Open access peer-reviewed chapter

Multidrug-Resistant Bacterial Foodborne Pathogens: Impact on Human Health and Economy

Written By

Lilia M. Mancilla-Becerra, Teresa Lías-Macías, Cristina L. Ramírez-Jiménez and Jeannette Barba León

Submitted: March 28th, 2019 Reviewed: July 24th, 2019 Published: September 4th, 2019

DOI: 10.5772/intechopen.88789

From the Edited Volume

Pathogenic Bacteria

Edited by Sahra Kırmusaoğlu and Sonia Bhonchal Bhardwaj

Chapter metrics overview

1,045 Chapter Downloads

View Full Metrics

Abstract

The drug abuse known to occur during growth of animals intended for food production, because of their use as either a prophylactic or therapeutic treatment, promotes the emergence of bacterial drug resistance. It has been reported that at least 25% of the foodborne isolates show drug resistance to one or more classes of antimicrobials (FAO 2018). There are diverse mechanisms that promote drug resistance. It is known that the use of sub-therapeutic doses of antibiotics in animals intended for food production promotes mutations of some chromosomal genes such as gyrA-parC and mphA, which are responsible for quinolone and azithromycin resistance, respectively. Also, the horizontal transfer of resistance genes as groups (“cassettes”) or plasmids makes the spread of resistance to different bacterial genera possible, among which there could be pathogens. The World Health Organization considers the emergence of multidrug-resistant pathogenic bacteria as a health problem, since the illnesses caused by them complicate the treatment and increase the morbidity and mortality rates. The complication in the illness treatment caused by a multidrug-resistant pathogen causes economic losses to patients for the payment of long stays in hospitals and also causes economic losses to companies due to the absenteeism of their workers.

Keywords

  • multidrug-resistant bacteria
  • MDR
  • foodborne pathogens
  • antimicrobial resistance
  • MDR bacteria human health
  • MDR microorganism economic impact

1. Introduction

Increasing antimicrobial resistance (AMR) is a global public health threat. The excessive use and abuse of drug therapies in humans and in the animals intended for human consumption, and its bad disposition as a waste, have tightened up the problem in recent years [1]. This phenomenon affects any person regardless of sex, age, origin, or social status and threats the ability to effectively solve the treatments of different diseases and also compromises the food security, economy, and development of the countries [2].

Microorganisms are sensitive to antimicrobials when they do not harbor components involved in degrading them. AMR occurs when bacteria, fungi, viruses, and parasites are exposed for a long time to sub-therapeutic doses of drugs such as antibiotics, antifungals, antivirals, antimalarials, or anthelmintics that modify the ecology of microorganism. In order to contend with the residues present in their environment, microorganisms may acquire genetic elements that allow them to cope with these compounds and survive. In some cases, the use of poor quality drug, counterfeit products, incorrect product, and modified dosage can accelerate the development of microbial resistance. Another relevant factor for development of AMR is the inadequate disposal of waste generated in the agricultural production and pharmaceutical and wastewater treatment plants as they can be spread through the environment [3]. One of the recently described phenomena observed is the association between the emergence of multiresistant microorganisms (MMR) and the increase in the isolates that show the production of extended-spectrum beta-lactamase enzymes (ESBL). Currently, more than 200 varieties of BLEE enzymes are recognized with different substrates, and the frequency of isolates producing these enzymes varies from country to country (from 20 to 48%) [3].

Although there are many factors that favor the spread of antibiotic resistance, it affects different sectors, such as human health, animal health, agriculture, environment, and commercial trade [4]. It is estimated that 700,000 people die each year from infections caused by microorganisms resistant to antimicrobials and a large number of sick animals that do not respond to treatments [5]. Within the agricultural and food industry, resistant microorganisms represent a risk for production that threatens the global economy. For this reason, it is important to implement supervised agricultural regulations and practices that ensure the responsible use of antimicrobials in the production of animals and crops.

Advertisement

2. Mechanisms and propagation of resistance

In microorganisms, drug resistance arises in order to contend against a harmful stimulus that threatens their survival. In bacteria, the mechanisms that confer the resistance against antibiotics could be classified as intrinsic (mutations originating in the organism itself) or acquired by transfer of genetics elements during the replication of DNA (vertical transfer) or from different species or genera (horizontal transfer) [6] (Figure 1).

Figure 1.

Schematic representation of the mechanisms of multidrug-resistance acquisition in bacteria.

2.1 Intrinsic mechanisms or natural resistance

The intrinsic mechanisms can be found in the cell in a natural manner. They are conditions that are universally found in bacterial species and that are independent of antibiotic selectivity [7]. Some of the intrinsic mechanisms are described below.

2.1.1 Permeability or impermeability of the outer membrane or cell wall

Gram-positive bacteria are more susceptible to various antibiotics since they have a thick outer layer of peptidoglycan with polymers of teichoic acid and covalently bound proteins, which allows the easy penetration of small molecules up to 30–57 kDa [8, 9]. In contrast, Gram-negative bacteria have an outer membrane that surrounds them with a relatively thin peptidoglycan layer. The composition of the outer membrane is based on lipid molecules covalently linked to polysaccharide units [10].

The lipid molecule has a large chain of fatty acids that contribute to reduce the fluidity of the lipopolysaccharide (LPS) membrane [10]. The central region of the LPS plays an important role providing a barrier to hydrophobic antibiotics and other compounds. It has been reported that strains that express full-length LPS have an intrinsic resistance to hydrophobic antibiotic class such as macrolides and aminoglycosides. Another modification observed is the alteration of the anionic nature of the LPS; the most common LPS modifications are the cationic substitution of phosphate groups with 4-amino-4-deoxy-L-arabinose (L-Ara4N) or phosphoethanolamine (PEtN), which decreases the net negative load of lipid A from minus 1.5 to minus 1 or from minus 1.5 to 0, respectively [11]. The net positive charge resulting from the LPS modification reduces the binding of some cationic antibiotics such as polymyxins, leading the resistance of the bacteria such as Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica[12].

On the other hand, embedded in the outer layer membrane of Gram-negative bacteria, there are proteins called porins that function as a channel through which the molecules can diffuse. Porins could restrict the influx of numerous antibiotics and contribute to the resistance against them [13]. The mechanism of resistance promoted by the porins consists in changing the hydrophilic composition of some antibiotics such as beta-lactam, chloramphenicol, fluoroquinolones, and tetracyclines. Likewise, the alteration of the amount or modification of the structure of the porins promotes resistance to antibiotics [11].

2.1.2 Expulsion of the antibiotic by active mechanisms

In general those mechanisms are mediated by bacterial flow pumps that actively transport many toxic molecules out of the cell [14]. The outflow pumps can interact with only one molecule (enzyme substrate specific), or they can have a broader spectrum and export distinct classes of molecules. Antibiotic resistance mediated by active outflow pumps may be incidental, since the pumps exhibit a broad-range substrate [9]. However, efflux pumps associated with antibiotic resistance have been described in Gram-positive and Gram-negative bacterial pathogens. The energy of some flow pumps depends of the antibiotic agents in order to extract it from the periplasm to the outside. The overexpression of one or more of these flow pumps prevents the intracellular accumulation of antibiotics at the thresholds necessary to exert their inhibitory activity [15].

2.1.3 Modification of the target site

Most of the antibiotics bind specifically to their targets with high affinity. Changes in target structure prevent an effective binding to antibiotics but still allow the target to carry out its normal function. The target modification could be originated by a mutation in the gene that encodes for the antibiotic target [14]. An example of this mutation mechanism is the linezolid antibiotic, a member of the oxazolidinone class, which inhibits the initiation of bacterial translation by altering multiple copies of the V domain of the 23S rRNA in Gram-positive bacteria. The mutation in one of these copies of the V domain can confer antibiotic resistance [16].

Another mechanism relies in avoiding or releasing the binding of the antibiotic to their target site [17]. One of the most representative examples of this mechanism and of current importance is that used by quinolones, which exert their function by inhibiting important enzymes of bacterial DNA replication such as gyrase and topoisomerases II and IV. The mechanism of evasion of the antibiotic function is by the expression of repeating pentapeptides (PRP), encoded by qrngenes, which bind and promote the release of the quinolone from the target enzymes, allowing the normal activity of the topoisomerases [18].

2.1.4 Enzymatic inactivation or modification of antibiotics

In this case, the mechanism of action could be by enzymatic hydrolysis [19] or modification of chemical groups by transfer or addition of different chemical compounds [14]. The classic example of a hydrolytic enzyme is the beta-lactamase, which hydrolyzes the beta-lactam ring, a common structural element in penicillins, cephalosporins, carbapenems, and monobactams [20]. Four classes of beta-lactamases have been described: the classes A, C, and D have a serine hydrolase activity; in contrast, class B has a metalloenzyme activity [21]. Another example of this type of resistance is provided by the enzymes erythromycin esterases EreA and EreB. These enzymes hydrolyze the macrolactone rings of macrolides such as erythromycin. It should be noted that EreB enzyme confers resistance to almost all members of the macrolide class, with the exception of telithromycin, a semisynthetic erythromycin derivative, which belongs to a new class of antibiotics called ketolides [22]. In contrast, the EreA enzyme does not hydrolyze azithromycin and also telithromycin [23].

The modification of antibiotics includes the modification of some element of their structure, which is essential in the union with the bacteria target diminishing its affinity. This mechanism involves the addition or transfer of groups such as N-acetyl, phosphoryl, O-nucleoside, O-ribosyl, and O-glycoside. Unlike hydrolysis, this modification does not destroy the essential structures of the antibiotic but obstructs the interaction of the antimicrobial with its target. An example of this mechanism occurs for polycationic antibiotics such as aminoglycosides, which act between the ionic bonds of the amino and hydroxyl groups of the antibiotics and the 16S rRNA region of the A site of the bacterial ribosome, deteriorating the translation mechanism. The enzymes responsible for the modification of the aminoglycosides are the aminoglycoside phosphotransferases (APH) and nucleotidyltransferases (ANT) that modify the hydroxyl groups and the aminoglycoside acetyltransferases (AAC) which modify the amino groups, changing the size, structure, and electronic properties of the antibiotic [24].

2.2 Genetic mobile elements transfer or acquired resistance mechanisms

Once the bacterial cell acquires some degree of antibiotic resistance by an intrinsic mechanism that implies DNA modification, it can transfer the gene or genes encoding for the resistance marker to the offspring (vertical transfer) or to a different specie or genus (horizontal transfer) [25]. The gene resistance can be acquired by genetic mobile elements such as plasmids, transposons, or integrons [19].

The vertical transfer or vertical evolution occurs when a spontaneous mutation in the bacterial chromosome confers resistance to some members of the bacterial population. Once the resistance genes have arisen, they are transferred to the progeny of the bacteria during DNA replication [6]. When the bacterial genes that confer resistance to antibiotics are mobile, because they are contained within plasmids or are flanked by sequences recognized by some DNA transposition enzymes, they can be transferred between bacteria of a different taxonomic and ecological group. Some genetic mobile elements are plasmids, transposons, integrases, and genetic cassettes; in general this mechanism is called horizontal transfer gene [19, 26].

2.2.1 Plasmids

In bacterial cells, there are circular portions of extrachromosomal DNA that improve the survival characteristics of bacteria. This genetic information could be dispensable when it is no longer necessary to contend with the specific stress to which it imparts protection. Plasmids are self-replicating, given that they do so independently of chromosomal DNA replication. When plasmids contain antibiotic resistance genes, they are called plasmids R, and they can be transferred between bacteria of the same or different genera. Plasmids can be transferred to another bacterial cell by mechanisms called transformation or conjugation [19]. Transformation involves the acquisition of free DNA available in the medium. For this process the recipient bacteria must be in a competitive state; and the translocated DNA must be stabilized, either by integration into the host receptor genome or by recircularization (in the case of plasmid DNA) [27]. In contrast, conjugation involves the transfer of DNA through a multistep process that requires cell-to-cell contact, via cell surface pili or adhesins [28]. The conjugative machinery is encoded by genes in plasmids or by integrative conjugative elements in the chromosome [29].

2.2.2 Transposons

These are already known as jumping genes. These are short chains of DNA that jump from chromosome to plasmid or vice versa. DNA transfer can occur between bacterial chromosome, plasmids, and bacteriophages. The most salient feature of transposons is that DNA acquired is easily integrated into the host chromosome or plasmids. Unlike plasmids, jumping genes are not self-replicating, and they must be kept within a self-replicating structure to replicate them [19].

2.2.3 Integrons and cassette system

Both of them provide a simple mechanism for the acquisition of new genes. The DNA acquisition implies a single event of a site-specific recombination that causes the integration or removal of a single gene or a group of antibiotic resistance genes called cassette [30]. The integrons have certain components which allow a site-specific recombination system that recognizes and captures mobile genes. An integron includes a gene that codes for an integrase (Intl) and a site of specific recombination (attI) [31]. The sequences of the integrase enzymes allow integron classification in different classes (I–III) [32].

Genetic cassettes are small mobile elements that include a short sequence of 57 to 141 bp that are a specific recombination site. Cassettes can exist as free circular DNA molecules, and frequently they do not contain a promoter [30]. The lack of the promoter and the recombination sites make the recognition of the cassettes by Intl and Int13 and also by integrases encoded in the integrons possible. The integration of the cassettes to the integron structure allows the cassette genes’ transcription from the characteristic integron promoter called Pant [30].

The dangerous feature of the transfer of antibiotic-resistant genes by transposons, integrons, or cassettes is the possibility that the bacterial receptor could acquire several classes of antibiotic resistance genes in a single event. A summary of the resistance to the different antibiotic classes, obtained by the intrinsic and acquired mechanisms, can be found in Table 1.

Antibiotic class/antibioticsMode of actionMechanism of resistance
Beta-lactam[33]
Penicillins*
Penicillin G and V Cloxacillin
Ampicillin
Carbenicillin
Cephalosporins*
Cephaloridine
Cephalexin
Cefuroxime
Moxalactam
Ceftiofur
Cefoperazone
Cefepime
Inhibitors
Beta-lactamase*
Clavulanate
Sulbactam
Tazobactam
Carbapenems*
Imipenem/cilastatin
Aztreonam
Act as suicide substrates for penicillin-binding proteins (PBP) (transpeptidases)
They inhibit cell wall biosynthesis, specifically the peptidoglycan structure
Acquired
  • Plasmids

  • Transposons

  • Integrons

(blaTEM-1, blaNDM-1, blaKPC, bla SHV, blaCTX-M, AmpC, blaVIM, blaOXA, and blaIMIgenes) [34]
Intrinsic
  • Bacterial flow pumps (RND, ABC, and 233 transporter)

Monobactams
[33, 35]
Aminoglycosides*
Streptomycin
Kanamycin
Neomycin
Gentamicin
Spectinomycin
Inhibits the synthesis of proteins by binding to the ribosomal 30S subunitIntrinsic
  • Bacterial flow pumps (MexXY and ABC transporter)

  • Enzymatic modification (blaKPC gene)

  • Ribosomal point mutation (rrsgene)

Diaminopyrimidines[33]
Trimethoprim
They inhibit DNA replication by binding to dihydrofolate reductase, an enzyme involved in the metabolism of folic acidAcquired
  • Transposon Tn7 (dhfrIgene) [36]

Intrinsic
  • Competitive inhibition of folic acid synthesis

Phenicols[33]
Chloramphenicol
Thiamphenicol
They bind to the peptidyl transferase (PTC) center of the 50S ribosomal subunit to inhibit the translation elongation stageIntrinsic
  • Target modification (cfrgen)

  • Bacterial flow pumps of amphenicols (Cml transporter)

Fluoroquinolones[37]
Enrofloxacin
Danofloxacin
Marbofloxacin
They inhibit DNA synthesis by topoisomerases II and IVIntrinsic
  • Target modification (gyrAand parCgenes)

  • Bacterial flow pumps of amphenicols (AcrA transporter)

Glycopeptides[33]
Vancomycin
Teicoplanin
Streptogramins
Virginamycin
They inhibit the cell wall biosynthesis in Gram-positive bacteria. They block the binding of the substrate and the transglycosylasesIntrinsic
  • Bacterial flow pumps of amphenicols (AcrF transporter)

Acquired
  • Transposon Tn1546 (vangene) [38]

Lincosamides[33]
Lincomycin
Clindamycin
Pirlimycin
They prevent protein elongation during translation by causing premature dissociation of the tRNA, inhibiting the 50S ribosomal subunitIntrinsic
  • Ribosomal modification by methylation or mutation (ermand msrgenes) [39]

  • Bacterial flow pumps (ABC and MFS transporter)

  • Drug inactivation (Lnuand Mphgenes) [39]

Macrolides[33]
Erythromycin
Oleandomycin
Tylosin
Spiramycin
Tilmicosin
Nitroimidazoles[40]
Metronidazole
They inhibit the synthesis of DNA by oxidation. The nitro group is reduced to toxic radical speciesIntrinsic
  • Bacterial flow pumps (RND and BME transporter)

  • Reductive activation by altering

  • The metabolism of pyruvate (PFOR)

Acquired
  • Chromosomal mutations or plasmids acquired (nimgen)

Peptides[41]
Polymyxin B
Colistin
They displace the Mg+2 and Ca+2 ions and interact electrostatically with the lipopolysaccharides (LPS) of the external Gram-negative cell membranesIntrinsic
  • Reduction of specific proteins of the membrane and LPS

  • Lipid modifications

Rifamycins[42]
Rifampicin
They stop transcription by interacting with the β subunit of RNA polymerase (RNAP)Intrinsic
  • Point mutations in the rifampicin-binding region of the β subunit of RNAP (rpoBgene)

  • Bacterial flow pumps (VceB and Acr transporter) [33]

Sulfonamides[36]
Sulfanilamide
Sulfadiazine
Sulfatiazole
They act as competitive inhibitors of DHPS; they block the folate biosynthesis in the bacterial cellAcquired
  • Integrons (sul1gene)

  • Plasmids (IncQclass: sul2gene)

Tetracyclines[43]
Doxycycline
Minocycline
Oxytetracycline
They block the access of the tRNA to the ribosome by binding to the 30S ribosomal subunitIntrinsic
  • Bacterial flow pumps (SMR, RND, or ABC transporter)

  • Ribosomal modification

  • Enzyme inhibition

(coded by different classes of tet, otr, and tcrgenes)

Table 1.

Modes of action to different classes of antibiotics and their mechanisms of resistance.

The subclasses of the class of beta-lactam


Advertisement

3. Overview of resistant pathogens isolated from food

Fruits, vegetables, and foods from animal origin can be contaminated with antibiotic-resistant bacteria at any time in the food chain FAO [2]. There has been an increase in drug resistance in pathogens isolated from food for human consumption since 2000. Salmonella entericaand Escherichia coliisolates have been considered among the most important pathogens, because they can make zoonotic transfer of resistant genes [44]. However other pathogens, such as Vibriospp., some species of Aeromonas, spores of Clostridium botulinumtype F, or enteric bacteria such as Campylobacter, have been linked to gastrointestinal diseases in humans who have consumed foods of animal and marine origin. It has been reported that multidrug-resistant plasmids are easily transferred to Aeromonas salmonicidaby E. coli[45, 46].

Salmonellais a pathogenic bacterium that cause a gastrointestinal disease called salmonellosis. In Latin America, Asia, and Africa, 200–500 cases of salmonellosis per 100,000 inhabitants per year have been documented, where the 95% of the infections come from the consumption of contaminated foods [47]. Worldwide, it was estimated that the infections caused by Salmonella entericaare above 93.8 million cases with 155,000 deaths per year [48].

Salmonella entericais one of the most frequently isolated foodborne pathogens from different kinds of food. In the United States, between 11 and 20% of strains isolated from animals destined to human consumption were resistant to more than five different antibiotics [49]. Other studies mention that 82% of the isolates in strains from food are resistant to at least one antibiotic, associated with high resistance levels to tetracycline, streptomycin, sulfamethoxazole, and ampicillin [49]. In Latin American countries, the average of Salmonellaresistant isolates is dependent on the region and analyzed food. In Brazil in a study conducted in a salami processing line, a 3.7% resistance to 1 antibiotic and 11.1% resistance to 3 or more antibiotics out of a total of 54 isolates have been reported [50]. In contrast, in a study conducted in pork carcasses, 147 out of 155 Salmonellastrains isolated (94.85%) were resistant to at least one or more antibiotics [51].

Escherichia coliis one of the most widespread microorganisms in nature, and it is a member of the normal intestinal flora of many organisms, including humans. In a study conducted in Havana, Cuba, 74 E. coli-resistant strains were isolated from foods involved in foodborne diseases (ETA). Among foods with the highest CFU of E. coliserogroups identified, there were soy yogurt (14.3% of isolates), pork steak (11.9%), chicken hash (11.9%), cheese (9.5%), ham (9.5%), and beef hash (7.1%). Resistance to ampicillin was present in 36.4% of the isolates, and some isolates were also resistant to streptomycin, sulfamethoxazole, and tetracycline [52]. In America, Eastern Mediterranean, Africa, Southeast Asia, and the Western Pacific regions, an increased resistance to third-generation cephalosporins and fluoroquinolones into E. coliisolates has been reported [53].

On the other hand, studies conducted in dairy products have shown that 73.3% (33/45) of the E. colistrains isolated were susceptible to all antibiotics tested and 24.4% (11/45) showed resistance to ampicillin. The phylogenetic analysis of the E. coliisolates resulted in grouping into two phylogroups, A and B1, which have a higher frequency of resistance genes than those that were grouped in B2 and D. It is worth to notice that E. coliisolates in this study that belonged to phylogroup A and B1 were commensal strains with few or no virulence factors [54]. These results suggest that the food chain is the vehicle for the transfer of resistant genes, and it has been suggested that E. colistrains present in food are the original carrier of many mechanisms of antibiotic resistance in the intestinal microbiota of humans.

Studies conducted in different food classes have isolated other bacterial genera different to Salmonella entericaand E. coli. One of the most studied is Staphylococcus aureus, which causes staphylococcal poisoning. Strains of S. aureushave been studied in the last decades because they show resistance to methicillin. The analyses done in 282 S. aureusstrains isolated from food and manipulators showed that 56.1% of the strains were resistant to one or more antimicrobials [55].

Another bacterial genus of health importance is Mycobacterium bovis. In the United States, outbreaks by M. bovishave been associated with the consumption of contaminated food. In 2007, 203 samples of cheese imported from Mexico were collected at the California customs office. Of the samples collected, 4.9% tested positive for Mycobacteriumgenus, with drug susceptibility test to streptomycin, isoniazid, rifampicin, ethambutol, and pyrazinamide, showing that they were susceptible to all the antibiotics tested except pyrazinamide [56]. In contrast, in Japan, 58 M. bovisstrain isolates from dairy cattle reported 7 strains resistant to the fluoroquinolones enrofloxacin, orbifloxacin, and danofloxacin. The fluoroquinolone resistance was associated with the mutation to quinolone resistance-determining regions of gyrAand parCgenes (QRDR). The strains that showed no fluoroquinolone resistance phenotype did not present mutations [57].

Listeria, Shigella, and Campylobacterare other bacterial genera that have been isolated from foods and have shown antibiotic resistance. Listeria monocytogenesstrains isolated from cheese have shown resistance to streptomycin, kanamycin, cephalothin, and tetracycline [58]. The analysis of 152 Shigellastrains isolated from various foods that caused outbreaks of shigellosis in Brazil showed that several strains were resistant to streptomycin (88.6%), followed by ampicillin (84.6%) and sulfamethoxazole/trimethoprim (80.5%). The resistant strains were grouped into 73 patterns, where pattern A (resistance to ampicillin, sulfamethoxazole/trimethoprim, tetracycline, streptomycin, and chloramphenicol and intermediate resistance to kanamycin) grouped the highest number of isolates (n = 36) [59]. In Malaysia, Campylobacterspp. was reported with a prevalence of 17.4%, from a total of 340 cattle samples. Campylobacterisolates showed resistant to tetracycline (76.9%) and ampicillin (69.2%), while resistance to chloramphenicol was low (7.6%) [60].

Even in farms of goldfish (Carassius auratus), 70 strains of bacterial genera such as Aeromonas hydrophila, Vibrio fluvialis, and V. furnissiihave been identified, with 45% of the isolates being resistant to 6 of the 14 antibiotics tested; 100% of the strains were resistant to cephalothin, 94% to ampicillin, 89% to chloramphenicol, 88% to tetracycline, 85.3% to nitrofurantoin, 61.3% to carbenicillin, and 65.3% to kanamycin. Twenty three percent of the isolates presented sensitivity to amikacin, trimethoprim, cefotaxime, netilmicin, pefloxacin, and gentamicin. Only one strain, A. hydrophila, showed resistance to all antibiotics tested. Twenty strains generated resistance to 7 different antibiotics, and 67 of the 70 strains generated resistance to more than 1 antibiotic [46].

As we can see in this overview, the resistance of the different bacterial genera isolated in a great diversity of foods is alarming, since many of these bacterial genera are the cause of many foodborne diseases. The diseases produced by these resistant pathogenic bacteria are difficult to treat, being able to provoke death in some patients.

Advertisement

4. Economic implications/economic impact of the resistant pathogens in food

As we previously mentioned, the resistance occurs when the antibiotics used for the control of bacterial diseases are no longer optimal for their elimination. The most common routes to get infected with pathogenic bacteria are air, direct contact with sick people, or consumption of contaminated water or food. Pathogenic bacteria can be spread through sick people and contaminated fruits, vegetables, or animals that are intended for consumption. Antimicrobial resistance is a risk factor and complication of the disease, being difficult to treat infections, and it could be eventually lead to death [61]. In 2019, 700,000 deaths worldwide can be attributed to antimicrobial resistance, and the figure would rise to 35 million in 35 years, due to the lack of treatments to cure diseases caused by resistant pathogens; the estimated cost for the treatment of these persons will be 100 billion dollars [62, 63].

Morbidity and mortality increase when the administration of effective treatments to counteract infections caused by resistant pathogens is delayed. The duration of the disease and hospitalization of patients with infections by resistant pathogens have an economic impact, since there are extra procedures for the treatment of the disease, the antibiotics that could be administered usually are more expensive than the ones used as first line, and also there are long hospitalization stays. The economic impact for the patient is due to the loss of productivity for taking care of themselves or a family member [61]. It is highlighted that 63.5% of infections are acquired in hospitals and that the groups with the highest incidence are under 1 year or over 65 years old [62, 63].

In Europe and the United States, more than 50,000 people die every year from infections with drug-resistant pathogens, while in India it is estimated that close to 60,000 newborns die due to resistant infections. There are at least 700,000 deaths every year caused by resistant microorganism that generate diseases such as bacterial infections, malaria, HIV/AIDS, or tuberculosis [64]. The Centers for Disease Control and Prevention estimated that 2 million patients will be treated each year for resistant bacteria, of which 23,000 die [65]. In United States, it was estimated that there are an average of 1400 sick people with infection caused by resistant microorganisms, with a medical cost per patient estimated in $18,588 to $29,069 US dollars with a mortality rate of 6.5%. In the European Union, the cost for loss of productivity due to an illness originated by resistant bacteria is estimated in 1.5 billion € per year [66].

It is evident that the problem of bacterial resistance has reached great impact not only in the health of the population but also on its economy. For this reason, it is necessary to undertake actions that help in stopping the acquisition of the genetic elements that promote antibiotic resistance. Without doubt, the implementation of government laws that avoid the excessive use of antibiotics in livestock and fish farming could help to hinder the problem. Also the use of alternative molecules to antibiotics for the prevention of diseases in animals and improvement of the hygiene and vaccination measures in the farming collection and food processes would help to stop the problem of bacterial resistance. It has been proven that countries that have implemented control measures in the use of antibiotics in animals for human consumption and their products reduce up to 39% resistant bacteria. Not less important is the implementation of control measures in hospitals and clinics as well as generation of awareness in the population to avoid the overprescription of antibiotics, elements that all together can make a difference.

Advertisement

Conflict of interest

The authors do not have any conflict of interest.

References

  1. 1. Cires Pujol M. La resistencia a los antimicrobianos, un problema mundial. Revista Cubana de Medicina General Integral. 2002;18(2):165-168
  2. 2. FAO. Food and Agriculture Organization of the United Nations and WHO World Health Organization. FAO/WHO expert meeting on foodborne antimicrobial resistance: Role of environment, crops and biocides [Internet]. 2018. Available from:https://www.who.int/foodsafety/areas_work/antimicrobial-resistance/FAO_WHO_AMR_Summary_Report_June2018.pdf[Accessed: 04 June 2019]
  3. 3. FAO Food and Agriculture Organization of the United Nations. Antimicrobial resistence: What you need to know [Internet]. 2017. Available from:http://www.fao.org/fao-stories/article/en/c/1056781/[Accessed: 04 June 2019]
  4. 4. Liliam CJ, Andrés MRL, Liliam HCM. Principios generales de la terapéutica antimicrobiana. Acta Medica. 1998;8(1):13-27
  5. 5. Pérez RD. Resistencia bacteriana a antimicrobianos: su importancia en la toma de decisiones en la práctica diaria. Información terapéutica del sistema nacional de salud. 1998;22(3):57-67
  6. 6. Van Wyk H. Antibiotic resistance. A Pharmaceutical Journal. 2015;82(3):20-23
  7. 7. Cox G, Wright GD. Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions. International Journal of Medical Microbiology. 2013;303(6-7):287-292. DOI: 10.1016/j.ijmm.2013.02.009
  8. 8. Schaffer C, Messner P. The structure of secondary cell wall polymers: How Gram-positive bacteria stick their cell walls together. Microbiology-Sgm. 2005;151:643-651. DOI: 10.1099/mic.0.27749-0
  9. 9. Scherrer R, Gerhardt P. Molecular sieving by theBacillus megateriumcell wall and protoplast. Journal of Bacteriology. 1971;107(3):718-735
  10. 10. Obst S, Kastowsky M, Bradaczek H. Molecular dynamics simulations of six different fully hydrated monomeric conformers ofEscherichia colire-lipopolysaccharide in the presence and absence of Ca2+. Biophysical Journal. 1997;72(3):1031-1046. DOI: 10.1016/s0006-3495(97)78755-1
  11. 11. Delcour AH. Outer membrane permeability and antibiotic resistance. Biochimica et Biophysica Acta. 2009;1794(5):808-816. DOI: 10.1016/j.bbapap.2008.11.005
  12. 12. Olaitan AO, Morand S, Rolain JM. Mechanisms of polymyxin resistance: Acquired and intrinsic resistance in bacteria. Frontiers in Microbiology. 2014;5:643. DOI: 10.3389/fmicb.2014.00643
  13. 13. Ruiz N, Montero T, Hernandez-Borrell J, Viñas M. The role ofSerratia marcescensporins in antibiotic resistance. Microbial Drug Resistance-Mechanisms Epidemiology and Disease. 2003;9(3):257-264. DOI: 10.1089/107662903322286463
  14. 14. Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. Molecular mechanisms of antibiotic resistance. Nature Reviews Microbiology. 2015;13(1):42-51. DOI: 10.1038/nrmicro3380
  15. 15. Mahamoud A, Chevalier J, Alibert-Franco S, Kern WV, Pages JM. Antibiotic efflux pumps in Gram-negative bacteria: The inhibitor response strategy. Journal of Antimicrobial Chemotherapy. 2007;59(6):1223-1229. DOI: 10.1093/jac/dkl493
  16. 16. Billal DS, Feng J, Leprohon P, Legare D, Ouellette M. Whole genome analysis of linezolid resistance inStreptococcus pneumoniaereveals resistance and compensatory mutations. BMC Genomics. 2011;12:512. DOI: 10.1186/1471-2164-12-512
  17. 17. Kumar N, Radhakrishnan A, Wright CC, Chou TH, Lei HT, Bolla JR, et al. Crystal structure of the transcriptional regulator Rv1219c ofMycobacterium tuberculosis. Protein Science. 2014;23(4):423-432. DOI: 10.1002/pro.2424
  18. 18. Hooper DC, Jacoby GA. Mechanisms of drug resistance: Quinolone resistance. Annals of the New York Academy of Sciences. 2015;1354:12-31. DOI: 10.1111/nyas.12830
  19. 19. Errecalde JO. Uso de antimicrobianos en animales de consumo [Internet]. 2004. Available from:http://www.fao.org/3/a-y5468s.pdf[Accessed: 05 June 2019]
  20. 20. Sauvage E, Terrak M. Glycosyltransferases and transpeptidases/penicillin-binding proteins: Valuable targets for new antibacterials. Antibiotics (Basel). 2016;5(1):1-27. DOI: 10.3390/antibiotics5010012
  21. 21. Bush K, Bradford PA. Beta-lactams and beta-lactamase inhibitors: An overview. Cold Spring Harbor Perspectives in Medicine. 2016;6(8). DOI: 10.1101/cshperspect.a025247
  22. 22. DrugBank database. Telithromycin [Internet]. 2019. Available from:https://www.drugbank.ca/drugs/DB00976[Accessed: 15 July 2019]
  23. 23. Gomes C, Martinez-Puchol S, Palma N, Horna G, Ruiz-Roldan L, Pons MJ, et al. Macrolide resistance mechanisms in Enterobacteriaceae: Focus on azithromycin. Critical Reviews in Microbiology. 2017;43(1):1-30. DOI: 10.3109/1040841X.2015.1136261
  24. 24. D'Costa V, Wright GD. Biochemical logic of antibiotic inactivation and modification. In: Mayers DL, editor. Antimicrobial Drug Resistance. Infectious Disease. New York, USA: Humana Press; 2009. pp. 81-95. DOI: 10.1007/978-1-59745-180-2_8
  25. 25. Hermsen R, Deris JB, Hwa T. On the rapidity of antibiotic resistance evolution facilitated by a concentration gradient. Proceedings of the National Academy of Sciences of the United States of America. 2012;109(27):10775-10780. DOI: 10.1073/pnas.1117716109
  26. 26. Jain R, Rivera MC, Lake JA. Horizontal gene transfer among genomes: The complexity hypothesis. Proceedings of the National Academy of Sciences of the United States of America. 1999;96(7):3801-3806. DOI: 10.1073/pnas.96.7.3801
  27. 27. Thomas CM, Nielsen KM. Mechanisms of, and barriers to, horizontal gene transfer between bacteria. Nature Reviews Microbiology. 2005;3(9):711-721. DOI: 10.1038/nrmicro1234
  28. 28. Wozniak RAF, Waldor MK. Integrative and conjugative elements: Mosaic mobile genetic elements enabling dynamic lateral gene flow. Nature Reviews Microbiology. 2010;8(8):552-563. DOI: 10.1038/nrmicro2382
  29. 29. Smillie C, Garcillán-Barcia MP, Francia MV, Rocha EPC, de la Cruz F. Mobility of plasmids. Microbiology and Molecular Biology Reviews. 2010;74(3):434-452. DOI: 10.1128/mmbr.00020-10
  30. 30. Hall RM, Collis CM. Antibiotic resistance in gram-negative bacteria: The role of gene cassettes and integrons. Drug Resistance Updates. 1998;1(2):109-119. DOI: 10.1016/S1368-7646(98)80026-5
  31. 31. Hall RM, Brookes DE, Stokes HW. Site-specific insertion of genes into integrons role of the 59-base element and determination of the recombination cross-over point. Molecular Microbiology. 1991;5(8):1941-1959. DOI: 10.1111/j.1365-2958.1991.tb00817.x
  32. 32. Kaushik M, Kumar S, Kapoor RK, Virdi JS, Gulati P. Integrons in Enterobacteriaceae: Diversity, distribution and epidemiology. International Journal of Antimicrobial Agents. 2018;51(2):167-176. DOI: 10.1016/j.ijantimicag.2017.10.004
  33. 33. Fair RJ, Tor Y. Antibiotics and bacterial resistance in the 21st century. Perspectives in Medicinal Chemistry. 2014;6:25-64. DOI: 10.4137/PMC.S14459
  34. 34. López-Velandia DP, Torres-Caycedo MI, Prada-Quiroga CF. Genes de resistencia en bacilos Gram negativos: Impacto en la salud pública en Colombia. La Revista Universidad y Salud. 2016;18(1):190-202
  35. 35. Palomino J, Pachon J. Aminoglycosides. Enfermedades Infecciosas y Microbiologia Clinica. 2003;21(2):105-115. DOI: 10.1157/13042869
  36. 36. Huovinen P, Sundström L, Swedberg G, Sköld O. Trimethoprim and sulfonamide resistance. Antimicrobial Agents and Chemotherapy. 1995;39(2):279-289. DOI: 10.1128/aac.39.2.279
  37. 37. Drlica K, Malik M. Fluoroquinolones: Action and resistance. Current Topics in Medicinal Chemistry. 2003;3(3):249-282. DOI: 10.2174/1568026033452537
  38. 38. Alekshun MN, Levy SB. Molecular mechanisms of antibacterial multidrug resistance. Cell. 2007;128(6):1037-1050. DOI: 10.1016/j.cell.2007.03.004
  39. 39. Leclercq R. Mechanisms of resistance to macrolides and lincosamides: Nature of the resistance elements and their clinical implications. Clinical Infectious Diseases. 2002;34(4):482-492. DOI: 10.1086/324626
  40. 40. Dingsdag SA, Hunter N. Metronidazole: An update on metabolism, structure-cytotoxicity and resistance mechanisms. Journal of Antimicrobial Chemotherapy. 2018;73(2):265-279. DOI: 10.1093/jac/dkx351
  41. 41. Falagas ME, Kasiakou SK. Colistin: the revival of polymyxins for the management of multidrug-resistant gram-negative bacterial infections (2005;40:1333). Clinical Infectious Diseases. 2006;42(12):1819-1819
  42. 42. Goldstein BP. Resistance to rifampicin: A review. Journal of Antibiotics. 2014;67(9):625-630. DOI: 10.1038/ja.2014.107
  43. 43. Roberts MC. Update on acquired tetracycline resistance genes. FEMS Microbiology Letters. 2005;245(2):195-203. DOI: 10.1016/j.femsle.2005.02.034
  44. 44. Cantón R, Novais A, Valverde A, Machado E, Peixe L, Baquero F, et al. Prevalence and spread of extended-spectrum β-lactamase-producing Enterobacteriaceae in Europe. European Society of Clinical Microbiology and Infectious Diseases. 2007;14(1):144-153. DOI: 10.1111/j.1469-0691.2007.01850.x
  45. 45. Kumar D, Taneja N, Singh Gill H, Kumar R.Vibrio choleraeO1 Ogawa serotype outbreak in a village of Ambala district in Haryana, India. Indian Journal of Community Medicine. 2011;36(1):66-68
  46. 46. Negrete Redondo P, Romero Jarero J, FJL A. Anatibiotic resistance and presence of plasmids in:Aeromonas hydrophila,Vibrio fluvialis, andVibrio furnissiiisolated fromCarassius auratus auratus. Veterinaria México. 2004;35(1):21-30
  47. 47. Campioni F, Moratto Bergamini AM, Falcao JP. Genetic diversity, virulence genes and antimicrobial resistance ofSalmonellaEnteritidis isolated from food and humans over a 24-year period in Brazil. Food Microbiology. 2012;32(2):254-264. DOI: 10.1016/j.fm.2012.06.008
  48. 48. Hendriksen RS, Vieira AR, Karlsmose S, Lo Fo Wong DM, Jensen AB, Wegener HC, et al. Global monitoring of Salmonella serovar distribution from the World Health Organization Global Foodborne Infections Network Country Data Bank: Results of quality assured laboratories from 2001 to 2007. Foodborne Pathogens and Disease. 2011;8(8): 887-900. DOI: 10.1089 / fpd.2010.0787
  49. 49. Puig-Peña Y, Leyva-Castillo V, Martino-Zagovalov TK. Estudio de susceptibilidad antimicrobiana en cepas deSalmonellasp aisladas de alimentos. Revista Habanera de Ciencias Médicas. 2008;7(2):1-9
  50. 50. Ribeiro VB, AndrighetoI C, BersotII LS, BarcellosII V, ReisIII EF, Destro MT. Serological and genetic diversity amongstSalmonellastrains isolated in a salami processing line. Brazilian Journal of Microbiology. 2007;38(1):178-182. DOI: 10.1590/S1517-83822007000100036
  51. 51. Bermúdez-D PM, Rincón-G SM, Suárez-A MC. Evaluation of antimicrobial susceptibility ofSalmonellaspp. strains isolated from pork carcasses on Colombia. Revista Facultad Nacional de Salud Pública. 2013;32(1):88-94
  52. 52. Puig-Peña Y, Leyva-Castillo V, Apórtela-López N, Campos-González N, Frerer-Marquez Y, Soto-Rodríguez P. Serogrupos y resistencia antimicrobiana de cepas deEscherichia coliaisladas en alimentos procedentes de brotes de enfermedades diarreicas. Revista Cubana de Alimentación y Nutrición. 2014;24(2):161-171
  53. 53. WHO. World Health Organizarion. WHO’s first global report on antibiotic resistance reveals serious, worldwide threat to public health [Internet]. 2014. Available from:https://www.who.int/mediacentre/news/releases/2014/amr-report/en/[Accessed: 06 June 2019]
  54. 54. Guillén L, Millán B, Araque M. Caracterización molecular de cepas deEscherichia coliaisladas de productos lácteos artesanales elaborados en Mérida, Venezuela. Infection. 2014;18(3):100-108. DOI: 10.1016/j.infect.2014.04.004
  55. 55. Puig-Peña Y, Espino-Hernández M, Leyva-Castillo V, Apórtela-López N, Pérez-Muñoz Y, Soto-Rodríguez P. Resistencia antimicrobiana en cepas de estafilococos coagulasa positiva aisladas en alimentos y manipuladores. Revista Cubana de Alimentación y Nutrición. 2015;25(2):245-260
  56. 56. Harris NB, Payeur J, Bravo D, Osorio R, Stuber T, Farrell D, et al. Recovery ofMycobacterium bovisfrom soft fresh cheese originating in Mexico. Applied and Environmental Microbiology. 2007;73(3):1025-1028. DOI: 10.1128/AEM.01956-06
  57. 57. Sato T, Okubo T, Usui M, Higuchi H, Tamura Y. Amino acid substitutions in GyrA and ParC are associated with fluoroquinolone resistance inMycoplasma bovisisolates from Japanese dairy calves. Journal of Veterinary Medical Science. 2013;75(8):1063-1065. DOI: 10.1292/jvms.12-0508
  58. 58. Carolina C, Laura AM. Caracterización de cepas deListeria monocytogenesrealizados a partir de queso fresco proveniente de diferentes zonas productoras costarricenses. Archivos Latinoamericanos de Nutrición. 2009;59(1):66-70
  59. 59. Daniel de Paula CM, Passos-Geimba M, Heidrich do Amaral P, Cesar Tondo E. Antimicrobial resistance and PCR-ribotyping ofShigellaresponsible for foodborne outbreaks occurred in southern Brazil. Brazilian Journal of Microbiology. 2010;41(4):966-977. DOI: 10.1590/S1517-83822010000400015
  60. 60. Premarathne J, Anuar AS, Thung TY, Satharasinghe DA, Jambari NN, Abdul-Mutalib NA, et al. Prevalence and antibiotic resistance against tetracycline inCampylobacter jejuniandC. coliin cattle and beef meat from Selangor, Malaysia. Frontiers in Microbiology. 2017;8:2254. DOI: 10.3389/fmicb.2017.02254
  61. 61. WHO. World Health Organization. Antibiotic resistance [Internet]. 2018. Available from:https://www.who.int/news-room/fact-sheets/detail/antibiotic-resistance[Accessed: 05 June 2019]
  62. 62. Londoño-Restrepo J. Factores de riesgo asociados a infecciones por bacterias multirresistentes derivadas de la atención en salud en una institución hospitalaria de la ciudad de Medellín. Infection. 2015;20(2):77-83. DOI: 10.1016/j.infect.2015.09.002
  63. 63. Red Nacional de Vigilancia Epidemiológica (RENAVE). Protocolo de vigilancia y control de microorganismos multirresistentes o de especial relevancia clínico-epidemiológica (ProtocoloMMR). Madrid, España: RENAVE; [Internet]. 2016. Available from:http://www.comunidad.madrid/sites/default/files/doc/sanidad/epid/iras_protocolo-mmr.pdf. [Accessed: 16 August 2019]
  64. 64. O’Neill J. Tackling drug-resistant infections globally: Final report and recommendations [Internet] United Kingdom: Wellcome Trust. 2006. Available from:https://amr-review.org/sites/default/files/160518_Finalpaper_with cover.pdf. [Accessed: 06 June 2019]
  65. 65. CDC. Centers for Disease Control and Prevention. Antibiotic resistance threats in the united states [Internet]. 2013. Available from:https://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf[Accessed: 06 June 2019]
  66. 66. IS Global Instituto de Salud Global Barcelona. Resistencia a los antibióticos: cuando el problema va más allá de las patentes [Internet]. 2017. Available from:https://www.isglobal.org/documents/10179/5808947/Informe+Resistencia+Antimicrobiana+ES/a74ac65e-7d4b-4f18-8c3b-ec86778034ee[Accessed: 06 June 2019]

Written By

Lilia M. Mancilla-Becerra, Teresa Lías-Macías, Cristina L. Ramírez-Jiménez and Jeannette Barba León

Submitted: March 28th, 2019 Reviewed: July 24th, 2019 Published: September 4th, 2019