Effah et al.

Ann Clin Microbiol Antimicrob

https://doi.org/10.1186/s12941-019-0343-8
(2020) 19:1
Annals of Clinical Microbiology
and Antimicrobials

REVIEW Open Access

Klebsiella pneumoniae: an increasing threat

to public health
Clement Yaw Effah1, Tongwen Sun2, Shaohua Liu2 and Yongjun Wu1*

Abstract
Objectives: This review fills the paucity of information on K. pneumoniae as a nosocomial pathogen by providing
pooled data on epidemiological risk factors, resistant trends and profiles and resistant and virulent genes of this
organism in Asia.
Methods: Exhaustive search was conducted using PubMed, Web of Science, and Google scholar for most studies
addressing the prevalence, risk factors, drug resistant-mediated genes and/or virulent factors of K. pneumoniae in Asia.
Data extracted for meta-analysis were analyzed using comprehensive meta-analysis version 3. Trends data for the
isolation rate and resistance rates were entered into Excel spread sheet and the results were presented in graphs.
Results: The prevalence rate of drug resistance in K. pneumoniae were; amikacin (40.8%) [95% CI 31.9–50.4], aztre-
onam (73.3%) [95% CI 59.9–83.4], ceftazidime (75.7%) [95% CI 65.4–83.6], ciprofloxacin (59.8%) [95% CI 48.6–70.1],
colistin (2.9%) [95% CI 1.8–4.4], cefotaxime (79.2%) [95% CI 68.0–87.2], cefepime (72.6) [95% CI 57.7–83.8] and imipe-
nem (65.6%) [95% CI 30.8–89.0]. TEM (39.5%) [95% CI 15.4–70.1], SHV-11 (41.8%) [95% CI 16.2–72.6] and KPC-2 (14.6%)
[95% CI 6.0–31.4] were some of the resistance mediated genes observed in this study. The most virulent factors
utilized by K. pneumoniae are; hypermucoviscous phenotype and mucoviscosity-related genes, genes for biosynthesis
of lipopolysaccharide, iron uptake and transport genes and finally, adhesive genes.
Conclusion: It can be concluded that, antimicrobial resistant in K. pneumoniae is a clear and present danger in Asia
which needs strong surveillance to curb this menace. It is very important for public healthcare departments to moni-
tor and report changes in antimicrobial-resistant isolates.
Keywords: Klebsiella pneumoniae, Antibiotic resistance profiles, Resistant genes, Virulent genes, Risk factors, Asia

Background merely does not have enough new medicines to maintain

The problem of antibiotic resistance has become an alba- pace with drug-resistant bacterial infections [1]. Kleb-
tross on the neck of clinicians, veterinarians and other siella pneumoniae is one of such clinically significant
infection control agents in their quest to treat and pre- organisms that have acquired much public health con-
vent infections caused by microorganisms that were cern. Klebsiella pneumoniae is a significant Enterobacte-
once thought to have been eradicated with antimicrobi- riaceae considered as one of the opportunistic pathogens
als. These organisms or superbugs are returning in new causing broad spectra of diseases and showing increas-
forms resistant to almost all clinically important anti- ingly frequent acquisition of resistance to antibiotics.
microbials. Unfortunately, the pharmaceutical pipeline According to Shiri et al. [2], this organism accounts
for about one-third of all Gram-negative infections such
as urinary tract infections, cystitis, pneumonia, surgical
*Correspondence: [email protected] wound infections, endocarditis and septicemia. It also
1
College of Public Health, Zhengzhou University, Zhengzhou 450001, causes necrotizing pneumonia, pyogenic liver abscesses
China
and endogenous endophthalmitis [3]. High mortality
Full list of author information is available at the end of the article

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Effah et al. Ann Clin Microbiol Antimicrob (2020) 19:1 Page 2 of 9

rates, extended hospitalization, coupled with high cost profiles of K. pneumoniae, resistance-mediated genes,
are often associated with infections caused by this organ- and virulent genes.
ism [4]. The drastic rise in the incidence of multidrug-
resistant (MDR) and extremely drug-resistant (XDR) Statistical analysis
pathogens belonging to the Enterobacteriaceae group is The comprehensive Meta-analysis software version 3
a major economic problem as these pathogens are preva- was used to analyze the data. Because of the heterogene-
lent natural residents of human and animal microbiome. ity among studies, random effects models was used and
Despites its numerous clinical importance, there is still tested with the Cochrane Q test. For trends in antimicro-
paucity of information on K. pneumoniae. bial resistance and isolation rates, data were entered into
This review was therefore designed to determine the excel spread sheet and graphs were plotted based on the
antibiotic-resistant profiles of Klebsiella pneumonia as available data.
a nosocomial pathogen and focuses on some differences
between classical and non-classical subtypes, antimi- Results
crobial resistance-mediated genes, some virulent factors From the literature search, a total of 143 studies or arti-
of this organism, and some epidemiological risk factors cles were screened from PubMed, Web of Science, and
through a systematic review and meta-analysis. This Google scholar. After the removal of duplicates and
review also looked at some trends in the isolation and evaluation of titles and abstract, 64 full text scripts were
resistance rates of K. pneumoniae using China as the tar- evaluated. After secondary full text evaluation, 20 stud-
get country. ies or articles (Table 1) addressing the prevalence, drug
resistant-mediated genes and/or virulent factors in K.
Methods pneumoniae in Asia were selected for the final meta-anal-
Search strategies ysis. From Fig. 1, it can be seen that there is an increas-
Exhaustive search was conducted using PubMed, Web ing trend in the isolation rate of K. pneumoniae (from
of Science, and Google scholar for most studies address- 9.8% in 2005 to 13.3% in 2012) in China. Interestingly, the
ing the prevalence and/or the molecular epidemiology of isolation rate decreased in 2007 but increased in the pre-
drug resistant strains of K. pneumoniae in some selected ceding years. In contrast, the resistant trends of K. pneu-
countries in Asia. The search filtered articles among the moniae in China was not congruent to the isolation rate
years of 2005 to 2019. The applied keywords included as there were decreasing resistance trends from 2005 to
Klebsiella pneumoniae, antibiotic resistance, resistant 2014. Imipenem recorded the lowest resistance rate but
genes, virulent genes, epidemiological risk factors and its resistance trends tend to increase steadily from 2005
Asia. to 2014. From Table 2, it can be seen that K. pneumo-
niae has a great resistance rate to most of the commonly
used antimicrobials. Cefotaxime recorded the highest
Inclusion and exclusion criteria
prevalence (79.2%) followed by aztreonam (73.3%) and
The original published articles on the prevalence of
cefepime (72.6%). Colistin recorded the lowest resistance
drug resistant strains of K. pneumoniae from hospital-
rate of 2.9%. The individual studies as seen in Table 3,
acquired infections in some selected countries in Asia
details the number of isolates which were resistant to
were considered. Before an article will be considered use-
these antimicrobials. These numbers in terms of percent-
ful to this study, its antibiotic susceptibility testing should
age resistance to the various antimicrobials ranges from
use reference standard methods and recommendations
‘’no isolate’’ (0%) to ‘’all isolates’’ (100%). From Table 4,
by the Clinical and Laboratory Standards Institute (CLSI)
it can be seen that K. pneumoniae harbor some genes
for drug susceptibility testing of K. pneumoniae against
that confers most of its resistance properties. In this
most commonly used antimicrobial agents. Due to the
review, the selected resistant-mediated genes were in the
following reasons, some studies were excluded from this
decreasing order of CTX-M-1 (41.9%), SHV-11 (41.8%),
studies; articles not following CLSI recommended drug
TEM (39.5%), CTX-M-15 (35.3%), KPC-2 (14.6%) and
susceptibility testing methods, case reports, meta analy-
NDM-1 (6.7%). The genes, Mag, Armp, ArmpA2, allS
ses or systematic reviews, letters to editor, review arti-
(hypermucoviscous phenotype and mucoviscosity-
cles, non-English, and duplicate publication.
related genes); wabG, uge, wcaG (biosynthesis of lipopol-
ysaccharide genes); iutA, icuA, iroN, iroB, ybtA, irp2, kfu,
Data extraction entB (iron uptake and transport genes) and Cf29a, fimH,
For the meta-analysis, information extracted from each mrkD (Adhesion genes) are all some virulent factors that
article were authors’ name, the publication time, year of are used by K. pneumoniae to cause various harm or
study, number of samples, antimicrobial drug resistant infections (Table 5).
Effah et al. Ann Clin Microbiol Antimicrob (2020) 19:1 Page 3 of 9

Table 1 Details of articles included in the meta-analysis

Ref nos. Refs Publication year Enrolment time Province/country No. of K.P Type of K.P strain used (n)
isolates (N)

[30] Liu et al. 2019 2013–2017 Anhui/China 106 CRKP (106)

[39] Tian et al. 2018 2016–2017 Shanghai/China 170 CRKP (170)
[40] Zhao et al. 2019 2015–2016 Anhui/China 63 CRKP (63)
[41] Meng et al. 2019 2014–2015 Central China 142 CRKP (142)
[42] Kim et al. 2019 2016–2017 South Korea 579 KP (579)
[43] Xu et al. 2019 2013–2015 Dalian/China 30 ESBL-P KP (30)
[44] Guo et al. 2017 2009–2014 Henan/China 8203 KP (8203)
[29] Dong et al. 2018 2011–2014 Beijing/China 146 CRKP (52)
[45] Cha et al. 2018 2010–2014 Seoul/Korea 260 ESBL:AmpC-KP (54)
[46] Alizade et al. 2018 2014–2015 Kerman/Iran 103 K.P (103)
[47] Lu et al. 2018 2015–2016 Sichuan/China 112 HvCoR-KP (5)
[48] van Dorp et al. 2019 2016–2017 Beijing/China 100 CRKp (100)
[49] Shanker et al. 2018 2015 India HvKP
[50] Huang et al. 2018 2012–2014 Taipei/Taiwan China 63 HvCR-KP (63)
[51] Abrar et al. 2019 2014–2017 Lahore/Pakistan 124 KP (124)
[52] Mitra et al. 2019 2012–2014 Kolkata/India 55 KP (55)
[53] Gautam et al. 2019 2014–2016 New Delhi, Chandigarh, 304 ESBL-KP and Non-ESBL-KP (304)
Vellore, Puducherry/India
[54] Mansury et al. 2016 2012–2013 Shiraz/Iran 38 ESBL KP (38)
[55] Heidary et al. 2017 2013–2014 Tehran/Iran 117 K.P (117)
[56] Ma et al. 2015 2012–2014 Taiwan China 760 CnSKP (760)
HvCoR-KP, hypervirulent colistin-resistant Klebsiella pneumonia; CRKP, carbapenem-resistant Klebsiella pneumoniae; hvKP, hypervirulent Klebsiella pneumoniae;
HvCR-KP, hypervirulent carbapenem-resistant Klebsiella pneumoniae; CnSKP, carbapenem non-susceptible Klebsiella pneumoniae; K.P, Klebsiella pneumoniae; ESBL-P KP,
extended spectrum β-lactamase producing Klebsiella pneumoniae

Klebsiella pneumoniae: the classical and other subtypes with hypermucoviscosity, (ii) virulent factors such as; K1,
Klebsiella pneumoniae can be broadly classified into K2, K20 capsular types, rmpA and rmpA2 mucoid-reg-
two subtypes; classical Klebsiella pneumoniae (cKp) and ulator genes [10]. The horizontal transfer of these plas-
non-classical Klebsiella pneumoniae (ncKp). The anti- mids and transposons has led to the multidrug resistance
microbial resistance profiles and the virulence profiles (MDR) and the extremely drug resistance (XDR) nature
of these strains vary with the former tagged as notori- of most of these subtypes. The high prevalence rate of
ous [3, 5]. Notwithstanding, several clones of these ncKp MDR and XDR K. pneumoniae subtypes reflects a mul-
have also been implicated in causing severe and difficult tifactorial dissemination processes that include but not
to threat infections due to their continuous mutation limited to: the spread of high risk global multi-resistant
and the acquisition of plasmids and transposons which genetic lineage [11]; acquisition of successful multi-
carries resistant and virulent genes. This has led to the resistant plasmids; and acquisition of resistant genes
emergences of strains such as hypervirulent Klebsiella located on successful transposons. Klebsiella is a major
pneumoniae (hvKp) or hypermucoviscous Klebsiella source of carbapenem resistance worldwide by the dis-
pneumoniae (HMKP). This strain was first identified in semination of its plasmids which is facilitated by high
Eastern part of Asia and has since spread worldwide [6]. genetic transfer (HGT) to other species. Spread of these
This subtype is non-resistant to most of the commonly extended-spectrum β-lactamase (ESBL) and Carbapene-
used antimicrobials such as colistin and carbapenems. mase-encoding plasmids poses a major threat, as acquisi-
But the recent reports of carbapenem-resistant hvKp tion of these plasmids turn bacteria into MDR and XDR.
strains which belong to the sequence types 11 (ST11) [7], In China, the most dominant MDR KPC-producing
ST25 and ST65 [8] poses a major clinical concern. clone is the ST11. Once the ­blaKPC-2 gene is introduces
HvKp strains can cause serious infections in both into a certain location, especially in a hospital setup,
immunocompetent, diseased and healthy young individ- under antibiotic selection pressure, further dissemination
uals [9]. This hvKp is known to habour (i) sidephore; pre- of this gene may occur which may lead to MDR and XDR
dominant of which is aerobactin which is concomitant strains. Hypermucoviscous K. pneumoniae (HMKP)
Effah et al. Ann Clin Microbiol Antimicrob (2020) 19:1 Page 4 of 9

a Isolaon rate (%) of K. pneumoniae

2012 13.3

2011 11.8

2010 11.6

2009 10.4

2008 9.5

2007 8.4

2006 10.2

2005 9.8
0 2 4 6 8 10 12 14

b
70
Resistance rate (%) of K. pneumoniae

60

50

40

30

20

10

0
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

Amikacin Gentamycin Cefazolin Imipenem Ciprofloxacin Cefotaxime

Fig. 1 Trends of resistance and isolation rate of K. pneumoniae in China. a The isolation rate of K. pneumoniae in China (Data extracted from CHINET
surveillance system 2015 which collected data from outpatients and inpatients in 19 big hospitals from 14 provinces. b The resistance rate of K.
pneumoniae commonly used antimicrobials in China (Data extracted from CHINET surveillance system 2015 which collected data from outpatients
and inpatients in 19 big hospitals from 14 provinces for a period of 10-year [57]

strain types which are sporadically distributed in Asia specific although there can be some form of interconti-
and the Middle East are the NDM-producing isolates [12, nental similarities.
13]. Liu et al. [14], had reported the first outbreak of CR- Some epidemiological risk factors associated with K.
HMKP strains which harbored ­blaNDM-1 gene, shared the pneumoniae infections may include socio-demographic
same pulsotypes (PT) and belong to the same Sequence factors such as gender, age, hospitalization status, source
types (ST). of domestic water (river, rain, well, bottled, piped,
boiled), companion animals (cats, dogs, birds), livestock
Epidemiological risk factors associated with K. pneumoniae (chicken, ducks, pigs, cow or water buffalo), malnutrition,
colonization and infections co-morbidity and the use and misuse of detergents and
It is believed that several factors can cause the coloni- antiseptics. In Asia, it has been reported that exposure
zation of K. pneumoniae in a community as well as in a to health care facility and history of previous overseas
hospital setting. The cases of K. pneumoniae infections hospitalization (OR: 33.667; 95% CI 4.539–259.700) is
vary from country to country. In a study by Ling et al. one of the notifiable risk factors associated with K. pneu-
[15], it was reported that, Chinese people had a coloni- moniae colonization but this had been disagreed by Ling
zation rate of 66.0% compared to Malay (14.3%), Indian et al. [15], who iterated that persons with no history of
(7.9%) and others nationals (11.8%). This is an indication overseas travel and overseas hospitalization are also at
that infections caused by K. pneumoniae can be locality risk of K. pneumoniae colonization and infections, hence,
Effah et al. Ann Clin Microbiol Antimicrob (2020) 19:1 Page 5 of 9

Table 2 Overall resistance rate of Klebsiella pneumoniae to various antimicrobials

Subgroups No. of events/studies Prevalence of drug resistance, Heterogeneity test
% (CI)
I2 (%) p value

Overall resistant to amikacin 11 40.8 (31.9–50.4) 93.7 < 0.001

Overall resistant to aztreonam 9 73.3 (59.9–83.4) 97.4 < 0.001
Overall resistant to ceftazidime 10 75.7 (65.4–83.6) 90.5 < 0.001
Overall resistant to ciprpfloxacin 11 59.8 (48.6–70.1) 96.4 < 0.001
Overall resistant to colistin 5 2.9 (1.8–4.4) 0.0 0.5250
Overall resistant to cefotaxime 8 79.2 (68.0–87.2) 93.8 < 0.001
Overall resistant to cefepime 8 72.6 (57.7–83.8) 96.9 < 0.001
Overall resistant to gentamicin 9 58 (49.2–66.3) 89.7 < 0.001
Overall resistant to imipenem 10 65.6 (30.8–89.0) 99.6 < 0.001
Overall resistant to levofloxacin 6 54.1 (36.0–71.2) 92.7 < 0.001
Overall resistant to meropenem 11 62.7 (31.1–86.2) 99.5 < 0.001
Overall resistant to trimethoprim_sulfameth- 7 58.2 (35.5–77.9) 98.8 < 0.001
oxazole
CI, confidence interval; n, number of events (drug resistance); N, total number of Klebsiella pneumoniae from the included studies

Table 3 The prevalence of antimicrobial drug resistance among Klebsiella pneumoniae isolates according to individual
studies
References N AMK ATM CAZ CIP COL CTX FEP GEN IPM LVX MEM SXT

Liu et al. [30] 106 33 49 106 49 0 – 92 33 106 49 106 16

Tian et al. [39] 170 99 161 170 107 5 170 – 105 163 105 162 139
Zhao et al. [40] 63 48 61 62 59 – – 58 50 62 56 63 –
Meng et al. [41] 142 45 89 78 67 – – 81 69 – 60 – 42
Kim et al. [42] 579 – 139 – 141 – – – – – – – 131
Xu et al. [43] 30 16 – 29 26 – 28 24 – – 23 – –
Guo et al. [44] 8203 2568 4323 4077 4184 – 6005 2887 4651 468 – 476 5357
Dong et al. [29] 52 3 47 52 8 0 – 51 37 46 4 49 47
Cha et al. [45] 54 – – 53 51 – 52 34 – 13 – 7 –
Mitra et al. [52] 55 45 50 – 52 – 53 – 52 – – 29 49
Gautam et al. [53] 304 109 – 159 115 8 157 155 – 103 – 120 –
Mansury et al. [54] 38 6 – – – – 19 – 16 6 – 4 –
Heidary et al. [55] 117 40 75 73 – 5 77 – 51 28 – 28 –
Ma et al. [56] 760 – – – – – – – – 568 – 519 –
Sum 3012 4994 4859 4859 18 6561 3382 5064 1563 297 1563 5781
Rate (%) 40.8 73.3 75.7 59.8 2.9 79.2 72.6 58 65.6 54.1 62.7 58.2
AMK, amikacin; ATM, aztreonam; CAZ, ceftazidime; CIP, ciprofloxacin; COL, colistin; CTX, cefotaxime; FEP, cefepime; GEN, gentamicin; IPM, imipenem; LVX, levofloxacin;
MEM, meropenem; SXT, trimethoprim-sulfamethoxazole

suggesting that K. pneumoniae is a persistent organism in the stool, 19% in the pharynx, and 42% on the hands
our community setting. [3]. The higher rates of colonization are primarily
Also, admission to an ICU facility (OR: 11.899; 95% related to the increasing use of antibiotics [3, 17, 18].
CI 4.986–28.399), antimicrobial exposure; particularly The increase in colonization rate of K. pneumoniae as
carbapenems and fluoroquinolones [14, 16], hematol- observed in these clinical samples is of epidemiological
ogy patients and patients with immunodeficiency are important because, Klebsiella nosocomial infection was
all high risk factors for K. pneumoniae colonization four times higher in stool carriers compared with non-
and infections. Carrier levels in hospitalized patients carriers [19]. In a study in Taiwan, antibiotic use (e.g.
are significantly higher, with reported rates of 77% in ampicillin or amoxicillin) within the last 30 days was
Effah et al. Ann Clin Microbiol Antimicrob (2020) 19:1 Page 6 of 9

Table 4 The prevalence of some resistant-mediated genes among Klebsiella pneumoniae isolates
Subgroups No. of events/ Prevalence of resistant n/N Heterogeneity Test
studies gene
% (CI) I2 (%) P-value

Overall prevalence of TEM genes 5 39.5 (15.4–70.1) 241/484 96.6 < 0.001
Overall prevalence of SHV-11 genes 7 41.8 (16.2–72.6) 350/1117 98.1 < 0.001
Overall prevalence of CTX-M-1 5 41.9 (21.6–65.4) 229/826 95.7 < 0.001
Genes
Overall prevalence of CTX-M-15 genes 5 35.3 (17.1–58.9) 153/548 95.0 < 0.001
Overall prevalence of KPC-2 genes 6 14.6 (6.0–31.4) 301/2031 97.1 < 0.001
Overall prevalence of NDM-1 genes 5 6.7 (1.7–23.4) 108/1452 95.6 < 0.001
CI, confidence interval; n, number of events (resistance-mediated genes); N, total number of Klebsiella pneumoniae from the included studies

Table 5 Some selected virulent factors encoded predispose individuals to K. pneumoniae colonization
by different strains of Klebsiella pneumoniae and infections.
Virulence factors References
Discussions
Hypermucoviscous phenotype and mucoviscosity- [30, 42, 47–50] Klebsiella pneumoniae is rapidly becoming known for
related genes
magA its resistance properties to most of the last-line antibi-
rmpA otics that are usually used. It is especially problematic
rmpA2 in hospitals, where it causes a range of acute infections.
allS
The increasing trends in the isolation rate of K. pneumo-
Biosynthesis of lipopolysaccharide [42]
wabG niae is of much concern. Economically developed areas
uge such as China have a more advanced medical system
wcaG which may increase the chance of exposure to antibiot-
Iron uptake and transport [30, 42, 47–50] ics and this will increase the possibility of bacterial resist-
iutA
icuA ance. In China, the higher population density may also
iroN have increased the isolation rate among the population.
iroB In this review, although there is an increasing trend in
ybtA
irp2 the isolation rate, their resistance rates were not in tan-
kfu dem as this was evident in the decreasing trends over the
entB years. Although, imipenem and meropenem have shown
Adhesion [42, 47, 49, 50] good activity against Enterobacteriaceae [22], the situa-
Cf29a
fimH
tion observed in this review reiterates the public health
mrkD implications of K. pneumoniae. In Fig. 1, there is a steady
increase in resistance of imipenem over the years and
this can be as a result of their increasing use among the
associated with an increased risk of liver abscess [20], populace. Generally, the decreasing resistant rate of K.
suggesting that an increasing exposure to antimicrobi- pneumoniae to most of the antimicrobials in China can
als and the last period of antimicrobial administration be attributed to; (i) the enforcement of taking various
is a major risk factor for K. pneumoniae colonization actions for prevention of bacterial infection such as sepa-
and infection. rating the pathogen carriers and enforcement of hand
In a study by Saleem et al. [21], it was reported that sanitization of medical professionals by the government
some risk factors associated with K. pneumoniae sepsis through the Nosocomial Infection Control Committee,
and mortality in a neonate intensive care units in Paki- (ii) the restriction and control of the use of antibiotics by
stan were; extremely low birth weight (p = 0.01, OR 6.1, the Chinese Ministry of Hygiene, which has implemented
95% CI 0.8–44.4), being a male (p = 0.06, OR 9.2, 95% guidelines for the rational use of antibiotics since 2006.
CI 1.3–66.9), severe thrombocytopenia (p = 0.07, OR The global emergence and spread of genes of anti-
3.9, 95% CI 1.2–13.0), and failure to achieve microbio- microbial resistance such as ESBL and carbapenemase
logical clearance (p < 0.001, OR 19.6, 95% CI 4.0–98.0). genes in K. pneumoniae isolates present a significant
The above listed factors can in combination or singly danger to public health. This is because carbapenems
Effah et al. Ann Clin Microbiol Antimicrob (2020) 19:1 Page 7 of 9

have long been deemed as the last therapeutic resort or outer membrane, by binding to the negatively charged
option of antibiotics used to treat diseases and infections lipopolysaccharides (LPS) which leads to cell lysis.
caused by multidrug-resistant gram-negative bacteria. Undoubtedly, the presence of resistance determinants
The rapid global emergence of K. pneumoniae strains, will allow K. pneumoniae strains to survive the barrage
resistant to almost all β-lactams, including carbapenems of antibiotics used in treatment of hospital infections.
as seen in this study shows the organism’s ability to react According to a report by Dong et al. [29], K. pneumo-
quickly to selective environmental pressure modifica- niae utilize an array of virulence factors to colonize and
tions. The extensive use and misuse of carbapenems is propagate in a host cell. These include at least (a) sur-
one of the attributable reasons that has led to the evolu- face antigen, particularly capsular polysaccharide (CPS,
tion of plasmid-mediated carbapenemases, i.e. enzymes K antigen); (b) siderophores responsible for binding
that hydrolyze all β-lactams including the last-line car- ferric iron secreted by the host’s iron-binding proteins;
bapenems [23]. Different resistance-mediated genes and (c) adherence variables responsible for binding to
mediate antimicrobial drug resistance in K. pneumoniae. host cell surfaces, such as fimbriae type 1 and type 3,
The high rate of resistance to carbapenems (imipenem and non-fimbrial adherence proteins.
and meropenem) observed in this study can be partly Hypermucoviscous phenotype and mucoviscosity-
be attributed to the presence of some carbapenemase related genes, genes for biosynthesis of lipopolysac-
resistant-mediated genes such as b ­ laOXA. bla NDM and charide, iron uptake and transport genes and Adhesive
­blaKPC realized in this study. In K. pneumoniae, the b
­ laKPC genes are all virulent factors that are employed by
genes which confers reduced susceptibility or resistance K. pneumoniae strains in pathogenesis. Iron is a key
to nearly all β-lactam antibiotics by various enterobac- component for K. pneumoniae’s survival. As free iron
teria are mostly carried on plasmids. The detection of is scarce in host plasma, K. Pneumoniae acquires
carbapenemases is important from an epidemiological iron predominantly through the secretion of sidero-
perspective as they are plasmid-mediated and may be phores; molecules with a greater iron affinity than the
transferred horizontally between different bacterial spe- host transport proteins [30]. Among the siderophores
cies [24]. Dissemination of resistant determinants have secreted by K. pneumoniae, aerobactin is considers
been recognized as a major challenge in the treatment the most important virulent factor [31, 32], as it can
of bacterial infections worldwide [25]. Also, resistance of cause severe infection by assisting in the transport of
K. pneumoniae to cephalosporin (ceftazidime, cefepime the organism from the intestinal tract to various tissues
and cefotaxime) as seen in this study can also be partly and also the multiplication of these organisms in the
be attributed to the KPC gene because the KPC enzyme tissues.
hydrolyzes extended-spectrum cephalosporins. This can The rmpA and rmpA2 are Plasmid-carried genes,
therefore be used to identify KPC-mediated genes that which contribute to the enhancement of capsular pro-
are resistant to these cephalosporins (e.g. ceftazidime, duction. Also, the MagA gene is an important gene
ceftriaxone, and cefotaxime). used by K. pneumoniae strains to demonstrate an
Klebsiella pneumoniae resistance to Aminoglycosides extraordinarily high resistance to human serum and
(amikacin and gentamicin) as seen in this review may phagocytosis. This gene can be used as a molecular
be as a result of modifications in cell permeability due to marker for quick diagnosis and can also be useful in
alterations in AcrAB-TolC and KpnEF efflux pump sys- tracing the roots of emerging infectious diseases caused
tems and due to loss of putative porin, KpnO. Also the by K. pneumoniae. According to Fang et al. [33], the
disruptions in AcrAB-TolC may increase the susceptibil- MagA protein could be a good candidate for new drug
ity of K. pneumoniae to gentamicin [26]. The 16S rRNA targets.
methylases which are encoded on the plasmids [27] con- It has been shown that fimbriae contribute to dis-
fers resistance to all aminoglycosides. Mutations which eases of the urinary tract [34], mediates the develop-
confer resistance via target modification can also be a ment of biofilms and also it is involve in the adherence
possible attributable reason for the increasing resistance of the organism to medical devices. Therefore, expres-
of K. pneumoniae to most aminoglycosides. sion of these genes could improve K. pneumoniae’s
The low prevalence of Polymyxin (Colistin) resist- adhesive ability to respiratory epithelial cells and also
ance in this review makes a lot of sense because of to surfaces of other medical devices such as ventila-
their restricted use in human medicine dating back tors, thereby, increasing their ability to cause ventilator-
between the 1980s and 2000s, due to their recognized associated diseases. Fimbria, according to Huang et al.
toxicity. According to Falagas and Kasiakou [28], Pol- [35] and Stahlhut et al. [36], may be a major factor for
ymyxin works by disrupting the membrane integrity biofilm-associated diseases and host entry abilities of K.
through displacement of cations (­Ca2+/Mg2+) in the pneumoniae.
Effah et al. Ann Clin Microbiol Antimicrob (2020) 19:1 Page 8 of 9

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