Alternatives For Treatment Of Infections Research Articles

Isolation and in vitro characterization of novel S. epidermidis phages for therapeutic applications.

S. epidermidis is an important opportunistic pathogen causing chronic prosthetic joint infections associated with biofilm growth. Increased tolerance to antibiotic therapy often requires prolonged treatment or revision surgery. Phage therapy is currently used as compassionate use therapy and continues to be evaluated for its viability as adjunctive therapy to antibiotic treatment or as an alternative treatment for infections caused by S. epidermidis to prevent relapses. In the present study, we report the isolation and in vitro characterization of three novel lytic S. epidermidis phages. Their genome content analysis indicated the absence of antibiotic resistance genes and virulence factors. Detailed investigation of the phage preparation indicated the absence of any prophage-related contamination and demonstrated the importance of selecting appropriate hosts for phage development from the outset. The isolated phages infect a high proportion of clinically relevant S. epidermidis strains and several other coagulase-negative species growing both in planktonic culture and as a biofilm. Clinical strains differing in their biofilm phenotype and antibiotic resistance profile were selected to further identify possible mechanisms behind increased tolerance to isolated phages.

Whole-genome sequencing analysis of highly prevalent Salmonella serovars in wild boars from a national park in Sardinia

The study investigated Salmonella prevalence in slaughtered wild boars from Asinara island National Park in Sardinia (Italy). Salmonella isolates were serotyped and the antimicrobial resistance profile was evaluated. Isolates were furthermore characterized with Whole Genome Sequencing. Additional analysis were performed in order to evaluate the microbial hygiene of wild boars carcasses. A total of 306 samples were tested for Salmonella presence, of which n. 270 were from n. 90 slaughtered wild boars and n. 36 were from slaughterhouse environment. Salmonella was detected in 32/90 (35.6%) colon content and 16/90 (17.8%) mesenteric lymph nodes samples. The overall prevalence of Salmonella carriers wild boars, either in colon content and/or lymph nodes, was 42/90 (46.7%) but only one animal was found positive at carcass level. Prevalence was not influenced ( P > 0.05) by the age and the gender of the animals. Eight different Salmonella serotypes were identified between 50 isolates, with the most common ones being Abony and Newport. The sequence analysis showed that S. Abony and S. Newport strains clustered separately from public genomes. This finding refects the origin of the animals from the geographical closed environment of Asinara island. Moreover, sequence analysis showed high similarity between strains belonging to the same serovar. S . Derby and S . Agona strains exhibited phenotypic resistance to fosfomycin and harboured the fosA7 gene. The mean aerobic colony count and Enterobacteriaceae values showed a good hygiene level of the carcasses. This study demonstrated that Salmonella enterica is widespread in wild boar population of Asinara island and could play an important role in transmission to humans. The finding of Salmonella strains resistant to fosfomycin is of primary importance as this drug is used as an alternative treatment for infections caused by multi-drug resistant microorganisms. • Salmonella in wild boar play a role in transmission to humans. • High variability of Salmonella serovars. • High similarity of Salmonella serovars with whole genome sequencing. • Extended sensitivity to antimicrobials. • Fosfomycin resistance encoded by the gene fosA 7 in S. Agona and S. Derby isolates.

Antimicrobial and phytochemical evaluation of Datura Stramonium (Jimsonweed) on selected microorganisms

The purpose of this work was to determine the antibacterial and antifungal activities of Datura stramonium on selected microorganisms, and to evaluate its phytochemical properties. The dry and wet leaves of D. stramonium were collected, extracted using ethanol and water, and assessed for antibacterial and antifungal activities at different concentrations (25mg, 12.5mg, 6.25mg, and 3.12mg) by disc diffusion method. The clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Salmonela typhi, Aspergillus fumigatus and Candida albicans were used. The highest zone of inhibition for bacteria was shown with ethanolic dry extract (11.3±3.4) at 25mg/ml and the lowest with aqueous dry extract (4.0±1.4) at 25mg/ml against Escherichia coli. The highest zone of inhibition for fungi was shown with ethanolic dry extract (10±1.4) at 25mg/ml against Aspergillus fumigatus and the lowest was with ethanolic wet extract (2.0±0.0) at 25mg/ml against Candida albican.The phytochemical analysis result showed the presence of tannin (1.757%), phenol (1.149%), flavonoid (6.325%), alkaloid (8.552%), phytate (2.671%), and hydrogen cyanide (4.175%). The chromatographic analysis showed the presence of over 40 elements with the highest as hydrazine (41%) and methyl hydrogen disulphide (41%). In this study, D. stramonium leaf extracts showed significant antibacterial and antifungal activities due to the presence of the phytochemical and bioactive compounds. This upholds the native utility of this plant to treat bacterial and fungal infections. Conclusively, this plant would serve as treatment alternatives for infections and basis for sources of antimicrobial agent.

Alternatives for the treatment of infections caused by ESKAPE pathogens.

The widespread use of antibiotics as therapeutic agents caused an increase of multidrug resistant bacteria (MDR) appearance. Regarding MDRs, we highlight the Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.., which are the ESKAPE group. New treatment alternatives for infections caused by ESKAPE are under current scientific research. The main suggestions are the use of actinomycetes that produce promising substances with antibiotic activity, the synergistic effect between antimicrobials and peptides, photoinactivation, peptide rich in cationic histidine, association of new antimicrobials; besides the repositioning of drugs already approved for the treatment of other diseases. These selected studies showed that researchers from many countries are focused on the development of effective alternative strategies for the treatment of infections caused by these microorganisms.

Antifungal and anti-biofilm effect of the calcium channel blocker verapamil on non-albicans Candida species.

Candida is a human fungal pathogen that causes a wide range of diseases. Candida albicans is the main etiologic agent in these diseases; however, infections can be caused by non-albicans Candida species. Virulence factors such as biofilm production, which protect the fungus from host immunity and anti-fungal drugs, are important for the infection. Therefore, available antifungal drugs for candidiasis treatment are limited and the investigation of new and effective drugs is needed. Verapamil is a calcium channel blocker with an inhibitory effect on hyphae development, adhesion, and colonization of C. albicans. In this study, we investigated the effect of verapamil on cell viability and its antifungal and anti-biofilm activity in non-albicans Candida species. Verapamil was not toxic to keratinocyte cells; moreover, C. krusei, C. parapsilosis, and C. glabrata were susceptible to verapamil with a minimal inhibitory concentration (MIC) of 1250 μM; in addition, this drug displayed fungistatic effect at the evaluated concentrations. After treatment with verapamil, reduced viability, biomass, and mitochondrial activity were observed in biofilms of the non-albicans Candida species C. krusei, C. glabrata, and C. parapsilosis. These findings highlight the importance of the study of verapamil as an alternative treatment for infections caused by non-albicans Candida species.

Antimicrobial Properties of the Probiotic Strain Bacillus Subtilis 534

The effectiveness of antibiotic therapy is constantly decreasing due to the increasing spread of resistant pathogens. One alternative treatment for infections is the use of probiotics - living microorganisms that contribute to the normalization of the human microbiota. The aim of this study is to determine the antibiotic properties of the strain 534 as the intended basis of its probiotic activity.

Partial two-stage exchange for periprosthetic joint infection after total hip arthroplasty

Objective To evaluate the early stage effects of partial two-stage exchange (PTE) for infection after total hip arthroplasty (THA) in order to improve surgical treatment outcomes. Methods Twelve patients (7 males and 5 females) of infected THA treated by PTE between September 2000 and February 2016 were included with an average of 59 years old (range, 40-74 years old). The femoral stem prosthesis was preserved when we ensured that it was not infected and with well fixation during operation. The acetabular prosthesis was totally replaced. Furthermore, the secondary surgery was performed on patients who were free from infection for at least 3 months. At the follow-up duration, the pelvic X-ray was examined to access the presence of loosening of the prosthesis. The inflammatory index was recorded. Hip function was assessed by the Harris hip score, and the visual analogue score (VAS) and patient's subjective satisfaction were recorded by the questionnaire. Results All of the 12 patients were followed up for a mean of 33.3 months (range, 24-48 months). We achieved a 92% (11/12) success rate. One patient resuffered infection, which was controlled after the second debridement. The preoperative Harris score of 12 patients was 23-57, with an average of 40.83±10.62. All patients had significant improvement in hip function after PTE. The Harris score reached 59.58±4.34 at one month after surgery, and reached 64.58±9.08 after three months and 86.75±4.58 at the last follow-up. There was significantly different when compared with the preoperative Harris score. At the last follow-up, the length difference between the lower limbs was less than 1cm in all patients. Two patients did not complain of pain, while other 10 patients got a VAS score of less than 2 points. The patient's subjective satisfaction rating was 100%. Conclusion PTE could be a valuable alternative treatment for infection after THA. The infection control rate and clinical outcomes are comparable to those of two-stage exchange. Key words: Arthroplasty, replacement, hip; Prosthesis-related infections; Device removal

PCR-Dipstick-Oriented Surveillance and Characterization of mcr-1- and Carbapenemase-Carrying Enterobacteriaceae in a Thai Hospital.

Colistin is used as an alternative therapeutic for carbapenemase-producing Enterobacteriaceae (CPE) infections which are spreading at a very high rate due to the transfer of carbapenemase genes through mobile genetic elements. Due to the emergence of mcr-1, the plasmid-mediated colistin resistance gene, mcr-1-positive Enterobacteriaceae (MCRPEn) pose a high risk for the transfer of mcr-1-carrying plasmid to CPE, leading to a situation with no treatment alternatives for infections caused by Enterobacteriaceae possessing both mcr-1 and carbapenemase genes. Here, we report the application of PCR-dipstick-oriented surveillance strategy to control MCRPEn and CPE by conducting the PCR-dipstick technique for the detection of MCRPEn and CPE in a tertiary care hospital in Thailand and comparing its efficacy with conventional surveillance method. Our surveillance results showed a high MCRPEn (5.9%) and CPE (8.7%) carriage rate among the 219 rectal swab specimens examined. Three different CPE clones were determined by pulsed-field gel electrophoresis (PFGE) whereas only two MCRPEn isolates were found to be closely related as shown by single nucleotide polymorphism-based phylogenetic analysis. Whole genome sequencing (WGS) and plasmid analysis showed that MCRPEn carried mcr-1 in two plasmids types—IncX4 and IncI2 with ~99% identity to the previously reported mcr-1-carrying plasmids. The identification of both MCRPEn and CPE in the same specimen indicates the plausibility of plasmid-mediated transfer of mcr-1 genes leading to the emergence of colistin- and carbapenem-resistant Enterobacteriaceae. The rapidity (<2 h) and robust sensitivity (100%)/specificity (~99%) of PCR-dipstick show that this specimen-direct screening method could aid in implementing infection control measures at the earliest to control the dissemination of MCRPEn and CPE.

Anti-herpes activity of polysaccharide fractions from Stevia rebaudiana leaves

The antiviral potential of natural polysaccharide compounds has been demonstrated, especially against enveloped viruses and members of the Herpesviridae family. Two polysaccharide fractions obtained from Stevia rebaudiana (Bertoni) leaves, that were active against Herpes simplex virus type 1 (HSV-1) were studied to investigate their mode of action. Both polysaccharides - SFW (crude faction) and SSFK (homogeneous alkaline fraction) - exerted antiviral effects on the initial stages of HSV-1 infection by inhibiting viral adsorption and penetration. When added after virus internalization, both fractions decreased plaque size. The effect of the fractions was confirmed by investigating viral glycoprotein expression. Based on the mode of action of the polysaccharides demonstrated in the present work and on their selectivity index, the polysaccharides obtained from S. rebaudiana could be an alternative treatment of infections caused by HSV-1.

Strong antimicrobial activity of xanthohumol and other derivatives from hops (Humulus lupulus L.) on gut anaerobic bacteria.

Anaerobic bacteria, such as Bacteroides fragilis or Clostridium perfringens, are part of indigenous human flora. However, Clostridium difficile represents also an important causative agent of nosocomial infectious antibiotic-associated diarrhoea. Treatment of C.difficile infection is problematic, making it imperative to search for new compounds with antimicrobial properties. Hops (Humulus lupulus L.) contain substances with antibacterial properties. We tested antimicrobial activity of purified hop constituents humulone, lupulone and xanthohumol against anaerobic bacteria. The antimicrobial activity was established against B.fragilis, C.perfringens and C.difficile strains according to standard testing protocols (CLSI, EUCAST), and the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBC) were calculated. All C.difficile strains were toxigenic and clinically relevant, as they were isolated from patients with diarrhoea. Strongest antimicrobial effects were observed with xanthohumol showing MIC and MBC values of 15-107μg/mL, which are close to those of conventional antibiotics in the strains of bacteria with increased resistance. Slightly higher MIC and MBC values were obtained with lupulone followed by higher values of humulone. Our study, thus, shows a potential of purified hop compounds, especially xanthohumol, as alternatives for treatment of infections caused by select anaerobic bacteria, namely nosocomial diarrhoea caused by resistant strains.

Curative or pre-emptive adenovirus-specific T cell transfer from matched unrelated or third party haploidentical donors after HSCT, including UCB transplantations: a successful phase I/II multicenter clinical trial

BackgroundAllogeneic hematopoietic stem cell transplantation (HSCT), the most widely used potentially curable cellular immunotherapeutic approach in the treatment of hematological malignancies, is limited by life-threatening complications: graft versus host disease (GVHD) and infections especially viral infections refractory to antiviral drugs. Adoptive transfer of virus-specific T cells is becoming an alternative treatment for infections following HSCT. We report here the results of a phase I/II multicenter study which includes a series of adenovirus-specific T cell (ADV-VST) infusion either from the HSCT donor or from a third party haploidentical donor for patients transplanted with umbilical cord blood (UCB).MethodsFourteen patients were eligible and 11 patients received infusions of ADV-VST generated by interferon (IFN)-γ-based immunomagnetic isolation from a leukapheresis from their original donor (42.9%) or a third party haploidentical donor (57.1%). One patient resolved ADV infection before infusion, and ADV-VST could not reach release or infusion criteria for two patients. Two patients received cellular immunotherapy alone without antiviral drugs as a pre-emptive treatment.ResultsOne patient with adenovirus infection and ten with adenovirus disease were infused with ADV-VST (mean 5.83 ± 8.23 × 103 CD3+IFN-γ+ cells/kg) up to 9 months after transplantation. The 11 patients showed in vivo expansion of specific T cells up to 60 days post-infusion, associated with adenovirus load clearance in ten of the patients (91%). Neither de novo GVHD nor side effects were observed during the first month post-infusion, but GVHD reactivations occurred in three patients, irrespective of the type of leukapheresis donor. For two of these patients, GVHD reactivation was controlled by immunosuppressive treatment. Four patients died during follow-up, one due to refractory ADV disease.ConclusionsAdoptive transfer of rapidly isolated ADV-VST is an effective therapeutic option for achieving in vivo expansion of specific T cells and clearance of viral load, even as a pre-emptive treatment. Our study highlights that third party haploidentical donors are of great interest for ADV-VST generation in the context of UCB transplantation. (N° Clinical trial.gov: NCT02851576, retrospectively registered).

A putative multi-replicon plasmid co-harboring beta-lactamase genes blaKPC-2, blaCTX-M-14 and blaTEM-1 and trimethoprim resistance gene dfrA25 from a Klebsiella pneumoniae sequence type (ST) 11 strain in China.

The global emergence of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae poses a major public health threat requiring immediate and aggressive action. Some older generation antibiotics, such as trimethoprim, serve as alternatives for treatment of infections. Here, we determined the complete nucleotide sequence of plasmid pHS091147, which co-harbored the carbapenemase (blaKPC-2) and trimethoprim resistance genes (dfrA25) from a Klebsiella pneumoniae sequence type (ST) 11 clone recovered in Shanghai, China. pHS091147 had three replication genes, several plasmid-stability genes and an intact type IV secretion system gene cluster. Besides blaKPC-2 and dfrA25, pHS091147 carried several other resistance genes, including β-lactamase genes blaTEM-1 and blaCTX-M-14, sulphonamide resistance gene sul1, a quinolone resistance gene remnant (ΔqnrB2), and virulence associated gene iroN. Notably, the multidrug-resistance region was a chimeric structure composed of three subregions, which shared strong sequence homology with several plasmids previously assigned in Genbank. To our knowledge, this is the first report of the co-localization of blaKPC-2 and dfrA25 on a novel putative multi-replicon plasmid in a Klebsiella pneumoniae ST11 clone.

USING ESSENTIAL OILS TO COMBAT THE THREAT OF MULTI-DRUG RESISTANT BACTERIA, PSEUDOMONAS AERUGINOSA

&lt;div class="WordSection1"&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The development of antibiotics was a revolutionary scientific discovery and medical advancement that greatly extended the life expectancy of mankind. Through less than 100 y of using antibiotics to treat infectious bacteria, some of these highly adaptive organisms have developed resistance to the drugs. The healthcare field is greatly concerned with the threat of many common infections that have been considered treatable for decades, regaining its ability to be severely fatal; thus, making alternative treatments currently in high demand. This study concentrated on investigating an alternative treatment for a specific gram-negative bacterium, &lt;em&gt;Pseudomonas aeruginosa (P. aeruginosa)&lt;/em&gt;, a resistance-gaining bacteria that commonly infects hospitalized patients with weakened immune systems and/or open wounds.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Prior to the age of modern medicine, human beings relied on nature for medicinal treatments. In our research, we focused on determining the &lt;em&gt;in vitro &lt;/em&gt;efficacy of using the essential oils, cassia and cinnamon bark, their major component, cinnamaldehyde, as well as the major component of manuka honey, methylglyoxal, as an alternative treatment against &lt;em&gt;P. aeruginosa&lt;/em&gt; We tested cassia, cinnamon bark, cinnamaldehyde, and methylglyoxal using the Kirby-Bauer disk diffusion method; the diameter of the zone of inhibition for each treated bacterial sample was measured and compared with the standard antibiotic treatments, tobramycin, and amikacin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;This study showed that the selected essential oils, cinnamaldehyde, and methylglyoxal were as effective or better in inhibiting the growth of &lt;em&gt;P. aeruginosa &lt;/em&gt;compared to the standard aminoglycoside antibiotics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The tested essential oils, cinnamaldehyde, and methylglyoxal may be useful as an alternative treatment for infections caused by &lt;em&gt;P. aeruginosa&lt;/em&gt; and may also provide communities where antibiotics are not readily available, a cost-effective way to treat this infectious disease.&lt;/p&gt;&lt;/div&gt;

An Inactivated Antibiotic-Exposed Whole-Cell Vaccine Enhances Bactericidal Activities Against Multidrug-Resistant Acinetobacter baumannii.

Vaccination may be an alternative treatment for infection with multidrug-resistance (MDR) Acinetobacter baumannii. The study reported here evaluated the bactericidal antibody responses following immunization of mice using an inactivated whole-cell vaccine derived from antibiotic-exposed MDR A. baumannii (I-M28-47-114). Mice inoculated with I-M28-47 (non-antibiotic-exposed control) and I-M28-47-114 showed a high IgG antibody response by day 5 post-inoculation. Sera from mice inoculated with I-M28-47-114 collected on day 30 resulted in 80.7 ± 12.0% complement-mediated bacteriolysis in vitro of the test MDR A. baumannii treated with imipenem, which was a higher level of bacteriolysis over sera from mice inoculated with I-M28-47. Macrophage-like U937 cells eliminated 49.3 ± 11.6% of the test MDR A. baumannii treated with imipenem when opsonized with sera from mice inoculated with I-M28-47-114, which was a higher level of elimination than observed for test MDR A. baumannii opsonized with sera from mice inoculated with I-M28-47. These results suggest that vaccination with I-M28-47-114 stimulated antibody responses capable of mounting high bactericidal killing of MDR A. baumannii. Therefore, the inactivated antibiotic-exposed whole-cell vaccine (I-M28-47-114) has potential for development as a candidate vaccine for broad clearance and protection against MDR A. baumannii infections.

Synergistic effects of sulbactam in multi-drug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a frequently isolated etiologic agent of nosocomial infections, especially in intensive care units. With the increase in multi-drug resistance of A. baumannii isolates, finding appropriate treatment alternatives for infections caused by these bacteria has become more difficult, and available alternate treatments include the use of older antibiotics such as colistin or a combination of antibiotics. The current study aimed to evaluate the in vitro efficacy of various antibiotic combinations against multi-drug resistant A. baumannii strains. Thirty multi-drug and carbapenem resistant A. baumannii strains isolated at the Ankara Training and Research Hospital between June 2011 and June 2012 were used in the study. Antibiotic susceptibility tests and species-level identification were performed using conventional methods and the VITEK 2 system. The effects of meropenem, ciprofloxacin, amikacin, tigecycline, and colistin alone and in combination with sulbactam against the isolates were studied using Etest (bioMérieux) in Mueller-Hinton agar medium. Fractional inhibitory concentration index (FIC) was used to determine the efficacy of the various combinations. While all combinations showed a predominant indifferent effect, a synergistic effect was also observed in 4 of the 5 combinations. Synergy was demonstrated in 43% of the isolates with the meropenem-sulbactam combination, in 27% of the isolates with tigecycline-sulbactam, and in 17% of the isolates with colistin-sulbactam and amikacin-sulbactam. No synergy was detected with the sulbactam-ciprofloxacin combination and antagonism was detected only in the sulbactam-colistin combination (6.66% of the isolates). Antibiotic combinations can be used as an alternative treatment approach in multi-drug resistant A. baumannii infections.

Actualités thérapeutiques : l’abiratérone, le bélatacept, le vandétanib et la fidaxomycine

Among the 35 new molecular entities approved by the FDA in 2011, 17 were particularly notable for their significant contributions to the health of patients, including abiraterone acetate, vandetanib, belatacept and fidaxomicin. Thus, abiraterone acetate, namely Zytiga®, was included as the first in a new class of drugs to treat late-stage prostate cancer. The ability of Zytiga® to prolong survival in these patients was considered as significant because they have few other treatments options and the benefits of Zytiga® outweighed the risks of reported side-effects. Vandetanib, namely Caprelsa®, was also considered as a relevant drug since it represents the first drug approved to treat particularly aggressive medullary thyroid cancer, an orphan disease. Despite huge progress in transplantation, renal transplantation remains a serious problem since patients treated with the calcineurin inhibitors cyclosporine and tacrolimus are at high risk of developing renal injury. With longer follow-up, the novel immunosuppressant belatacept continued to show better renal function compared with a cyclosporine-based regimen, as well as a consistent safety profile and comparable efficacy. It was approved by the Food and Drug Administration in June 2011 for the prophylaxis of organ rejection in adult recipients of a kidney transplant acting by a selective T-cell costimulation blocker given as an infusion. Clostridium difficile is currently the most important cause of infectious diarrhea in the United States. Fidaxomicin, a macrolide antibiotic, was recently approved for treatment of these infections (CDIs). It could be an alternative treatment for infection with C. difficile, with similar efficacy and safety to vancomycin. Fidaxomicin has minimal activity against Bacteroides species, which may be advantageous in maintaining colonization resistance and protecting the gastrointestinal tract from colonization by C. difficile.

Fecal microbiota transplantation as an alternative treatment for infection and inflammation

Fecal microbiota transplantation as an alternative treatment for infection and inflammation

Antimicrobial photodynamic therapy with RLP068 kills methicillin‐resistant Staphylococcus aureus and improves wound healing in a mouse model of infected skin abrasion PDT with RLP068/Cl in infected mouse skin abrasion

Photodynamic therapy (PDT) is an alternative treatment for infections that can kill drug resistant bacteria without damaging host-tissue. In this study we used bioluminescent methicillin-resistant Staphylococcus aureus, in a mouse skin abrasion model, to investigate the effect of PDT on bacterial inactivation and wound healing. RLP068/Cl, a tetracationic Zn(II)phthalocyanine derivative and toluidine blue (TBO) were used. The light-dose response of PDT to kill bacteria in vivo and the possible recurrence in the days post-treatment were monitored by real-time bioluminescence imaging, and wound healing by digital photography. The results showed PDT with RLP068/Cl (but not TBO) was able to kill bacteria, to inhibit bacterial re-growth after the treatment and to significantly accelerate the wound healing process (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).

Bacteriophage: time to re-evaluate the potential of phage therapy as a promising agent to control multidrug-resistant bacteria.

Nowadays the most difficult problem in treatment of bacterial infections is the appearance of resistant bacteria to the antimicrobial agents so that the attention is being drawn to other potential targets. In view of the positive findings of phage therapy, many advantages have been mentioned which utilizes phage therapy over chemotherapy and it seems to be a promising agent to replace the antibiotics. This review focuses on an understanding of phages for the treatment of bacterial infectious diseases as a new alternative treatment of infections caused by multiple antibiotic resistant bacteria. Therefore, utilizing bacteriophage may be accounted as an alternative therapy. It is appropriate time to re-evaluate the potential of phage therapy as an effective bactericidal and a promising agent to control multidrug-resistant bacteria.

Fidaxomicin versus vancomycin for infection with Clostridium difficile in Europe, Canada, and the USA: a double-blind, non-inferiority, randomised controlled trial

Infection with Clostridium difficile is the primary infective cause of antibiotic-associated diarrhoea. We aimed to compare efficacy and safety of fidaxomicin and vancomycin to treat patients with C difficile infection in Europe, Canada, and the USA. In this multicentre, double-blind, randomised, non-inferiority trial, we enrolled patients from 45 sites in Europe and 41 sites in the USA and Canada between April 19, 2007, and Dec 11, 2009. Eligible patients were aged 16 years or older with acute, toxin-positive C difficile infection. Patients were randomly allocated (1:1) to receive oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was clinical cure, defined as resolution of diarrhoea and no further need for treatment. An interactive voice-response system and computer-generated randomisation schedule gave a randomisation number and medication kit number for each patient. Participants and investigators were masked to treatment allocation. Non-inferiority was prespecified with a margin of 10%. Modified intention-to-treat and per-protocol populations were analysed. This study is registered with ClinicalTrials.gov, number NCT00468728. Of 535 patients enrolled, 270 were assigned fidaxomicin and 265 vancomycin. After 26 patients were excluded, 509 were included in the modified intention-to-treat (mITT) population. 198 (91·7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90·6%) of 235 given vancomycin, meeting the criterion for non-inferiority (one-sided 97·5% CI -4·3%). Non-inferiority was also shown for clinical cure in the mITT population, with 221 (87·7%) of 252 patients given fidaxomicin and 223 (86·8%) of 257 given vancomycin cured (one-sided 97·5% CI -4·9%). In most subgroup analyses of the primary endpoint in the mITT population, outcomes in the two treatment groups did not differ significantly; although patients receiving concomitant antibiotics for other infections had a higher cure rate with fidaxomicin (46 [90·2%] of 51) than with vancomycin (33 [73·3%] of 45; p=0·031). Occurrence of treatment-emergent adverse events did not differ between groups. 20 (7·6%) of 264 patients given at least one dose of fidaxomicin and 17 (6·5%) of 260 given vancomycin died. Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin. Optimer Pharmaceuticals.