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The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections

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

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 27629

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Dr. Alberto Enrico Maraolo

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Section of Infectious Diseases, Department of Clinical Medicine and Surgery, University of Naples Federico II, 80131 Naples, Italy
Interests: evidence-based medicine; infectious diseases; meta-analysis; antimicrobial stewardship; nosocomial infections
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Special Issue Information

Dear Colleagues,

Infections by multidrug-resistant pathogens, especially in the nosocomial setting, represent a new pandemic throughout the world. The present Special Issue is aimed at collecting high-quality scientific papers conveying the multiple facets of the problem. Both primary research and secondary research papers are welcomed. The defining keywords of the included articles will be the following:

bacterial infections
fungal infections
multidrug-resistance
antibiotics
antifungals
antimicrobial stewardship
nosocomial infections
novel drugs

Dr. Alberto Enrico Maraolo
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.

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Related Special Issue

The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections, 2nd Edition in Antibiotics

Published Papers (9 papers)

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Editorial

Jump to: Research, Review, Other

4 pages, 206 KiB

Open AccessEditorial

Editorial for the Special Issue: “The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections”

by Alberto Enrico Maraolo

Antibiotics 2023, 12(12), 1683; https://doi.org/10.3390/antibiotics12121683 - 30 Nov 2023

Viewed by 1130

Abstract

Antimicrobial resistance (AMR) is a global problem; in 2019, before the Coronavirus Disease 2019 (COVID-19) pandemic, it was responsible of more deaths than any other infectious diseases, including human immunodeficiency virus and malaria [...] Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

Research

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12 pages, 1263 KiB

Open AccessArticle

Trends in Antibiotic-Resistant Bacteria Isolated from Screening Clinical Samples in a Tertiary Care Hospital over the 2018–2022 Period

by Delphine Lemonnier, Marine Machuel, Odile Obin, Gaëtan Outurquin, Crespin Adjidé and Catherine Mullié

Antibiotics 2023, 12(8), 1314; https://doi.org/10.3390/antibiotics12081314 - 14 Aug 2023

Cited by 2 | Viewed by 1472

Abstract

To assess the putative impact of the COVID-19 pandemic on multidrug-resistant (MDR) bacteria recovered from routine screening samples and, more globally, the trends in time to first positive screening sample and carriage duration of those bacteria in patients admitted to a tertiary hospital, data from laboratory results were retrospectively mined over the 2018–2022 period. No significant differences could be found in the number of positive patients or MDR isolates per year, time to positive screening, or carriage duration. Extended-spectrum beta-lactamase producers were dominant throughout the studied period but their relative proportion decreased over time as well as that of meticillin-resistant Staphylococcus aureus. Meanwhile, carbapenemase-producing enterobacteria (CPE) proportion increased. Among the 212 CPE isolates, Klebsiella pneumoniae and Escherichia coli were the more frequent species but, beginning in 2020, a significant rise in Enterobacter cloacae complex and Citrobacter freundii occurred. OXA48 was identified as the leading carbapenemase and, in 2020, a peak in VIM-producing enterobacteria linked to an outbreak of E. cloacae complex during the COVID-19 pandemic was singled out. Finally, a worrisome rise in isolates producing multiple carbapenemases (NDM/VIM and mostly NDM/OXA48) was highlighted, especially in 2022, which could lead to therapeutic dead-ends if their dissemination is not controlled. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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15 pages, 637 KiB

Open AccessArticle

Effectiveness of First-Line Therapy with Old and Novel Antibiotics in Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii: A Real Life, Prospective, Observational, Single-Center Study

by Lidia Dalfino, Monica Stufano, Davide Fiore Bavaro, Lucia Diella, Alessandra Belati, Stefania Stolfa, Federica Romanelli, Luigi Ronga, Rosa Di Mussi, Francesco Murgolo, Daniela Loconsole, Maria Chironna, Adriana Mosca, Maria Teresa Montagna, Annalisa Saracino and Salvatore Grasso

Antibiotics 2023, 12(6), 1048; https://doi.org/10.3390/antibiotics12061048 - 14 Jun 2023

Cited by 17 | Viewed by 2230

Abstract

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64–78) vs. 62 (IQR 52–69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6–8) vs. 4 (IQR 2–6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9–11) vs. 9 (IQR 7–11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04–1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19–0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17–0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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13 pages, 434 KiB

Open AccessArticle

Clinical Characteristics and Outcomes of Persistent Staphylococcal Bacteremia in a Tertiary Care Hospital

by Shiori Kitaya, Hajime Kanamori, Yukio Katori and Koichi Tokuda

Antibiotics 2023, 12(3), 454; https://doi.org/10.3390/antibiotics12030454 - 24 Feb 2023

Cited by 2 | Viewed by 1636

Abstract

Clinical outcomes of persistent staphylococcal bacteremia vary depending on the causative organism. This secondary data analysis study compared the clinical characteristics of persistent Staphylococcus aureus (S. aureus)- and coagulase-negative staphylococci (CoNS)-caused bacteremia, focusing on the methicillin-resistant status. This study used data collected from patients who underwent blood cultures between January 2012 and December 2021 at Tohoku University Hospital, Japan. Patients with persistent staphylococcal bacteremia were divided into groups based on the pathogen and methicillin-resistant status, and their characteristics were analyzed. The primary outcomes were early (30-day), late (30–90 days), and 90-day mortality rates. The early, late, and 90-day mortality rates were similar between the persistent CoNS and S. aureus bacteremia groups. Patients with persistent methicillin-resistant S. aureus (MRSA) bacteremia tended to have higher early, late, and 90-day mortality rates than those with persistent methicillin-susceptible S. aureus bacteremia (not statistically significant). No differences were observed between the methicillin-resistant and-susceptible CoNS groups. In patients with persistent CoNS bacteremia, mortality tended to increase, especially in debilitated or immunocompromised patients with distant metastases, underscoring the importance of infection source control. Mortality tended to be high in patients with persistent MRSA bacteremia, especially when persistent bacteremia clearance was not confirmed, illustrating the need for careful therapeutic management. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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15 pages, 460 KiB

Open AccessArticle

Impact of Persistent Multidrug-Resistant Gram-Negative Bacteremia on Clinical Outcome and Mortality

by Shiori Kitaya, Hajime Kanamori, Yukio Katori and Koichi Tokuda

Antibiotics 2023, 12(2), 313; https://doi.org/10.3390/antibiotics12020313 - 3 Feb 2023

Cited by 4 | Viewed by 2181

Abstract

The clinical aspects of persistent bacteremia (PB) caused by gram-negative rods (GNRs) in terms of antimicrobial resistance (AMR) and PB clearance status are unclear. This secondary analysis of a retrospective cohort study investigated differences in PB caused by Enterobacterales and glucose non-fermentative GNRs (NF-GNRs) based on AMR and PB clearance. We retrospectively surveyed medical records at Tohoku University Hospital. Patients for whom blood cultures were performed between January 2012 and December 2021 were recruited. PB cases were grouped based on AMR and PB clearance; the characteristics of PB due to each bacterial pathogen were examined. The main outcome variable was mortality. The late (30–90-day) mortality rate was significantly higher in the multidrug-resistant (MDR) group than in the non-MDR group for Enterobacterales. However, no significant difference was noted in mortality rates between NF-GNRs with and without AMR. Mortality rates tended to be higher in the non-PB-clearance group than in the clearance group for both Enterobacterales and NF-GNRs. Since the mortality rate was higher in the MDR group in the case of Enterobacterales PB, more careful management is necessary for this condition. Follow-up blood cultures and confirming the clearance of PB are useful for improving the survival rate. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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13 pages, 687 KiB

Open AccessArticle

Development of a Clinical Score to Stratify the Risk for Carbapenem-Resistant Enterobacterales Bacteremia in Patients with Cancer and Hematopoietic Stem Cell Transplantation

by Fabián Herrera, Diego Torres, Ana Laborde, Lorena Berruezo, Rosana Jordán, Inés Roccia Rossi, Alejandra Valledor, Patricia Costantini, Miguel Dictar, Andrea Nenna, María Laura Pereyra, Sandra Lambert, José Benso, Fernando Poletta, María Luz Gonzalez Ibañez, Nadia Baldoni, María José Eusebio, Fiorella Lovano, Laura Barcán, Martín Luck, Agustina Racioppi, Lucas Tula, Fernando Pasterán, Alejandra Corso, Melina Rapoport, Federico Nicola, María Cristina García Damiano, Ruth Carbone, Renata Monge, Mariana Reynaldi, Graciela Greco, Marcelo Bronzi, Sandra Valle, María Laura Chaves, Viviana Vilches, Miriam Blanco and Alberto Ángel Carena Show full author list Hide full author list

Antibiotics 2023, 12(2), 226; https://doi.org/10.3390/antibiotics12020226 - 20 Jan 2023

Cited by 9 | Viewed by 3027

Abstract

Identifying the risk factors for carbapenem-resistant Enterobacterales (CRE) bacteremia in cancer and hematopoietic stem cell transplantation (HSCT) patients would allow earlier initiation of an appropriate empirical antibiotic treatment. This is a prospective multicenter observational study in patients from 12 centers in Argentina, who presented with cancer or hematopoietic stem-cell transplant and developed Enterobacterales bacteremia. A multiple logistic regression model identified risk factors for CRE bacteremia, and a score was developed according to the regression coefficient. This was validated by the bootstrap resampling technique. Four hundred and forty-three patients with Enterobacterales bacteremia were included: 59 with CRE and 384 with carbapenem-susceptible Enterobacterales (CSE). The risk factors that were identified and the points assigned to each of them were: ≥10 days of hospitalization until bacteremia: OR 4.03, 95% CI 1.88–8.66 (2 points); previous antibiotics > 7 days: OR 4.65, 95% CI 2.29–9.46 (2 points); current colonization with KPC-carbapenemase-producing Enterobacterales: 33.08, 95% CI 11.74–93.25 (5 points). With a cut-off of 7 points, a sensitivity of 35.59%, specificity of 98.43%, PPV of 77.7%, and NPV of 90.9% were obtained. The overall performance of the score was satisfactory (AUROC of 0.85, 95% CI 0.80–0.91). Finally, the post-test probability of CRE occurrence in patients with none of the risk factors was 1.9%, which would virtually rule out the presence of CRE bacteremia. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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Review

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22 pages, 1365 KiB

Open AccessReview

Preventing Multidrug-Resistant Bacterial Transmission in the Intensive Care Unit with a Comprehensive Approach: A Policymaking Manual

by Georgios Schinas, Elena Polyzou, Nikolaos Spernovasilis, Charalambos Gogos, George Dimopoulos and Karolina Akinosoglou

Antibiotics 2023, 12(8), 1255; https://doi.org/10.3390/antibiotics12081255 - 30 Jul 2023

Cited by 9 | Viewed by 3446

Abstract

Patients referred to intensive care units (ICU) commonly contract infections caused by multidrug-resistant (MDR) bacteria, which are typically linked to complications and high mortality. There are numerous independent factors that are associated with the transmission of these pathogens in the ICU. Preventive multilevel measures that target these factors are of great importance in order to break the chain of transmission. In this review, we aim to provide essential guidance for the development of robust prevention strategies, ultimately ensuring the safety and well-being of patients and healthcare workers in the ICU. We discuss the role of ICU personnel in cross-contamination, existing preventative measures, novel technologies, and strategies employed, along with antimicrobial surveillance and stewardship (AMSS) programs, to construct effective and thoroughly described policy recommendations. By adopting a multifaceted approach that combines targeted interventions with broader preventive strategies, healthcare facilities can create a more coherent line of defense against the spread of MDR pathogens. These recommendations are evidence-based, practical, and aligned with the needs and realities of the ICU setting. In conclusion, this comprehensive review offers a blueprint for mitigating the risk of MDR bacterial transmission in the ICU, advocating for an evidence-based, multifaceted approach. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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Other

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26 pages, 1747 KiB

Open AccessSystematic Review

Stenotrophomonas maltophilia Infections: A Systematic Review and Meta-Analysis of Comparative Efficacy of Available Treatments, with Critical Assessment of Novel Therapeutic Options

by Alberto Enrico Maraolo, Federica Licciardi, Ivan Gentile, Annalisa Saracino, Alessandra Belati and Davide Fiore Bavaro

Antibiotics 2023, 12(5), 910; https://doi.org/10.3390/antibiotics12050910 - 15 May 2023

Cited by 10 | Viewed by 7198

Abstract

Stenotrophomonas maltophilia (SM) represents a challenging pathogen due to its resistance profile. A systematic review of the available evidence was conducted to evaluate the best treatment of SM infections to date, focusing on trimethoprim/sulfamethoxazole (TMP/SMX), fluoroquinolones (FQs), and tetracycline derivatives (TDs). Materials: PubMed/MEDLINE and Embase were searched from inception to 30 November 2022. The primary outcome was all-cause mortality. Secondary outcomes included clinical failure, adverse events, and length of stay. A random effects meta-analysis was performed. This study was registered with PROSPERO (CRD42022321893). Results: Twenty-four studies, all retrospective, were included. A significant difference in terms of overall mortality was observed when comparing as a monotherapy TMP/SMX versus FQs (odds ratio (OR) 1.46, 95% confidence interval (CI) 1.15–1.86, I² = 33%; 11 studies, 2407 patients). The prediction interval (PI) did not touch the no effect line (1.06–1.93), but the results were not robust for the unmeasured confounding (E-value for point estimate of 1.71). When comparing TMP/SMX with TDs, the former showed an association with higher mortality but not significant and with a wide PI (OR 1.95, 95% CI 0.79–4.82, PI 0.01–685.99, I² = 0%; 3 studies, 346 patients). Monotherapies in general exerted a protective effect against death opposed to the combination regimens but were not significant (OR 0.71, 95% CI 0.41–1.22, PI 0.16–3.08, I² = 0%; 4 studies, 438 patients). Conclusions: Against SM infections, FQs and, possibly, TDs seem to be reasonable alternative choices to TMP/SMX. Data from clinical trials are urgently needed to better inform therapeutic choices in this setting by also taking into account newer agents. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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11 pages, 430 KiB

Open AccessSystematic Review

Trends in Pseudomonas aeruginosa (P. aeruginosa) Bacteremia during the COVID-19 Pandemic: A Systematic Review

by Qin Xiang Ng, Natasha Yixuan Ong, Dawn Yi Xin Lee, Chun En Yau, Yu Liang Lim, Andrea Lay Hoon Kwa and Ban Hock Tan

Antibiotics 2023, 12(2), 409; https://doi.org/10.3390/antibiotics12020409 - 18 Feb 2023

Cited by 21 | Viewed by 4367

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is among the most common pathogens associated with healthcare-acquired infections, and is often antibiotic resistant, causing significant morbidity and mortality in cases of P. aeruginosa bacteremia. It remains unclear how the incidence of P. aeruginosa bacteremia changed during the Coronavirus Disease 2019 (COVID-19) pandemic, with studies showing almost contradictory conclusions despite enhanced infection control practices during the pandemic. This systematic review sought to examine published reports with incidence rates for P. aeruginosa bacteremia during (defined as from March 2020 onwards) and prior to the COVID-19 pandemic. A systematic literature search was conducted in accordance with PRISMA guidelines and performed in Cochrane, Embase, and Medline with combinations of the key words (pseudomonas aeruginosa OR PAE) AND (incidence OR surveillance), from database inception until 1 December 2022. Based on the pre-defined inclusion criteria, a total of eight studies were eligible for review. Prior to the pandemic, the prevalence of P. aeruginosa was on an uptrend. Several international reports found a slight increase in the incidence of P. aeruginosa bacteremia during the COVID-19 pandemic. These findings collectively highlight the continued importance of good infection prevention and control and antimicrobial stewardship during both pandemic and non-pandemic periods. It is important to implement effective infection prevention and control measures, including ensuring hand hygiene, stepping up environmental cleaning and disinfection efforts, and developing timely guidelines on the appropriate prescription of antibiotics. Full article

(This article belongs to the Special Issue The Issue of Multidrug-Resistant Pathogens in Nosocomial Infections)

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