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A two pulse drug delivery system for amoxicillin: An attempt to counter the scourge of bacterial resistance against antibiotics
Bearing in mind the present scenario of the increasing biological tolerance of bacteria against antibiotics, a time controlled two pulse dosage form of amoxicillin was developed. The compression coating inlay tablet approach was used to deliver the drug in two pulses to different parts of the GIT after a well defined lag time between the two releases. This was made possible by formulating a core containing one of the two drug fractions (intended to be delivered as the second pulse), which was spray coated with a suspension of ethyl cellulose and a hydrophilic but water insoluble agent as a pore former (microcrystalline cellulose). Coating of up to 5 % (m/m) was applied over the core tablet, giving a corresponding lag of 3, 5, 7 and 12 h. Increasing the level of coating led to retardation of the water uptake capacity of the core, leading to prolongation of the lag time. Microcrystalline cellulose was used as a hydrophilic but water insoluble porosity modifier in the barrier layer, varying the concentration of which had a significant effect on shortening or prolongation of the lag time. This coated system was further partially compression coated with the remaining drug fraction (to be released as the first immediate release pulse) with a disintegrant, giving a final tablet. The core tablet and the final two pulse inlay tablet were further investigated for their in vitro performance.
Alcohol based solutions are among the most convenient and wide spread aid in the prevention of nosocomial infections. The current study followed the efficacy of several types and isomers of alcohols on different bacterial species. Seven alcohols (ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl alcohol, and ethylene glycol) were used to evaluate their minimal inhibitory and bactericidal effects by microdilution method on bacteria that express many phenotypical characteristics: different cell-wall structure (Gram positive/negative bacteria), capsule production (Klebsiella pneumoniae), antibiotic resistance (MRSA vs MSSA) or high environmental adaptability (Pseudomonas aeruginosa). Results: The best inhibitory effect was noticed for n-propyl, followed by iso-propyl, n-butyl, and iso-butyl alcohols with equal values. Ethylene glycol was the most inefficient alcohol on all bacteria. In K. pneumoniae and P. aeruginosa, the bactericidal concentrations were higher than the inhibitory one, and to a level similar to that encountered for most of the Gram-positive bacteria. Among Gram-positive cocci, E. faecalis presented the lowest susceptibility to alcohols. Conclusions: All alcohols presented good effect on bacteria, even in low concentrations. Compared to ethanol as standard, there are better alternatives that can be used as antimicrobials, namely longer-chain alcohols such as propyl or butyric alcohols and their iso- isomers. Ethylene glycol should be avoided, due to its toxicity hazard and low antimicrobial efficacy. Bacterial phenotype (highly adaptable bacteria, biofilm formation) and structure (cell wall structure, presence of capsule) may drastically affect the responsiveness to the antimicrobial activity of alcohols, leading to higher bactericidal than inhibitory concentrations.
The aim of the study was to evaluate the drug resistance of Enterococcus faecalis and Enterococcus faecium isolated from different types of poultry waste. The study material consisted of feather samples (duck, turkey, chicken), sludge and centrifuge sediment, originating from three poultry farms. The study was conducted in two stages; isolation and identification of Enterococcus bacteria from the waste and evaluation of their drug resistance using Kirby-Bauer method. Contamination of the poultry waste with Enterococcus isolates included E. faecium species (79 %) and E. faecalis (21 %). The most contaminated were sludge and sediment from the centrifuge as well as chicken feathers, irrespective of the place and time of sampling. Tested isolates showed multiple resistance and similar reaction to all antibiotics used in the study and E. faecalis strain was more resistant. Enterococcus isolates showed the highest resistance to streptogramins, carbapenems, fluoroquinones, aminoglycosides and penicillins, and the lowest for nitrofurantions and phenicols.
The aim of this study was to determine quantities of antibiotics used mainly or exclusively for urinary tract infections in Croatia between 2005 and 2014, to describe utilisation trends, and general consequences of antibiotic consumption on antimicrobial resistance.
Antibiotic utilisation data were obtained from annual reports of both the Croatian Drug Agency and Croatian Academy of Medical Sciences. Antibiotic consumption was expressed in DDD/1000 inhabitants/day (DDD TID). Antimicrobial resistance was analysed for E. coli, E. faecalis, E. faecium, P. aeruginosa, Klebsiella spp., P. mirabilis. Descriptive statistics were used to process data and calculate trends.
Overall, utilisation of antibacterials decreased by 4.8% (from 3,35 to 3,19 DDD TID), while trends of individual agents varied substantially – from 87% decline for ceftibuten to 160% rise for levofloxacin. The consumption of quinolones increased by 32.3%. This was mostly due to increased ciprofloxacin consumption (144% raise). Sulfamethoxazole-trimethoprim declined by 57%, while nitrofurantoin increased by 86%. The use of fosfomycin was marginal. Antimicrobial resistance of E. coli increased against quinolones by 54.5%, and against nitrofurantoin by 2–3%. Quinolone resistance of other pathogens (Klebiella spp, Proteus mirabilis), increased variably – between 17.2% (Klebsiella) and 90% (Proteus), while for P. aeruginosa remained the same at 22%.
High rates of antimicrobial utilisation require prescribing restrictions and educational interventions. The increased use of fluoroquinolones is a potentially serious public health threat due to the rapid development of resistance among uropathogens. This threat can be avoided by greater use of nitrofurantoin and fosfomycin.
The ongoing control of virulent bacteria strains is a challenge for today’s medicine. An example of this, is one widely used drug employed in treating less serious external oral and ocular bacterial infections. This is a gel containing both cetalkonium chloride and choline salicylate. However, whether in the era of expanding bacterial resistance this gel is still effective, is not clear. Hence, in our work, its antibacterial effect was studied against 13 strains of Pseudomonas aeruginosa, 6 strains of Staphylococcus spp. and 6 strains of Streptococcus spp. drawn from the collection of the Department of Microbiology, Virology and Immunology, Kazakh National Medical University, as well as against 30 strains of Staphylococcus spp. recently isolated from Kazakh medical students. This work demonstrated that Pseudomonas aeruginosa was insensitive to this preparation in all samples, while the sensitivity of Staphylococcus spp. and Streptococcus spp. was almost halved, compared to untreated samples. An interesting discovery was the greater resistance of strains obtained from student volunteers than from the collection. However, despite the evident resistance of some strains to the combined cetalkonium chloride and choline salicylate gel, we put forward that it can still be used in less serious external bacterial infections.
Antibiotic resistance represents a serious threat worldwide. When considering the increasing ability of bacteria to effectively resist antibacterial agents, it is necessary to reduce the consumption of antibiotic substances in animal production in order to preserve their effectiveness in the future. Attention should be paid to the multidrug resistant microorganisms’ occurrence, which can be very exhausting for the breeder not only from the economic point of view. Therefore, alternative sources of antibacterials should be considered due to the limited possibilities of using conventional antibiotics in animal breeding, e.g. application of various substances including organic acids, clay minerals, etc. Nowadays, the research in this field also focuses on the combinatory effect of such compounds, which can also find the perspective for use in animal breeding. This article provides an overview of problems connected with the resistance of diverse bacteria to antibiotic treatment in livestock breeding. It emphasises the need for alternate resources usage with the aim to lower the environmental burden caused by overuse of antimicrobials used in subclinical doses in the past and with the expanding bacterial resistance.
We surveyed antibiotics in drinking water in Austria. Testing for 37 antimicrobials was performed by online solid-phase extraction–liquid chromatography–high-resolution mass spectroscopy method. Selection of sample sites for drinking water resources focused on areas considered susceptible to contamination and on geographic population distribution. Sulfamethoxazole was detected in 10 (5%) of 200 samples collected in 2014. Five samples showed concentrations above the limit of quantification (2.5 ng/l). Concentrations measured were ≤8.9 ng/l, making toxic effects highly unlikely. However, even low-level concentrations of antibiotics could increase bacterial resistance. The presence of antibiotics is presently not regulated. We assume anthropogenic pollution (not animal husbandry) as source and ask for a maximum permissible value of antibiotics in drinking water.
Due to the threat and emergence of bacterial resistance against antibiotics, the use of in-feed antibiotics at therapeutic and subtherapeutic levels has been limited. Complete withdrawal of antibiotics as growth promoters (AGP) has led to poor gut health signs in chickens that include conditions like wet litter, intestinal bacteria overgrowth, poor growth performance, malabsorption and various diseases. Two of the most common alternatives to AGP are prebiotics and probiotics. Both prebiotics and probiotics have become the potential feed additives that improve the gut health, immune system and microbiota by various mechanisms of action, and enhance growth performance of chickens. The review discusses the modes of action like antibacterial, competitive exclusion (CE), and immunomodulatory properties of prebiotics and probiotics, particularly in poultry. In ovo feeding of prebiotics and probiotics with promising effect on growth performance and reduction of pathogens like Salmonella is also discussed in this review. However, it is necessary to conduct more research with prebiotics and probiotics as well as other feed additives to understand the detailed mechanisms of action and identify better alternatives for poultry production and health.