Colistin Resistance in Enterobacterales Strains – A Current View

Colistin is a member of cationic polypeptide antibiotics known as polymyxins. It is widely used in animal husbandry, plant cultivation, animal and human medicine and is increasingly used as one of the last available treatment options for patients with severe infections with carbapenem-resistant Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant (MDR) bacteria, the resistance to this antibiotic ought to be monitored. Bacterial resistance to colistin may be encoded on transposable genetic elements (e.g. plasmids with the mcr genes). Thus far, nine variants of the mcr gene, mcr-1 – mcr-9, have been identified. Chromosomal resistance to colistin is associated with the modification of lipopolysaccharide (LPS). Various methods, from classical microbiology to molecular biology methods, are used to detect the colistin-resistant bacterial strains and to identify resistance mechanisms. The broth dilution method is recommended for susceptibility testing of bacteria to colistin.

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The Burden of the Serious and Difficult-to-Treat Infections and a New Antibiotic Available: Cefiderocol

Frontiers in Pharmacology ◽

10.3389/fphar.2020.578823 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yasaman Taheri ◽

Nataša Joković ◽

Jelena Vitorović ◽

Oliver Grundmann ◽

Alfred Maroyi ◽

...

Keyword(s):

Bacterial Infections ◽

Treatment Options ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Antimicrobial Treatment ◽

Bacterial Cells ◽

Gram Negative ◽

Pubmed Database ◽

Severe Infections ◽

Unique Cell

Background: Infection is a disease that can occur due to the entrance of a virus, bacteria, and other infectious agents. Cefiderocol is innovative cephalosporin drug that belongs to a special class of antibiotics, sideromycins, which are taken up by bacterial cells through active transport. The unique cell entry and stability to β-lactamases allow cefiderocol to overcome the most common resistance mechanisms in Gram-negative bacteria.Objective: This article aims to highlight the therapeutic efficacy, safety and tolerability of cefiderocol, with a focus on the FDA label.Methods: The pharmacological properties of cefiderocol are also summarized. In this review, we conducted literature research on the PubMed database using the following keywords: “antimicrobial treatment”, “new antibiotic”, “cefiderocol”, “siderophore cephalosporin”; “multidrug-resistant”, “Gram-negative bacilli”, “critically ill patients”; “severe bacterial infections”.Results: There were identified the most relevant data about the pathophysiology of serious bacterial infections, antibacterial mechanism of action, microbiology, mechanisms of resistance, pharmacokinetic and pharmacodynamic properties of cefiderocol.Conclusion: The results highlighted there appeared to be clinical benefit from cefiderocol in the treatment of infections caused by Gram-negative aerobic microorganisms in adult patients with severe infections and limited treatment options.

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Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

Journal of Medical Microbiology ◽

10.1099/jmm.0.001347 ◽

2021 ◽

Vol 70 (4) ◽

Author(s):

Balaram Khamari ◽

Prakash Kumar ◽

Bulagonda Eswarappa Pradeep

Keyword(s):

Antimicrobial Agents ◽

Efflux Pump ◽

Treatment Options ◽

Strong Association ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Resistant Bacteria ◽

Drug Resistant ◽

Content Type ◽

Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

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Clinical Validation of SensiTest Colistin, a Broth Microdilution-Based Method To Evaluate Colistin MICs

Journal of Clinical Microbiology ◽

10.1128/jcm.01523-17 ◽

2018 ◽

Vol 56 (4) ◽

Cited By ~ 16

Author(s):

Edoardo Carretto ◽

Flavia Brovarone ◽

Giuseppe Russello ◽

Paola Nardini ◽

Maisra M. El-Bouseary ◽

...

Keyword(s):

Room Temperature ◽

Susceptibility Testing ◽

Reference Method ◽

Multidrug Resistant ◽

Clinical Validation ◽

Gram Negative Bacteria ◽

Broth Microdilution ◽

Bacterial Strains ◽

Global Spread ◽

Severe Infections

ABSTRACT The global spread of multidrug-resistant Gram-negative bacteria has led to the return of colistin for treating severe infections. Recently, different plasmid-mediated genes conferring resistance to this drug were described and reported worldwide. International committees (EUCAST/CLSI) reevaluated inconsistencies surrounding colistin antimicrobial susceptibility testing (AST), concluding that broth microdilution (BMD) should serve as the reference method for AST. The development of an accurate, reproducible commercial test based on BMD is therefore highly desirable. SensiTest Colistin (STC), a BMD-based compact 4-test panel containing the lyophilized antibiotic in 7 2-fold dilutions (0.25 to 16 μg/ml) was here compared with the EUCAST-CLSI standard reference method (BMD) and, for some isolates, with the automated Phoenix 100 system (PHX). A total of 353 bacterial strains were evaluated by two different laboratories; 137 isolates were resistant to colistin (19 were intrinsically resistant, 83 harbored the mcr-1 gene). Essential agreement (EA) between STC and BMD was obtained for 339 out of the 353 strains tested (96.0%). Overall categorical agreement was obtained for 349 out of the 353 strains analyzed (98.9%). Two major errors (MEs; 0.93%) and two very major errors (VMEs; 1.46%) were documented. STC appeared to be a simple but highly reliable test with good reproducibility even with panels stored at room temperature or at 35°C. Moreover, STC showed a good performance with strains carrying the mcr-1 gene, with a 98.8% EA. As the secondary endpoint of our study, VMEs for PHX were documented for 6 isolates (10%).

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Insights into Acinetobacter baumannii: A Review of Microbiological, Virulence, and Resistance Traits in a Threatening Nosocomial Pathogen

Antibiotics ◽

10.3390/antibiotics9030119 ◽

2020 ◽

Vol 9 (3) ◽

pp. 119 ◽

Cited By ~ 12

Author(s):

Carole Ayoub Moubareck ◽

Dalal Hammoudi Halat

Keyword(s):

Acinetobacter Baumannii ◽

Virulence Factors ◽

Efflux Pump ◽

Iron Acquisition ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Biofilm Production ◽

Resistant Phenotype ◽

Severe Infections ◽

Hydrolyzing Enzymes

Being a multidrug-resistant and an invasive pathogen, Acinetobacter baumannii is one of the major causes of nosocomial infections in the current healthcare system. It has been recognized as an agent of pneumonia, septicemia, meningitis, urinary tract and wound infections, and is associated with high mortality. Pathogenesis in A. baumannii infections is an outcome of multiple virulence factors, including porins, capsules, and cell wall lipopolysaccharide, enzymes, biofilm production, motility, and iron-acquisition systems, among others. Such virulence factors help the organism to resist stressful environmental conditions and enable development of severe infections. Parallel to increased prevalence of infections caused by A. baumannii, challenging and diverse resistance mechanisms in this pathogen are well recognized, with major classes of antibiotics becoming minimally effective. Through a wide array of antibiotic-hydrolyzing enzymes, efflux pump changes, impermeability, and antibiotic target mutations, A. baumannii models a unique ability to maintain a multidrug-resistant phenotype, further complicating treatment. Understanding mechanisms behind diseases, virulence, and resistance acquisition are central to infectious disease knowledge about A. baumannii. The aims of this review are to highlight infections and disease-producing factors in A. baumannii and to touch base on mechanisms of resistance to various antibiotic classes.

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Cefiderocol, a new antibiotic against multidrug-resistant Gram-negative bacteria

Revista Española de Quimioterapia ◽

10.37201/req/s01.12.2021 ◽

2021 ◽

Vol 34 (Suppl 1) ◽

pp. 41-43

Author(s):

José Tiago Silva ◽

Francisco López-Medrano

Keyword(s):

Bacterial Pneumonia ◽

Treatment Options ◽

Multidrug Resistant ◽

Resistance Mechanisms ◽

Phase Iii ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Tract Infections ◽

Transport Channels ◽

Hospital Acquired

Cefiderocol is a novel catechol-substituted siderophore cephalosporin that binds to the extracellular free iron, and uses the bacterial active iron transport channels to penetrate in the periplasmic space of Gram-negative bacteria (GNB). Cefiderocol overcomes many resistance mechanisms of these bacteria. Cefiderocol is approved for the treatment of complicated urinary tract infections, hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia in the case of adults with limited treatment options, based on the clinical data from the APEKS-cUTI, APEKS-NP and CREDIBLE-CR trials. In the CREDIBLE-CR trial, a higher all-cause mortality was observed in the group of patients who received cefiderocol, especially those with severe infections due to Acinetobacter spp. Further phase III clinical studies are necessary in order to evaluate cefiderocol´s efficacy in the treatment of serious infections.

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A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options

Future Science OA ◽

10.2144/fsoa-2019-0098 ◽

2020 ◽

Vol 6 (3) ◽

pp. FSO438 ◽

Cited By ~ 7

Author(s):

Ann A Elshamy ◽

Khaled M Aboshanab

Keyword(s):

Public Health ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Treatment Options ◽

Carbapenem Resistance ◽

Multidrug Resistant ◽

Mechanisms Of Resistance ◽

Carbapenem Resistant ◽

Public Health Threat ◽

Carbapenem Resistant Enterobacteriaceae

Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.

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Combating bacterial resistance by combination of antibiotics with antimicrobial peptides

Pure and Applied Chemistry ◽

10.1515/pac-2018-0707 ◽

2019 ◽

Vol 91 (2) ◽

pp. 199-209 ◽

Cited By ~ 8

Author(s):

Dean E. Sheard ◽

Neil M. O’Brien-Simpson ◽

John D. Wade ◽

Frances Separovic

Keyword(s):

Antimicrobial Peptides ◽

Bacterial Infections ◽

Bacterial Resistance ◽

Synergistic Effects ◽

Resistance Mechanisms ◽

Bacterial Strains ◽

Diverse Range ◽

Recent Emergence ◽

Agricultural Industries ◽

Conventional Antibiotics

Abstract The overuse of antibiotics in the healthcare and agricultural industries has led to the worldwide spread of bacterial resistance. The recent emergence of multidrug resistant (MDR) bacteria has resulted in a call for the development of novel strategies to address this global issue. Research on a diverse range of antimicrobial peptides (AMPs) has shown promising activity against several resistant strains. Increased understanding of the mode of action of AMPs has shown similarity and complementarity to conventional antibiotics and the combination of both has led to synergistic effects in some cases. Combination therapy has been widely used to combat MDR bacterial infections and the recent focus on their application with AMPs may allow antibiotics to be effective against resistant bacterial strains. By conjugation of an antibiotic onto an AMP, a compound may be produced with possibly greater activity and with reduced side-effects and toxicity. The AMP in these conjugates may also act as a unique adjuvant for the antibiotic by disrupting the resistance mechanisms used by bacteria thus allowing the antibiotic to once again be effective. This mini-review outlines some of the current and past work in combining AMPs with conventional antibiotics as strategies to address bacterial resistance.

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Comparative analysis of disk diffusion and liquid medium microdillution methods for testing the antibiotic susceptibility patterns of anaerobic bacterial strains isolated from intra-abdominal infections

Biointerface Research in Applied Chemistry ◽

10.33263/briac16.209220 ◽

2011 ◽

Vol 1 (6) ◽

pp. 209-220 ◽

Cited By ~ 6

Keyword(s):

Antibiotic Susceptibility ◽

Bacterial Resistance ◽

Empiric Therapy ◽

Disk Diffusion ◽

Diffusion Method ◽

Dilution Method ◽

Bacterial Strains ◽

Disk Diffusion Method ◽

Broth Microdilution Method ◽

Abdominal Infections

The antibiotic resistance aspects concerning the bacterial strains isolated from intra-abdominal infections signify at present a major problem of therapy. The empiric pre-operatory antimicrobial therapy plays a key role in the management and course of the intra-abdominal infections, an inappropriate therapy resulting in a poor outcome of the clinical cases and an increase of bacterial resistance. The purpose of the present paper was to compare the results of the antibiotic susceptibility of some selected anaerobic strains to certain antibiotics used in the empiric therapy of intra-abdominal infections, achieved by two different methods, in order to select for the current practice the most reliable, simple and rapid one. We have found a good correlation between the results obtained by the standard, Brucella broth microdilution method recommended by CLSI and the disk diffusion method (recommended by Bailey and Scott, 2002), for all tested antibiotics, demonstrating the possibility to use this last simplified method as an alternative to the laborious and time-consuming dilution method, for the routine testing of the antibiotic susceptibility of anaerobic stranis isolated in severe infections.

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Short Communication: Antibacterial activity of certain Saudi Arabian medicinal plants used in folk medicine against different groups of bacteria

Nusantara Bioscience ◽

10.13057/nusbiosci/n090409 ◽

2017 ◽

Vol 9 (4) ◽

pp. 392-395

Author(s):

ABDULLAH A. AL-GHANAYEM ◽

SANAD M. AL SOBEAI ◽

MOHAMMED S. ALHUSSAINI ◽

BABU JOSEPH ◽

ABDULMONEIM MOHAMMAD SAADABI

Keyword(s):

Antibacterial Activity ◽

Medicinal Plants ◽

Folk Medicine ◽

Saudi Arabian ◽

Multidrug Resistant ◽

Diffusion Method ◽

Calotropis Procera ◽

Dilution Method ◽

Bacterial Strains ◽

Gram Positive

Al-Ghanayem AA, Al Sobeai SM, Alhussaini MS, Joseph B, Saadabi AM. 2017. Antibacterial activity of certain Saudi Arabian medicinal plants used in folk medicine against different groups of bacteria. Nusantara Bioscience 9: 392-395. Medicinal plants from Saudi Arabia has been used in folk medicine for treatment of many diseases. The present research is on medicinal plants, which are locally available such as Acacia ehrenbergiana (Arabic: Salam) (Fabaceae), Calotropis procera (Arabic: Ausher) (Apocynaceae), Haloxylon salicornicum (Arabic: Rimth) (Amaranthaceae), Panicum turgidum (Arabic: Thuman) (Poaceae), Tamarix arabica (Arabic: Athal) (Tamaricaceae), Rhazya stricta (Arabic: Harmal) (Apocynaceae) Rumex vesicarius (Arabic: Humeid) (Polygonaceae) for antimicrobial activity by agar well diffusion method. Minimum Inhibitory Concentration (MIC) has been determined by broth micro dilution method. A. ehrenbergiana was active against Klebsiella pneumoniae. R. vesicarius and T. arabica showed antibacterial activity against Proteus vulgaris. C. procera showed a moderate inhibitory activity against the bacterial pathogens tested. H. salicornicum extract was more effective towards Gram-positive bacteria. However, other extracts such as P. turgidum and R. stricta were less active against both Gram-positive and negative bacteria tested. The results will be helpful in discovering new phytochemical components with antibacterial activity that can be used against multidrug-resistant bacterial strains.

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Enhancement of Antibiotic Activity by 1,8-Naphthyridine Derivatives against Multi-Resistant Bacterial Strains

Molecules ◽

10.3390/molecules26237400 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7400

Author(s):

José B. de Araújo-Neto ◽

Maria M. C. da Silva ◽

Cícera D. de M. Oliveira-Tintino ◽

Iêda M. Begnini ◽

Ricardo A. Rebelo ◽

...

Keyword(s):

Bacterial Infections ◽

Bacterial Resistance ◽

Antimicrobial Properties ◽

Multidrug Resistant ◽

Antibiotic Activity ◽

Bacterial Strains ◽

Microdilution Method ◽

Fluoroquinolone Antibiotics ◽

Broth Microdilution Method ◽

Resistant Strains

The search for new antibacterial agents has become urgent due to the exponential growth of bacterial resistance to antibiotics. Nitrogen-containing heterocycles such as 1,8-naphthyridine derivatives have been shown to have excellent antimicrobial properties. Therefore, the purpose of this study was to evaluate the antibacterial and antibiotic-modulating activities of 1,8-naphthyridine derivatives against multi-resistant bacterial strains. The broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of the following compounds: 7-acetamido-1,8-naphthyridin-4(1H)-one and 3-trifluoromethyl-N-(5-chloro-1,8-naphthyridin-2-yl)-benzenesulfonamide. The antibiotic-modulating activity was analyzed using subinhibitory concentrations (MIC/8) of these compounds in combination with norfloxacin, ofloxacin, and lomefloxacin. Multi-resistant strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were used in both tests. Although the compounds had no direct antibacterial activity (MIC ≥ 1.024 µg/mL), they could decrease the MIC of these fluoroquinolones, indicating synergism was obtained from the association of the compounds. These results suggest the existence of a structure–activity relationship in this group of compounds with regard to the modulation of antibiotic activity. Therefore, we conclude that 1,8-naphthyridine derivatives potentiate the activity of fluoroquinolone antibiotics against multi-resistant bacterial strains, and thereby interesting candidates for the development of drugs against bacterial infections caused by multidrug resistant strains.

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