Antimicrobial resistance (AMR) is one of the most important concerns in the world, occurring for both Gram-positive and Gram-negative bacteria. Klebsiella pneumoniae (K. pneumoniae) is a Gram-negative bacterium belonging to the family of Enterobacteriaceae and also plays an important role in development of nosocomial infections. Three forms have emerged as a result of AMR including multi-drug resistant (MDR), extensively drug-resistant, and pan-drug-resistant. Nowadays, physicians cannot save most of the patients that suffer from MDR K. pneumoniae infections by typical antibiotics, so they should try other useful alternative treatments. Our aim in this review study was to search about the latest useful alternative methods against MDR K. pneumoniae infections. We collected some articles from PubMed, MEDLINE, and Google Scholar by the keywords of multi-drug-resistant K. pneumoniae, AMR, and alternative treatments, where finally 183 articles were selected. Also, inclusion criteria and exclusion criteria were identified separately. It was understood that there are novel therapeutic options against MDR K. pneumoniae infections, which include odilorhabdins, drug delivery systems, antibody drug conjugation treatments, nano-antibiotics, bacteriocins, probiotics, fecal transplant therapy, predatory bacteria, combined antibiotics, double-carbapenem therapy, synthetic lipopeptides, and phage therapy.
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References
1.
Gómara-LomeroM, López-CallejaAI, RezustaA, et al.Repurposing azithromycin in combination with last-line fosfomycin, colistin and tigecycline against Multi-Drug Resistant Klebsiella pneumoniae. bioRxiv, 2022.
2.
LaiCC, ChenSY, KoWC, et al.Increased antimicrobial resistance during the COVID-19 pandemic. Int J Antimicrob Agents, 2021; 57(4):106324.
3.
BassettiM, GarauJ. Current and future perspectives in the treatment of multidrug-resistant Gram-negative infections. J Antimicrob Chemother, 2021; 76(Suppl 4):iv23–iv37.
4.
Al-OuqailiDMTS. Biofilm antimicrobial susceptibility pattern for selected antimicrobial agents against planktonic and sessile cells of clinical isolates of staphylococci using MICs, BICs and MBECs. Asian J Pharm, 2019; 12(04).
5.
MurshidRM, Al-OuqailiMTS, KanaanBAJ. Microbial Vaginosis and its Relation to Single or Multi-Species Biofilm in Iraqi Women: Clinical and Microbiological Study. Pak J Biol Sci, 2024; 27(8):404–412.
6.
BelayWY, GetachewM, TegegneBA, et al.Mechanism of antibacterial resistance, strategies and next-generation antimicrobials to contain antimicrobial resistance: A review. Front Pharmacol, 2024; 15:1444781.
7.
Al-OuqailiMT. Identification of an OprD and blaIMP gene-mediated carbapenem resistance in Acinetobacter baumannii and Pseudomonas aeruginosa among patients with wound infections in Iraq. Asian Journal of Pharmaceutics (AJP), 2018; 12(03).
8.
SalamMA, Al-AminMY, SalamMT, et al.Antimicrobial resistance: A growing serious threat for global public health. Healthcare (Basel), 2023; 11(13):1946.
9.
AldredKJ, KernsRJ, OsheroffN. Mechanism of quinolone action and resistance. Biochemistry, 2014; 53(10):1565–1574.
10.
AlabdaliA, KzarMS, ChinnappanS, et al.Application of nanoantibiotics approach against anti-bacterial resistance. Int J Appl Pharm, 2022; 14:34–39.
11.
BaqueroF, NegriM. Strategies to minimize the development of antibiotic resistance. J Chemother, 1997; 9(Suppl 3):29–37.
12.
BalabanN, CirioniO, GiacomettiA, et al.Treatment of Staphylococcus aureus biofilm infection by the quorum-sensing inhibitor RIP. Antimicrob Agents Chemother, 2007; 51(6):2226–2229.
13.
BallP, ShalesS, ChopraI. Plasmid-mediated tetracycline resistance in Escherichia coli involves increased efflux of the antibiotic. Biochem Biophys Res Commun, 1980; 93(1):74–81.
14.
BaranA, KwiatkowskaA, PotockiL. Antibiotics and bacterial resistance—A short story of an endless arms race. Int J Mol Sci, 2023; 24(6):5777.
15.
BeheshtiM, ArdebiliA, BeheshtiF, et al.Tetracycline resistance mediated by tet efflux pumps in clinical isolates of Acinetobacter baumannii. Rev Inst Med Trop Sao Paulo, 2020; 62:e88.
16.
BenvenisteR, DaviesJ. Mechanisms of antibiotic resistance in bacteria. Annu Rev Biochem, 1973; 42(1):471–506.
17.
WilliamsPC, WaichungoJ, GordonNC, et al.The potential of fosfomycin for multi-drug resistant sepsis: An analysis of in vitro activity against invasive paediatric Gram-negative bacteria. J Med Microbiol, 2019; 68(5):711–719.
18.
BanerjeeS, SenguptaM, SarkerTK. Fosfomycin susceptibility among multidrug-resistant, extended-spectrum beta-lactamase-producing, carbapenem-resistant uropathogens. Indian J Urol, 2017; 33(2):149–154.
19.
HusseinRA, Al-KubaisySH, Al-OuqailiMT. The influence of efflux pump, outer membrane permeability and β-lactamase production on the resistance profile of multi, extensively and pandrug resistant Klebsiella pneumoniae. J Infect Public Health, 2024; 17(11):102544.
20.
OwaidHA, Al-OuqailiMTS. Whole genome sequencing insights on extensive drug resistant Klebsiella pneumoniae and Pseudomonas aeruginosa traumatic infection. Pak J Biol Sci, 2025; 28(2):78–87.
21.
Prevention ECfD, Control. Assessing the health burden of infections with antibiotic-resistant bacteria in the EU/EEA, 2016–2020. ECDC; Stockholm; 2022.
22.
FalagasME, KyriakidouM, VoulgarisGL, et al.Clinical use of intravenous polymyxin B for the treatment of patients with multidrug-resistant Gram-negative bacterial infections: An evaluation of the current evidence. J Glob Antimicrob Resist, 2021; 24:342–359.
23.
Gómara-LomeroM, López-CallejaAI, RezustaA, et al.Zidovudine multi-combos with last-line fosfomycin, ceftazidime-avibactam, colistin and tigecycline against Multi-Drug Resistant Klebsiella pneumoniae. bioRxiv, 2025.
24.
GnanasekaranC, AlobaidiAS, GovindanR, et al.Piperacillin/tazobactum and cefotaxime decrease the effect of beta lactamase production in multi-drug resistant K. pneumoniae. J Infect Public Health, 2021; 14(12):1777–1782.
25.
Kowalska-KrochmalB, MączyńskaB, Rurańska-SmutnickaD, et al.Assessment of the susceptibility of clinical gram-negative and gram-positive bacterial strains to fosfomycin and significance of this antibiotic in infection treatment. Pathogens, 2022; 11(12):1441.
26.
Ocampo-IbáñezID, LiscanoY, Rivera-SánchezSP, et al.A novel cecropin D-Derived short cationic antimicrobial peptide exhibits antibacterial activity against wild-type and multidrug-resistant strains of Klebsiella pneumoniae and Pseudomonas aeruginosa. Evol Bioinform Online, 2020; 16:1176934320936266.
27.
Papp-WallaceKM. The latest advances in β-lactam/β-lactamase inhibitor combinations for the treatment of Gram-negative bacterial infections. Expert Opin Pharmacother, 2019; 20(17):2169–2184.
28.
ZhangF, ChengW. The mechanism of bacterial resistance and potential bacteriostatic strategies. Antibiotics (Basel), 2022; 11(9):1215.
29.
LutgringJD., ed. Carbapenem-resistant Enterobacteriaceae: an emerging bacterial threat. In Seminars in diagnostic pathology. Elsevier; 2019.
30.
MączyńskaB, PalecznyJ, Oleksy-WawrzyniakM, et al.In vitro susceptibility of multi-drug resistant Klebsiella pneumoniae strains causing nosocomial infections to fosfomycin. a comparison of determination methods. Pathogens, 2021; 10(5):512.
31.
HerridgeWP, ShibuP, O’SheaJ, et al.Bacteriophages of Klebsiella spp., their diversity and potential therapeutic uses. J Med Microbiol, 2020; 69(2):176–194.
32.
PaulM, BhatiaM, RajAK, et al.Ceftriaxone-sulbactam-EDTA susceptibility profile of multi-drug resistant gramnegative bacterial isolates: Experience from a tertiary care teaching hospital in Rishikesh, Uttarakhand. J Nat Sci Biol Med, 2020; 11(2):189.
33.
LiN, ZengY, BaoR, et al.Isolation and characterization of novel phages targeting pathogenic Klebsiella pneumoniae. Front Cell Infect Microbiol, 2021; 11:792305.
34.
AbdelhalimMM, SaafanGS, El-SayedHS, et al.In vitro antibacterial effect of probiotics against Carbapenamase-producing multidrug-resistant Klebsiella pneumoniae clinical isolates, Cairo, Egypt. J Egypt Public Health Assoc, 2022; 97(1):19.
35.
PantelL, FlorinT, Dobosz-BartoszekM, et al.Odilorhabdins, antibacterial agents that cause miscoding by binding at a new ribosomal site. Mol Cell, 2018; 70(1):83–94.e7.
36.
RacineE, GualtieriM. From worms to drug candidate: The story of odilorhabdins, a new class of antimicrobial agents. Front Microbiol, 2019; 10:2893.
37.
RacineE, NordmannP, PantelL, et al.In vitro and in vivo characterization of NOSO-502, a novel inhibitor of bacterial translation. Antimicrob Agents Chemother, 2018; 62(9):e01016–e01018; doi: 10.1128/aac.01016-18
38.
AttwoodML, NoelA, GriffinP, et al.In vitro activity of NOSO-502, a novel-action antimicrobial, against clinical strains of Enterobacterales including MDR strains. J Antimicrob Chemother, 2025; 80(7):1942–1946.
39.
van den BergS, AttwoodMG, GriffinP, et al.Pharmacodynamics of NOSO-502 studied in vitro and in vivo: Determination of the dominant pharmacodynamic index driver. J Antimicrob Chemother, 2025; 80(3):dkae469–d759.
40.
LiuY, DingS, ShenJ, et al.Nonribosomal antibacterial peptides that target multidrug-resistant bacteria. Nat Prod Rep, 2019; 36(4):573–592.
41.
ZhaoM, LepakAJ, MarchilloK, et al.In vivo pharmacodynamic characterization of a novel odilorhabdin antibiotic, NOSO-502, against Escherichia coli and Klebsiella pneumoniae in a murine thigh infection model. Antimicrob Agents Chemother, 2018; 62(9):e01067–e01018; doi: 10.1128/aac.01067-18
42.
ZongT-X, SilveiraAP, MoraisJAV, et al.Recent advances in antimicrobial nano-drug delivery systems. Nanomaterials (Basel), 2022; 12(11):1855.
43.
LiZ, HuJ, MaX, et al.Promising treatments for refractory pneumonia caused by multidrug-resistant Klebsiella pneumoniae. J Drug Deliv Sci Technol, 2023; 87:104874.
44.
WangQ, ChangC-S, PenniniM, et al.Target-agnostic identification of functional monoclonal antibodies against Klebsiella pneumoniae multimeric MrkA fimbrial subunit. J Infect Dis, 2016; 213(11):1800–1808.
45.
Diago-NavarroE, Calatayud-BaselgaI, SunD, et al.Antibody-based immunotherapy to treat and prevent infection with hypervirulent Klebsiella pneumoniae. Clin Vaccine Immunol, 2017; 24(1):e00456–e00416.
46.
CavacoM, CastanhoMA, NevesV. The use of antibody-antibiotic conjugates to fight bacterial infections. Front Microbiol, 2022; 13:835677.
47.
JamilB, HabibH, AbbasiSA, et al.Development of cefotaxime impregnated chitosan as nano-antibiotics: De novo strategy to combat biofilm forming multi-drug resistant pathogens. Front Microbiol, 2016; 7:330.
48.
LiuJ, ZhangX, ZouP, et al.Peptide-based nano-antibiotic transformers with antibiotic adjuvant effect for multidrug resistant bacterial pneumonia therapy. Nano Today, 2022; 44:101505.
49.
LiuT, ZhongG, TangD, et al.Nano-antibiotics combined with laser irradiation to reduce the development of drug resistance of K. Pneumoniae and accelerate wound healing. Authorea Preprints, 2021.
50.
DenkovskienėE, PaškevičiusŠ, MisiūnasA, et al.Broad and efficient control of Klebsiella pathogens by peptidoglycan-degrading and pore-forming bacteriocins klebicins. Sci Rep, 2019; 9(1):15422.
51.
MortzfeldBM, PalmerJD, BhattaraiSK, et al.Microcin MccI47 selectively inhibits enteric bacteria and reduces carbapenem-resistant Klebsiella pneumoniae colonization in vivo when administered via an engineered live biotherapeutic. Gut Microbes, 2022; 14(1):2127633.
52.
Pérez-NadalesE, CanoÁ, RecioM, et al.Randomised, double-blind, placebo-controlled, phase 2, superiority trial to demonstrate the effectiveness of faecal microbiota transplantation for selective intestinal decolonisation of patients colonised by carbapenemase-producing Klebsiella pneumoniae (KAPEDIS). BMJ Open, 2022; 12(4):e058124.
53.
AlexakisK, BaliouS, IoannouP. Predatory bacteria in the treatment of infectious diseases and beyond. Infect Dis Rep, 2024; 16(4):684–698.
54.
MoyaB, BarceloIM, CabotG, et al.In vitro and in vivo activities of β-lactams in combination with the novel β-lactam enhancers zidebactam and WCK 5153 against multidrug-resistant metallo-β-lactamase-producing Klebsiella pneumoniae. Antimicrob Agents Chemother, 2019; 63(5):e00128–e00119; doi: 10.1128/aac.00128-19
55.
NicholsWW, BradfordPA, StoneGG. The primary pharmacology of ceftazidime/avibactam: Microbiology from clinical studies, and development of resistance during treatment. J Antimicrob Chemother, 2023; 78(4):871–892.
56.
NicholsWW, BradfordPA, StoneGG. The primary pharmacology of ceftazidime/avibactam: In vivo translational biology and pharmacokinetics/pharmacodynamics (PK/PD). J Antimicrob Chemother, 2022; 77(9):2341–2352.
57.
BouzaE. The role of new carbapenem combinations in the treatment of multidrug-resistant Gram-negative infections. J Antimicrob Chemother, 2021; 76(Suppl 4):iv38–iv45.
58.
AveryLM, NicolauDP. Investigational drugs for the treatment of infections caused by multidrug-resistant Gram-negative bacteria. Expert Opin Investig Drugs, 2018; 27(4):325–338.
59.
LiY-y, WangJ, WangR, et al.Double-carbapenem therapy in the treatment of multidrug resistant Gram-negative bacterial infections: A systematic review and meta-analysis. BMC Infect Dis, 2020; 20(1):408–413.
60.
PoirelL, KiefferN, NordmannP. In vitro evaluation of dual carbapenem combinations against carbapenemase-producing Enterobacteriaceae. J Antimicrob Chemother, 2016; 71(1):156–161.
61.
OlivaA, ScorzoliniL, CipollaA, et al.In vitro evaluation of different antimicrobial combinations against carbapenemase-producing Klebsiella pneumoniae: The activity of the double-carbapenem regimen is related to meropenem MIC value. J Antimicrob Chemother, 2017; 72(7):1981–1984.
62.
FredborgM, SondergaardTE, WangM. Synergistic activities of meropenem double and triple combinations against carbapenemase-producing Enterobacteriaceae. Diagn Microbiol Infect Dis, 2017; 88(4):355–360.
63.
CuiA-L, YangH-X, YiH, et al.Design, synthesis, and bioactivity investigation of novel cyclic lipopeptide antibiotics targeting top-priority multidrug-resistant gram-negative bacteria. Eur J Med Chem, 2024; 280:116924.
64.
FayezMS, HakimTA, AgwaMM, et al.Topically applied bacteriophage to control multi-drug resistant Klebsiella pneumoniae infected wound in a rat model. Antibiotics (Basel), 2021; 10(9):1048.
65.
HungC-H, KuoC-F, WangC-H, et al.Experimental phage therapy in treating Klebsiella pneumoniae-mediated liver abscesses and bacteremia in mice. Antimicrob Agents Chemother, 2011; 55(4):1358–1365.
66.
GuJ, LiuX, LiY, et al.A method for generation phage cocktail with great therapeutic potential. PLoS One, 2012; 7(3):e31698.
67.
SăndulescuO, ViziteuI, Streinu-CercelA, et al.Novel antimicrobials, drug delivery systems and antivirulence targets in the pipeline—from bench to bedside. Applied Sciences, 2022; 12(22):11615.
68.
FanX, FanJ, WangX, et al.S-thanatin functionalized liposome potentially targeting on Klebsiella pneumoniae and its application in sepsis mouse model. Front Pharmacol, 2015; 6:249.
69.
BheemidiVS, TiruckovelaM, VaranasiP. An imperative note on novel drug delivery systems. J Nanomed Nanotech, 2011; 2:100125.
70.
KhanR, IrchhaiyaR. Niosomes: A potential tool for novel drug delivery. J Pharm Investig, 2016; 46(3):195–204.
71.
JiangL, LinJ, TaggartCC, et al.Nanodelivery strategies for the treatment of multidrug‐resistant bacterial infections. J Interdiscip Nanomed, 2018; 3(3):111–121.
72.
YoussefEG, ZhangL, AlkhazrajiS, et al.Monoclonal IgM antibodies targeting Candida albicans Hyr1 provide cross-kingdom protection against gram-negative bacteria. Front Immunol, 2020; 11:76.
73.
PenniniME, De MarcoA, PelletierM, et al.Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae. Nat Commun, 2017; 8(1):1991.
74.
MotleyMP, Diago-NavarroE, BanerjeeK, et al.The role of IgG subclass in antibody-mediated protection against carbapenem-resistant Klebsiella pneumoniae. mBio, 2020; 11(5):e02059–e02020; doi: 10.1128/mbio.02059-20
IvinM, DumiganA, de VasconcelosFN, et al.Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection. PLoS Pathog, 2017; 13(11):e1006696.
77.
MurakamiT, HatanoS, YamadaH, et al.Two types of interleukin 17A–producing Γδ T cells in protection against pulmonary infection with Klebsiella pneumoniae. J Infect Dis, 2016; 214(11):1752–1761.
78.
KerrAR, PatersonGK, Riboldi-TunnicliffeA, et al.Innate immune defense against pneumococcal pneumonia requires pulmonary complement component C3. Infect Immun, 2005; 73(7):4245–4252.
79.
Mueller-OrtizSL, DrouinSM, WetselRA. The alternative activation pathway and complement component C3 are critical for a protective immune response against Pseudomonas aeruginosa in a murine model of pneumonia. Infect Immun, 2004; 72(5):2899–2906.
80.
MoitraD, MiraclinP, GulN, et al.Antibody therapy: Past, present and future. Austin Biochem, 2021; 6(1):1029.
81.
WangQ, ChenY, CvitkovicR, et al.Anti-MrkA monoclonal antibodies reveal distinct structural and antigenic features of MrkA. PLoS One, 2017; 12(1):e0170529.
82.
ChenC-W, HsuC-Y, LaiS-M, et al.Metal nanobullets for multidrug resistant bacteria and biofilms. Adv Drug Deliv Rev, 2014; 78:88–104.
83.
LiH, ChenQ, ZhaoJ, et al.Enhancing the antimicrobial activity of natural extraction using the synthetic ultrasmall metal nanoparticles. Sci Rep, 2015; 5(1):11033.
84.
HossainZ, YasmeenF, KomatsuS. Nanoparticles: Synthesis, morphophysiological effects, and proteomic responses of crop plants. Int J Mol Sci, 2020; 21(9):3056.
85.
YinIX, ZhangJ, ZhaoIS, et al.The antibacterial mechanism of silver nanoparticles and its application in dentistry. Int J Nanomedicine, 2020; 15:2555–2562.
86.
HajipourMJ, FrommKM, AshkarranAA, et al.Antibacterial properties of nanoparticles. Trends Biotechnol, 2012; 30(10):499–511.
87.
JijieR, BarrasA, TeodorescuF, et al.Advancements on the molecular design of nanoantibiotics: Current level of development and future challenges. Mol Syst Des Eng, 2017; 2(4):349–369.
88.
JiaG, RaoZ, ZhangJ, et al.Tetraether biomarker records from a loess-paleosol sequence in the western Chinese Loess Plateau. Front Microbiol, 2013; 4:199.
89.
EnginAB, EnginA. Nanoantibiotics: A novel rational approach to antibiotic resistant infections. Curr Drug Metab, 2019; 20(9):720–741.
90.
HadiyaS, IbrahemRA, Abd El-BakyRM, et al.Nanoparticles based combined antimicrobial drug delivery system as a solution for bacterial resistance. Bull Pharm Sci Assiut University, 2022; 45(2):1121–1141.
91.
ArafatM, KirchhoeferC, MikovM, et al.Nanosized liposomes containing bile salt: A vesicular nanocarrier for enhancing oral bioavailability of BCS Class III Drug. J Pharm Pharm Sci, 2017; 20(0):305–318.
92.
MamunMM, SorinoluAJ, MunirM, et al.Nanoantibiotics: Functions and properties at the nanoscale to combat antibiotic resistance. Front Chem, 2021; 9:687660.
93.
ÇalışkanN, BayramC, ErdalE, et al.Titania nanotubes with adjustable dimensions for drug reservoir sites and enhanced cell adhesion. Mater Sci Eng C Mater Biol Appl, 2014; 35:100–105.
94.
MeadeE, SlatteryMA, GarveyM. Bacteriocins, potent antimicrobial peptides and the fight against multi drug resistant species: Resistance is futile? Antibiotics (Basel), 2020; 9(1):32.
95.
BiswasK, UpadhayayS, RapsangGF, et al.Antibacterial and synergistic activity against β-Lactamase-producing nosocomial bacteria by bacteriocin of LAB isolated from lesser known traditionally fermented products of India. HAYATI Journal of Biosciences, 2017; 24(2):87–95.
96.
BehrensHM, SixA, WalkerD, et al.The therapeutic potential of bacteriocins as protein antibiotics. Emerg Top Life Sci, 2017; 1(1):65–74.
97.
LashinGM, TohamyE, AskoraA. Use of probiotic acid bacteria for the control of multidrug resistant bacteria isolated from clinical infections. Bull Faculty Sci Zagazig University, 2017; 2017(2017):61–81.
98.
ShehabHAH, ShahatMSA, ElhosinyIM, et al.Study of the anti-bacterial efficacy of probiotics culture extracts on extended spectrum beta lactamase-producing multi-drug resistant isolates, bearing BLA-TEM-1 gene, in patients with wound infections in hospitals. Int J Med Arts, 2022; 4(4).
99.
SavinovaOS, GlazunovaOA, MoiseenkoKV, et al.Exoproteome analysis of antagonistic interactions between the probiotic bacteria Limosilactobacillus reuteri LR1 and Lacticaseibacillus rhamnosus F and multidrug resistant strain of klebsiella pneumonia. Int J Mol Sci, 2021; 22(20):10999.
100.
RarasTYM, FirdausyAF, KinantiIR, et al.Anti-biofilm activity of lactic acid bacteria isolated from kefir against multidrug-resistant Klebsiella pneumoniae. J Pure Applied Microbiol, 2019; 13(2).
101.
YüksekFK, GümüşD, TuranDBTB, et al.Cell-free supernatants of lactobacilli inhibit methicilin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and carbapenem-resistant Klebsiella strains. Ege Tıp Dergisi, 2021; 60(4):332–339.
102.
WieërsG, VerbelenV, Van Den DriesscheM, et al.Do probiotics during in-hospital antibiotic treatment prevent colonization of gut microbiota with multi-drug-resistant bacteria? A randomized placebo-controlled trial comparing Saccharomyces to a mixture of Lactobacillus, Bifidobacterium, and Saccharomyces. Front Public Health, 2020; 8:578089.
103.
ZhangC, WangC, XiuZ. Regulation of c-di-GMP in biofilm formation of Klebsiella pneumoniae in response to antibiotics and probiotic supernatant in a chemostat system. Curr Microbiol, 2021; 78(1):133–143.
104.
OlivaA, MieleMC, De AngelisM, et al.Antibacterial effectiveness of fecal water and in vitro activity of a multi-strain probiotic formulation against multi-drug resistant microorganisms. Microorganisms, 2020; 8(3):332.
105.
MandalS, HalderD. Exploring Anti-Klebsiella pneumoniae activity of probiotic lactobacilli of curd origin. Acta Scient Microb, 2018; 1(4):49–53.
106.
TangH-J, ChenC-C, LuY-C, et al.The effect of Lactobacillus with prebiotics on KPC-2-producing Klebsiella pneumoniae. Front Microbiol, 2022; 13:1050247.
107.
UeckermannV, HoosienE, De VilliersN, et al.Fecal microbial transplantation for the treatment of persistent multidrug-resistant Klebsiella pneumoniae infection in a critically ill patient. Case Rep Infect Dis, 2020; 2020:8462659.
108.
MangesAR, SteinerTS, WrightAJ. Fecal microbiota transplantation for the intestinal decolonization of extensively antimicrobial-resistant opportunistic pathogens: A review. Infect Dis (Lond), 2016; 48(8):587–592.
109.
Macareño-CastroJ, Solano-SalazarA, MohiuddinM, et al.Fecal microbiota transplantation for Carbapenem-Resistant Enterobacteriaceae: A systematic review. J Infect, 2022; 84(6):749–759.
110.
UeckermannV, HoosienE, De VilliersN, et al.Case Report Fecal Microbial Transplantation for the Treatment of Persistent Multidrug-Resistant Klebsiella pneumoniae Infection in a Critically Ill Patient. 2020.
111.
WangJ, LiX, WuX, et al.Fecal microbiota transplantation as an effective treatment for carbapenem-resistant Klebsiella pneumoniae infection in a renal transplant patient. Infect Drug Resist, 2021; 14:1805–1811.
112.
HyunJ, LeeSK, CheonJH, et al.Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms. Antimicrob Resist Infect Control, 2022; 11(1):20.
113.
Bar-YosephH, CarassoS, ShklarS, et al.Oral capsulized fecal microbiota transplantation for eradication of carbapenemase-producing enterobacteriaceae colonization with a metagenomic perspective. Clin Infect Dis, 2021; 73(1):e166–e1675.
114.
BilsenMP, LambregtsMM, van PrehnJ, et al.Faecal microbiota replacement to eradicate antimicrobial resistant bacteria in the intestinal tract–a systematic review. Curr Opin Gastroenterol, 2022; 38(1):15–25.
115.
BakerM, NegusD, RaghunathanD, et al.Measuring and modelling the response of Klebsiella pneumoniae KPC prey to Bdellovibrio bacteriovorus predation, in human serum and defined buffer. Sci Rep, 2017; 7(1):8329.
116.
AtterburyRJ, TysonJ. Predatory bacteria as living antibiotics–where are we now? Microbiology, 2021; 167(1):e001025.
117.
ShatzkesK, SingletonE, TangC, et al.Predatory bacteria attenuate Klebsiella pneumoniae burden in rat lungs. mBio, 2016; 7(6):e01847–e01816; doi: 10.1128/mbio.01847-16
118.
DharaniS, KimDH, ShanksRM, et al.Susceptibility of colistin-resistant pathogens to predatory bacteria. Res Microbiol, 2018; 169(1):52–55.
119.
KodeM, Waso-ReynekeM, ReynekeB, et al.Integration of Bdellovibrio spp. with SODIS and Moringa oleifera flocculation to target multi-drug resistant Klebsiella pneumoniae and Pseudomonas aeruginosa. J Environ Chem Eng, 2022; 10(3):107962.
120.
JangH, ChoiSY, MunW, et al.Predation of colistin-and carbapenem-resistant bacterial pathogenic populations and their antibiotic resistance genes in simulated microgravity. Microbiol Res, 2022; 255:126941.
121.
ImH, ChoiSY, SonS, et al.Combined application of bacterial predation and violacein to kill polymicrobial pathogenic communities. Sci Rep, 2017; 7(1):14415.
122.
PérezJ, Contreras-MorenoFJ, Marcos-TorresFJ, et al.The antibiotic crisis: How bacterial predators can help. Comput Struct Biotechnol J, 2020; 18:2547–2555.
123.
ShatzkesK, SingletonE, TangC, et al.Examining the efficacy of intravenous administration of predatory bacteria in rats. Sci Rep, 2017; 7(1):1864.
124.
Al-KubaisySH, HusseinRA, Al-OuqailiM. Molecular Screening of Ambler class C and extended-spectrum β-lactamases in multi-drug resistant Pseudomonas aeruginosa and selected species of Enterobacteriaceae. Int J Pharm Res, 2020; 12:3605–3613.
125.
IosifidisE, ChorafaE, AgakidouE, et al.Use of ceftazidime-avibactam for the treatment of extensively drug-resistant or pan drug-resistant Klebsiella pneumoniae in neonates and children< 5 years of age. Pediatric Infect Dis J, 2019; 38(8):812–815.
126.
VendittiC, ButeraO, MeledandriM, et al.Molecular analysis of clinical isolates of ceftazidime-avibactam-resistant Klebsiella pneumoniae. Clin Microbiol Infection, 2021; 27(7):1040.e1–e6.
127.
GiddinsMJ, MacesicN, AnnavajhalaMK, et al.Successive emergence of ceftazidime-avibactam resistance through distinct genomic adaptations in bla KPC-2-harboring Klebsiella pneumoniae sequence type 307 isolates. Antimicrob Agents Chemother, 2018; 62(3):e02101–e02117; doi: 10.1128/aac.02101-17
128.
GalaniI, KaraiskosI, GiamarellouH. Multidrug-resistant Klebsiella pneumoniae: Mechanisms of resistance including updated data for novel β-lactam-β-lactamase inhibitor combinations. Expert Rev Anti Infect Ther, 2021; 19(11):1457–1468.
129.
CarattoliA, ArcariG, BibbolinoG, et al.Evolutionary Trajectories toward Ceftazidime-Avibactam Resistance in Klebsiella pneumoniae Clinical Isolates. Antimicrob Agents Chemother, 2021; 65(10):e0057421.
130.
WinklerML, Papp-WallaceKM, BonomoRA. Activity of ceftazidime/avibactam against isogenic strains of Escherichia coli containing KPC and SHV β-lactamases with single amino acid substitutions in the Ω-loop. J Antimicrob Chemother, 2015; 70(8):2279–2286.
131.
SantevecchiBA, SmithTT, MacVaneSH. Clinical experience with ceftazidime/avibactam for treatment of antibiotic-resistant organisms other than Klebsiella pneumoniae. Int J Antimicrob Agents, 2018; 51(4):629–635.
132.
KaraiskosI, DaikosG, GkoufaA, et al.; Hellenic Ceftazidime/Avibactam Registry Study Group. Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: Experience from a national registry study. J Antimicrob Chemother, 2021; 76(3):775–783.
133.
NovelliA, Del GiacomoP, RossoliniGM, et al.Meropenem/vaborbactam: A next generation β-lactam β-lactamase inhibitor combination. Expert Rev Anti Infect Ther, 2020; 18(7):643–655.
134.
AmerehS, KelishomiFZ, GhayazF, et al.Activity of meropenem-vaborbactam against different beta-lactamase producing Klebsiella pneumoniae and Escherichia coli isolates in Iran. Acta Microbiol Immunol Hung, 2022; 69(3):201–208.
135.
Al-OuqailiMT. Molecular detection of medically important carbapenemases genes expressed by Metallo-Î2-lactamase producer isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae. Asian J Pharm (AJP), 2018; 12(03).
136.
Denervaud-TendonV, PoirelL, ConnollyLE, et al.Plazomicin activity against polymyxin-resistant Enterobacteriaceae, including MCR-1-producing isolates. J Antimicrob Chemother, 2017; 72(10):2787–2791.
137.
WalktyA, KarlowskyJA, BaxterMR, et al.In vitro activity of plazomicin against gram-negative and gram-positive bacterial pathogens isolated from patients in Canadian hospitals from 2013 to 2017 as part of the CANWARD surveillance study. Antimicrob Agents Chemother, 2019; 63(1):e02068–e02018; doi: 10.1128/aac.02068-18
138.
TiseoG, SuardiLR, LeonildiA, et al.Meropenem/vaborbactam plus aztreonam for the treatment of New Delhi metallo-β-lactamase-producing Klebsiella pneumoniae infections. J Antimicrob Chemother, 2023; 78(9):2377–2379.
139.
CultreraR, LibanoreM, BarozziA, et al.Ceftolozane/tazobactam and ceftazidime/avibactam for multidrug-resistant Gram-negative infections in immunocompetent patients: A single-center retrospective study. Antibiotics (Basel), 2020; 9(10):640.
140.
BalabanianG, RoseM, ManningN, et al.Effect of porins and bla KPC expression on activity of imipenem with relebactam in Klebsiella pneumoniae: Can antibiotic combinations overcome resistance? Microb Drug Resist, 2018; 24(7):877–881.
141.
LaiC-C, ChenC-C, LuY-C, et al.Appropriate composites of cefoperazone-sulbactam against multidrug-resistant organisms. Infect Drug Resist, 2018; 11:1441–1445.
142.
XuC, WeiX, JinY, et al.Development of resistance to eravacycline by Klebsiella pneumoniae and collateral sensitivity-guided design of combination therapies. Microbiol Spectr, 2022; 10(5):e01390-22.
143.
ZhengJ-X, LinZ-W, SunX, et al.Overexpression of OqxAB and MacAB efflux pumps contributes to eravacycline resistance and heteroresistance in clinical isolates of Klebsiella pneumoniae. Emerg Microbes Infect, 2018; 7(1):139–111.
144.
DaoudL, Al-MarzooqF, GhazawiA, et al.High efficacy and enhanced synergistic activity of the novel siderophore-cephalosporin cefiderocol against multidrug-resistant and extensively drug-resistant Klebsiella pneumoniae from inpatients attending a single hospital in the United Arab Emirates. J Infect Public Health, 2023; 16(Suppl 1):33–44.
145.
ZhanelGG, GoldenAR, ZelenitskyS, et al.Cefiderocol: A siderophore cephalosporin with activity against carbapenem-resistant and multidrug-resistant gram-negative bacilli. Drugs, 2019; 79(3):271–289.
146.
ThomsonKS, AbdelGhaniS, SnyderJW, et al.Activity of cefepime-zidebactam against multidrug-resistant (MDR) Gram-negative pathogens. Antibiotics (Basel), 2019; 8(1):32.
147.
JoshiP, ShrivastavaR, BhagwatS, et al.Activity of β-lactam plus β-lactam-enhancer combination cefepime/zidebactam against Klebsiella pneumoniae harbouring defective OmpK35/36 porins and carbapenemases. Diagn Microbiol Infect Dis, 2021; 101(2):115481.
HagiharaM, KatoH, SuganoT, et al.In vivo pharmacodynamics of β-lactams/nacubactam against carbapenem-resistant and/or carbapenemase-producing Enterobacter cloacae and Klebsiella pneumoniae in murine pneumonia model. Antibiotics (Basel), 2021; 10(10):1179.
150.
Vázquez-UchaJC, Lasarte-MonterrubioC, Guijarro-SánchezP, et al.; GEMARA-SEIMC/REIPI Enterobacterales Study Group. Assessment of activity and resistance mechanisms to cefepime in combination with the novel β-lactamase inhibitors zidebactam, taniborbactam, and enmetazobactam against a multicenter collection of carbapenemase-producing Enterobacterales. Antimicrob Agents Chemother, 2022; 66(2):e01676-21.
151.
LeeY-L, KoW-C, LeeW-S, et al.In-vitro activity of cefiderocol, cefepime/zidebactam, cefepime/enmetazobactam, omadacycline, eravacycline and other comparative agents against carbapenem-nonsusceptible Enterobacterales: Results from the Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART) in 2017–2020. Int J Antimicrob Agents, 2021; 58(3):106377.
152.
JohnsonA, McEnteeL, FarringtonN, et al.Pharmacodynamics of cefepime combined with the novel extended-spectrum-β-lactamase (ESBL) inhibitor enmetazobactam for murine pneumonia caused by ESBL-producing Klebsiella pneumoniae. Antimicrob Agents Chemother, 2020; 64(6):e00180–e00120; doi: 10.1128/aac.00180-20
153.
AsbelLE, LevisonME. Cephalosporins, carbapenems, and monobactams. Infect Dis Clin North Am, 2000; 14(2):435–447, ix.
154.
JacobyGA, Munoz-PriceLS. The new β-lactamases. N Engl J Med, 2005; 352(4):380–391.
155.
BonomoRA. β-lactamases: A focus on current challenges. Cold Spring Harb Perspect Med, 2017; 7(1):a025239.
JeanS-S, LeeW-S, LamC, et al.Carbapenemase-producing Gram-negative bacteria: Current epidemics, antimicrobial susceptibility and treatment options. Future Microbiol, 2015; 10(3):407–425.
158.
Walther-RasmussenJ, HøibyN. Class A carbapenemases. J Antimicrob Chemother, 2007; 60(3):470–482.
159.
ZusmanO, AvniT, LeiboviciL, et al.Systematic review and meta-analysis of in vitro synergy of polymyxins and carbapenems. Antimicrob Agents Chemother, 2013; 57(10):5104–5111.
160.
ReesVE, YadavR, RogersKE, et al.Meropenem combined with ciprofloxacin combats hypermutable pseudomonas aeruginosa from respiratory infections of cystic fibrosis patients. Antimicrob Agents Chemother, 2018; 62(11):e01150–e01118.
161.
ErdemF, AbulailaA, AktasZ, et al.In vitro evaluation of double carbapenem and colistin combinations against OXA-48, NDM carbapenemase-producing colistin-resistant Klebsiella pneumoniae strains. Antimicrob Resist Infect Control, 2020; 9(1):1–9.
162.
GalaniI, NafpliotiK, ChatzikonstantinouM, et al.In vitro evaluation of double-carbapenem combinations against OXA-48-producing Klebsiella pneumoniae isolates using time–kill studies. J Med Microbiol, 2018; 67(5):662–668.
163.
CancelliF, OlivaA, De AngelisM, et al.Role of double-carbapenem regimen in the treatment of infections due to carbapenemase producing carbapenem-resistant Enterobacteriaceae: A single-center, observational study. Biomed Res Int, 2018; 2018:2785696.
164.
MoodyRO. The effect of double-carbapenem therapy on mortality rates and microbiological cure rates in patients diagnosed with carbapenem-resistant Klebsiella pneumoniae infections in comparison to monotherapy and currently used combinations of antibiotics. J Med Res Innov, 2021; 5(1):e000243-e.
165.
El NekidyWS, MootyMY, AttallahN, et al.Successful treatment of multidrug resistant Klebsiella pneumoniae using dual carbapenem regimen in immunocompromised patient. IDCases, 2017; 9:53–55.
166.
SheuC-C, ChangY-T, LinS-Y, et al.Infections caused by carbapenem-resistant Enterobacteriaceae: An update on therapeutic options. Front Microbiol, 2019; 10:80.
167.
CprekJB, GallagherJC. Ertapenem-containing double-carbapenem therapy for treatment of infections caused by carbapenem-resistant Klebsiella pneumoniae. Antimicrob Agents Chemother, 2016; 60(1):669–673.
168.
VenugopalanV, NogidB, LeTN, et al.Double carbapenem therapy (DCT) for bacteremia due to carbapenem-resistant Klebsiella pneumoniae (CRKP): from test tube to clinical practice. Infect Dis (Lond), 2017; 49(11–12):867–870.
ZouP, LiuJ, LiX, et al.A membrane curvature modulated lipopeptide to broadly combat multidrug-resistant bacterial pneumonia with low resistance risk. ACS Nano, 2022; 16(12):20545–20558.
171.
DomhanC, UhlP, MeinhardtA, et al.A novel tool against multiresistant bacterial pathogens: Lipopeptide modification of the natural antimicrobial peptide ranalexin for enhanced antimicrobial activity and improved pharmacokinetics. Int J Antimicrob Agents, 2018; 52(1):52–62.
172.
de Souza FreitasF, Coelho de Assis LageT, AyupeBAL, et al.Bacillus subtilis TR47II as a source of bioactive lipopeptides against Gram-negative pathogens causing nosocomial infections. 3 Biotech, 2020; 10(11):474–410.
173.
ChakrabortyT, ShawR, ChatterjeeDS, et al.Review on recent advancement of therapeutic interventions in combating multidrug resistant bacteria. Int J Life Sci Pharma Res, 2020; 10(5):166–179.
174.
HesseS, RajaureM, WallE, et al.Phage resistance in multidrug-resistant Klebsiella pneumoniae ST258 evolves via diverse mutations that culminate in impaired adsorption. mBio, 2020; 11(1):e02530–e02519; doi: 10.1128/mbio.02530-19
175.
TabassumR, ShafiqueM, KhawajaKA, et al.Complete genome analysis of a Siphoviridae phage TSK1 showing biofilm removal potential against Klebsiella pneumoniae. Sci Rep, 2018; 8(1):17904.
176.
WangZ, CaiR, WangG, et al.Combination therapy of phage vB_KpnM_P-KP2 and gentamicin combats acute pneumonia caused by K47 serotype Klebsiella pneumoniae. Front Microbiol, 2021; 12:674068.
177.
ShreeS, SumanE, KotianH, et al.Effect of Klebsiella-specific phage on multidrug-resistant Klebsiella pneumoniae-an experimental study. Indian J Med Microbiol, 2024; 47:100515.
MorrisseyI, MagnetS, HawserS, et al.In vitro activity of cefepime-enmetazobactam against Gram-negative isolates collected from US and European hospitals during 2014–2015. Antimicrob. Agents Chemother, 2019; 63:e00514-19.
BarnesMD, TaracilaMA, GoodCE, et al.Nacubactam enhances meropenem activity against carbapenem-resistant Klebsiella pneumoniae producing KPC. Antimicrob. Agents Chemother, 2019; 63:e00432-19.
182.
JadhavRA, AhirraoVK, PathanAR, et al.An efficient HPLC–MS method for impurity profile of ertapenem. Chromatographia, 2020; 83(9):1095–1105.
183.
TuonFF, RochaJL, Formigoni-PintoMR. Pharmacological aspects and spectrum of action of ceftazidime–avibactam: A systematic review. Infection, 2018; 46(2):165–181.
