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Antibiotics
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Severe Infections Due to Carbapenem-Resistant Pathogens
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Severe Infections Due to Carbapenem-Resistant Pathogens

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 33273

Special Issue Editor

Prof. Dr. Maria Caterina Pace

E-Mail Website
Guest Editor
Department of Anaesthesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy
Interests: intensive care unit infections

Special Issue Information

Dear Colleagues,

The increasing prevalence of resistance to antibiotics used to treat severe infections, particularly to carbapenems, is the cause of a dramatic increase in hospital mortality, which poses an urgent threat to public health. Thus, the phenomenon of carbapenem resistance deserves more attention for the sake of public health.

This Special Issue aims to collect multidisciplinary research related to severe infections due to carbapenem-resistant pathogens. The papers in this issue will constitute a valuable knowledge reservoir for scientists working in the field.

Prof. Dr. Maria Caterina Pace
Guest Editor

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

  • Carbapenem resistance
  • multidrug resistance
  • life-threatening infections
  • critical illness
  • antibiotics

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Published Papers (6 papers)

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Research

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10 pages, 509 KiB  
Article
Clinical Characteristics and Outcome of MDR/XDR Bacterial Infections in a Neuromuscular Semi-Intensive/Sub-Intensive Care Unit
by Arta Karruli, Alessia Massa, Lorenzo Bertolino, Roberto Andini, Pasquale Sansone, Salvatore Dongiovanni, Maria Caterina Pace, Vincenzo Pota and Emanuele Durante-Mangoni
Antibiotics 2022, 11(10), 1411; https://doi.org/10.3390/antibiotics11101411 - 13 Oct 2022
Cited by 3 | Viewed by 1888
Abstract
(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to [...] Read more.
(1) Background: The aim of this study was to assess the clinical and microbiological characteristics of multidrug-resistant infections in a neuromuscular semi-intensive/sub-intensive care unit; (2) Methods: Retrospective analysis on data from 18 patients with NMD with proven MDRO/XDRO colonisation/infection from August 2021 to March 2022 was carried out; (3) Results: Ten patients were males (55.6%), with a median age of 54 years, and there were fourteen patients (77.8%) with amyotrophic lateral sclerosis. All patients had at least one invasive device. Ten (55.6%) patients developed MDRO/XDRO infection (with a median time of 24 days) while six (33.3%) were colonised. The Charlson comorbidity index was >2 in both groups but higher in the infected compared with the colonised (4.5 vs. 3). Infected patients were mostly females (seven patients) with a median age of 62 years. The most common pathogens were Acinetobacter baumannii and Pseudomonas aeruginosa, infecting four (28.6%) patients each. Of eighteen infectious episodes, nine were pneumonia (hospital-acquired in seven cases). Colistin was the most commonly active antibiotic while carbapenems were largely inactive. Eradication of infection occurred in seven infectious episodes (38.9%). None of those with infection died; (4) Conclusions: MDRO/XDRO infections are common in patients with neuromuscular diseases, with carbapenem-resistant non-fermenting Gram-negative bacilli prevailing. These infections were numerically associated with the female sex, greater age, and comorbidities. Both eradication and infection-related mortality appeared low. We highlight the importance of infection prevention in this vulnerable population. Full article
(This article belongs to the Special Issue Severe Infections Due to Carbapenem-Resistant Pathogens)
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11 pages, 555 KiB  
Article
Epidemiological, Clinical and Microbiological Characteristics of Patients with Bloodstream Infections Due to Carbapenem-Resistant K. Pneumoniae in Southern Italy: A Multicentre Study
by Lorenzo Onorato, Bruno Sarnelli, Federica D’Agostino, Giuseppe Signoriello, Ugo Trama, Angelo D’Argenzio, Maria Vittoria Montemurro and Nicola Coppola
Antibiotics 2022, 11(5), 633; https://doi.org/10.3390/antibiotics11050633 - 8 May 2022
Cited by 7 | Viewed by 3805
Abstract
Background: In the present study, our aim was to evaluate the clinical and microbiological characteristics of a cohort of patients with bloodstream infections (BSI) due to Carbapenem-Resistant Enterobacteriaceae (CRE) and investigate the independent predictors of mortality. Methods: All episodes of carbapenem-resistant E.  [...] Read more.
Background: In the present study, our aim was to evaluate the clinical and microbiological characteristics of a cohort of patients with bloodstream infections (BSI) due to Carbapenem-Resistant Enterobacteriaceae (CRE) and investigate the independent predictors of mortality. Methods: All episodes of carbapenem-resistant E. coli (CREc) or K. pneumoniae (CRKp) BSI that were subject to a mandatory notification from January to December 2020 in all acute care hospitals and long-term care facilities of the Campania region in southern Italy were enrolled. All carbapenem-resistant strains were assessed through molecular tests for the presence of five carbapenemase gene families, i.e., K. pneumoniae Carbapenemase (KPC), oxacillinase-48 (OXA-48), New Delhi Metallo-β-lactamase (NDM), Verona integron encoded metallo-β-lactamase (VIM) and Imipenemase (IMP). Results: During the study period, a total of 154 consecutive non-repeated CRE BSI, all due to CRKp, were reported. The most frequently identified genes were KPC in 108 cases (70.1%), followed by metallo-betalactamases (MBL) (16.2%), and OXA-48 (2.6%); in 17 isolates (11%) no carbapenemase was detected. The overall mortality at 90 days was 41.9%. Using a log-rank test, patients without risk factors for CRE infections showed a significantly lower cumulative mortality (p = 0.001). After multivariate logistic regression analysis, the presence of at least one risk factor was the only predictor of mortality (OR: 1.7, 95% CI 1.2–6.1, p = 0.015). Conclusions. The study reported a non-negligible prevalence of MBL-producing organisms among CRKp isolated from blood cultures in our region. This data highlights the importance of molecular characterization of all clinical isolates of carbapenem-resistant organisms. Full article
(This article belongs to the Special Issue Severe Infections Due to Carbapenem-Resistant Pathogens)
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14 pages, 3576 KiB  
Article
Dynamic Gene Clusters Mediating Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates
by Samy Selim, Osama Ahmed Faried, Mohamed S. Almuhayawi, Osama A. Mohammed, Fayez M. Saleh and Mona Warrad
Antibiotics 2022, 11(2), 168; https://doi.org/10.3390/antibiotics11020168 - 28 Jan 2022
Cited by 6 | Viewed by 2837
Abstract
Acinetobacter baumanni (A. baumannii), a nonfermenting Gram-negative bacterium, has recently been associated with a broad range of nosocomial infections. To gain more meaningful insight into the problem of nosocomial illnesses caused by the multidrug-resistant (MDR) A. baumannii, as well as [...] Read more.
Acinetobacter baumanni (A. baumannii), a nonfermenting Gram-negative bacterium, has recently been associated with a broad range of nosocomial infections. To gain more meaningful insight into the problem of nosocomial illnesses caused by the multidrug-resistant (MDR) A. baumannii, as well as the factors that increase the risk of catching these infections, this investigation included a total of 86 clinical A. baumannii infections. Repetitive extragenic palindromic (REP)-PCR was used to investigate imipenem-resistant A. baumannii isolates for dynamic gene clusters causing carbapenem resistance. Four distinct A. baumannii lineages were found in the REP-PCR-DNA fingerprints of all isolates, with 95% of the samples coming from two dominant lineages. Imipenem, amikacin, and ciprofloxacin were less effective against genotype (A) isolates because of enhanced antibiotic tolerance. Lastly, to gain more insight into the mode of action of imipenem, we explored the binding affinity of imipenem toward different Acinetobacter baumannii OXA beta-lactamase class enzymes. Full article
(This article belongs to the Special Issue Severe Infections Due to Carbapenem-Resistant Pathogens)
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Review

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17 pages, 2406 KiB  
Review
A Literature Overview of Secondary Peritonitis Due to Carbapenem-Resistant Enterobacterales (CRE) in Intensive Care Unit (ICU) Patients
by Sveva Di Franco, Aniello Alfieri, Marco Fiore, Ciro Fittipaldi, Vincenzo Pota, Francesco Coppolino, Pasquale Sansone, Maria Caterina Pace and Maria Beatrice Passavanti
Antibiotics 2022, 11(10), 1347; https://doi.org/10.3390/antibiotics11101347 - 2 Oct 2022
Cited by 4 | Viewed by 2118
Abstract
This comprehensive review of the recently published literature offers an overview of a very topical and complex healthcare problem: secondary peritonitis from multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales (CRE). Spontaneous secondary peritonitis and postsurgical secondary peritonitis are among the major causes of community- and [...] Read more.
This comprehensive review of the recently published literature offers an overview of a very topical and complex healthcare problem: secondary peritonitis from multidrug-resistant pathogens, especially carbapenem-resistant Enterobacterales (CRE). Spontaneous secondary peritonitis and postsurgical secondary peritonitis are among the major causes of community- and healthcare- acquired sepsis, respectively. A large number of patients enter ICUs with a diagnosis of secondary peritonitis, and a high number of them reveal infection by CRE, P. aeruginosa or A. baumannii. For this reason, we conceived the idea to create a synthetic report on this topic including updated epidemiology data, a description of CRE resistance patterns, current strategies of antimicrobial treatment, and future perspectives. From this update it is clear that antimicrobial stewardship and precision medicine are becoming essential to fight the emergence of antimicrobial resistance and that even if there are new drugs effective against CRE causing secondary peritonitis, these drugs have to be used carefully especially in empirical therapy. Full article
(This article belongs to the Special Issue Severe Infections Due to Carbapenem-Resistant Pathogens)
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8 pages, 244 KiB  
Review
Mechanisms of Action of Carbapenem Resistance
by Caterina Aurilio, Pasquale Sansone, Manlio Barbarisi, Vincenzo Pota, Luca Gregorio Giaccari, Francesco Coppolino, Alfonso Barbarisi, Maria Beatrice Passavanti and Maria Caterina Pace
Antibiotics 2022, 11(3), 421; https://doi.org/10.3390/antibiotics11030421 - 21 Mar 2022
Cited by 99 | Viewed by 19393
Abstract
Carbapenem antibiotics are the most effective antimicrobials for the treatment of infections caused by the most resistant bacteria. They belong to the category of β-lactams that include the penicillins, cephalosporins, monobactams and carbapenems. This class of antimicrobials has a broader spectrum of activity [...] Read more.
Carbapenem antibiotics are the most effective antimicrobials for the treatment of infections caused by the most resistant bacteria. They belong to the category of β-lactams that include the penicillins, cephalosporins, monobactams and carbapenems. This class of antimicrobials has a broader spectrum of activity than most other beta-lactams antibiotics and are the most effective against Gram-positive and Gram-negative bacteria. All β-lactams antibiotics have a similar molecular structure: the carbapenems together with the β-lactams. This combination gives an extraordinary stability to the molecule against the enzymes inactivating the β-lactams. They are safe to use and therefore widespread use in many countries has given rise to carbapenem resistance which is a major global public health problem. The carbapenem resistance in some species is intrinsic and consists of the capacity to resist the action of antibiotics with several mechanisms: for the absence of a specific target, or an intrinsic difference in the composition of cytoplasmatic membrane or the inability to cross the outer membrane. In addition to intrinsic resistance, bacteria can develop resistance to antibiotics with several mechanisms that can be gathered in three main groups. The first group includes antibiotics with poor penetration into the outer membrane of bacterium or antibiotic efflux. The second includes bacteria that modify the target of the antibiotics through genetic mutations or post-translational modification of the target. The third includes bacteria that act with enzyme-catalyzed modification and this is due to the production of beta-lactamases, that are able to inactivate carbapenems and so called carbapenemases. In this review, we focus on the mode of action of carbapenem and the mechanisms of carbapenem resistance. Full article
(This article belongs to the Special Issue Severe Infections Due to Carbapenem-Resistant Pathogens)
17 pages, 325 KiB  
Review
Prevalence and Therapeutic Management of Infections by Multi-Drug-Resistant Organisms (MDROs) in Patients with Liver Cirrhosis: A Narrative Review
by Lorenzo Onorato, Caterina Monari, Salvatore Capuano, Pierantonio Grimaldi and Nicola Coppola
Antibiotics 2022, 11(2), 232; https://doi.org/10.3390/antibiotics11020232 - 11 Feb 2022
Cited by 5 | Viewed by 2343
Abstract
Bacterial infections are common events that significantly impact the clinical course of patients with cirrhosis. As in the general population, infections caused by multi-drug-resistant organisms (MDROs) are progressively increasing in cirrhotic patients, accounting for up to 30–35% of all infections. Nosocomial acquisition and [...] Read more.
Bacterial infections are common events that significantly impact the clinical course of patients with cirrhosis. As in the general population, infections caused by multi-drug-resistant organisms (MDROs) are progressively increasing in cirrhotic patients, accounting for up to 30–35% of all infections. Nosocomial acquisition and prior exposure to antimicrobial treatment or invasive procedures are well-known risk factors for MDRO infections. Several studies have demonstrated that infections due to MDROs have a poorer prognosis and higher rates of treatment failure, septic shock, and hospital mortality. Due to the increasing rate of antimicrobial resistance, the approach to empirical treatment in cirrhotic patients with life-threatening infections has become significantly more challenging. In order to ensure a prompt administration of effective antibiotic therapy while avoiding unnecessary antibiotic exposure at the same time, it is of utmost importance to choose the correct antimicrobial therapy and administration schedule based on individual clinical characteristics and risk factors and rapidly adopt de-escalation strategies as soon as microbiological data are available. In the present paper, we aimed to provide an overview of the most frequent infections diagnosed in cirrhotic patients, the prevalence and impact of antimicrobial resistance, and potential therapeutic options in this population. Full article
(This article belongs to the Special Issue Severe Infections Due to Carbapenem-Resistant Pathogens)
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