Microorganisms

Editorial

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5 pages, 185 KiB

Open AccessEditorial

Editorial for Special Issue “Multidrug-Resistant Pathogens”

by Despoina Koulenti, Paraskevi C. Fragkou and Sotirios Tsiodras

Microorganisms 2020, 8(9), 1383; https://doi.org/10.3390/microorganisms8091383 - 10 Sep 2020

Cited by 6 | Viewed by 2130

Abstract

The era of injudicious use of antibiotics in both humans and animals has led to the selection of multidrug-resistant (MDR) pathogens, which in turn has left the medical community with limited therapeutic options [...] Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

Research

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22 pages, 2033 KiB

Open AccessArticle

Extensive Therapeutic Drug Monitoring of Colistin in Critically Ill Patients Reveals Undetected Risks

by Stefan Felix Ehrentraut, Stefan Muenster, Stefan Kreyer, Nils Ulrich Theuerkauf, Christian Bode, Folkert Steinhagen, Heidi Ehrentraut, Jens-Christian Schewe, Matthias Weber, Christian Putensen and Thomas Muders

Microorganisms 2020, 8(3), 415; https://doi.org/10.3390/microorganisms8030415 - 15 Mar 2020

Cited by 18 | Viewed by 3253

Abstract

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last [...] Read more.

(1) Background: With the rise of multi-/pan-drug resistant (MDR/PDR) pathogens, the less utilized antibiotic Colistin has made a comeback. Colistin fell out of favor due to its small therapeutic range and high potential for toxicity. Today, it is used again as a last resort substance in treating MDR/PDR pathogens. Although new guidelines with detailed recommendations for Colistin dosing are available, finding the right dose in critically ill patients with renal failure remains difficult. Here, we evaluate the efficiency of the current guidelines’ recommendations by using high resolution therapeutic drug monitoring of Colistin. (2) Methods: We analyzed plasma levels of Colistin and its prodrug colisthimethate sodium (CMS) in 779 samples, drawn from eight PDR-infected ICU patients, using a HPLC-MS/MS approach. The impact of renal function on proper Colistin target levels was assessed. (3) Results: CMS levels did not correlate with Colistin levels. Over-/Underdosing occurred regardless of renal function and mode of renal replacement therapy. Colistin elimination half-time appeared to be longer than previously reported. (4) Conclusion: Following dose recommendations from the most current guidelines does not necessarily lead to adequate Colistin plasma levels. Use of Colistin without therapeutic drug monitoring might be unsafe and guideline adherence does not warrant efficient target levels in critically ill patients. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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12 pages, 980 KiB

Open AccessArticle

Colistin-Resistant Acinetobacter Baumannii Bacteremia: A Serious Threat for Critically Ill Patients

by Georgios Papathanakos, Ioannis Andrianopoulos, Athanasios Papathanasiou, Efthalia Priavali, Despoina Koulenti and Vasilios Koulouras

Microorganisms 2020, 8(2), 287; https://doi.org/10.3390/microorganisms8020287 - 20 Feb 2020

Cited by 42 | Viewed by 5609

Abstract

The prevalence of acinetobacter baumannii (AB) as a cause of hospital infections has been rising. Unfortunately, emerging colistin resistance limits therapeutic options and affects the outcome. The aim of the study was to confirm our clinically-driven hypothesis that intensive care unit (ICU) patients [...] Read more.

The prevalence of acinetobacter baumannii (AB) as a cause of hospital infections has been rising. Unfortunately, emerging colistin resistance limits therapeutic options and affects the outcome. The aim of the study was to confirm our clinically-driven hypothesis that intensive care unit (ICU) patients with AB resistant-to-colistin (ABCoR) bloodstream infection (BSI) develop fulminant septic shock and die. We conducted a 28-month retrospective observational study including all patients developing AB infection on ICU admission or during ICU stay. From 622 screened patients, 31 patients with BSI sepsis were identified. Thirteen (41.9%) patients had ABCoR BSI and 18/31 (58.1%) had colistin-susceptible (ABCoS) BSI. All ABCoR BSI patients died; of them, 69% (9/13) presented with fulminant septic shock and died within the first 3 days from its onset. ABCoR BSI patients compared to ABCoS BSI patients had higher mortality (100% vs. 50%, respectively (p = 0.001)), died sooner (p = 0.006), had lower pH (p = 0.004) and higher lactate on ICU admission (p = 0.0001), and had higher APACHE II (p = 0.01) and Charlson Comorbidity Index scores (p = 0.044). In conclusion, we documented that critically ill patients with ABCoR BSI exhibit fulminant septic shock with excessive mortality. Our results highlight the emerging clinical problem of AB colistin resistance among ICU patients. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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11 pages, 574 KiB

Open AccessArticle

Impact of Chronic Obstructive Pulmonary Disease on Incidence, Microbiology and Outcome of Ventilator-Associated Lower Respiratory Tract Infections

by Anahita Rouzé, Pauline Boddaert, Ignacio Martin-Loeches, Pedro Povoa, Alejandro Rodriguez, Nassima Ramdane, Jorge Salluh, Marion Houard and Saad Nseir

Microorganisms 2020, 8(2), 165; https://doi.org/10.3390/microorganisms8020165 - 23 Jan 2020

Cited by 9 | Viewed by 3182

Abstract

Objectives: To determine the impact of chronic obstructive pulmonary disease (COPD) on incidence, microbiology, and outcomes of ventilator-associated lower respiratory tract infections (VA-LRTI). Methods: Planned ancillary analysis of TAVeM study, including 2960 consecutive adult patients who received invasive mechanical ventilation (MV) > 48 [...] Read more.

Objectives: To determine the impact of chronic obstructive pulmonary disease (COPD) on incidence, microbiology, and outcomes of ventilator-associated lower respiratory tract infections (VA-LRTI). Methods: Planned ancillary analysis of TAVeM study, including 2960 consecutive adult patients who received invasive mechanical ventilation (MV) > 48 h. COPD patients (n = 494) were compared to non-COPD patients (n = 2466). The diagnosis of ventilator-associated tracheobronchitis (VAT) and ventilator-associated pneumonia (VAP) was based on clinical, radiological and quantitative microbiological criteria. Results: No significant difference was found in VAP (12% versus 13%, p = 0.931), or VAT incidence (13% versus 10%, p = 0.093) between COPD and non-COPD patients. Among patients with VA-LRTI, Escherichia coli and Stenotrophomonas maltophilia were significantly more frequent in COPD patients as compared with non-COPD patients. However, COPD had no significant impact on multidrug-resistant bacteria incidence. Appropriate antibiotic treatment was not significantly associated with progression from VAT to VAP among COPD patients who developed VAT, unlike non-COPD patients. Among COPD patients, patients who developed VAT or VAP had significantly longer MV duration (17 days (9–30) or 15 (8–27) versus 7 (4–12), p < 0.001) and intensive care unit (ICU) length of stay (24 (17–39) or 21 (14–40) versus 12 (8–19), p < 0.001) than patients without VA-LRTI. ICU mortality was also higher in COPD patients who developed VAP (44%), but not VAT(38%), as compared to no VA-LRTI (26%, p = 0.006). These worse outcomes associated with VA-LRTI were similar among non-COPD patients. Conclusions: COPD had no significant impact on incidence or outcomes of patients who developed VAP or VAT. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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18 pages, 4933 KiB

Open AccessArticle

Global Burden of Colistin-Resistant Bacteria: Mobilized Colistin Resistance Genes Study (1980–2018)

by Mohammed Elbediwi, Yan Li, Narayan Paudyal, Hang Pan, Xiaoliang Li, Shaohua Xie, Andreja Rajkovic, Youjun Feng, Weihuan Fang, Shelley C. Rankin and Min Yue

Microorganisms 2019, 7(10), 461; https://doi.org/10.3390/microorganisms7100461 - 16 Oct 2019

Cited by 181 | Viewed by 9618

Abstract

Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of [...] Read more.

Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of mcr genes, their reservoirs and the potential pathways for human transmission are required to implement control and prevention strategies, yet such data are lacking. Publications from four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases published between 18 November 2015 and 30 December 2018 were identified. In this systematic review and meta-analysis, the prevalence of mcr genes in bacteria isolated from humans, animals, the environment and food products were investigated. A total of 974 publications were identified. 202 observational studies were included in the systematic review and 71 in the meta-analysis. mcr genes were reported from 47 countries across six continents and the overall average prevalence was 4.7% (0.1–9.3%). China reported the highest number of mcr-positive strains. Pathogenic Escherichia coli (54%), isolated from animals (52%) and harboring an IncI2 plasmid (34%) were the bacteria with highest prevalence of mcr genes. The estimated prevalence of mcr-1 pathogenic E. coli was higher in food-animals than in humans and food products, which suggests a role for foodborne transmission. This study provides a comprehensive assessment of prevalence of the mcr gene by source, organism, genotype and type of plasmid. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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19 pages, 926 KiB

Open AccessArticle

Prevalence of Resistance to β-Lactam Antibiotics and bla Genes Among Commensal Haemophilus parainfluenzae Isolates from Respiratory Microbiota in Poland

by Sylwia Andrzejczuk, Urszula Kosikowska, Edyta Chwiejczak, Dagmara Stępień-Pyśniak and Anna Malm

Microorganisms 2019, 7(10), 427; https://doi.org/10.3390/microorganisms7100427 - 9 Oct 2019

Cited by 8 | Viewed by 4326

Abstract

(1) Background: Beta-lactams are the most frequently used antimicrobials, and are the first-line drugs in many infectious diseases, e.g., pneumonia, otitis media. Due to this fact, various bacteria have developed resistance to this group of drugs. (2) Methods: Eighty-seven Haemophilus parainfluenzae isolates were [...] Read more.

(1) Background: Beta-lactams are the most frequently used antimicrobials, and are the first-line drugs in many infectious diseases, e.g., pneumonia, otitis media. Due to this fact, various bacteria have developed resistance to this group of drugs. (2) Methods: Eighty-seven Haemophilus parainfluenzae isolates were obtained from adults 18–70 years old in eastern Poland. The presence of 10 bla genes and 2 substitutions in ftsI reported as the most frequent in H. parainfluenzae were analyzed. (3) Results: Among 57 beta-lactam-resistant isolates, 63.2% encoded bla genes; bla_TEM-1 predominated (54.4%), followed by bla_OXA (19.3%), bla_DHA (12.3%), bla_SHV (10.5%), bla_GES (7.0%), bla_CMY (5.3%), bla_VEB (1.8%) and bla_ROB-1 (1.8%). Lys-526 was the most common substitution in ftsI gene. The resistance genotypes were as follows: gBLNAS (17.5%), low-gBLNAR I (1.8%), low-gBLNAR II (1.8%), gBLNAR II (15.8%), gBLPAS (15.8%), gBLPAR (19.3%), gBLPBS I (8.8%) and gBLPBS II (1.8%); (4) Conclusions: This has been the first study to report on the high diversity of bla genes in H. parainfluenzae isolates in Poland. High sensitivity and specificity of benzylpenicillin test, as well as PCR of bla genes were shown, indicating that these methods may be useful as tools for the rapid screening of beta-lactamase prevalence and resistance to beta-lactams among H. parainfluenzae isolated from respiratory microbiota. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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10 pages, 2106 KiB

Open AccessArticle

Z/I1 Hybrid Virulence Plasmids Carrying Antimicrobial Resistance genes in S. Typhimurium from Australian Food Animal Production

by Ethan R. Wyrsch, Jane Hawkey, Louise M. Judd, Ruth Haites, Kathryn E. Holt, Steven P. Djordjevic and Helen Billman-Jacobe

Microorganisms 2019, 7(9), 299; https://doi.org/10.3390/microorganisms7090299 - 29 Aug 2019

Cited by 7 | Viewed by 5683

Abstract

Knowledge of mobile genetic elements that capture and disseminate antimicrobial resistance genes between diverse environments, particularly across human–animal boundaries, is key to understanding the role anthropogenic activities have in the evolution of antimicrobial resistance. Plasmids that circulate within the Enterobacteriaceae and the Proteobacteria [...] Read more.

Knowledge of mobile genetic elements that capture and disseminate antimicrobial resistance genes between diverse environments, particularly across human–animal boundaries, is key to understanding the role anthropogenic activities have in the evolution of antimicrobial resistance. Plasmids that circulate within the Enterobacteriaceae and the Proteobacteria more broadly are well placed to acquire resistance genes sourced from separate niche environments and provide a platform for smaller mobile elements such as IS26 to assemble these genes into large, complex genomic structures. Here, we characterised two atypical Z/I1 hybrid plasmids, pSTM32-108 and pSTM37-118, hosting antimicrobial resistance and virulence associated genes within endemic pathogen Salmonella enterica serovar Typhimurium 1,4,[5],12:i:-, sourced from Australian swine production facilities during 2013. We showed that the plasmids found in S. Typhimurium 1,4,[5],12:i:- are close relatives of two plasmids identified from Escherichia coli of human and bovine origin in Australia circa 1998. The older plasmids, pO26-CRL₁₂₅ and pO111-CRL₁₁₅, encoded a putative serine protease autotransporter and were host to a complex resistance region composed of a hybrid Tn21-Tn1721 mercury resistance transposon and composite IS26 transposon Tn6026. This gave a broad antimicrobial resistance profile keyed towards first generation antimicrobials used in Australian agriculture but also included a class 1 integron hosting the trimethoprim resistance gene dfrA5. Genes encoding resistance to ampicillin, trimethoprim, sulphonamides, streptomycin, aminoglycosides, tetracyclines and mercury were a feature of these plasmids. Phylogenetic analyses showed very little genetic drift in the sequences of these plasmids over the past 15 years; however, some alterations within the complex resistance regions present on each plasmid have led to the loss of various resistance genes, presumably as a result of the activity of IS26. These alterations may reflect the specific selective pressures placed on the host strains over time. Our studies suggest that these plasmids and variants of them are endemic in Australian food production systems. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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13 pages, 226 KiB

Open AccessArticle

Infections Due to Multidrug-Resistant Bacteria in Oncological Patients: Insights from a Five-Year Epidemiological and Clinical Analysis

by Eleni Isidora A. Perdikouri, Kostoula Arvaniti, Dimitrios Lathyris, Fani Apostolidou Kiouti, Eleni Siskou, Anna Bettina Haidich and Christos Papandreou

Microorganisms 2019, 7(9), 277; https://doi.org/10.3390/microorganisms7090277 - 21 Aug 2019

Cited by 34 | Viewed by 3981

Abstract

Bacterial infections are frequent complications in cancer patients. Among them, those caused by multidrug-resistant (MDR) bacteria increase morbidity and mortality mainly because of limited therapeutic options. Current knowledge regarding MDR infections in patients with solid tumors is limited. We assessed the epidemiology and [...] Read more.

Bacterial infections are frequent complications in cancer patients. Among them, those caused by multidrug-resistant (MDR) bacteria increase morbidity and mortality mainly because of limited therapeutic options. Current knowledge regarding MDR infections in patients with solid tumors is limited. We assessed the epidemiology and risk factors of increased mortality in these patients. In this retrospective five-year single cohort observational study, we included all oncological patients with MDR infections. Cancer-related parameters, comorbidities, prior use of antibiotics, previous surgical interventions and hospitalization, as well as the use of invasive procedures were investigated as potential risk factors causing adverse outcomes. Seventy-three patients with MDR infection were included: 37% with carbapenem-resistant Klebsiella pneumoniae, 24% with oxacillin-resistant Staphylococcus aureus (MRSA) and 21% with carbapenem-resistant Acinetobacter baumanni. Previous colonization with MDR bacteria was detected in 14% patients, while 20% of the patients presented MDR colonization or infection at ward admission. Mortality during the infection episode was 32%. Duration of hospitalization and CRP were statistically significant risk factors of mortality, whereas administration of guided antibiotics was a protective factor. Knowledge of local epidemiology of MDR bacteria can help physicians promptly identify cancer patients at risk of MDR infections and initiate timely effective empirical antibiotic treatment that can eventually improve the overall therapeutic management. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

14 pages, 648 KiB

Open AccessArticle

Community- and Hospital-Acquired Klebsiella pneumoniae Urinary Tract Infections in Portugal: Virulence and Antibiotic Resistance

by Cátia Caneiras, Luis Lito, José Melo-Cristino and Aida Duarte

Microorganisms 2019, 7(5), 138; https://doi.org/10.3390/microorganisms7050138 - 16 May 2019

Cited by 87 | Viewed by 9372

Abstract

Klebsiella pneumoniae is a clinically relevant pathogen and a frequent cause of hospital-acquired (HA) and community-acquired (CA) urinary tract infections (UTI). The increased resistance of this pathogen is leading to limited therapeutic options. To investigate the epidemiology, virulence, and antibiotic resistance profile of [...] Read more.

Klebsiella pneumoniae is a clinically relevant pathogen and a frequent cause of hospital-acquired (HA) and community-acquired (CA) urinary tract infections (UTI). The increased resistance of this pathogen is leading to limited therapeutic options. To investigate the epidemiology, virulence, and antibiotic resistance profile of K. pneumoniae in urinary tract infections, we conducted a multicenter retrospective study for a total of 81 isolates (50 CA-UTI and 31 HA-UTI) in Portugal. The detection and characterization of resistance and virulence determinants were performed by molecular methods (PCR, PCR-based replicon typing, and multilocus sequence typing (MLST)). Out of 50 CA-UTI isolates, six (12.0%) carried β-lactamase enzymes, namely bla_TEM-156 (n = 2), bla_TEM-24 (n = 1), bla_SHV-11 (n = 1), bla_SHV-33 (n = 1), and bla_CTX-M-15 (n = 1). All HA-UTI were extended-spectrum β-lactamase (ESBL) producers and had a multidrug resistant profile as compared to the CA-UTI isolates, which were mainly resistant to ciprofloxacin, levofloxacin, tigecycline, and fosfomycin. In conclusion, in contrast to community-acquired isolates, there is an overlap between virulence and multidrug resistance for hospital-acquired UTI K. pneumoniae pathogens. The study is the first to report different virulence characteristics for hospital and community K. pneumoniae pathogens, despite the production of β-lactamase and even with the presence of CTX-M-15 ESBL, a successful international ST15 clone, which were identified in both settings. This highlights that a focus on genomic surveillance should remain a priority in the hospital environment. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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7 pages, 483 KiB

Open AccessArticle

Competence for Natural Transformation Is Common among Clinical Strains of Resistant Acinetobacter spp.

by Sara Domingues, Natasha Rosário, Ângela Cândido, Daniela Neto, Kaare M. Nielsen and Gabriela J. Da Silva

Microorganisms 2019, 7(2), 30; https://doi.org/10.3390/microorganisms7020030 - 24 Jan 2019

Cited by 34 | Viewed by 5532

Abstract

Horizontal gene transfer events provide the basis for extensive dissemination of antimicrobial resistance traits between bacterial populations. Conjugation is considered to be the most frequent mechanism behind new resistance acquisitions in clinical pathogens but does not fully explain the resistance patterns seen in [...] Read more.

Horizontal gene transfer events provide the basis for extensive dissemination of antimicrobial resistance traits between bacterial populations. Conjugation is considered to be the most frequent mechanism behind new resistance acquisitions in clinical pathogens but does not fully explain the resistance patterns seen in some bacterial genera. Gene transfer by natural transformation has been described for numerous clinical isolates, including some Acinetobacter species. The main aim of this study was to determine to what extent clinical, resistant Acinetobacter spp. isolates, express competence for natural transformation. Twenty-two clinical Acinetobacter spp. isolates collected over a 16-year time period, from five different geographical separated and/or distinct Portuguese Hospitals were tested for natural transformability. Fourteen isolates, including 11 A. baumannii, 2 A. nosocomialis and 1 Acinetobacter sp., were identified as competent on semisolid media facilitating surface-motility. Competent Acinetobacter isolates were found in all the hospitals tested. Furthermore, osmolarity was shown to influence the uptake of exogenous DNA by competent A. baumannii A118. Our study demonstrates that natural competence is common among clinical isolates of Acinetobacter spp., and hence likely an important trait for resistance acquisition. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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7 pages, 375 KiB

Open AccessCommunication

Susceptibility of Virulent Yersinia pestis Bacteria to Predator Bacteria in the Lungs of Mice

by Riccardo Russo, Irina Kolesnikova, Thomas Kim, Shilpi Gupta, Androulla Pericleous, Daniel E. Kadouri and Nancy D. Connell

Microorganisms 2019, 7(1), 2; https://doi.org/10.3390/microorganisms7010002 - 21 Dec 2018

Cited by 22 | Viewed by 5716

Abstract

Multi-drug resistant bacterial infections are a serious threat to global public health. Changes in treatment modalities and prudent use of antibiotics can assist in reducing the threat, but new approaches are also required for untreatable cases. The use of predatory bacteria, such as [...] Read more.

Multi-drug resistant bacterial infections are a serious threat to global public health. Changes in treatment modalities and prudent use of antibiotics can assist in reducing the threat, but new approaches are also required for untreatable cases. The use of predatory bacteria, such as Bdellovibrio bacteriovorus, is among the novel approaches being considered as possible therapeutics for antibiotic resistant and/or unidentified bacterial infections. Previous studies have examined the feasibility of using predatory bacteria to reduce colony-forming units (CFUs) in the lungs of rats exposed to lethal doses of Klebsiella pneumoniae; here we apply the approach to the Tier 1 select agent Yersinia pestis, and show that three doses of B. bacteriovorus introduced every six hours reduces the number of CFUs of Y. pestis in the lungs of inoculated mice by 86% after 24 h of infection. These experiments further demonstrate that predatory bacteria may serve to combat Gram negative bacterial infections, including those considered potential bioweapon agents, in the future. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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Review

Jump to: Editorial, Research, Other

17 pages, 328 KiB

Open AccessReview

Pathogenesis-Targeted Preventive Strategies for Multidrug Resistant Ventilator-Associated Pneumonia: A Narrative Review

by Antonella Cotoia, Savino Spadaro, Guido Gambetti, Despoina Koulenti and Gilda Cinnella

Microorganisms 2020, 8(6), 821; https://doi.org/10.3390/microorganisms8060821 - 30 May 2020

Cited by 14 | Viewed by 4740

Abstract

Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit (ICU), accounting for relevant morbidity and mortality among critically ill patients, especially when caused by multidrug resistant (MDR) organisms. The rising problem of MDR etiologies, which has led to [...] Read more.

Ventilator-associated pneumonia (VAP) is the most common hospital-acquired infection in the intensive care unit (ICU), accounting for relevant morbidity and mortality among critically ill patients, especially when caused by multidrug resistant (MDR) organisms. The rising problem of MDR etiologies, which has led to a reduction in treatment options, have increased clinician’s attention to the employment of effective prevention strategies. In this narrative review we summarized the evidence resulting from 27 original articles that were identified through a systematic database search of the last 15 years, focusing on several pathogenesis-targeted strategies which could help preventing MDR-VAP. Oral hygiene with Chlorhexidine (CHX), CHX body washing, selective oral decontamination (SOD) and/or digestive decontamination (SDD), multiple decontamination regimens, probiotics, subglottic secretions drainage (SSD), special cuff material and shape, silver-coated endotracheal tubes (ETTs), universal use of gloves and contact isolation, alcohol-based hand gel, vaporized hydrogen peroxide, and bundles of care have been addressed. The most convincing evidence came from interventions directly addressed against the key factors of MDR-VAP pathogenesis, especially when they are jointly implemented into bundles. Further research, however, is warranted to identify the most effective combination. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

17 pages, 1172 KiB

Open AccessReview

Gut Microbiota, Antibiotic Therapy and Antimicrobial Resistance: A Narrative Review

by Benoit Pilmis, Alban Le Monnier and Jean-Ralph Zahar

Microorganisms 2020, 8(2), 269; https://doi.org/10.3390/microorganisms8020269 - 17 Feb 2020

Cited by 65 | Viewed by 10344

Abstract

Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, [...] Read more.

Antimicrobial resistance is a major concern. Epidemiological studies have demonstrated direct relationships between antibiotic consumption and emergence/dissemination of resistant strains. Within the last decade, authors confounded spectrum activity and ecological effects and did not take into account several other factors playing important roles, such as impact on anaerobic flora, biliary elimination and sub-inhibitory concentration. The ecological impact of antibiotics on the gut microbiota by direct or indirect mechanisms reflects the breaking of the resistance barrier to colonization. To limit the impact of antibiotic therapy on gut microbiota, consideration of the spectrum of activity and route of elimination must be integrated into the decision. Various strategies to prevent (antimicrobial stewardship, action on residual antibiotics at colonic level) or cure dysbiosis (prebiotic, probiotic and fecal microbiota transplantation) have been introduced or are currently being developed. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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40 pages, 583 KiB

Open AccessReview

Emerging Treatment Options for Infections by Multidrug-Resistant Gram-Positive Microorganisms

by Despoina Koulenti, Elena Xu, Andrew Song, Isaac Yin Sum Mok, Drosos E. Karageorgopoulos, Apostolos Armaganidis, Sotirios Tsiodras and Jeffrey Lipman

Microorganisms 2020, 8(2), 191; https://doi.org/10.3390/microorganisms8020191 - 30 Jan 2020

Cited by 34 | Viewed by 8540

Abstract

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread [...] Read more.

Antimicrobial agents are currently the mainstay of treatment for bacterial infections worldwide. However, due to the increased use of antimicrobials in both human and animal medicine, pathogens have now evolved to possess high levels of multi-drug resistance, leading to the persistence and spread of difficult-to-treat infections. Several current antibacterial agents active against Gram-positive bacteria will be rendered useless in the face of increasing resistance rates. There are several emerging antibiotics under development, some of which have been shown to be more effective with an improved safety profile than current treatment regimens against Gram-positive bacteria. We will extensively discuss these antibiotics under clinical development (phase I-III clinical trials) to combat Gram-positive bacteria, such as Staphylococcus aureus, Enterococcus faecium and Streptococcus pneumoniae. We will delve into the mechanism of actions, microbiological spectrum, and, where available, the pharmacokinetics, safety profile, and efficacy of these drugs, aiming to provide a comprehensive review to the involved stakeholders. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

15 pages, 278 KiB

Open AccessReview

Bacterial, Gut Microbiome-Modifying Therapies to Defend against Multidrug Resistant Organisms

by Amy Feehan and Julia Garcia-Diaz

Microorganisms 2020, 8(2), 166; https://doi.org/10.3390/microorganisms8020166 - 24 Jan 2020

Cited by 15 | Viewed by 3946

Abstract

Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected [...] Read more.

Antibiotics have revolutionized human and animal healthcare, but their utility is reduced as bacteria evolve resistance mechanisms over time. Thankfully, there are novel antibiotics in the pipeline to overcome resistance, which are mentioned elsewhere in this special issue, but eventually bacteria are expected to evolve resistance to most new compounds as well. Multidrug resistant organisms (MDROs) that cause infections increase morbidity, mortality, and readmissions as compared with susceptible organisms. Consequently, many research and development pipelines are focused on non-antibiotic strategies, including fecal microbiota transplantation (FMT), probiotics and prebiotics, and a range of therapies in between. Studies reviewed here focus on efforts to directly treat or prevent MDRO infections or colonization. The studies were collected through clinicaltrials.gov, PubMed, and the International Conference on the Harmonisation Good Clinical Practice website (ichgcp.net). While the gold standard of clinical research is randomized controlled trials (RCTs), several pilot studies are included because the field is so young. Although a vast preclinical body of research has led to studies in humans, animal and in vitro studies are not within the scope of this review. This narrative review discusses microbiome-modifying therapies targeting MDROs in the gut and includes current results, ongoing clinical trials, companies with therapies in the pipeline specifically for MDROs, and commentary on clinical implementation and challenges. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

21 pages, 521 KiB

Open AccessReview

Nanomaterials as Delivery Vehicles and Components of New Strategies to Combat Bacterial Infections: Advantages and Limitations

by Atanu Naskar and Kwang-sun Kim

Microorganisms 2019, 7(9), 356; https://doi.org/10.3390/microorganisms7090356 - 16 Sep 2019

Cited by 79 | Viewed by 5142

Abstract

Life-threatening bacterial infections have been well-controlled by antibiotic therapies and this approach has greatly improved the health and lifespan of human beings. However, the rapid and worldwide emergence of multidrug resistant (MDR) bacteria has forced researchers to find alternative treatments for MDR infections [...] Read more.

Life-threatening bacterial infections have been well-controlled by antibiotic therapies and this approach has greatly improved the health and lifespan of human beings. However, the rapid and worldwide emergence of multidrug resistant (MDR) bacteria has forced researchers to find alternative treatments for MDR infections as MDR bacteria can sometimes resist all the present day antibiotic therapies. In this respect, nanomaterials have emerged as innovative antimicrobial agents that can be a potential solution against MDR bacteria. The present review discusses the advantages of nanomaterials as potential medical means and carriers of antibacterial activity, the types of nanomaterials used for antibacterial agents, strategies to tackle toxicity of nanomaterials for clinical applications, and limitations which need extensive studies to overcome. The current progress of using different types of nanomaterials, including new emerging strategies for the single purpose of combating bacterial infections, is also discussed in detail. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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24 pages, 409 KiB

Open AccessReview

Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms

by Despoina Koulenti, Elena Xu, Isaac Yin Sum Mok, Andrew Song, Drosos E. Karageorgopoulos, Apostolos Armaganidis, Jeffrey Lipman and Sotirios Tsiodras

Microorganisms 2019, 7(8), 270; https://doi.org/10.3390/microorganisms7080270 - 18 Aug 2019

Cited by 71 | Viewed by 9250

Abstract

Increasing multidrug-resistance to Gram-positive pathogens, particularly to staphylococci, enterococci and streptococci, is a major problem, resulting in significant morbidity, mortality and healthcare costs. In recent years, only a small number of novel antibiotics effective against Gram-positive bacteria has been approved. This review will [...] Read more.

Increasing multidrug-resistance to Gram-positive pathogens, particularly to staphylococci, enterococci and streptococci, is a major problem, resulting in significant morbidity, mortality and healthcare costs. In recent years, only a small number of novel antibiotics effective against Gram-positive bacteria has been approved. This review will discuss the current evidence for novel branded antibiotics that are highly effective in the treatment of multidrug-resistant infections by Gram-positive pathogens, namely ceftobiprole, ceftaroline, telavancin, oritavancin, dalbavancin, tedizolid, besifloxacin, delafloxacin, ozenoxacin, and omadacycline. The mechanism of action, pharmacokinetics, microbiological spectrum, efficacy and safety profile will be concisely presented. As for any emerging antibiotic agent, resistance is likely to develop against these highly effective antibiotics. Only through appropriate dosing, utilization and careful resistance development monitoring will these novel antibiotics continue to treat Gram-positive pathogens in the future. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

20 pages, 851 KiB

Open AccessReview

The Role of Minocycline in the Treatment of Nosocomial Infections Caused by Multidrug, Extensively Drug and Pandrug Resistant Acinetobacter baumannii: A Systematic Review of Clinical Evidence

by Paraskevi C. Fragkou, Garyfallia Poulakou, Andromachi Blizou, Myrto Blizou, Vasiliki Rapti, Drosos E. Karageorgopoulos, Despoina Koulenti, Antonios Papadopoulos, Dimitrios K. Matthaiou and Sotirios Tsiodras

Microorganisms 2019, 7(6), 159; https://doi.org/10.3390/microorganisms7060159 - 1 Jun 2019

Cited by 48 | Viewed by 6811

Abstract

Treatment options for multidrug resistant Acinetobacter baumannii strains (MDR-AB) are limited. Minocycline has been used alone or in combination in the treatment of infections associated with AB. A systematic review of the clinical use of minocycline in nosocomial infections associated with MDR-AB was [...] Read more.

Treatment options for multidrug resistant Acinetobacter baumannii strains (MDR-AB) are limited. Minocycline has been used alone or in combination in the treatment of infections associated with AB. A systematic review of the clinical use of minocycline in nosocomial infections associated with MDR-AB was performed according to the PRISMA-P guidelines. PubMed-Medline, Scopus and Web of Science ^TM databases were searched from their inception until March 2019. Additional Google Scholar free searches were performed. Out of 2990 articles, 10 clinical studies (9 retrospective case series and 1 prospective single center trial) met the eligibility criteria. In total, 223 out of 268 (83.2%) evaluated patients received a minocycline-based regimen; and 200 out of 218 (91.7%) patients with available data received minocycline as part of a combination antimicrobial regimen (most frequently colistin or carbapenems). Pneumonia was the most common infection type in the 268 cases (80.6% with 50.4% ventilator-associated pneumonia). The clinical and microbiological success rates following minocycline treatment were 72.6% and 60.2%, respectively. Mortality was 20.9% among 167 patients with relevant data. In this systematic review, minocycline demonstrated promising activity against MDR-AB isolates. This review sets the ground for further studies exploring the role of minocycline in the treatment of MDR-AB associated infections. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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17 pages, 262 KiB

Open AccessReview

Plasmid-Mediated Colistin Resistance in Salmonella enterica: A Review

by Tiago Lima, Sara Domingues and Gabriela Jorge Da Silva

Microorganisms 2019, 7(2), 55; https://doi.org/10.3390/microorganisms7020055 - 19 Feb 2019

Cited by 75 | Viewed by 7946

Abstract

Colistin is widely used in food-animal production. Salmonella enterica is a zoonotic pathogen, which can pass from animal to human microbiota through the consumption of contaminated food, and cause disease, often severe, especially in young children, elderly and immunocompromised individuals. Recently, plasmid-mediated colistin [...] Read more.

Colistin is widely used in food-animal production. Salmonella enterica is a zoonotic pathogen, which can pass from animal to human microbiota through the consumption of contaminated food, and cause disease, often severe, especially in young children, elderly and immunocompromised individuals. Recently, plasmid-mediated colistin resistance was recognised; mcr-like genes are being identified worldwide. Colistin is not an antibiotic used to treat Salmonella infections, but has been increasingly used as one of the last treatment options for carbapenem resistant Enterobacteria in human infections. The finding of mobilizable mcr-like genes became a global concern due to the possibility of horizontal transfer of the plasmid that often carry resistance determinants to beta-lactams and/or quinolones. An understanding of the origin and dissemination of mcr-like genes in zoonotic pathogens such as S. enterica will facilitate the management of colistin use and target interventions to prevent further spread. The main objective of this review was to collect epidemiological data about mobilized colistin resistance in S. enterica, describing the mcr variants, identified serovars, origin of the isolate, country and other resistance genes located in the same genetic platform. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

13 pages, 793 KiB

Open AccessReview

PES Pathogens in Severe Community-Acquired Pneumonia

by Catia Cillóniz, Cristina Dominedò, Antonello Nicolini and Antoni Torres

Microorganisms 2019, 7(2), 49; https://doi.org/10.3390/microorganisms7020049 - 12 Feb 2019

Cited by 20 | Viewed by 7123

Abstract

Worldwide, there is growing concern about the burden of pneumonia. Severe community-acquired pneumonia (CAP) is frequently complicated by pulmonary and extra-pulmonary complications, including sepsis, septic shock, acute respiratory distress syndrome, and acute cardiac events, resulting in significantly increased intensive care admission rates and [...] Read more.

Worldwide, there is growing concern about the burden of pneumonia. Severe community-acquired pneumonia (CAP) is frequently complicated by pulmonary and extra-pulmonary complications, including sepsis, septic shock, acute respiratory distress syndrome, and acute cardiac events, resulting in significantly increased intensive care admission rates and mortality rates. Streptococcus pneumoniae (Pneumococcus) remains the most common causative pathogen in CAP. However, several bacteria and respiratory viruses are responsible, and approximately 6% of cases are due to the so-called PES (Pseudomonas aeruginosa, extended-spectrum β-lactamase Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus) pathogens. Of these, P. aeruginosa and methicillin-resistant Staphylococcus aureus are the most frequently reported and require different antibiotic therapy to that for typical CAP. It is therefore important to recognize the risk factors for these pathogens to improve the outcomes in patients with CAP. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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4 pages, 185 KiB

Open AccessComment

Lefamulin. Comment on: “Novel Antibiotics for Multidrug-Resistant Gram-Positive Microorganisms. Microorganisms, 2019, 7, 270”

by Despoina Koulenti, Elena Xu, Isaac Yin Sum Mok, Andrew Song, Drosos E. Karageorgopoulos, Apostolos Armaganidis, Jeffrey Lipman and Sotirios Tsiodras

Microorganisms 2019, 7(10), 386; https://doi.org/10.3390/microorganisms7100386 - 24 Sep 2019

Cited by 28 | Viewed by 3338

Abstract

On 18 August 2019, an article was published in Microorganisms presenting novel, approved anti-Gram-positive antibiotics. On 19 August 2019, the U.S. Food and Drug Administration announced the approval of lefamulin, a representative of a new class of antibiotics, the pleuromutilins, for the treatment [...] Read more.

On 18 August 2019, an article was published in Microorganisms presenting novel, approved anti-Gram-positive antibiotics. On 19 August 2019, the U.S. Food and Drug Administration announced the approval of lefamulin, a representative of a new class of antibiotics, the pleuromutilins, for the treatment of adult community-acquired bacterial pneumonia. We present a brief description of lefamulin. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

2 pages, 185 KiB

Open AccessAddendum

Addendum: Cillóniz, C.; Dominedò, C.; Nicolini, A.; Torres, A. PES Pathogens in Severe Community-Acquired Pneumonia. Microorganisms 2019, 7, 49

by Catia Cillóniz, Cristina Dominedò, Antonello Nicolini and Antoni Torres

Microorganisms 2019, 7(6), 168; https://doi.org/10.3390/microorganisms7060168 - 6 Jun 2019

Cited by 2 | Viewed by 2432

Abstract

In the article recently published in Microorganisms [...] Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

11 pages, 845 KiB

Open AccessBrief Report

Characterization of Antimicrobial Resistance in Serratia spp. and Citrobacter spp. Isolates from Companion Animals in Japan: Nosocomial Dissemination of Extended-Spectrum Cephalosporin-Resistant Citrobacter freundii

by Kazuki Harada, Takae Shimizu, Hiroichi Ozaki, Yui Kimura, Tadashi Miyamoto and Yuzo Tsuyuki

Microorganisms 2019, 7(3), 64; https://doi.org/10.3390/microorganisms7030064 - 28 Feb 2019

Cited by 8 | Viewed by 4869

Abstract

In many countries including Japan, the status of emerging antimicrobial resistance among Serratia spp. and Citrobacter spp. in companion animals remains unknown because these genera are rarely isolated from animals. In this study, 30 Serratia spp. and 23 Citrobacter spp. isolates from companion [...] Read more.

In many countries including Japan, the status of emerging antimicrobial resistance among Serratia spp. and Citrobacter spp. in companion animals remains unknown because these genera are rarely isolated from animals. In this study, 30 Serratia spp. and 23 Citrobacter spp. isolates from companion animals underwent susceptibility testing for 10 antimicrobials. Phenotypic and genetic approaches were used to identify the mechanisms of extended-spectrum cephalosporins (ESC). Subsequently, ESC-resistant Citrobacter spp. strains underwent multilocus sequence typing and pulsed-field gel electrophoresis (PFGE). A significantly higher rate (34.8%) of ESC resistance was observed in Citrobacter spp. isolates than in Serratia spp. isolates (0%). ESC resistance was detected in five C. freundii strains, two C. portucalensis strains, and one C. koseri strain. All of the ESC-resistant Citrobacter spp. strains harbored CMY-type and/or DHA-type AmpC β-lactamases. Three C. freundii strains harbored the CTX-M-3-type extended-spectrum β-lactamases. Notably, the three blaCTX-3-producing and two blaCMY-117-bearing C. freundii strains (obtained from different patients in one hospital) had the same sequence type (ST156 and ST18, respectively) and similar PFGE profiles. We believe that ESC-resistant Citrobacter spp. are important nosocomial pathogens in veterinary medicine. Therefore, infection control in animal hospitals is essential to prevent dissemination of these resistant pathogens. Full article

(This article belongs to the Special Issue Multidrug-Resistant Pathogens)

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