scholarly journals LL-37-Derived Peptides Eradicate Multidrug-Resistant Staphylococcus aureus from Thermally Wounded Human Skin Equivalents

2014 ◽  
Vol 58 (8) ◽  
pp. 4411-4419 ◽  
Author(s):  
Elisabeth M. Haisma ◽  
Anna de Breij ◽  
Heelam Chan ◽  
Jaap T. van Dissel ◽  
Jan W. Drijfhout ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Human Skin ◽  
Synthetic Peptides ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Mitochondrial Activity ◽  
Bacterial Strains ◽  
Burn Wound ◽  
Content Type ◽  
Skin Equivalents

ABSTRACTBurn wound infections are often difficult to treat due to the presence of multidrug-resistant bacterial strains and biofilms. Currently, mupirocin is used to eradicate methicillin-resistantStaphylococcus aureus(MRSA) from colonized persons; however, mupirocin resistance is also emerging. Since we consider antimicrobial peptides to be promising candidates for the development of novel anti-infective agents, we studied the antibacterial activities of a set of synthetic peptides against different strains ofS. aureus, including mupirocin-resistant MRSA strains. The peptides were derived from P60.4Ac, a peptide based on the human cathelicidin LL-37. The results showed that peptide 10 (P10) was the only peptide more efficient than P60.4Ac, which is better than LL-37, in killing MRSA strain LUH14616. All three peptides displayed good antibiofilm activities. However, both P10 and P60.4Ac were more efficient than LL-37 in eliminating biofilm-associated bacteria. No toxic effects of these three peptides on human epidermal models were detected, as observed morphologically and by staining for mitochondrial activity. In addition, P60.4Ac and P10, but not LL-37, eradicated MRSA LUH14616 and the mupirocin-resistant MRSA strain LUH15051 from thermally wounded human skin equivalents (HSE). Interestingly, P60.4Ac and P10, but not mupirocin, eradicated LUH15051 from the HSEs. None of the peptides affected the excretion of interleukin 8 (IL-8) by thermally wounded HSEs upon MRSA exposure. In conclusion, the synthetic peptides P60.4Ac and P10 appear to be attractive candidates for the development of novel local therapies to treat patients with burn wounds infected with multidrug-resistant bacteria.

scholarly journals Targeting Methicillin-Resistant Staphylococcus aureus with Short Salt-Resistant Synthetic Peptides

2014 ◽  
Vol 58 (7) ◽  
pp. 4113-4122 ◽  
Author(s):  
Mohamed F. Mohamed ◽  
Maha I. Hamed ◽  
Alyssa Panitch ◽  
Mohamed N. Seleem
Keyword(s):  
Staphylococcus Aureus ◽  
Synthetic Peptides ◽  
Bactericidal Effect ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Net Charge ◽  
Methicillin Resistant ◽  
Content Type ◽  
C Terminus ◽  
Conventional Antibiotics

ABSTRACTThe seriousness of microbial resistance combined with the lack of new antimicrobials has increased interest in the development of antimicrobial peptides (AMPs) as novel therapeutics. In this study, we evaluated the antimicrobial activities of two short synthetic peptides, namely, RRIKA and RR. These peptides exhibited potent antimicrobial activity againstStaphylococcus aureus, and their antimicrobial effects were significantly enhanced by addition of three amino acids in the C terminus, which consequently increased the amphipathicity, hydrophobicity, and net charge. Moreover, RRIKA and RR demonstrated a significant and rapid bactericidal effect against clinical and drug-resistantStaphylococcusisolates, including methicillin-resistantStaphylococcus aureus(MRSA), vancomycin-intermediateS. aureus(VISA), vancomycin-resistantS. aureus(VRSA), linezolid-resistantS. aureus, and methicillin-resistantStaphylococcus epidermidis. In contrast to many natural AMPs, RRIKA and RR retained their activity in the presence of physiological concentrations of NaCl and MgCl2. Both RRIKA and RR enhanced the killing of lysostaphin more than 1,000-fold and eradicated MRSA and VRSA isolates within 20 min. Furthermore, the peptides presented were superior in reducing adherent biofilms ofS. aureusandS. epidermidiscompared to results with conventional antibiotics. Our findings indicate that the staphylocidal effects of our peptides were through permeabilization of the bacterial membrane, leading to leakage of cytoplasmic contents and cell death. Furthermore, peptides were not toxic to HeLa cells at 4- to 8-fold their antimicrobial concentrations. The potent and salt-insensitive antimicrobial activities of these peptides present an attractive therapeutic candidate for treatment of multidrug-resistantS. aureusinfections.

scholarly journals Identification of Pyruvate Kinase in Methicillin-Resistant Staphylococcus aureus as a Novel Antimicrobial Drug Target

2011 ◽  
Vol 55 (5) ◽  
pp. 2042-2053 ◽  
Author(s):  
Roya Zoraghi ◽  
Raymond H. See ◽  
Peter Axerio-Cilies ◽  
Nag S. Kumar ◽  
Huansheng Gong ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pyruvate Kinase ◽  
Drug Target ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibacterial Drug ◽  
Methicillin Resistant ◽  
Content Type ◽  
Antistaphylococcal Activity

ABSTRACTNovel classes of antimicrobials are needed to address the challenge of multidrug-resistant bacteria such as methicillin-resistantStaphylococcus aureus(MRSA). Using the architecture of the MRSA interactome, we identified pyruvate kinase (PK) as a potential novel drug target based upon it being a highly connected, essential hub in the MRSA interactome. Structural modeling, including X-ray crystallography, revealed discrete features of PK in MRSA, which appeared suitable for the selective targeting of the bacterial enzyme.In silicolibrary screening combined with functional enzymatic assays identified an acyl hydrazone-based compound (IS-130) as a potent MRSA PK inhibitor (50% inhibitory concentration [IC50] of 0.1 μM) with >1,000-fold selectivity over human PK isoforms. Medicinal chemistry around the IS-130 scaffold identified analogs that more potently and selectively inhibited MRSA PK enzymatic activity andS. aureusgrowthin vitro(MIC of 1 to 5 μg/ml). These novel anti-PK compounds were found to possess antistaphylococcal activity, including both MRSA and multidrug-resistantS. aureus(MDRSA) strains. These compounds also exhibited exceptional antibacterial activities against other Gram-positive genera, including enterococci and streptococci. PK lead compounds were found to be noncompetitive inhibitors and were bactericidal. In addition, mutants with significant increases in MICs were not isolated after 25 bacterial passages in culture, indicating that resistance may be slow to emerge. These findings validate the principles of network science as a powerful approach to identify novel antibacterial drug targets. They also provide a proof of principle, based upon PK in MRSA, for a research platform aimed at discovering and optimizing selective inhibitors of novel bacterial targets where human orthologs exist, as leads for anti-infective drug development.

scholarly journals Intravitreal Injection of the Chimeric Phage Endolysin Ply187 Protects Mice from Staphylococcus aureus Endophthalmitis

2014 ◽  
Vol 58 (8) ◽  
pp. 4621-4629 ◽  
Author(s):  
Pawan Kumar Singh ◽  
David M. Donovan ◽  
Ashok Kumar
Keyword(s):  
Staphylococcus Aureus ◽  
Intravitreal Injection ◽  
Structural Integrity ◽  
Therapeutic Potential ◽  
Neutrophil Infiltration ◽  
Multidrug Resistant ◽  
Lytic Enzyme ◽  
Resistant Bacteria ◽  
Content Type ◽  
Mrsa Strains

ABSTRACTThe treatment of endophthalmitis is becoming very challenging due to the emergence of multidrug-resistant bacteria. Hence, the development of novel therapeutic alternatives for ocular use is essential. Here, we evaluated the therapeutic potential of Ply187AN-KSH3b, a chimeric phage endolysin derived from the Ply187 prophage, in a mouse model ofStaphylococcus aureusendophthalmitis. Our data showed that the chimeric Ply187 endolysin exhibited strong antimicrobial activity against both methicillin-sensitiveS. aureusand methicillin-resistantS. aureus(MRSA) strains, as evidenced by MIC determinations, reductions in turbidity, and disruption of biofilms. Moreover, exposure ofS. aureusto Ply187 for up to 10 generations did not lead to resistance development. The intravitreal injection of chimeric Ply187 (at 6 or 12 h postinfection) significantly improved the outcome of endophthalmitis, preserved retinal structural integrity, and maintained visual function as assessed by electroretinogram analysis. Furthermore, phage lysin treatment significantly reduced the bacterial burden and the levels of inflammatory cytokines and neutrophil infiltration in the eyes. These results indicate that the intravitreal administration of a phage lytic enzyme attenuates the development of bacterial endophthalmitis in mice. To the best of our knowledge, this is the first study demonstrating the therapeutic use of phage-based antimicrobials in ocular infections.

scholarly journals Phage-Antibiotic Synergy Is Driven by a Unique Combination of Antibacterial Mechanism of Action and Stoichiometry

mBio ◽  
2020 ◽  
Vol 11 (4) ◽  
Author(s):  
Carmen Gu Liu ◽  
Sabrina I. Green ◽  
Lorna Min ◽  
Justin R. Clark ◽  
Keiko C. Salazar ◽  
...  
Keyword(s):  
Bacterial Growth ◽  
Therapeutic Option ◽  
Microtiter Plate ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Dependent Manner ◽  
Drug Resistant ◽  
Bacterial Strains ◽  
Content Type ◽  
Drug Resistant Strains

ABSTRACT The continued rise in antibiotic resistance is precipitating a medical crisis. Bacteriophage (phage) has been hailed as one possible therapeutic option to augment the efficacy of antibiotics. However, only a few studies have addressed the synergistic relationship between phage and antibiotics. Here, we report a comprehensive analysis of phage-antibiotic interaction that evaluates synergism, additivism, and antagonism for all classes of antibiotics across clinically achievable stoichiometries. We combined an optically based real-time microtiter plate readout with a matrix-like heat map of treatment potencies to measure phage and antibiotic synergy (PAS), a process we term synography. Phage-antibiotic synography was performed against a pandemic drug-resistant clonal group of extraintestinal pathogenic Escherichia coli (ExPEC) with antibiotic levels blanketing the MIC across seven orders of viral titers. Our results suggest that, under certain conditions, phages provide an adjuvating effect by lowering the MIC for drug-resistant strains. Furthermore, synergistic and antagonistic interactions are highly dependent on the mechanism of bacterial inhibition by the class of antibiotic paired to the phage, and when synergism is observed, it suppresses the emergence of resistant cells. Host conditions that simulate the infection environment, including serum and urine, suppress PAS in a bacterial growth-dependent manner. Lastly, two different related phages that differed in their burst sizes produced drastically different synograms. Collectively, these data suggest lytic phages can resuscitate an ineffective antibiotic for previously resistant bacteria while also synergizing with antibiotics in a class-dependent manner, processes that may be dampened by lower bacterial growth rates found in host environments. IMPORTANCE Bacteriophage (phage) therapy is a promising approach to combat the rise of multidrug-resistant bacteria. Currently, the preferred clinical modality is to pair phage with an antibiotic, a practice thought to improve efficacy. However, antagonism between phage and antibiotics has been reported, the choice of phage and antibiotic is not often empirically determined, and the effect of the host factors on the effectiveness is unknown. Here, we interrogate phage-antibiotic interactions across antibiotics with different mechanisms of action. Our results suggest that phage can lower the working MIC for bacterial strains already resistant to the antibiotic, is dependent on the antibiotic class and stoichiometry of the pairing, and is dramatically influenced by the host microenvironment.

scholarly journals Histatin-Derived Monomeric and Dimeric Synthetic Peptides Show Strong Bactericidal Activity towards Multidrug-Resistant Staphylococcus aureus In Vivo

2007 ◽  
Vol 51 (9) ◽  
pp. 3416-3419 ◽  
Author(s):  
Mick M. Welling ◽  
Carlo P. J. M. Brouwer ◽  
Wim van ′t Hof ◽  
Enno C. I. Veerman ◽  
Arie V. Nieuw Amerongen
Keyword(s):  
Staphylococcus Aureus ◽  
Soft Tissue ◽  
Bactericidal Activity ◽  
Synthetic Peptides ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria

ABSTRACT Homodimerization of histatin-derived peptides generally led to improved bactericidal activity against Staphylococcus aureus in vitro. In vivo, monomers and dimers were equally active in killing bacteria in mice with a soft tissue infection. Altogether, these peptides are promising compounds for the development of novel therapeutics against infections with drug-resistant bacteria.

scholarly journals Antimicrobial Activities of Teucrium creticum against Reference Microbial Strains and Multi-drug Resistant Bacteria Isolated at an Oncology Ward

2019 ◽  
pp. 1-7
Author(s):  
Motasem Al-Masri ◽  
Ghadeer Omar ◽  
Adham Taha ◽  
Amira Abu Alsoud ◽  
Eman Tawafsha ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Aqueous Extract ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Resistant Bacteria ◽  
Dilution Method ◽  
Bacterial Strains ◽  
Patients With Cancer ◽  
Oncology Ward ◽  
National University

Aim: To determine antimicrobial activity of Teucrium creticum (T. creticum) leaves extract against bacterial and fungal reference strains and multidrug resistant bacteria isolated at an oncology ward. Study Design: Cross-sectional study. Place and Duration of Study: The study was carried out in department of biology and biotechnology in An-Najah National University in cooperation with the laboratory of the hospital of the university.  An-Najah National University is located in West Bank in Palestine. The research was performed from 8th of February to the 15th of April 2017.  Methodology: Teucrium creticum plant leaves were collected in Palestine, from which aqueous and methanolic extracts were prepared. Antimicrobial activities of T. creticum extracts were determined against reference bacterial and fungal strains as well as against 8 multidrug resistant bacteria isolated at an oncology ward.  Antibacterial and anti-yeast activities were determined by Micro broth dilution method, while anti-mold activities were determined by agar dilution method. Teucrium creticum methanolic extract strongly inhibited the growth of the studied reference bacterial strains, which were Staphylococcus aureus (MIC= 1.56 mg/ml) and Shigella sonnie (MIC=3.125 mg/ml).  In addition, most of the 8 multi-drug resistant bacterial strains isolated from patients with cancer (Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia Coli and Enterobacter cloacae) were also highly susceptible to methanolic extract (MIC=3.125 mg/ml).  Both the Staphylococcus aureus and Shigella sonnie reference strains were inhibited at lower level by the aqueous extract (MIC=12.5 mg/ml). All the bacterial strains isolated from patients with cancer were susceptible to aqueous extract at different levels (3.125 – 25 mg/ml).  Epidermophyton floccosum mold and Candida albicans yeast were strongly inhibited by aqueous extract, where the MIC values were 1.56 and 3.125 mg/ml, respectively.   Conclusion: T. creticum plant extracts showed promising antimicrobial activities against multidrug resistant bacterial isolates as well as against reference bacterial and fungal strains.

scholarly journals A Putative Cro-Like Repressor Contributes to Arylomycin Resistance in Staphylococcus aureus

2015 ◽  
Vol 59 (6) ◽  
pp. 3066-3074 ◽  
Author(s):  
Arryn Craney ◽  
Floyd E. Romesberg
Keyword(s):  
Staphylococcus Aureus ◽  
Ex Vivo ◽  
Transcriptional Regulator ◽  
Signal Peptidase ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Type I ◽  
Wall Teichoic Acid ◽  
Content Type ◽  
Wide Range

ABSTRACTAntibiotic-resistant bacteria are a significant public health concern and motivate efforts to develop new classes of antibiotics. One such class of antibiotics is the arylomycins, which target type I signal peptidase (SPase), the enzyme responsible for the release of secreted proteins from their N-terminal leader sequences. Despite the essentiality, conservation, and relative accessibility of SPase, the activity of the arylomycins is limited against some bacteria, including the important human pathogenStaphylococcus aureus. To understand the origins of the limited activity againstS. aureus, we characterized the susceptibility of a panel of strains to two arylomycin derivatives, arylomycin A-C16and its more potent analog arylomycin M131. We observed a wide range of susceptibilities to the two arylomycins and found that resistant strains were sensitized by cotreatment with tunicamycin, which inhibits the first step of wall teichoic acid synthesis. To further understand howS. aureusresponds to the arylomycins, we profiled the transcriptional response ofS. aureusNCTC 8325 to growth-inhibitory concentrations of arylomycin M131 and found that it upregulates the cell wall stress stimulon (CWSS) and an operon consisting of a putative transcriptional regulator and three hypothetical proteins. Interestingly, we found that mutations in the putative transcriptional regulator are correlated with resistance, and selection for resistanceex vivodemonstrated that mutations in this gene are sufficient for resistance. The results begin to elucidate howS. aureuscopes with secretion stress and how it evolves resistance to the inhibition of SPase.

scholarly journals Environmental Spread of New Delhi Metallo-β-Lactamase-1-Producing Multidrug-Resistant Bacteria in Dhaka, Bangladesh

2017 ◽  
Vol 83 (15) ◽  
Author(s):  
Mohammad Aminul Islam ◽  
Moydul Islam ◽  
Rashedul Hasan ◽  
M. Iqbal Hossain ◽  
Ashikun Nabi ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Resistance Genes ◽  
Tap Water ◽  
Antibiotic Resistance Genes ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
New Delhi ◽  
Multidrug Resistant Bacteria ◽  
Content Type ◽  
Wastewater Samples

ABSTRACT Resistance to carbapenem antibiotics through the production of New Delhi metallo-β-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor the possible source of the spread of these organisms in Dhaka, Bangladesh, we conducted a comparative analysis of wastewater samples from hospital-adjacent areas (HAR) and from community areas (COM), as well as public tap water samples, for the occurrence and characteristics of NDM-1-producing bacteria. Of 72 HAR samples tested, 51 (71%) samples were positive for NDM-1-producing bacteria, as evidenced by phenotypic tests and the presence of the bla NDM-1 gene, compared to 5 of 41 (12.1%) samples from COM samples (P < 0.001). All tap water samples were negative for NDM-1-producing bacteria. Klebsiella pneumoniae (44%) was the predominant bacterial species among bla NDM-1-positive isolates, followed by Escherichia coli (29%), Acinetobacter spp. (15%), and Enterobacter spp. (9%). These bacteria were also positive for one or more other antibiotic resistance genes, including bla CTX-M-1 (80%), bla CTX-M-15 (63%), bla TEM (76%), bla SHV (33%), bla CMY-2 (16%), bla OXA-48-like (2%), bla OXA-1 (53%), and bla OXA-47-like (60%) genes. Around 40% of the isolates contained a qnr gene, while 50% had 16S rRNA methylase genes. The majority of isolates hosted multiple plasmids, and plasmids of 30 to 50 MDa carrying bla NDM-1 were self-transmissible. Our results highlight a number of issues related to the characteristics and source of spread of multidrug-resistant bacteria as a potential public health threat. In view of the existing practice of discharging untreated liquid waste into the environment, hospitals in Dhaka city contribute to the potential dissemination of NDM-1-producing bacteria into the community. IMPORTANCE Infections caused by carbapenemase-producing Enterobacteriaceae are extremely difficult to manage due to their marked resistance to a wide range of antibiotics. NDM-1 is the most recently described carbapenemase, and the bla NDM-1 gene, which encodes NDM-1, is located on self-transmissible plasmids that also carry a considerable number of other antibiotic resistance genes. The present study shows a high prevalence of NDM-1-producing organisms in the wastewater samples from hospital-adjacent areas as a potential source for the spread of these organisms to community areas in Dhaka, Bangladesh. The study also examines the characteristics of the isolates and their potential to horizontally transmit the resistance determinants. The significance of our research is in identifying the mode of spread of multiple-antibiotic-resistant organisms, which will allow the development of containment measures, leading to broader impacts in reducing their spread to the community.

Therapeutic Potential of Green Synthesized Metallic Nanoparticles against Staphylococcus aureus

2021 ◽  
Vol 13 ◽  
Author(s):  
Meron Moges Tsegaye ◽  
Garima Chouhan ◽  
Molla Fentie ◽  
Priya Tyagi ◽  
Parma Nand
Keyword(s):  
Staphylococcus Aureus ◽  
Metallic Nanoparticles ◽  
Therapeutic Potential ◽  
Multidrug Resistant ◽  
Health Condition ◽  
World Health ◽  
Therapeutic Modality ◽  
Effective Control ◽  
Bacterial Strains ◽  
Synthesis Of Nanoparticles

Background: The recent treatment challenges posed by the widespread emergence of pathogenic Multidrug‐Resistant (MDR) bacterial strains are a cause of huge health troubles worldwide. Infections caused by MDR organisms are associated with longer period of hospitalization, increased mortality, and inflated healthcare costs. Staphylococcus aureus is one of these MDR organisms identified as an urgent threat to human health by the World Health Organization. Infections caused by S. aureus may range from simple cutaneous infestations to life threatening bacteremia. S. aureus infections get easily escalated in severely ill, hospitalized and or immunocompromised patients with incapacitated immune system. Also, in HIV-positive patients S. aureus ranks amongst one of the most common comorbidities where it can further worsen a patient’s health condition. At present anti-staphylococcal therapy is reliant typically on chemotherapeutics that are gathering resistance and pose unfavorable side-effects. Thus, newer drugs are required that can bridge these shortcomings and aid effective control against S. aureus. Objective: In this review, we summarize drug resistance exhibited by S. aureus and lacunae in current anti-staphylococcal therapy, nanoparticles as an alternative therapeutic modality. The focus lays on various green synthesized nanoparticles, their mode of action and application as potent antibacterial compounds against S. aureus. Conclusion: Use of nanoparticles as anti-bacterial drugs has gained momentum in recent past and green synthesized nanoparticles, which involves microorganisms and plants or their byproducts for synthesis of nanoparticles offer a potent, as well as environment friendly solution in warfare against MDR bacte.

Resistance to nitrofurantoin is an indicator of extensive drug-resistant (XDR) Enterobacteriaceae

2021 ◽  
Vol 70 (4) ◽  
Author(s):  
Balaram Khamari ◽  
Prakash Kumar ◽  
Bulagonda Eswarappa Pradeep
Keyword(s):  
Antimicrobial Agents ◽  
Efflux Pump ◽  
Treatment Options ◽  
Strong Association ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Content Type ◽  
Link Type

Introduction. Nitrofurantoin is one of the preferred antibiotics in the treatment of uropathogenic multidrug-resistant (MDR) infections. However, resistance to nitrofurantoin in extensively drug-resistant (XDR) bacteria has severely limited the treatment options. Gap statement. Information related to co-resistance or collateral sensitivity (CS) with reference to nitrofurantoin resistant bacteria is limited. Aim. To study the potential of nitrofurantoin resistance as an indicator of the XDR phenotype in Enterobacteriaceae . Methods. One hundred (45 nitrofurantoin-resistant, 21 intermediately resistant and 34 nitrofurantoin-susceptible) Enterobacteriaceae were analysed in this study. Antibiotic susceptibility testing (AST) against nitrofurantoin and 17 other antimicrobial agents across eight different classes was performed by using the Vitek 2.0 system. The isolates were screened for the prevalence of acquired antimicrobial resistance (AMR) and efflux pump genes by PCR. Results. In total, 51 % of nitrofurantoin-resistant and 28 % of intermediately nitrofurantoin resistant isolates exhibited XDR characteristics, while only 3 % of nitrofurantoin-sensitive isolates were XDR (P=0.0001). Significant co-resistance was observed between nitrofurantoin and other tested antibiotics (β-lactam, cephalosporin, carbapenem, aminoglycoside and tetracycline). Further, the prevalence of AMR and efflux pump genes was higher in the nitrofurantoin-resistant strains compared to the susceptible isolates. A strong association was observed between nitrofurantoin resistance and the presence of bla PER-1, bla NDM-1, bla OXA-48, ant(2) and oqxA-oqxB genes. Tigecycline (84 %) and colistin (95 %) were the only antibiotics to which the majority of the isolates were susceptible. Conclusion. Nitrofurantoin resistance could be an indicator of the XDR phenotype among Enterobacteriaceae , harbouring multiple AMR and efflux pump genes. Tigecycline and colistin are the only antibiotics that could be used in the treatment of such XDR infections. A deeper understanding of the co-resistance mechanisms in XDR pathogens and prescription of AST-based appropriate combination therapy may help mitigate this problem.

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