A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset

Abstract Background: Hospital-acquired infections (HAIs) are an emerging global problem that increases in-hospital mortality, length of stay, and cost. We performed a 6-year retrospective study to provide valuable insight into appropriate antibiotic use in HAI cases. We also aimed to understand how hospitals could reduce pathogen drug resistance in a population that overuses antibiotics.Methods: All data (2012–2017) were obtained from the Hospital Information Warehouse and Clinical Microbiology Laboratory.Results: We isolated 1392 pathogen strains from patients admitted to the orthopedics department during 2012–2017. Escherichia coli (14.7%, 204/1392), Enterobacter cloacae (13.9%, 193/1392), and Staphylococcus aureus (11.3%, 157/1392) were the most common pathogens causing nosocomial infections. The dominant Gram-negative bacterium was E. coli, with high resistance to ampicillin, levofloxacin, cotrimoxazole, gentamicin, and ciprofloxacin, in that order. E. coli was least resistant to amikacin, cefoperazone-sulbactam. The most dominant Gram-positive bacterium was S. aureus, highly resistant to penicillin and ampicillin, but not resistant to fluoroquinolones and cotrimoxazole. Analysis of risk factors related to multidrug-resistant bacteria showed that patients with open fractures were significantly more susceptible to methicillin-resistant S. aureus infections (p < 0.05). Additionally, extended-spectrum β-lactamase-producing E. coli infections occurred significantly more often in patients with degenerative diseases (p < 0.05). Elderly patients tended to be more susceptible to multidrug-resistant bacterial infections, but this outcome was not statistically significant.Conclusions:Antimicrobial resistance is a serious problem in orthopedics. To effectively control antimicrobial resistance among pathogens, we advocate extensive and dynamic monitoring of MDR bacteria, coupled with careful use of antibiotics.

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Haemolysin and Shigella Toxin Production in Multidrug Resistant Escherichia Coli Pathotypes from Clinical Specimens

Open Access Journal of Microbiology & Biotechnology ◽

10.23880/oajmb-16000188 ◽

2021 ◽

Vol 6 (1) ◽

pp. 1-9

Author(s):

Iliyasu MY

Keyword(s):

Drug Resistance ◽

Bacterial Infections ◽

Virulence Genes ◽

Strong Relationship ◽

Toxin Production ◽

Multidrug Resistant ◽

Luria Bertani ◽

Antimicrobial Treatment ◽

Diffusion Method ◽

E Coli

The acquisition and dissemination of virulent traits represent a survival advantage to bacterial pathogens. Drug resistance is on the rise among E. coli strains that cause human infections. Proper selection of antimicrobial treatment depends on the susceptibility test outcomes. A total of 178 bacterial isolates were phenotypically screened for Haemolysin and Shigatoxin production, then to obtain Multidrug Resistant (MDR) E. coli . Twelve isolates were identified and selected based on the ability to grow on Luria-Bertani (LB) agar medium containing 100μg/ml Ampicillin. The isolates, coded as; U01, U02, U03, U04, U08, U10 and U11 were from urine specimens, S05, S06, S07 and S12 from stool, while B09 was from blood. The isolates were screened for multidrug resistant pattern according to Kirby-Bauer disc diffusion method. Genes hlyA and stx1 encoding the virulence factors; Haemolysin A and Shigatoxin1 was PCR amplified and sequenced. All the isolates were resistant to Ampicillin, Cephalothin, Erythromycin, Fusidic acid, Novobiocin and Oxacillin, but sensitive to Colistin sulphate and Imipenem. Nine isolates (75%) are sensitive to Augmentin. All the virulence genes ( hlyA and stx1 ) are present in isolates S07 and U08. The isolates (75%) produced 2 to 4 of each of the genes indicating a strong relationship in determining multidrug resistance. Haemolysin ( hlyA ) was the most common (66.7%) gene in urine, stool and blood isolates. Most of the virulence genes sequence (61.8%) in this study had significant alignment (95 to 100% homology) with E.coli genome in the NCBI database. This study revealed the interplay of drug resistance and virulence at genetic levels, so advocate for further identification of the mechanisms regulating the expression of these traits, to improve the management of bacterial infections.

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Bacteremia Among Febrile Patients Attending Selected Healthcare Facilities in Ibadan, Nigeria

Clinical Infectious Diseases ◽

10.1093/cid/ciz516 ◽

2019 ◽

Vol 69 (Supplement_6) ◽

pp. S466-S473 ◽

Cited By ~ 4

Author(s):

Oluwafemi Popoola ◽

Aderemi Kehinde ◽

Veronica Ogunleye ◽

Oluwafemi J Adewusi ◽

Trevor Toy ◽

...

Keyword(s):

Antimicrobial Susceptibility ◽

Bacterial Infections ◽

Common Species ◽

Epidemiological Studies ◽

Multidrug Resistant ◽

African Countries ◽

Healthcare Facilities ◽

Relative Contribution ◽

Polymerase Chain ◽

Ibadan Nigeria

Abstract Background The relative contribution of bacterial infections to febrile disease is poorly understood in many African countries due to diagnostic limitations. This study screened pediatric and adult patients attending 4 healthcare facilities in Ibadan, Nigeria, for bacteremia and malaria parasitemia. Methods Febrile patients underwent clinical diagnosis, malaria parasite testing, and blood culture. Bacteria from positive blood cultures were isolated and speciated using biochemical and serological methods, and Salmonella subtyping was performed by polymerase chain reaction. Antimicrobial susceptibility was tested by disk diffusion. Results A total of 682 patients were recruited between 16 June and 16 October 2017; 467 (68.5%) were <18 years of age. Bacterial pathogens were cultured from the blood of 117 (17.2%) patients, with Staphylococcus aureus (69 [59.0%]) and Salmonella enterica (34 [29.1%]) being the most common species recovered. Twenty-seven (79.4%) of the Salmonella isolates were serovar Typhi and the other 7 belonged to nontyphoidal Salmonella serovarieties. Thirty-four individuals were found to be coinfected with Plasmodium falciparum and bacteria. Five (14.7%) of these coinfections were with Salmonella, all in children aged <5 years. Antimicrobial susceptibility testing revealed that most of the Salmonella and Staphylococcus isolates were multidrug resistant. Conclusions The study demonstrates that bacteria were commonly recovered from febrile patients with or without malaria in this location. Focused and extended epidemiological studies are needed for the introduction of typhoid conjugate vaccines that have the potential to prevent a major cause of severe community-acquired febrile diseases in our locality.

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Analysis of drug resistance and mutation profiles in Mycobacterium tuberculosis isolates in a surveillance site in Beijing, China

Journal of International Medical Research ◽

10.1177/0300060520984932 ◽

2021 ◽

Vol 49 (1) ◽

pp. 030006052098493

Author(s):

Jie Zhang ◽

Yixuan Ren ◽

Liping Pan ◽

Junli Yi ◽

Tong Guan ◽

...

Keyword(s):

Drug Resistance ◽

Mycobacterium Tuberculosis ◽

Drug Testing ◽

Multidrug Resistant ◽

High Rate ◽

Drug Resistant ◽

Surveillance Site ◽

Mdr Tb ◽

Previously Treated Patients ◽

Beijing China

Objective This study analyzed drug resistance and mutations profiles in Mycobacterium tuberculosis isolates in a surveillance site in Huairou District, Beijing, China. Methods The proportion method was used to assess drug resistance profiles for four first-line and seven second-line anti-tuberculosis (TB) drugs. Molecular line probe assays were used for the rapid detection of resistance to rifampicin (RIF) and isoniazid (INH). Results Among 235 strains of M. tuberculosis, 79 (33.6%) isolates were resistant to one or more drugs. The isolates included 18 monoresistant (7.7%), 19 polyresistant (8.1%), 28 RIF-resistant (11.9%), 24 multidrug-resistant (MDR) (10.2%), 7 pre-extensively drug-resistant (XDR, 3.0%), and 2 XDR strains (0.9%). A higher rate of MDR-TB was detected among previously treated patients than among patients with newly diagnosed TB (34.5% vs. 6.8%). The majority (62.5%) of RIF-resistant isolates exhibited a mutation at S531L in the DNA-dependent RNA polymerase gene. Meanwhile, 62.9% of INH-resistant isolates carried a mutation at S315T1 in the katG gene. Conclusion Our results confirmed the high rate of drug-resistant TB, especially MDR-TB, in Huairou District, Beijing, China. Therefore, detailed drug testing is crucial in the evaluation of MDR-TB treatment.

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Antibiotic-Resistant Bacteria in Clams—A Study on Mussels in the River Rhine

Antibiotics ◽

10.3390/antibiotics10050571 ◽

2021 ◽

Vol 10 (5) ◽

pp. 571

Author(s):

Nicole Zacharias ◽

Iris Löckener ◽

Sarah M. Essert ◽

Esther Sib ◽

Gabriele Bierbaum ◽

...

Keyword(s):

Bacterial Infections ◽

Sewage Treatment ◽

Sewage Treatment Plant ◽

Treatment Plant ◽

Multidrug Resistant ◽

Resistant Bacteria ◽

River Rhine ◽

Antibiotic Resistant Bacteria ◽

Surrounding Water ◽

Antibiotic Resistant

Bacterial infections have been treated effectively by antibiotics since the discovery of penicillin in 1928. A worldwide increase in the use of antibiotics led to the emergence of antibiotic resistant strains in almost all bacterial pathogens, which complicates the treatment of infectious diseases. Antibiotic-resistant bacteria play an important role in increasing the risk associated with the usage of surface waters (e.g., irrigation, recreation) and the spread of the resistance genes. Many studies show that important pathogenic antibiotic-resistant bacteria can enter the environment by the discharge of sewage treatment plants and combined sewage overflow events. Mussels have successfully been used as bio-indicators of heavy metals, chemicals and parasites; they may also be efficient bio-indicators for viruses and bacteria. In this study an influence of the discharge of a sewage treatment plant could be shown in regard to the presence of E. coli in higher concentrations in the mussels downstream the treatment plant. Antibiotic-resistant bacteria, resistant against one or two classes of antibiotics and relevance for human health could be detected in the mussels at different sampling sites of the river Rhine. No multidrug-resistant bacteria could be isolated from the mussels, although they were found in samples of the surrounding water body.

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Liposomes as Antibiotic Delivery Systems: A Promising Nanotechnological Strategy against Antimicrobial Resistance

Molecules ◽

10.3390/molecules26072047 ◽

2021 ◽

Vol 26 (7) ◽

pp. 2047

Author(s):

Magda Ferreira ◽

Maria Ogren ◽

Joana N. R. Dias ◽

Marta Silva ◽

Solange Gil ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Bacterial Infections ◽

Private Investment ◽

Therapeutic Index ◽

Multidrug Resistant ◽

Current Treatment ◽

Delivery Systems ◽

Resistant Bacteria ◽

Bacterial Cells ◽

Antimicrobial Drugs

Antimicrobial drugs are key tools to prevent and treat bacterial infections. Despite the early success of antibiotics, the current treatment of bacterial infections faces serious challenges due to the emergence and spread of resistant bacteria. Moreover, the decline of research and private investment in new antibiotics further aggravates this antibiotic crisis era. Overcoming the complexity of antimicrobial resistance must go beyond the search of new classes of antibiotics and include the development of alternative solutions. The evolution of nanomedicine has allowed the design of new drug delivery systems with improved therapeutic index for the incorporated compounds. One of the most promising strategies is their association to lipid-based delivery (nano)systems. A drug’s encapsulation in liposomes has been demonstrated to increase its accumulation at the infection site, minimizing drug toxicity and protecting the antibiotic from peripheral degradation. In addition, liposomes may be designed to fuse with bacterial cells, holding the potential to overcome antimicrobial resistance and biofilm formation and constituting a promising solution for the treatment of potential fatal multidrug-resistant bacterial infections, such as methicillin resistant Staphylococcus aureus. In this review, we aim to address the applicability of antibiotic encapsulated liposomes as an effective therapeutic strategy for bacterial infections.

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Three-Year Trend in Escherichia coli Antimicrobial Resistance among Children’s Urine Cultures in an Italian Metropolitan Area

Children ◽

10.3390/children8070597 ◽

2021 ◽

Vol 8 (7) ◽

pp. 597

Author(s):

Luca Pierantoni ◽

Laura Andreozzi ◽

Simone Ambretti ◽

Arianna Dondi ◽

Carlotta Biagi ◽

...

Keyword(s):

Escherichia Coli ◽

Metropolitan Area ◽

Bacterial Infections ◽

Asymptomatic Bacteriuria ◽

Multidrug Resistant ◽

Resistance Rate ◽

First Line ◽

E Coli ◽

First Line Therapy ◽

Tract Infections

Urinary tract infections (UTIs) are among the most common bacterial infections in children, and Escherichia coli is the main pathogen responsible. Several guidelines, including the recently updated Italian guidelines, recommend amoxicillin-clavulanic acid (AMC) as a first-line antibiotic therapy in children with febrile UTIs. Given the current increasing rates of antibiotic resistance worldwide, this study aimed to investigate the three-year trend in the resistance rate of E. coli isolated from pediatric urine cultures (UCs) in a metropolitan area of northern Italy. We conducted a retrospective review of E. coli-positive, non-repetitive UCs collected in children aged from 1 month to 14 years, regardless of a diagnosis of UTI, catheter colonization, urine contamination, or asymptomatic bacteriuria. During the study period, the rate of resistance to AMC significantly increased from 17.6% to 40.2% (p < 0.001). Ciprofloxacin doubled its resistance rate from 9.1% to 16.3% (p = 0.007). The prevalence of multidrug-resistant E. coli rose from 3.9% to 9.2% (p = 0.015). The rate of resistance to other considered antibiotics remained stable, as did the prevalence of extended spectrum beta-lactamases and extensively resistant E. coli among isolates. These findings call into question the use of AMC as a first-line therapy for pediatric UTIs in our population, despite the indications of recent Italian guidelines.

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Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽

10.3390/antibiotics10060627 ◽

2021 ◽

Vol 10 (6) ◽

pp. 627

Author(s):

Sławomir Letkiewicz ◽

Marzanna Łusiak-Szelachowska ◽

Ryszard Międzybrodzki ◽

Maciej Żaczek ◽

Beata Weber-Dąbrowska ◽

...

Keyword(s):

Clinical Trial ◽

Bacterial Infections ◽

Phage Therapy ◽

Serum Antibody ◽

Multidrug Resistant ◽

Antibody Responses ◽

Urogenital Infections ◽

Reliable Model ◽

Tract Infections ◽

Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

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Genomic Characterization of New Variant of Hydrogen Sulfide (H2S)-Producing Escherichia coli with Multidrug Resistance Properties Carrying the mcr-1 Gene in China

Antibiotics ◽

10.3390/antibiotics9020080 ◽

2020 ◽

Vol 9 (2) ◽

pp. 80 ◽

Cited By ~ 7

Author(s):

Silpak Biswas ◽

Mohammed Elbediwi ◽

Guimin Gu ◽

Min Yue

Keyword(s):

Escherichia Coli ◽

Hydrogen Sulfide ◽

Multidrug Resistance ◽

Bacterial Infections ◽

Multidrug Resistant ◽

Health Concern ◽

Colistin Resistance ◽

New Variant ◽

Genomic Characterization ◽

Human Infections

Colistin is considered to be a ‘last-resort’ antimicrobial for the treatment of multidrug-resistant Gram-negative bacterial infections. Identification of Enterobacteriaceae, carrying the transferable colistin resistance gene mcr-1, has recently provoked a global health concern. This report presents the first detection of a hydrogen sulfide (H2S)-producing Escherichia coli variant isolated from a human in China, with multidrug resistance (MDR) properties, including colistin resistance by the mcr-1 gene, which could have great implications for the treatment of human infections.

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