Mechanisms of Antibiotic Resistance in Important Gram-Positive and Gram-Negative Pathogens and Novel Antibiotic Solutions

Multidrug-resistant bacteria have on overwhelming impact on human health, as they cause over 670,000 infections and 33,000 deaths annually in the European Union alone. Of these, the vast majority of infections and deaths are caused by only a handful of species—multi-drug resistant Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterococcus spp., Acinetobacter spp. and Klebsiella pneumoniae. These pathogens employ a multitude of antibiotic resistance mechanisms, such as the production of antibiotic deactivating enzymes, changes in antibiotic targets, or a reduction of intracellular antibiotic concentration, which render them insusceptible to multiple antibiotics. The purpose of this review is to summarize in a clinical manner the resistance mechanisms of each of these 6 pathogens, as well as the mechanisms of recently developed antibiotics designed to overcome them. Through a basic understanding of the mechanisms of antibiotic resistance, the clinician can better comprehend and predict resistance patterns even to antibiotics not reported on the antibiogram and can subsequently select the most appropriate antibiotic for the pathogen in question.

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Report of Antibiotic Resistance in Urban and Rural Wastewaters from West Bengal, India

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i53a33660 ◽

2021 ◽

pp. 274-285

Author(s):

Meesha Singh ◽

Rupsha Karmakar ◽

Sayak Ganguli ◽

Mahashweta Mitra Ghosh

Keyword(s):

Antibiotic Resistance ◽

Biochemical Characterization ◽

Chemical Properties ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Medical Facility ◽

Antibiotic Resistant ◽

Two Samples ◽

Resistance Patterns ◽

Antibiotic Resistance Patterns

Aims: This study aims at comparative identification of antibiotic resistance patterns in bacteria isolated from samples collected from rural environment (LS) and urban environments (SS). Metagenomic profiling gave us insights into the microbial abundance of the two samples. This study focused on culture-based methods for complete identification of antibiotic resistant isolates and estimation of comparative antibiotic resistance among the two samples. Study Design: Untreated medical waste and anthropogenic waste disposal can lead to the propagation of different antibiotic resistant strains in wastewater environments both in urban and rural set ups which provide an insight towards this study approach mentioned in the methodology segment. Place and Duration of Study: Sewer system of a medical facility located in Purulia, India was the collection site for liquid sludge. Solid sludge and associated wastewater were collected in vicinity of a large urban medical facility from central Kolkata, India. Methodology: Physico-chemical properties were analyzed followed by microbiological and biochemical characterization. The antibiotic resistance patterns were determined by Kirby-Bauer disc diffusion assay. Potent multidrug resistant isolates were identified using 16srRNA gene amplification followed by Phylogenetic profiling, using CLC Genomics workbench. Results: We observed maximum resistance in an E. coli isolate which was resistant up to 22 antibiotics. Combined data for resistance from urban and rural samples were found to exhibit 83.9% resistance to beta lactams, 85.7% to macrolides, 44.2% to fluoroquinolones, 50% to glycopeptides and cephalosporins, 35.7 % to carbapenems and sulfonamides, 28.5 % to tetracycline, and 23.8 % to aminoglycosides. Conclusion: The high prevalence of antibiotic-resistant bacteria harbouring diverse resistance traits across samples indicated towards probable horizontal gene transfer across environmental niches. This study can prove to be useful to understand and map the patterns of resistance and stringently apply the counter measures related to public health practices.

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Virulence Factors, Antibiotic Resistance patterns, and Molecular Types of Clinical Isolates of Klebsiella Pneumoniae

10.21203/rs.3.rs-331542/v1 ◽

2021 ◽

Author(s):

Mitra Ahmadi ◽

Payam Behzadi ◽

Reza Ranjbar

Keyword(s):

Antibiotic Resistance ◽

Klebsiella Pneumoniae ◽

Molecular Typing ◽

Virulence Genes ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Aminoglycoside Resistance ◽

Wide Range ◽

Resistance Patterns ◽

Esbl Producers

Abstract Background Klebsiella pneumoniae is armed with a wide range of antibiotic resistance mechanisms which mostly challenges effective treatment. Due to this fact, the aims of the current study were to identify the clinical strains of K . pneumoniae as well as to determine their phenotypes and molecular characterization related to antimicrobial resistance and virulence genes. Methods In this investigation, specimens from a hospital and different laboratories located in Shahr-e-Qods, Tehran, Iran were collected during a period of nine-month (December 2018 to August 2019). The isolated strains of K. pneumoniae were then identified through standard microbial and biochemical assays. Additionally, disk diffusion, combined disk, modified Hodge test and PCR were performed for antibiotic resistance of the strains and virulence genes profiling, respectively. The molecular typing was accomplished by ERIC-PCR. Results Eighty-four isolates of K. pneumoniae were identified and subjected to the study. Fifty- two percent of the isolated strains of K. pneumoniae were detected as multidrug resistant (MDR) pathotypes with the highest resistance to ceftriaxone (65%) and the lowest resistance to colistin (23%). Twenty-seven (52%) out of 52 (100%) MDR pathotypes of isolated K. pneumoniae were identified as ESBL producers. According to Modified Hodge Test (MHT) results, out of 24 resistant strains of isolated K. pneumoniae to imipenem and meropenem, 15 pathotypes (62.5%) were detected as KPC producers. The gene of blaCTX (encoding carbapenemase) with 96% ranked first, while the blaKPC gene with the prevalence of 71% ranked second among ESBL producers. The aminoglycoside resistance gene of Aac6-Ib showed the highest frequency with the prevalence percentage of 90%. The virulence genes of mrkD (94%) and magA (11%) were the highest and lowest among isolates, respectively. According to ERIC-PCR results the isolated strains of K. pneumoniae were divided into four clusters in which the cluster 4 was predominant group. Conclusions The high prevalence of antibiotic resistance and virulence genes in conjunction with a significant relationship between the strains reveals a high pathogenic capacity of the isolated pathotypes of K. pneumoniae . These findings emphasize the choose of more effective antibiotic regimens for treatment of infections caused by K. pneumoniae. Keywords: Klebsiella pneumoniae , antibiotic resistance, ESBL, virulence genes, molecular typing.

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Isolation of Multidrug Resistant Bacteria from Patients Medical Charts

Journal of Nepal Health Research Council ◽

10.3126/jnhrc.v15i2.18204 ◽

2017 ◽

Vol 15 (2) ◽

pp. 146-149

Author(s):

Roshan Thapa ◽

Narayan Dutt Pant ◽

Uday Narayan Yadav ◽

Eliza Thapa ◽

Anjana Singh ◽

...

Keyword(s):

Pathogenic Bacteria ◽

Methicillin Resistance ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Coagulase Negative Staphylococcus ◽

Biochemical Tests ◽

Multidrug Resistant Bacteria ◽

Enterococcus Spp ◽

Bacillus Spp ◽

Acinetobacter Spp

Background: Patient’s medical charts in hospitals are potentially contaminated by pathogenic bacteria and might act as vehicles for transmission of bacterial infections.This study was aimed to determine the rate of contamination of medical charts by multidrug resistant bacteria.Methods: Sampling of total 250 patient’s medical charts from different wards was done with the help of cotton swabs soaked in sterile normal saline. The swabs thus collected were cultured using standard microbiological procedures.The colonies grown were then identified with the help of colony morphology, Gram’s stain and biochemical tests. Antimicrobial susceptibility testing was performed by using Kirby-Bauer disc diffusion technique. Results: Of the total 250 charts sampled, 98.8% grew bacteria; Bacillus spp. in 40.7%, followed by Staphylococcus aureus (17%), coagulase-negative Staphylococcus spp.(CoNS) (17%), Citrobacter freundii (9.6%) and Acinetobacter spp. (4.5%). Rate of multidrug resistance was highest in Acinetobacter spp. (50%). Among 83 isolates of S. aureus, methicillin resistance was found in 29 isolates. Similarly, two out of total 9 isolates of Enterococcus spp. were vancomycin resistant.Conclusions: This study showed that patient’s medical charts were contaminated with multidrug resistant bacteria including methicillin resistant S. aureus and vancomycin resistant Enterococcus spp. Strict hand washing before and after handling medical charts is recommended.

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Antibiotic resistance patterns in infections associated with health care in a Third Level Center with hospital reconversion in the COVID-19 pandemic

10.21203/rs.3.rs-685126/v1 ◽

2021 ◽

Author(s):

Jorge Almeida ◽

José Alfonso Gutiérrez Gutiérrez ◽

Silvia León Quirino ◽

Patricia Albarrán Calzonzin ◽

Alejandro Acosta Ramírez ◽

...

Keyword(s):

Health Care ◽

Antibiotic Resistance ◽

Medical Center ◽

Demographic Data ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistance To Antibiotics ◽

Improper Use ◽

Resistance Patterns ◽

Antibiotic Resistance Patterns

Abstract Objective:Description of the different isolated microorganisms and their prevalence in infections associated with health care, in addition to determining their patterns of resistance to antibiotics in patients admitted with a confirmed or suspected diagnosis of COVID-19 in the Intensive Care Unit, during a third-level medical center with hospital reconversion.Method:Patient demographic data was obtained from the clinical record, with defined criteria. Antibiotic resistance patterns were evaluated as well as the identification of isolated bacteria in cultures of expectoration, pleural fluid, catheter tips. For bacterial identification and resistance mechanisms, automated equipment and phenotypic tests were used, following the CLSI criteria.ResultsA total of 100 patients with bacterial infection added to the main COVID-19 picture were obtained, of which he represented pneumonia, urinary tract infection, catheter infections and bacteremia. A total of 100 strains were isolated, of which 84 are Extremely Drug Resistant, 12 Multidrug Resistant and only 4 variable sensitivity. The bacteria with the highest prevalence is Staphylococcus aureus with, followed by Peudonomas aeruginosa and Stenotrophomonas maltophilia. 100% of the patients admitted to the ICU had death.ConclusionThe increase in resistance to antibiotics in the COVID-19 pandemic has set off alarms due to the complication that this brings, and the improper use of drugs as prophylaxis or attempted treatment only generates selective pressure that leads to an increase in resistance as observed in the isolated strains in this study, where the vast majority present enzymes as well as other resistance mechanisms that confer them to be XDR

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Antimicrobial Resistance and Presence of Class 1 Integrons Among Different Serotypes of Salmonella spp. Recovered From Children with Diarrhea in Tehran, Iran

Infectious Disorders - Drug Targets ◽

10.2174/1871526519666190130171020 ◽

2020 ◽

Vol 20 (2) ◽

pp. 160-166

Author(s):

Seyedeh Hanieh Eshaghi Zadeh ◽

Hossein Fahimi ◽

Fatemeh Fardsanei ◽

Mohammad Mehdi Soltan Dallal

Keyword(s):

Antibiotic Resistance ◽

Antimicrobial Resistance ◽

Multidrug Resistant ◽

Salmonella Spp ◽

Class 1 Integron ◽

Class 1 Integrons ◽

Food Borne ◽

Class 1 ◽

Resistance Patterns ◽

C 30

Background: Salmonellosis is a major food-borne disease worldwide. The increasing prevalence of antimicrobial resistance among food-borne pathogens such as Salmonella spp. is concerning. Objective: The main objective of this study is to identify class 1 integron genes and to determine antibiotic resistance patterns among Salmonella isolates from children with diarrhea. Methods: A total of 30 Salmonella isolates were recovered from children with diarrhea. The isolates were characterized for antimicrobial susceptibility and screened for the presence of class 1 integron genes (i.e. intI1, sulI1, and qacEΔ1). Results: The most prevalent serotype was Enteritidis 36.7%, followed by Paratyphi C (30%), and Typhimurium (16.7%). The highest rates of antibiotic resistance were obtained for nalidixic acid (53.3%), followed by streptomycin (40%), and tetracycline (36.7%). Regarding class 1 integrons, 36.7%, 26.7%, and 33.3% of the isolates carried intI1, SulI, and qacEΔ1, respectively, most of which (81.8%) were multidrug-resistant (MDR). Statistical analysis revealed that the presence of class 1 integron was significantly associated with resistance to streptomycin and tetracycline (p = 0.042). However, there was no association between class 1 integron and other antibiotics used in this study (p > 0.05). Conclusion: The high frequency of integron class 1 gene in MDR Salmonella strains indicates that these mobile genetic elements are versatile among different Salmonella serotypes, and associated with reduced susceptibility to many antimicrobials.

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Testudines as Sentinels for Monitoring the Dissemination of Antibiotic Resistance in Marine Environments: An Integrative Review

Antibiotics ◽

10.3390/antibiotics10070775 ◽

2021 ◽

Vol 10 (7) ◽

pp. 775

Author(s):

Kezia Drane ◽

Roger Huerlimann ◽

Michelle Power ◽

Anna Whelan ◽

Ellen Ariel ◽

...

Keyword(s):

Antibiotic Resistance ◽

Anthropogenic Activities ◽

Sea Turtles ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Marine Environments ◽

Beta Lactam ◽

Antibiotic Resistant ◽

Sensitivity Tests ◽

Standard Culture

Dissemination of antibiotic resistance (AR) in marine environments is a global concern with a propensity to affect public health and many ecosystems worldwide. We evaluated the use of sea turtles as sentinel species for monitoring AR in marine environments. In this field, antibiotic-resistant bacteria have been commonly identified by using standard culture and sensitivity tests, leading to an overrepresentation of specific, culturable bacterial classes in the available literature. AR was detected against all major antibiotic classes, but the highest cumulative global frequency of resistance in all represented geographical sites was against the beta-lactam class by a two-fold difference compared to all other antibiotics. Wastewater facilities and turtle rehabilitation centres were associated with higher incidences of multidrug-resistant bacteria (MDRB) accounting for an average of 58% and 49% of resistant isolates, respectively. Furthermore, a relatively similar prevalence of MDRB was seen in all studied locations. These data suggest that anthropogenically driven selection pressures for the development of AR in sea turtles and marine environments are relatively similar worldwide. There is a need, however, to establish direct demonstrable associations between AR in sea turtles in their respective marine environments with wastewater facilities and other anthropogenic activities worldwide.

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Rethinking Manure Application: Increase in Multidrug-Resistant Enterococcus spp. in Agricultural Soil Following Chicken Litter Application

Microorganisms ◽

10.3390/microorganisms9050885 ◽

2021 ◽

Vol 9 (5) ◽

pp. 885

Author(s):

Dorcas Oladayo Fatoba ◽

Akebe Luther King Abia ◽

Daniel G. Amoako ◽

Sabiha Y. Essack

Keyword(s):

Antimicrobial Resistance ◽

Agricultural Soil ◽

Multidrug Resistant ◽

Diffusion Method ◽

Resistant Bacteria ◽

Manure Application ◽

Unamended Soil ◽

Enterococcus Spp ◽

Chicken Litter ◽

Amended Soil

The current study investigated the impact of chicken litter application on the abundance of multidrug-resistant Enterococcus spp. in agricultural soil. Soil samples were collected from five different strategic places on a sugarcane farm before and after manure application for four months. Chicken litter samples were also collected. Enterococci were enumerated using the Enterolert®/Quanti-Tray 2000® system and confirm and differentiated into species using real-time PCR. The antibiotic susceptibility profile of the isolates was determined using the disk diffusion method following the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The overall mean bacterial count was significantly higher (p < 0.05) in manure-amended soil (3.87 × 107 MPN/g) than unamended soil (2.89 × 107 MPN/g). Eight hundred and thirty-five enterococci (680 from soil and 155 from litter) were isolated, with E. casseliflavus being the most prevalent species (469; 56.2%) and E. gallinarum being the least (16; 1.2%). Approximately 56% of all the isolates were resistant to at least one antibiotic tested, with the highest resistance observed against tetracycline (33%) and the lowest against chloramphenicol (0.1%); 17% of E. faecium were resistant to quinupristin-dalfopristin. Additionally, 27.9% (130/466) of the isolates were multidrug-resistant, with litter-amended soil harbouring more multidrug-resistant (MDR) isolates (67.7%; 88/130) than unamended soil (10.0%; 13/130). All isolates were susceptible to tigecycline, linezolid and gentamicin. About 7% of the isolates had a multiple antimicrobial resistance index > 0.2, indicative of high antibiotic exposure. Although organic fertilizers are regarded as eco-friendly compared to chemical fertilizers for improving soil fertility, the application of untreated animal manure could promote the accumulation of antibiotics and their residues and antibiotic-resistant bacteria in the soil, creating an environmental reservoir of antimicrobial resistance, with potential human and environmental health risks.

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Antibiotic Resistance in Pediatric Infections: Global Emerging Threats, Predicting the Near Future

Antibiotics ◽

10.3390/antibiotics10040393 ◽

2021 ◽

Vol 10 (4) ◽

pp. 393

Author(s):

Alessandra Romandini ◽

Arianna Pani ◽

Paolo Andrea Schenardi ◽

Giulia Angela Carla Pattarino ◽

Costantino De Giacomo ◽

...

Keyword(s):

Antibiotic Resistance ◽

Pediatric Population ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Pediatric Age ◽

Carbapenem Resistant ◽

Pediatric Infections ◽

Surgical Treatments ◽

Developing System ◽

Near Future

Antibiotic resistance is a public health threat of the utmost importance, especially when it comes to children: according to WHO data, infections caused by multidrug resistant bacteria produce 700,000 deaths across all ages, of which around 200,000 are newborns. This surging issue has multipronged roots that are specific to the pediatric age. For instance, the problematic overuse and misuse of antibiotics (for wrong diagnoses and indications, or at wrong dosage) is also fueled by the lack of pediatric-specific data and trials. The ever-evolving nature of this age group also poses another issue: the partly age-dependent changes of a developing system of cytochromes determine a rather diverse population in terms of biochemical characteristics and pharmacokinetics profiles, hard to easily codify in an age- or weight-dependent dosage. The pediatric population is also penalized by the contraindications of tetracyclines and fluoroquinolones, and by congenital malformations which often require repeated hospitalizations and pharmacological and surgical treatments from a very young age. Emerging threats for the pediatric age are MRSA, VRSA, ESBL-producing Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae and the alarming colistin resistance. Urgent actions need to be taken in order to step back from a now likely post-antibiotic era, where simple infections might cause infant death once again.

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Antibiotic Resistance of Uropathogens Isolated from Patients Hospitalized in District Hospital in Central Poland in 2020

Antibiotics ◽

10.3390/antibiotics10040447 ◽

2021 ◽

Vol 10 (4) ◽

pp. 447

Author(s):

Barbara Kot ◽

Agata Grużewska ◽

Piotr Szweda ◽

Jolanta Wicha ◽

Urszula Parulska

Keyword(s):

Antibiotic Resistance ◽

Multidrug Resistant ◽

Diffusion Method ◽

Disk Diffusion Method ◽

Beta Lactamases ◽

E Coli ◽

Central Poland ◽

Resistance Patterns ◽

Extended Spectrum Beta Lactamases ◽

Tract Infections

The aim of this study was to determine antibiotic resistance patterns and the prevalence of uropathogenes causing urinary tract infections (UTIs) in patients hospitalized in January–June 2020 in central Poland. Antimicrobial susceptibility testing was performed using the disk-diffusion method. Escherichia coli (52.2%), Klebsiella pneumoniae (13.7%), Enterococcus faecalis (9.3%), E. faecium (6.2%), and Proteus mirabilis (4,3%) were most commonly isolated from urine samples. E. coli was significantly more frequent in women (58.6%) (p = 0.0089) and in the age group 0–18, while K. pneumoniae was more frequent in men (24.4%) (p = 0.0119) and in individuals aged 40–60 and >60. Gram-negative species showed resistance to ampicillin. K. pneumoniae were resistant to amoxicillin plus clavulanic acid (75.0%), piperacillin plus tazobactam (76.2%), cefotaxime (76.2%), cefuroxime (81.0%), ciprofloxacin (81.0%), and trimethoprim plus sulphamethoxazole (81.0%). Carbapenems were effective against all E. coli and P. mirabilis. Some K. pneumoniae (13.6%) produced metallo-β-lactamases (MBLs). E. coli (22.6%), K. pneumoniae (81.8%), and all E. faecium were multidrug-resistant (MDR). Some E. coli (26.2%), K. pneumoniae (63.6%), and P. mirabilis (14.3%) isolates produced extended-spectrum beta-lactamases (ESBL). Vancomycin-resistant E. faecium was also found. This study showed that the possibilities of UTIs therapy using available antibiotics become limited due to the increasing number of antibiotic-resistant uropathogens.

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Prevalence of Antibiotic-Resistant Bacteria ESKAPE among Healthy People Estimated by Monitoring of Municipal Wastewater

Antibiotics ◽

10.3390/antibiotics10050495 ◽

2021 ◽

Vol 10 (5) ◽

pp. 495

Author(s):

Masateru Nishiyama ◽

Susan Praise ◽

Keiichi Tsurumaki ◽

Hiroaki Baba ◽

Hajime Kanamori ◽

...

Keyword(s):

Antibiotic Resistance ◽

General Population ◽

Municipal Wastewater ◽

Treatment Plant ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

Municipal Wastewater Treatment ◽

Antibiotic Resistant ◽

Carbapenem Resistant ◽

Wastewater Samples

There is increasing attention toward factors that potentially contribute to antibiotic resistance (AR), as well as an interest in exploring the emergence and occurrence of antibiotic resistance bacteria (ARB). We monitored six ARBs that cause hospital outbreaks in wastewater influent to highlight the presence of these ARBs in the general population. We analyzed wastewater samples from a municipal wastewater treatment plant (MWWTP) and hospital wastewater (HW) for six species of ARB: Carbapenem-resistant Enterobacteria (CARBA), extended-spectrum β-lactamase producing Enterobacteria (ESBL), multidrug-resistant Acinetobacter (MDRA), multidrug-resistant Pseudomonas aeruginosa (MDRP), methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE). We registered a high percentage of ARBs in MWWTP samples (>66%) for all ARBs except for MDRP, indicating a high prevalence in the population. Percentages in HW samples were low (<78%), and no VRE was detected throughout the study. CARBA and ESBL were detected in all wastewater samples, whereas MDRA and MRSA had a high abundance. This result demonstrated the functionality of using raw wastewater at MWWTP to monitor the presence and extent of ARB in healthy populations. This kind of surveillance will contribute to strengthening the efforts toward reducing ARBs through the detection of ARBs to which the general population is exposed.

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