ENTEROBACTERIACEAE AND ANTIBIOTIC RESISTANCE

Perrella A, Martinotti G, Lauri A, Romualdi A. Enterobacteriaceae and antibiotic resistance. International Journal of Infection. 2022;6(3):90-93

A. Perrella^1*, G. Martinotti², A. Lauri³ and P. Romualdi⁴

¹ Unit of Infectious Disease and Immunology, Hospital Domenico Cotugno, Naples, Italy;
² Department of Neurosciences, Imaging and Clinical Sciences, University “G. D’Annunzio” of Chieti-Pescara, Chieti, Italy;
³ Department of Gastroenterology, Pescara Civil Hospital, Pescara, Italy;
⁴ Department of Otolaryngology, “G.Mazzini” Civil Hospital, Teramo, Italy.

*Correspondence to:
Alessandro Perrella,
Unit of Infectious Disease and Immunology,
Hospital Domenico Cotugno,
Naples, Italy.
e-mail: alex.perrella@hotmail.com

Received: 28 July, 2022 Accepted: 15 November, 2022

ISSN 1972-6945 [online] Copyright 2022 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Enterobacteriaceae such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter species are non-spore-forming, Gram-negative bacilli found in the intestine, urinary tract, bloodstream, and lung of humans. These bacteria can cause meningitis and be potentially lethal. In anaerobic conditions, Enterobacteriaceae produce cytochrome and obtain energy by oxidizing pyruvic acid. Resistant Enterobacteriaceae are an unsolved problem, due to their ability to evade standard antibiotic treatments. Their resistance is mediated by the production of beta-lactamases, efflux pumps, loss of porins, modification of target sites, and metabolic bypass. Bacteria can alter the sites of action of antibiotics, rendering them ineffective, and bacterial resistance at the genetic level can involve plasmids that can carry multiple antibiotic resistance genes. New antibiotics are now being used against Enterobacteriaceae, but with still unsatisfactory results. Carbapenem-resistant Enterobacteriaceae are a clinical and public health problem due to their high transmission capacity.

KEYWORDS: Enterobacteriaceae, antibiotic resistance, meningitis, infection, Enterobacter species, Escherichia coli, Klebsiella pneumoniae

INTRODUCTION

The Enterobacteriaceae are a large family of Gram-negative, non-spore-forming bacilli, which usually inhabit the intestines of humans and other mammals (1). This family includes many pathogens such as Escherichia coli, Klebsiella pneumoniae, and Enterobacter species that are common causes of urinary tract infections (UTIs), bloodstream infections, and pneumonia (2,3).

The Enterobacteriaceae family presents antigenic and biochemical characteristics typical of the entire group (4). Their classification is important on a clinical level, but difficult, as their characteristics can appear to varying degrees (5). They are bacteria equipped with filamentous protein appendages called “pili” and can be mobile or immobile. Enterobacteriaceae are facultative aerobic-anaerobic bacteria that can be grown in normal culture media (6). If they are grown aerobically, they are producers of cytochrome and obtain energy through the Krebs cycle by oxidizing pyruvic acid, an effect that is inhibited by small concentrations of potassium cyanide (7).

Treatment for infections resistant to Enterobacteriaceae can cause meningitis and are life-threatening (3). Therefore, the clinical symptoms of the infection, the risk factors, and the therapy are increasingly of interest to the scientific community even if the cases of infection are limited (8). Rigorous infection control practices, including hand hygiene, use of personal protective equipment, and isolation of infected patients, are essential to prevent the spread of resistant Enterobacteriaceae (9). In addition, the prudent use of antibiotics, guided by susceptibility testing and clinical guidelines, is critical to reduce the selection pressure that drives the emergence of resistance (10).

DISCUSSION

Resistant Enterobacteriaceae infections are a significant concern in both clinical and public health contexts due to their ability to evade standard antibiotic treatments (11). Understanding the biology and molecular aspects of these infections is crucial for developing effective strategies to combat them.

The resistance in Enterobacteriaceae is mediated through several mechanisms including beta-lactamase production, efflux pumps, porin loss, modification of target sites, and metabolic bypass (12). For example, certain enzymes, such as extended-spectrum beta-lactamases and carbapenemases, can hydrolyze beta-lactamase production. In addition, bacterial efflux pumps can expel a wide range of antibiotics from the cell, reducing the intracellular concentration of the drug to sub-lethal levels.  These pumps can be specific to one antibiotic class or can handle multiple classes. Changes or loss of porin channels in the bacterial outer membrane can also decrease antibiotic uptake (13). This is particularly relevant for carbapenem resistance where the combination of porin loss and beta-lactamase production can lead to high-level resistance (14).

Bacteria can alter the target sites of antibiotics through mutations or enzymatic modifications, rendering the antibiotic ineffective (15). For instance, modifications in penicillin-binding proteins can lead to resistance to beta-lactam antibiotics. Some bacteria can also bypass the metabolic pathways inhibited by antibiotics (16). For example, resistance to trimethoprim-sulfamethoxazole can occur through the acquisition of a resistant dihydrofolate reductase enzyme.

Bacterial resistance at the genetic level may involve plasmids, which are extrachromosomal DNA elements that can carry multiple antibiotic resistance genes (17). They can be transferred between bacteria through conjugation, leading to resistance. Transposons and integrons are mobile genetic elements that can capture and spread resistance genes. Furthermore, spontaneous mutations in chromosomal genes can confer resistance. Genetic resistance can be rapidly detected using polymerase chain reaction (PCR) and quantitative PCR (qPCR) (18). Whole genome sequencing can also provide complete data on the genetic composition of resistant strains. Molecular typing techniques, such as multilocus sequential typing and pulsed-field gel electrophoresis, can also help monitor the spread of resistant strains (19).

Today, new antibiotics are available that can better contain the infectious state of Enterobacteriaceae, but they are still unsatisfactory.  In addition, meningitis caused by the Enterobacteriaceae family can cause obstructive hydrocephalus and brain abscesses, which are difficult to treat and can cause death.  These infections can occur after neurosurgery and have poor prognosis, leading to disability and possible mortality. Therefore, to reduce the infection rate it is necessary to use strong disinfectant treatment and rigorous aseptic operations. Therapy is difficult because most antibiotics cannot cross the blood-brain barrier (BBB) and reach the central nervous system (CNS). With resistance, the cytostatic effect of antibiotics does not prevent the bacterium from causing serious and often lethal infections.

The diagnosis of species within the Enterobacteriaceae family is of considerable practical importance since the isolation and identification of these germs from pathological materials and the environment are indispensable premises both for the correct therapy of pathological processes and for the prophylaxis of infectious diseases. However, the diagnostic procedures that bring results of almost absolute certainty are based on very numerous biochemical tests, and sometimes, on the use of specific immune sera, and these methods can be too complex. To meet these needs, some laboratories have developed equipment that allows the simultaneous detection of different bacterial biochemical activities in a relatively short time, which allows to reach diagnoses of species that are found to be in unsatisfactory agreement with those obtained with the use of the most extensive classical methods. On the other hand, it should be kept in mind that differences have been highlighted in the detection of individual biochemical characters depending on the method used, and there are variable percentages of false results with the use of some of the said equipment (20).

The spread of Enterobacteriaceae strains that are resistant to carbapenems represents an important clinical problem, as they present multiple resistance to different classes of antibiotics. Enterobacteriaceae are also a public health problem, due to their high capacity for diffusion and transmission in the population which occurs through genetic elements (21).

The most common Enterobacter carbapenemase are classes A and B, which spread via plasmids (22).  Less frequently, carbapenem resistance is due to excessive production of extended-spectrum β-Lactamase or AmpC enzymes or by the presence of class D carbapenems (23).

CONCLUSIONS

Ongoing research is needed to develop new antibiotics and alternative therapies, such as bacteriophage therapy and antimicrobial peptides, to treat infections caused by resistant Enterobacteriaceae. Combating resistant Enterobacteriaceae infections requires a multifaceted approach involving molecular biology to understand the mechanisms of resistance, advanced diagnostics for rapid detection, and coordinated public health efforts to control the spread of these pathogens.

Conflict of interest

The authors declare that they have no conflict of interest.

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