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Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition

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A special issue of Antibiotics (ISSN 2079-6382).

Deadline for manuscript submissions: closed (30 September 2021) | Viewed by 46338

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Prof. Dr. Yuji Morita

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Department of Infection Control Science, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, Japan
Interests: antimicrobial resistance; antimicrobial action; development of antimicrobial agents or adjuvant; microbial transporter; microbial molecular genetics
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Dear Colleagues,

This is the 2nd edition of the Special Issue “Antimicrobial Resistance in Gram-negative Bacteria”. Gram-negative bacteria possess an intrinsic resistance to many antimicrobials because of the bacterium’s outer-membrane barrier, the presence of multidrug efflux transporters, endogenous antimicrobial inactivation, etc. Moreover, Gram-negative bacteria readily acquire resistance to antimicrobial agents via chromosomal mutations and lateral gene transfers. In order to overcome this problem, it is necessary to tackle the development of antibacterial agents, drug resistance inhibitors, antipathogenic factors, and vaccines. Thus, this Special Issue features interdisciplinary studies that build our understanding of the underlying antimicrobial resistance in Gram-negative bacteria. It also covers studies on the development of antibacterial agents and adjuvants against antimicrobial-resistant Gram-negative bacteria.

Prof. Dr. Yuji Morita
Guest Editor

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Keywords

antimicrobial resistance
antimicrobial responce
development of antimicrobial agents or adjuvant

Published Papers (11 papers)

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16 pages, 3236 KiB

Open AccessArticle

Antimicrobial Resistance and Genomic Characterization of Six New Sequence Types in Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates from Pakistan

by Sidra Irum, Kanwal Naz, Nimat Ullah, Zeeshan Mustafa, Amjad Ali, Muhammad Arslan, Kashaf Khalid and Saadia Andleeb

Antibiotics 2021, 10(11), 1386; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10111386 - 12 Nov 2021

Cited by 5 | Viewed by 2915

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is a major bacterial pathogen associated with a variety of infections with high mortality rates. Most of the clinical P. aeruginosa isolates belong to a limited number of genetic subgroups characterized by multiple housekeeping genes’ sequences (usually 5–7) through the Multi-Locus Sequence Typing (MLST) scheme. The emergence and dissemination of novel multidrug-resistant (MDR) sequence types (ST) in P. aeruginosa pose serious clinical concerns. We performed whole-genome sequencing on a cohort (n = 160) of MDR P. aeruginosa isolates collected from a tertiary care hospital lab in Pakistan and found six isolates belonging to six unique MLST allelic profiles. The genomes were submitted to the PubMLST database and new ST numbers (ST3493, ST3494, ST3472, ST3489, ST3491, and ST3492) were assigned to the respective allele combinations. MLST and core-genome-based phylogenetic analysis confirmed the divergence of these isolates and positioned them in separate branches. Analysis of the resistome of the new STs isolates revealed the presence of genes blaOXA-50, blaPAO, blaPDC, blaVIM-2, aph(3′)-IIb, aac(6′)-II, aac(3)-Id, fosA, catB7, dfrB2, crpP, merP and a number of missense and frame-shift mutations in chromosomal genes conferring resistance to various antipseudomonal antibiotics. The exoS, exoT, pvdE, rhlI, rhlR, lasA, lasB, lasI, and lasR genes were the most prevalent virulence-related genes among the new ST isolates. The different genotypic features revealed the adaptation of these new clones to a variety of infections by various mutations in genes affecting antimicrobial resistance, quorum sensing and biofilm formation. Close monitoring of these antibiotic-resistant pathogens and surveillance mechanisms needs to be adopted to reduce their spread to the healthcare facilities of Pakistan. We believe that these strains can be used as reference strains for future comparative analysis of isolates belonging to the same STs. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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17 pages, 1896 KiB

Open AccessArticle

Evidence-Based Tracking of MDR E. coli from Bovine Endometritis and Its Elimination by Effective Novel Therapeutics

by Laiba Shafique, Siwen Wu, Amjad Islam Aqib, Muhammad Muddassir Ali, Misbah Ijaz, Muhammad Aamir Naseer, Zaeem Sarwar, Rais Ahmed, Arslan Saleem, Qudratullah, Abdullah Saghir Ahmad, Hongping Pan and Qingyou Liu

Antibiotics 2021, 10(8), 997; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10080997 - 18 Aug 2021

Cited by 5 | Viewed by 3363

Abstract

Antibiotic-resistant bacteria have become the predominant etiology of endometritis and thus require effective treatment approaches. We used ultrasonography coupled with clinical signs and presented complaints of reproductive issues to investigate the epidemiology, phylogenetic analysis, antimicrobial resistance, and development of novel therapeutics against Escherichia coli isolated from endometritis in bovine (n = 304 from 10 commercial dairy farms). The prevalence of bovine endometritis in this study was 43.75%, while among these, 72.18% samples were positive for E. coli. Nucleotide analysis performed through BLAST and MEGAX showed 98% similarity to the nucleotide sequence of the reference E. coli strain (accession number CP067311.1). The disk diffusion assay revealed pathogen resistance to most antibiotics. Pattern of MIC order of resistance was as follows: enrofloxacin < gentamicin < co-amoxiclav < streptomycin < amoxicillin < metronidazole < oxytetracycline. Field trials revealed the highest recovery rate (in terms of clearance of endometritis and establishment of pregnancy) in case of gentamicin + enrofloxacin (100%) and gentamicin alone (100%), followed by co-amoxiclav + gentamicin (84.61%), oxytetracycline alone (78.57%), and metronidazole + enrofloxacin (33.33%). Hence, the current study reported a higher prevalence of multidrug-resistant E. coli showing considerable similarity with reference strain, and finally, the effective response of novel antibiotics to treat cases. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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17 pages, 999 KiB

Open AccessArticle

Multidrug-Resistant Klebsiella pneumoniae Causing Severe Infections in the Neuro-ICU

by Nadezhda K. Fursova, Evgenii I. Astashkin, Olga N. Ershova, Irina A. Aleksandrova, Ivan A. Savin, Tatiana S. Novikova, Galina N. Fedyukina, Angelina A. Kislichkina, Mikhail V. Fursov, Ekaterina S. Kuzina, Sergei F. Biketov and Ivan A. Dyatlov

Antibiotics 2021, 10(8), 979; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10080979 - 13 Aug 2021

Cited by 22 | Viewed by 3386

Abstract

The purpose of this study was the identification of genetic lineages and antimicrobial resistance (AMR) and virulence genes in Klebsiella pneumoniae isolates associated with severe infections in the neuro-ICU. Susceptibility to antimicrobials was determined using the Vitek-2 instrument. AMR and virulence genes, sequence types (STs), and capsular types were identified by PCR. Whole-genome sequencing was conducted on the Illumina MiSeq platform. It was shown that K. pneumoniae isolates of ST14^K2, ST23^K57, ST39^K23, ST76^K23, ST86^K2, ST218^K57, ST219^KL125/114, ST268^K20, and ST2674^K47 caused severe systemic infections, including ST14^K2, ST39^K23, and ST268^K20 that were associated with fatal incomes. Moreover, eight isolates of ST395^K2 and ST307^{KL102/149/155} were associated with manifestations of vasculitis and microcirculation disorders. Another 12 K. pneumoniae isolates of ST395^K2,KL39, ST307^{KL102/149/155}, and ST147^K14/64 were collected from patients without severe systemic infections. Major isolates (n = 38) were XDR and MDR. Beta-lactamase genes were identified: bla_SHV (n = 41), bla_CTX-M (n = 28), bla_TEM (n = 21), bla_OXA-48 (n = 21), bla_NDM (n = 1), and bla_KPC (n = 1). The prevalent virulence genes were wabG (n = 41), fimH (n = 41), allS (n = 41), and uge (n = 34), and rarer, detected only in the genomes of the isolates causing severe systemic infections—rmpA (n = 8), kfu (n = 6), iroN (n = 5), and iroD (n = 5) indicating high potential of the isolates for hypervirulence. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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15 pages, 7727 KiB

Open AccessArticle

Antimicrobial Activity of Quasi-Enantiomeric Cinchona Alkaloid Derivatives and Prediction Model Developed by Machine Learning

by Alma Ramić, Mirjana Skočibušić, Renata Odžak, Ana Čipak Gašparović, Lidija Milković, Ana Mikelić, Karlo Sović, Ines Primožič and Tomica Hrenar

Antibiotics 2021, 10(6), 659; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060659 - 31 May 2021

Cited by 4 | Viewed by 2144

Abstract

Bacterial infections that do not respond to current treatments are increasing, thus there is a need for the development of new antibiotics. Series of 20 N-substituted quaternary salts of cinchonidine (CD) and their quasi-enantiomer cinchonine (CN) were prepared and their antimicrobial activity was assessed against a diverse panel of Gram-positive and Gram-negative bacteria. All tested compounds showed good antimicrobial potential (minimum inhibitory concentration (MIC) values 1.56 to 125.00 μg/mL), proved to be nontoxic to different human cell lines, and did not influence the production of reactive oxygen species (ROS). Seven compounds showed very strong bioactivity against some of the tested Gram-negative bacteria (MIC for E. coli and K. pneumoniae 6.25 μg/mL; MIC for P. aeruginosa 1.56 μg/mL). To establish a connection between antimicrobial data and potential energy surfaces (PES) of the compounds, activity/PES models using principal components of the disc diffusion assay and MIC and data towards PES data were built. An extensive machine learning procedure for the generation and cross-validation of multivariate linear regression models with a linear combination of original variables as well as their higher-order polynomial terms was performed. The best possible models with predicted R²(CD derivatives) = 0.9979 and R²(CN derivatives) = 0.9873 were established and presented. This activity/PES model can be used for accurate prediction of activities for new compounds based solely on their potential energy surfaces, which will enable wider screening and guided search for new potential leads. Based on the obtained results, N-quaternary derivatives of Cinchona alkaloids proved to be an excellent scaffold for further optimization of novel antibiotic species. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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6 pages, 1065 KiB

Open AccessCommunication

Overexpression of the MexXY Multidrug Efflux System Correlates with Deficient Pyoverdine Production in Pseudomonas aeruginosa

by Kei Ikarashi, Ryo Kutsuna, Junko Tomida, Yoshiaki Kawamura and Yuji Morita

Antibiotics 2021, 10(6), 658; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10060658 - 31 May 2021

Cited by 2 | Viewed by 2593

Abstract

Multidrug-resistant Pseudomonas aeruginosa poses a serious problem due to hospital- and healthcare-associated infections. A major drug resistance mechanism of P. aeruginosa involves active efflux via resistance nodulation cell division (RND)-type multidrug efflux pumps of which MexXY is increasingly recognized as a primary determinant of aminoglycoside resistance in P. aeruginosa. MexXY overexpression is often observed in drug-resistant P. aeruginosa clinical isolates. MexXY deficiency increased pyoverdine production in all four P. aeruginosa strains we tested. MexXY-overproducing multidrug-resistant P. aeruginosa PA7 exhibited the greatest effect among the strains. Complementation with a MexXY-expressing plasmid restored low-level pyoverdine production in a MexXY-deficient P. aeruginosa mutant from PA7, indicating that MexXY expression decreases pyoverdine production. Because P. aeruginosa produces pyoverdine to acquire iron, MexXY-deficient mutants might be more susceptible to iron deficiency than MexXY-producing strains or might require extra iron. High-risk clones of multidrug-resistant P. aeruginosa reportedly tend to be MexXY overproducers but defective pyoverdine producers. This study suggests that P. aeruginosa reduces production of a virulence factor after acquiring a drug resistance factor. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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12 pages, 1461 KiB

Open AccessArticle

Multimodal Interventions to Prevent and Control Carbapenem-Resistant Enterobacteriaceae and Extended-Spectrum β-Lactamase Producer-Associated Infections at a Tertiary Care Hospital in Egypt

by Noha A. Kamel, Khaled M. Elsayed, Mohamed F. Awad, Khaled M. Aboshanab and Mervat I. El Borhamy

Antibiotics 2021, 10(5), 509; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10050509 - 30 Apr 2021

Cited by 10 | Viewed by 2182

Abstract

The current rise of multidrug-resistant (MDR) Gram-negative Enterobacteriaceae including the extended-spectrum β-lactamase (ESBL)-producing organisms and carbapenem-resistant Enterobacteriaceae (CRE) has been increasingly reported worldwide, posing new challenges to health care facilities. Accordingly, we evaluated the impact of multimodal infection control interventions at one of the major tertiary healthcare settings in Egypt for the aim of combating infections by the respective pathogens. During the 6-month pre-intervention period, the incidence rate of CRE and ESBL-producing clinical cultures were 1.3 and 0.8/1000 patient days, respectively. During the post-intervention period, the incidence of CRE and ESBL producers continued to decrease, reaching 0.5 and 0.28/1000 patient days, respectively. The susceptibility rate to carbapenems among ESBL producers ranged from 91.4% (ertapenem) to 98.3% (imipenem), amikacin (93%), gentamicin (56.9%), and tobramycin (46.6%). CRE showed the highest resistance pattern toward all of the tested β-lactams and aminoglycosides, ranging from 87.3% to 94.5%. Both CRE and ESBL producers showed a high susceptibility rate (greater than 85.5%) to colistin and tigecycline. In conclusion, our findings revealed the effectiveness of implementing multidisciplinary approaches in controlling and treating infections elicited by CRE and ESBL producers. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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10 pages, 599 KiB

Open AccessArticle

Molecular Detection of Antibiotic Resistance Genes in Shiga Toxin-Producing E. coli Isolated from Different Sources

by Momna Rubab and Deog-Hwan Oh

Antibiotics 2021, 10(4), 344; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10040344 - 24 Mar 2021

Cited by 5 | Viewed by 3186

Abstract

Shiga toxin-producing Escherichia coli (STEC) is an enteric pathogen associated with human gastroenteritis outbreaks. Extensive use of antibiotics in agriculture selects resistant bacteria that may enter the food chain and potentially causes foodborne illnesses in humans that are less likely to respond to treatment with conventional antibiotics. Due to the importance of antibiotic resistance, this study aimed to investigate the combination of phenotypic and genotypic antibiotic resistance in STEC isolates belonging to serogroups O26, O45, O103, O104, O111, O121, O145, and O157 using disc diffusion and polymerase chain reaction (PCR), respectively. All strains were phenotypically resistant to at least one antibiotic, with 100% resistance to erythromycin, followed by gentamicin (98%), streptomycin (82%), kanamycin (76%), and ampicillin (72%). The distribution of antibiotic resistance genes (ARGs) in the STEC strains was ampC (47%), aadA1 (70%), ere(A) (88%), bla_SHV (19%), bla_CMY (27%), aac(3)-I (90%), and tet(A) (35%), respectively. The results suggest that most of the strains were multidrug-resistant (MDR) and the most often observed resistant pattern was of aadA1, ere(A), and aac(3)-I genes. These findings indicate the significance of monitoring the prevalence of MDR in both animals and humans around the globe. Hence, with a better understanding of antibiotic genotypes and phenotypes among the diverse STEC strains obtained, this study could guide the administration of antimicrobial drugs in STEC infections when necessary. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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9 pages, 538 KiB

Open AccessCommunication

Antimicrobial Resistance and Genomic Characterization of OXA-48- and CTX-M-15-Co-Producing Hypervirulent Klebsiella pneumoniae ST23 Recovered from Nosocomial Outbreak

by Elvira Shaidullina, Andrey Shelenkov, Yuri Yanushevich, Yulia Mikhaylova, Dmitriy Shagin, Irina Alexandrova, Olga Ershova, Vasiliy Akimkin, Roman Kozlov and Mikhail Edelstein

Antibiotics 2020, 9(12), 862; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9120862 - 03 Dec 2020

Cited by 28 | Viewed by 2967

Abstract

Multidrug resistance (MDR) and hypervirulence (hv) have been long considered distinct evolutionary traits for Klebsiella pneumoniae (Kp), a versatile human pathogen. The recent emergence of Kp strains combining these traits poses a serious global threat. In this article, we describe the phenotypic and genomic characteristics of an MDR hvKp isolate, MAR14-456, representative of a nosocomial outbreak in Moscow, Russia, that was recovered from a postoperative wound in a patient who later developed multiple abscesses, fatal sepsis, and septic shock. Broth microdilution testing revealed decreased susceptibility of MAR14-456 to carbapenems (MICs 0.5–2 mg/L) and a high-level resistance to most β-lactams, β-lactam-β-lactamase-inhibitor combinations, and non-β-lactam antibiotics, except ceftazidime-avibactam, amikacin, tigecycline, and colistin. Whole-genome sequencing using Illumina MiSeq and ONT MinION systems allowed to identify and completely assemble two conjugative resistance plasmids, a typical ‘European’ epidemic IncL/M plasmid that carries the gene of OXA-48 carbapenemase, and an IncFIIK plasmid that carries the gene of CTX-M-15 ESBL and other resistance genes. MLST profile, capsular, lipopolysaccharide, virulence genes encoded on chromosome and IncHI1B/FIB plasmid, and the presence of apparently functional type I-E* CRISPR-Cas system were all characteristic of hvKp ST23, serotype K1-O1v2. Phylogenetic analysis showed the closest relatedness of MAR14-456 to ST23 isolates from China. This report highlights the threat of multiple resistance acquisition by hvKp strain and its spread as a nosocomial pathogen. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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9 pages, 681 KiB

Open AccessArticle

Increased Azithromycin Susceptibility of Multidrug-Resistant Gram-Negative Bacteria on RPMI-1640 Agar Assessed by Disk Diffusion Testing

by Milton Meerwein, Andrea Tarnutzer, Michelle Böni, Françoise Van Bambeke, Michael Hombach and Annelies S. Zinkernagel

Antibiotics 2020, 9(5), 218; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9050218 - 29 Apr 2020

Cited by 16 | Viewed by 7471

Abstract

Increasing antibiotic resistances and a lack of new antibiotics render the treatment of Gram-negative bacterial infections increasingly difficult. Therefore, additional approaches are being investigated. Macrolides are not routinely used against Gram-negative bacteria due to lack of evidence of in vitro effectiveness. However, it has been shown that Pseudomonas spp. are susceptible to macrolides in liquid RPMI-1640 and clinical data suggest improvement in patients’ outcomes. So far, these findings have been hardly applicable to the clinical setting due to lack of routine low-complexity antimicrobial susceptibility testing (AST) for macrolides. We therefore optimized and compared broth microdilution and disk diffusion AST. Multidrug-resistant Gram-negative bacteria (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa) were tested for azithromycin susceptibility by disk diffusion and broth microdilution in Mueller–Hinton and RPMI-1640 media. Azithromycin susceptibility of Enterobacteriaceae and a subgroup of P. aeruginosa increased significantly on RPMI-1640 agar compared to Mueller–Hinton agar. Further, a significant correlation (Kendall, τ, p) of zone diameters and minimal inhibitory concentrations (MICs) was found on RPMI-1640 agar for E. coli (−0.4279, 0.0051), E. cloacae (−0.3783, 0.0237) and P. aeruginosa (−0.6477, <0.0001). Performing routine disk diffusion AST on RPMI-1640 agar may lead to the identification of additional therapeutic possibilities for multidrug-resistant bacterial infections in the routine clinical diagnostic setting. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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Review

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17 pages, 2007 KiB

Open AccessReview

Carbapenem Therapeutic Drug Monitoring in Critically Ill Adult Patients and Clinical Outcomes: A Systematic Review with Meta-Analysis

by Sharon Lechtig-Wasserman, Hans Liebisch-Rey, Nicolas Diaz-Pinilla, Jhosep Blanco, Yuli-Viviana Fuentes-Barreiro and Rosa-Helena Bustos

Antibiotics 2021, 10(2), 177; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics10020177 - 10 Feb 2021

Cited by 12 | Viewed by 3758

Abstract

Drug monitoring is one strategy of antibiotic stewardship to face antimicrobial resistance. This strategy could have a determinant role in critically ill patients treated with carbapenems to overcome pharmacokinetic variability, reduce the risk of subtherapeutic dosage or toxicity, and reduce the risks inherent to treatment. However, the effectiveness of therapeutic drug monitoring (TDM) is unknown. This paper aims to identify TDM effectiveness in critically ill patients treated with carbapenems. English and ClinicalTrials.gov databases were searched to identify relevant studies evaluating carbapenem TDM. Randomized controlled trials (RCTs) and comparative cohort studies were selected for inclusion if they compared carbapenem TDM to standard care in adult critically ill or sepsis/septic shock patients. The primary outcome was mortality. Secondary outcomes included morbidity, clinical cure, microbiological eradication, antimicrobial resistance, drug-related side effects, and achievement of target plasma concentrations. Overall, performing carbapenem TDM was not associated with a decrease in mortality. However, it could be evidence for a relationship with clinical cure as well as target attainment. Some studies found favorable outcomes related to clinical and microbiological responses, such as lower procalcitonin levels at the end of the monitored therapy compared to standard care. For the primary and secondary outcomes analyzed, strong evidence was not identified, which could be due to the size, risk of bias, and design of selected studies. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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20 pages, 321 KiB

Open AccessReview

Trends, Epidemiology, and Management of Multi-Drug Resistant Gram-Negative Bacterial Infections in the Hospitalized Setting

by Sabrina Morris and Elizabeth Cerceo

Antibiotics 2020, 9(4), 196; https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics9040196 - 20 Apr 2020

Cited by 112 | Viewed by 10795

Abstract

The increasing prevalence of antibiotic resistance is a threat to human health, particularly within vulnerable populations in the hospital and acute care settings. This leads to increasing healthcare costs, morbidity, and mortality. Bacteria rapidly evolve novel mechanisms of resistance and methods of antimicrobial evasion. Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii have all been identified as pathogens with particularly high rates of resistance to antibiotics, resulting in a reducing pool of available treatments for these organisms. Effectively combating this issue requires both preventative and reactive measures. Reducing the spread of resistant pathogens, as well as reducing the rate of evolution of resistance is complex. Such a task requires a more judicious use of antibiotics through a better understanding of infection epidemiology, resistance patterns, and guidelines for treatment. These goals can best be achieved through the implementation of antimicrobial stewardship programs and the development and introduction of new drugs capable of eradicating multi-drug resistant Gram-negative pathogens (MDR GNB). The purpose of this article is to review current trends in MDR Gram-negative bacterial infections in the hospitalized setting, as well as current guidelines for management. Finally, new and emerging antimicrobials, as well as future considerations for combating antibiotic resistance on a global scale are discussed. Full article

(This article belongs to the Special Issue Antimicrobial Resistance in Gram-Negative Bacteria, 2nd Edition)

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