A comparative study to evaluate the effects of antibiotics, plant extracts and fluoride-based toothpaste on the oral pathogens isolated from patients with gum diseases in Pakistan

Oral diseases caused by various microorganisms are common around the world. Scientific research has now been focusing on novel medicines to overcome bacterial resistance and antibiotics side effects; therefore, the current study was designed to assess the efficacy of certain antibiotics, toothpaste, and medicinal plant extracts (Ajuga bracteosa and Curcuma longa) versus the bacterial pathogens isolated from the human oral cavity. A total of 130 samples were collected from Khyber Teaching Hospital Peshawar, Pakistan, among those 27 species isolated, and eight bacterial species were identified from the samples. Among all the bacterial species, Staphylococcus aureus (29.62%) and Proteus mirabilis (22.2%) were found to be more prevalent oral pathogens. In comparison, the least pervasive microbes were Proteus vulgaris, Shigella sonnei, Escherichia coli and Aeromonas hydrophila. The study also suggested that dental problems were more prevalent in males (41-50 years of age) than females. Among the eight antibiotics used in the study, the most promising results were shown by Foxicillin against A. hydrophila. The survey of TP1 revealed that it showed more potent antagonist activity against Proteus vulgaris as compared TP2 and TP3 that might be due to the high content of fluoride. The Curcuma longa showed more significant activity than Ajuga bracteosa (Stem, leaves and root) extracts. The data obtained through this study revealed that antibiotics were more effective for oral bacterial pathogens than toothpaste and plant extracts which showed moderate and low activity, respectively. Therefore, it is suggested that the active compounds in individual medicinal plants like Curcuma longa and Ajuga bracteosa could replace the antibiotics when used in daily routine as tooth cleansers or mouth rinses.

Potential of Sambiloto (Andrographis paniculata Nees) Extract against Salmonella Pullorum

Background: Salmonella Pullorum are pathogenic bacteria that causes salmonellosis and causes heavy economic losses in the poultry industry and are zoonotic. Treatment of diseases caused by bacteria generally use antibiotics, but excessive administration of antibiotics causes bacterial resistance and residues in livestock. Major chemical constituents of Sambiloto are andrographolide and flavonoids. Andrographolide has antibacterial effect in addition to being antitoxic, anticancer, anti-inflammatory and antiallergic. Methods: The research was conducted by isolating and identifying Salmonella Pullorum on SSA media and a series of biochemical tests (TSIA, SIM, SCA, urea media and sugar test), manufacturing sambiloto extract, testing the sensitivity of several antibiotics using the disk diffusion method and testing the activation of sambiloto extract against Salmonella Pullorum using the disk diffusion and dilution methods. Result: The result show that sambiloto had antibacterial activity because it contained andrographolide, flavonoids, saponins, alkaloids and tannins and the lowest extract dose that effectively killed Salmonella Pullorum is concentrations of 20%.

Phage therapy of wound-associated infections

Phages are viruses which can specifically infect bacteria, resulting in their destruction. Bacterial infections are a common complication of wound healing, and experimental evidence from animal models demonstrates promising potential for phage-dependent eradication of wound-associated infections. The studies discussed suggest that phage therapy may be an effective treatment, with important advantages over some current antibacterial treatments. Phage cocktails, as well as co-administration of phages and antibiotics, have been reported to minimise bacterial resistance. Further, phage-antibiotic synergism has been reported in some studies. The ideal dose of phages is still subject to debate, with evidence for both high and low doses to yield therapeutic effects. Novel delivery methods, such as hydrogels, are being explored for their advantages in topical wound healing. There are more and more Good Manufacturing Practice facilities dedicated to manufacturing phage products and phage therapy units across the world, showing the changing perception of phages which is occurring. However, further research is needed to secure the place of phages in modern medicine, with some scientists calling upon the World Health Organisation to help promote phage therapy.

Pseudomonas aeruginosa Oligoribonuclease Controls Susceptibility to Polymyxin B by Regulating Pel Exopolysaccharide Production

Polymyxins are considered as the last resort antibiotics to treat infections caused by multidrug-resistant Gram negative pathogens. Pseudomonas aeruginosa is an opportunistic pathogen that causes various infections in humans. Proteins involved in lipopolysaccharide modification and maintaining inner and outer membrane integrities have been found to contribute to the bacterial resistance to polymyxins. Oligoribonuclease (Orn) is an exonuclease that regulates the homeostasis of intracellular (3'-5')-cyclic dimeric guanosine monophosphate (c-di-GMP), thereby regulating the production of extracellular polysaccharide in P. aeruginosa . Previously, we demonstrated that Orn affects the bacterial resistance to fluoroquinolone, β-lactam and aminoglycoside antibiotics. In this study, we found that mutation of orn increased the bacterial survival following polymyxin B treatment in a wild type P. aeruginosa strain PA14. Overexpression of c-di-GMP degradation enzymes in the orn mutant reduced the bacterial survival. By using a fluorescence labeled polymyxin B, we found that mutation of orn increased the bacterial surface bound polymyxin B. Deletion of the Pel synthesis genes or treatment with a Pel hydrolase reduced the surface bound polymyxin B and bacterial survival. We further demonstrated that Pel binds to extracellular DNA (eDNA), which traps polymyxin B and thus protects the bacterial cells. Collectively, our results revealed a novel defense mechanism against polymyxin in P. aeruginosa .

Antimicrobial Stewardship Program: Reducing Antibiotic’s Spectrum of Activity Is not the Solution to Limit the Emergence of Multidrug-Resistant Bacteria

Overconsumption of antibiotics in hospitals has led to policy implementation, including the control of antibiotic prescriptions. The impact of these policies on the evolution of antimicrobial resistance remains uncertain. In this work, we review the possible limits of such policies and focus on the need for a more efficient approach. Establishing a causal relationship between the introduction of new antibiotics and the emergence of new resistance mechanisms is difficult. Several studies have demonstrated that many resistance mechanisms existed before the discovery of antibiotics. Overconsumption of antibiotics has worsened the phenomenon of resistance. Antibiotics are responsible for intestinal dysbiosis, which is suspected of being the source of bacterial resistance. The complexity of the intestinal microbiota composition, the impact of the pharmacokinetic properties of antibiotics, and the multiplicity of other factors involved in the acquisition and emergence of multidrug-resistant organisms, lead us to think that de-escalation, in the absence of studies proving its effectiveness, is not the solution to limiting the spread of multidrug-resistant organisms. More studies are needed to clarify the ecological risk caused by different antibiotic classes. In the meantime, we need to concentrate our efforts on limiting antibiotic prescriptions to patients who really need it, and work on reducing the duration of these treatments.

The characteristic and potential therapeutic effect of isolated multidrug-resistant Acinetobacter baumannii lytic phage

Background Widespread misuse of antibiotics caused bacterial resistance increasingly become a serious threat. Bacteriophage therapy promises alternative treatment strategies for combatting drug-resistant bacterial infections. In this study, we isolated and characterized a novel, potent lytic bacteriophage against multi-drug resistant (MDR) Acinetobacter baumannii and described the lytic capability and endolysin activity of the phage to evaluate the potential in phage therapy. Methods A novel phage, pIsf-AB02, was isolated from hospital sewage. The morphological analysis, its host range, growth characteristics, stability under various conditions, genomic restriction pattern were systematically investigated. The protein pattern of the phage was analyzed, and the endolysin activity of the phage was determined under the non-denaturing condition on SDS-PAGE. The optimal lytic titer of phage was assessed by co-culture of the phage with clinical MDR A. baumannii isolates. Finally, HeLa cells were used to examine the safety of the phage. Results The morphological analysis revealed that the pIsf-AB02 phage displays morphology resembling the Myoviridae family. It can quickly destroy 56.3% (27/48) of clinical MDR A. baumannii isolates. This virulent phage could decrease the bacterial host cells (from 108 CFU/ml to 103 CFU/ml) in 30 min. The optimum stability of the phage was observed at 37 °C. pH 7 is the most suitable condition to maintain phage stability. The 15 kDa protein encoded by pIsf-AB02 was detected to have endolysin activity. pIsf-AB02 did not show cytotoxicity to HeLa cells, and it can save HeLa cells from A. baumannii infection. Conclusion In this study, we isolated a novel lytic MDR A. baumannii bacteriophage, pIsf-AB02. This phage showed suitable stability at different temperatures and pHs, and demonstrated potent in vitro endolysin activity. pIsf-AB02 may be a good candidate as a therapeutic agent to control nosocomial infections caused by MDR A. baumannii.

Characterization and in vitro testing of newly isolated lytic bacteriophages for the biocontrol of Pseudomonas aeruginosa

Aim: Two lytic phages were isolated using P. aeruginosa DSM19880 as host and fully characterized. Materials & methods: Phages were characterized physicochemically, biologically and genomically. Results & conclusion: Host range analysis revealed that the phages also infect some multidrug-resistant (MDR) P. aeruginosa clinical isolates. Increasing MOI from 1 to 1000 significantly increased phage efficiency and retarded bacteria regrowth, but phage ph0034 (reduction of 7.5 log CFU/ml) was more effective than phage ph0031 (reduction of 5.1 log CFU/ml) after 24 h. Both phages belong to Myoviridae family. Genome sequencing of phages ph0031 and ph0034 showed that they do not carry toxin, virulence, antibiotic resistance and integrase genes. The results obtained are highly relevant in the actual context of bacterial resistance to antibiotics.

A Wake-Up Call: Determination of Antibiotics Residue Level in Raw Meat in Abattoir and Selected Slaughterhouses in Five Local Government in Kano State, Nigeria.

The frequent use of antibiotics may result in drug residues that can be discovered at varying quantities in animal products such as milk or meat. The presence of pharmaceutical residues in food above the MRLs has been perceived globally by various persons. Antibiotics residues are present in food, which can endanger human health by causing antibiotic sensitivity, allergic reactions, microflora imbalance, bacterial resistance to antibiotics in microorganisms, and financial loss to the food industry. Farmers around the world utilize them on a sporadic basis for both preventative and curative purposes. This study assessed the antibiotics residues in raw meat sold in 6 slaughter houses in Kano States. The study is a descriptive cross-sectional study involving six (6) major slaughter house in Kano state. Muscle, Kidney and liver samples were collected from each slaughterhouse. The antibiotic residues in the meat samples were analysed using high performance liquid chromatography (HPLC) for tetracycline, ciprofloxacin and oxytetracycline residue results were presented in charts and tables. Out of a total of 18 beef samples analyzed during this study, 15 (83%) of the total samples had detectable levels of tetracycline residues from which 6(33.3%) had tetracycline residues at violative levels above the WHO/FAO maximum residue limits (MRLs), out of those 18 beef samples analyzed during this study, 6(33%) of the total samples had detectable levels of oxytetracycline residues from which 3(17%) had oxytetracycline residues at violative levels above the WHO/FAO maximum residue limits (MRLs) and out of those 18 beef samples analyzed during this study, 12(67%) of the total samples had detectable levels of ciprofloxacin, all levels are below the WHO/FAO maximum residue limits (MRLs). This high level of tetracycline and oxytetracycline residues in greater proportion of meat destined for human consumption at violative levels could be as a result of the indiscriminate use and misuse of veterinary drugs as commonly practiced among livestock producers and marketers without observing withdrawal period prior to slaughter. These results indicate that consumers may be predisposed to health hazards and hinder international meat trade from Nigeria. Regulatory authorities should therefore ensure compliance with good agricultural practices including withdrawal period of drugs used for treatment of food animals.

Evaluation of the current guidelines for antibacterial therapy strategies in patients with cirrhosis or liver failure

Background Bacterial infections are common complications in patients with cirrhosis or liver failure and are correlated with high mortality. Clinical practice guideline (CPG) is a reference used to help clinicians make decisions. This systematic appraisal aimed to evaluate the methodological quality and summarize the recommendations of reported CPGs in these patients. Methods We systematically searched CPGs published from 2008 to 2019. The methodological quality of the included CPGs was assessed using the AGREE II instrument. We extracted and compared recommendations for prophylactic and empirical treatment strategies. Results Fourteen CPGs with a median overall score of 56.3% were included. The highest domain score was Clarity of Presentation (domain 4, 85.4%), and the lowest was for Stakeholder Involvement (domain 2, 31.3%). Three CPGs had an overall score above 80%, and 6 CPGs had a score above 90% in domain 4. Prophylaxis should be strictly limited to patients with varicose bleeding, low ascites protein levels and a history of spontaneous bacterial peritonitis. Fluoroquinolones (norfloxacin and ciprofloxacin), third-generation cephalosporins (G3) (ceftriaxone and cefotaxime) and trimethoprim–sulfamethoxazole (SXT) are recommended for preventing infections in patients with cirrhosis or liver failure. G3, β-lactam/β-lactamase inhibitor combinations (BLBLIs) and carbapenems are recommended as the first choice in empirical treatment according to local epidemiology of bacterial resistance. Conclusions The methodological quality of CPGs focused on patients with cirrhosis or liver failure evaluated by the AGREE II instrument is generally poor. Three CPGs that were considered applicable without modification and 6 CPGs that scored above 90% in domain 4 should also be paid more attention to by healthcare practitioners. Regarding recommendations, norfloxacin, ciprofloxacin, ceftriaxone, cefotaxime, and SXT are recommended for prophylactic treatment appropriately. G3, BLBLIs, and carbapenems are recommended for use in empirical treatment strategies.