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Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria

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A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Mechanism and Evolution of Antibiotic Resistance".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 14394

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Special Issue Editors

Dr. Georgios Meletis

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Department of Microbiology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Interests: antibiotic resistance mechanisms; phenotypic and molecular methods for antibiotic resistance detection; Klebsiella pneumoniae; Pseudomonas aeruginosa; Acinetobacter baumannii; SARS-CoV-2; clinical microbiology

Dr. Lemonia Skoura

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Department of Microbiology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Interests: nosocomial infections; antimicrobial resistance mechanisms; HIV immunology; SARS-CoV-2 infection
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Dr. Efthymia Protonotariou

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Department of Microbiology, AHEPA University Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
Interests: antibiotic resistance mechanisms; phenotypic and molecular methods for antibiotic resistance detection; Klebsiella pneumoniae; Pseudomonas aeruginosa; Acinetobacter baumannii; SARS-CoV-2; clinical microbiology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antimicrobial resistance is a public health problem of major importance, and the World Health Organization (WHO) has warned that the current antibiotic armamentarium is not sufficient to face future challenges. The antibiotic pipeline is not providing new compounds at a sufficient speed for various reasons, and thus few novel drugs have reached clinical practice lately and old, formerly abandoned antimicrobials are increasingly used as last-resort treatment options. At this pace, untreatable infections could emerge on a large scale, and the world may experience in some cases dramatic situations of the pre-antibiotic era. Already, clinicians in endemic areas routinely encounter patients with infections that do not respond to available treatments, and laboratories often report multidrug-resistant (MDR) or even pan-drug-resistant (PDR) bacteria. In this context, continuous monitoring of the resistance mechanisms’ epidemiology as well as knowledge regarding treatment options for clinically relevant bacteria are of great interest to health-care professionals. This Special Issue seeks manuscript submissions that further our understanding of antimicrobial resistance in clinically relevant bacteria, improvements in the detection of these mechanisms in laboratory practice as well as treatment solutions and observations. Submissions on the development of new antibiotic compounds or the in-vitro susceptibility of relevant bacteria to these compounds are especially encouraged.

Dr. Georgios Meletis
Dr. Lemonia Skoura
Dr. Efthymia Protonotariou
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

antimicrobial resistance mechanisms
antimicrobial resistance detection
antimicrobial resistance epidemiology
antimicrobial treatment
new antibiotics
MDR
Klebsiella pneumoniae
Acinetobacter baumannii
Pseudomonas aeruginosa
MRSA

Published Papers (8 papers)

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Research

13 pages, 1630 KiB

Open AccessArticle

Competition between H₄PteGlu and H₂PtePAS Confers para-Aminosalicylic Acid Resistance in Mycobacterium tuberculosis

by Ji-Fang Yu, Jin-Tian Xu, Ao Feng, Bao-Ling Qi, Jing Gu, Jiao-Yu Deng and Xian-En Zhang

Antibiotics 2024, 13(1), 13; https://doi.org/10.3390/antibiotics13010013 (registering DOI) - 21 Dec 2023

Viewed by 984

Abstract

Tuberculosis remains a serious challenge to human health worldwide. para-Aminosalicylic acid (PAS) is an important anti-tuberculosis drug, which requires sequential activation by Mycobacterium tuberculosis (M. tuberculosis) dihydropteroate synthase and dihydrofolate synthase (DHFS, FolC). Previous studies showed that loss of function mutations of a thymidylate synthase coding gene thyA caused PAS resistance in M. tuberculosis, but the mechanism is unclear. Here we showed that deleting thyA in M. tuberculosis resulted in increased content of tetrahydrofolate (H₄PteGlu) in bacterial cells as they rely on the other thymidylate synthase ThyX to synthesize thymidylate, which produces H₄PteGlu during the process. Subsequently, data of in vitro enzymatic activity experiments showed that H₄PteGlu hinders PAS activation by competing with hydroxy dihydropteroate (H₂PtePAS) for FolC catalysis. Meanwhile, over-expressing folC in ΔthyA strain and a PAS resistant clinical isolate with known thyA mutation partially restored PAS sensitivity, which relieved the competition between H₄PteGlu and H₂PtePAS. Thus, loss of function mutations in thyA led to increased H₄PteGlu content in bacterial cells, which competed with H₂PtePAS for catalysis by FolC and hence hindered the activation of PAS, leading to decreased production of hydroxyl dihydrofolate (H₂PtePAS-Glu) and finally caused PAS resistance. On the other hand, functional deficiency of thyA in M. tuberculosis pushes the bacterium switch to an unidentified dihydrofolate reductase for H₄PteGlu biosynthesis, which might also contribute to the PAS resistance phenotype. Our study revealed how thyA mutations confer PAS resistance in M. tuberculosis and provided new insights into studies on the folate metabolism of the bacterium. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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11 pages, 792 KiB

Open AccessArticle

Neonatal Bloodstream Infection with Ceftazidime-Avibactam-Resistant bla_KPC-2-Producing Klebsiella pneumoniae Carrying bla_VEB-25

by Charalampos Zarras, Elias Iosifidis, Maria Simitsopoulou, Styliani Pappa, Angeliki Kontou, Emmanuel Roilides and Anna Papa

Antibiotics 2023, 12(8), 1290; https://doi.org/10.3390/antibiotics12081290 - 05 Aug 2023

Viewed by 1243

Abstract

Background: Although ceftazidime/avibactam (CAZ/AVI) has become an important option for treating adults and children, no data or recommendations exist for neonates. We report a neonatal sepsis case due to CAZ/AVI-resistant bla_KPC-2-harboring Klebsiella pneumoniae carrying bla_VEB-25 and the use of a customized active surveillance program in conjunction with enhanced infection control measures. Methods: The index case was an extremely premature neonate hospitalized for 110 days that had been previously treated with multiple antibiotics. Customized molecular surveillance was implemented at hospital level and enhanced infection control measures were taken for early recognition and prevention of outbreak. Detection and identification of bla_VEB-25 was performed using next-generation sequencing. Results: This was the first case of a bloodstream infection caused by KPC-producing K. pneumoniae that was resistant to CAZ/AVI without the presence of a metalo-β-lactamase in the multiplex PCR platform in a neonate. All 36 additional patients tested (12 in the same NICU and 24 from other hospital departments) carried wild-type bla_VEB-1 but they did not harbor bla_VEB-25. Conclusion: The emergence of bla_VEB-25 is signal for the horizontal transfer of plasmids at hospital facilities and it is of greatest concern for maintaining a sharp vigilance for the surveillance of novel resistance mechanisms. Molecular diagnostics can guide appropriate antimicrobial therapy and the early implementation of infection control measures against antimicrobial resistance. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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10 pages, 2304 KiB

Open AccessArticle

Prevalence of Carbapenemases in Carbapenem-Resistant Acinetobacter baumannii Isolates from the Kingdom of Bahrain

by Nouf Al-Rashed, Khalid M. Bindayna, Mohammad Shahid, Nermin Kamal Saeed, Abdullah Darwish, Ronni Mol Joji and Ali Al-Mahmeed

Antibiotics 2023, 12(7), 1198; https://doi.org/10.3390/antibiotics12071198 - 17 Jul 2023

Cited by 2 | Viewed by 1486

Abstract

Background: Acinetobacter baumannii is regarded as a significant cause of death in hospitals. The WHO recently added carbapenem-resistant Acinetobacter baumannii (CRAB) to its global pathogen priority list. There is a dearth of information on CRAB from our region. Methods: Fifty CRAB isolates were collected from four main hospitals in Bahrain for this study. Bacterial identification and antibiotic susceptibility tests were carried out using the BD Phoenix^TM and VITEK-2 compact, respectively. Using conventional PCR, these isolates were further screened for carbapenem resistance markers (bla_OXA-51, bla_OXA-23, blaO_XA-24, bla_OXA-40, bla_IMP, bla_NDM, bla_VIM, and bla_KPC). Results: All of the isolates were resistant to imipenem (100%), meropenem (98%), and cephalosporins (96–98%), followed by other commonly used antibiotics. All these isolates were least resistant to gentamicin (64%). The detection of resistance determinants showed that the majority harbored bla_OXA-51 (100%) and bla_IMP (94%), followed by bla_OXA-23 (82%), bla_OXA-24 (46%), bla_OXA-40 (14%), bla_NDM (6%), bla_VIM (2%), and bla_KPC (2%). Conclusion: The study isolates showed a high level of antibiotic resistance. Class D carbapenemases were more prevalent in our CRAB isolate collection. The resistance genes were found in various combinations. This study emphasizes the importance of strengthening surveillance and stringent infection control measures in clinical settings to prevent the emergence and further spread of such isolates. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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14 pages, 2168 KiB

Open AccessArticle

Evaluation of Five Host Inflammatory Biomarkers in Early Diagnosis of Ventilator-Associated Pneumonia in Critically Ill Children: A Prospective Single Center Cohort Study

by Maria Sdougka, Maria Simitsopoulou, Elena Volakli, Asimina Violaki, Vivian Georgopoulou, Argiro Ftergioti, Emmanuel Roilides and Elias Iosifidis

Antibiotics 2023, 12(5), 921; https://doi.org/10.3390/antibiotics12050921 - 17 May 2023

Cited by 1 | Viewed by 1425

Abstract

Background: Early diagnosis of ventilator-associated pneumonia (VAP) remains a challenge due to subjective clinical criteria and the low discriminative power of diagnostic tests. We assessed whether rapid molecular diagnostics in combination with Clinically Pulmonary Index Score (CPIS) scoring, microbiological surveillance and biomarker measurements of PTX-3, SP-D, s-TREM, PTX-3, IL-1β and IL-8 in the blood or lung could improve the accuracy of VAP diagnosis and follow-up in critically ill children. Methods: A prospective pragmatic study in a Pediatric Intensive Care Unit (PICU) was conducted on ventilated critically ill children divided into two groups: high and low suspicion of VAP according to modified Clinically Pulmonary Index Score (mCPIS). Blood and bronchial samples were collected on days 1, 3, 6 and 12 after event onset. Rapid diagnostics were used for pathogen identification and ELISA for PTX-3, SP-D, s-TREM, IL-1β and IL-8 measurements. Results: Among 20 enrolled patients, 12 had a high suspicion (mCPIS > 6), and 8 had a low suspicion of VAP (mCPIS < 6); 65% were male; and 35% had chronic disease. IL-1β levels at day 1 correlated significantly with the number of mechanical ventilation days (r_s = 0.67, p < 0.001) and the PICU stay (r = 0.66; p < 0.002). No significant differences were found in the levels of the other biomarkers between the two groups. Mortality was recorded in two patients with high VAP suspicion. Conclusions: PTX-3, SP-D, s-TREM, IL-1β and IL-8 biomarkers could not discriminate patients with a high or low suspicion of VAP diagnosis. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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11 pages, 1836 KiB

Open AccessArticle

Replacement of the Double Meropenem Disc Test with a Lateral Flow Assay for the Detection of Carbapenemase-Producing Enterobacterales and Pseudomonas aeruginosa in Clinical Laboratory Practice

by Areti Tychala, Georgios Meletis, Paraskevi Mantzana, Angeliki Kassomenaki, Charikleia Katsanou, Aikaterini Daviti, Lydia Kouroudi, Lemonia Skoura and Efthymia Protonotariou

Antibiotics 2023, 12(4), 771; https://doi.org/10.3390/antibiotics12040771 - 17 Apr 2023

Viewed by 1626

Abstract

The prompt detection of carbapenemases among Gram-negative bacteria isolated from patients’ clinical infection samples and surveillance cultures is important for the implementation of infection control measures. In this context, we evaluated the effectiveness of replacing phenotypic tests for the detection of carbapenemase producers with the immunochromatographic Carbapenem-Resistant K.N.I.V.O. Detection K-Set lateral flow assay (LFA). In total, 178 carbapenem-resistant Enterobacterales and 32 carbapenem-resistant Pseudomonas aeruginosa isolated in our hospital were tested with both our established phenotypic and molecular testing procedures and the LFA. The Kappa coefficient of agreement for Enterobacterales was 0.85 (p < 0.001) and 0.6 (p < 0.001) for P. aeruginosa. No major disagreements were observed and notably, in many cases, the LFA detected more carbapenemases than the double meropenem disc test, especially regarding OXA-48 in Enterobacterales and VIM in P. aeruginosa. Overall, the Carbapenem-Resistant K.N.I.V.O. Detection K-Set was very effective and at least equivalent to the standard procedures used in our lab. However, it was much faster as it provided results in 15 min compared to a minimum of 18–24 h for the phenotypic tests. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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17 pages, 5755 KiB

Open AccessArticle

Identification of Efflux Pump Mutations in Pseudomonas aeruginosa from Clinical Samples

by Sonia Quddus, Zainab Liaqat, Sadiq Azam, Mahboob Ul Haq, Sajjad Ahmad, Metab Alharbi and Ibrar Khan

Antibiotics 2023, 12(3), 486; https://doi.org/10.3390/antibiotics12030486 - 01 Mar 2023

Cited by 1 | Viewed by 1722

Abstract

Efflux pumps are a specialized tool of antibiotic resistance used by Pseudomonas aeruginosa to expel antibiotics. The current study was therefore conducted to examine the expression of MexAB-OprM and MexCD-OprJ efflux pump genes. In this study, 200 samples were collected from Khyber Teaching Hospital (KTH) and Hayatabad Medical Complex (HMC) in Peshawar, Pakistan. All the isolates were biochemically identified by an Analytical Profile Index kit and at the molecular level by Polymerase Chain Reaction (PCR) utilizing specific primers for the OprL gene. A total of 26 antibiotics were tested in the current study using the guidelines of the Clinical and Laboratory Standard Institute (CLSI) and high-level resistance was shown to amoxicillin-clavulanic acid (89%) and low-level to chloramphenicol (1%) by the isolates. The antibiotic-resistant efflux pump genes MexA, MexB, OprM, MexR, MexC, MexD, OprJ, and NfxB were detected in 178 amoxicillin-clavulanic acid-resistant isolates. Mutations were detected in MexA, MexB, and OprM genes but no mutation was found in the MexR gene as analyzed by I-Mutant software. Statistical analysis determined the association of antibiotics susceptibility patterns by ANOVA: Single Factor p = 0.05. The in silico mutation impact on the protein structure stability was determined via the Dynamut server, which revealed the mutations might increase the structural stability of the mutants. The docking analysis reported that MexA wild protein showed a binding energy value of −6.1 kcal/mol with meropenem and the mexA mutant (E178K) value is −6.5 kcal/mol. The mexB wild and mutant binding energy value was −5.7 kcal/mol and −8.0 kcal/mol, respectively. Efflux pumps provide resistance against a wide range of antibiotics. Determining the molecular mechanisms of resistance in P. aeruginosa regularly will contribute to the efforts against the spread of antibiotic resistance globally. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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12 pages, 859 KiB

Open AccessFeature PaperArticle

In Vitro Synergistic Activity of Antimicrobial Combinations against Carbapenem- and Colistin-Resistant Acinetobacter baumannii and Klebsiella pneumoniae

by Paraskevi Mantzana, Efthymia Protonotariou, Angeliki Kassomenaki, Georgios Meletis, Areti Tychala, Eirini Keskilidou, Maria Arhonti, Charikleia Katsanou, Aikaterini Daviti, Olga Vasilaki, Georgia Kagkalou and Lemonia Skoura

Antibiotics 2023, 12(1), 93; https://doi.org/10.3390/antibiotics12010093 - 05 Jan 2023

Cited by 9 | Viewed by 2588

Abstract

Polymyxins are commonly used as the last resort for the treatment of MDR Acinetobacter baumannii and Klebsiella pneumoniae nosocomial infections; however, apart from the already known toxicity issues, resistance to these agents is emerging. In the present study, we assessed the in vitro synergistic activity of antimicrobial combinations against carbapenem-resistant and colistin-resistant A. baumannii and K. pneumoniae in an effort to provide more options for their treatment. Two hundred A. baumannii and one hundred and six K. pneumoniae single clinical isolates with resistance to carbapenems and colistin, recovered between 1 January 2021 and 31 July 2022,were included. A. baumannii were tested by the MIC test strip fixed-ratio method for combinations of colistin with either meropenem or rifampicin or daptomycin. K. pneumoniae were tested for the combinations of colistin with meropenem and ceftazidime/avibactam with aztreonam. Synergy was observed at: 98.99% for colistin and meropenem against A. baumannii; 91.52% for colistin and rifampicin; and 100% for colistin and daptomycin. Synergy was also observed at: 73.56% for colistin and meropenem against K. pneumoniae and; and 93% for ceftazidime/avibactam with aztreonam. The tested antimicrobial combinations presented high synergy rates, rendering them valuable options against A. baumannii and K. pneumoniae infections. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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13 pages, 1513 KiB

Open AccessArticle

Curcumin Stimulates the Overexpression of Virulence Factors in Salmonella enterica Serovar Typhimurium: In Vitro and Animal Model Studies

by Martin Zermeño-Ruiz, Itzia A. Rangel-Castañeda, Daniel Osmar Suárez-Rico, Leonardo Hernández-Hernández, Rafael Cortés-Zárate, José M. Hernández-Hernández, Gabriela Camargo-Hernández and Araceli Castillo-Romero

Antibiotics 2022, 11(9), 1230; https://doi.org/10.3390/antibiotics11091230 - 10 Sep 2022

Cited by 2 | Viewed by 2152

Abstract

Salmonella spp. is one of the most common food poisoning pathogens and the main cause of diarrheal diseases in humans in developing countries. The increased Salmonella resistance to antimicrobials has led to the search for new alternatives, including natural compounds such as curcumin, which has already demonstrated a bactericidal effect; however, in Gram-negatives, there is much controversy about this effect, as it is highly variable. In this study, we aimed to verify the antibacterial activity of curcumin against the Salmonella enterica serovar Typhimurium growth rate, virulence, and pathogenicity. The strain was exposed to 110, 220 or 330 µg/mL curcumin, and by complementary methods (spectrophotometric, pour plate and MTT assays), we determined its antibacterial activity. To elucidate whether curcumin regulates the expression of virulence genes, Salmonella invA, fliC and siiE genes were investigated by quantitative real-time reverse transcription (qRT-PCR). Furthermore, to explore the effect of curcumin on the pathogenesis process in vivo, a Caenorhabditis elegans infection model was employed. No antibacterial activity was observed, even at higher concentrations of curcumin. All concentrations of curcumin caused overgrowth (35–69%) and increased the pathogenicity of the bacterial strain through the overexpression of virulence factors. The latter coincided with a significant reduction in both the lifespan and survival time of C. elegans when fed with curcumin-treated bacteria. Our data provide relevant information that may support the selective antibacterial effects of curcumin to reconsider the indiscriminate use of this phytochemical, especially in outbreaks of pathogenic Gram-negative bacteria. Full article

(This article belongs to the Special Issue Antimicrobial Resistance and Antimicrobial Therapy of Clinically Relevant Bacteria)

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