Systematic Review: Clinical Features, Antimicrobial Treatment, and Outcomes of Human Tularemia, 1993-2023.

BACKGROUND: Francisella tularensis, the causative agent of tularemia, is endemic throughout the Northern Hemisphere and requires as few as 10 organisms to cause disease, making this potential bioterrorism agent one of the most infectious bacterial pathogens known. Aminoglycosides, tetracyclines, and, more recently, fluoroquinolones are used for treatment of tularemia; however, data on the relative effectiveness of these and other antimicrobial classes are limited. METHODS: Nine databases, including Medline, Global Health, and Embase, were systematically searched for articles containing terms related to tularemia. Articles with case-level data on tularemia diagnosis, antimicrobial treatment, and patient outcome were included. Patient demographics, clinical findings, antimicrobial administration, and outcome (eg, intubation, fatality) were abstracted using a standardized form. RESULTS: Of the 8878 publications identified and screened, 410 articles describing 870 cases from 1993 to 2023 met inclusion criteria. Cases were reported from 35 countries; more than half were from the United States, Turkey, or Spain. The most common clinical forms were ulceroglandular, oropharyngeal, glandular, and pneumonic disease. Among patients treated with aminoglycosides (n = 452 [52%]), fluoroquinolones (n = 339 [39%]), or tetracyclines (n = 419 [48%]), the fatality rate was 0.7%, 0.9%, and 1.2%, respectively. Patients with pneumonic disease who received ciprofloxacin had no fatalities and the lowest rates of thoracentesis/pleural effusion drainage and intubation compared to those who received aminoglycosides and tetracyclines. CONCLUSIONS: Aminoglycosides, fluoroquinolones, and tetracyclines are effective antimicrobials for treatment of tularemia, regardless of clinical manifestation. For pneumonic disease specifically, ciprofloxacin may have slight advantages compared to other antimicrobials.

A Retrospective Case-Control Study of Eravacycline for the Treatment of Carbapenem-Resistant Acinetobacter Infections in Patients With Burn Injuries.

Thermal injuries lead to a deficiency in one's natural, protective barrier, resulting in increased susceptibility to pathogens, and often require multiple courses of broad-spectrum antibiotics. Eravacycline (ERA) has shown adequate in vitro activity against multiple multi-drug resistant (MDR) pathogens including Acinetobacter sp. Due to the increasing prevalence of MDR bacteria and the heightened susceptibility of patients with burns to infection, studies are needed to examine the clinical effect of eravacycline in this population. The objective of this retrospective, case-control study was to compare the outcomes of patients with thermal injuries treated with eravacycline versus a matched control for carbapenem-resistant Acinetobacter baumannii (CRAB) infections. Patients with thermal injury admitted to an American Burn Associated-verified burn center from May 1, 2019 to July 31, 2022, who received eravacycline, were randomly matched 4:1 to a historical cohort using a previously established, de-identified dataset of patients treated with colistimethate sodium (CMS) in the same burn center (March 1, 2009 to March 31, 2014), based on % total body surface area (%TBSA), age, and CRAB. A composite favorable outcome was defined as 30-day survival, completion of the course, lack of 14-day recurrence, and lack of acute kidney injury (AKI). Treatment with eravacycline over CMS was not more or less likely to be associated with a favorable response [odds ratio (95% confidence interval), 2.066 (0.456-9.361), P = .347]. Patients treated with CMS had nearly 9-fold higher odds of new-onset AKI versus ERA [8.816 (0.911-85.308), P = .06]. Adverse events were uncommon in the ERA group. There was no difference in mortality.

Honeybee symbiont Bombella apis could restore larval-to-pupal transition disrupted by antibiotic treatment.

Numerous studies have demonstrated the vital roles of gut microbes in the health, immunity, nutrient metabolism, and behavior of adult worker honeybees. However, a few studies have been conducted on gut microbiota associated with the larval stage of honeybees. In the present study, we explored the role of a gut bacterium in larval development and larval-pupal transition in the Asian honeybee, Apis cerana. First, our examination of gut microbial profiling showed that Bombella apis, a larvae-associated bacterium, was the most dominant bacterium colonized in the fifth instar larvae. Second, we demonstrated that tetracycline, an antibiotic used to treat a honeybee bacterial brood disease, could cause the complete depletion of gut bacteria. This antibiotic-induced gut microbiome depletion in turn, significantly impacted the survivorship, pupation rate and emergence rate of the treated larvae. Furthermore, our analysis of gene expression pattens revealed noteworthy changes in key genes. The expression of genes responsible for encoding storage proteins vitellogenin (vg) and major royal jelly protein 1 (mrjp1) was significantly down-regulated in the tetracycline-treated larvae. Concurrently, the expression of krüppel homolog 1(kr-h1), a pivotal gene in endocrine signaling, increased, whilethe expression of broad-complex (br-c) gene that plays a key role in the ecdysone regulation decreased. These alterations indicated a disruption in the coordination of juvenile hormone and ecdysteroid synthesis. Finally, we cultivated B. apis isolated from the fifth instar worker larval of A. cerana and fed tetracycline-treated larvae with a diet replenished by B. apis. This intervention resulted in a significant improvement in the pupation rate, emergence rate, and overall survival rate of the treated larvae. Our findings demonstrate the positive impact of B. apis on honeybee larvae development, providing new evidence of the functional capacities of gut microbes in honeybee growth and development.

The pharmacokinetic evaluation of omadacycline (Oral Only Dosing Regimen) for the treatment of Community-Acquired Bacterial Pneumonia (CABP).

INTRODUCTION: Omadacycline is a new analog of the tetracycline class active against atypical bacteria, as well as against staphylococci, including methicillin-resistant strains, and Streptococcus pneumoniae. AREAS COVERED: This review has summarized the available clinical evidence on the use of oral omadacycline in the treatment of community-acquired pneumonia (CAP) and described the mechanism of action, pharmacokinetic/pharmacodynamic (PK/PD) parameters in healthy and special populations and the latest research on omadacycline. EXPERT OPINION: The available clinical evidence on oral omadacycline for the treatment of CAP shows that its properties provide reliable empirical coverage for pathogens such as Haemophilus influenzae, Moraxella catarrhalis, and species of Legionella, Chlamydia, and Mycoplasma. Omadacycline is also active against methicillin-resistant Staphylococcus aureus (MRSA); penicillin-resistant and multidrug-resistant Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae; and vancomycin-resistant Enterococcus spp. A dose of 450 mg orally once daily is recommended, followed by a maintenance dose of 300 mg orally once daily. Importantly, omadacycline does not require dose adjustment for patients based on BMI, age, gender, or renal or hepatic impairment.

[Multidisciplinary expert consensus on the rational use of tetracyclines commonly used in clinical practice].

In recent years, the emergence of newly detected pathogens and the increase of drug resistant bacterial bring serious challenges for the diagnosis and treatment of infectious diseases. Tetracycline drugs are widely used in clinical practice, and the varieties of these drugs are constantly being updated. However, there is still a lack of guidance documents for the rational clinical application of tetracycline drugs in China. Meanwhile, some healthcare workers have doubts about their pharmaceutical characteristics, timing and methods of clinical application. In order to further standardize the clinical application of tetracycline drugs and provide professional evidence-based medicine suggestions for medical personnel in medical institutions, under the leadership of Hospital Infection Control Branch of Chinese Preventive Medicine Association and Clinical Pharmacology Branch of Chinese Pharmacological Society, experts from areas of infection, respiratory medicine, critical care medicine, emergency, infection control, pharmacy and other disciplines organized a consensus meeting and formulated multidisciplinary expert consensus on the rational use of tetracyclines commonly used in clinical practice. This expert consensus is based on the pharmaceutical characteristics of tetracyclines commonly used in China, the mechanism of action and drug resistance status of tetracyclines, combined with the infection site, pathogen characteristics and bacterial drug resistance. This expert consensus also pays attention to special populations and off-label drug use, and integrates domestic and foreign recommendations and the latest evidence-based medicine evidence, and 17 expert consensus opinions for clinical physicians, pharmacists, and other professionals in medical institutions to refer to were formed. In view of the particularity and complexity of infectious diseases and the individual differences of patients, in order to benefit patients, individualized anti-infection strategies should be implemented.

Synergistic combination of carvedilol, amlodipine, amitriptyline, and antibiotics as an alternative treatment approach for the susceptible and multidrug-resistant A. baumannii infections via drug repurposing.

We evaluated in vitro activity of 13 drugs used in the treatment of some non-communicable diseases via repurposing to determine their potential use in the treatment of Acinetobacter baumannii infections caused by susceptible and multidrug-resistant strains. A. baumannii is a multidrug-resistant Gram-negative bacteria causing nosocomial infections, especially in intensive care units. It has been identified in the WHO critical pathogen list and this emphasises urgent need for new treatment options. As the development of new therapeutics is expensive and time consuming, finding new uses of existing drugs via drug repositioning has been favoured. Antimicrobial susceptibility tests were conducted on all 13 drugs according to CLSI. Drugs with MIC values below 128 µg/mL and control antibiotics were further subjected to synergetic effect and bacterial time-kill analysis. Carvedilol-gentamicin (FICI 0.2813) and carvedilol-amlodipine (FICI 0.5625) were determined to have synergetic and additive effect, respectively, on the susceptible A. baumannii strain, and amlodipine-tetracycline (FICI 0.75) and amitriptyline-tetracycline (FICI 0.75) to have additive effect on the multidrug-resistant A. baumannii strain. Most remarkably, both amlodipine and amitriptyline reduced the MIC of multidrug-resistant, including some carbapenems, A. baumannii reference antibiotic tetracycline from 2 to 0.5 µg/mL, for 4-folds. All these results were further supported by bacterial time-kill assay and all combinations showed bactericidal activity, at certain hours, at 4XMIC. Combinations proposed in this study may provide treatment options for both susceptible and multidrug-resistant A. baumannii infections but requires further pharmacokinetics and pharmacodynamics analyses and in vivo re-evaluations using appropriate models.

Omadacycline therapy for Mycobacterium abscessus species infections.

BACKGROUND: Antimicrobial resistance and therapy-related adverse effects make Mycobacterium abscessus treatment challenging. Omadacycline is a novel, bioavailable aminomethylcycline with favourable in vitro activity against M. abscessus. AIMS: To describe a case report and review the published literature describing outcomes for M. abscessus infections treated with omadacycline. METHODS: Systematic literature review. RESULTS: We identified three articles that, in addition to our case report, describe 18 patients. Pulmonary infections were most frequent. Minimum inhibitory concentrations were reported for two isolates (0.25 and 0.5 mg/L). Despite half the patients starting omadacycline because of failure of prior therapy, 15 (83%) had a favourable outcome, defined as 'cure', 'improvement' or 'clinical success' as determined by the primary study authors. One patient (6%) discontinued omadacycline because of gastrointestinal intolerance. CONCLUSIONS: Although the limited observational data and in vitro susceptibility results are encouraging, randomised control trials are required to determine the role of omadacycline as part of combination therapy for this most difficult-to-treat pathogen.

Highly Specific Antibiotic Detection on Water-Stable Black Phosphorus Field-Effect Transistors.

Two-dimensional (2D) black phosphorus (BP) has been reported to have appealing semiconducting properties as the sensing channel in field-effect transistor (FET) sensors. However, the intrinsic instability of BP in water greatly hinders its application, and little is known about its sensing performance and mechanism in aqueous medium. Herein, a water-stable BP FET sensor for antibiotic detection is reported. A novel surface engineering strategy with Ag+ coordination and melamine cyanurate (MC) supramolecular passivation is utilized to enhance the stability and transistor performance of BP. With molecularly imprinted polymers (MIPs) as the detection probe for tetracycline, the BPAg(+)/MC/MIPs sensor shows high sensitivity to tetracycline with a detection limit of 7.94 nM and a quick response within 6 s as well as high selectivity against other antibiotics with similar molecular structures. A new sensing mechanism relying on the conjugation effect of the probe structure is proposed, and new knowledge about alkalinity-enhanced and ionic strength-related response from the electrostatic gating effect is given based on the solution chemistry impact study. This work offers an efficient surface engineering strategy to enable the application of 2D BP for antibiotic detection in aqueous medium and presents a new sensing mechanism in chemical analysis by FET sensors.

Comparison of conventional and dispersive solid phase extraction clean-up approaches for the simultaneous analysis of tetracyclines and sulfonamides in a variety of fresh vegetables.

The extensive use of antibiotics in agriculture has led to the occurrence of residual drugs in different vegetables frequently consumed by humans. This could pose a potential threat to human health, not only because of the possible effects after ingestion but also because the transmission of antibiotic-resistant genes could occur. In this work, two accurate sample preparation procedures were developed and validated for the simultaneous analysis of sulfonamides (SAs) and tetracyclines (TCs) in four of the most widely consumed vegetables (lettuce, onion, tomato, and carrot) in Europe. The evaluated protocols were based on QuECHERS for extraction and subsequent clean-up by SPE (solid phase extraction) or dispersive SPE. Parameters affecting both extraction and clean-up were carefully evaluated and selected for accuracy of results and minimal matrix effect. Overall, apparent recoveries were above 70% for most of the target analytes with both analytical procedures, and adequate precision (RSD<30%) was obtained for all the matrices. The procedural limits of quantification (LOQPRO) values for SPE clean-up remained below 4.4 µg kg-1 for TCs in all vegetables except for chlortetracycline (CTC) in lettuce (11.3 µg kg-1) and 3.0 µg kg-1 for SAs, with the exception of sulfadiazine (SDZ) in onion (3.9 µg kg-1) and sulfathiazole (STZ) in carrot (5.0 µg kg-1). Lower LOQPRO values (0.1-3.7 µg kg-1) were obtained, in general, when dSPE clean-up was employed. Both methods were applied to twenty-five market vegetable samples from ecological and conventional agriculture and only sulfamethazine (SMZ) and sulfapyridine (SPD) were detected in lettuce at 1.2 µg kg-1 and 0.5 µg kg-1, respectively.

Adsorption and transformation of tetracyclines on alpha alumina particles with surface modification by anionic surfactant.

The adsorption and transformation of tetracyclines (TCs) antibiotics, including oxytetracycline (OTC), chlortetracycline (CTC), and tetracycline (TC), on the sodium dodecyl sulfate (SDS) surfactant-modified α-Al2O3 particles were comprehensively investigated in this study. The TCs adsorption was significantly enhanced by using the modified adsorbents compared with the use of the unmodified adsorbents. The experimental conditions were systematically optimized and found to be pH 4, NaCl 1 mM, the contact time of 180 min, and the adsorbent dosage of 25 mg. mL-1. The high maximum adsorption capacities were approximately 320, 85, and 91 mg. g-1 for TC, OTC, and CTC, respectively. Meanwhile, the great removal efficiencies of the three antibiotics TC, OTC, and CTC were correspondingly 91.85, 88.4, and 98.3%. The TCs adsorption isotherm and kinetics on the SDS-modified α-Al2O3 particles mainly governed by the electrostatic and hydrophobic interactions were clarified by a suitable two-step model, the Fourier transform infrared spectroscopy (FT-IR) and zeta potential measurements. Meanwhile, the TCs structural transformation determined by the liquid chromatography with tandem mass spectrometry (LC-MS/MS) measurement was promoted through the adsorption on the α-Al2O3 surface. The TCs transformation rates strongly affected by the TCs adsorption were in the order of CTC > TC > OTC. The found results are promised that the SDS-modified α-Al2O3 particles might behave as high-performance adsorbents to remove the TCs from aqueous solutions.

Postexposure Prophylaxis and Treatment of Bacillus anthracis Infections: A Systematic Review and Meta-analyses of Animal Models, 1947-2019.

BACKGROUND: Anthrax is endemic to many countries, including the United States. The causative agent, Bacillus anthracis, poses a global bioterrorism threat. Without effective antimicrobial postexposure prophylaxis (PEPAbx) and treatment, the mortality of systemic anthrax is high. To inform clinical guidelines for PEPAbx and treatment of B. anthracis infections in humans, we systematically evaluated animal anthrax treatment model studies. METHODS: We searched for survival outcome data in 9 scientific search engines for articles describing antimicrobial PEPAbx or treatment of anthrax in animals in any language through February 2019. We performed meta-analyses of efficacy of antimicrobial PEPAbx and treatment for each drug or drug combination using random-effects models. Pharmacokinetic/pharmacodynamic relationships were developed for 5 antimicrobials with available pharmacokinetic data. Monte Carlo simulations were used to predict unbound drug exposures in humans. RESULTS: We synthesized data from 34 peer-reviewed studies with 3262 animals. For PEPAbx and treatment of infection by susceptible B. anthracis, effective monotherapy can be accomplished with fluoroquinolones, tetracyclines, ß-lactams (including penicillin, amoxicillin-clavulanate, and imipenem-cilastatin), and lipopeptides or glycopeptides. For naturally occurring strains, unbound drug exposures in humans were predicted to adequately cover the minimal inhibitory concentrations (MICs; those required to inhibit the growth of 50% or 90% of organisms [MIC50 or MIC90]) for ciprofloxacin, levofloxacin, and doxycycline for both the PEPAbx and treatment targets. Dalbavancin covered its MIC50 for PEPAbx. CONCLUSIONS: These animal studies show many reviewed antimicrobials are good choices for PEPAbx or treatment of susceptible B. anthracis strains, and some are also promising options for combating resistant strains. Monte Carlo simulations suggest that oral ciprofloxacin, levofloxacin, and doxycycline are particularly robust choices for PEPAbx or treatment.

Short Communication: Enterotoxin Genes and Antibiotic Susceptibility of Bacillus cereus Isolated from Garlic Chives and Agricultural Environment.

This study aims to investigate the enterotoxin profiles and antibiotic susceptibility of Bacillus cereus isolated from garlic chives and environmental samples. A total of 103 B. cereus isolates were used to identify enterotoxin genes, including hblA, hblC, hblD, nheA, nheB, and nheC. The hemolysin BL enterotoxin complex (hblACD) was detected in 38 isolates (36.9%), and the non-hemolytic enterotoxin complex (nheABC) was detected in 8 (7.8%) isolates. Forty-five isolates (43.7%) had hblACD and nheABC genes. B. cereus was resistant to ß-lactam antibiotics and susceptible to non-ß-lactam antibiotics. However, some B. cereus strains showed intermediate resistance to ß-lactam and non-ß-lactam antibiotics. B. cereus isolated from garlic chives showed intermediate resistance to cefotaxime (7.7%), rifampin (15.4%), clindamycin (30.8%), erythromycin (7.7%), and tetracycline (7.7%). B. cereus isolates from the agricultural environment were moderately resistant to cefotaxime (18.9%), rifampin (15.6%), clindamycin (12.2%), erythromycin (4.4%), and tetracycline (5.6%). Moreover, B. cereus isolates from garlic chives and cultivation environments could change their antibiotic resistance profile from susceptible to intermediate-resistant to rifampin, clindamycin, erythromycin, and tetracycline and exhibit multidrug resistance. These results indicate that continuous monitoring of B. cereus contamination in the produce and agricultural environment might be needed to ensure the safety of consuming fresh vegetables.

Bioremediation of copper in sediments from a constructed wetland ex situ with the novel bacterium Cupriavidus basilensis SRS.

The H-02 constructed wetland was designed to remove metals (primarily copper and zinc) to treat building process water and storm water runoff from multiple sources associated with the Tritium Facility at the DOE-Savannah River Site, Aiken, SC. The concentration of Cu and Zn in the sediments has increased over the lifetime of the wetland and is a concern. A bioremediation option was investigated at the laboratory scale utilizing a newly isolated bacterium of the copper metabolizing genus Cupriavidus isolated from Tim's Branch Creek, a second-order stream that eventually serves as a tributary to the Savannah River, contaminated with uranium and other metals including copper, nickel, and mercury. Cupriavidus basilensis SRS is a rod-shaped, gram-negative bacterium which has been shown to have predatory tendencies. The isolate displayed resistance to the antibiotics ofloxacin, tetracycline, ciprofloxacin, select fungi, as well as Cu2+ and Zn2+. Subsequent ribosomal sequencing demonstrated a 100% confidence for placement in the genus Cupriavidus and a 99.014% match to the C. basilensis type strain. When H-02 wetland samples were inoculated with Cupriavidus basilensis SRS samples showed significant (p < 0.05) decrease in Cu2+ concentrations and variability in Zn2+ concentrations. Over the 72-h incubation there were no significant changes in the inoculate densities (106-108 cells/ML) indicating Cupriavidus basilensis SRS resiliency in this environment. This research expands our understanding of the Cupriavidus genus and demonstrates the potential for Cupriavidus basilensis SRS to bioremediate sites impacted with heavy metals, most notably copper.

Resistance to beta-lactams in Gram-negative bacilli: relevance and potential therapeutic alternatives.

The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health problem that entails high morbidity and mortality: the antibiotic multi-drug resistance. In 2017 and 2019, the World Health Organization published a list of urgent threats and priorities in the context of drug resistance, which only included Gram-negative bacteria and specially focused on carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem and third generation cephalosporin-resistant Enterobacteriaceae. This scenario emphasizes the need of developing and testing new antibiotics from different families, such as new beta-lactams, highlighting cefiderocol and its original mechanism of action; new beta-lactamase inhibitors, with vaborbactam or relebactam among others; new quinolones such as delafloxacin, and also omadacycline or eravacycline, as members of the tetracycline family. The present work reviews the importance and impact of Gram-negative bacterial infections and their resistance mechanisms, and analyzes the current therapeutic paradigm as well as the role of new antibiotics with a promising future in the era of multi and pan-drug resistance.

Antimicrobial Resistance of Tannin Extract against E. coli Isolates from Sheep.

Plants have been long valuable sources of natural materials that have served to preserve human and animal health; as a result, pharmacological purposes have arisen from the use of plant compounds in most countries, according to a World Health Organization report. The present study aimed to assess the antimicrobial resistance of tannin extract against Escherichia coli (E. coli) isolates in sheep. A total of 100 samples from sheep were used to isolate E. coli and treated with tannin extract (90% purity) to investigate the in vitro effect, as compared to some antibiotics (Clindamycin, Cephalexin, Kanamycin, Tetracycline, and Vancomycin). The bacterial samples were cultured in a selective and differential medium, and Gram staining was used to examine them. The biochemical assays were performed to purify and expose these cultures; moreover, the API 20E system and RapidTM ONE kits were utilized to confirm the bacterial strain. Based on the findings, 50% of the samples showed a positive result for the presence of E. coli. The well diffusion technique was used to investigate the antibacterial activity to confirm the antibacterial action of tannin extract (from pomegranate peel) in different concentrations against E. coli. The highest zone of inhibition for the bacteria ranged from 12±0.5 to 30.3±0.2 at 50% concentrations, proving that tannins extract was significantly effective against E. coli. The presence of E. coli was detected in 50 % of the samples. The well-diffusion technique was used to evaluate the antimicrobial property of tannin extract through various concentrations with the highest zone of inhibition for the bacteria ranging from 12.5 to 30.30.2 at 50%, demonstrating that tannin extract was significantly effective on E. coli.

Treating Multi-Drug-Resistant Bacterial Infections by Functionalized Nano-Bismuth Sulfide through the Synergy of Immunotherapy and Bacteria-Sensitive Phototherapy.

Owing to its flexibility and high treatment efficiency, phototherapy is rapidly emerging for treating bacteria-induced diseases, but how to improve the sensitivity of bacteria to reactive oxygen species (ROS) and heat simultaneously to kill bacteria under mild conditions is still a challenge. Herein, we designed a NIR light catalyst (Bi2S3-S-nitrosothiol-acetylcholine (BSNA)) by transforming •O2- into peroxynitrite in situ, which can enhance the bacterial sensibility to ROS and heat and kill bacteria under a mild temperature. The transformed peroxynitrite in situ possessed a stronger ability to penetrate cell membranes and antioxidant capacity. The BSNA nanoparticles (NPs) inhibited the bacterial glucose metabolic process through down-regulated xerC/xerD expression and disrupted the HSP70/HSP90 secondary structure through nitrifying TYR179. Additionally, the synergistic effect of the designed BSNA and clinical antibiotics increased the antibacterial activity. In the case of tetracycline-class antibiotics, BSNA NPs induced phenolic hydroxyl group structure changes and inhibited the interaction between tetracycline and targeted t-RNA recombinant protein. Besides, BSNA stimulated production of more CD8+ T cells and reduced common complications in peritonitis, which provided immunotherapy activity. The targeted and anti-infective effect of BSNA suggested that we propose a nanotherapeutic strategy to achieve more efficient synergistic therapy under mild temperatures.

Isolation and Characterization of Aeromonas jandaei from Nile Tilapia in Lake Volta, Ghana, and Its Response to Antibiotics and Herbal Extracts.

Production of Nile Tilapia Oreochromis niloticus contributes to economic growth in many countries. However, there has been a decline in its production over the years due to the influx of bacterial infections, with Aeromonas jandaei as an emerging threat. In this study, we identified and characterized A. jandaei from cage-cultured Nile Tilapia in Akosombo Stratum II of Lake Volta in Ghana and evaluated its response to commonly used antibiotics using the disc diffusion and agar well diffusion methods for herbal extracts at various concentrations (10, 30, 50, 70, and 100 mg/mL). The herbs considered included guava Psidium guajava leaf, bitter leaf Vernonia amygdalina, neem Azadirachta indica leaf, and their cocktail (GBNL in the ratio of 1:1:1). The bacterium was isolated from swab samples from the head kidneys of 27 moribund Nile Tilapia collected from nine fish farms. Samples were screened for A. jandaei by culturing and identification using morphological and molecular techniques. The bacterium isolate from fish in the study, identified as A. jandaei GH-AS II, had 92-93% identity to A. jandaei reference strains. Infection of healthy Nile Tilapia (n = 210) with the bacterium isolate showed that 1.0 × 105 CFU/mL was the lethal dose causing 50% mortality. Antibiotic susceptibility testing showed that A. jandaei GH-AS II was resistant to tetracycline and ampicillin. Herbal extracts at the various concentrations inhibited the growth of the bacterium isolate, with a significant increment in the zones of inhibition with increasing concentrations of leaf extracts. However, GBNL showed prominence compared to the other extracts only at 100 mg/mL. Management of A. jandaei GH-AS II by using herbal extracts at Nile Tilapia farms in Lake Volta may be recommended since the use of antibiotics, such as tetracycline and ampicillin, may not yield the needed result.

Omadacycline Pharmacokinetics/Pharmacodynamics in the Hollow Fiber System Model and Potential Combination Regimen for Short Course Treatment of Mycobacterium kansasii Pulmonary Disease.

The 12-month therapy duration for the treatment of Mycobacterium kansasii pulmonary disease calls for more efficacious drugs for better treatment outcomes and to shorten the therapy duration. We performed (i) omadacycline MIC with M. kansasii ATCC 12478 strain and 21 clinical isolates, (ii) dose-response study in the hollow fiber system model of M. kansasii (HFS-Mkn) with six human equivalent omadacycline daily doses to determine the optimal drug exposure for the maximal kill, and (iii) a second HFS-Mkn study to determine the efficacy of omadacycline (300 mg/day) plus moxifloxacin (600 mg/day) plus tedizolid (200 mg/day) combination regimen with standard regimen as comparator. GraphPad Prism was used for data analysis and graphing. MIC of the reference strain was 4 mg/L but ranged from 8 to 32 mg/L among the 21 clinical isolates. In the HFS-Mkn, the exposure required for 50% of the maximal effect (EC50) was an omadacycline area under the concentration-time curve to MIC (AUC0-24/MIC) ratio of 1.95. The optimal exposure was an AUC0-24/MIC of 3.05, which could be achieved with 300 mg/day clinical dose. The omadacycline-moxifloxacin-tedizolid combination sterilized the HFS-Mkn in 14 days with a linear-regression based kill rate of -0.309 ± 0.044 log10 CFU/mL/day compared to the kill rate of -0.084 ± 0.036log10 CFU/mL/day with the standard regimen or 3.7-times faster. Omadacycline has efficacy against M. kansasii and could be used at 300 mg/day in combination with moxifloxacin and tedizolid for the treatment of M. kansasii pulmonary diseases with the potential to shorten the currently recommended 12-month therapy duration.

Assessment of nationally recommended antibiotics for treatment of UTI in U.S.-Mexico border emergency departments.

BACKGROUND: Urinary tract infections (UTIs) seen in the emergency department are commonly treated as an outpatient with oral antibiotics. Given that antibiotics are available for over-the-counter purchase in Mexico, there is speculation that potential misuse and overuse of antibiotics in United States-Mexico border areas could lead to antibiotic resistance patterns that would render some empiric treatments for UTIs less effective. The purpose of this study was to examine the effectiveness of Infectious Disease Society of America (IDSA) guideline-recommended antibiotics for treatment of outpatient UTI diagnosed in the emergency department. Data were collected from a county hospital on the U.S.-Mexico border with a metropolitan area of over 2 million people. Secondary analysis included frequency of urine culture isolated, resistance rates of urine pathogens, and prescriber habits. METHODS: This study was a retrospective chart review of adult patients diagnosed and treated for UTI from August 1, 2019, to February 29, 2020. Culture results of included patients were analyzed against in vitro-tested antibiotics. Bacterial isolate frequency, resistance rates, and prescribing habits were collected. RESULTS: A total of 985 patient charts were reviewed, of which 520 patients met inclusion criteria for analysis of prescribing habits. Of these, 329 positive bacterial culture growths were included in the analysis of antibiotic resistance rates. Oral antibiotics with comparatively lower resistance rates were amoxicillin/clavulanate, cefdinir, cefuroxime, and nitrofurantoin. Oral antibiotics with notably high resistance rates included trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, ciprofloxacin, levofloxacin, and cephalexin. Nitrofurantoin was prescribed most frequently for outpatient treatment of UTI/cystitis (41.6%) while cephalexin was the most commonly prescribed antibiotic for outpatient treatment of pyelonephritis (50%). CONCLUSION: Our findings suggest that, while part of standard IDSA guidelines, fluoroquinolones and TMP-SMX are not ideal empiric antibiotics for treatment of outpatient UTI in the U.S.-Mexico border region studied due to high resistance rates. Although not listed as first line agents per current IDSA recommendations, 2nd and 3rd generation cephalosporins, and amoxicillin/clavulanate would be acceptable options given resistance patterns demonstrated in accordance with IDSA allowance for tailoring selection to local resistance. Nitrofurantoin appears to be consistent with recommendations and demonstrates a favorable resistance profile for treatment of outpatient UTI within this region.

Development of Resistance to Eravacycline by Klebsiella pneumoniae and Collateral Sensitivity-Guided Design of Combination Therapies.

The evolution of bacterial antibiotic resistance is exhausting the list of currently used antibiotics and endangers those in the pipeline. The combination of antibiotics is a promising strategy that may suppress resistance development and/or achieve synergistic therapeutic effects. Eravacycline is a newly approved antibiotic that is effective against a variety of multidrug-resistant (MDR) pathogens. However, the evolution of resistance to eravacycline and strategies to suppress the evolution remain unexplored. Here, we demonstrated that a carbapenem-resistant Klebsiella pneumoniae clinical isolate quickly developed resistance to eravacycline, which is mainly caused by mutations in the gene encoding the Lon protease. The evolved resistant mutants display collateral sensitivities to ß-lactam/ß-lactamase inhibitor (BLBLI) combinations aztreonam/avibactam and ceftazidime-avibactam. Proteomic analysis revealed upregulation of the multidrug efflux system AcrA-AcrB-TolC and porin proteins OmpA and OmpU, which contributed to the increased resistance to eravacycline and susceptibility to BLBLIs, respectively. The combination of eravacycline with aztreonam/avibactam or ceftazidime-avibactam suppresses resistance development. We further demonstrated that eravacycline-resistant mutants evolved from an NDM-1-containing K. pneumoniae strain display collateral sensitivity to aztreonam/avibactam, and the combination of eravacycline with aztreonam/avibactam suppresses resistance development. In addition, the combination of eravacycline with aztreonam/avibactam or ceftazidime-avibactam displayed synergistic therapeutic effects in a murine cutaneous abscess model. Overall, our results revealed mechanisms of resistance to eravacycline and collateral sensitivities to BLBLIs and provided promising antibiotic combinations in the treatment of multidrug-resistant K. pneumoniae infections. IMPORTANCE The increasing bacterial antibiotic resistance is a serious threat to global public health, which demands novel antimicrobial medicines and treatment strategies. Eravacycline is a newly approved antibiotic that belongs to the tetracycline antibiotics. Here, we found that a multidrug-resistant Klebsiella pneumoniae clinical isolate rapidly developed resistance to eravacycline and the evolved resistant mutants displayed collateral sensitivity to antibiotics aztreonam/avibactam and ceftazidime-avibactam. We demonstrated that the combination of eravacycline with aztreonam/avibactam or ceftazidime-avibactam repressed resistance development and improved the treatment efficacies. We also elucidated the mechanisms that contribute to the increased resistance to eravacycline and susceptibility to aztreonam/avibactam and ceftazidime-avibactam. This work demonstrated the mechanisms of antibiotic resistance and collateral sensitivity and provided a new therapeutically option for effective antibiotic combinations.