Spread Of Antibiotic-resistant Pathogens Research Articles

Design of Novel Saposin-like Bacteriocins Using a Hybrid Approach.

A multitude of approaches will be required to respond to the threat posed by the emergence and spread of antibiotic resistant pathogens. Bacteriocins have gained increasing attention as a possible alternative to antibiotics, as such peptide antimicrobials have mechanisms of action different from antibiotics and are therefore equally potent against antibiotic resistant bacteria as their susceptible counterparts. A group of bacteriocins known as saposin-like bacteriocins is believed to act directly on the bacterial membrane. Based on seven saposin-like leaderless bacteriocins, we have constructed a library of hybrid peptides containing all combinations of the N- and C-terminal halves of the native bacteriocins. All hybrid peptides were synthesized using in vitro protein expression and assayed for antimicrobial activity towards several pathogens. Of the 42 hybrid peptides, antimicrobial activity was confirmed for 11 novel hybrid peptides. Furthermore, several of the hybrid peptides exhibited altered antimicrobial spectra and apparent increase in potency compared to the peptides from which they were derived. The most promising hybrid, termed ISP26, was then obtained synthetically and shown to inhibit most of the Gram-positive species tested, including opportunistic pathogens and food spoilage bacteria. Additionally, ISP26 was shown to inhibit Acinetobacter, a species of Gram-negative bacteria frequently isolated from nosocomial infections. The activity of the hybrid library provides valuable insights into the design and screening of new active bacteriocins.

Plant phenolics inhibit focal adhesion kinase and suppress host cell invasion by uropathogenic Escherichia coli.

Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses and likely contribute to the development of chronic and recurrent infections. In cell culture-based assays, only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic-resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenic Escherichia coli (UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here, we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds, resveratrol, effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds could be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues and help explain some of the benefits attributed to traditional plant-based medicines.

Acute conjunctivitis – antibiotic susceptibility and resistance to different antibiotics in main Eye Hospital, Tripoli, Libya

Acute conjunctivitis is characterized by inflammation of the conjunctiva of less than 3 to 4 weeks duration, cellular infiltration, and exudation. It may also result in corneal, lid, or orbital involvement which may lead to various complications. Bacterial conjunctivitis is a self-limiting process, but topical antibiotic treatment is recommended to eradicate the pathogen and reduce symptom duration. A hospital-based prospective study was conducted in the emergency and casualty department in Zawyat Aldahmani Eye Hospital, Tripoli /Libya comprising out-patients (OPD) visiting the department from June to December 2019 (186 cases). The primary objective was to evaluate the bacteriological pattern and the secondary objectives were to evaluate seasonal variation and antibiotic sensitivity pattern of the isolates. Conjunctival swabs included patients from both sexes (males n_106 and females n_80) and different ages; 80.1% of adults of the whole studied cases and the rest were children under 12 years old. Staph. hominis (26.17%) was the predominant organism isolated throughout the study. The commonest single organism isolates were Staph. haemolyticus (11.21%) Staph. aureus (9.35%). All isolates were identified and susceptibility patterns towards about 34 different antibiotics were studied. There were 186 patients enrolled. Of all cultures, 57.5% (107) yielded one of the study pathogens. Gram-positive organisms were isolated from 83 (77.57%) of cultures, gram-negative organisms were isolated from 15 (14.02%), and 9 (8.4%) were fungal growth. From 107 gram-positive isolates, 19 samples (22.9%) gave coagulase-positive results and 64 samples (77.1%) gave negative results. All the major organisms (S. aureus, S. hominis, S. hemolytic, S. epidermidis, E. coli, Mycobacterium, and Moraxilla catarrhalis) susceptible to cephalosporins, macrolides, aminoglycosides and fluoroquinolones (levofloxacin). Tetracycline has the lowest effect on both gram-positive and gram-negative isolates. In conclusion, our findings should alert physicians on the choice of appropriate antibiotic treatment after applying AST to the identified strains and on the potential role of conjunctivitis in the spread of antibiotic-resistant pathogens. In addition, external bacterial infections of the eye were most frequently caused by the common skin bacteria. Staphylococci spp. was by far the most common bacterial pathogen.

Mathematical modelling of antibiotic interaction on evolution of antibiotic resistance: an analytical approach.

The emergence and spread of antibiotic-resistant pathogens have led to the exploration of antibiotic combinations to enhance clinical effectiveness and counter resistance development. Synergistic and antagonistic interactions between antibiotics can intensify or diminish the combined therapy's impact. Moreover, these interactions can evolve as bacteria transition from wildtype to mutant (resistant) strains. Experimental studies have shown that the antagonistically interacting antibiotics against wildtype bacteria slow down the evolution of resistance. Interestingly, other studies have shown that antibiotics that interact antagonistically against mutants accelerate resistance. However, it is unclear if the beneficial effect of antagonism in the wildtype bacteria is more critical than the detrimental effect of antagonism in the mutants. This study aims to illuminate the importance of antibiotic interactions against wildtype bacteria and mutants on the deacceleration of antimicrobial resistance. To address this, we developed and analyzed a mathematical model that explores the population dynamics of wildtype and mutant bacteria under the influence of interacting antibiotics. The model investigates the relationship between synergistic and antagonistic antibiotic interactions with respect to the growth rate of mutant bacteria acquiring resistance. Stability analysis was conducted for equilibrium points representing bacteria-free conditions, all-mutant scenarios, and coexistence of both types. Numerical simulations corroborated the analytical findings, illustrating the temporal dynamics of wildtype and mutant bacteria under different combination therapies. Our analysis provides analytical clarification and numerical validation that antibiotic interactions against wildtype bacteria exert a more significant effect on reducing the rate of resistance development than interactions against mutants. Specifically, our findings highlight the crucial role of antagonistic antibiotic interactions against wildtype bacteria in slowing the growth rate of resistant mutants. In contrast, antagonistic interactions against mutants only marginally affect resistance evolution and may even accelerate it. Our results emphasize the importance of considering the nature of antibiotic interactions against wildtype bacteria rather than mutants when aiming to slow down the acquisition of antibiotic resistance.

A new acridine-based photosensitizer with ultra-low light requirement efficiently inactivates carbapenem-resistant Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus and degrades their antibiotic resistance genes

The spread of antibiotic resistant pathogens and antibiotic resistance genes (ARGs) in the environment poses a serious threat to public health. However, existing methods are difficult to effectively remove antibiotic resistant pathogens and ARGs from the environment. In this study, we synthesized a new acridine-based photosensitizer, 2,7-dibromo-9-mesityl-10-methylacridinium perchlorate (YM-3), by the heavy atom effect, which could photodynamically inactivate antibiotic resistant pathogens and reduce ARGs by generating singlet oxygen (1O2) in an aqueous environment. The 1O2 yield of YM-3 was 4.9 times that of its modified precursor. YM-3 could reduce the culturable number and even the viable counts of methicillin-resistant Staphylococcus aureus and carbapenem-resistant Acinetobacter baumannii to 0 (inactivation rate > 99.99999%) after 2 and 8 h of low-intensity blue light (15 W/m2) irradiation, respectively. After 20 h of light exposure, the copy numbers of ARGs in both bacteria were reduced by 5.80 and 4.48 log, respectively, which might indicate that ARGs had been degraded. In addition, YM-3 still had an efficient bactericidal effect after five inactivation cycle. These characteristics of ultra-low light intensity requirement and efficient bactericidal ability make YM-3 have good application prospects for disinfection in indoor and sunlight environment.

Main-chain flexibility and hydrophobicity of ionenes strongly impact their antimicrobial activity: an extended study on drug resistance strains and Mycobacterium.

The spread of antibiotic-resistant pathogens and the resurgence of tuberculosis disease are major motivations to search for novel antimicrobial agents. Some promising candidates in this respect are cationic polymers, also known as synthetic mimics of antimicrobial peptides (SMAMPs), which act through the membrane-lytic mechanism. Development of resistance toward SMAMPs is less likely than toward currently employed antibiotics; however, further studies are needed to better understand their structure–activity relationship. The main objective of this work is to understand the cross-influence of hydrophobicity, main-chain flexibility, and the topology of ionenes (polycations containing a cationic moiety within the main-chain) on activity. To fulfill this goal, a library of ionenes was developed and compared with previously investigated molecules. The obtained compounds display promising activity against the model microorganisms and drug-resistance clinical isolates, including Mycobacterium tuberculosis. The killing efficiency was also investigated, and results confirm a strong effect of hydrophobicity, revealing higher activity for molecules possessing the flexible linker within the polymer main-chain.

230. Nontyphoidal Salmonella from Clinical and Retail Meat Sources Reveal Antimicrobial Resistance Genes for Ceftriaxone and Ciprofloxacin

BackgroundPennsylvania participates in the National Antimicrobial Resistance Monitoring System (NARMS), which includes monitoring of Nontyphoidal Salmonella (NTS), a leading cause of bacterial foodborne illnesses in the United States.MethodsClinical NTS isolates submitted to the Pennsylvania Department of Health (2015-18) were tested for susceptibility to 15 antimicrobial agents and analyzed by whole-genome sequencing (WGS). Concurrently, we conducted a prospective microbiological survey of NTS in retail meat products (chicken breasts, ground turkey, and pork chops) with susceptibility testing and WGS. ResultsOf a sample of 426 clinical Salmonella isolates from humans analyzed for antimicrobial susceptibility, 65 (15.3%) had decreased susceptibility to ciprofloxacin (DSC). Ampicillin resistance was observed in 39 (9.2%) and 15 (3.5%) were ceftriaxone-resistant. Ten ceftriaxone-resistant isolates had genetic elements that confer resistance to third generation extended-spectrum cephalosporins (ESC) [blaCMY−2, n=8 and blaCTX-M-65, n=2]. The blaCTX-M-65- positive isolates had a mutation in gyrA that confers fluoroquinolone resistance. Thirteen clinical isolates carried plasmid-mediated fluoroquinolone resistance genes (PMQR) [qnrB19, qnrS1, qnrA1]. We detected NTS in 131 (3.8%) of 3480 meat samples tested. 7 (5.3%) had DSC, while 38 (29%) and 21 (16%) were resistant to ampicillin and ceftriaxone, respectively. Four S. Infantis isolates had DSC and a blaCTX-M-65 gene plus a mutation in gyrA. Thirteen meat isolates had the blaCMY-2 gene. One additional blaCTX-M-65-positive S. Infantis without gyrA from ground turkey (SRR6351119) differed from four clinical isolates by ≤10 single-nucleotide polymorphisms. Percent of isolates from patients and meat sources that demonstrated resistance to amoxicillin-clavulanate (AMC), ceftriaxone, and decreased susceptibility to ciprofloxacin (DSC) to nine antimicrobial classes tested. Among isolates from patients, resistance to ceftriaxone, a third-generation cephalosporin preferred for severe infections in children, increased from zero in 2015 to 5.8% in 2017. Overall, DSC increased in isolates from human sources while in strains from meat sources, DSC increased from zero in 2015 to over five percent in 2018.ConclusionNTS isolated from human and meat sources were multi-drug resistant. Demonstration of similar resistance genes in meat and in ill humans may be consistent with spread of antibiotic-resistant pathogens from food sources. Dissemination of genes that confer resistance to third generation cephalosporins and fluoroquinolones, including some on mobile plasmids, may undermine recommended treatment for severe NTS infections. These results underscore the need for antimicrobial stewardship efforts in both agriculture and human medicine.Disclosures All Authors: No reported disclosures

Bacterial metal nanoparticles to develop new weapons against bacterial biofilms and infections.

The widespread use of antibiotics has resulted in the outbreak and spread of antibiotic-resistant pathogens. Bacterial antibiotic resistance may develop at cellular and community levels. In the latter case, it is based on tolerance which implicates the shift from a free-living form of life (i.e., planktonic) to a sessile multi-stratified community (i.e., biofilm). Metal nanoparticles (MNPs) have been shown to be promising candidates as antimicrobial agents. MNPs are able to interact with and penetrate bacterial biofilms, thus, resulting effective antibiofilm compounds. Another interesting aspect is the possibility of using plants, fungi, yeasts, and bacteria to obtain biogenic MNPs (BMNP). Bacteria are able to grow in presence of many different toxic heavy metal ions thanks to different metal resistance gene clusters that allow a variety of biochemical counters (formation of harmless complexes, efflux, precipitation, reduction, etc.). The formation of BMNPs by bacterial cells could be, in most cases, just a consequence of metal detoxification mechanisms. This review focuses on BMNPs from bacterial origin that may represent a good source of compounds with a broad spectrum of activity against common Gram-positive and Gram-negative pathogens and bacterial biofilms thereof. In particular, the state of art on BMNP synthesis by bacteria is presented and potential applications in the fight against biofilm-associated infections and resistant pathogens are highlighted. In addition, critical aspects on BMNP bacterial synthesis and utilization are commented.Key points• New antimicrobials to fight antibiotic-resistant pathogens are urgently needed.• Biogenic metal nanoparticles can efficiently hit biofilm-forming pathogens.• Metal-nanoparticle composition could confer specific antibiofilm activity.

Carbapenem-resistant Enterobacteriaceae infections among patients admitted to intensive care units in Kano, Nigeria

Background: Globally, intensive care units (ICUs) are encountering emergence and spread of antibiotic-resistant pathogens, and for some pathogens, there are few therapeutic options available. Objectives: The study assessed prevalence, susceptibility pattern, and risk factors of carbapenem-resistant Enterobacteriaceae (CRE) infections among ICU patients in Kano, Nigeria. Materials and Methods: A descriptive cross-sectional study was used to study 190 patients admitted to the ICUs of two tertiary hospitals in Kano. Antibiotic susceptibility of isolated organisms was determined by disc diffusion technique. Suspected carbapenemase producers were further subjected to the modified Hodge test (MHT) method for confirmation. Results: A total of 76 out of the 190 samples yielded clinical isolates of Enterobacteriaceae as follows: 34 (44.7%) Escherichia coli, 19 (25%) Klebsiella pneumoniae, 3 (3.9%) Proteus mirabilis, 4 (5.3%) Enterobacter aerogenes, 3 (3.9%) Proteus vulgaris, 2 (2.6%) Citrobacter freundii, 2 (2.6%) Klebsiella ozaenae, 2 (2.6%) Klebsiella oxytoca, 2 (2.6%) Salmonella subsp. 3b, 2 (2.6%) Enterobacter agglomerans, 2 (2.6%) Enterobacter cloacae, and 1 (1.3%) Serratia odorifera. Screening the Enterobacteriaceae-positive samples for carbapenem resistance using ertapenem disc (10 μg) showed 8 samples (10.5%) as resistant while MHT gave a carbapenem resistance prevalence of 7.9% (6 out of 76). Based on multiplex polymerase chain reaction; the distributions of genotypes of the carbapenemase producers were as follows: Verona Integron Metallo-beta-lactamase (VIM) genes only (4 [50%]) New Delhi Metallo-beta-lactamase (NDM) genes only (2 [25%]), and 1 (12.5%) had Klebsiella pneumoniae carbapenemase (KPC) and VIM gene coexisting. Surgical procedure (P = 0.009) and history of recent admission (P = 0.001) were found to be risk factors for CRE. Conclusion: The study provided evidence of the presence of CRE infections among patients admitted to ICUs in the study centers. This underscores the need for effective infection prevention and control measures to avoid the spread of CRE in hospital setting.

Incidence and antibiotic susceptibility of bacteria in goat milk in Ibadan, Nigeria

Goat milk and its products are highly nutritious and widely consumed in several countries. In Nigeria, little attention has been given to goats as dairy animals; hence the raw milk can be a potential source of bacterial contamination and spread of antibiotic resistant pathogens within human, animal and environment. In this study, the incidence and antibiotic susceptibility of bacteria in goat milk in Ibadan, Nigeria was evaluated. The bacteriological quality and antibiotic resistance characteristics of the isolates from105 raw milk samples collected from does in five goat herds in Ibadan in Oyo-State, Nigeria were carried out. A total of 126 bacterial isolates belonging to six bacteria genera [Lactobacillus spp (23.81%), Staphylococcus aureus (23.02%), E.coli (20.63%), Klebsiella pneumonia (15.08%), Pseudomonas aeruginosa (10.35%), Streptococcus spp (07.14%)] were obtained from the samples. The Gramnegative isolates exhibited resistance toamoxillin (84.50%), augmentin (77.59%), septrin (75.86%), sparfloxacin (72.41%), chloramphenicol (68.97%), streptomycin (65.52%), perfloxacin (56.90%), tarivid (51.72%), gentamycin (48.28%), ciprofloxacin (48.27%).While the Gram positive bacteria also exhibited resistance to ampiclox ( 69.12%), septrin (42.65%), erythromycin (33.82%), streptomycin (14.71%), gentamycin (11.76%), rocephin (07.35%), zinnacef (02.94%), ciprofloxacin (01.47%). Multi-drug resistance (MDR) to three or more antimicrobials was observed in some of the isolates. This study revealed high prevalence of MDR bacteria in goat milk that can contribute to the global antibiotic resistance menace through primary or secondary infections associated with husbandry, milking and consumption of improperly pasteurized goat milk.

Pathogenetic effects of antibiotic resistance on a woman’s reproductive health

Background. Over the last decade, women in many countries around the world have seen an increase in the number of urogenital infections, which occupy the first place in the structure of obstetric and gynecological morbidity. Risk factors for the development of inflammatory diseases include the invasive procedures and irrigations, sexual activity, unreasonable treatment, refusal to restore eubiosis after antimicrobial and antifungal therapy, the presence of intrauterine devices, etc.
 Objective. To characterize the influence of the spread of antibiotic-resistant pathogens on the course of gynecological diseases.
 Materials and methods. Analysis of literature data on this issue.
 Results and discussion. Peculiarities of the vaginal infections course’ nowadays include prevalence of self-treatment, uncontrolled antibiotics (AB) use, the development of AB resistance, and the presence of extragenital pathology. Pelvic inflammatory disease (PID) comprise 75 % of all gynecological diseases. PID cause such complications as chronic pelvic pain syndrome, purulent tubo-ovarian tumors, cervical neoplasia, and infertility. The risk of the latter increases depending on the number of episodes of PID. Principles of PID treatment include comprehensiveness, etiopathogenetic orientation, individualization and recurrence prevention. Antibacterial therapy (ABT), nonsteroidal anti-inflammatory drugs, infusions, transfusions, detoxification therapy, medications aimed at the improvement of hemodynamics and microcirculation, immunotherapy, and topical therapy are used in the treatment of PID. The consequences of irrational ABT include an increase in the resistance of pathogenic flora, disruption of the normal body biocenosis, increased risk of adverse reactions, impaired immune function and increased treatment costs. Macrolides, cephalosporins, fluoroquinolones and aminoglycosides are the main groups of AB used for the systemic ABT in PID. Tobramycin (one of the latter group) is active against 83.4 % of pathogens that cause urogenital infections. Other advantages of tobramycin include synergism with β-lactams and high activity against Pseudomonas aeruginosa – a bacterium with a high and dangerous potential for AB resistance. In turn, fluoroquinolones are active against 94 % of pathogens that cause urogenital infections; they are able to penetrate cell membranes and have a low potential for the formation of AB resistance. The combination of fluoroquinolone levofloxacin with ornidazole (Grandazole, “Yuria-Pharm”) can improve the general condition and reduce pain on the 3rd day of treatment of PID, normalize the temperature, reduce hospital stay. Co-administration of levofloxacin and ornidazole as part of an infusion solution is more rational than their separate use. Such treatment minimizes the risk of allergic reactions and side effects. For local sanitation of vagina and vulva, it is advisable to use decamethoxine (Dekasan, “Yuria-Pharm”) – a basic antiseptic that acts on various types of bacteria, viruses, fungi and protozoa. Additional benefits are anti-inflammatory, desensitizing and antispasmodic action. Decamethoxine also effectively reduces the adhesion of staphylococci and Escherichia coli. One of the main advantages of decamethoxine is the lack of effect on human cells.
 Conclusions. 1. PID are the most common diseases in the field of obstetrics and gynecology. 2. Care should be taken when choosing a drug for ABT. 3. The combination of levofloxacin and ornidazole can effectively treat PID, reducing the duration of inpatient treatment. 4. For local sanitation of the vagina and vulva, it is advisable to use decamethoxine.

Use of Probiotics in Commercially Important Finfish Aquaculture

Finfish aquaculture is one of the quickly developing food industries in the world. But, the major drawbacks of this industry are the frequent outbreak of infectious diseases due to elevated stress in an intensive culture system. Antibiotics are extensively used to combat these diseases. Prophylactic administrations of antibiotics in aquaculture lead to the emergence and spread of antibiotic-resistant pathogens which indirectly cause a risk to health of human. Therefore, hard rules and regulations have been established in various countries to minimize or ban the application of antibiotics in finfish aquaculture. Recently probiotics have garnered significant attraction as an alternative measure for disease prevention in aquaculture. Probiotics increase health status, disease resistance, growth performance and feed utilization through improving hosts microbial balance. This review presents the summary and discussion of the results of the effects of probiotic administration in the culture of commercially important finfish. Besides, the current study attempts to explore the gap in present scientific information as well as suggests concerns that worth further research.

Excessive use of medically important antimicrobials in food animals in Pakistan: a five-year surveillance survey

ABSTRACT Demand for poultry meat is rising in low- and middle-countries, driving the expansion of large commercial farms where antimicrobials are used as surrogates for hygiene, good nutrition. This routine use of antimicrobials in animal production facilitates the emergence and spread of antibiotic-resistant pathogens. Despite potentially serious consequences for the animal industry, few studies have documented trends in antimicrobial use (AMU) at the farm-level in low- and middle-income countries. The objective of this study was to estimate AMU in a broiler chicken farm in Pakistan over a five-year period and to extrapolate national AMU in commercial broiler farming. Between 2013 and 2017, we monitored AMU in 30 flocks from a commercial broiler farm in Punjab, the most populous province of Pakistan. The amount of antimicrobials administered was calculated in milligram/population unit of the final flock weight (mg/fPU) and in used daily dose (UDD). The annual on-farm antimicrobial use was 250.84 mg of active ingredient per kilogram of the final flock weight. This consumption intensity exceeds the amount of antimicrobial used per kilogram of chicken of all countries in the world except China. Measured in mg per kg of final flock weight or population unit (fPU), medically important drugs such as colistin (31.39 mg/fPU), tylosin (41.71 mg/fPU), doxycycline (81.81 mg/fPU), and enrofloxacin (26.19 mg/fPU) were the most frequently used antimicrobials for prophylactic or therapeutic use. Lincomycin was the most frequently used antimicrobial used in-feed (29.09 mg/fPU). Our findings suggest that the annual consumption of antimicrobials in the broiler sector in Pakistan could be as high as 568 tons. This alarmingly high consumption estimate is the first baseline study on antimicrobial use in animals in Pakistan. Our findings call for immediate actions to reduce antimicrobial use in Pakistan, and countries with comparable farming practices.

Antimicrobial Resistance Factors of Extended-Spectrum Beta-Lactamases Producing Escherichia coli and Klebsiella pneumoniae Isolated from Cattle Farms and Raw Beef in North-West Province, South Africa.

Background Extended spectrum beta-lactamases (ESBLs) producing Enterobacteriaceae cause severe infections in humans which leads to complicated diseases. There is increasing evidence that cattle contribute to the development and spread of multidrug resistant pathogens and this raises public health concern. Despite this, data on the concurrence of ESBL producing pathogens in cattle, especially in the North-West province are rare. Therefore, the aim of the present study was to isolate, identify and characterise ESBL producing E. coli and K. pneumoniae species from cattle faeces and raw beef samples. Results A total of 151 samples comprising 55 faeces samples and 96 raw beef samples were collected and 259 nonreplicative potential isolates of Enterobacteriaceae were obtained. One hundred and ninety-six isolates were confirmed as E. coli (114; 44%) and K. pneumoniae (82; 32%) species through amplification of uspA and uidA and ntrA gene fragments, respectively. Antimicrobial susceptibility test revealed that large proportions (66.7–100%) of the isolates were resistant to Amoxicillin, Aztreonam, Ceftazidime, Cefotaxime, and Piperacillin and were multidrug resistant isolates. Cluster analysis of antibiotic inhibition zone diameter data revealed close similarities between isolates from different sources or species thus suggested a link in antibiotic exposures. The isolates showing phenotypic resistance against ESBL antimicrobial susceptibility tests were screened for the presence of ESBL gene determinants. It was observed that 53.1% of the isolates harboured ESBL gene determinants. The blaTEM, blaSHV and blaCTX-M genes were detected in E. coli isolates (85.5%, 69.6%, and 58%, respectively) while blaCTX-M and blaOXA were detected in K. pneumoniae (40% and 42.9%, respectively). All the genetically confirmed ESBL producing E. coli and K. pneumoniae isolates were subjected to Enterobacterial Repetitive Intergenic Consensus (ERIC) PCR analysis. Fingerprinting data revealed great similarities between isolates from different areas and sources which indicates cross-contamination between cattle and beef. Conclusion This study revealed that cattle and its associated food products, beef in particular, harbour ESBL producing pathogens. And this warrants a need to enforce hygiene measures and to develop other mitigation strategies to minimise the spread of antibiotic resistant pathogens from animals to human.

A study of microbiological profile and antibiotic susceptibility pattern of the organisms isolated from blood stream infection in patients of critical care units in tertiary care hospital in Western India

Introduction: BSI is a major cause of mortality in hospitalized patients. ICU patients are more likely to acquire nosocomial infections than other hospitalised patients. The nature of ICU environment is such, that makes it a focus for the emergence and spread of antibiotic resistant pathogens. Aim and Objectives: To Study the spectrum of bacteria causing blood stream infection and their antibiotic susceptibility patterns in patients of critical care units. Materials and Methods: The study was carried out in the Department of Microbiology, PDU Medical College, Rajkot from January 2018 to June 2018. Blood samples were collected in BHIB and processed for culture on blood agar and MacConkey agar, Gram stain and biochemical tests. Antimicrobial susceptibility testing was performed by modified Kirby Bauer method as per the CLSI guidelines. Results: 464(29.83%) were isolated from 1555 specimens. Out of these, 443 from NICU, 19 from PICU, 1 from ICCU and 1 from SICU, predominantly males (57.11%). GNB sensitivite to Imipenem (100%), Amikacin (95.67%), followed by Levoflox (95%) and Gentamicin (84.33%) and GPC to Linezolid (100%), Vancomicine (100%) followed by Gentamicin (99%) and Tetracycline (89%). Maximum resistance observed to Cephtazidim, Co-trimoxazole in GNB and Erythromicin, Clindamicin in GPC. Conclusion: Excessive use of broad spectrum antibiotics, immunocompromised hosts, invasive procedures make the ICU patients susceptible to colonization with highly resistant pathogens. This study helps to know the spectrum of bacteria causing BSIs and will guide the clinicians to use appropriate management strategies and to formulate local antibiotic policy, thereby will help in early cure and reduced hospital stay of the patients. Keywords: BSI, Blood stream Infection, Blood culture, Neonatal sepsis.

The Concept of an Ideal Antibiotic: Implications for Drug Design.

The emergence and spread of antibiotic-resistant pathogens is a major public health issue, which requires global action of an intersectoral nature. Multidrug-resistant (MDR) pathogens—especially “ESKAPE” bacteria—can withstand lethal doses of antibiotics with various chemical structures and mechanisms of action. Pharmaceutical companies are increasingly turning away from participating in the development of new antibiotics, due to the regulatory environment and the financial risks. There is an urgent need for innovation in antibiotic research, as classical discovery platforms (e.g., mining soil Streptomycetes) are no longer viable options. In addition to discovery platforms, a concept of an ideal antibiotic should be postulated, to act as a blueprint for future drugs, and to aid researchers, pharmaceutical companies, and relevant stakeholders in selecting lead compounds. Based on 150 references, the aim of this review is to summarize current advances regarding the challenges of antibiotic drug discovery and the specific attributes of an ideal antibacterial drug (a prodrug or generally reactive compound with no specific target, broad-spectrum antibacterial activity, adequate penetration through the Gram-negative cell wall, activity in biofilms and in hard-to-treat infections, accumulation in macrophages, availability for oral administration, and for use in sensitive patient groups).

Search for Shorter Portions of the Proline-Rich Antimicrobial Peptide Fragment Bac5(1-25) That Retain Antimicrobial Activity by Blocking Protein Synthesis.

The spread of antibiotic-resistant pathogens has boosted the search for new antimicrobial drugs. Proline-rich antimicrobial peptides are promising lead compounds for the development of next-generation antibiotics, given their very low cytotoxicity and their good antimicrobial activity targeting the bacterial ribosome. Bac5(1-25) is an N-terminal fragment of the bovine proline-rich antimicrobial peptide Bac5, whose mode of action has been recently described. In this work we tested a number of Bac5(1-25) fragments, and we characterized their antimicrobial activity against Escherichia coli, Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus, Salmonella enterica, and Pseudomonas aeruginosa. We evaluated their cytotoxicity toward human cells and their efficacy in inhibiting bacterial protein synthesis. This allowed us to identify some shorter fragments of Bac5(1-25) with a good balance between antibacterial efficacy, protein synthesis inhibition, and ease/cost-effectiveness of synthesis, suitable as lead compounds to develop new antibacterials.

Total Synthesis and Structure-Activity Relationships Study of Odilorhabdins, a New Class of Peptides Showing Potent Antibacterial Activity.

The spread of antibiotic-resistant pathogens is a growing concern, and new families of antibacterials are desperately needed. Odilorhabdins are a new class of antibacterial compounds that bind to the bacterial ribosome and kill bacteria through inhibition of the translation. NOSO-95C, one of the first member of this family, was synthesized for the first time, and then a structure-activity relationships study was performed to understand which groups are important for antibacterial activity and for inhibition of the bacterial translation. Based on this study an analogue showing improved properties compared to the parent compound was identified and showed promising in vitro and in vivo efficacy against Enterobacteriaceae.

Fecal Carriage of Antimicrobial-Resistant Enterobacteriaceae in Healthy Korean Adults.

The spread of antibiotic-resistant Enterobacteriaceae in the community is one of the main challenges for antibiotic treatment of community-onset infections. We evaluated the microbiological and molecular characteristics of stool samples from adults with comprehensive health examinations. Of 109 fecal samples, bacterial growth was observed in 86 samples and 61 gram-negative bacterial isolates were identified, of which 45 were Escherichia coli isolates (73.8%). Two isolates of Raoultella showed imipenem resistance, and both E. coli and Citrobacter freundii showed intermediate resistance to imipenem. Colistin resistance was identified in isolates of Klebsiella variicola and Salmonella subterranean, but no isolates carried mcr-1. As for E. coli genotypes, 35 sequence types were identified. blaTEM-1, blaTEM-30, and blaCTX-M were identified in 15, 1, and 4 E. coli isolates, respectively. In addition, all four Klebsiella pneumoniae isolates carried blaSHV. Many genotypes that have been identified in isolates causing human infections were found in isolates in this study. There is a need to control the rise and spread of antibiotic-resistant pathogens by fecal carriage.

D-BMAP18 Antimicrobial Peptide Is Active In vitro, Resists to Pulmonary Proteases but Loses Its Activity in a Murine Model of Pseudomonas aeruginosa Lung Infection.

The spread of antibiotic resistant-pathogens is driving the search for new antimicrobial compounds. Pulmonary infections experienced by cystic fibrosis (CF) patients are a dramatic example of this health-care emergency. Antimicrobial peptides could answer the need for new antibiotics but translating them from basic research to the clinic is a challenge. We have previously evaluated the potential of the small membranolytic peptide BMAP-18 to treat CF-related infections, discovering that while this molecule had a good activity in vitro it was not active in vivo because of its rapid degradation by pulmonary proteases. In this study, we synthesized and tested the proteases-resistant all-D enantiomer. In spite of a good antimicrobial activity against Pseudomonas aeruginosa and Stenotrophomonas maltophilia clinical isolates and of a tolerable cytotoxicity in vitro, D-BMAP18 was ineffective to treat P. aeruginosa pulmonary infection in mice, in comparison to tobramycin. We observed that different factors other than peptide degradation hampered its efficacy for pulmonary application. These results indicate that D-BMAP18 needs further optimization before being suitable for clinical application and this approach may represent a guide for optimization of other anti-infective peptides eligible for the treatment of pulmonary infections.