The Epidemiology of Klebsiella Pneumoniae: A Review
Thualfakar Hayder Hasan1, ShaimaaA. Shlash2, SaadeAbdalkareem Jasim3, Ehsan F. Hussein4, Kasim Kadhim Alasedi5, Ahmed AbduljabbarJaloob Aljanaby6
1Medical Laboratories Techniques department, Altoosi University College, Najaf, Iraq.
2Pharmacy College/Kufa University, Najaf, Iraq.
3Medical Laboratory Techniques Department, Al-maarif University College, Iraq
4Department of Pathological Analyses, College of Science, University of Sumer, Iraq
5Nursing department, Altoosi University College, Najaf, Iraq.
6Department of Biology, University of Kufa, Faculty of Science, Najaf, Iraq
[email protected],[email protected],[email protected], [email protected], [email protected] , [email protected]
Corresponding Author: [email protected]
ABSTRACT
In alcohol and diabetes mellitus patient populations, Klebsiella pneumoniae is associated with pneumonia.
Usually, the bacterium colonizes the human oropharynx and GI mucosal surfaces. Klebsiella pneumoniae has been extensively studied and a beta-lactamase that induces antibiotic beta-lactam ring hydrolysis has been shown to develop. Human beings represent K. pneumoniae as the main reservoir.
Relationship between multidrug resistance and epidemiological study of K. pneumoniae in hospital environment.There are (5%-38%) of individuals in the population have the organism in their stomach and (1%-6%) in the nasopharynx.Additional research on resistance and survival mechanisms for K. pneumoniae can inform infection prevention and control strategies to decrease K. pneumoniae transmission.
Klebsiella pneumoniae was an urgently defined threat in the rise of multi-drug-resistant hospitals and hyper virulent strains. The appearance of these hazardous isolates and their global distribution has left very few therapeutic options to clinicians and determined one of the essential strains of nosocomial infections.
Keywords: Enterobacteriaceae,Klebsiella pneumoniae, virulence factors
Introduction
In alcohol and diabetes mellitus patient populations, Klebsiella pneumoniaeis associated with pneumonia (Siu et al.,2012). Usually, the bacterium colonizes the human oropharynx and GI mucosal surfaces (Nadasyet al.,2007). The bacterium can be shown high levels of virulence and antibiotic resistance once it reaches the body (Lenchenkoet al.,2020). K. pneumoniae is also the world's most common cause of hospital-acquired pneumonia thatdetermined between(3% to 8%) of all bacterial infections (Yuet
al.,2020).Klebsiella pneumoniae is a gram-negative, encapsulate, and nonmobile bacterium in the Enterobacteriaceae family (Walker et al.,2020). A wide variety of factors contributing to infection and antibiotic resistance include bacterium virulence (Zhang et al.,2020). The organism's polysaccharide capsule is the most important virulence factor and can prevent the host organism from developing opsonophagocytosis and bacterium eradication (Sun et al.,2020).To date, 77 capsules were studied, and those without capsules are often less virulent for Klebsiella species. Lipopolysaccharides coating the external surface of gram-negative bacteria is a second virulence factor (Ma et al.,2020).
Lipopolysaccharide sensation releases an inflamed cascade to the host organism and has proved to be a significant culprit in septic and septic sequelae(Anand et al.,2020). The organism can bind itself to host cells via a particular virulence factor, fimbriae. Another virulence factor used by the organism for hosts is siderophores (Rodrigues et al.,2020). To enable the spread of the contaminating organism, siderophores obtain iron from their host (Liu et al.,2020).Klebsiella pneumoniae is one of the bacteria with a high antibiotic resistance rate secondary to changes in the core genome of the cell (Ruanet al.,2020). Fleming first discovered resistance in gram-negative species to beta-lactam antibiotics in 1929. From then on, K.
pneumoniae has been extensively studied and a beta-lactamase that induces antibiotic beta-lactam ring hydrolysis has been shown to develop (Farzandet al.2021). Extensive-spectrum beta-lactamase (ESBL) ESBLs may be able to hydrolyze oxyimino cephalosporins which render cephalosporins of third-generation ineffective,because of this, carbapenems have become a choice for the treatment of ESBL (Hayder&
Aljanaby,2019A ;Hayder& Aljanaby,2019B).
Epidemiology:
Human beings represent K. pneumoniae as the main reservoir (Kadhum& Hasan,2019).
There are (5%-38%) of individuals in the population have the organism in their stomach and 1%-6% in the nasopharynx (Hasan & Al-Harmoosh,2020). The main sources of infection are the gastrointestinal tract and the medical staff19. It can lead to an outbreak of nosocomial infections (Majeed et al.,2020). The carrier prevalence of K. pneumoniae is substantially higher in hospitalized patients than in the population (Hasan et al.,2020).
Carrier concentrations of up to 77 percent in one study are seen on the stool of those admitted to hospital and are believed to have been linked to the number of antibiotics (Hasan,2020A).K. pneumoniaewas divided into two types: pneumonia acquired by the population or pneumonia acquired by the hospitals (Hasan,2020B). Although a typical diagnosis is community-acquired pneumonia, K.pneumoniae infection is very rare (Ablaaet al.,2021). It is estimated that about (3 to 5%) of all pneumonia population infections that caused due to K. pneumoniae in Western culture but it is approximately 15% of all pneumonia cases in developing countries, such as Africa (Hasan et
al.,2021A).K. pneumoniae constitutes around 11,8% of all pneumonia acquired by hospitals worldwide (Hasan et al.,2021B). In people with pneumonia in the ventilator, K.
pneumoniae causes between (8% and 12%), while in those that do not ventilate, just 7%,although mortality differs from that of patients with alcoholism and septicemia from 50 % to 100 % (Munoz-Price et al.,2013).
Klebsiella pneumonia is poorly expected, especially in patients with alcoholic, diabetic, nosocomial, or septicemic conditions,this pneumonia mortality is more than 50%(Patel et al.,2008; Bengoechea& Sa Pessoa, 2019). Also,K. pneumoniae cancause bacteremia, lung abscesses, and the development of empyema can cause pneumonia(Ye et al.,2001).
In nature, Klebsiella probably has two environments common to them; one is the ecosystem in which they find themselves and their colonized mucosal areas of humans, horses, or swine on surface waters, sewage and soils, and plants(Tumbarelloet al.,2012).
The Klebsiella genus is like Enterobacter and Citrobacter in this regard, but it is different from Shigella spp. or E. coli, common to individuals, but not environmentally (Nordmann et al.,2009).
K. pneumoniae is present in humans in the nasopharynx and intestinal tract as a commensal (Paczosa&Mecsas, 2016). Carrier rates vary widely from one study to the next. The rate of detection in stool samples is between 5% and 38%, while in the nasopharynx range between (1% and 6%) (Elemamet al.,2009).Klebsiellaspp is not good for human skin as gram-negative bacteria do not find good conditions for growth. It's seldom found and is simply called transient flora members(Lautenbach et al.,2001).
In hospital settings, these carrier rates change significantly, where colonization rates are directly proportionate to the duration of the stay. The number of Klebsiella carriages is also high for hospital staff37. In hospitalized patients, the reported carriers’ rates are 77%
in stools, 19% in pharynxes, and 42% in patients' hands (Martin & Bachman,2018).
The high rate of nosocomial Klebsiella colonization appears to be associated with the use of antibiotics rather than with factors connected with the delivery of care in the hospital (Cano et al.,2020). Previous antibiotic therapy is significantly associated with the acquisition of Klebsiella by the patient (Wyreset al.,2020). The increase occurred
primarily in patients receiving antibiotics, especially in persons receiving broad-spectrum or multiple antibiotics(Wang et al.,2018).
The local antibiotic policy in the hospital setting is a significant determinant of the pattern of colonization (Tumbarelloet al,2019). It was found that the attack rate for Klebsiellanosocomial was four times higher in patients carrying Klebsiella intestinal infection than in patients who were acquired with the hospital (Gorrie et al.,2017).
Moreover, routine use of antibiotic care in hospitals has also been known to be responsible for multiplying resistant Klebsiella strains (Galvãoet al.,2018). Because these undesirable effects can be reversed by rigorous antibiotic treatment, techniques to prevent overuse of antibiotics are increasingly being called for in prophylaxis and empirical therapy (Gu et al., 2018).
In addition to medical equipment and blood products, the main sources for Klebsiella transmission in hospitals are the gastrointestinal tract of patients and hands of the hospital staff and are contaminated by faulty hygiene procedures (Petrosilloet al.,2019). The capacity of the organism, particularly in neonatal units, to spread rapidly frequently causes nosocomial diseases (Ramos-Castañedaet al.,2018).
Klebsiella spp. are implicated with many epidemic hospital infections,in the 1970s, these strains were primarily Klebsiella strains that were aminoglycoside resistant. Production of ESBLs that make them safe to cephalosporins of a wider range have developed since 1982 (Falcone et al.,2020). Both K. pneumoniae and K. oxytoca isolates are distinguished by their resistance to ceftazidime (Shields et al.,2017). In Europe, ceftazidime-resisting Klebsiella strains are usually β-lactamases of an SHV-5 type whereas the US has a higher prevalence of TEM-10 and TEM-12 (Caneiraset al.,2019).
In the US 5 % of the K. pneumoniae strains tested in the National Nosocomial Infection Research System have been identified for ESBL-producing Klebsiella Isolates (Mohammed &Aljanaby, 2020). Europe appears to be much more common with such strains. For France and Britain, a proportion of 14-16% of ESBL producers has been identified among clinical Klebsiella isolates. Incidence can be up to 25 to 40% in regions or hospitals (Al-labban and Aljanaby, 2020).
Even so, this is possible because the percentage of ceftazidime-resistant strains in the routine laboratory underestimates the occurrence of these isolates (Alfaham, &Aljanaby, 2020).
The plasmid is normally mediated by ESBLs. Since plasmids can be transmitted easily among various Enterobacteriaceae members, the accumulation of resistance genes leads to strains containing multi-resistant plasmids. Therefore, isolates developed by ESBL are resistant to several antibiotic groups (Lee et al.2017; Mohamed & Aljanaby,2020).
Also, the appearance of these multi-drug resistant strains in Klebsiella accompanies relatively high stability of the ESBL-encoding plasmids (Temkin et al.,2018). There has been continued colonization of patients using ESBL-producing Klebsiella strains many years after ceftazidime and other extended-spectrum cephalosporins had ceased (Thorenoor et al.,2018). A long period of stay in the hospital and the success of invasive procedures tend to be the risk factors for the acquisition of these strains (Giannellaet al.,2019).
In that ESBL development is often accompanied by antibiotic resistance, therapeutic options are minimal (Shimasakiet al.,2019). However, Klebsiella strains developed by ESBL were previously responsive to carbapenems like imipenem or meropenem. In the treatment of infections caused by ESBL-produced species, both antibiotics are the drugs of choice. A recent comment is extremely troubling in this regard (Thorenooret al.,2018).
Over the first time, K. pneumoniae strains to produce ESBL which demonstrated additional imipenem resistance was isolated (Quan et al.,2017). These strains have an AmpC-type β-lactamase transmissible by the plasmid. The advent of imipenem ESBL- producing Klebsiella strains will be watched closely, as it will have a significant effect on other therapeutic options (Dunn et al.,2019).
Over the first time, K. pneumoniae strains to produce ESBL which demonstrated additional imipenem resistance was isolated (Kidd et al.,2017). These strains have an AmpC-type β-lactamase transmissible by the plasmid. The advent of imipenem ESBL- producing Klebsiella strains will be watched closely, as it will have a significant effect on other therapeutic options (Zhang et al.,2020).
Treatment for the spread of nosocomial Klebsiella infections is aided by strict observance of the basic epidemiological principles of urinary catheter management, injection, and tracheostomy, wound, maintenance, and hand-washing procedures (Decraeneet al.2018).
The regulation of antibiotic use in hospitals to avoid abuses and overuse of antibiotics is another step to manage Klebsiella infectionsBesides, nosocomial infection monitoring is important for collecting data for the prevention and control of nosocomial infection rates of Klebsiella(Gomez-Simmonds et al.,2017).
Conclusion
Klebsiella pneumoniae was an urgently defined threat inthe rise of multi-drug-resistant hospitals andhyper virulent strains. The appearance of these hazardous isolates and their global distribution has left very few therapeutic options to clinicians and determined one of the essential strains of nosocomial infections.Additional research on resistance and survival mechanisms for K. pneumoniae can inform infection prevention and control strategies to decrease K. pneumoniae transmission.
Conflict of Interest
The authors have no conflicts of interest.
Source of Funding
Personal fund.
References
1. Siu LK, Yeh KM, Lin JC, Fung CP, Chang FY. Klebsiella pneumoniae liver abscess: a new invasive syndrome. The Lancet infectious diseases.
2012;12(11):881-7.
2. Nadasy KA, Domiati-Saad R, Tribble MA. Invasive Klebsiella pneumoniae syndrome in North America. Clinical Infectious Diseases. 2007;45(3):e25-8.
3. Lenchenko E, Blumenkrants D, Sachivkina N, Shadrova N, Ibragimova A.
Morphological and adhesive properties of Klebsiella pneumoniae biofilms.
Veterinary world. 2020;13(1):197.
4. Yu, Yang, et al. "A Klebsiella pneumoniae strain co-harbouring mcr-1 and mcr-3 from a human in Thailand." Journal of Antimicrobial Chemotherapy 75.8. 2020;
2372-2374.
5. Walker KA, Miller VL. The intersection of capsule gene expression, hypermucoviscosity and hypervirulence in Klebsiella pneumoniae. Current opinion in microbiology. 2020; 1; 54:95-102.
6. Zhang P, Shi Q, et al. Emergence of ceftazidime/avibactam resistance in carbapenem-resistant Klebsiella pneumoniae in China. Clinical Microbiology and Infection. 2020;26(1):124-e1.
7. Sun L, Chen W, et al. Phenotypic and genotypic analysis of KPC-51 and KPC-52, two novel KPC-2 variants conferring resistance to ceftazidime/avibactam in the KPC-producing Klebsiella pneumoniae ST11 clone background. Journal of Antimicrobial Chemotherapy. 2020;75(10):3072-4.
8. Ma K, Feng Y, Liu L, Yao Z, Zong Z. A cluster of colistin-and carbapenem- resistant Klebsiella pneumoniae carrying bla NDM-1 and mcr-8.2. The Journal of infectious diseases. 2020;221(Supplement_2): S237-42.
9. Anand T, Virmani N, et al. Phage therapy for treatment of virulent Klebsiella pneumoniae infection in a mouse model. Journal of global antimicrobial resistance. 2020; 21:34-41.
10. Rodrigues C, d’Humières C, Papin G, Passet V, Ruppé E, Brisse S. Community- acquired infection caused by the uncommon hypervirulent Klebsiella pneumoniae ST66-K2 lineage. Microbial genomics. 2020;6(8).
11. Liu W, et al. Tea polyphenols inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances resistance to Klebsiella pneumoniae infection in Caenorhabditis elegans model. Microbial pathogenesis. 2020;
147:104266.
12. Ruan Z, Wu J, Chen H, Draz MS, Xu J, He F. Hybrid genome assembly and annotation of a pandrug-resistant klebsiella pneumoniae strain using nanopore and illumina sequencing. Infection and drug resistance. 2020; 13:199.
13. Lu B, Lin C, Liu H, Zhang X, Tian Y, Huang Y, Yan H, Qu M, Jia L, Wang Q.
Molecular Characteristics of Klebsiella pneumoniae Isolates from Outpatients in
Sentinel Hospitals, Beijing, China, 2010–2019. Frontiers in cellular and infection microbiology. 2020;10:85.
14. Farzand R, et al. A Virulence Associated Siderophore Importer Reduces Antimicrobial Susceptibility of Klebsiella pneumoniae. Frontiers in Microbiology. 2021; 12:52.
15. Hayder T, Aljanaby AA. Antibiotics susceptibility patterns of Citrobacter freundii isolated from pa-tients with urinary tract infection in Al-Najaf governorate–Iraq.
International Journal of Research in Pharmaceutical Sciences. 2019;10(2):1481-8.
16. Hayder T, Aljanaby AA. Genotypic Characterization of Antimicrobial Resistance- Associated Genes in Citrobacter Freundii Isolated from Patients with Urinary Tract Infection in Al-Najaf Governorate-Iraq. OnLine Journal of Biological Sciences. 2019;19(2):132-45.
17. Kadhum HA, Hasan TH. The Study of Bacillus Subtils Antimicrobial Activity on Some of the Pathological Isolates. International Journal of Drug Delivery Technology. 2019; 21;9(02):193-6.
18. Hasan TH, Al-Harmoosh RA. Mechanisms of Antibiotics Resistance in Bacteria.
Sys Rev Pharm. 2020;11(6):817-23.
19. Hasan TH. Extended Spectrum Beta Lactamase E. Coli isolated from UTI Patients in Najaf Province, Iraq. International Journal of Pharmaceutical Research. 2020;12(4).
20. Majeed HT, Hasan TH, Aljanaby AA. Epidemiological study in women infected with toxoplasma gondii, rubella virus, and cytomegalo virus in Al-Najaf Governorate-Iraq. International Journal of Pharmaceutical Research. 2020;
12:1442-7.
21. Hasan TH, Al-Harmoosh RA, Al-Khilkhali HJ. Identification of HIV virus in najaf city, Iraq. International Journal of Research in Pharmaceutical Sciences.
2020;11(3):4866-71.
22. Hasan TH. Extended Spectrum Beta-Lactamase Producing Klebsiella Pneumonia Isolated from Patients with Urinary Tract Infection in Al-Najaf Governorate–Iraq.
International Journal of Advances in Science, Engineering and Technology (IJASEAT). 2020;8(1):13-6.
23. Hasan TH. Prevalence of hepatitis virus B and C in patients in Al Najaf Governorate, Iraq. International Journal of Pharmaceutical Research.
2020;12(3):1297-303.
24. Ablaa HA, Al-Mehana WN, Mahdi IK, Hasan TH. Gene therapy by studying the effect of single nucleotide polymorphism (rs11886868 & rs766432) at the BcL11A gene on the severity of beta-thalassemia disease in the province of AL- Najaf. International Journal of Pharmaceutical Research. 2021;13(1).
25. Hasan TH, Alasedi KK, Jaloob AA. Proteus Mirabilis Virulence Factors.
International Journal of Pharmaceutical Research. 2021;13(1).
26. Hasan TH, Kadhum HA, Alasedi KK. Brucella spp. Virulence Factors.
International Journal of Pharmaceutical Research. 2021;13(1).
27. Munoz-Price LS, Poirel L, Bonomo RA, et al. Clinical epidemiology of the global expansion of Klebsiella pneumoniae carbapenemases. The Lancet infectious diseases. 2013 Sep 1;13(9):785-96.
28. Patel G, Huprikar S, Factor SH, Jenkins SG, Calfee DP. Outcomes of carbapenem-resistant Klebsiella pneumoniae infection and the impact of antimicrobial and adjunctive therapies. Infect Control Hosp Epidemiol. 2008 Dec 1;29(12):1099-106.
29. Bengoechea JA, Sa Pessoa J. Klebsiella pneumoniae infection biology: living to counteract host defences. FEMS microbiology reviews. 2019 Mar;43(2):123-44.
30. Ye P, et al. Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. American journal of respiratory cell and molecular biology. 2001 Sep 1;25(3):335-40.
31. Tumbarello M, et al. Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase–producing K. pneumoniae: importance of combination therapy. Clinical Infectious Diseases. 2012 Oct 1;55(7):943-50.
32. Nordmann P, Cuzon G, Naas T. The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria. The Lancet infectious diseases. 2009 Apr 1;9(4):228-36.
33. Paczosa MK, Mecsas J. Klebsiella pneumoniae: going on the offense with a strong defense. Microbiology and Molecular Biology Reviews. 2016 Sep 1;80(3):629-61.
34. Elemam A, Rahimian J, Mandell W. Infection with panresistant Klebsiella pneumoniae: a report of 2 cases and a brief review of the literature. Clinical infectious diseases. 2009 Jul 15;49(2):271-4.
35. Lautenbach E, Patel JB, Bilker WB, Edelstein PH, Fishman NO. Extended- spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae: risk factors for infection and impact of resistance on outcomes. Clinical Infectious Diseases. 2001 Apr 15;32(8):1162-71.
36. Martin RM, Bachman MA. Colonization, infection, and the accessory genome of Klebsiella pneumoniae. Frontiers in cellular and infection microbiology. 2018 Jan 22;8:4.
37. Cano EJ, et al. Phage therapy for limb-threatening prosthetic knee Klebsiella pneumoniae infection: case report and in vitro characterization of anti-biofilm activity. Clinical Infectious Diseases. 2020 Jul 23.
38. Wyres KL, Lam MM, Holt KE. Population genomics of Klebsiella pneumoniae.
Nature Reviews Microbiology. 2020 Jun;18(6):344-59.
39. Wang Z, Qin RR, Huang L, Sun LY. Risk factors for carbapenem-resistant Klebsiella pneumoniae infection and mortality of Klebsiella pneumoniae infection. Chinese medical journal. 2018 Jan 5;131(1):56.
40. Tumbarello M, et al. Efficacy of ceftazidime-avibactam salvage therapy in patients with infections caused by Klebsiella pneumoniae carbapenemase–
producing K. pneumoniae. Clinical Infectious Diseases. 2019 Jan 18;68(3):355- 64.
41. Gorrie CL, et al. Gastrointestinal carriage is a major reservoir of Klebsiella pneumoniae infection in intensive care patients. Clinical infectious diseases. 2017 Jul 15;65(2):208-15.
42. Harris PN, et al. Effect of piperacillin-tazobactam vs meropenem on 30-day mortality for patients with E coli or Klebsiella pneumoniae bloodstream infection
and ceftriaxone resistance: a randomized clinical trial. Jama. 2018 Sep 11;320(10):984-94.
43. Lou W, et al. Antimicrobial polymers as therapeutics for treatment of multidrug- resistant Klebsiella pneumoniae lung infection. Acta biomaterialia. 2018 Sep 15;78:78-88.
44. Galvão I, et al. The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung. Frontiers in immunology. 2018 Feb 20;9:142.
45. Gu D, et al. A fatal outbreak of ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae in a Chinese hospital: a molecular epidemiological study.
The Lancet infectious diseases. 2018 Jan 1;18(1):37-46.
46. Petrosillo N, Taglietti F, Granata G. Treatment options for colistin resistant Klebsiella pneumoniae: present and future. Journal of clinical medicine. 2019 Jul;8(7):934.
47. Ramos-Castañeda JA, et al. Mortality due to KPC carbapenemase-producing Klebsiella pneumoniae infections: Systematic review and meta-analysis:
Mortality due to KPC Klebsiella pneumoniae infections. Journal of Infection.
2018 May 1;76(5):438-48.
48. Falcone M, et al. Time to appropriate antibiotic therapy is a predictor of outcome in patients with bloodstream infection caused by KPC-producing Klebsiella pneumoniae. Critical Care. 2020 Dec 1;24(1):29.
49. Shields RK,et al. Ceftazidime-avibactam is superior to other treatment regimens against carbapenem-resistant Klebsiella pneumoniae bacteremia. Antimicrobial agents and chemotherapy. 2017 Aug 1;61(8).
50. Caneiras C, Lito L, Melo-Cristino J, Duarte A. Community-and hospital-acquired Klebsiella pneumoniae urinary tract infections in Portugal: virulence and antibiotic resistance. Microorganisms. 2019 May;7(5):138.
51. Mohammed, E.H., Aljanaby, A.A.J. Galectin3 and cd16 play an important immunological role in patients infected with salmonella typhi. International Journal of Research in Pharmaceutical Sciences, 2020; 11(3), pp. 4162–4169.
52. Al-labban, H.M.Y. and Aljanaby, A.A.J. An overview of some heterocyclic organic compounds; synthesis, characterization, thermal properties and antibacterial activity. International Journal of Pharmaceutical Research, 2020;(1).
53. Alfaham, Q. and Aljanaby, A.A.J. Interleukin 12 has an important role in patients infected with Mycobacterium tuberculosis. International Journal of Pharmaceutical Research,2020; (1).
54. MOHAMED, K.G. and ALJANABY, A.A.J. Urinary tract infections in Al-Kufa City Iraq and phenotypic detection of antimicrobial sensitivity pattern of bacterial isolates. International Journal of Pharmaceutical Research,2020; (1).
55. Lee CR, et al. Antimicrobial resistance of hypervirulent Klebsiella pneumoniae:
epidemiology, hypervirulence-associated determinants, and resistance mechanisms. Frontiers in cellular and infection microbiology. 2017 Nov 21;7:483.
56. Temkin E, et al. Estimating the number of infections caused by antibiotic- resistant Escherichia coli and Klebsiella pneumoniae in 2014: a modelling study.
The Lancet Global Health. 2018 Sep 1;6(9):e969-79.
57. Thorenoor N, Umstead TM, Zhang X, Phelps DS, Floros J. Survival of surfactant protein-A1 and SP-A2 transgenic mice after Klebsiella pneumoniae infection, exhibits sex-, gene-, and variant specific differences; treatment with surfactant protein improves survival. Frontiers in immunology. 2018 Oct 16;9:2404.
58. Giannella M, Pascale R, Gutiérrez-Gutiérrez B, Cano A, Viale P. The use of predictive scores in the management of patients with carbapenem-resistant Klebsiella pneumoniae infection. Expert review of anti-infective therapy. 2019 Apr 3;17(4):265-73.
59. Shimasaki T, et al. Increased relative abundance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae within the gut microbiota is associated with risk of bloodstream infection in long-term acute care hospital patients. Clinical Infectious Diseases. 2019 May 30;68(12):2053-9.
60. Thorenoor N, Zhang X, Umstead TM, Halstead ES, Phelps DS, Floros J.
Differential effects of innate immune variants of surfactant protein-A1 (SFTPA1)
and SP-A2 (SFTPA2) in airway function after Klebsiella pneumoniae infection and sex differences. Respiratory research. 2018 Dec;19(1):1-4.
61. Quan J, Li X, Chen Y, et al. Prevalence of mcr-1 in Escherichia coli and Klebsiella pneumoniae recovered from bloodstream infections in China: a multicentre longitudinal study. The Lancet Infectious Diseases. 2017 Apr 1;17(4):400-10.
62. Dunn SJ, Connor C, McNally A. The evolution and transmission of multi-drug resistant Escherichia coli and Klebsiella pneumoniae: the complexity of clones and plasmids. Current opinion in microbiology. 2019 Oct 1;51:51-6.
63. Kidd TJ, et al. A Klebsiella pneumoniae antibiotic resistance mechanism that subdues host defences and promotes virulence. EMBO molecular medicine. 2017 Apr;9(4):430-47.
64. Zhang Y, et al. Evolution of hypervirulence in carbapenem-resistant Klebsiella pneumoniae in China: a multicentre, molecular epidemiological analysis. Journal of Antimicrobial Chemotherapy. 2020 Feb 1;75(2):327-36.
65. Decraene V, et al. A large, refractory nosocomial outbreak of Klebsiella pneumoniae carbapenemase-producing Escherichia coli demonstrates carbapenemase gene outbreaks involving sink sites require novel approaches to infection control. Antimicrobial agents and chemotherapy. 2018 Dec 1;62(12).
66. Gomez-Simmonds A, Uhlemann AC. Clinical implications of genomic adaptation and evolution of carbapenem-resistant Klebsiella pneumoniae. The Journal of infectious diseases. 2017 Feb 15;215(suppl_1):S18-27.
