Antibiotics for treatment of leptospirosis.

BACKGROUND: Leptospirosis is a disease transmitted from animals to humans through water, soil, or food contaminated with the urine of infected animals, caused by pathogenic Leptospira species. Antibiotics are commonly prescribed for the management of leptospirosis. Despite the widespread use of antibiotic treatment for leptospirosis, there seems to be insufficient evidence to determine its effectiveness or to recommend antibiotic use as a standard practice. This updated systematic review evaluated the available evidence regarding the use of antibiotics in treating leptospirosis, building upon a previously published Cochrane review. OBJECTIVES: To evaluate the benefits and harms of antibiotics versus placebo, no intervention, or another antibiotic for the treatment of people with leptospirosis. SEARCH METHODS: We identified randomised clinical trials following standard Cochrane procedures. The date of the last search was 27 March 2023. SELECTION CRITERIA: We searched for randomised clinical trials of various designs that examined the use of antibiotics for treating leptospirosis. We did not impose any restrictions based on the age, sex, occupation, or comorbidities of the participants involved in the trials. Our search encompassed trials that evaluated antibiotics, regardless of the method of administration, dosage, and schedule, and compared them with placebo or no intervention, or compared different antibiotics. We included trials regardless of the outcomes reported. DATA COLLECTION AND ANALYSIS: During the preparation of this review, we adhered to the Cochrane methodology and used Review Manager. The primary outcomes were all-cause mortality and serious adverse events (nosocomial infection). Our secondary outcomes were quality of life, proportion of people with adverse events considered non-serious, and days of hospitalisation. To assess the risk of bias of the included trials, we used the RoB 2 tool, and for evaluating the certainty of evidence we used GRADEpro GDT software. We presented dichotomous outcomes as risk ratios (RR) and continuous outcomes as mean differences (MD), both accompanied by their corresponding 95% confidence intervals (CI). We used the random-effects model for all our main analyses and the fixed-effect model for sensitivity analyses. For our primary outcome analyses, we included trial data from the longest follow-up period. MAIN RESULTS: We identified nine randomised clinical trials comprising 1019 participants. Seven trials compared two intervention groups and two trials compared three intervention groups. Amongst the trials comparing antibiotics versus placebos, four trials assessed penicillin and one trial assessed doxycycline. In the trials comparing different antibiotics, one trial evaluated doxycycline versus azithromycin, one trial assessed penicillin versus doxycycline versus cefotaxime, and one trial evaluated ceftriaxone versus penicillin. One trial assessed penicillin with chloramphenicol and no intervention. Apart from two trials that recruited military personnel stationed in endemic areas or military personnel returning from training courses in endemic areas, the remaining trials recruited people from the general population presenting to the hospital with fever in an endemic area. The participants' ages in the included trials was 13 to 92 years. The treatment duration was seven days for penicillin, doxycycline, and cephalosporins; five days for chloramphenicol; and three days for azithromycin. The follow-up durations varied across trials, with three trials not specifying their follow-up periods. Three trials were excluded from quantitative synthesis; one reported zero events for a prespecified outcome, and two did not provide data for any prespecified outcomes. Antibiotics versus placebo or no intervention The evidence is very uncertain about the effect of penicillin versus placebo on all-cause mortality (RR 1.57, 95% CI 0.65 to 3.79; I2 = 8%; 3 trials, 367 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin or chloramphenicol versus placebo on adverse events considered non-serious (RR 1.05, 95% CI 0.35 to 3.17; I2 = 0%; 2 trials, 162 participants; very low-certainty evidence). None of the included trials assessed serious adverse events. Antibiotics versus another antibiotic The evidence is very uncertain about the effect of penicillin versus cephalosporin on all-cause mortality (RR 1.38, 95% CI 0.47 to 4.04; I2 = 0%; 2 trials, 348 participants; very low-certainty evidence), or versus doxycycline (RR 0.93, 95% CI 0.13 to 6.46; 1 trial, 168 participants; very low-certainty evidence). The evidence is very uncertain about the effect of cefotaxime versus doxycycline on all-cause mortality (RR 0.18, 95% CI 0.01 to 3.78; 1 trial, 169 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus doxycycline on serious adverse events (nosocomial infection) (RR 0.62, 95% CI 0.11 to 3.62; 1 trial, 168 participants; very low-certainty evidence) or versus cefotaxime (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of doxycycline versus cefotaxime on serious adverse events (nosocomial infection) (RR 1.01, 95% CI 0.15 to 7.02; 1 trial, 175 participants; very low-certainty evidence). The evidence is very uncertain about the effect of penicillin versus cefotaxime (RR 3.03, 95% CI 0.13 to 73.47; 1 trial, 175 participants; very low-certainty evidence), versus doxycycline (RR 2.80, 95% CI 0.12 to 67.66; 1 trial, 175 participants; very low-certainty evidence), or versus chloramphenicol on adverse events considered non-serious (RR 0.74, 95% CI 0.15 to 3.67; 1 trial, 52 participants; very low-certainty evidence). Funding Six of the nine trials included statements disclosing their funding/supporting sources and three trials did not mention funding source. Four of the six trials mentioning sources received funds from public or governmental sources or from international charitable sources, and the remaining two, in addition to public or governmental sources, received support in the form of trial drug supply directly from pharmaceutical companies. AUTHORS' CONCLUSIONS: As the certainty of evidence is very low, we do not know if antibiotics provide little to no effect on all-cause mortality, serious adverse events, or adverse events considered non-serious. There is a lack of definitive rigorous data from randomised trials to support the use of antibiotics for treating leptospirosis infection, and the absence of trials reporting data on clinically relevant outcomes further adds to this limitation.

Comprehensive stability analysis of 13 ß-lactams and ß-lactamase inhibitors in in vitro media, and novel supplement dosing strategy to mitigate thermal drug degradation.

Non-clinical antibiotic development relies on in vitro susceptibility and infection model studies. Validating the achievement of the targeted drug concentrations is essential to avoid under-estimation of drug effects and over-estimation of resistance emergence. While certain ß-lactams (e.g., imipenem) and ß-lactamase inhibitors (BLIs; clavulanic acid) are believed to be relatively unstable, limited tangible data on their stability in commonly used in vitro media are known. We aimed to determine the thermal stability of 10 ß-lactams and 3 BLIs via LC-MS/MS in cation-adjusted Mueller Hinton broth at 25 and 36°C as well as agar at 4 and 37°C, and in water at -20, 4, and 25°C. Supplement dosing algorithms were developed to achieve broth concentrations close to their target over 24 h. During incubation in broth (pH 7.25)/agar, degradation half-lives were 16.9/21.8 h for imipenem, 20.7/31.6 h for biapenem, 29.0 h for clavulanic acid (studied in broth only), 23.1/71.6 h for cefsulodin, 40.6/57.9 h for doripenem, 46.5/64.6 h for meropenem, 50.8/97.7 h for cefepime, 61.5/99.5 h for piperacillin, and >120 h for all other compounds. Broth stability decreased at higher pH. All drugs were ≥90% stable for 72 h in agar at 4°C. Degradation half-lives in water at 25°C were >200 h for all drugs except imipenem (14.7 h, at 1,000 mg/L) and doripenem (59.5 h). One imipenem supplement dose allowed concentrations to stay within ±31% of their target concentration. This study provides comprehensive stability data on ß-lactams and BLIs in relevant in vitro media using LC-MS/MS. Future studies are warranted applying these data to antimicrobial susceptibility testing and assessing the impact of ß-lactamase-related degradation.

Successful transfer of passive immunity: the natural alternative to antibiotics for boosting the survival of intensively reared dairy goat kids.

In dairy operations, antibiotics have traditionally been used to treat, prevent, and control diseases. However, given the mounting global crisis of antimicrobial resistance (AMR), farmers are urged to re-assess and reduce their reliance on antibiotics. Thus, this randomized, double-blinded cohort study aimed to estimate the prevalence of failed and successful transfer of passive immunity (FTPI and STPI) in dairy goat kids reared under commercial conditions, and the effects of antibiotic metaphylaxis on the pre-weaning (≤42 d old) mortality in FTPI and STPI kids. Plasma concentration of immunoglobulin G at 1d old (pIgG-24 h) was measured in 747 male Saanen kids for the determination of FTPI and STPI (pIgG-24 h < 12 and ≥12 g/L, respectively). Kids were then randomly divided into two groups: those receiving a single penicillin injection at 1 d old (PEN), and those receiving no treatment (CTR). The mean (±SD) pIgG-24 h and initial BW (IBW) were 17 ± 9.8 g/L and 4.1 ± 0.64 kg. The prevalence of FTPI was 29% (220/747 kids). Gastrointestinal complications were the primary cause of death (41%), followed by septicemia (22%) and arthritis (17%). A single penicillin injection reduced preweaning mortality by 55% (10 vs 22%, PEN vs CTR). However, results suggest that such a decline was mainly driven by the improved survival rates among FTPI kids, which increased by 19% (from 62% in CTR-FTPI to 82% in PEN-FTPI), as opposed to an 8% increase among STPI kids (from 85% in CTR-STPI to 93% in PEN-STPI). Additionally, the odds of mortality ≤ 42 d old were threefold higher in the CTR-FTPI group when compared to both the CTR-STPI and PEN-FTPI groups, suggesting a potential parity between STPI and PEN for mortality rate reduction. Taken together, the results indicate that although metaphylactic antibiotics can halve preweaning mortality, similar improvements are likely to be achieved via increased STPI rates. Furthermore, by targeting metaphylactic interventions to high-risk groups (i.e., those displaying signs of inadequate colostrum intake and/or low birth BW), farmers could reduce treatment costs and mitigate AMR risks. While these findings carry considerable weight for commercial dairy goat practices, their applicability to other systems (i.e., extensive, semi-intensive, mohair, meat systems) warrants further investigation.

The Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA): investigating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin pharmacokinetics from birth to adolescence.

BACKGROUND: Pharmacokinetic (PK) data underlying paediatric penicillin dosing remain limited, especially in critical care. OBJECTIVES: The primary objective of the Neonatal and Paediatric Pharmacokinetics of Antimicrobials study (NAPPA) was to characterize PK profiles of commonly used penicillins using data obtained during routine care, to further understanding of PK variability and inform future evidence-based dosing. METHODS: NAPPA was a multicentre study of amoxicillin, co-amoxiclav, benzylpenicillin, flucloxacillin and piperacillin/tazobactam. Patients were recruited with informed consent. Antibiotic dosing followed standard of care. PK samples were obtained opportunistically or at optimal times, frozen and analysed using UPLC with tandem MS. Pharmacometric analysis was undertaken using NONMEM software (v7.3). Model-based simulations (n = 10 000) tested PTA with British National Formulary for Children (BNFC) and WHO dosing. The study had ethical approval. RESULTS: For the combined IV PK model, 963 PK samples from 370 participants were analysed simultaneously incorporating amoxicillin, benzylpenicillin, flucloxacillin and piperacillin data. BNFC high-dose regimen simulations gave these PTA results (median fT>MIC at breakpoints of specified pathogens): amoxicillin 100% (Streptococcus pneumoniae); benzylpenicillin 100% (Group B Streptococcus); flucloxacillin 48% (MSSA); and piperacillin 100% (Pseudomonas aeruginosa). Oral population PK models for flucloxacillin and amoxicillin enabled estimation of first-order absorption rate constants (1.16 h-1 and 1.3 h-1) and bioavailability terms (62.7% and 58.7%, respectively). CONCLUSIONS: NAPPA represents, to our knowledge, the largest prospective combined paediatric penicillin PK study undertaken to date, and the first paediatric flucloxacillin oral PK model. The PTA results provide evidence supportive of BNFC high-dose IV regimens for amoxicillin, benzylpenicillin and piperacillin.

Nickel sulfide and dysprosium-doped nickel sulfide nanoparticles: Dysprosium-induced variation in properties, in vitro chemo-photothermal behavior, and antibacterial activity.

Newer materials for utilization in multi-directional therapeutic actions are investigated, considering delicate design principles involving size and shape control, surface modification, and controllable drug loading and release. Multi-faceted properties are imparted to the engineered nanoparticles, like magnetism, near-infrared absorption, photothermal efficiency, and suitable size and shape. This report presents nickel sulfide and dysprosium-doped nickel sulfide nanoparticles with poly-ß-cyclodextrin polymer coating. The nanoparticles belong to the orthorhombic crystal systems, as indicated by X-ray diffraction studies. The size and shape of the nanoparticles are investigated using Transmission Electron Microscope (TEM) and a particle-size analyzer. The particles show soft ferromagnetic characteristics with definite and moderate saturation magnetization values. The nickel sulfide nanoparticles' in vitro anticancer and antibacterial activities are investigated in free and 5-fluorouracil/penicillin benzathine-loaded forms. The 5-fluorouracil-encapsulation efficiency of the nanoparticles is around 87%, whereas it is above 92% in the case of penicillin benzathine. Both drugs are released slowly in a controlled fashion. The dysprosium-doped nickel sulfide nanoparticles show better anticancer activity, and the efficacy is more significant than the free drug. The nanoparticles are irradiated with a low-power 808 nm laser. The dysprosium-doped nickel sulfide nanoparticles attain a higher temperature on irradiation, i.e., above 59 °C. The photothermal conversion efficiency of this material is determined, and the significance of dysprosium doping is discussed. Contrarily, the undoped nickel sulfide nanoparticles show more significant antibacterial activity. This study presents a novel designed nanoparticle system and the exciting variation of properties on dysprosium doping in nickel sulfide nanoparticles.

A complete graph-based approach with multi-task learning for predicting synergistic drug combinations.

MOTIVATION: Drug combination therapy shows significant advantages over monotherapy in cancer treatment. Since the combinational space is difficult to be traversed experimentally, identifying novel synergistic drug combinations based on computational methods has become a powerful tool for pre-screening. Among them, methods based on deep learning have far outperformed other methods. However, most deep learning-based methods are unstable and will give inconsistent predictions even by simply changing the input order of drugs. In addition, the insufficient experimental data of drug combination screening limits the generalization ability of existing models. These problems prevent the deep learning-based models from being in service. RESULTS: In this article, we propose CGMS to address the above problems. CGMS models a drug combination and a cell line as a heterogeneous complete graph, and generates the whole-graph embedding to characterize their interaction by leveraging the heterogeneous graph attention network. Based on the whole-graph embedding, CGMS can make a stable, order-independent prediction. To enhance the generalization ability of CGMS, we apply the multi-task learning technique to train the model on drug synergy prediction task and drug sensitivity prediction task simultaneously. We compare CGMS's generalization ability with six state-of-the-art methods on a public dataset, and CGMS significantly outperforms other methods in the leave-drug combination-out scenario, as well as in the leave-cell line-out and leave-drug-out scenarios. We further present the benefit of eliminating the order dependency and the discrimination power of whole-graph embeddings, interpret the rationality of the attention mechanism, and verify the contribution of multi-task learning. AVAILABILITY AND IMPLEMENTATION: The code of CGMS is available via https://github.com/TOJSSE-iData/CGMS.

Epsilon poly-lysine in buffalo semen extender: A step towards reducing the development of antibiotic resistance.

The use of antibiotics in semen extenders can contribute to the development of antibiotic resistance. The objective of the study was to evaluate epsilon-polylysine (Ɛ-PL) as a substitute for antibiotics in the buffalo semen extender. For this, 20 semen ejaculates were collected from four Murrah buffalo bulls. Each ejaculate was divided into three equal aliquots and extended into an egg yolk-based semen extender containing either antibiotics (strepto-penicillin) or different concentrations of Ɛ-PL (0.64 and 1.28 g/L) to make the final concentration 80 million sperm/mL and cryopreserved as per the standard procedure. The antibiogram sensitivity test confirmed that Ɛ-PL is an effective antimicrobial against microbes present in buffalo semen ejaculates. Furthermore, the addition of Ɛ-PL in the semen extender significantly reduces the colony forming unit (CFU)/mL in cryopreserved semen equivalent to strepto-penicillin. The sperm motility and kinematic parameters assessed by a computer-assisted sperm analyser showed that Ɛ-PL did not inhibit either sperm motility not kinematic parameters of cryopreserved sperm. The flow-cytometric evaluation of frozen-thawed sperm revealed interesting results. The extender supplemented with Ɛ-PL protected sperm acrosome and mitochondrial membrane potential greater than the extender supplemented with strepto-penicillin. Further, Ɛ-PL reduced significantly the production of superoxide anions from mitochondria during the cryopreservation process. In this way, Ɛ-PL may be a suitable alternative to antibiotics in semen extenders. In conclusion, Ɛ-PL at a concentration of 0.64 g/L acts as an effective antimicrobial as well as antioxidant in semen extender for cryopreservation of buffalo sperm.

Preconception use of antibiotics and fecundability: a Danish prospective cohort study.

OBJECTIVE: To assess the association between preconception antibiotic use and fecundability, the per menstrual cycle probability of conception. DESIGN: SnartForaeldre.dk, a Danish prospective cohort study of women trying to conceive (2007-2020). SETTING: Not applicable. SUBJECT(S): 9462 female participants, median age 29 years at enrollment. EXPOSURE: Antibiotic use was defined by filled prescriptions retrieved from the Danish National Prescription Registry, using Anatomical Therapeutic Chemical codes, and modeled as time-varying (menstrual cycle-varying) exposure. MAIN OUTCOME MEASURE(S): Pregnancy status was reported on female follow-up questionnaires every 8 weeks for up to 12 months or until conception. Fecundability ratios (FR) and 95% confidence intervals (CI) were computed using proportional probabilities regression models, with adjustment for age, partner age, education, smoking, folic acid supplementation, body mass index, parity, cycle regularity, timing of intercourse, and sexually transmitted infections. RESULT(S): During all cycles of observation, the percentage of participants filing at least 1 antibiotic prescription was 11.9%; 8.6% had a prescription for penicillins, 2.1% for sulfonamides, and 1.8% for macrolides. Based on life-table methods, 86.5% of participants conceived within 12 cycles of follow-up. Recent preconception antibiotic use was associated with reduced fecundability (≥1 prescription vs. none: adjusted FR = 0.86; 95% CI, 0.76-0.99). For participants using penicillins, sulfonamides, or macrolides, the adjusted FRs were 0.97 (95% CI, 0.83-1.12), 0.68 (95% CI, 0.47-0.98), and 0.59 (95% CI, 0.37-0.93), respectively. CONCLUSION(S): Preconception use of antibiotics, specifically sulfonamides and macrolides, was associated with decreased fecundability compared with no use. The observed associations may be explained plausibly by confounding by indication, as we lacked data on indications for the prescribed antibiotics. Consequently, we cannot separate the effect of the medication from the effect of the underlying infection.

An overview of penicillin allergies for nurses.

ABSTRACT: Antibiotics are frequently reported as allergies by patients, particularly antibiotics from the penicillin family. Most of these reported allergies are benign, and the consequences of alternative therapies can be significant. This article provides background information on penicillin allergies and serves as a guide to penicillin allergy management.Reprinted with permission from Wrynn, A.F. An overview of penicillin allergies for nurses. Nurse Pract 2022; 47(9): 30-36. Copyright Wolters Kluwer. All rights reserved.

Syphilis in Dermatology: Recognition and Management.

The incidence of syphilis has been increasing in the USA since 2000. Notably, the coronavirus disease 2019 pandemic negatively impacted the public health efforts to contain the spread of sexually transmitted diseases including syphilis and congenital syphilis. Clinical manifestations of syphilis are predominantly mucocutaneous lesions, thus dermatologists are primed to recognize the myriad presentations of this disease. Primary syphilis is classically characterized by a painless transient chancre most often located in the genital area. Secondary syphilis typically manifests clinically as systemic symptoms in addition to a mucocutaneous eruption of which a variety of forms exist. Although less common in the era of effective penicillin treatment, late clinical manifestations of syphilis are described as well. In addition to recognition of syphilis on physical examination, several diagnostic tools may be used to confirm infection. Treponema pallidum spirochetes may be detected directly using histopathologic staining, darkfield microscopy, direct fluorescent antibody, and polymerase chain reaction assays. A table detailing the histopathologic features of syphilis is included in this article. Serologic testing, non-treponemal and treponemal tests, is the preferred method for screening and diagnosing syphilis infections. Two serologic testing algorithms exist to aid clinicians in diagnosing positive syphilis infection. Determining the correct stage of syphilis infection combines results of serologic tests, patient history, and physical examination findings. Using the current Centers for Disease Control and Prevention case definitions and treatment guidelines, a management algorithm is proposed here. Penicillin remains the pharmacological treatment of choice although specific clinical situations allow for alternative therapies. Syphilis is a reportable disease in every state and should be reported by stage according to individual state requirements. Screening recommendations are largely based upon risks encountered through sexual exposures. Likewise, sexual partner management includes evaluating and treating persons exposed to someone diagnosed with an infective stage of syphilis. Close clinical follow-up and repeat testing are recommended to ensure appropriate response to treatment. This guide will discuss the current epidemiology of syphilis and focus on practice aspects of diagnosis and management, including public health reporting.

Antibacterial activity and synergistic antibiotic mechanism of trialdehyde phloroglucinol against methicillin-resistant Staphylococcus aureus.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) has become a critical global concern. Identifying new anti-S. aureus agents or therapeutic strategies are urgently needed to treat S. aureus infection. The present study investigated the antibacterial activity of 16 phenolic compounds against MRSA, four of which exhibited antibacterial activity. Their antibacterial activities increased in a dose-dependent manner but showed different responses with the extension of treatment time. Trialdehyde phloroglucinol (TPG) and 2-nitrophloroglucinol (NPG) maintained stable antibacterial activity; however, that of dichlorophenol and myricetin decreased rapidly over 24 hr of treatment. Checkerboard and time-kill assays indicated that TPG and NPG exhibited strong synergistic antibacterial activities with penicillin or bacitracin. Microscopic observation and membrane integrity analysis showed that the combination of TPG and penicillin destroyed the MRSA cell membrane, resulting in the leakage of intracellular biomacromolecules, marked changes in surface zeta potential, and the collapse of membrane potential. Moreover, the combination significantly decreased penicillinase activity and penicillin-binding protein 2a mRNA expression, inhibiting MRSA growth. Taken together, these results demonstrated that the combination of the phloroglucinol derivative TPG and penicillin has significant synergistic anti-MRSA activity and can serve as a potential therapeutic strategy to treat MRSA infections.

Clinical and Epidemiologic Characteristics and Therapeutic Management of Patients with Vibrio Infections, Bay of Biscay, France, 2001-2019.

Noncholera vibriosis is a rare, opportunistic bacterial infection caused by Vibrio spp. other than V. cholerae O1/O139 and diagnosed mainly during the hot summer months in patients after seaside activities. Detailed knowledge of circulating pathogenic strains and heterogeneities in infection outcomes and disease dynamics may help in patient management. We conducted a multicenter case-series study documenting Vibrio infections in 67 patients from 8 hospitals in the Bay of Biscay, France, over a 19-year period. Infections were mainly caused by V. alginolyticus (34%), V. parahaemolyticus (30%), non-O1/O139 V. cholerae (15%), and V. vulnificus (10%). Drug-susceptibility testing revealed intermediate and resistant strains to penicillins and first-generation cephalosporins. The acute infections (e.g., those involving digestive disorder, cellulitis, osteitis, pneumonia, and endocarditis) led to a life-threatening event (septic shock), amputation, or death in 36% of patients. Physicians may need to add vibriosis to their list of infections to assess in patients with associated risk factors.

Phytochemical Screening and Antibacterial Activities of Aqueous and Alcoholic Extracts of Averrhoa bilimbi Leaf against Bacteria Isolated from Oral Cavity.

Medicinal herbs have been used as traditional treatments for many pathogens and extracted bioactive compounds from medicinal plants with a suitable therapeutic index for the production of new drugs. Moreover, they are utilized to evaluate different concentrations of aqueous and alcoholic extracts of Averrhoa bilimbi leaves and antibiotics against bacteria isolated from the oral cavity. This study was conducted simultaneously at the Departments of Botany and Biology, Shatrah Hospital, Thi-Qar, Iraq, during March and August 2021. A. bilimbi leaf extracts were utilized in the plant component examination and the assessment of the antibacterial activity. The bacterial strain of Escherichia coli and Klebsiella pneumoniae was isolated from the oral cavity. To test the antibacterial impact of the extracts on bacteria, the agar well diffusion method was used. The phytochemical screening indicated the presence of Alkaloids, Flavonoids, Sapiens, Steroids, Tannins, Glycosides, and Carbohydrates, followed by the absence of Tannins in aqueous extract. Due to the A. bilimbi leaf aqueous and methanol extract against E. coli, areas of inhibition were found (0.20 cm and 0.19 cm) at the concentration of 100 mg/ml, respectively. However, there were no regions of inhibition of the K. pneumoniae trend for both extracts. The sensitivity of bacterial isolates of E. coli and K. pneumonia to antibiotics was also tested through Gentamicin, Amoxycillin, Azithromycin, Ciprofloxacin, Penicillin, and Polymyxin B, and the regions of inhibition appeared against E. coli (0.5cm, 0 cm, 0.34 cm, 0.45 cm, 0 cm, and 0.12 cm, respectively). Furthermore, the regions of inhibition appeared against K. pneumoniae (3 cm, 0.3 cm, 0.4 cm, 0.55 cm, 0 cm, 0.66 cm, respectively). The antibiotics showed a higher inhibition zone, compared to the aqueous and alcoholic extracts; however, further studies are required to be conducted to validate its reliability.

The effect of vitamin E supplementation on brain tissue element levels in epileptic rats.

The aim of this study was to investigate how the application of vitamin E affected the levels of chemical elements in the brain tissues of epilepsy-induced rats. The sample of 40 adult male rats was separated into 4 equal groups: Group 1: control, Group 2: vitamin E; Group 3: penicillin to promote epileptic form activity and Group 4: penicillin + vitamin E. After three months of treatment, an Atomic Absorption Spectrophotometer was used to analyze the presence of the elements in brain tissue sections (brain, brainstem, cerebellum) of the decapitated animals. The levels of magnesium in the groups that received vitamin E (G2 and 4) were significantly higher than in the control group (G1) and the first epilepsy group (G3) (p.05).Chrome and zinc levels in brain, brainstem, and cerebellum tissue of the two epilepsy groups (G3-4) decreased significantly compared to the control group (G1) and the vitamin E group (G2) (p.05). The levels of copper in the brainstem and lead in the cerebellum of the first epilepsy group (G3) were higher than in all other groups (p.05). The findings showed that the application of vitamin E in experimental epilepsy may have a limited effect on element metabolism in brain tissue. A decline in zinc levels in the brain, brainstem and cerebellum tissues in epilepsy groups constitutes another result of our study. This should be examined further to determine whether decreased levels of zinc play a role in epilepsy pathogenesis.

Penicillin allergies: A guide for NPs.

ABSTRACT: Antibiotics are frequently reported as allergies by patients, particularly antibiotics from the penicillin family. Most of these reported allergies are benign, and the consequences of alternative therapies can be significant. This article will deliver background information on penicillin allergies and serve as a guide to penicillin allergy management.

Evaluation of antibacterial and wound-healing activities of alcoholic extract of Boswellia carterii, in vitro and in vivo study.

BACKGROUND: Today, despite the existence of various chemical and physical treatments for wound healing, the use of traditional medicine including herbal medicine is still widely used in most developed and developing countries. OBJECTIVES: To investigate the antimicrobial and wound-healing activities of alcoholic extract of Boswellia carterii (BC) plant. METHODS: The BC extract was prepared using alcohol 70%. The chemical groups and extract compounds were determined using Fourier transform infrared spectroscopy (FTIR) and high-performance liquid chromatography (HPLC) analysis, respectively. The antimicrobial and wound-healing activities of different concentrations of BC extract and its combination with penicillin-streptomycin were assessed by agar well diffusion and infected wound model in albino rabbits, respectively. RESULTS: FTIR revealed the presence of hydroxyl, amide, carboxyl, alkyl C-H stretches, aromatic C=C bends, and aromatic C-H bends in the BC extract. The HPLC revealed 14 different compounds including thujene (48.0%) as the most abundant ingredient. All BC concentrations showed antibacterial and wound-healing activities. The 10% concentration of BC extract had the strongest antibacterial effect. Also, the combination of penicillin-streptomycin with BC extract showed synergistic antibacterial effect. The 5% concentration of BC was the best wound-healing compound which healed the wound in 6 days and decreased the wound size 10 mm each day. CONCLUSIONS: This study demonstrated the potential abilities of BC as an antibacterial and wound-healing medicinal plant. Further studies are required to justify the in vivo use of this plant.

Detection of Serum-Specific IgE by Fluoro-Enzyme Immunoassay for Diagnosing Type I Hypersensitivity Reactions to Penicillins.

Diagnosis of type I hypersensitivity reactions (IgE-mediated reactions) to penicillins is based on clinical history, skin tests (STs), and drug provocation tests (DPTs). Among in vitro complementary tests, the fluoro-enzyme immunoassay (FEIA) ImmunoCAP® (Thermo-Fisher, Waltham, MA, USA) is the most widely used commercial method for detecting drug-specific IgE (sIgE). In this study, we aimed to analyze the utility of ImmunoCAP® for detecting sIgE to penicillin G (PG) and amoxicillin (AX) in patients with confirmed penicillin allergy. The study includes 139 and 250 patients evaluated in Spain and Italy, respectively. All had experienced type I hypersensitivity reactions to penicillins confirmed by positive STs. Additionally, selective or cross-reactive reactions were confirmed by DPTs in a subgroup of patients for further analysis. Positive ImmunoCAP® results were 39.6% for PG and/or AX in Spanish subjects and 52.4% in Italian subjects. When only PG or AX sIgE where analyzed, the percentages were 15.1% and 30.4%, respectively, in Spanish patients; and 38.9% and 46% in Italian ones. The analysis of positive STs showed a statistically significant higher percentage of positive STs to PG determinants in Italian patients. False-positive results to PG (16%) were detected in selective AX patients with confirmed PG tolerance. Low and variable sensitivity values observed in a well-defined population with confirmed allergy diagnosis, as well as false-positive results to PG, suggest that ImmunoCAP® is a diagnostic tool with relevant limitations in the evaluation of subjects with type I hypersensitivity reactions to penicillins.

Epibenthic microbial mats behavior as phosphorus sinks or sources in relation to biological and physicochemical conditions.

Microbial mats are complex microecosystems that have shown promise as possible green filters to remediate polluted seawater. This usage would possibly require changing the natural conditions under which these microbial mats prosper in order to maximize their contact with the water. Thus, it is necessary to evaluate the adaptation of the mats to different environmental conditions, while monitoring their short-term efficiency at nutrient removal. To that aim, epibenthic microbial mats collected from a tidal flat in the Bahía Blanca Estuary, were incubated under different flooding conditions (periodically exposed to the air or continuously flooded), with and without the addition of a high phosphorus concentration (5 mg PO43- L-1), and with and without the presence of penicillin. This last condition was added to understand the influence of penicillin-sensitive microbes on cyanobacteria and diatom communities and their importance for P remediation. The presence of high P concentrations as well as the continual flooding of the mats resulted in the decrease of the dominant cyanobacterium, Coleofasciculus (Microcoleus) chthonoplastes, giving rise to the dominance of other genera such as Arthrospira sp. Or Oscillatoria sp., depending on the presence or absence of the antibiotic, respectively. Water P removal was highly efficient (60-87%) when the mats were treated with the high-P water. However, microbial mat behavior changed from P sink to source when mats where incubated in seawater with no P addition, suggesting that mats can both function as P sinks and sources, depending on the condition of the water they come in contact with.

Empirical Second-Line Therapy in 5000 Patients of the European Registry on Helicobacter pylori Management (Hp-EuReg).

BACKGROUND & AIMS: After a first Helicobacter pylori eradication attempt, approximately 20% of patients will remain infected. The aim of the current study was to assess the effectiveness and safety of second-line empiric treatment in Europe. METHODS: This international, multicenter, prospective, non-interventional registry aimed to evaluate the decisions and outcomes of H pylori management by European gastroenterologists. All infected adult cases with a previous eradication treatment attempt were registered with the Spanish Association of Gastroenterology-Research Electronic Data Capture until February 2021. Patients allergic to penicillin and those who received susceptibility-guided therapy were excluded. Data monitoring was performed to ensure data quality. RESULTS: Overall, 5055 patients received empiric second-line treatment. Triple therapy with amoxicillin and levofloxacin was prescribed most commonly (33%). The overall effectiveness was 82% by modified intention-to-treat analysis and 83% in the per-protocol population. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy or levofloxacin-containing quadruple therapy (with bismuth). In patients receiving triple therapy containing levofloxacin or moxifloxacin, and levofloxacin-bismuth quadruple treatment, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors. However, 3-in-1 single capsule or levofloxacin-bismuth quadruple therapy produced reliable eradication rates regardless of proton pump inhibitor dose, duration of therapy, or previous first-line treatment. The overall incidence of adverse events was 28%, and most (85%) were mild. Three patients developed serious adverse events (0.3%) requiring hospitalization. CONCLUSIONS: Empiric second-line regimens including 14-day quinolone triple therapies, 14-day levofloxacin-bismuth quadruple therapy, 14-day tetracycline-bismuth classic quadruple therapy, and 10-day bismuth quadruple therapy (as a single capsule) provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates. ClincialTrials.gov number: NCT02328131.

Is a single dose of preoperative antibiotic therapy effective for patients treated with megaendoprosthesis after metastatic bone tumour resection?

Purpose The timing and number of doses of antibiotics required for megaendoprosthetic replacement (MPR) in metastatic bone disease (MBD) is a matter of debate. The aim of our study is to present the results of a prospective cohort of MPR for MBD receiving a single dose of antibiotic at induction of anaesthesia. METHODS: All patients who underwent primary MPR in MBD were included in this prospective study. All penicillin-sensitive patients received one dose of cefuroxime 1.5gm intravenous at induction. In penicillin-allergic patients, teicoplanin 1.2gm and ciprofloxacin 500 mg intravenous was administered. The patients were followed up in the wound clinic and the specialist MBD clinic at 2 weeks, 3 months, 6 months and then annually. Data collected included demographics, primary tumours, surgical procedures, complications and duration of follow-up. All calculations were performed using SPSS® 25(IBM, USA). A p value ≤ 0.05 was considered to be significant. RESULTS: There were 51 patients with a mean age of 65.4 years. Procedures included proximal femoral replacement (35), distal femoral replacement (7), proximal humeral replacement (4), distal humeral replacement (3) and total femoral replacement (2). Thirty-seven patients received cefuroxime, and fourteen patients received teicoplanin and ciprofloxacin at induction of anaesthesia. The deep infection rate was 1.9%. Thirty-seven patients died with a median survival of 10 months (1 to 51 months). Mean follow-up was 18.9 months (1 to 70 months). CONCLUSION: Single dose of preoperative antibiotics at anaesthetic induction seems to be safe and effective for preoperative prophylaxis in orthopaedic oncology.