Broad-spectrum Bactericidal Antibiotic Research Articles

Improving the Safety of Clinical Management of COVID-19 Patients Receiving Aminoglycosides and Parenteral Nutrition: Y-site Compatibility Studies

PurposeAminoglycosides (AMGs) are broad-spectrum bactericidal antibiotics that can resolve bacterial infections co-existing with COVID-19 or exploit their potential antiviral activities. Patients presenting the most severe forms of COVID-19 due to escalating catabolism and significant lean body mass loss often require the concomitant administration of parenteral nutrition (PN) and antibiotics. The Y-site administration is one of the approaches allowing the co-administration of two intravenous medications in patients with limited vascular access. Our study aimed to investigate the compatibility of AMGs and selected commercial PN admixtures enriched in omega-3 fatty acids. MethodsGentamycin (GM), amikacin (AM), and tobramycin (TM) solutions for infusion were combined with Nutriflex Omega Special (NOS) and Smofkabiven (SFK). Three different volume ratios were investigated: 1:2, 1:1, and 2:1, simulating Y-site administration. Samples underwent visual examination and determination of the lipid emulsion particle size, zeta potential, and pH immediately after preparation and after four hours of storage at room temperature (22 ± 2 °C) with sunlight exposure. ResultsGM and AM combined with NOS in all studied ratios met the set-up acceptance criteria. The addition of TM to NOS in a 2:1 volume ratio and all tested AMGs to SFK in all studied combinations significantly influenced the stability of the oil-water system leading to the appearance of globules larger than 5 µm exceeding the pharmacopeial limit of 0.05% immediately after preparation or after four hours of storage. ConclusionIn conclusion, our study showed that NOS was less prone to destabilization of oil-in-water systems by AMGs than SFK. In justified clinical cases, due to the lack of appearance of precipitate or enlarged lipid droplets, the combined administration of GM and AM with the NOS could be considered, provided tested volume ratios of the drug and MCB in the infusion line are maintained. However, it should be noted that such an infusion may be associated with the risk of changes in the pharmacokinetics of the drug.

Fosfomycin: An old antibiotic and new perspectives. A review

Urinary tract infection (UTI) is one of the most common urological diseases and presents a problem for rational antibiotic therapy due to the growing antibiotic resistance. Fosfomycin is one of the older low molecular weight, broad-spectrum bactericidal antibiotics with activity against uropathogens, particularly Escherichia coli and others. Fosfomycin is administered as a single dose that achieves very high concentrations of the antibiotic in the urine and bladder, sufficient to eliminate most common uropathogens, including those with multidrug resistance (MDR). Many factors have contributed to the persistence of fosfomycin's antibacterial activity, including the use of a single dose, limited use for UTIs only, and very high and persistent urinary concentrations that rapidly kill bacteria, reducing the possibility of mutant selection. In addition to its antimicrobial properties, fosfomycin has an immunomodulatory effect by altering the function of lymphocytes, monocytes, and neutrophils. It affects the acute inflammatory cytokine response. New data have been obtained on the activity of fosfomycin against biofilms formed by uropathogens and against biofilm-associated bacterial strains with MDR. A new 2020 meta-analysis compared the efficacy of fosfomycin with equivalent antibiotics (β-lactams/cephalosporins, quinolones, sulfonamides, nitrofurantoin) in women in the broad categories of uncomplicated UTI or asymptomatic bacteriuria and found no difference in clinical and microbiological cure rates with comparison groups. A number of other studies in patients with UTIs with MDR or complicated course also showed a high sensitivity of uropathogens to fosfomycin and the effectiveness of treatment with multiple doses (2–3 doses with an interval of 48–72 hrs). Fosfomycin is being considered as a potentially useful antibiotic for the treatment of prostatitis. Current data indicate that sufficient concentrations in prostate tissue are achieved after a single dose of fosfomycin. Recent reviews in 2019 and 2022 present results of studies of fosfomycin for the prevention of infectious complications after transurethral prostate biopsy and in patients with chronic bacterial prostatitis whose pathogens are resistant to other antibiotics. Thus, the accumulation of new scientific data on the mechanisms of action and resistance of fosfomycin reveals more potential advantages of its practical application.

Identification and Quantification of the Component Composition of the Active Substance Gentamicin Sulfate by <sup>1</sup>Н and <sup>13</sup>С NMR Spectroscopy

Gentamicin sulfate is a broad-spectrum bactericidal aminoglycoside antibiotic produced by Micromonospora purpurea and used in clinical practice as an active substance containing a mixture of gentamicins C1 and C2. Gentamicin content is a standardised parameter controlled as part of a pharmaceutical product review. Currently, the quality control of the active substance gentamicin sulfate involves the use of high-performance liquid chromatography (HPLC) for the indirect identification of the component composition by comparison with a reference standard and for its quantification by calibration against the reference standard.The aim of the study was to develop a procedure for identifying and quantifying the components of the active substance gentamicin sulfate using nuclear magnetic resonance (NMR) spectroscopy that would not require reference standards.Materials and methods. The authors studied a sample of the active substance gentamicin sulfate using an Agilent DD2 NMR spectrometer operating at 600 MHz to record NMR spectra and an Agilent 1200 HPLC system equipped with a multiple wavelength detector (MWD) to obtain chromatograms.Results. Having determined the spectral properties of the C1, C1A, C2, C2A and C2B gentamicins comprising the active substance, the authors observed characteristic signals of the same type that corresponded to each of the gentamicins and did not overlap with other signals in the 1H and 13C spectra. These characteristic signals provided spectral markers indicative of the gentamicins of interest in the sample, with normalised integrated intensities equal to the mole fractions of the analytes. The authors compared NMR and HPLC measurements of the active substance composition.Conclusions. The authors developed a procedure for identifying and quantifying the constituents of the active substance gentamicin sulfate by 1H and 13C NMR spectroscopy, which requires less effort than HPLC procedures and no reference standards for the intended applications.

Does attendance in outdoor kindergartens reduce the use of antibiotics in children?

To determine whether children enrolled in rural outdoor kindergartens had a lower risk of redeeming at least one prescription for antibiotics compared to children enrolled in urban conventional kindergartens, and if type of antibiotics prescribed differed according to kindergarten type. Two Danish municipalities provided data including civil registration numbers from children enrolled in a rural outdoor kindergarten in 2011-2019, and a subsample of all children enrolled in urban conventional kindergartens in the same period. Civil registration numbers were linked to individual-level information on redeemed prescriptions for antibiotics from the Danish National Prescription Registry. Regression models were performed on 2,132 children enrolled in outdoor kindergartens, and 2,208 children enrolled in conventional kindergartens. There was no difference between groups in risk of redeeming at least one prescription for all types of antibiotics (Adjusted Risk Ratio: 0.97 (95% Confidence Intervals 0.93,1.02, p=0.26)). Similarly, there were no differences between kindergarten type and risk of redeeming at least one prescription for systemic, narrow-spectrum systemic antibacterial, broad-spectrum systemic antibacterial, or topical antibiotics. Compared to children who were enrolled in conventional kindergartens, children who were enrolled in outdoor kindergartens did not have a lower risk of redeeming prescriptions for any type of antibiotics.

A clinical pharmacological experimental research analysis of the evidence-based rational pharmacotherapeutics of pefloxacin and newer quinolones

Background: Pefloxacin is a newer broad-spectrum bactericidal fluoroquinolone antibiotic, with superior antibacterial activity in vivo against pathogenic ocular gram-negative and anaerobic microorganisms and better pharmacokinetic properties.Methods: 100 bacterial conjunctivitis patients were prescribed topical pefloxacin 0.3% ophthalmological drops monotherapy, 2 drops in each eye after every 3 hours for 2 days, and 2 drops in each eye after every 6 hours for next 5 days. The overall recovery of the patients was clinically examined and assessed. The patients who did not recover completely with 0.3% pefloxacin monotherapy ophthalmological drops, were administered topical pefloxacin 0.3% ophthalmological drops, 2 drops in each eye after every 6 hours for the next 3 days, as combination therapy, with other required ophthalmological eye drops, depending on the prognostic follow-up, on days 0, 3, 5, 7, 10, 15, 30, and on further follow-ups. The evidence-based rational pharmacotherapeutic patient percentage topical application requirements of 0.3% pefloxacin ophthalmological drops monotherapy and subsequent combination therapy for complete recovery from bacterial conjunctivitis was thoroughly analysed and assessed.Results: In this study, the patient percentage topical application requirements of pefloxacin 0.3% ophthalmological drops monotherapy and combination therapy in bacterial conjunctivitis patients showed that 93% patients had completely recovered with pefloxacin monotherapy, and 7% patients required pefloxacin combination therapy for complete recovery. The evidence-based rational pharmacotherapeutics of newer quinolones, in global multi-centre tertiary care hospitals, was also well characterized and analytically described.Conclusions: Therefore, 93% patients had completely recovered with the ocular antibiotic pefloxacin 0.3% ophthalmological drops monotherapy, and 7% patients required pefloxacin combination therapy for complete recovery. The evidence-based rational pharmacotherapeutics of newer quinolones was also distinctly delineated.

Decreased cyclic-AMP caused by ATP contributes to fosfomycin heteroresistance in avian Escherichia coli.

Fosfomycin is an important broad-spectrum bactericidal antibiotic to treat multidrug-resistant bacteria infections. It is generally accepted that heteroresistant bacteria are an intermediate stage in the formation of drug resistance, but there are few studies on the formation mechanism underlying fosfomycin heteroresistance (FHR). To reveal the characteristics and formation mechanisms of FHR in Escherichia coli isolates obtained from chickens. We identified the FHR according to the population analysis profile (PAP) test and in vitro time-kill assay. Growth curves for FHR E. coli and their subpopulations were measured. Also, the subpopulations were repeatedly cultured in fosfomycin-free medium for 5-20 overnight incubation periods. The formation mechanisms of FHR in E. coli isolates were identified through accumulation assay, carbohydrate utilization testing, real-time relative quantitative PCR analysis, DNA sequencing, transcriptomic analysis, intracellular ATP and cAMP-level assessment. Four of six E. coli strains were confirmed to show FHR, with a total of six subpopulations. The subpopulations restored phenotypic susceptibilities to fosfomycin within 5-20 overnight incubation sessions, but four of six subpopulations still maintained FHR characteristics. Differing from their parental isolates, the uptake of fosfomycin in the subpopulations through GlpT was reduced remarkably. Further studies identified that the low expression of glpT was due to the decrease of intracellular cAMP levels in the subpopulations, which was caused by the decreased ATP levels in cells. Our findings revealed the formation mechanism of E. coli isolates showing FHR obtained from chicken in China and characterized the dynamic change traits in vitro of the subpopulations.

A rational pharmacovigilance safety appraisal of topical pefloxacin 0.3% ophthalmological drops in bacterial conjunctivitis, in global multi-centre tertiary care hospitals

Background: Pefloxacin is a newer broad-spectrum bactericidal fluoroquinolone antibiotic, with superior antibacterial activity in vivo against pathogenic ocular gram-negative and anaerobic microorganisms and better pharmacokinetic properties. The objective of this clinical research study was the rational pharmacovigilance safety appraisal of topical pefloxacin 0.3% ophthalmological drops in bacterial conjunctivitis, in global multi-centre tertiary care hospitals.Methods: The 43 bacterial conjunctivitis patients were prescribed topical pefloxacin 0.3% ophthalmological drops, 2 drops in each eye after every 3 hours for 2 days, and 2 drops in each eye after every 6 hours for next 5 days. The pharmacovigilance safety appraisal was performed by monitoring the occurrence of adverse drug reactions, like, transient ocular burning or discomfort, ocular irritation, redness, stinging, pruritis, photophobia, ocular watering and dryness, and recording in Adverse Event Case Report Forms, on days 0, 3, 5, 7, 10, 15, 30, and on further follow-ups.Results: In this study, the safety assessment showed that only 1 patient had ocular discomfort in the eye. The occurrence of adverse effects was statistically non-significant. Thus, 0.3% pefloxacin ophthalmological drops treatment was safe and tolerable, among all 43 patients.Conclusions: Therefore, pefloxacin is a safe ocular antibiotic for treating bacterial conjunctivitis, with adequate drug tolerability exhibited by the patients.

Genomic Characterization of Ciprofloxacin Resistance in Laboratory-Derived Mutants of Vibrio parahaemolyticus

The quinolone ciprofloxacin is a broad-spectrum bactericidal antibiotic used for human medicine as well as the aquaculture industry. The emergence of ciprofloxacin-resistant Vibrio parahaemolyticus strains is currently a global public health concern. However, the mechanism of ciprofloxacin resistance in V. parahaemolyticus is not yet fully clarified. We generated mutants with decreased ciprofloxacin susceptibility using in vitro selection and investigated genes associated with ciprofloxacin resistance on a genetic level. Our selection process yielded mutants that possessed altered minimal inhibitory concentrations (MICs) for ciprofloxacin and other unrelated antibiotics. These included Ser83Ile mutations in GyrA and Val461Glu in ParE as well as mutations in the resistance nodulation cell division (RND) family transporter gene vmeD and the putative TetR family regulator gene vp0040 upstream of the vmeCD operon. Measurements of steady-state mRNA levels revealed that the ciprofloxacin-resistant mutants overexpressed vmeCD. Further, the introduction of the vp0040 mutated allele from H512 into the sensitive parental strain increased the MIC for ciprofloxacin 31.25-fold. Taken together, these results indicated that ciprofloxacin resistance in these mutants was due to the quinolone resistance determining region mutation as well as overexpression of vmeCD caused by a loss of vp0040 gene repression. This also accounted for the presence of the multidrug resistance phenotype for these mutant strains since RND efflux system can export structurally unrelated antibiotics.

Assessment of various veterinary drug residues in animal originated food products.

The veterinary drugs are broad-spectrum antibacterial antibiotics; it uses to cure the animal disease. Many countries have banned veterinary drug residues like nitrofurans metabolites, chloramphenicol. However, the people were administrated veterinary drugs to animals as illegal to increase the milk production in animals for economic benefit. The results of illegally use of veterinary drugs remain as a residue in animal product like milk and it is very harmful to whom consume it cause cancer and allergic for human being which has entered the concern among milk consumers. To control illegal use of veterinary drugs, the government of India has restricted its use in animals. For the identification and confirmation of veterinary drug residues in animal products, analytical techniques such as liquid chromatography and mass spectrometry are available. These are very sophisticated equipments which are available nowadays and their methodologies for the analytical method validation are described by European commission 2002/657/EC. The use of veterinary drugs is a big challenge to effectively identify and authorization of their use. There are so many analytical techniques are using very effectively and taking very less time to protect the consumers from their adverse effects. These techniques take very less time to identify more groups of compounds such as tetracycline, sulfonamides, anthelmintic, and macrolides in single multi-residue method. These methods having validation parameters include system precision, calibration curve, accuracy, limit of detection, and quantification. Therefore, improvement in the existing technologies and accessibility of new screening methodologies will give opportunities for automation that helps in obtaining the results in very less time and improved sensitivity and specificity which contribute to better safety assurance, standard, and quality of various food products of animal origin.

Metabolites Potentiate Nitrofurans in Nongrowing Escherichia coli.

Nitrofurantoin (NIT) is a broad-spectrum bactericidal antibiotic used in the treatment of urinary tract infections. It is a prodrug that once activated by nitroreductases goes on to inhibit bacterial DNA, RNA, cell wall, and protein synthesis. Previous work has suggested that NIT retains considerable activity against nongrowing bacteria. Here, we have found that Escherichia coli grown to stationary phase in minimal or artificial urine medium is not susceptible to NIT. Supplementation with glucose under conditions where cells remained nongrowing (other essential nutrients were absent) sensitized cultures to NIT. We conceptualized NIT sensitivity as a multi-input AND gate and lack of susceptibility as an insufficiency in one or more of those inputs. The inputs considered were an activating enzyme, cytoplasmic abundance of NIT, and reducing equivalents required for NIT activation. We systematically assessed the contribution of each of these inputs and found that NIT import and the level of activating enzyme were not contributing factors to the lack of susceptibility. Rather, evidence suggested that the low abundance of reducing equivalents is why stationary-phase E. coli are not killed by NIT and catabolites can resensitize those cells. We found that this phenomenon also occurred when using nitrofurazone, which established generality to the nitrofuran antibiotic class. In addition, we observed that NIT activity against stationary-phase uropathogenic E. coli (UPEC) could also be potentiated through metabolite supplementation. These findings suggest that the combination of nitrofurans with specific metabolites could improve the outcome of uncomplicated urinary tract infections.

Accelerating the Design of β-CD-PVDF-based Molecularly Imprinted Nanocomposite Membrane for Selective Separation: A Surface Functional Monomer-Directing Strategy

Enoxacin, as the broad-spectrum antibacterial activity antibiotics, has been widely used in treatment of bacterial diseases in animals and humans around the world. The extensive use of enoxacin in healthcare has also caused increasingly serious environmental risk as a matter of course. In this work, enoxacin imprinted poly (vinylidene fluoride) (PVDF) composite membranes (EIPCMs) were developed by strategy of surface grafting beta-cyclodextrin ([Formula: see text]-CD) for the improved hydrophilic and antifouling properties of the basal membrane. PVDF membrane was prepared by phase inversion method, and [Formula: see text]-CD was grafted onto the surface after hydroxyl groups modification. The effects of adding amount of [Formula: see text]-CD on performance of basal membranes were systematically examined. Further, the specific recognition sites were fabricated via sol–gel surface imprinting method using 3-aminopropyltriethoxysilane (APTES) and tetraethoxysilane (TEOS) as functional monomer and cross-linker, respectively. The specific adsorption and permeation experiments were investigated and explored the separation performance and mechanism of EIPCM. The results indicated that the as-prepared EIPCMs not only exhibited highly favorable features and high rebinding strength (31.25[Formula: see text]mg g[Formula: see text], but also possessed superior selective performance toward enoxacin (imprinted factor [Formula: see text] is 3.15). Furthermore, in order to investigate the practical applications of EIPCMs, the adsorption experiments were carried out using environmental sewage. The work developed here shows great potential for further applications in selective recognition and separation antibiotics pollution from the environment.

A comparative study of moxifloxacin versus combination of doxycycline and metronidazole for treatment of uncomplicated pelvic inflammatory disease

Background: Pelvic inflammatory disease (PID), a common condition among women of reproductive age caused by various aerobic and anaerobic organisms, may sometimes lead to complications like infertility, ectopic pregnancy and chronic pelvic pain. Moxifloxacin is a broad spectrum bactericidal antibiotic acting against many gram positive, gram negative aerobic organisms and anaerobes. Rapid absorption and high bioavailability allow single daily dosing and improves compliance. The present study was done to compare the clinical and microbiological outcomes in PID patients treated with conventional doxycycline- metronidazole and moxifloxacin therapy.Methods: Women with uncomplicated PID, randomized into two groups either received 400 mg single dose of moxifloxacin daily for 14 days (group A) or doxycycline 100 mg + metronidazole 500 mg twice daily for 14 days (group B). Temperature, TLC count, ESR, CRP, microbiological assessment, Visual analogue score for pain, vaginal discharge, dyspareunia and backache were noted. The bacteriological cure was assessed by high vaginal swab for organism identification by gram stain, 10% KOH and blood sample by ELISA.Results: Total 60 women were enrolled and randomized into two groups. There was significant reduction of CRP and improved TLC in the moxifloxacin treated group. Visual analogue scores for pain, vaginal discharge and malaise were significantly reduced in the group treated with moxifloxacin. Nausea, vomiting, metallic taste, dyspepsia and diarrhoea were complained by a significant number of patients of doxycycline + metronidazole group, in contrast to the patients receiving moxifloxacin.Conclusions: Moxifloxacin 400 mg once daily, is effective and safe for treatment of PID.

Identification and characterization of capsule depolymerase Dpo48 from Acinetobacter baumannii phage IME200

BackgroundThe emergence of multidrug- or extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. It is urgently necessary to search for alternatives to conventional antibiotics for control of severe A. baumannii infections. In recent years, bacteriophages and their derivatives, such as depolymerases, showed great potential as antibacterial or antivirulence agents against bacterial infections. Nonetheless, unlike broad-spectrum bactericidal antibiotics, phage-encoded depolymerase targets only a limited number of bacterial strains. Therefore, identification of novel depolymerases and evaluation of their ability to control A. baumannii infections is important.MethodsA bacteriophage was isolated from hospital sewage using an extensively drug-resistant A. baumannii strain as the host bacterium, and the phage’s plaque morphology and genomic composition were studied. A polysaccharide depolymerase (Dpo48) was expressed and identified, and the effects of pH and temperature on its activity were determined. Besides, a serum killing assay was conducted, and amino acid sequences homologous to those of putative polysaccharide depolymerases were compared.ResultsPhage IME200 yielded clear plaques surrounded by enlarged halos, with polysaccharide depolymerase activity against the host bacterium. A tail fiber protein with a Pectate_lyase_3 domain was identified as Dpo48 and characterized . Dpo48 was found to degrade the capsule polysaccharide of the bacterial surface, as revealed by Alcian blue staining. Dpo48 manifested stable activity over a broad range of pH (5.0–9.0) and temperatures (20–70 °C). Results from in vitro serum killing assays indicated that 50% serum was sufficient to cause a five log reduction of overnight enzyme-treated bacteria, with serum complement playing an important role in these killing assays. Moreover, Dpo48 had a spectrum of activity exactly the same as its parental phage IME200, which was active against 10 out of 41 A. baumannii strains. Amino acid sequence alignment showed that the putative tail fiber proteins had a relatively short, highly conserved domain in their N-terminal sequences, but their amino acid sequences containing pectate lyase domains, found in the C-terminal regions, were highly diverse.ConclusionsPhage-encoded capsule depolymerases may become promising antivirulence agents for preventing and controlling A. baumannii infections.

Intravenous fosfomycin for pulmonary exacerbation of cystic fibrosis: Real life experience of a large adult CF centre

BackgroundThe increased prevalence of multi-drug resistant strains of P.aeruginosa and allergic reactions among adult patients with cystic fibrosis (CF) limits the number of antibiotics available to treat pulmonary exacerbations. Fosfomycin, a unique broad spectrum bactericidal antibiotic, might offer an alternative therapeutic option in such cases. AimTo describe the clinical efficacy, safety and tolerability of intravenous fosfomycin in combination with a second anti-pseudomonal antibiotic to treat pulmonary exacerbations in adult patients with CF. MethodA retrospective analysis of data captured prospectively, over a 2-years period, on the Unit electronic medical records for patients who received IV fosfomycin was performed. Baseline characteristics in the 12 months prior treatment, lung function, CRP, renal and liver function and electrolytes at start and end of treatment were retrieved. Results54 patients received 128 courses of IV fosfomycin in combination with a second antibiotic, resulting in improved FEV1 (0.94 L vs 1.24 L, p < 0.01) and reduced CRP (65 mg/L vs 19.3 mg/L, p < 0.01). Renal function pre- and post-treatment remained stable. 4% (n = 5) of courses were complicated with AKI at mid treatment, which resolved at the end of the course. Electrolyte supplementation was required in 18% of cases for potassium and magnesium and 7% for phosphate. Nausea was the most common side effect (48%), but was well controlled with anti-emetics. ConclusionAntibiotic regimens including fosfomycin appear to be clinically effective and safe. Fosfomycin should, therefore, be considered as an add-on therapy in patients who failed to respond to initial treatment and with multiple drug allergies.

Molecular docking studies on thirteen fluoroquinolines with human topoisomerase II a and b

DNA relaxation is an important step in DNA replication. DNA topoisomerases play a major role in DNA relaxation. Hence these enzymes are important targets for cancer drugs. DNA topoisomerase inhibitors bind to the transient enzyme–DNA complex and inhibit DNA replication. Various inhibitors of topoisomerase I and II are prescribed as drugs. Topoisomerase II is considered as an important target for the development of anticancer drugs. In this study we have demonstrated molecular docking of thirteen fluoroquinolines with human DNA topoisomerase II alpha (a) and beta (b). Fluoroquinolines are broad spectrum antibacterial antibiotics and it is highly effective against various bacterial infections. Some of the fluoroquinolines like moxifloxacin exert antifungal as well as anti-cancer activity. It forms complexes with topoisomerase II a and are responsible for stoppage DNA replication. Molecular docking studies showed that fluoroquinolines has shown formation of hydrogen bond and good binding affinity with human Topo2a and Topo2b. Hence FQs may inhibit the activity of enzyme topoisomerase by binding at its active site. Ofloxacin, sparafloxacin, ciprofloxacin and moxifloxacin are predicted to be the most potent inhibitors among the thirteen FQs docked. GLN773, ASN770, LYS723 and TRP931 amino acid residues of Topo2a are involved in binding with FQs while ASP479, SER480, ARG820, ARG503, LYS456 and GLN778 amino acid residues of Topo2b are involved in binding with FQs. Our in silico study suggests that fluoroquinolines could be repositioned as DNA topoisomerase II inhibitors hence can be used as anticancer drugs. In vitro and in vivo experiments need to be done to confirm their efficacy.

Clinical Pharmacology of Ciprofloxacin in Neonates: Effects and Pharmacokinetics

Ciprofloxacin is the most commonly used fluoroquinolone. Ciprofloxacin is prescribed for 1 in 44 Americans. Ciprofloxacin is a broad-spectrum bactericidal antibiotic, effective against both gram-positive and gram-negative bacteria, being especially active against the Enterobacteriacae, including many microorganisms resistant to penicillins, cephalosporins and aminoglycosides, and also is effective against Haemophilus influenzae, penicillinase-producing Neisseria gonorrhea, Campylobacter and Pseudomonas aeruginosa. Streptococci and pneumococci are weakly inhibited and there is a high incidence of staphylococcal resistance to ciprofloxacin. In neonates, the dose of ciprofloxacin is 10 mg/kg intravenously over 30-60 min infusion, and 20 mg/kg is used to treat Pseudomonas aeruginosa infection. Ciprofloxacin treatment is effective in life-threatening multi-drug resistant Pseudomonas aeruginosa. Ciprofloxacin may be administered by mouth and has a bioavailability of 70% and is mainly recovered unchanged in the urine. Ciprofloxacin is safe and well tolerated in infants. In neonates, the half-life of ciprofloxacin is 3-4 hours. For meningococcal prophylaxis, give a single dose of 30 mg/kg (up to a maximum of 125 mg) orally. Ciprofloxacin is active against Citrobacter kosery that produces brain abscesses. The mortality rate for meningitis due to Citrobacter kosery is approximately 30%. Third-generation cephalosporins and aminoglycosides failed to prevent the high rates of morbidity and mortality caused by Citrobacter infections. Ciprofloxacin is the antibiotic treatment option for systemic infection or meningitis caused by Citrobacter kosery. Ciprofloxacin has been used to treat neonatal pneumonia, meningitis, and septicemia and was effective in all cases. The aim of this study is to review the clinical pharmacology of ciprofloxacin in neonates.

Reasonable antimicrobial therapy in patients with pyodermatosis

The data are given about the history of the invention and development of antimicrobial therapy in the XX-th and the beginning of the XXI-th centuries. There are presented data on the pharmacological effects of antibacterial agents from different groups that are used for the treatment of patients with pyodermatosis, dose schedules, pharmacokinetics, adverse effects, contraindications, and medicine interactions. The main causes leading to the formation of resistant microorganism strains are pointed. Advances of broad-spectrum antibacterial antibiotics for treatment the pyodermic patients are demonstrated on the example of amoxicillin+clavulinic acid, josamycin and doxycycline monohydrate. The arguments justifying the need to refuse empiric administration of antibacterial therapy are presented. To select a rational causal initial therapy of patients with pyoderma it is necessary to use the results of microbiological study of etiology and pathogenic microflora sensitivity to antimicrobial preparations.

Metabolism in anoxic permeable sediments is dominated by eukaryotic dark fermentation.

Permeable sediments are common across continental shelves and are critical contributors to marine biogeochemical cycling. Organic matter in permeable sediments is dominated by microalgae, which as eukaryotes have different anaerobic metabolic pathways to prokaryotes such as bacteria and archaea. Here we present analyses of flow-through reactor experiments showing that dissolved inorganic carbon is produced predominantly as a result of anaerobic eukaryotic metabolic activity. In our experiments, anaerobic production of dissolved inorganic carbon was consistently accompanied by large dissolved H2 production rates, suggesting the presence of fermentation. The production of both dissolved inorganic carbon and H2 persisted following administration of broad spectrum bactericidal antibiotics, but ceased following treatment with metronidazole. Metronidazole inhibits the ferredoxin/hydrogenase pathway of fermentative eukaryotic H2 production, suggesting that pathway as the source of H2 and dissolved inorganic carbon production. Metabolomic analysis showed large increases in lipid production at the onset of anoxia, consistent with documented pathways of anoxic dark fermentation in microalgae. Cell counts revealed a predominance of microalgae in the sediments. H2 production was observed in dark anoxic cultures of diatoms (Fragilariopsis sp.) and a chlorophyte (Pyramimonas) isolated from the study site, substantiating the hypothesis that microalgae undertake fermentation. We conclude that microalgal dark fermentation could be an important energy-conserving pathway in permeable sediments.

GSH Induced Controlled Release of Levofloxacin from a Purpose-Built Prodrug: Luminescence Response for Probing the Drug Release in Escherichia coli and Staphylococcus aureus.

Fluoroquinolones are third-generation broad spectrum bactericidal antibiotics and work against both Gram-positive and Gram-negative bacteria. Levofloxacin (L), a fluoroquinolone, is widely used in anti-infective chemotherapy and treatment of urinary tract infection and pneumonia. The main pathogen for urinary tract infections is Escherichia coli, and Streptococcus pneumoniae is responsible for pneumonia, predominantly a lower respiratory tract infection. Poor permeability of L leads to the use of higher dose of this drug and excess drug in the outer cellular fluid leads to central nervous system (CNS) abnormality. One way to counter this is to improve the lipophilicity of the drug molecule, and accordingly, we have synthesized two new Levofloxacin derivatives, which participated in the spatiotemporal release of drug via disulfide bond cleavage induced by glutathione (GSH). Recent studies with Streptococcus mutants suggest that it is localized in epithelial lining fluid (ELF) of the normal lower respiratory tract and the effective [GSH] in ELF is ∼430 μM. E. coli typically cause urinary tract infections and the concentration of GSH in porcine bladder epithelium is reported as 0.6 mM for a healthy human. Thus, for the present study we have chosen two important bacteria (Gram + ve and Gram - ve), which are operational in regions having high extracellular GSH concentration. Interestingly, this supports our design of new lipophilic Levofloxacin based prodrugs, which released effective drug on reaction with GSH. Higher lipophilicity favored improved uptake of the prodrugs. Site specific release of the drug (L) could be achieved following a glutathione mediated biochemical transformation process through cleavage of a disulfide bond of these purpose-built prodrugs. Further, appropriate design helped us to demonstrate that it is possible also to control the kinetics of the drug release from respective prodrugs. Associated luminescence enhancement helps in probing the release of the drug from the prodrug in bacteria and helps in elucidating the mechanistic pathway of the transformation. Such an example is scarce in the contemporary literature.

Combinations of Carbapenem with Fluoroquinolones or 1,3,4 -Oxadiazole-2 -Thione Derivatives as New Broad Spectrum Bactericidal Antibiotics for Ophthalmic Preparation

The present work describes the preparation and evaluation of an ophthalmic eye drops of antibacterial agent. The active ingredients (mereopenem, fluoroquinolones & 1,3,4 oxadiazole -2-thione derivatives) have been used in the formulation as eye drops with different doses as broad spectrum antibiotics to minimize the emergence of resistance lesion such as conjunctivitis or corneal ulcers. The experimental effectiveness of single or combination ophthalmic preparation as eye drop is well documented against different types of bacteria e.g. P.aeruginosa and other G(+)ve & G(-)ve bacteria. Other parameters pH, sterility, particulates and contents were calculated. All solutions are sterile, clear, isotonic and pH (5.1-6.3). These solutions didn’t cause any eye irritation in rabbits after daily application for four consecutive days. The potential clinical significant of combination therapy over monotherapy for different types of bacteria has been a controversial subjects for many years especially for ophthalmic purposes. The mechanism of carbapenem and fluoroquinolones are well known, while oxadiazole derivative is expected to inhibit p-amino benzoic acid. The uses of combination drug is thought to minimize the emergence of resistance, safe, potent and increase their synergistic activities.