', 'pharmacotherapy' and 'antibiotics'. Relevant articles were selected, and the reference list of selected articles was reviewed to identify additional references.

Results

Antibiotic treatment benefits a subset of irritable bowel syndrome patients. The non-absorbed antibiotic rifaximin has a favourable safety and tolerability profile compared with systemic antibiotics and demonstrates a therapeutic efficacy comparable with symptom-based irritable bowel syndrome pharmacotherapies.

Conclusion

Rifaximin is the only antibiotic with demonstrated sustained benefit beyond therapy cessation in irritable bowel syndrome patients in a placebo-controlled trial. Whether antibiotics can improve quality of life in patients with irritable bowel syndrome warrants further research.

PMID: 17509095 [PubMed - in process]

Fengycin antibiotics isolated from B-FS01 culture inhibit the growth of Fusarium moniliforme Sheldon ATCC 38932.

Fengycin antibiotics isolated from B-FS01 culture inhibit the growth of Fusarium moniliforme Sheldon ATCC 38932.
FEMS Microbiol Lett. 2007 May 8

Hu LB,
Shi ZQ,
Zhang T,
Yang ZM.
College of Life Sciences, Nanjing Agricultural University, Nanjing, China.

Strain B-FS01, isolated from rape (Brassica napus) stem infected by Slerotinia sclerotiorum and identified as Bacillus subtilis, exhibited predominantly antagonistic activities against Fusarium moniliforme Sheldon ATCC 38932. Antifungal active compounds (AAC) were isolated and purified from the cultures of strain B-FS01 against ATCC 38932. The HPLC/electron spray ionization/collision-induced dissociation mass spectrum of AAC revealed a cluster of fengycin homologues containing fengycins A, fengycins B and a new type of fengycin. Further toxic assay of AAC in vitro against F. moniliforme indicated that AAC could strongly inhibit the growth of both mycelia and spores. In addition, treatment with AAC significantly modified the maize seed infection by ATCC 38932.

PMID: 17490402 [PubMed - as supplied by publisher]

Antibiotic Treatment of the Tick Vector Amblyomma americanum Reduced Reproductive Fitness.

Antibiotic Treatment of the Tick Vector Amblyomma americanum Reduced Reproductive Fitness.

PLoS ONE. 2007 May

Zhong J,
Jasinskas A,
Barbour AG.
Department of Microbiology and Molecular Genetics, Department of Medicine and Pacific-Southwest Center for Biodefense and Emerging Infections, University of California Irvine, Irvine, California, United States of America.

BACKGROUND: The lone star tick Amblyomma americanum is a common pest and vector of infectious diseases for humans and other mammals in the southern and eastern United States. A Coxiella sp. bacterial endosymbiont was highly prevalent in both laboratory-reared and field-collected A. americanum. The Coxiella sp. was demonstrated in all stages of tick and in greatest densities in nymphs and adult females, while a Rickettsia sp. was less prevalent and in lower densities when present.

METHODOLOGY/PRINCIPAL FINDINGS: We manipulated the numbers of both bacterial species in laboratory-reared A. americanum by injecting engorged nymphs or engorged, mated females with single doses of an antibiotic (rifampin or tetracycline) or buffer alone. Burdens of the bacteria after molting or after oviposition were estimated by quantitative polymerase chain reaction with primers and probes specific for each bacterial species or, as an internal standard, the host tick. Post-molt adult ticks that had been treated with rifampin or tetracycline had lower numbers of the Coxiella sp. and Rickettsia sp. and generally weighed less than ticks that received buffer alone. Similarly, after oviposition, females treated previously with either antibiotic had lower burdens of both bacterial species in comparison to controls. Treatment of engorged females with either antibiotic was associated with prolonged time to oviposition, lower proportions of ticks that hatched, lower proportions of viable larvae among total larvae, and lower numbers of viable larvae per tick. These fitness estimators were associated with reduced numbers of the Coxiella sp. but not the Rickettsia sp.

CONCLUSION/SIGNIFICANCE: The findings indicate that the Coxiella sp. is a primary endosymbiont, perhaps provisioning the obligately hematophagous parasites with essential nutrients. The results also suggest that antibiotics could be incorporated into an integrated pest management plan for control of these and other tick vectors of disease.

PMID: 17476327 [PubMed - in process]

Locally Administered Antibiotics for Prophylaxis Against Surgical Wound Infection

Locally Administered Antibiotics for Prophylaxis Against Surgical Wound Infection
The Journal of Bone and Joint Surgery (American). 2007;89:929-933.doi:10.2106/JBJS.F.00919

An in Vivo Study Seth R. Yarboro, BS1, Elyse J. Baum, BS1 and Laurence E. Dahners, MD1
1 Department of Orthopaedics, University of North Carolina at Chapel Hill, CB 7055, Chapel Hill, NC 27599-7055. E-mail address for L.E. Dahners: led@med.unc.edu

Investigation performed at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants of less than $10,000 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

A commentary is available with the electronic versions of this article, on our web site and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).

Background: Currently, the standard for prophylaxis against surgical infection consists of perioperative systemic antibiotics. In this study, we investigated the relative efficacy of various methods of antibiotic delivery for the prevention of surgical wound infections. We hypothesized that sustained release of local antibiotics inside the wound cavity by a drug delivery system would be more effective than systemically administered antibiotics.

Methods: Using a rat model, we inoculated a surgical wound in the quadriceps muscle with 8.0 x 105 colony-forming units of Staphylococcus aureus and then administered one of seven types of treatment: no treatment (control), bacitracin irrigation, calcium sulfate flakes, systemic gentamicin, local aqueous gentamicin, local gentamicin-loaded calcium sulfate flakes, and a combination of local gentamicin-loaded calcium sulfate and systemic gentamicin. The seven treatment groups consisted of ten rats each. To further evaluate a trend, the group treated with systemic gentamicin and the one treated with local gentamicin solution were extended to include twenty-five and twenty-seven rats, respectively. At forty-eight hours postoperatively, specimens from the wounds were obtained for quantitative culture.

Results: The control group, the group treated with bacitracin irrigation, and the one treated with plain calcium sulfate had very high bacterial counts and high mortality rates while the groups treated with gentamicin had low bacterial counts and a 100% survival rate. Local gentamicin was significantly more effective than systemic gentamicin in reducing bacterial counts.

Conclusions: The gentamicin-loaded calcium sulfate flakes did not result in bacterial counts that were significantly lower than those following systemic administration of gentamicin, which refuted our hypothesis. However, gentamicin solution injected directly into the closed wound did result in levels of bacteria that were significantly lower than those following treatment with the systemic gentamicin.

Clinical Relevance: We believe that a high initial concentration of locally applied antibiotic inside the wound effectively kills bacteria present in the wound cavity, where systemic antibiotics have poor penetration, suggesting that this method of antibiotic administration may be a desirable adjunct for prophylaxis against infection in surgical wounds.

The Journal of Bone and Joint Surgery (American)

Antibiotics for Superbacteria

New antibiotics discovered that could beat back superbacteria

Researchers hope to stop virulent form of staph

By LEE BOWMANSCRIPPS HOWARD NEWS SERVICE

Researchers reported Friday they have found four promising antibiotics in chemical families never used before against germs through a novel testing tool that can screen dozens of compounds at once.

The four compounds appear to kill bacteria, at least in a lab dish. Because they probably attack bacteria in different ways, germs should take some time to develop resistant strains.
"These represent whole new classes of antibiotic agents," said Helen Blackwell, lead author of a University of Wisconsin-Madison report on the discoveries published in the journal Chemistry and Biology.

Also, while the most potent compounds were able to kill several dangerous strains of bacteria, the strongest activity was against a highly drug-resistant strain of staph infection (Staphylococcus aureus) that has been plaguing hospitals for years and has recently become common in community settings.

"Strains are emerging that are drug-resistant to all known antibiotics," Blackwell said. "This is not a problem that is going to go away, and actually it's going to get worse. There's a sense of urgency."

The best approach is to be able to hit bacteria with drugs they have not seen before. But finding a potentially useful drug against a broad spectrum of germs is not much different from finding a needle in a haystack.

Blackwell's team designed a way to sift through a lot of hay at once with a device it calls a small-molecule macroarray. The scientists synthesize molecules on a flexible, paperlike sheet, building a compound from the bottom up by adding ingredients to the sheet one at a time.

Each array has dozens of compounds arranged in grids of dots that are about the size of a pencil eraser.

They put each array up against a battery of germs, testing the potency of each compound against various bacterial strains.

The whole process of building and testing a batch of 50 to 300 compounds takes about two days.
Only about 2 percent of the compounds tested using the arrays show any potential against bacteria. And that's just a first step on a long path to drug development.

The next stage is to understand how the compounds work to kill bacteria. "What features of compounds are necessary for activity, and can we improve them?" Blackwell said.

Once the active elements and mechanism are understood, researchers can begin testing doses and evaluating the compounds for safety in animals and eventually humans, if trials go well.

The key is that with the new macroarray, Blackwell said it's possible to see which molecules are active fairly quickly, and "we can gather information on how to improve them fairly quickly."

Seattlepi

Hydrates and solid-state reactivity: A survey of beta-lactam antibiotics.

Hydrates and solid-state reactivity: A survey of beta-lactam antibiotics.

J Pharm Sci. 2007 Apr 23

Hickey MB,
Peterson ML,
Manas ES,
Alvarez J,
Haeffner F,
Almarsson O.

TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, Lexington, Massachusetts 02421.

Crystalline hydrates of hydrolytically susceptible pharmaceuticals are commonly encountered, and are particularly prevalent in the beta-lactam class of antibiotics. In order to rationalize how the apparent chemical incompatibility between water and beta-lactams is reduced through crystallization, a review of the published literature and available structural information on the solid state stability was undertaken. A search in the CSD yielded a total of 32 crystal structures of water-containing beta-lactams which were examined and classified in terms of hydrogen-bonded networks.

In most cases the waters of hydration in the single crystal structures were found to fulfill structural roles and were not sufficiently close in proximity to react with the beta-lactam ring. Published data for the solid-state of several hydrates were also considered. In general, the stability data indicate high thermal stability for the crystalline hydrates. Moreover, even when water molecules are in appropriate proximity and orientation with respect to the beta-lactam moiety for a reaction to occur, the crystalline solids remain stable.

The use of the crystal structure information along with computational modeling suggests that a combination of proximal relationships, steric and mechanistic arguments can explain the observed solid-state stability of crystalline beta-lactam hydrates.

(c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1090-1099, 2007.

PMID: 17455335 [PubMed - as supplied by publisher]

Sequential Therapy Beats Standard Therapy For Helicobacter Pylori

Sequential Therapy Beats Standard Therapy For Helicobacter Pylori

Four antibiotics versus three

Main Category: GastroIntestinal / Gastroentorology News

Article Date: 19 Apr 2007 - 21:00 PDT

In a clinical trial testing two different ways to treat Helicobacter pylori infection (a common cause of stomach ulcers), researchers found that four antibiotics given sequentially cured the infection more often than standard treatment with three antibiotics taken together for 10 days (Article, p. 556). The cure rate for the sequential treatment was 91 percent compared to 71 percent for the standard treatment. The sequential regimen was also more effective than conventional therapy for patients with certain antibiotic-resistant H. pylori bacteria. (The article and editorial are published online. They will be available in the May 1, 2007, print edition of Annals of Internal Medicine.) Note: Annals of Internal Medicine is published by the American College of Physicians.

Dental Work and Antibiotics

Guidelines: Only Some Need Dental Antibiotics

Risks May Outweigh Benefits

POSTED: 9:46 am EDT April 20, 2007

Taking antibiotics before visiting the dentist may do more harm than good, the American Heart Association says.

Some dentists prescribe antibiotics before routine cleanings or extractions to prevent infective endocarditis, an infection of the heart's inner lining or valves. But the AHA now says that is only needed for people at high risk, such as those with artificial valves, a history of endocarditis or serious heart problems.

The doctor who led the work, Walter Wilson, said there is no evidence that the antibiotics prevent infection, and they may increase resistance of bacteria when infections do occur.

A news release said that everyday tooth brushing causes 154,000 times the risk of exposure to bacteria that could cause problems than having a tooth pulled.

Original Post

Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus: Management Principles and Selection of Antibiotic Therapy.

Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus: Management Principles and Selection of Antibiotic Therapy.
Dermatol Clin. 2007 Apr

Elston DM.
Department of Dermatology, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA; Department of Pathology, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA.

Strains of community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as an important group of pathogens. Most infections present as cutaneous abscess and most of these may respond to drainage alone. Sulfonamide and tetracycline antibiotics remain valuable agents for most CA-MRSA infections, but inducible resistance to clindamycin is problematic in some areas. Linezolid, and the newer parenteral antibiotics should be reserved for serious infections.

PMID: 17430753 [PubMed - as supplied by publisher]

Antibiotic-containing collagen for the treatment of bone defects

Antibiotic-containing collagen for the treatment of bone defects
J Biomed Mater Res B Appl Biomater. 2007 Apr 5

Rupprecht S,
Petrovic L,
Burchhardt B,
Wiltfang J,
Neukam FW,
Schlegel KA.
Oral and Maxillofacial Surgery, Friedrich Alexander University Erlangen-Nuremberg, Germany.

Recent studies have explored the use of biodegradable implants that incorporate antibiotics for the treatment of bone infections. In this study, a biodegradable composite containing bovine collagen and teicoplanin (Targobone(R)) was used for the treatment of mandibular nonunion defects. Patients with mandibular nonunion defects subsequent to osteosynthesis were treated with Targobone(R) (n = 9) or with autologous bone grafts (n = 12). Clinical and radiological evaluations were performed preoperatively, immediately postoperatively, and 4 and 24 weeks postoperatively. Bone regeneration was defined relative to the original defect area in the panoramic radiograph by using image analysis software. In the Targobone(R) group, the defect area decreased to 78% (SD +/- 21.8%) of the preoperative area within 4 weeks and to 21% (SD +/- 9.7%) of the preoperative area within 24 weeks. In the autologous bone graft group, the defect area decreased to 69% (SD +/- 32.4%) of the preoperative area within 4 weeks and to 4.7% (SD +/- 5.6%) of the preoperative area within 24 weeks. Thus, Targobone(R) is a promising option for the treatment of bone defects.

2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007.

PMID: 17415766 [PubMed - as supplied by publisher]

Parental knowledge about antibiotic use: results of a cluster-randomized, multicommunity intervention

Parental knowledge about antibiotic use: results of a cluster-randomized, multicommunity intervention
Pediatrics. 2007 Apr

Huang SS,
Rifas-Shiman SL,
Kleinman K,
Kotch J,
Schiff N,
Stille CJ,
Steingard R,
Finkelstein JA.
Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, 133 Brookline Ave, 6th Floor, Boston, MA 02215. sshuang@partners.org.

OBJECTIVE. The goal was to determine the impact of a community-wide educational intervention on parental misconceptions likely contributing to pediatric antibiotic overprescribing.

METHODS. We conducted a cluster-randomized trial of a 3-year, community-wide, educational intervention directed at parents of children <6>

RESULTS. There were 1106 (46%) and 2071 (40%) respondents to the 2000 and 2003 surveys, respectively. Between 2000 and 2003, the proportion of parents who answered >/=7 of 10 knowledge questions correctly increased significantly in both intervention (from 52% to 64%) and control (from 54% to 61%) communities. We did not detect a significant intervention impact on knowledge regarding appropriate antibiotic use in the population overall. In a subanalysis, we did observe a significant intervention effect among parents of Medicaid-insured children, who began with lower baseline knowledge scores.

CONCLUSIONS. Although knowledge regarding appropriate use of antibiotics is improving without additional targeted intervention among more socially advantaged populations, parents of Medicaid-insured children may benefit from educational interventions to promote judicious antibiotic use. These findings may have implications for other health education campaigns.

PMID: 17403840 [PubMed - in process]

Colistin is Effective in the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections in Cancer Patients.

Colistin is Effective in the Treatment of Multidrug-Resistant Pseudomonas aeruginosa Infections in Cancer Patients.
Antimicrob Agents Chemother. 2007 Mar 26

Hachem RY,
Chemaly RF,
Ahmar CA,
Jiang Y,
Boktour MR,
Rjaili GA,
Bodey GP,
Raad II.
The University of Texas M. D. Anderson Cancer Center, Department of Infectious Diseases, Houston, Texas, and Staten Island University Hospital, Staten Island, New York.

Background: The increasing incidence of infections caused by multidrug-resistant Pseudomonas aeruginosa is a worldwide health problem. Because no new anti-pseudomonal agents are expected to be available in the near future, we evaluated the safety and efficacy of colistin, an old drug with bactericidal activity against this organism.

Methods: We collected clinical and demographic data on 95 cancer patients diagnosed with multidrug-resistant P. aeruginosa between January 2001 and January 2004 and treated with either colistin (colistin group) or at least one active anti-pseudomonal agent (a beta-lactam antibiotic or quinolone) (control group). We compared both groups.

Results: Thirty-one patients had been treated with colistin and 64 had been treated with an anti-pseudomonal non-colistin-containing regimen. Compared with the control group, patients in the colistin group had lower median age (52 vs 62 years; P = 0.012), but more likely to have had nosocomial infections (87% vs 64%; P = 0.02). Twenty-five patients (81%) in the colistin group and 40 patients (63%) in the control group had an APACHE II score of >15 (P = 0.074). Overall clinical response rate was 52% in the colistin group versus 31% in the non-colistin group (P = 0.055). Multiple logistic regression analysis showed that those patients treated with colistin were 2.9 times (95% CI: 1.1 to 7.6) more likely to experience a clinical response to therapy than were those in the control group (P = 0.026).

Conclusions: Colistin therapy was at least as effective and as safe as beta-lactam antibiotics and quinolones in the treatment of multidrug-resistant P. aeruginosa infections and, hence, may be a useful or preferred alternative therapy for this infection in cancer patients.

Antimicrobial Agents and Chemotherapy Online

Will The Plague Pathogen Become Resistant To Antibiotics?

Will The Plague Pathogen Become Resistant To Antibiotics?
Mar 21 2007

Science Daily — A small piece of DNA that helps bacteria commonly found in US meat and poultry resist several antibiotics has also been found in the plague bacillus Yersinia pestis, gene sequence researchers report.

The ability to resist many of the antibiotics used against plague has been found so far in only a single case of the disease in Madagascar. But because the same ability is present in other kinds of bacteria from a broad range of livestock, antibiotic resistance could potentially spread to other Y. pestis and also other bacterial pathogens. In a paper published March 21 in the new journal PLoS ONE, the authors say this possibility "represents a significant public health concern."
Genetic ability to disable antibiotics, including multidrug resistance (MDR) sequences, is carried on plasmids, small circles of DNA that are passed easily between bacteria. In this study, the same MDR plasmids found in the Y. pestis from Madagascar were also present in bacteria such as Salmonella and Escherichia coli found in retail samples of beef, pork, chicken, and turkey from several US states.

"What we've done is revealed a mechanism for the acquisition of multidrug resistance in Y. pestis. Obviously, this is an event that might have serious human health consequences. But the sequencing work we've done has given us a way to monitor this plasmid in future," says senior author Jacques Ravel of The Institute for Genomic Research (TIGR) in Rockville, MD.
"The fact that we found a plasmid usually found in Salmonella in Y. pestis is a big problem. It also raises a question about how this happened, how it went from one to the other. But that's a question we cannot answer in this paper," Ravel notes. He urges a new monitoring program to track MDR in Y. pestis.

MDR Salmonella and E. coli have been found in droppings from wild geese, raising the possibility that wild animals might be able to spread MDR far beyond the livestock where it originated, Ravel notes.

"When we identified the first Y. pestis strain resistant to multiple antibiotics, we warned that if this type of strain spreads or emerges again, it would pose a serious health problem" says co-author Elisabeth Carniel, head of the Yersinia Research Unit at the Institut Pasteur in Paris. "The discovery that the multiresistance plasmid acquired by the plague bacillus is widespread in environmental bacteria reinforces this warning".

There have been many plague epidemics in human history, and Y. pestis is believed to have killed an estimated 200 million people. Plague is now regarded as a re-emerging disease, with small outbreaks all over the world. Because plague is often fatal, Y. pestis is a potential agent for bioterrorism. There is no vaccine, but antibiotics are useful for treatment and for preventing the disease's spread. The researchers observe, "Our data imply that high levels of MDR in the causative agent of plague may rapidly evolve naturally, and present a vital biomedical, public health, and biodefense threat."

The paper resulted from an international collaboration among researchers at TIGR, a division of the J. Craig Venter Institute, the Institut Pasteur in Paris, the Agricultural Research Service of the US Department of Agriculture, and the US Food and Drug Administration. This work was performed at the National Institute of Allergy and Infectious Diseases-funded Microbial Sequencing Center managed by TIGR.

Citation: Welch TJ, Fricke WF, McDermott PF, White DG, Rosso M, et al (2007) Multiple Antimicrobial Resistance in Plague: An Emerging Public Health Risk. PLoS ONE 2(3): e309. doi:10.1371/journal.pone.0000309

Science Daily

Prevention of Brain Injury by Daptomycin in Experimental Pneumococcal Meningitis.

Prevention of Brain Injury by the Non Bacteriolytic Antibiotic Daptomycin in Experimental Pneumococcal Meningitis.
Antimicrob Agents Chemother. 2007 Mar 19

Grandgirard D,
Schurch C,
Cottagnoud P,
Leib SL.
Institute for Infectious Diseases, University of Bern, Switzerland, Department of Internal Medicine; and Clinic for Infectious Diseases, University Hospital, Inselspital, Bern, Switzerland.

Background: Bacteriolytic antibiotics cause the release of bacterial components that augment the host inflammatory response which in turn contributes to the pathophysiology of brain injury in bacterial meningitis. In the present study in experimental pneumococcal meningitis, antibiotic therapy with non-bacteriolytic daptomycin vs. bacteriolytic ceftriaxone was evaluated for an effect on inflammation and brain injury.

Methods: Eleven day old rats were injected intracisternally with 1.3 +/- 0.5 x 10(4) colony forming units (cfu) of Streptococcus pneumoniae serotype 3 and randomized for therapy with ceftriaxone (100 mg/kg s.c., n=55) or daptomycin (50 mg/kg s.c., n=56) starting at 18 h after infection. Cerebrospinal fluid was assessed for bacterial count, matrix metalloprotease-9 and TNF-alpha at different time intervals after infection. Cortical brain damage was evaluated at 40 h after infection.

Results: Daptomycin vs. ceftriaxone cleared bacteria more efficiently from the CSF within two hours after initiation of therapy (log10 3.6+/-1.0 vs. log10 6.3+/-1.4 cfu/ml, P<0.02),>

Conclusion: Compared to ceftriaxone, daptomycin cleared bacteria more rapidly from the CSF and caused less CSF inflammation. This combined effect provides an explanation for the observation that daptomycin prevented the development of cortical brain injury in experimental pneumococcal meningitis.

Further research is needed to investigate whether non-bacteriolytic antibiotic therapy with Daptomycin represents an advantageous alternative over current bacteriolytic antibiotics for the therapy of pneumococcal meningitis.

PMID: 17371820 [PubMed - as supplied by publisher]

Amikacin-induced nephropathy: is there any protective way?

Amikacin-induced nephropathy: is there any protective way?
Ren Fail. 2007

Kaynar K,
Gul S,
Ersoz S,
Ozdemir F,
Ulusoy H,
Ulusoy S.
Department of Nephrology, School of Medicine, Karadeniz Technical University.

Amikacin is a commonly used antibacterial drug that can cause significant nephrotoxic effects in both humans and experimental animals. It has been reported that one mechanism of the toxic effects of aminoglycoside antibiotics are the result of oxidative reactions. The aim of this study is to examine the effects of N-acetylcysteine, a thiol-containing antioxidant, on renal function (serum creatinine) and morphology (renal tubular damage) in mice subjected to amikacin-induced nephrotoxicity. A total of 32 mice were equally divided into four groups that were injected with either saline, amikacin (1.2g/kg intraperitoneally), N-acetylcysteine (150mg/kg intraperitoneally for three days) plus amikacin (1.2 g/kg intraperitoneally on the third day as a single dose), or N-acetylcysteine (150mg/kg intraperitoneally).

Amikacin administration led to granulovacuolar tubular degeneration in light microscopic examination and myeloid bodies, mitochondrial electron-dense material deposition, and mitochondrial swelling in the proximal tubule epithelium in the electron microscopic evaluation. N-acetylcysteine administration before amikacin injection caused significant decreases in myeloid body and mitochondrial swelling and granulovacuolar tubular degeneration formation. Serum creatinine levels did not change as a result of any treatment.

The results show that N-acetylcysteine has a protective effect on nephrotoxicity induced by amikacin. Higher doses of amikacin should be tried to observe biochemical effects.

Meta Press

Gentamicin-loaded bioresorbable films for prevention of bacterial infections associated with orthopedic implants.

Gentamicin-loaded bioresorbable films for prevention of bacterial infections associated with orthopedic implants.
J Biomed Mater Res A. 2007 Mar 5

Aviv M,
Berdicevsky I,
Zilberman M.
Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv 69978, Israel.

Adhesion of bacteria to biomaterials and the ability of many microorganisms to form biofilms on foreign bodies are well-established as major contributors to the pathogenesis of implant-associated infections. Treatment of bone infection remains problematic, due to the difficulty of systemically administered antibiotics to locally penetrate bone. The current research addresses this issue by focusing on the development and study of novel gentamicin-loaded bioresorbable films designed to serve as "coatings" for fracture fixation devices and prevent implant-associated infections.

Poly(L-lactic acid) and poly (D,L-lactic-co-glycolic acid) films containing gentamicin were developed through solution processing. The effects of polymer type, drug content, and processing conditions on the drug release profile were studied with respect to film morphology. The examined films generally exhibited a burst effect followed by a moderate approximately constant rate of release. The drug contents in the surrounding medium exceeded the required minimal effective concentration.

Various gentamicin concentrations that were released from the films with time exhibited efficacy against bacterial species known to be involved in orthopedic infections. The developed systems can be applied on the surface of any metallic or polymeric fracture fixation device, and may therefore comprise a significant contribution to the field of orthopedic implants.

Keywords:
bioresorbable films • poly(lactic acid) • poly(D,L-lactic-co-glycolic acid) • gentamicin • controlled drug delivery

2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007.

Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.

Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide.

J Antimicrob Chemother. 2007 Mar 2;

Musher DM,
Logan N,
Mehendiratta V,
Melgarejo NA,
Garud S,
Hamill RJ.
Medical Service (Infectious Disease Section), Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.

Objectives Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. Methods In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >/=14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. Results Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). Conclusions Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.

PMID: 17337513 [PubMed - as supplied by publisher]