1. Introduction
Antimicrobial resistance is generally described as the ability of microorganisms to survive in the presence of antimicrobial agents at concentrations typically sufficient to inhibit or kill them. It can further be explained as a multifactorial process that from a bacterial standpoint depicts an evolution in action, associated with continuous exposure to antibiotics and microbial genome plasticity
[1][2][3]. Consequently, this evolution has led to the emergence of multidrug-resistant (MDR) and extremely drug-resistant (XDR)
Enterobacteriaceae strains that are resistant to almost all antibiotics currently in use
[4]. The spread of MDR
Klebsiella pneumoniae is mostly associated with clinical settings where it is facilitated by factors such as closed space and spread between patients who are typically immunocompromised through what is termed, hospital-acquired infections. The increasing global climatic variations and the interconnectedness of the world have brought an increase in the community spread of these multidrug-resistant pathogens.
Klebsiella pneumoniae has been recognized as one of the multidrug-resistant pathogens of global concern and it is part of the ESKAPE (
Enterococcus faecium,
Staphylococcus aureus,
Klebsiella pneumoniae,
Acinetobacter baumannii,
Pseudomonas aeruginosa, and
Enterobacter species) organisms
[5]. The
Klebsiella genus is characterized by its Gram-negative, facultatively anaerobic, mostly capsulated, and non-motile bacteria that belong to the
Enterobacteriaceae family
[2][6].
Klebsiella pneumoniae is commonly associated with nosocomial infections such as urinary and respiratory tract infections as well as bloodstream infections
[7][8]. It is a significant opportunistic pathogen mostly affecting individuals with weakened immune systems, such as those with cancer, diabetes, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) as well as infants and the elderly
[9]. This organism is particularly common in hospitals, where it can be spread from patient to patient through contact with contaminated surfaces or equipment such as catheters or ventilators
[10]. Owing to its prevalence in hospital settings,
K. pneumoniae is constantly exposed to antibiotics, in intensive care units (ICU)
[11], maternity wards, and surgical theatres, thus subjecting it to constant selective pressure which leads to the occurrence of multiple genetic mechanisms conferring resistance to antibiotics
[12].
On the other hand, environmental isolates of
K. pneumoniae are often susceptible to antibiotics
[13]. In non-clinical habitats,
K. pneumoniae is ubiquitous in soil, surface water sources, plants, and the gastrointestinal tract of mammals, and environmental
K. pneumoniae is not typically associated with human infections
[13][14][15][16]. There is a major public health concern regarding the potential spread of community-associated MDR
K. pneumoniae due to the rise in the number of reported cases. One of the possible considerations is that since
K. pneumoniae is widespread in soil and water, the environment poses a potential reservoir for the infection of human beings and animals with these bacteria
[13]. The emerging evidence suggests that some of the environmental isolates are identical to clinical isolates regarding their biochemical characteristics and virulence properties
[14]. Global climate change is having a significant impact on the evolution of resistance in regular environmental
Klebsiella species that are typically not pathogenic. Climatic variations lead to changes in temperature, precipitation, and other environmental factors that are creating new selective pressures for bacteria. These selective pressures are driving the evolution of new strains of
Klebsiella that are resistant to antibiotics
[17][18]. For example, intense precipitations will lead to increased runoff and inevitably higher levels of pollution in our surface and groundwater sources. Some of the pollutants that include antibiotics and heavy metals can then induce the expression of antibiotic-resistance genes and facilitate bacterial mutagenesis
[18].
2. Klebsiella pneumoniae in Clinical Settings
Klebsiella pneumoniae is a notorious hospital-associated pathogen responsible for most bloodstream infections, urinary tract infections, pneumonia, and meningitis
[7][19]. It is reported to spread from person to person in clinical settings, although not all carriers of
K. pneumoniae develop the disease state
[13]. Owing to its hospital association,
K. pneumoniae is the dominant carbapenem-resistant
Enterobacteriaceae globally
[20], as well as the major extended-spectrum beta-lactamases (ESBL)-carrying pathogen responsible for nosocomial infections
[2]. In a study conducted by Buys et al.
[21] in a South African hospital, 83% of bloodstream infections were caused by ESBL-producing
K. pneumoniae isolates with a 26% mortality rate. The study also revealed that 95% of the infections were hospital-acquired while 5% were community-acquired. Exposure to cephalosporins, pediatric ICU admission, and prolonged hospitalization were named as risk factors for these infections.
Klebsiella pneumoniae possesses the ability to adhere to hospital equipment and this is thought to be what facilitates its distribution. All ESBL-producing isolates were resistant to ampicillin, cefotaxime, ceftazidime, and cefepime, but least resistant to amikacin and ciprofloxacin. Non-ESBL-producing isolates were, however, only 100% resistant to ampicillin and sensitive to the aforementioned antibiotics
[21]. Major concerns are raised with the emergence and proliferation of carbapenem-resistant
K. pneumoniae (CRKP) particularly because carbapenems are often administered as antibiotics of last resort
[22]. Carbapenem-resistant Enterobacteriaceae (CRE) strains constitute a special challenge because they are resistant to β-lactams and there are few effective treatments for CRE-induced illnesses
[22]. Taking this into consideration, the prevalence of risk factors for CRKP in hospitalized patients has been evaluated. Risk factors identified include previous hospitalization and prolonged stay in intensive care units (ICU).
[23], previous use of carbapenems and β-lactam inhibitors
[24], as well as subjection of patients to invasive procedures such as central venous catheterization
[25][26]. Additionally, long-term care facilities are thought to be the major role players in the spread of MDR
K. pneumoniae between clinical settings and community settings
[27]. Al-Zalaban et al.
[28] conducted a study that reported on the prevalence and trends of
Klebsiella pneumoniae antibiotic resistance in King Fahad Hospital in Medina from 2014 until 2018. Out of a total of 15,708 isolates, 38.4% and 46.1% were resistant to imipenem and meropenem, respectively; third and fourth cephalosporins displayed resistance ranging from 57.5% to 77.8%. The research highlighted an increased resistance to beta-lactams as well as the emergence of resistance to carbapenems and alternative last-resort antibiotics such as colistin and tigecycline.
The development of antibiotic resistance in K. pneumoniae is a serious problem. Several measures can be put in place to treat infections or preventive measures for surveillance and to curb the spread of drug-resistant bacteria such as Klebsiella species. By working together, we can help to protect ourselves from this and other infections caused by antibiotic-resistant bacterial species.
3. Klebsiella pneumoniae in the Environment
Klebsiella pneumoniae is also found ubiquitous in non-clinical habitats such as the mucosal surface of humans and animals, vegetation, soil, and surface waters
[29]. There is growing evidence that some of the environmental isolates of
K. pneumoniae present identical genetic and phenotypic features to their clinical counterparts
[15][30]. Although human pathogenic strains of
K. pneumoniae are mainly associated with clinical settings, there is a noticeable shift in virulence oozing into the environmental isolates thus raising concerns about the factors driving this distribution of resistance factors. There is a growing concern that some strains of
K. pneumoniae may be acquiring antibiotic-resistance genes from other bacteria in the environment
[31]. In addition, the concurrent evolution and antimicrobial-resistant determinants acquisition by
K. pneumoniae in the clinical settings and the environment has led to environmental habitats being considered as a possible reservoir for hyper-resistant
K. pneumoniae [32]. The genetic determinants that specify resistance to different antimicrobial drugs are spread in strongly selective environments, with the presence of persistent antimicrobial residues in ecosystems significantly contributing to environmental pollution with resistant genes
[33]. It is thought that environmental bacteria that generate and release antibacterial elements to influence microbial populations with which they compete for nutrients are a source of antimicrobial-resistant genes
[34]. Additionally, Booth et al.
[35] suggest that a high concentration of antimicrobials in the environment exists because of their stability.
Several studies have been conducted to understand the genetic similarities between the environmental and clinical
K. pneumoniae isolates
[15][30][32]. The environmental reservoirs of
K. pneumoniae associated with human infections are not well known. In a study by Podschun et al.
[14], they used hemagglutination assay and serotyped
K. pneumoniae isolates obtained from surface water (from various streams, lakes, and baltic sea in Germany) by the capsular swelling method to check for the similarity of their virulence factors to those of clinical isolates. Their study determined that
K. pneumoniae isolates obtained from surface water resembled clinical isolates in their expression of virulence factors, although their relevance to public health could not be established. Similarly, Struve and Krogfelt
[15] also compared the virulence of environmental
K. pneumoniae isolates from surface waters in Denmark to clinical isolates. Struve and Krogfelt
[15] utilised counter-current immunoelectrophoresis for capsule typing, dot-blotting using radio-labelled DNA for the detection of adhesin genes and hemagglutination assays to test for the expression of fimbriae. Their study revealed that environmental isolates were as virulent as clinical strains as per their detection methods. Recently, Rocha et al.
[30] conducted a comparative genomics study between environmental and clinically associated
K. pneumoniae strains of distinct geographical locations. They found environmental strains that were closely related to those found in clinical settings.
Multidrug-resistant
K. pneumoniae has previously been isolated from raw wastewater
[6] and sewage plants
[36]. This incidence reveals two scenarios, which include the exposure of clinical waste to the environment and possible active dissemination of antibiotic-resistance genes to aquatic environments and from there to agricultural settings and eventually to humans. In a study by Salifu et al.
[37], ESBL-producing MDR
K. pneumoniae has also been isolated in wastewater from a public healthcare facility in Nigeria, further justifying the assumption that water sources play a major role in the dissemination of disease-causing MDR
K. pneumoniae in the environment. Additionally, Devarajan et al.
[38] investigated the incidence of antibiotic resistance genes (ARGs) in a tropical river in Congo receiving hospital and urban wastewater. Although their study targeted the detection of
E. coli and
Pseudomonas spp genes, it still supported the notion that water sources could act as reservoirs for ARGs of
K. pneumoniae and other
Enterobacteriaceae species as their study revealed the presence of these genes in the said river.
Limited studies recognise
K. pneumoniae as a food-borne pathogen that can utilize plants as reservoirs and find its way back to humans and animals
[39]. Thus, various vegetables and food commodities have been identified as possibly harbouring this pathogen and these include carrots, spinach, cucumber, and tomatoes among others
[40]. Animals are no exception, an extended-spectrum beta-lactamase (ESBL) blaCTX-M-IS, which is most prevalent in
K. pneumoniae has since been found in humans. This inherently implies the possible transmission of
K. pneumoniae from animals to humans because this ESBL is a zoonotic agent commonly applicable to animals
[41]. A study in Germany identified multiple MDR-ESBL strains from companion animals including cats, dogs, and horses. The
K. pneumoniae isolates from these animals were found to share the same characteristics as those from humans with regard to the presence of plasmid-encoded quinolone resistance genes, ESBLs, and carbapenemase OXA-48
[41]. This incidence of common
K. pneumoniae genes between animals and humans is thought to be evidence of the transmission of MDR genes between humans and animals.
Overall, studies reporting on environment-acquired
K. pneumoniae infections are based on a single event or case series. Currently, there is limited research on the estimation of incidences of community-acquired multidrug-resistant
K. pneumoniae. Controversies arise when one must determine the significance of each reservoir in the spread of MDR
K. pneumoniae. It can be argued that environmental reservoirs such as contaminated surface water sources can serve as primary sources of transmission and dissemination of multidrug-resistant bacterial strains. In contrast, the prolonged stay in hospital or frequent use of antibiotics by patients are also drivers of transmission. There is a need for understanding the interplay between the clinical and environmental reservoirs for the designing of effective prevention and control strategies
[42][43][44]. Research is currently exploring the use of various techniques for the detection and identification of multidrug-resistant bacteria including
K. pneumoniae, to unravel the complexities of the primary sources of dissemination
[42]. In the developing world, details concerning the methods for full characterization of the bacterial isolates are limited, which is an important limitation for the reporting of multidrug-resistant microbial strains.