Different Classes Of Antibiotics Research Articles

The hypersusceptible antibiotic screening strain Staphylococcus aureus SG511-Berlin harbors multiple mutations in regulatory genes

The genetic plasticity of Staphylococcus aureus has facilitated the evolution of many virulent and drug-resistant strains. Here we present the sequence of the 2.74 Mbp genome of S. aureus SG511-Berlin, which is frequently used for antibiotic screening. Although S. aureus SG511 and the related methicillin-resistant S. aureus MRSA252 share a high similarity in their core genomes, indicated by an average nucleotide identity (ANI) of 99.83%, the accessory genomes of these strains differed, as nearly no mobile elements and resistance determinants were identified in the genome of S. aureus SG511. Susceptibility testing showed that S. aureus SG511 was susceptible to most of the tested antibiotics of different classes. Intriguingly, and in contrast to the standard laboratory strain S. aureus HG001, S. aureus SG511 was even hyper-susceptible towards cell wall and membrane targeting agents, with the exception of the MurA-inhibitor fosfomycin. In depth comparative genome analysis revealed that, in addition to the loss of function mutation in the antibiotic sensor histidine kinase gene graS, further mutations had occurred in the lysyltransferase gene mprF, the structural giant protein gene ebh, and the regulator genes codY and saeR, which might contribute to antibiotic susceptibility. In addition, an insertion element in agrC abolishes Agr-activity in S. aureus SG511, and the spa and sarS genes, which encode the surface protein SpA and its transcriptional regulator, were deleted. Thus, the lack of mobile resistance genes together with multiple mutations affecting cell envelope morphology may render S. aureus SG511 hyper-susceptible towards most cell wall targeting agents.

Development of experimental techniques for antibiotics detection in aqueous solutions: Real-time microwave dielectrometry and UV-Vis spectrophotometry study

Microwave dielectrometry and UV/Vis spectrophotometry methods have been used to study the aqueous solutions of selected antibiotics of different classes: lincomycin hydrochloride, levofloxacin hemihydrate, amikacin sulfate, and gentamicin sulfate. The microwave dielectrometry technique demonstrates high sensitivity of complex permittivity values of antibiotics water solutions from antibiotics concentration in such solutions. In our study, the microwave dielectrometry data are validated by the UV-Vis spectrophotometry results for levofloxacin and lincomycin aqueous solutions. The Fisher’s correlation coefficients for the electromagnetic waves absorbance values, obtained by the different methods, are close to unity for the mentioned antibiotics. The obtained experimental results confirm that the microwave dielectrometry method developed by us is prospective to be applied for antibiotics determination in aqueous solutions including environmental water samples.

Genomic and Metabolic Characteristics of the Pathogenicity in Pseudomonas aeruginosa.

In recent years, the effectiveness of antimicrobials in the treatment of Pseudomonas aeruginosa infections has gradually decreased. This pathogen can be observed in several clinical cases, such as pneumonia, urinary tract infections, sepsis, in immunocompromised hosts, such as neutropenic cancer, burns, and AIDS patients. Furthermore, Pseudomonas aeruginosa causes diseases in both livestock and pets. The highly flexible and versatile genome of P. aeruginosa allows it to have a high rate of pathogenicity. The numerous secreted virulence factors, resulting from its numerous secretion systems, the multi-resistance to different classes of antibiotics, and the ability to produce biofilms are pathogenicity factors that cause numerous problems in the fight against P. aeruginosa infections and that must be better understood for an effective treatment. Infections by P. aeruginosa represent, therefore, a major health problem and, as resistance genes can be disseminated between the microbiotas associated with humans, animals, and the environment, this issue needs be addressed on the basis of an One Health approach. This review intends to bring together and describe in detail the molecular and metabolic pathways in P. aeruginosa’s pathogenesis, to contribute for the development of a more targeted therapy against this pathogen.

The Relationship between Antibiotic Susceptibility and pH in the Case of Uropathogenic Bacteria.

Urinary tract infections (UTIs) are common bacterial infections caused mainly by enteric bacteria. Numerous virulence factors assist bacteria in the colonization of the bladder. Bacterial efflux pumps also contribute to bacterial communication and to biofilm formation. In this study, the phenotypic and genetic antibiotic resistance of clinical UTI pathogens such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis were determined by disk diffusion method and polymerase chain reaction (PCR). Following this, different classes of antibiotics were evaluated for their antibacterial activity at pH 5, 6, 7 and 8 by a microdilution method. Gentamicin (GEN) was the most potent antibacterial agent against E. coli strains. The effect of GEN on the relative expression of marR and sdiA genes was evaluated by quantitative PCR. The slightly acidic pH (pH 6) and GEN treatment induced the upregulation of marR antibiotic resistance and sdiA QS activator genes in both E. coli strains. Consequently, bacteria had become more susceptible to GEN. It can be concluded that antibiotic activity is pH dependent and so the artificial manipulation of urinary pH can contribute to a more effective therapy of multidrug resistant bacterial infections.

Global antibiotic consumption and usage in humans, 2000–18: a spatial modelling study

SummaryBackgroundAntimicrobial resistance (AMR) is a serious threat to global public health. WHO emphasises the need for countries to monitor antibiotic consumption to combat AMR. Many low-income and middle-income countries (LMICs) lack surveillance capacity; we aimed to use multiple data sources and statistical models to estimate global antibiotic consumption.MethodsIn this spatial modelling study, we used individual-level data from household surveys to inform a Bayesian geostatistical model of antibiotic usage in children (aged <5 years) with lower respiratory tract infections in LMICs. Antibiotic consumption data were obtained from multiple sources, including IQVIA, WHO, and the European Surveillance of Antimicrobial Consumption Network (ESAC-Net). The estimates of the antibiotic usage model were used alongside sociodemographic and health covariates to inform a model of total antibiotic consumption in LMICs. This was combined with a single model of antibiotic consumption in high-income countries to produce estimates of antibiotic consumption covering 204 countries and 19 years.FindingsWe analysed 209 surveys done between 2000 and 2018, covering 284 045 children with lower respiratory tract infections. We identified large national and subnational variations of antibiotic usage in LMICs, with the lowest levels estimated in sub-Saharan Africa and the highest in eastern Europe and central Asia. We estimated a global antibiotic consumption rate of 14·3 (95% uncertainty interval 13·2–15·6) defined daily doses (DDD) per 1000 population per day in 2018 (40·2 [37·2–43·7] billion DDD), an increase of 46% from 9·8 (9·2–10·5) DDD per 1000 per day in 2000. We identified large spatial disparities, with antibiotic consumption rates varying from 5·0 (4·8–5·3) DDD per 1000 per day in the Philippines to 45·9 DDD per 1000 per day in Greece in 2018. Additionally, we present trends in consumption of different classes of antibiotics for selected Global Burden of Disease study regions using the IQVIA, WHO, and ESAC-net input data. We identified large increases in the consumption of fluoroquinolones and third-generation cephalosporins in North Africa and Middle East, and south Asia.InterpretationTo our knowledge, this is the first study that incorporates antibiotic usage and consumption data and uses geostatistical modelling techniques to estimate antibiotic consumption for 204 countries from 2000 to 2018. Our analysis identifies both high rates of antibiotic consumption and a lack of access to antibiotics, providing a benchmark for future interventions.FundingFleming Fund, UK Department of Health and Social Care; Wellcome Trust; and Bill & Melinda Gates Foundation.

Liposomal delivery systems and their applications against Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus.

Liposomal delivery systems have been widely explored for targeting superbugs such as S. aureus and MRSA, overcoming antimicrobial resistance associated with conventional dosage forms. They have the significant advantage of delivering hydrophilic and lipophilic antimicrobial agents, either singularly as monotherapy or in combination as combination therapy, due to their bilayers with action-site-specificity, resulting in improved targeting compared to conventional dosage forms. Herein, we present an extensive and critical review of the different liposomal delivery systems employed in the past two decades for the delivery of both antibiotics of different classes and non-antibiotic antibacterial agents, as monotherapy and combination therapy to eradicate infections caused by S. aureus and MRSA. The review also identifies future research and strategies potentiating the applications of liposomal delivery systems against S. aureus and MRSA. This review confirms the potential application of liposomal delivery systems for effective delivery and specific targeting of S. aureus and MRSA infections.

Complete genome sequence of an extensively drug-resistant Pseudomonas aeruginosa ST773 clinical isolate from North India

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen causing a wide range of community- and hospital-acquired infections. Here we report the complete genome sequence of an extensively drug-resistant (XDR) P. aeruginosa strain (PA790) in order to understand the antibiotic resistance genes (ARGs) harboured by such a strain. Whole-genome sequencing (WGS) was performed using Illumina HiSeq and Nanopore MinION platforms. Genome assembly was performed using Unicycler v.0.4.8. The genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline (PGAP). In silico predictions were fulfilled using curated bioinformatics tools. Pseudomonas aeruginosa PA790 was classified as XDR and belongs to sequence type 773 (ST773). The complete genome size is 6 932 250 bp with a G+C content of 66.02% and a BUSCO (Benchmarking Universal Single-Copy Orthologs) score of 100. Strain PA790 harboured 12 different ARGs conferring resistance to eight different classes of antibiotics. It was identified as the nineteenth ST773 strain among 5785 whole-genome sequences of P. aeruginosa available in the NCBI database. Pseudomonas aeruginosa PA790 belongs to ST773 and was identified as the nineteenth such isolate to be submitted to NCBI and the first complete ST773 genome from India. The WGS data with multiple ARGs of P. aeruginosa PA790 (ST773) will aid in understanding the evolution and phylogeny of such high-risk clones and provide a solid basis for further research on XDR strains.

Profiles of antimicrobial resistance of enterobacteria isolated at livestock enterprises of the Ural region

Abstract. A study of the antibiotic susceptibility of bacteria of the genus Enterobacter, selected at regional dairy enterprises, was carried out. The purpose of this work was to assess the phenotypic resistance profiles of Enterobacter spp. in the loci of fermenal microbiocenoses related to milk production. Research methodology and methods. In the course of the work carried out, milk, mammary gland secretions, and udder washes from cows at dairy cattle breeding enterprises located in different districts of the Ural region were examined. The phenotypic resistance of Enterobacter spp. Isolates was analyzed to 10 antibacterial drugs: ciprofloxacin, enrofloxacin, ofloxacin, meropenem, doxycycline, chloramphenicol, ceftriaxone, amoxicillin, ampicillin, rifampicin. Results. Average sensitivity values of Enterobacter spp. for all surveyed enterprises were at the level of 2.0–3.3 conventional units (at maximum = 4) to target antibiotics, and at the level of 2.0–2.1 conventional units to non-target antibiotics. The highest bactericidal efficacy was found in fluoroquinolones, the lowest in doxycycline and chloramphenicol. For individual enterprises, the average resistance profile included good sensitivity to 3–4 antibiotics, reduced to 4–5 and resistance to 1–2 antibiotics. The main conclusion is that in eight surveyed enterprises, the usual pattern was the resistance of isolates or their low sensitivity to several antibiotics of different classes, which indicates an unfavorable situation with AMR. Scientific novelty. The results obtained in the course of the work performed made it possible to assess the current and actual levels of resistance of Enterobacter spp. Isolates inhabiting those loci of fermenal microbiocenoses that are directly related to milk production.

Correlation Analysis among Environmental Antibiotic Resistance Genes Abundance, Antibiotics Concentrations, and Heavy Metals Concentrations Based on Web of Science Searches

Antibiotics and heavy metals are both important environmental pollutants and selective stressors for antibiotic resistance. However, the impact of their environmental concentrations on antibiotic resistance levels is still unclear. In this paper, research published before 2019 reporting the abundance of antibiotic resistance genes(ARGs), antibiotics concentrations, or heavy metal concentrations were extracted from the Web of Science database, and then statistical regression was used to investigate their correlative association. The results show that antibiotic selection pressure has a statistically significant effect on the increase in the abundance of ARGs in environmental media such as surface water, sediment, and soil, even at very low antibiotic concentrations(P<0.05). Different classes of antibiotics show different potential to select and enrich ARGs. Heavy metals and the interaction between antibiotics and heavy metals also have significant effects on ARG transmission(P<0.05). Multivariate statistical regression models can better explain the variance of ARG abundance, with R2 values for the water phase and solid phase environmental samples of 0.482 and 0.707 respectively, which are much higher than those achieved using univariate regression models. However, additional environmental factors not included may also affect ARG abundance. The results of this work provide a basis for the evaluation and control of environmental antibiotic resistance.

CAPNOCYTOPHAGA CANIMORSUS CAUSING SEPTIC SHOCK IN AN ASPLENIC PATIENT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: The Capnocytophaga spp. are fusiform, gram-negative rods with gliding motility and grow best in capnophilic environments. There has been concern for antimicrobial resistance among the Capnocytophaga spp. The purpose of this case is to present a patient with isolated C. canimorsus bacteremia causing septic shock and to discuss antimicrobial treatments. CASE PRESENTATION: The patient is a 63-year-old male with a past medical history of Epstein Barr Virus infection resulting in a splenectomy however, his vaccinations were up to date. The patient presented with fatigue for one day and had petechiae on his abdomen, lower extremities and nose. He was febrile at 38.9 degrees Celsius and was started on vancomycin, azithromycin and piperacillin-tazobactam. He then became hypotensive and received the sepsis fluid bolus with no change in his blood pressure. The patient required vasopressor support and then became hypoxic requiring endotracheal intubation. Due to worsening acidosis and vasopressor support the patient was started on continuous renal replacement therapy. The patient's initial blood cultures revealed gram negative rods however, the Biofire BCID (Biomérieux) molecular probe was negative. C. canimorsus was isolated from blood cultures. The antibiotic was then de-escalated to ceftriaxone. Literature review showed the possibility of beta-lactamase production in this bacterium. Given the overall critical illness of the patient, his antibiotic was changed to a combination of ampicillin-sulbactam and clindamycin. He finished a 7-day course of clindamycin and 14-day course of ampicillin-sulbactam. He received a total of 21 days of antibiotic therapy. DISCUSSION: The Capnocytophaga spp. found in the oral cavity of cats and dogs can cause wound infections, endocarditis, sepsis and meningitis. Capnocytophaga spp. have been known to cause more severe infections in immunocompromised patients. The Capnocytophaga spp. have been susceptible to many different classes of antibiotics including penicillins, macrolides, fluoroquinolones, cephalosporins and clindamycin. Recent literature has shown that there are strains of Capnocytophaga that produce beta-lactamase. Other literature has shown some Capnocytophaga spp. to be resistant to 3rd generation cephalosporins and fluoroquinolones. There was one report of a strain of C. sputigena with production of an extended spectrum beta-lactamase. CONCLUSIONS: The patient presented had C. canimorsus bacteremia. Sensitivities were unable to be done as there are no clear Clinical Laboratory and Standards Institute breakpoints for this organism. Literature had shown that C. canimorsus to be sensitive to penicillins. However, there have also been reports of beta-lactam production among other Capnocytophaga spp. Since the patient was critically ill and, sensitivities were unable to be done, the patient was switched to ampicillin-sulbactam and clindamycin. REFERENCE #1: Jolivet-Gougeon, A., Sixou, J., Tamanai-Shacoori, Z., & Bonnaure-Mallet, M. (2007). Antimicrobial treatment of Capnocytophaga infections. International Journal of Antimicrobial Agents, 29(4), 367-373. doi:10.1016/j.ijantimicag.2006.10.005 REFERENCE #2: Zangenah, S., Andersson, A. F., Özenci, V., & Bergman, P. (2017). Genomic analysis reveals the presence of a class D beta-lactamase with broad substrate specificity in animal bite associated Capnocytophaga species. European Journal of Clinical Microbiology & Infectious Diseases?: Official Publication of the European Society of Clinical Microbiology, 36(4), 657–662. https://doi-org.cuhsl.creighton.edu/10.1007/s10096-016-2842-2 REFERENCE #3: Gomez-Garces, J. L., Alos, J. I., Sanchez, J., & Cogollos, R. (1994). Bacteremia by multidrug-resistant Capnocytophaga sputigena. Journal of Clinical Microbiology, 32(4), 1067-1069. doi:10.1128/jcm.32.4.1067-1069.1994 DISCLOSURES: No relevant relationships by Muhammad Khan, source=Web Response No relevant relationships by Kenneth Mueller, source=Web Response No relevant relationships by David Quimby, source=Web Response

Chemical Fate and Partitioning Behavior of Antibiotics in the Aquatic Environment-A Review.

Antibiotics in the aquatic environment is a major problem because of the emergence of antibiotic resistance. The long-term ecological impact on the aquatic environment is unknown. Many sources allow entry of antibiotics into the environment, including wastewater-treatment plants (WWTPs), agricultural runoff, hospital effluent, and landfill leachate. Concentrations of antibiotics in the aquatic environment vary significantly; studies have shown fluoroquinolones, tetracycline, macrolides, sulfonamides, and penicillins to reach 2900, 1500, 9700, 21 400, and 1600 ng L-1 in wastewater effluent samples, respectively. However, concentrations are highly variable between different countries and depend on several factors including seasonal variation, prescription, and WWTP operating procedures. Likewise, the reported concentrations that cause environmental effects vary greatly between antibiotics, even within the same class; however, this predicted concentration for the antibiotics considered was frequently <1000 ngL-1 , indicating that when discharged into the environment along with treated effluent, these antibiotics have a potentially detrimental effect on the environment. Antibiotics are generally quite hydrophilic in nature; however, they can ionize in the aquatic environment to form charged structures, such as cations, zwitterions, and anions. Certain classes, particularly fluoroquinolones and tetracyclines, can adsorb onto solid matrices, including soils, sediment, and sludge, making it difficult to fully understand their chemical fate in the aquatic environment. The adsorption coefficient (Kd ) varies between different classes of antibiotics, with tetracyclines and fluoroquinolones showing the highest Kd values. The Kd values for fluoroquinolones, tetracyclines, macrolides, and sulfonamides have been reported as 54 600, 7600, 130, and 1.37 L kg-1 , respectively. Factors such as pH of the environment, solid matrix (sediment/soil sludge), and ionic strength can influence the Kd ; therefore, several values exist in literature for the same compound. Environ Toxicol Chem 2021;40:3275-3298. © 2021 SETAC.

Comparison between Phenotypic and Genotypic Detection of Metallo Beta Lactamase Enzyme among Gram Negative Bacteria Isolated from Burn Patient

Background: -lactamases (MBLs) are emerging worldwide as powerful resistance determinants in Gram negative bacteria Rapid dissemination and spread between different bacterial species by large gene transfer favor by globalization and travel represent a high risk of worldwide pandemic among Enterobacteriaceae Objective:This study design to screen for phenotypic detection of MBL and genes coding for metallo - lactamase(MBL) such as, blaVIM, blaIMP and bla NDM among infected burn wound patients in Sulaimani city /Iraq. Materials and Methods: Out of 230 burn wound samples, 201 wound swabs and 29 tissue biopsy were collected from hospitalized burn patients with second and third degrees burnfrom Burn and Plastic Surgery Hospital in Sulaimani city from the period of April to October 2011. According to direct gram stain , bacterial cultural , biochemical tests, analytic profile identification(API) system and vitek 2 Compact system , antimicrobial susceptibility Testing by using Kirby-Bauer disk diffusion method and vitek compact system, -lactamase by Double disk synergy test and Combined EDTA disk test and Modified Hodge test and -lactamase enzyme by using polymerase chain reaction. Results: Out of 230 burn wound samples177 samples gram negative bacteria were isolated; inflammatory cells showed significantly associated with positive bacterial culture. The most frequent bacteria isolated were Pseudomonas species 48(27.12%), in which Pseudomonas aeruginosa account for a higher percentage 46(25.98%) and one species (0.56%) of each P. stutzeri and P.florescence wasisolated followed by Acinetobacterspecies 44 (24.86%) in which Acinetobacterbaumanniiwas the commonest and accounts for a higher percentage 41 (23.16%) and one species(0.56%) of each of A. ursingi, A. hemolyticasandA.complexwere identified. On the other hand in the family of Enterobacteriaceae,the most common bacteria were Klebsiellapneumoniae44(24.86%), Enterobacter cloacae 18 (10.17%) and Escherichia species 11(6.21%). The susceptibility of bacterial isolates against 18 antibiotics from different classes of antibiotics was tested and it was found that most of the isolated species of non fermenter bacteria such as Acinetobacterand Pseudomonas species show multidrug resistant pattern and high resistance against most of the antibiotics commonly used. The most resistant antibiotics against non fermenter bacteria were Ticarcillin (81.82%) against Pseudomonas species and Ticarcillin, Tazobactam- Pipracillin and Cefoxitin (93.18%) against Acinetobacterspecies .The most resistant antibiotic against K. pneumonia andE.cloacaewere Cefoxitin(84.9%)and Amoxicillin Clavulanic acid (84.9%).The most resistant antibiotics against Escherichia specieswere Cefotaxime, Trimethoprim and Cefipime (90.91%) but the most effective antibiotic with a highsensitivity rate was Imipenem (90.91).Phenotypic tests were carried out for the detection of MBL enzyme for all studied isolates and it was found that Combined disk test was the most sensitive test giving the highest percentage (31.07%) followed by Double disk synergy test(28.8%), Modified Hodge test (20.9%) .Polymerase chain reaction assay was used for genotypic detection of MBL genes (blaIMP,blaVIM, ,blaNDM ) in all isolates and the results revealed that the gene blaIMPwas locatedin 33(18.64%),blaVIM,in19 (10.73%), 2(1.12%)forblaNDM Also these genes were detected in 25 stock cultures of Gram negative bacteria preserved in 25 °C since 2008 to 2010. blaIMP gene was detected in11(44%) , blaVIM in 12(48%) and 2(8%) for blaNDM, all these genes were detected in K. pneumonae,P. aeruginosa and A. baumanniiwith length amplified genes (230) bp for IMP and (390)bp for VIM and( 621)bp for NDM. Conclusions:These results indicate that most of the Meropenem resistant strains from infected burn wound strains in this study were producing MBL enzymes The presence of MBL genes among Meropenem sensitive strains indicates that there might be a hidden MBL gene among isolated strains which cannot be diagnosed by phenotypic tests leading to the dissemination of these genes in the hospital silently among patients even within normal health workers who act as carriers for MBL genes in future

A Comprehensive Computer Aided Vaccine Design Approach to Propose a Multi-Epitopes Subunit Vaccine against Genus Klebsiella Using Pan-Genomics, Reverse Vaccinology, and Biophysical Techniques.

Klebsiella is a genus of nosocomial bacterial pathogens and is placed in the most critical list of World Health Organization (WHO) for development of novel therapeutics. The pathogens of the genus are associated with high mortality and morbidity. Owing to their strong resistance profile against different classes of antibiotics and nonavailability of a licensed vaccine, urgent efforts are required to develop a novel vaccine candidate that can tackle all pathogenic species of the Klebsiella genus. The present study aims to design a broad-spectrum vaccine against all species of the Klebsiella genus with objectives to identify the core proteome of pathogen species, prioritize potential core vaccine proteins, analyze immunoinformatics of the vaccine proteins, construct a multi-epitopes vaccine, and provide its biophysical analysis. Herein, we investigated all reference species of the genus to reveal their core proteome. The core proteins were then subjected to multiple reverse vaccinology checks that are mandatory for the prioritization of potential vaccine candidates. Two proteins (TonB-dependent siderophore receptor and siderophore enterobactin receptor FepA) were found to fulfill all vaccine parameters. Both these proteins harbor several potent B-cell-derived T-cell epitopes that are antigenic, nonallergic, nontoxic, virulent, water soluble, IFN-γ producer, and efficient binder of DRB*0101 allele. The selected epitopes were modeled into a multi-epitope peptide comprising linkers and Cholera Toxin B adjuvant. For docking with innate immune and MHC receptors and afterward molecular dynamics simulations and binding free energy analysis, the vaccine structure was modeled for tertiary structure and refined for structural errors. To assess the binding affinity and presentation of the designed vaccine construct, binding mode and interactions analysis were performed using molecular docking and molecular dynamics simulation techniques. These biophysical approaches illustrated the vaccine as a good binder to the immune receptors and revealed robust interactions energies. The vaccine sequence was further translated to nucleotide sequence and cloned into an appropriate vector for expressing it at high rate in Escherichia coli K12 strain. In addition, the vaccine was illustrated to generate a good level of primary, secondary, and tertiary immune responses, proving good immunogenicity of the vaccine. Based on the reported results, the vaccine can be a good candidate to be evaluated for effectiveness in wet laboratory validation studies.

Occurrence of Multi-Drug-Resistant Escherichia coli in Chickens, Humans, Rodents and Household Soil in Karatu, Northern Tanzania.

We investigated antibiotic resistance profiles of Escherichia coli among 960 samples obtained from chickens (236), humans (243), rodents (101) and soil (290). E. coli was isolated from 650 (67.7%) samples. Isolation frequency varied significantly between chickens, humans, rodents and soil samples, being 81.6%, 86.5%, 79.2% and 31.0%, respectively (p < 0.001). Resistance rates were particularly higher against imipenem (79.8%), cefotaxime (79.7%) and tetracycline (73.7%) and moderate against amoxicillin-clavulanate (49.4%). Overall, 78.8% of the isolates were multidrug-resistant (MDR) among which, 38.8%, 25.1%, 12.9% and 2.5% exhibited resistance to three, four, five and six different classes of antibiotics, respectively. Multidrug-resistant E. coli were observed in 27.7%, 30.3%, 10.8% and 10.0% of the isolates from chickens, humans, rodents and soil samples, respectively. Our results show high levels of antimicrobial resistance including MDR in E. coli isolated from chickens, humans, rodents and soil samples in Karatu, Northern Tanzania. Comprehensive interventions using a one-health approach are needed and should include improving (i) awareness of the community on judicious use of antimicrobial agents in humans and animals, (ii) house conditions and waste management and (iii) rodent control measures.

Trend of antibiotic consumption and its association with influenza-like illnesses in France between 2004 and 2018.

Antibiotic consumption has been reported to be driven by the treatment of respiratory tract infections. Our objectives were to describe the trend of antibiotic consumption in France compared with that of other European countries; to describe the evolution of each antibiotic class in France; and to explore the relationship between antibiotic consumption and incidence of influenza-like illnesses. In this observational study, antibiotic consumption was reported as defined daily doses per 1000 inhabitants per day in the community and hospital sectors in descriptive and graphical formats, using data from the European Surveillance of Antimicrobial Consumption Network database. The total consumption and the consumption of different classes of antibiotics in France according to time and influenza-like illnesses were studied using multiple linear regression models. The total consumption of antibiotics in France was constant over the 15 years. It was driven by the community sector (92.8%) and was higher than the consumption of other European Union countries (P-value < 0.001). The beta-lactam penicillins were the most consumed antibiotic class and the only class that increased with time. The multiple linear regression models showed a positive correlation between antibiotic consumption in the community sector and incidence of influenza-like illnesses [B = 0.170, 95% CI (0.088-0.252)]. Similar significant results were shown between other antibiotic classes used in the management of influenza-like illnesses (other beta-lactams, and macrolides, lincosamides and streptogramins) and influenza-like illnesses. Our results suggest that antibiotics used in the management of respiratory tract infections might be involved in the irrational use of antibiotics.

The Results of the Study of Microbiologic Pattern of the Urinary Tract Infection in Children from Kyiv and Kyiv Region

The article presents the results of a retrospective analysis of the species composition of microbial pathogens of the urinary tract infection according to the results of urine culture and their sensitivity to antibiotics of different classes in children with the active stage of the disease (mainly with pyelonephritis), who were treated in the nephrology unit of Kyiv Children’s City Hospital № 1 in 2009–2014. A consistently high sensitivity (94.1 %) and low resistance (3.2 %) of Escherichia coli strains to a modern derivative of nitrofuran — furazidin K (Furamag) has been shown compared with other classes of antibacterial agents. The findings correspond with the international literature data and allow us to recommend this drug for empiric therapy of uncomplicated infections of the urinary system in children.

Antibiotics Used in Empiric Treatment of Ocular Infections Trigger the Bacterial Rcs Stress Response System Independent of Antibiotic Susceptibility.

The Rcs phosphorelay is a bacterial stress response system that responds to envelope stresses and in turn controls several virulence-associated pathways, including capsule, flagella, and toxin biosynthesis, of numerous bacterial species. The Rcs system also affects antibiotic tolerance, biofilm formation, and horizontal gene transfer. The Rcs system of the ocular bacterial pathogen Serratia marcescens was recently demonstrated to influence ocular pathogenesis in a rabbit model of keratitis, with Rcs-defective mutants causing greater pathology and Rcs-activated strains demonstrating reduced inflammation. The Rcs system is activated by a variety of insults, including β-lactam antibiotics and polymyxin B. In this study, we developed three luminescence-based transcriptional reporters for Rcs system activity and used them to test whether antibiotics used for empiric treatment of ocular infections influence Rcs system activity in a keratitis isolate of S. marcescens. These included antibiotics to which the bacteria were susceptible and resistant. Results indicate that cefazolin, ceftazidime, polymyxin B, and vancomycin activate the Rcs system to varying degrees in an RcsB-dependent manner, whereas ciprofloxacin and tobramycin activated the promoter fusions, but in an Rcs-independent manner. Although minimum inhibitory concentration (MIC) analysis demonstrated resistance of the test bacteria to polymyxin B and vancomycin, the Rcs system was activated by sub-inhibitory concentrations of these antibiotics. Together, these data indicate that a bacterial stress system that influences numerous pathogenic phenotypes and drug-tolerance is influenced by different classes of antibiotics despite the susceptibility status of the bacterium.

Phenotypic and Molecular Patterns of Resistance among Campylobacter coli and Campylobacter jejuni Isolates, from Pig Farms.

Simple SummaryCampylobacter spp. has been the leading cause of human diarrhea in EU since 2005. Although poultry and poultry meat are considered as the primary source of transmission of campylobacteriosis to humans, pigs can be a significant reservoir of the pathogen, as well. Moreover, the increase of antibiotic resistance in the specific pathogen, especially against fluroquinolones and macrolides is considered a significant threat for public health. The purpose of the current study was to evaluate and molecularly characterize the antimicrobial resistance of Campylobacter infection in pig farms in Greece at both phenotypic and molecular level.The purpose of this research was to characterize the antibiotic resistance patterns of Campylobacter spp. isolated from commercial farrow to finish farms in Greece, and analyze the relevant molecular resistance mechanisms among the resistant Campylobacter isolates. Susceptibility testing to five different classes of antibiotics was performed in 100 C. coli and 100 C. jejuni, previously isolated and identified. All isolates were found susceptible to meropenem. Very high rates of resistance were recorded for tetracyclines (84.5%), medium rates of resistance were recorded regarding quinolones (23%), and low and very low rates of resistance were identified for macrolides such as erythromycin and aminoglycosides (12% and 4%, respectively). Only 12.5% of the Campylobacter isolates displayed MDR. Regarding the molecular mechanisms of resistance, all ciprofloxacin resistant isolates hosted the mutant type Thr-86-Ile region of the quinolone resistance-determining region (QRDR) of the gyrA gene. In all erythromycin resistant isolates, the transitional mutations A2075G and A2074C in the 23S rRNA gene were only amplified. Molecular screening of tetracycline resistance genes indicated that the vast majority of Campylobacter isolates (92.3%) were positive for the tet(O) gene. In summary, these findings and especially the very high and medium rates of resistance for tetracyclines and fluroquinolones, respectively recommend that a continuous monitoring of Campylobacter isolates susceptibility in combination with the proper use of antimicrobials in livestock production is of great importance for public health.

Occurrence of Multidrug-Resistant Staphylococcus aureus among Humans, Rodents, Chickens, and Household Soils in Karatu, Northern Tanzania.

We conducted this study to investigate the isolation frequency and phenotypic antibiotic resistance pattern of Staphylococcus aureus isolated from rodents, chickens, humans, and household soils. Specimens were plated onto mannitol salt agar (Oxoid, Basingstoke, UK) and incubated aerobically at 37 °C for 24 h. Presumptive colonies of S. aureus were subjected to Gram staining, as well as catalase, deoxyribonuclease (DNAse), and coagulase tests for identification. Antibiotic susceptibility testing was performed by using the Kirby–Bauer disc diffusion method on Mueller–Hinton agar (Oxoid, Basingstoke, UK). The antibiotics tested were tetracycline (30 μg), erythromycin (15 μg), gentamicin (10 μg), ciprofloxacin (5 μg), clindamycin (2 μg), and amoxicillin-clavulanate (20 μg/10 μg). The S. aureus strain American Type Culture Collection (ATCC) 25,923 was used as the standard organism. We found that 483 out of 956 (50.2%) samples were positive for S. aureus. The isolation frequencies varied significantly between samples sources, being 52.1%, 66.5%, 74.3%, and 24.5%, respectively, in chickens, humans, rodents, and soil samples (p < 0.001). S. aureus isolates had high resistance against clindamycin (51.0%), erythromycin (50.9%), and tetracycline (62.5%). The overall prevalence of multidrug-resistant (MDR) S. aureus isolates was 30.2%, with 8.7% resistant to at least four different classes of antibiotics.

Characterization of Tigecycline Resistance Among Tigecycline Non-susceptible Klebsiella pneumoniae Isolates From Humans, Food-Producing Animals, and in vitro Selection Assay.

Emergence of extensively drug-resistant isolates of Klebsiella pneumoniae has prompted increased reliance on the last-resort antibiotics such as tigecycline (TGC) for treating infections caused by these pathogens. Consumption of human antibiotics in the food production industry has been found to contribute to the current antibiotic resistance crisis. In the current study, we aimed to investigate the mechanisms of TGC resistance among 18 TGC-non-susceptible (resistant or intermediate) K. pneumoniae (TGC-NSKP) isolates obtained from human (n = 5), food animals (n = 7), and in vitro selection experiment (n = 6). Isolates were genotyped by multilocus sequence typing (MLST). ramR, acrR, rpsJ, tetA, and mgrB (for colistin resistance) genes were sequenced. The presence of tetX, tetX1, and carbapenemase genes was examined by PCR. Susceptibility to different classes of antibiotics was evaluated by disc diffusion and broth macrodilution methods. The expression level of acrB was quantified by RT-qPCR assay. The 12 TGC-NSKP isolates [minimum inhibitory concentrations (MICs) = 4–32 mg/l] belonged to 10 distinct sequence types including ST37 (n = 2), ST11, ST15, ST45, ST1326 (animal isolates); ST147 (n = 2, human and animal isolates); and ST16, ST377, ST893, and ST2935 (human isolates). Co-resistance to TGC and colistin was identified among 57 and 40% of animal and human isolates, respectively. All human TGC-NSKP isolates carried carbapenemase genes (blaOXA–48, blaNDM–1, and blaNDM–5). tetX/X1 genes were not detected in any isolates. About 83% of TGC-NSKP isolates (n = 15) carried ramR and/or acrR alterations including missense/nonsense mutations (A19V, L44Q, I141T, G180D, A28T, R114L, T119S, Y59stop, and Q122stop), insertions (positions +205 and +343), or deletions (position +205) for ramR, and R90G substitution or frameshift mutations for acrR. In one isolate ramR amplicon was not detected using all primers used in this study. Among seven colistin-resistant isolates, five harbored inactivated/mutated MgrB due to premature termination by nonsense mutations, insertion of IS elements, and frameshift mutations. All isolates revealed wild-type RpsJ and TetA (if present). Increased expression of acrB gene was detected among all resistant isolates, with the in vitro selected mutants showing the highest values. A combination of RamR and AcrR alterations was involved in TGC non-susceptibility in the majority of studied isolates.