Gram-positive Aerobes Research Articles

Application of an LC-ESI-QTOF-MS method for evaluating clindamycin concentrations in plasma and prostate microdialysate of rats.

Clindamycin is used for infections caused by Gram-positive and Gram-negative anaerobic pathogens and Gram-positive aerobes. Propionibacterium acnes is an important opportunistic microorganism of the human skin and is related to prostatitis. An LC-electrospray ionization-quadrupole time-of-flight-MS method was validated for determining clindamycin concentrations in plasma and prostate microdialysate. Clindamycin separation was carried out on a C18 column at 0.5 mL/min. The mobile phase employed gradient elution of formic acid and methanol. A mass spectrometer was operated in positive electrospray ionization mode to monitor ion 425.1784 and 253.1152 for clindamycin and cimetidine (internal standard), respectively. Linearity was obtained at 0.5-10.0 μg/mL (plasma) and 0.05-1.0 μg/mL (microdialysate) with coefficients of determination ≥0.999. The intra- and inter-day precision (coefficient of variation - CV%) values were ≤13.83% and 12.51% for plasma, respectively, and ≤10.90% and 9.35% for microdialysate, respectively. The accuracy was between 90.82% and 108.25% for plasma, and 96.97% and 106.98% for microdialysate. The present method was fully validated and applied to investigate clindamycin concentrations in both plasma and prostate by microdialysis in Wistar rats (80 mg/kg, intravenous). Because the penetration of antibiotics into the prostate may be restricted, this method allows us to investigate the prostate concentrations of clindamycin for the first time.

A clinical study of commonly isolated organism and its antibiotic sensitivity in diabetic foot ulcers in Sri Manakula Vinayagar Medical College and Hospital, Pondicherry

Background: Diabetic foot ulcer is one of the major surgical problem leading to hospital admission. Diabetic foot ulcer patients with uncontrolled diabetes may end up in forefoot amputation. Early aggressive debridement, control of blood sugar and empirical antibiotic therapy would reduce the morbidities in patients with diabetic foot ulcer. Further the knowledge of commonly isolated microbes and their antibiotic sensitivity pattern would be helpful to start empirical therapy. The purpose of this study was to determine the microbiological profile of diabetic foot infections (DFIs) and assess the antibiotic susceptibility of the causative agents.Methods: This cross-sectional study was conducted in 115 patients admitted with diabetic foot ulcer over a period of 9 months from October 2015 to June 2016 at the department of general surgery, Sri Manakula Vinayagar Medical College and Hospital, Pondicherry. Tissue scrapping samples were collected and processed as per standard guidelines.Results: 167 organisms were isolated from 115 patients. 52% of culture showed polymicrobial growth. There was increased prevalence of gram-negative organisms 53% compared to gram positive organisms 47%. When comes to individual isolate, Staphylococcus aureus was the most common organism isolated 24.6% followed by Pseudomonas aeruginosa 21%. All gram-positive aerobes were sensitive to vancomycin and gram-negative isolates were sensitive to amikacin, piperacillin-tazobactum, gentamycin and cefotaxime.Conclusions: Staphylococcus aureus and Pseudomonas were the common pathogens isolated. This study recommends use of vancomycin along with piperacillin-tazobactum as an empirical therapy along with adequate blood sugar control and early debridement of devitalized tissues in patients with diabetic foot infections.

Detection of the frequency of microbial defilement “in-use” soap products at various dental departments: A microbiological research

Context: Hand washing by a dental health professional before having contact with a patient's oral cavity is considered a fundamental dental clinic infection control measure. Aims: The aim of this study was to evaluate bar soap and liquid soap from dental departments for microbial contamination while it was in use. Settings and Design: This exploratory, cross-sectional study was carried out to identify microorganisms' presence in handwashing with liquid and bar soap at clinical and nonclinical departments in a dental college. Subjects and Methods: In the 2-month study period, all the dental students, dental faculty, and the other auxiliaries present were the participants, and a total of 35 handwashing place samples from 15 different dental departments were collected. The test tube samples of bar soap and liquid soap were all transferred to the microbiology laboratory for microbiological analysis of the samples. Statistical Analysis Used: Data were analyzed using a one-sample paired t-test and independent Student's t-test. Results: Nine different microbial species were identified. In both soaps, the abundance of Staphylococcus aureus was higher as compared to that of other microorganisms. Further, in both soaps, the mean number of microorganisms increased statistically significantly (P 0.05) between the two groups (soaps). Conclusions: The microbial load of the in-use bar soap and liquid soap constituted a mixed flora of Gram-positive bacteria, Gram-negative bacteria, aerobes, anaerobes, and fungi. The results indicate that the bar soap under “in-use” condition harbors more of microorganisms as compared to that of liquid soap, and handwashing with such a soap may lead to the spread of infection.

SEVERE HYPERSENSITIVITY REACTION WITH ERYTHROMYCIN ETHYLSUCCINATE: A CASE REPORT

Erythromycin is considered to be one of the safest antimicrobials exhibiting good activity against Gram-positive aerobes and some Gram-negative aerobes but rare cases of hypersensitivity reactions to erythromycin alone or with its base (esteolate or ethylsuccinate) can occur. Here, we report the case of severe hypersensitivity reaction in a female patient with upper respiratory tract infection and underwent treatment with erythromycin ethylsuccinate (400mg TDS). Twenty-four hours after the initiation of therapy with erythromycin ethylsuccinate, the patient developed severe rash starting from the nape of the neck spreading throughout the body with generalized pruritus and mild icterus. Marked improvement was noticed within 2 days after cessation of erythromycin ethylsuccinate. Physicians must be aware of the adverse effects of erythromycin ethylsuccinate before prescribing the drug.

Integrating Bacterial Identification and Susceptibility Testing: A Simple and Rapid Approach to Reduce the Turnaround Time in the Management of Blood Cultures.

We evaluated a rapid bacterial identification (rID) and a rapid antimicrobial susceptibility testing by disk diffusion (rAST) from positive blood culture to overcome the limitations of the conventional methods and reduce the turnaround time in bloodstream infection diagnostics. The study included hemocultures flagged as positive by bacT/ALERT®, identification by MALDI-TOF MS, and rAST. The results were compared to identification and antimicrobial susceptibility testing (AST) results by current standard methods, after 24 h incubation. For rAST categorical agreement (CA), very major errors (VME), major errors (ME), and minor errors (mE) were calculated. A total of 524 bacterial samples isolated from blood cultures were obtained, including 246 Gram-negative (GN) and 278 Gram-positive (GP) aerobes. The overall concordance of rID was 88.6%, and it was highest among GN (96%). A total of 2196 and 1476 antimicrobial agent comparisons were obtained for GN and GP, respectively. Evaluation of rAST, CA, VME, ME, and mE disclosed 97.7, 0.7, 0.5, and 1.1% for GN and 98.0, 0.5, 0.7, and 0.8% for GP, respectively. Meropenem CA, VME, and ME were 98.3, 0.5, and 0.5%, respectively; mE was not observed. Oxacillin CA, ME, and mE were 97.4, 1.6, and 0.6%, respectively; VME was not observed. Overall, kappa scores of the results of the comparisons demonstrated the high agreement between rAST and the standard method. Identification and AST of aerobic bacteria from positive blood cultures after a short period of incubation on solid blood agar is a fast and reliable method that may improve the management of bloodstream infections.

Differential effects of inappropriate empirical antibiotic therapy in adults with community-onset gram-positive and gram-negative aerobe bacteremia

Bacteremia is associated with high morbidity and mortality, which contribute substantially to health care costs. A beneficial influence of appropriate empirical antimicrobial therapy (EAT) on patient outcome is evidenced; However, the evidence highlighting a comparison of clinical manifestations and of the effects of inappropriate EAT between Gram-positive and Gram-negative bacteremia is insufficient. In a retrospective 6-year cohort study, the total 2053 adults (Gram-positive, 566; Gram-negative 1487) presenting with community-onset monomicrobial aerobes bacteremia were recruited. Inappropriate EAT was defined as the first dose of an appropriate antimicrobial agent not being administered within the first 24 h after blood cultures were drawn. Although the bacteremia severity (a Pitt bacteremia score) at onset, comorbidity severity (the McCabe-Johnson classification), and 28-day mortality rate were similar in the two groups. Furthermore, after adjustment of independent predictors of 28-day mortality respectively recognized by the multivariate regression model in Gram-negative and Gram-positive groups, the Kaplan–Meier curve and Cox regression analysis revealed a significant difference (adjust odds ratio [AOR], 2.68; P < 0.001) between appropriate and inappropriate EAT in the Gram-negative group, but not in the Gram-positive group (AOR, 1.54; P = 0.06). Conclusively, patients with Gram-positive and Gram-negative bacteremia exhibited the similar presentation in bacteremia severity, but a greater impact of inappropriate EAT on survival of patients with Gram-negative aerobe bacteremia was evidenced.

Dynamics of Biofilm Formation by Salmonella Typhimurium and Beef Processing Plant Bacteria in Mono- and Dual-Species Cultures.

This study aimed to determine the impact of bacteria from a beef plant conveyor belt on the biofilm formation of Salmonella in dual-species cultures. Beef plant isolates (50) including 18 Gram-negative aerobes (GNA), 8 Gram-positive aerobes (GPA), 5 lactic acid bacteria (LAB), 9 Enterobacteriaceae (EB), and 10 generic Escherichia coli (GEC) were included for developing biofilms in mono- and co-culture with S. Typhimurium at 15°C for 6days. Five selected cultures in planktonic form and in biofilms were tested for susceptibility to two commonly used sanitizers (i.e. E-San and Perox-EPlus). In mono-cultures, ≥ 80, 67, 61, 20, and 13% of GEC, EB, GNA, LAB, and GPA, respectively, developed measurable biofilms after 2days, while all co-culture pairings with S. Typhimurium achieved some level of biofilm production. The predominant effect of EB and only effect of GEC strains on the biofilm formation of S. Typhimuriumwas antagonistic, while that of Gram-positive bacteria was synergistic, with the effect being more prominent on day 6. The effect was highly variable for the GNA isolates. Six aerobic isolates that formed moderate/strong biofilms by day 2 greatly boosted the co-culture biofilm formation. Seven Gram-negative bacteria were antagonistic against the biofilm formation of the co-cultures. Both sanitizers completely inactivated the selected planktonic cultures, but were largely ineffective against biofilms. In conclusion, all beef plant isolates assessed formed biofilms when paired with S. Typhimurium. Aerobic biofilm formers may create a more favorable condition for Salmonella biofilm formation, while some beef plant isolates have potential as a biocontrol strategy for Salmonella biofilms.

In Vitro and In Vivo Activities of DS-2969b, a Novel GyrB Inhibitor, and Its Water-Soluble Prodrug, DS11960558, against Methicillin-Resistant Staphylococcus aureus.

DS-2969b is a novel GyrB inhibitor under clinical development. In this study, the in vitro activity of DS-2969b and the in vivo activities of DS-2969b and its water-soluble prodrug, DS11960558, against methicillin-resistant Staphylococcus aureus (MRSA) were evaluated. DS-2969b inhibited the supercoiling activity of S. aureus DNA gyrase and the decatenation activity of its topoisomerase IV. DS-2969b showed antibacterial activity against Gram-positive aerobes but not against Gram-negative aerobes, except for Moraxella catarrhalis and Haemophilus influenzae DS-2969b was active against MRSA with an MIC90 of 0.25 μg/ml, which was 8-fold lower than that of linezolid. The presence of a pulmonary surfactant did not affect the MIC of DS-2969b. DS-2969b showed time-dependent slow killing against MRSA. The frequency of spontaneous resistance development was less than 6.2 × 10-10 in all four S. aureus isolates at 4× MIC of DS-2969b. In a neutropenic MRSA-induced murine muscle infection model, DS-2969b was more efficacious than linezolid by both the subcutaneous and oral routes. DS-2969b and DS11960558 showed efficacy in a neutropenic murine MRSA lung infection model. The pharmacokinetics and pharmacodynamics of DS-2969b and DS11960558 against MRSA were characterized in a neutropenic murine thigh infection model; the percentage of time during the dosing period in which the free drug concentration exceeded the MIC (fTMIC) correlated best with in vivo efficacy, and the static percent fTMIC was 43 to 49%. A sufficient fTMIC was observed in a phase 1 multiple-ascending-dose study of DS-2969b given orally at 400 mg once a day. These results suggest that DS11960558 and DS-2969b have potential for use as intravenous-to-oral step-down therapy for treating MRSA infections with a higher efficacy than linezolid.

Spectrum of microbiota in diabetic foot infections in a teaching hospital of Uttar Pradesh

Background: Diabetic foot ulcer is the leading cause of non-traumatic lower extremity amputations. A prospective case–control study was carried out on 50 patients with diabetic foot ulcers (cases) and 50 with non-diabetic foot ulcers (controls) to determine the microbiological profile, their antibiotic sensitivity patterns along with different demographic parameters. The prevalence of extended-spectrum beta-lactamases (ESBLs) producers, carbapenemase producers, and methicillin-resistant Staphylococcus aureus among the isolates and the potential risk factors for infection of ulcers with these multidrug-resistant organisms (MDROs) was also studied along with the outcome of these infections. Objectives: The present study aims at identifying the microbiological spectrum in these diabetic foot infections and their antibiotic sensitivity pattern in a developing country, like India. Materials and Methods: Clinical specimens were taken from each patient with diabetic and non-diabetic foot ulcers. These specimens were processed for culture (aerobic and anaerobic), further identification and antibiotic sensitivity testing. ESBL and carbapenemase production was detected by phenotypic methods and automated VITEK-2 system, and the results were mutually compared by the two methods. Results: A total of 158 organisms (155 bacteria and 3 fungi) were isolated giving an average of two organisms/patient. Cases were mostly positive for polymicrobial growth (77%) as compared to controls, and tissue was the most yielding sample. Gram-negative aerobes were predominantly isolated, followed by Gram-positive aerobes. Anaerobic Gram-negative (3%) and fungal (3%) isolates were also seen in the case samples. Conclusion: Escherichia coli among the Gram-negative (33%) and S. aureus among the Gram-positive (7%) were the predominantly isolated organisms, while Candida was the most predominantly isolated fungus. A strong association of peripheral vascular disease (PVD), smoking (P = 0.001), as well as neuropathy (P 5 cm2, and osteomyelitis (P

Nocardia spp. – characteristics, pathogenicity, treatment

Abstract Nocardia spp. bacteria are Gram-positive aerobes occurring worldwide. They cause nocardiosis, of which the most common forms are pulmonary nocardiosis and cutaneous nocardiosis. The pulmonary form progresses as a result of aspiration of pathogens into the respiratory tract, whereas the cutaneous nocardiosis, can spread to other organs (often to CNS) and includes Madura foot, both mycetoma and systemic. Infections usually affect people with immunodeficiency, for example infected with HIV or after immunosupression therapy. Nocardia asteroides is responsible for the majority of infections in humans. Diagnostic methods include cell culture and PCR. The symptoms vary depending on the form of the illness. Cough and hemoptysis are characteristic for pulmonary nocardiosis, while abscesses are typical for the cutaneous form. When the illness spreads, the symptoms vary depending on the organ. The treatment of choice is sulfonamide. 1. Introduction. 2. History. 3. Characteristics of Nocardia spp. 4. Systematics. 5. Pathogenicity. 6. Diagnostics. 7. Treatment. 8. Summary

Draft Genome Sequence of Paenarthrobacter nicotinovorans Hce-1.

ABSTRACTPaenarthrobacter nicotinovorans Hce-1 is a Gram-positive obligate aerobe actinomycete. We report here the complete genome sequence of this organism. The genome has a length of 4,174,362 bp and contains 4,568 protein-coding genes, 64 tRNA operons, and 22 rRNA operons. Its GC content in the gene region is 63.4%.

Sinonasal T2R-mediated nitric oxide production in response to Bacillus cereus.

Upper airway epithelial cells produce bactericidal nitric oxide (NO) in response to both gram-positive and gram-negative bacteria. Our previous work demonstrated that T2R38, a bitter taste receptor (T2R) expressed in airway epithelium, produces NO in response to quorum-sensing molecules secreted by Pseudomonas aeruginosa. We also demonstrated that Staphylococci products elicit an NO response when using a T2R-independent pathway. When screening additional human pathogens for epithelial T2R activation, we found that the gram-positive aerobe Bacillus cereus secretes a T2R agonist that yields NO production. The objective of this study was to characterize the activating B. cereus product(s) and to describe the epithelial cell signaling pathway involved. Sinonasal air-liquid interface cultures were treated with B. cereus conditioned medium (CM), and NO production was measured by using 4-amino-5-methylamino-2',7'-difluorofluorescein fluorescence imaging. Ciliary beat frequency (CBF) was assessed in response to B. cereus CM. Pharmacologic studies that use inhibitors of the T2R-signaling pathway were used to determine if the production of NO was mediated by a T2R. Purification studies were performed to analyze the physical properties of the activating product(s) contained in the CM. A product(s) secreted by B. cereus induced NO production and increased CBF. The response varied markedly between individual patients and involved two important components of bitter taste signaling, phospholipase C isoform β-2 and the transient receptor potential melastatin isoform 5 ion channel. This study demonstrated that a B. cereus product(s) elicited an NO-mediated innate defense response in upper airway epithelium that seemed to be partially mediated by a T2R signaling pathway. The active product that elicited the NO response was likely a small nonpeptide compound, but further purification is required for identification. Patient variation in the NO response to B. cereus products could potentially be due to genetic differences in T2Rs.

A simple method for rapid microbial identification from positive monomicrobial blood culture bottles through matrix-assisted laser desorption ionization time-of-flight mass spectrometry.

Rapid identification of microbes in the bloodstream is crucial in managing septicemia because of its high disease severity, and direct identification from positive blood culture bottles through matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) can shorten the turnaround time. Therefore, we developed a simple method for rapid microbiological identification from positive blood cultures by using MALDI-TOF MS. We modified previously developed methods to propose a faster, simpler and more economical method, which includes centrifugation and hemolysis. Specifically, our method comprises two-stage centrifugation with gravitational acceleration (g) at 600g and 3000g, followed by the addition of a lysis buffer and another 3000g centrifugation. In total, 324 monomicrobial bacterial cultures were identified. The success rate of species identification was 81.8%, which is comparable with other complex methods. Theidentification success rate was the highest for Gram-negative aerobes (85%), followed by Gram-positive aerobes (78.2%) and anaerobes (67%). The proposed method requires less than 10min, costs less than US$0.2 per usage, and facilitates batch processing. We conclude that this method is feasible for clinical use in microbiology laboratories, and can serve as a reference for treatments or further complementary diagnostic testing.

Inflammatory markers as risk factors for infection with multidrug-resistant microbes in diabetic foot subjects

BackgroundDiabetic foot ulcers (DFUs), a dreadful microvascular complication of diabetes is responsible for substantial increase in morbidity and mortality. Infection, not a cause, but a consequence in DFUs that accounts for minor or major limb loss. The current study aimed to evaluate the microbial etiology of infected diabetic foot ulcers in northern tertiary care hospital, assessment of risk factors and role of inflammatory markers involved in colonization of multidrug-resistant organisms (MDROs) and their impact on the outcome. MethodsPus aspirates and soft tissue samples from 65 patients with infected DFUs were collected and processed for aerobic culture analysis. Serum concentrations of IL-6 and TNF-α were determined by enzyme linked immuno-sorbent assay. ResultsAerobic gram-negative isolates were more commonly present (74.7%), followed by gram-positive aerobes (25.2%). Fifty-seven percent patients were positive for MDROs. IL-6 (pg/mL) was significantly lower in diabetic patients with MDROs infected foot ulcers than without (47.0±17.2 vs. 78.3±22.1 vs. p=<0.001) and TNF-α (pg/mL) was also significantly diminished in MDROs infected subjects than without (144.2±25.8 vs. 168.7±20.9, p<0.001) respectively. ConclusionsIn this study diabetic foot wounds harbored by MDROs were associated with longer duration of ulcer and increased ulcer size. Poor glycemic control was also a confounding factor in mounting MDROs infected ulcers. The declined levels WBCs and neutrophils as well as of cytokines IL-6 and TNF-alpha explains compromised immune responses of host in multi drug resistant infections.

Randomized, Open-Label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects.

Omadacycline is a first-in-class aminomethylcycline antibiotic with microbiological activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacteria that is being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The bioavailability of a phase 3 tablet formulation relative to that obtained via intravenous (i.v.) administration (and of other oral formulations relative to that of the phase 3 tablet) was investigated in an open-label, randomized, four-period, crossover study with healthy subjects age 18 to 50 years. Subjects received omadacycline at 100 mg i.v., 300 mg orally as two different tablet formulations with different dissolution profiles, and 300 mg as an oral solution. Plasma omadacycline concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Twenty of 24 subjects completed all treatment periods. The two tablet formulations produced equivalent total exposures. The phase 3 tablet produced an exposure equivalent to that of the 100-mg i.v. dose, with a geometric mean ratio (90% confidence intervals [CI]) for area under the concentration-time curve from 0 h to infinity [AUC∞]) of 1.00 (0.93, 1.07). The absolute bioavailability of the tablets was approximately 34.5%. Intersubject variability was consistent among the oral formulations (∼20 to 25%). Single oral and i.v. doses of omadacycline were well tolerated; three subjects experienced mild adverse events (dizziness, nausea, and vomiting) that resolved without intervention. A 300-mg dose of the tablet formulation of omadacycline intended for use in phase 3 studies produced a total exposure equivalent to that of a 100-mg i.v. dose.

The underappreciated in vitro activity of tedizolid against Bacteroides fragilis species, including strains resistant to metronidazole and carbapenems

Because Bacteroides fragilis has the ability to develop mechanisms of resistance to almost all antibiotics, we studied the comparative in vitro activity of tedizolid against 124 Bacteroides group species clinical isolates, including carbapenem, metronidazole and piperacillin-tazobactam resistant strains. Tedizolid had an MIC90 of 2 μg/ml (range, 0.5–4 μg/ml) and was 1–4 times more active than linezolid that had an MIC90 of 8 μg/ml (range, 2–16 μg/ml). It was also active (MICs 0.5–2 μg/ml) against the 27 ertapenem, 2 metronidazole and 12 piperacillin-tazobactam resistant strains tested. This suggests that tedizolid may be useful treating infections, including bacteremias, due to resistant B. fragilis group species, as well as, mixed skin and soft tissue infections such as diabetic foot infections caused by Gram-positive aerobes and B. fragilis group species.

In Vitro and In Vivo Assessments of Cardiovascular Effects with Omadacycline.

Omadacycline is a first-in-class aminomethylcycline antibiotic with a broad spectrum of activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacterial pathogens. A series of nonclinical studies, including mammalian pharmacologic receptor binding studies, human ether-a-go-go-related gene (hERG) channel binding studies, studies of the effects on ex vivo sinoatrial (SA) node activity, and studies of in vivo effects on cardiovascular function in the cynomolgus monkey, was undertaken to assess the cardiovascular risk potential. Omadacycline was found to bind almost exclusively to the muscarinic subtype 2 acetylcholine receptor (M2), and in the SA node model it antagonized the effect of a pan-muscarinic agonist (carbamylcholine) in a concentration-dependent manner. Omadacycline exhibited no effect on hERG channel activity at 100 μg/ml (179.5 μM), with a 25% inhibitory concentration of 166 μg/ml (298.0 μM). Omadacycline had no effect on QTc in conscious monkeys at doses up to 40 mg/kg of body weight. Overall, omadacycline appears to attenuate the parasympathetic influence on the heart rate but has a low potential to induce cardiac arrhythmia or to have clinically significant cardiovascular toxicity.

Enhanced efficacy of clindamycin hydrochloride encapsulated in PLA/PLGA based nanoparticle system for oral delivery.

Clindamycin hydrochloride (CLH) is a clinically important oral antibiotic with wide spectrum of antimicrobial activity that includes gram-positive aerobes (staphylococci, streptococci etc.), most anaerobic bacteria, Chlamydia and certain protozoa. The current study was focused to develop a stabilised clindamycin encapsulated poly lactic acid (PLA)/poly (D,L-lactide-co-glycolide) (PLGA) nano-formulation with better drug bioavailability at molecular level. Various nanoparticle (NPs) formulations of PLA and PLGA loaded with CLH were prepared by solvent evaporation method varying drug: polymer concentration (1:20, 1:10 and 1:5) and characterised (size, encapsulation efficiency, drug loading, scanning electron microscope, differential scanning calorimetry [DSC] and Fourier transform infrared [FTIR] studies). The ratio 1:10 was found to be optimal for a monodispersed and stable nano formulation for both the polymers. NP formulations demonstrated a significant controlled release profile extended up to 144 h (both CLH-PLA and CLH-PLGA). The thermal behaviour (DSC) studies confirmed the molecular dispersion of the drug within the system. The FTIR studies revealed the intactness as well as unaltered structure of drug. The CLH-PLA NPs showed enhanced antimicrobial activity against two pathogenic bacteria Streptococcus faecalis and Bacillus cereus. The results notably suggest that encapsulation of CLH into PLA/PLGA significantly increases the bioavailability of the drug and due to this enhanced drug activity; it can be widely applied for number of therapies.

Discovery, pharmacology, and clinical profile of omadacycline, a novel aminomethylcycline antibiotic

Omadacycline is novel, aminomethyl tetracycline antibiotic being developed for oral and intravenous (IV) administration for the treatment of community-acquired bacterial infections. Omadacycline is characterized by an aminomethyl substituent at the C9 position of the core 6-member ring. Modifications at this position result in an improved spectrum of antimicrobial activity by overcoming resistance known to affect older generation tetracyclines via ribosomal protection proteins and efflux pump mechanisms. In vitro, omadacycline has activity against Gram-positive and Gram-negative aerobes, anaerobes, and atypical pathogens including Legionella and Chlamydia spp. Omadacycline offers once daily oral and IV dosing and a clinical tolerability and safety profile that compares favorably with contemporary antibiotics used across serious community-acquired infections where resistance has rendered many less effective. In studies in patients with complicated skin and skin structure infections, including those with MRSA infections, omadacycline exhibited an efficacy and tolerability profile that was comparable to linezolid. Ongoing and planned clinical studies are evaluating omadacycline as monotherapy for treating serious community-acquired bacterial infections including Acute Bacterial Skin and Skin Structure Infections (ABSSSI) and Community-Acquired Bacterial Pneumonia (CABP). This review provides an overview of the discovery, microbiology, nonclinical data, and available clinical safety and efficacy data for omadacycline, with reference to other contemporary tetracycline-derived antibiotics.

Pharmacokinetic study of benzylpenicillin potassium after intramuscular administration in rabbits

BACTERIAL diseases are common in laboratory and pet rabbits, and successful treatment depends on careful and accurate diagnosis, correction of underlying husbandry deficits and management of concurrent disease processes (Lennox...