Search

The aim of this study was to investigate the antibacterial activity, antibiotic-associated synergy, and anti-biofilm activity of the ruthenium complex, cis-[RuCl2 (dppb) (bqdi)]2+ (RuNN). RuNN exhi...

The prevalence of multidrug resistant bacterial diseases is a major global health risk. Multidrug resistant bacterial diseases are prevalent, and the need for novel methods of treatment is essential to the preservation of public health. Annually foodborne pathogens cause 1.35 million infections and 26,500 hospitalizations in the United States alone. Foodborne pathogens such as Salmonella spp. are a major threat to public health. Bacteriophages offer a unique method for the treatment of these multidrug resistant bacteria. We studied the infection dynamics of a potential mono-phage therapy of Salmonella typhimurium under various pathophysiological conditions. Furthermore, we determined the resistance dynamics of Salmonella typhimurium against P22 phage treatment. We also determined synergy with antibiotics such as ampicillin and kanamycin. This research helps to further define and show the versatility of bacteriophages as potential novel treatment methods.

The research carried out so far for phage-antibiotic synergy (PAS) differs as regards the technique of modifying the double-layer agar (DLA) method to show the PAS effect on Petri plates, which may contribute to non-uniform research results. Therefore, there is a need to unify the method to effectively detect the PAS effect, at its most basic in vitro test. In this study, bacteriophage T45 and 43 antibiotics belonging to different antibiotic classes were used. Seven different DLA method modifications were tested, in terms of antibiotic addition placement and presence or absence of the base agar. The overall number of phage plaques per plate mainly depended on the antibiotic used. Differences in plaque quantity depended on the type of the DLA method modification. The largest total number of plaques was obtained by the addition of an antibiotic to a bottom agar with the presence of a top agar. This indicates that even though an antibiotic could manifest the PAS effect by a standard disk method, it would be worth examining if the effect is equally satisfactory when applying antibiotics directly into the agar, with regards to using the same bacteriophage and bacterial host.

Combination therapy of bacteriophage and antibiotics offers promise to treat multiple drug resistant bacterial infections through phage antibiotic synergy. However, its usage requires careful assessment as most antibiotics with mechanisms dependent upon inhibiting cell growth through interfering bacterial protein synthesis machinery were found to have an antagonistic effect on phage activity.

The continued rise of antibiotic resistance threatens to undermine the utility of the world’s current antibiotic arsenal. This problem is particularly troubling when it comes to Gram-negative pathogens for which there are inherently fewer antibiotics available. To address this challenge, recent attention has been focused on finding compounds capable of disrupting the Gram-negative outer membrane as a means of potentiating otherwise Gram-positive-specific antibiotics. In this regard, agents capable of binding to the lipopolysaccharide (LPS) present in the Gram-negative outer membrane are of particular interest as synergists. Recently, thrombin-derived C-terminal peptides (TCPs) were reported to exhibit unique LPS-binding properties. We here describe investigations establishing the capacity of TCPs to act as synergists with the antibiotics erythromycin, rifampicin, novobiocin, and vancomycin against multiple Gram-negative strains including polymyxin-resistant clinical isolates. We further assessed the structural features most important for the observed synergy and characterized the outer membrane permeabilizing activity of the most potent synergists. Our investigations highlight the potential for such peptides in expanding the therapeutic range of antibiotics typically only used to treat Gram-positive infections.

Bacteriophage (phage) therapy is a promising approach to combat the rise of multidrug-resistant bacteria. Currently, the preferred clinical modality is to pair phage with an antibiotic, a practice thought to improve efficacy. However, antagonism between phage and antibiotics has been reported, the choice of phage and antibiotic is not often empirically determined, and the effect of the host factors on the effectiveness is unknown. Here, we interrogate phage-antibiotic interactions across antibiotics with different mechanisms of action. Our results suggest that phage can lower the working MIC for bacterial strains already resistant to the antibiotic, is dependent on the antibiotic class and stoichiometry of the pairing, and is dramatically influenced by the host microenvironment., The continued rise in antibiotic resistance is precipitating a medical crisis. Bacteriophage (phage) has been hailed as one possible therapeutic option to augment the efficacy of antibiotics. However, only a few studies have addressed the synergistic relationship between phage and antibiotics. Here, we report a comprehensive analysis of phage-antibiotic interaction that evaluates synergism, additivism, and antagonism for all classes of antibiotics across clinically achievable stoichiometries. We combined an optically based real-time microtiter plate readout with a matrix-like heat map of treatment potencies to measure phage and antibiotic synergy (PAS), a process we term synography. Phage-antibiotic synography was performed against a pandemic drug-resistant clonal group of extraintestinal pathogenic Escherichia coli (ExPEC) with antibiotic levels blanketing the MIC across seven orders of viral titers. Our results suggest that, under certain conditions, phages provide an adjuvating effect by lowering the MIC for drug-resistant strains. Furthermore, synergistic and antagonistic interactions are highly dependent on the mechanism of bacterial inhibition by the class of antibiotic paired to the phage, and when synergism is observed, it suppresses the emergence of resistant cells. Host conditions that simulate the infection environment, including serum and urine, suppress PAS in a bacterial growth-dependent manner. Lastly, two different related phages that differed in their burst sizes produced drastically different synograms. Collectively, these data suggest lytic phages can resuscitate an ineffective antibiotic for previously resistant bacteria while also synergizing with antibiotics in a class-dependent manner, processes that may be dampened by lower bacterial growth rates found in host environments.

Introduction This review summarizes single vs dual antibiotic cement literature, evaluating for synergistic activity with dual antibiotics. Methods A systematic review was performed for literature regarding dual antibiotics in cement, identifying 13 studies to include for review. Results Many in vitro studies reported higher elution from cement and/or improved bacteria inhibition with dual antibiotics, typically at higher dosages with a manual mixing technique. Limited clinical data from hip hemiarthroplasties and spacers demonstrated that dual antibiotics were associated with improved infection prevention and higher intra-articular antibiotic concentrations. Conclusion In addition to broader pathogen coverage, several studies document synergy of elution and increased antibacterial activity when dual antibiotics are added to cement. Limited clinical evidence suggests that dual antibiotic cement may be associated with reduced infection rates.

Increasingly, clinical infections are becoming recalcitrant or completely resistant to antibiotics treatment and multidrug resistance is rising alarmingly. Patients suffering from infections that used to be treated successfully by antibiotic regimens are running out of the treatment options. Bacteriophage (phage) therapy, long practiced in parts of Eastern Europe and the states of the former Soviet Union, is now being reevaluated as a treatment option complementary to and synergistic with antibiotic treatments. We discuss some current studies that have addressed synergistic killing activity between phages and antibiotics, the issues of treatment order and antibiotic class, and point to considerations that will have to be addressed by future studies. Overall, co-treatments with phages and antibiotics promise to extend the utility of antibiotics in current use. Nevertheless, a lot of work, both basic and clinical, remains to be done before such co-treatments become routine options in the hospital setting.

Patients with cystic fibrosis (CF) suffer from chronic bacterial infection of the airways, and many patients are infected with multiresistant bacteria. Combination antibiotic susceptibility tests, or antibiotic synergy tests, are in vitro tests that have been developed to allow clinicians to choose combinations of antibiotics that should be more effective at killing, or inhibiting, multiresistant bacterial pathogens. Only one randomised controlled clinical trial has been performed to determine whether combination antibiotic susceptibility testing leads to an improved clinical outcome for patients with acute pulmonary exacerbations of CF. The results of this clinical trial were disappointing - treatment based on combination antibiotic susceptibility testing was no more effective than treatment based on conventional culture and sensitivity testing. The adoption of antibiotic synergy testing as routine practice for patients with CF would be costly and would not be justified as there is insufficient evidence to suggest that the routine use of these tests improves clinical outcomes.

The emergence of multidrug-resistant (MDR) pathogens is a major cause of infection-related mortality among critically ill patients. The synergistic effect between commonly used antibiotics against difficult to treat nosocomial MDR Gram-negative strains, if present, could provide a viable option as an alternative therapy. The aim of this study was to investigate the potential of antibiotic synergy against MDR A. baumannii, K. pneumonia and P. aeruginosa strains, isolated from critically ill patients in a Greek ICU.

Combination of antibiotics in order to achieve antimicrobial synergy is often necessary in the treatment of infections due to resistant bacterial strains. Therefore, several in-vitro test systems have been developed with the purpose of predicting in-vivo action of antibiotics, and the fractional inhibitory concentration (FIC) index has been used to interpret results obtained in different test systems. Using these systems it seems that only antibiotic synergy in vitro is predictive of the results of treatment. It is therefore of interest to have an in-vivo test system that makes it possible to describe antibiotic interaction in detail. Animal infection models such as the foreign body model system enable the measurement of many parameters at the site of infection, such as bactericidal effect (BE) and antibiotic concentrations. A new calculation of drug interaction is suggested in which the measurements used are the BE and the time during which the MIC is exceeded, for the individual drugs and the combination. This calculation enables us to penetrate into observed antibiotic efficacy in vivo to find out whether an observed high BE is due to real synergy or simply to optimal pharmacokinetics of antibiotics at the site of infection.

We assessed the reproducibility of the microdilution checkerboard method for measuring antibiotic synergy. Five strains of Pseudomonas aeruginosa were tested with four antibiotic combinations by using 10 replicates each. Twenty-five percent of replicate sets gave discordant classification results (i.e., a 7:3 or worse split in categorization). Determination of the individual MICs of each antibiotic alone was excellent; all 10 replicates were within 1 twofold dilution for 95% of the 80 sets of 10 replicates. The microdilution checkerboard method either should not be used or should be used with at least five replicates per determination, with > or = 80% agreement among the replicates required for classification.

▴ Aaron SD, Vandemheen KL, Ferris W, et al . Combination antibiotic susceptibility testing to treat exacerbations of cystic fibrosis associated with multiresistant bacteria: a randomised, double-blind, controlled clinical trial. Lancet2005;366:463–71 [OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Patients with cystic fibrosis (CF) are often colonised with multiresistant organisms. In vitro data suggest that bactericidal activity may result from antibiotic synergy even if species are resistant to individual agents on routine resistance testing. Simultaneously testing the bactericidal activity of two or more antibiotics (multiple combination bactericidal antibiotic testing, MCBT) is one approach that has been suggested to … [1]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DAaron%26rft.auinit1%253DS.%2BD.%26rft.volume%253D366%26rft.issue%253D9484%26rft.spage%253D463%26rft.epage%253D471%26rft.atitle%253DCombination%2Bantibiotic%2Bsusceptibility%2Btesting%2Bto%2Btreat%2Bexacerbations%2Bof%2Bcystic%2Bfibrosis%2Bassociated%2Bwith%2Bmultiresistant%2Bbacteria%253A%2Ba%2Brandomised%252C%2Bdouble-blind%252C%2Bcontrolled%2Bclinical%2Btrial.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252805%252967060-2%26rft_id%253Dinfo%253Apmid%252F16084254%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1016/S0140-6736(05)67060-2&link_type=DOI [3]: /lookup/external-ref?access_num=16084254&link_type=MED&atom=%2Fthoraxjnl%2F60%2F11%2F915.atom [4]: /lookup/external-ref?access_num=000231022300027&link_type=ISI

The in vitro activities of three aminoglycosides [Schering 21420 (a 1N-HAPA derivative of gentamicin B), amikacin and gentamicin] plus carbenicillin or piperacillin were tested against 16 clinical iso

Current methods of measuring bactericidal antibiotic synergy are particularly susceptible to error because of their use of arbitrary endpoints and criteria; their results are not easily tested for statistical significance and the procedures require considerable time and effort. A single-stage method is described in which bacteria are exposed to antibiotics for a short period and then transferred twice to drug-free medium by means of a filter membrane. The results are available the next day in the form of survival counts which can be compared statistically. In an examination of 21 strains of faecal streptococcus exposed to penicillin and gentamicin the bactericidal synergy observed was smoothly variable, a finding with a bearing on the management of infections with this organism, in that the recognition of strains showing an intermediate degree of synergy is possible.

Thirty-two human isolates of enterococci were tested for antibiotic synergy by using penicillin and one of six aminoglycosides. Three methods were used: synergy screen, microdilution checkerboard, and time-kill curves. The synergy screen accurately predicted synergy for gentamicin-penicillin combinations, and this synergy was later confirmed by time-kill curves. The microdilution checkerboard method suffered from inherent variation, and agreement with time-kill curves ranged from 92% (twofold reduction in minimum inhibitory concentration) to 4.2% (fourfold reduction in minimum inhibitory concentration). We suggest that enterococci be screened for synergy (i.e., presence or absence of high-level resistance) by using the criterion of growth or no growth in the presence of 2,000 microgram of an aminoglycoside per ml. The microdilution checkerboard test for synergy is not recommended.